![](media/image1.png){width="4.883333333333334in"
height="0.8819444444444444in"}

July 8, 2003

Dockets Management Branch (HFA 305)

Food and Drug Administration

5630 Fishers Lane, Room 1061

Rockville, MD 20852

**RE: DOCKET NO. 96N-0417, GOOD MANUFACTURING PRACTICES**

**FOR DIETARY SUPPLEMENTS**

The Council for Responsible Nutrition (CRN) is one of the leading trade
associations representing the dietary supplement industry. CRN has been
a strong supporter of Good Manufacturing Practices (GMPs) over the
years, and we have an active Regulatory Affairs Committee composed of
industry experts in dietary supplement regulation and in the technical
aspects of production processes, including GMPs. CRN's member company
experts in this arena drafted the guidelines for nutritional supplement
manufacturing practices adopted by USP over a decade ago and also
prepared the industry draft GMPs submitted to FDA in November 1995 by
CRN, joined by other industry trade associations. FDA published the
industry draft verbatim as the ANPR on dietary supplement GMPs in 1997.

**SUBMISSION OF FOUR-WAY COMPARISON**

**OF THE CURRENT PROPOSAL, THE ANPR,**

**THE FOOD GMP, AND THE DRUG GMP**

During the next month, CRN will be submitting a wave of comments on the
FDA proposed CGMPs for dietary supplements, addressing several major
topics in a series of separate documents. At this time, we are
submitting a comprehensive 4-way comparison of the existing food and
drug GMPs, the industry draft published in 1997 as the ANPR, and the
current FDA proposed rule. This submission is relevant to the question
of whether the proposal is sufficiently "modeled after" food GMP
regulations. (NOTICE: For those wishing to print this comment, please
note that it is 103 pages in length.)

CRN fully accepts the fact that, when Congress enacted the provision of
the Dietary Supplement Health and Education Act authorizing FDA to adopt
dietary supplement GMPs "modeled after" food GMP regulations, Congress
did not mean to require that the new GMPs be identical to the food GMPs.
If this were the case, there would have been no need for a separate
regulation. Indeed, the industry draft that was published as the ANPR
also departed from the food GMPs and incorporated additional procedures
and practices that CRN members and other industry representatives
believed to represent CGMPs.

It is nevertheless relevant during this comment period to consider the
origins of each component of the FDA proposal and to consider whether
the total document is sufficiently modeled after food GMPs.

The 4-way comparison attached was prepared by the Chairman of CRN's
Regulatory Affairs Committee, Paul Bolar, Vice President for Regulatory
and Legal Affairs of the Pharmavite Corporation. It has proved
invaluable in our consideration of the current proposal, and we are
submitting it for the record to assist FDA and other parties in their
analysis.

The comparison clearly identifies those portions of the rule that are
virtually identical to the food GMPs and thus might actually be omitted
from the document, with a cross-reference indicating that the food GMPs
in 21 CFR Part 110 also apply. It also identifies some areas in which
the drug GMPs or other provisions appear to have served as the model. We
are currently analyzing GMPs for other food categories to identify
potential models that may be useful. The comparison also illustrates the
fact that some provisions included in the industry draft published as
the ANPR were omitted from the current FDA proposal, including a number
of provisions that would have required written procedures for key
operations and that would have provided for expiration dating or other
features considered essential to the marketing of today's dietary
supplements. We will be giving these topics further careful
consideration and will be recommending that some of them be restored to
the proposal on the grounds that they are essential to a company's
ability to develop and maintain a well-controlled production process or
to manufacture and market products acceptable in today's business
environment.

Sincerely,

![](media/image2.png){width="2.2569444444444446in" height="0.6in"}

Annette Dickinson, Ph.D.

President

**GMP COMPARISON**

+------------------+----------------+----------------+----------------+
| **PHARMACEUTICAL | **Food cGMP    | **Advanced     | **Proposed     |
| cGMP**           | (21 CFR Part   | Notice of      | cGMP for       |
|                  | 110)**         | Proposed       | Dietary        |
| **(21 CFR Part   |                | Rulemaking     | Ingredients    |
| 210 & 211)**     |                | (ANPR) (FR:    | and Dietary    |
|                  |                | 2-6-97)**      | Supplements    |
|                  |                |                | (FR:           |
|                  |                |                | 3-13-03)**     |
+==================+================+================+================+
|                  |                |                | ### *PAR       |
|                  |                |                | T 111\--CURREN |
|                  |                |                | T GOOD MANUFAC |
|                  |                |                | TURING PRACTIC |
|                  |                |                | E IN MANUFACTU |
|                  |                |                | RING, PACKING, |
|                  |                |                |  OR HOLDING DI |
|                  |                |                | ETARY INGREDIE |
|                  |                |                | NTS AND DIETAR |
|                  |                |                | Y SUPPLEMENTS* |
|                  |                |                |                |
|                  |                |                | ### Sub        |
|                  |                |                | part A\--Gener |
|                  |                |                | al Provisions  |
|                  |                |                |                |
|                  |                |                | **§ 111.1 [Who |
|                  |                |                | is subject to  |
|                  |                |                | these          |
|                  |                |                | regulations?]  |
|                  |                |                | {.underline}** |
|                  |                |                | You are        |
|                  |                |                | subject to the |
|                  |                |                | regulations in |
|                  |                |                | this part if   |
|                  |                |                | you            |
|                  |                |                | manufacture,   |
|                  |                |                | package, or    |
|                  |                |                | hold a dietary |
|                  |                |                | ingredient or  |
|                  |                |                | dietary        |
|                  |                |                | supplement.    |
+------------------+----------------+----------------+----------------+
|                  |                |                | **§ 111.2      |
|                  |                |                | [What are      |
|                  |                |                | these          |
|                  |                |                | regulations    |
|                  |                |                | intended to    |
|                  |                |                | accomplish?]{  |
|                  |                |                | .underline}**\ |
|                  |                |                | The            |
|                  |                |                | regulations in |
|                  |                |                | this part      |
|                  |                |                | establish the  |
|                  |                |                | minimum        |
|                  |                |                | current good   |
|                  |                |                | manufacturing  |
|                  |                |                | practices that |
|                  |                |                | you must use   |
|                  |                |                | to the extent  |
|                  |                |                | that you       |
|                  |                |                | manufacture,   |
|                  |                |                | package, or    |
|                  |                |                | hold a dietary |
|                  |                |                | ingredient or  |
|                  |                |                | dietary        |
|                  |                |                | supplement.    |
+------------------+----------------+----------------+----------------+
| ## § 21          | **¶110.3       | ##             | **§ 111.3      |
| 0.3 Definitions. | Definitions**  | ## Definitions | [What          |
|                  |                |                | definitions    |
| \(a\) The        | The            | The            | apply to this  |
| definitions and  | definitions    | definitions    | Part?]{        |
| interpretations  | and            | and            | .underline}**\ |
| contained in     | i              | i              | The            |
| section 201 of   | nterpretations | nterpretations | definitions    |
| the act shall be | of terms in    | of terms in    | and            |
| applicable to    | section 201 of | section 201 of | i              |
| such terms when  | the Federal    | the Federal    | nterpretations |
| used in this     | Food, Drug,    | Food, Drug,    | of terms in    |
| part and in      | and Cosmetic   | and Cosmetic   | section 201 of |
| parts 211        | Act (the act)  | Act (the act)  | the Federal    |
| through 226 of   | are applicable | are applicable | Food, Drug,    |
| this chapter.    | to such terms  | to such terms  | and Cosmetic   |
|                  | when used in   | when used in   | Act (the act)  |
| \(b\) The        | this part. The | this part. The | apply to such  |
| following        | following      | following      | terms when     |
| definitions of   | definitions    | definitions    | used in these  |
| terms apply to   | shall also     | shall also     | regulations.   |
| this part and to | apply:         | apply:         | For the        |
| parts 211        |                |                | purpose of     |
| through 226 of   |                |                | these          |
| this chapter.    |                |                | regulations,   |
|                  |                |                | the following  |
|                  |                |                | definitions    |
|                  |                |                | also apply:    |
+------------------+----------------+----------------+----------------+
| \(20\)           |                |                |                |
| *Acceptance      |                |                |                |
| criteria* means  |                |                |                |
| the product      |                |                |                |
| specifications   |                |                |                |
| and              |                |                |                |
| acce             |                |                |                |
| ptance/rejection |                |                |                |
| criteria, such   |                |                |                |
| as acceptable    |                |                |                |
| quality level    |                |                |                |
| and unacceptable |                |                |                |
| quality level,   |                |                |                |
| with an          |                |                |                |
| associated       |                |                |                |
| sampling plan,   |                |                |                |
| that are         |                |                |                |
| necessary for    |                |                |                |
| making a         |                |                |                |
| decision to      |                |                |                |
| accept or reject |                |                |                |
| a lot or batch   |                |                |                |
| (or any other    |                |                |                |
| convenient       |                |                |                |
| subgroups of     |                |                |                |
| manufactured     |                |                |                |
| units).          |                |                |                |
+------------------+----------------+----------------+----------------+
|                  | \(a\) Acid     |                |                |
|                  | foods or       |                |                |
|                  | acidified      |                |                |
|                  | foods means    |                |                |
|                  | foods that     |                |                |
|                  | have an        |                |                |
|                  | equilibrium pH |                |                |
|                  | of 4.6 or      |                |                |
|                  | below.         |                |                |
+------------------+----------------+----------------+----------------+
| \(1\) *Act*      |                |                |                |
| means the        |                |                |                |
| Federal Food,    |                |                |                |
| Drug, and        |                |                |                |
| Cosmetic Act, as |                |                |                |
| amended (21      |                |                |                |
| U.S.C. 301 *et   |                |                |                |
| seq.*).          |                |                |                |
+------------------+----------------+----------------+----------------+
| \(7\) *Active    |                |                |                |
| ingredient*      |                |                |                |
| means any        |                |                |                |
| component that   |                |                |                |
| is intended to   |                |                |                |
| furnish          |                |                |                |
| pharmacological  |                |                |                |
| activity or      |                |                |                |
| other direct     |                |                |                |
| effect in the    |                |                |                |
| diagnosis, cure, |                |                |                |
| mitigation,      |                |                |                |
| treatment, or    |                |                |                |
| prevention of    |                |                |                |
| disease, or to   |                |                |                |
| affect the       |                |                |                |
| structure or any |                |                |                |
| function of the  |                |                |                |
| body of man or   |                |                |                |
| other animals.   |                |                |                |
| The term         |                |                |                |
| includes those   |                |                |                |
| components that  |                |                |                |
| may undergo      |                |                |                |
| chemical change  |                |                |                |
| in the           |                |                |                |
| manufacture of   |                |                |                |
| the drug product |                |                |                |
| and be present   |                |                |                |
| in the drug      |                |                |                |
| product in a     |                |                |                |
| modified form    |                |                |                |
| intended to      |                |                |                |
| furnish the      |                |                |                |
| specified        |                |                |                |
| activity or      |                |                |                |
| effect.          |                |                |                |
+------------------+----------------+----------------+----------------+
| \(18\) *Actual   |                |                | [Actual        |
| yield* means the |                |                | yiel           |
| quantity that is |                |                | d]{.underline} |
| actually         |                |                | means the      |
| produced at any  |                |                | quantity that  |
| appropriate      |                |                | is actually    |
| phase of         |                |                | produced at    |
| manufacture,     |                |                | any            |
| processing, or   |                |                | appropriate    |
| packing of a     |                |                | step of        |
| particular drug  |                |                | manufacture or |
| product.         |                |                | packaging of a |
|                  |                |                | particular     |
|                  |                |                | dietary        |
|                  |                |                | ingredient or  |
|                  |                |                | dietary        |
|                  |                |                | supplement.    |
+------------------+----------------+----------------+----------------+
|                  | \(b\) Adequate | \(a\)          |                |
|                  | means that     | \"Adequate\"   |                |
|                  | which is       | means that     |                |
|                  | needed to      | which is       |                |
|                  | accomplish the | needed to      |                |
|                  | intended       | accomplish the |                |
|                  | purpose in     | intended       |                |
|                  | keeping with   | purpose in     |                |
|                  | good public    | keeping with   |                |
|                  | health         | good public    |                |
|                  | practice.      | health         |                |
|                  |                | practice.      |                |
+------------------+----------------+----------------+----------------+
| \(2\) *Batch*    |                | \(b\) \"Batch  | [Batc          |
| means a specific |                | or Lot\" means | h]{.underline} |
| quantity of a    |                | a specific     | means a        |
| drug or other    |                | quantity of a  | specific       |
| material that is |                | finished       | quantity of a  |
| intended to have |                | product or     | dietary        |
| uniform          |                | other material | ingredient or  |
| character and    |                | that is        | dietary        |
| quality, within  |                | intended to    | supplement     |
| specified        |                | have uniform   | that is        |
| limits, and is   |                | character and  | intended to    |
| produced         |                | quality,       | meet           |
| according to a   |                | within         | specifications |
| single           |                | specified      | for identity,  |
| manufacturing    |                | limits, and is | purity,        |
| order during the |                | produced       | quality,       |
| same cycle of    |                | according to a | strength, and  |
| manufacture.     |                | single         | composition,   |
|                  |                | manufacturing  | and is         |
|                  |                | order during   | produced       |
|                  |                | the same cycle | during a       |
|                  |                | of             | specified time |
|                  |                | manufacture.   | period         |
|                  |                |                | according to a |
|                  |                |                | single         |
|                  |                |                | manufacturing  |
|                  |                |                | record during  |
|                  |                |                | the same cycle |
|                  |                |                | of             |
|                  |                |                | manufacture.   |
+------------------+----------------+----------------+----------------+
| \(11\) *Lot      |                | \(j\) \"Lot    | [Batch number, |
| number, control  |                | number\" means | lot number, or |
| number, or batch |                | any            | control        |
| number* means    |                | distinctive    | numbe          |
| any distinctive  |                | combination of | r]{.underline} |
| combination of   |                | letters,       | means any      |
| letters,         |                | numbers, or    | distinctive    |
| numbers, or      |                | symbols, or    | group of       |
| symbols, or any  |                | any            | letters,       |
| combination of   |                | combination of | numbers, or    |
| them, from which |                | them from      | symbols, or    |
| the complete     |                | which the      | any            |
| history of the   |                | complete       | combination of |
| manufacture,     |                | history of the | them, from     |
| processing,      |                | manufacture,   | which the      |
| packing,         |                | processing,    | complete       |
| holding, and     |                | packing,       | history of the |
| distribution of  |                | holding, and   | manufacturing, |
| a batch or lot   |                | distribution   | packaging, or  |
| of drug product  |                | of a batch or  | holding of a   |
| or other         |                | lot of a       | batch or lot   |
| material can be  |                | finished       | of dietary     |
| determined.      |                | dietary        | ingredients or |
|                  |                | ingredient,    | dietary        |
|                  |                | dietary        | supplements    |
|                  |                | supplement or  | can be         |
|                  |                | other material | determined.    |
|                  |                | can be         |                |
|                  |                | determined.    |                |
+------------------+----------------+----------------+----------------+
|                  | \(c\) Batter   |                |                |
|                  | means a        |                |                |
|                  | semifluid      |                |                |
|                  | substance,     |                |                |
|                  | usually        |                |                |
|                  | composed of    |                |                |
|                  | flour and      |                |                |
|                  | other          |                |                |
|                  | ingredients,   |                |                |
|                  | into which     |                |                |
|                  | principal      |                |                |
|                  | components of  |                |                |
|                  | food are       |                |                |
|                  | dipped or with |                |                |
|                  | which they are |                |                |
|                  | coated, or     |                |                |
|                  | which may be   |                |                |
|                  | used directly  |                |                |
|                  | to form bakery |                |                |
|                  | foods.         |                |                |
+------------------+----------------+----------------+----------------+
|                  | \(d\)          | \(c\)          |                |
|                  | Blanching,     | \"Blanching\"  |                |
|                  | except for     | means a        |                |
|                  | tree nuts and  | prepackaging   |                |
|                  | peanuts, means | heat treatment |                |
|                  | a prepackaging | of a dietary   |                |
|                  | heat treatment | product for a  |                |
|                  | of foodstuffs  | sufficient     |                |
|                  | for a          | time and at a  |                |
|                  | sufficient     | sufficient     |                |
|                  | time and at a  | temperature to |                |
|                  | sufficient     | partially or   |                |
|                  | temperature to | completely     |                |
|                  | partially or   | inactivate the |                |
|                  | completely     | naturally      |                |
|                  | inactivate the | occurring      |                |
|                  | naturally      | enzymes and to |                |
|                  | occurring      | effect other   |                |
|                  | enzymes and to | physical or    |                |
|                  | effect other   | bio-chemical   |                |
|                  | physical or    | changes in the |                |
|                  | bio-chemical   | product.       |                |
|                  | changes in the |                |                |
|                  | food.          |                |                |
+------------------+----------------+----------------+----------------+
| \(3\)            |                | \(q\) \"Raw    | [Componen      |
| *Component*      |                | material\"     | t]{.underline} |
| means any        |                | means any      | means any      |
| ingredient       |                | ingredient     | substance      |
| intended for use |                | intended for   | intended for   |
| in the           |                | use in the     | use in the     |
| manufacture of a |                | manufacture of | manufacture of |
| drug product,    |                | a dietary      | a dietary      |
| including those  |                | ingredient or  | ingredient or  |
| that may not     |                | dietary        | dietary        |
| appear in such   |                | supplement,    | supplement     |
| drug product.    |                | including      | including      |
|                  |                | those that may | those that may |
|                  |                | not appear in  | not appear in  |
|                  |                | such finished  | the finished   |
|                  |                | product.       | dietary        |
|                  |                |                | ingredient or  |
|                  |                |                | dietary        |
|                  |                |                | supplement.    |
|                  |                |                | Component      |
|                  |                |                | includes       |
|                  |                |                | ingredients    |
|                  |                |                | and dietary    |
|                  |                |                | ingredients    |
|                  |                |                | as, described  |
|                  |                |                | in section     |
|                  |                |                | 20l(ff) of the |
|                  |                |                | act.           |
+------------------+----------------+----------------+----------------+
|                  |                | \(d\)          |                |
|                  |                | \              |                |
|                  |                | "Composition\" |                |
|                  |                | means, as      |                |
|                  |                | appropriate:   |                |
|                  |                |                |                |
|                  |                | \(1\) the      |                |
|                  |                | identity of a  |                |
|                  |                | dietary        |                |
|                  |                | ingredient or  |                |
|                  |                | dietary        |                |
|                  |                | supplement,    |                |
|                  |                | and            |                |
|                  |                |                |                |
|                  |                | \(2\) the      |                |
|                  |                | concentration  |                |
|                  |                | of a dietary   |                |
|                  |                | ingredient     |                |
|                  |                | (e.g., weight  |                |
|                  |                | or other unit  |                |
|                  |                | of use/weight  |                |
|                  |                | or volume), or |                |
|                  |                | the potency or |                |
|                  |                | activity of    |                |
|                  |                | one or more    |                |
|                  |                | dietary        |                |
|                  |                | ingredients,   |                |
|                  |                | as indicated   |                |
|                  |                | by appropriate |                |
|                  |                | procedures.    |                |
+------------------+----------------+----------------+----------------+
|                  |                |                | [Consumer      |
|                  |                |                | complain       |
|                  |                |                | t]{.underline} |
|                  |                |                | means          |
|                  |                |                | communication  |
|                  |                |                | that contains  |
|                  |                |                | any            |
|                  |                |                | allegation,    |
|                  |                |                | written or     |
|                  |                |                | oral,          |
|                  |                |                | expressing     |
|                  |                |                | d              |
|                  |                |                | issatisfaction |
|                  |                |                | with the       |
|                  |                |                | quality of a   |
|                  |                |                | dietary        |
|                  |                |                | ingredient or  |
|                  |                |                | a dietary      |
|                  |                |                | supplement     |
|                  |                |                | related to     |
|                  |                |                | good           |
|                  |                |                | manufacturing  |
|                  |                |                | practices.     |
|                  |                |                | Examples of    |
|                  |                |                | product        |
|                  |                |                | quality        |
|                  |                |                | related to     |
|                  |                |                | good           |
|                  |                |                | manufacturing  |
|                  |                |                | practices are: |
|                  |                |                | Foul odor, off |
|                  |                |                | taste,         |
|                  |                |                | super-potent,  |
|                  |                |                | subpotent,     |
|                  |                |                | wrong          |
|                  |                |                | ingredient,    |
|                  |                |                | drug           |
|                  |                |                | contaminant,   |
|                  |                |                | other          |
|                  |                |                | contaminant    |
|                  |                |                | (e.g.,         |
|                  |                |                | bacteria,      |
|                  |                |                | pesticide,     |
|                  |                |                | mycotoxin,     |
|                  |                |                | glass, lead),  |
|                  |                |                | disintegration |
|                  |                |                | time, color    |
|                  |                |                | variation,     |
|                  |                |                | mycotoxin,     |
|                  |                |                | glass, lead),  |
|                  |                |                | disintegration |
|                  |                |                | time, color    |
|                  |                |                | variation,     |
|                  |                |                | tablet size or |
|                  |                |                | size           |
|                  |                |                | variation,     |
|                  |                |                | under-filled   |
|                  |                |                | container,     |
|                  |                |                | foreign        |
|                  |                |                | material in a  |
|                  |                |                | dietary        |
|                  |                |                | supplement     |
|                  |                |                | container,     |
|                  |                |                | improper       |
|                  |                |                | packaging, or  |
|                  |                |                | mislabeling.   |
|                  |                |                | For the        |
|                  |                |                | purposes of    |
|                  |                |                | the            |
|                  |                |                | regulations in |
|                  |                |                | this part, a   |
|                  |                |                | consumer       |
|                  |                |                | complaint      |
|                  |                |                | about product  |
|                  |                |                | quality may or |
|                  |                |                | may not        |
|                  |                |                | include        |
|                  |                |                | concerns about |
|                  |                |                | a possible     |
|                  |                |                | hazard to      |
|                  |                |                | health.        |
|                  |                |                | However, a     |
|                  |                |                | consumer       |
|                  |                |                | complaint does |
|                  |                |                | not include an |
|                  |                |                | adverse event, |
|                  |                |                | illness, or    |
|                  |                |                | injury related |
|                  |                |                | to the safety  |
|                  |                |                | of a           |
|                  |                |                | particular     |
|                  |                |                | dietary        |
|                  |                |                | ingredient     |
|                  |                |                | independent of |
|                  |                |                | whether the    |
|                  |                |                | product is     |
|                  |                |                | produced under |
|                  |                |                | good           |
|                  |                |                | manufacturing  |
|                  |                |                | practices.     |
+------------------+----------------+----------------+----------------+
|                  | \(e\) Critical |                |                |
|                  | control point  |                |                |
|                  | means a point  |                |                |
|                  | in a food      |                |                |
|                  | process where  |                |                |
|                  | there is a     |                |                |
|                  | high           |                |                |
|                  | probability    |                |                |
|                  | that improper  |                |                |
|                  | control may    |                |                |
|                  | cause, allow,  |                |                |
|                  | or contribute  |                |                |
|                  | to a hazard or |                |                |
|                  | to filth in    |                |                |
|                  | the final food |                |                |
|                  | or             |                |                |
|                  | decomposition  |                |                |
|                  | of the final   |                |                |
|                  | food.          |                |                |
+------------------+----------------+----------------+----------------+
|                  |                | \(e\)          |                |
|                  |                | \"Dietary      |                |
|                  |                | ingredient\"   |                |
|                  |                | means an       |                |
|                  |                | ingredient     |                |
|                  |                | intended for   |                |
|                  |                | use or used in |                |
|                  |                | a dietary      |                |
|                  |                | supplement     |                |
|                  |                | that is:       |                |
|                  |                |                |                |
|                  |                | \(1\) a        |                |
|                  |                | vitamin,       |                |
|                  |                |                |                |
|                  |                | \(2\) a        |                |
|                  |                | mineral,       |                |
|                  |                |                |                |
|                  |                | \(3\) an herb  |                |
|                  |                | or other       |                |
|                  |                | botanical,     |                |
|                  |                |                |                |
|                  |                | \(4\) an amino |                |
|                  |                | acid,          |                |
|                  |                |                |                |
|                  |                | \(5\) a        |                |
|                  |                | dietary        |                |
|                  |                | substance for  |                |
|                  |                | use by man to  |                |
|                  |                | supplement the |                |
|                  |                | diet by        |                |
|                  |                | increasing the |                |
|                  |                | total dietary  |                |
|                  |                | intake, or     |                |
|                  |                |                |                |
|                  |                | \(6\) a        |                |
|                  |                | concentrate,   |                |
|                  |                | metabolite,    |                |
|                  |                | constituent,   |                |
|                  |                | extract, or    |                |
|                  |                | combination of |                |
|                  |                | any of the     |                |
|                  |                | foregoing      |                |
|                  |                | ingredients.   |                |
+------------------+----------------+----------------+----------------+
|                  |                | \(f\)          |                |
|                  |                | \"Dietary      |                |
|                  |                | product\"      |                |
|                  |                | means either a |                |
|                  |                | dietary        |                |
|                  |                | ingredient or  |                |
|                  |                | dietary        |                |
|                  |                | supplement as  |                |
|                  |                | defined in     |                |
|                  |                | this part.     |                |
+------------------+----------------+----------------+----------------+
|                  |                | \(g\)          |                |
|                  |                | \"Dietary      |                |
|                  |                | supplement\"   |                |
|                  |                | means dietary  |                |
|                  |                | supplement as  |                |
|                  |                | defined in     |                |
|                  |                | section 201    |                |
|                  |                | (ff) of the    |                |
|                  |                | act.           |                |
+------------------+----------------+----------------+----------------+
| \(4\) *Drug      |                |                |                |
| product* means a |                |                |                |
| finished dosage  |                |                |                |
| form, for        |                |                |                |
| example, tablet, |                |                |                |
| capsule,         |                |                |                |
| solution, etc.,  |                |                |                |
| that contains an |                |                |                |
| active drug      |                |                |                |
| ingredient       |                |                |                |
| generally, but   |                |                |                |
| not necessarily, |                |                |                |
| in association   |                |                |                |
| with inactive    |                |                |                |
| ingredients. The |                |                |                |
| term also        |                |                |                |
| includes a       |                |                |                |
| finished dosage  |                |                |                |
| form that does   |                |                |                |
| not contain an   |                |                |                |
| active           |                |                |                |
| ingredient but   |                |                |                |
| is intended to   |                |                |                |
| be used as a     |                |                |                |
| placebo.         |                |                |                |
+------------------+----------------+----------------+----------------+
| \(5\) *Fiber*    |                |                |                |
| means any        |                |                |                |
| particulate      |                |                |                |
| contaminant with |                |                |                |
| a length at      |                |                |                |
| least three      |                |                |                |
| times greater    |                |                |                |
| than its width.  |                |                |                |
+------------------+----------------+----------------+----------------+
|                  | \(f\) Food     |                |                |
|                  | means food as  |                |                |
|                  | defined in     |                |                |
|                  | section 201(f) |                |                |
|                  | of the act and |                |                |
|                  | includes raw   |                |                |
|                  | materials and  |                |                |
|                  | ingredients.   |                |                |
+------------------+----------------+----------------+----------------+
|                  | \(g\)          |                | [Contact       |
|                  | Food-contact   |                | surfac         |
|                  | surfaces are   |                | e]{.underline} |
|                  | those surfaces |                | means any      |
|                  | that contact   |                | surface that   |
|                  | human food and |                | contacts a     |
|                  | those surfaces |                | component,     |
|                  | from which     |                | dietary        |
|                  | drainage onto  |                | ingredient,    |
|                  | the food or    |                | dietary        |
|                  | onto surfaces  |                | supplement,    |
|                  | that contact   |                | and those      |
|                  | the food       |                | surfaces from  |
|                  | ordinarily     |                | which drainage |
|                  | occurs during  |                | onto the       |
|                  | the normal     |                | component,     |
|                  | course of      |                | dietary        |
|                  | operations.    |                | ingredient,    |
|                  | \"Food-contact |                | dietary        |
|                  | surfaces\"     |                | supplement, or |
|                  | includes       |                | onto surfaces  |
|                  | utensils and   |                | that contact   |
|                  | food-contact   |                | the component, |
|                  | surfaces of    |                | dietary        |
|                  | equipment.     |                | ingredient, or |
|                  |                |                | dietary        |
|                  |                |                | supplement     |
|                  |                |                | ordinarily     |
|                  |                |                | occurs during  |
|                  |                |                | the normal     |
|                  |                |                | course of      |
|                  |                |                | operations.    |
|                  |                |                | Examples of    |
|                  |                |                | contact        |
|                  |                |                | surfaces       |
|                  |                |                | include, but   |
|                  |                |                | are not        |
|                  |                |                | limited to,    |
|                  |                |                | containers,    |
|                  |                |                | utensils,      |
|                  |                |                | tables,        |
|                  |                |                | contact        |
|                  |                |                | surfaces of    |
|                  |                |                | equipment, and |
|                  |                |                | packaging.     |
+------------------+----------------+----------------+----------------+
| \(22\)           |                |                |                |
| *Gang-printed    |                |                |                |
| labeling* means  |                |                |                |
| labeling derived |                |                |                |
| from a sheet of  |                |                |                |
| material on      |                |                |                |
| which more than  |                |                |                |
| one item of      |                |                |                |
| labeling is      |                |                |                |
| printed.         |                |                |                |
+------------------+----------------+----------------+----------------+
| \(8\) *Inactive  |                |                |                |
| ingredient*      |                |                |                |
| means any        |                |                |                |
| component other  |                |                |                |
| than an active   |                |                |                |
| ingredient.      |                |                |                |
+------------------+----------------+----------------+----------------+
|                  |                |                | [Ingredien     |
|                  |                |                | t]{.underline} |
|                  |                |                | means any      |
|                  |                |                | substance that |
|                  |                |                | is used in the |
|                  |                |                | manufacture of |
|                  |                |                | a dietary      |
|                  |                |                | ingredient or  |
|                  |                |                | dietary        |
|                  |                |                | supplement     |
|                  |                |                | that is        |
|                  |                |                | intended to be |
|                  |                |                | present in the |
|                  |                |                | finished       |
|                  |                |                | dietary        |
|                  |                |                | ingredient or\ |
|                  |                |                | dietary        |
|                  |                |                | supplement. An |
|                  |                |                | ingredient     |
|                  |                |                | includes, but  |
|                  |                |                | is not         |
|                  |                |                | necessarily    |
|                  |                |                | limited to, a  |
|                  |                |                | dietary        |
|                  |                |                | ingredient as  |
|                  |                |                | described in   |
|                  |                |                | section        |
|                  |                |                | 201(ff) of the |
|                  |                |                | act.           |
+------------------+----------------+----------------+----------------+
| \(9\)            |                | \(h\)          | [Inprocess     |
| *In-process      |                | \"In-process   | materia        |
| material* means  |                | material\"     | l]{.underline} |
| any material     |                | means any      | means any      |
| fabricated,      |                | material       | material that  |
| compounded,      |                | fabricated,    | is fabricated, |
| blended, or      |                | compounded,    | compounded,    |
| derived by       |                | blended,       | blended,       |
| chemical         |                | ground,        | ground,        |
| reaction that is |                | extracted,     | extracted;     |
| produced for,    |                | sifted,        | sifted,        |
| and used in, the |                | sterilized,    | sterilized,    |
| preparation of   |                | derived by     | derived by     |
| the drug         |                | chemical       | chemical       |
| product.         |                | reaction or    | reaction, or   |
|                  |                | processed in   | processed in   |
|                  |                | any other way  | any other way  |
|                  |                | that is        | for use in the |
|                  |                | produced for,  | manufacture of |
|                  |                | and used in,   | a dietary      |
|                  |                | the            | ingredient or  |
|                  |                | preparation of | dietary        |
|                  |                | a dietary      | supplement.    |
|                  |                | product.       |                |
+------------------+----------------+----------------+----------------+
| \(10\) *Lot*     | \(h\) Lot      | \(i\) \"Lot\"  | [Lo            |
| means a batch,   | means the food | means          | t]{.underline} |
| or a specific    | produced       | \"batch\" as   | means a batch, |
| identified       | during a       | defined in     | or a specific  |
| portion of a     | period of time | this part.     | identified     |
| batch, having    | indicated by a |                | portion of a   |
| uniform          | specific code. |                | batch intended |
| character and    |                |                | to have        |
| quality within   |                |                | uniform        |
| specified        |                |                | identity,      |
| limits; or, in   |                |                | purity,        |
| the case of a    |                |                | quality,       |
| drug product     |                |                | strength, and  |
| produced by      |                |                | composition;   |
| continuous       |                |                | or, in the     |
| process, it is a |                |                | case of a      |
| specific         |                |                | dietary        |
| identified       |                |                | ingredient or  |
| amount produced  |                |                | dietary        |
| in a unit of     |                |                | supplement     |
| time or quantity |                |                | produced by    |
| in a manner that |                |                | continuous     |
| assures its      |                |                | process, a     |
| having uniform   |                |                | specific       |
| character and    |                |                | identified     |
| quality within   |                |                | amount         |
| specified        |                |                | produced in a  |
| limits.          |                |                | specified unit |
|                  |                |                | of time or     |
|                  |                |                | quantity in a  |
|                  |                |                | manner that is |
|                  |                |                | intended to    |
|                  |                |                | have uniform   |
|                  |                |                | identity,      |
|                  |                |                | purity,        |
|                  |                |                | quality,       |
|                  |                |                | strength, and  |
|                  |                |                | composition.   |
+------------------+----------------+----------------+----------------+
| \(12\)           |                | \(k\)          |                |
| *Manufacture,    |                | \              |                |
| processing,      |                | "Manufacture\" |                |
| packing, or      |                | or             |                |
| holding of a     |                | \"m            |                |
| drug product*    |                | anufacturing\" |                |
| includes         |                | includes all   |                |
| packaging and    |                | operations     |                |
| labeling         |                | associated     |                |
| operations,      |                | with the       |                |
| testing, and     |                | production of  |                |
| quality control  |                | dietary        |                |
| of drug          |                | products,      |                |
| products.        |                | including      |                |
|                  |                | packaging and  |                |
|                  |                | labeling       |                |
|                  |                | operations,    |                |
|                  |                | testing, and   |                |
|                  |                | quality        |                |
|                  |                | control of a   |                |
|                  |                | dietary        |                |
|                  |                | ingredient or  |                |
|                  |                | dietary        |                |
|                  |                | supplement.    |                |
+------------------+----------------+----------------+----------------+
| \(13\) The term  |                |                |                |
| *medicated feed* |                |                |                |
| means any Type B |                |                |                |
| or Type C        |                |                |                |
| medicated feed   |                |                |                |
| as defined in    |                |                |                |
| §558.3 of this   |                |                |                |
| chapter. The     |                |                |                |
| feed contains    |                |                |                |
| one or more      |                |                |                |
| drugs as defined |                |                |                |
| in section       |                |                |                |
| 201(g) of the    |                |                |                |
| act. The         |                |                |                |
| manufacture of   |                |                |                |
| medicated feeds  |                |                |                |
| is subject to    |                |                |                |
| the requirements |                |                |                |
| of part 225 of   |                |                |                |
| this chapter.    |                |                |                |
+------------------+----------------+----------------+----------------+
| \(14\) The term  |                |                |                |
| *medicated       |                |                |                |
| premix* means a  |                |                |                |
| Type A medicated |                |                |                |
| article as       |                |                |                |
| defined in       |                |                |                |
| §558.3 of this   |                |                |                |
| chapter. The     |                |                |                |
| article contains |                |                |                |
| one or more      |                |                |                |
| drugs as defined |                |                |                |
| in section       |                |                |                |
| 201(g) of the    |                |                |                |
| act. The         |                |                |                |
| manufacture of   |                |                |                |
| medicated        |                |                |                |
| premixes is      |                |                |                |
| subject to the   |                |                |                |
| requirements of  |                |                |                |
| part 226 of this |                |                |                |
| chapter.         |                |                |                |
+------------------+----------------+----------------+----------------+
|                  | \(i\)          | \(l\)          | [Microorganism |
|                  | Microorganisms | \"Mi           | s]{.underline} |
|                  | means yeasts,  | croorganisms\" | means yeasts,  |
|                  | molds,         | means yeasts,  | molds,         |
|                  | bacteria, and  | molds,         | bacteria,      |
|                  | viruses and    | bacteria, and  | viruses, and   |
|                  | includes, but  | viruses and    | other similar  |
|                  | is not limited | includes, but  | microscopic    |
|                  | to, species    | is not limited | organisms      |
|                  | having public  | to, species    | having public  |
|                  | health         | having public  | health or      |
|                  | significance.  | health         | sanitary       |
|                  | The term       | significance.  | concern. This  |
|                  | \"undesirable  | The term       | definition     |
|                  | mi             | \"undesirable  | includes, but  |
|                  | croorganisms\" | mi             | is not limited |
|                  | includes those | croorganisms\" | to, species    |
|                  | microorganisms | includes those | that:          |
|                  | that are of    | microorganisms |                |
|                  | public health  | that are of    | \(1\) Have     |
|                  | significance,  | public health  | public health  |
|                  | that subject   | significance,  | significance;  |
|                  | food to        | that subject a |                |
|                  | decomposition, | dietary        | \(2\) Could    |
|                  | that indicate  | product to     | cause a        |
|                  | that food is   | decomposition, | component,     |
|                  | contaminated   | that indicate  | dietary        |
|                  | with filth, or | that a dietary | ingredient, or |
|                  | that otherwise | ingredient or  | dietary        |
|                  | may cause food | dietary        | supplement to  |
|                  | to be          | supplement is  | decompose;     |
|                  | adulterated    | contaminated   |                |
|                  | within the     | with filth, or | \(3\) Indicate |
|                  | meaning of the | that otherwise | that the       |
|                  | act.           | may cause a    | component,     |
|                  | Occasionally   | dietary        | dietary        |
|                  | in these       | product to be  | ingredient, or |
|                  | regulations,   | adulterated    | dietary        |
|                  | FDA used the   | within the     | supplement is  |
|                  | adjective      | meaning of the | contaminated   |
|                  | \"microbial\"  | act.           | with filth; or |
|                  | instead of     | Occasionally   |                |
|                  | using an       | in these       | \(4\)          |
|                  | adjectival     | regulations,   | Otherwise may  |
|                  | phrase         | the adjective  | cause the      |
|                  | containing the | \"microbial\"  | component,     |
|                  | word           | is used        | dietary        |
|                  | microorganism. | instead of an  | ingredient, or |
|                  |                | adjectival     | dietary        |
|                  |                | phrase         | supplement to  |
|                  |                | containing the | be             |
|                  |                | word           | adulterated.   |
|                  |                | microorganism. |                |
+------------------+----------------+----------------+----------------+
|                  | \(p\) Shall is | \(u\)          | [Mus           |
|                  | used to state  | \"Shall\" is   | t]{.underline} |
|                  | mandatory      | used to state  | is used to     |
|                  | requirements.  | mandatory      | state          |
|                  |                | requirements.  | mandatory      |
|                  |                |                | requirements.  |
+------------------+----------------+----------------+----------------+
| \(6\)            |                |                |                |
| *Non             |                |                |                |
| -fiber-releasing |                |                |                |
| filter* means    |                |                |                |
| any filter,      |                |                |                |
| which after any  |                |                |                |
| appropriate      |                |                |                |
| pretreatment     |                |                |                |
| such as washing  |                |                |                |
| or flushing,     |                |                |                |
| will not release |                |                |                |
| fibers into the  |                |                |                |
| component or     |                |                |                |
| drug product     |                |                |                |
| that is being    |                |                |                |
| filtered. All    |                |                |                |
| filters composed |                |                |                |
| of asbestos are  |                |                |                |
| deemed to be     |                |                |                |
| fiber-releasing  |                |                |                |
| filters.         |                |                |                |
+------------------+----------------+----------------+----------------+
| \(19\)           |                |                |                |
| *Percentage of   |                |                |                |
| theoretical      |                |                |                |
| yield* means the |                |                |                |
| ratio of the     |                |                |                |
| actual yield (at |                |                |                |
| any appropriate  |                |                |                |
| phase of         |                |                |                |
| manufacture,     |                |                |                |
| processing, or   |                |                |                |
| packing of a     |                |                |                |
| particular drug  |                |                |                |
| product) to the  |                |                |                |
| theoretical      |                |                |                |
| yield (at the    |                |                |                |
| same phase),     |                |                |                |
| stated as a      |                |                |                |
| percentage.      |                |                |                |
+------------------+----------------+----------------+----------------+
|                  | \(j\) Pest     | \(m\) \"Pest\" | [Pes           |
|                  | refers to any  | refers to any  | t]{.underline} |
|                  | objectionable  | objectionable  | means any      |
|                  | animals or     | animals or     | objectionable  |
|                  | insects        | insects        | insects or     |
|                  | including, but | including, but | other animals  |
|                  | not limited    | not limited    | including, but |
|                  | to, bird,      | to, bird,      | not limited    |
|                  | rodents,       | rodents,       | to, birds,     |
|                  | flies, and     | flies, and     | rodents,       |
|                  | larvae.        | larvae.        | flies, mites,  |
|                  |                |                | and larvae.    |
+------------------+----------------+----------------+----------------+
|                  | \(k\) Plant    | \(n\)          | [Physical      |
|                  | means the      | \"Plant\"      | plan           |
|                  | building or    | means the      | t]{.underline} |
|                  | facility or    | building or    | means all or   |
|                  | parts thereof, | facility or    | parts of a     |
|                  | used for or in | parts thereof, | building or    |
|                  | connection     | used for or in | facility used  |
|                  | with the       | connection     | for or in      |
|                  | manufacturing, | with the       | connection     |
|                  | packaging,     | manufacturing, | with           |
|                  | labeling, or   | packaging,     | manufacturing, |
|                  | holding of     | labeling, or   | packaging, or  |
|                  | human food.    | holding of a   | holding a      |
|                  |                | dietary        | dietary        |
|                  |                | product.       | ingredient or  |
|                  |                |                | dietary        |
|                  |                |                | supplement.    |
+------------------+----------------+----------------+----------------+
|                  | \(l\) Quality  | \(o\)          | [Quality       |
|                  | control        | \"Quality      | contro         |
|                  | operation      | control        | l]{.underline} |
|                  | means a        | operation\"    | means a        |
|                  | planned and    | means a        | planned and    |
|                  | systematic     | planned and    | systematic     |
|                  | procedure for  | systematic     | operation or   |
|                  | taking all     | procedure for  | procedure for  |
|                  | actions        | taking all     | preventing a   |
|                  | necessary to   | actions        | dietary        |
|                  | prevent food   | necessary to   | ingredient or  |
|                  | from being     | prevent a      | dietary        |
|                  | adulterated    | dietary        | supplement     |
|                  | within the     | product from   | from being     |
|                  | meaning of the | being          | adulterated.   |
|                  | act.           | adulterated    |                |
|                  |                | within the     |                |
|                  |                | meaning of the |                |
|                  |                | act.           |                |
+------------------+----------------+----------------+----------------+
| \(15\) *Quality  |                | \(p\)          | [Quality       |
| control unit*    |                | \"Quality      | control        |
| means any person |                | control unit\" | uni            |
| or               |                | means any      | t]{.underline} |
| organizational   |                | person or      | means any      |
| element          |                | organizational | person or      |
| designated by    |                | element        | group that you |
| the firm to be   |                | designated by  | designate to   |
| responsible for  |                | the firm to be | be responsible |
| the duties       |                | responsible    | for quality    |
| relating to      |                | for the duties | control        |
| quality control. |                | relating to    | operations.    |
|                  |                | quality        |                |
|                  |                | control        |                |
|                  |                | operations.    |                |
+------------------+----------------+----------------+----------------+
| \(21\)           |                | \(r\)          | [              |
| *Representative  |                | \"             | Representative |
| sample* means a  |                | Representative | sampl          |
| sample that      |                | sample\" means | e]{.underline} |
| consists of a    |                | a sample that  | means a sample |
| number of units  |                | consists of a  | that consists  |
| that are drawn   |                | number of      | of a number of |
| based on         |                | units that are | units that are |
| rational         |                | drawn based on | drawn based on |
| criteria such as |                | rational       | rational       |
| random sampling  |                | criteria, such | criteria, such |
| and intended to  |                | as random      | as random      |
| assure that the  |                | sampling, and  | sampling, and  |
| sample           |                | is intended to | intended to    |
| accurately       |                | assure that    | ensure that    |
| portrays the     |                | the sample     | the sample     |
| material being   |                | accurately     | accurately     |
| sampled.         |                | portrays the   | portrays the   |
|                  |                | material being | material being |
|                  |                | sampled.       | sampled.       |
+------------------+----------------+----------------+----------------+
|                  | \(m\) Rework   | \(s\)          | [Reprocessin   |
|                  | means clean,   | \"Rework\"     | g]{.underline} |
|                  | unadulterated  | means clean,   | means using,   |
|                  | food that has  | unadulterated  | in the         |
|                  | been removed   | material that  | manufacture of |
|                  | from           | has been       | a dietary      |
|                  | processing for | removed from   | ingredient or  |
|                  | reasons other  | processing for | a dietary      |
|                  | than           | reasons other  | supplement,    |
|                  | insanitary     | than           | clean,         |
|                  | conditions or  | insanitary     | unadulterated  |
|                  | that has been  | conditions or  | components,    |
|                  | successfully   | that has been  | dietary        |
|                  | reconditioned  | successfully   | ingredients,   |
|                  | by             | reconditioned  | or dietary     |
|                  | reprocessing   | by             | supplements    |
|                  | and that is    | reprocessing   | that have been |
|                  | suitable for   | and that is    | previously     |
|                  | use as food.   | suitable for   | removed from   |
|                  |                | use in the     | manufacturing  |
|                  |                | manufacture of | for reasons    |
|                  |                | a dietary      | other than     |
|                  |                | product.       | insanitary     |
|                  |                |                | conditions and |
|                  |                |                | that have been |
|                  |                |                | made suitable  |
|                  |                |                | for use in the |
|                  |                |                | manufacture of |
|                  |                |                | a diet any     |
|                  |                |                | ingredient or  |
|                  |                |                | dietary        |
|                  |                |                | supplement.    |
+------------------+----------------+----------------+----------------+
|                  | \(n\) Safe     |                |                |
|                  | moisture level |                |                |
|                  | is a level of  |                |                |
|                  | moisture low   |                |                |
|                  | enough to      |                |                |
|                  | prevent the    |                |                |
|                  | growth of      |                |                |
|                  | undesirable    |                |                |
|                  | microorganisms |                |                |
|                  | in the         |                |                |
|                  | finished       |                |                |
|                  | product under  |                |                |
|                  | the intended   |                |                |
|                  | conditions of  |                |                |
|                  | manufacturing, |                |                |
|                  | storage, and   |                |                |
|                  | distribution.  |                |                |
|                  | The maximum    |                |                |
|                  | safe moisture  |                |                |
|                  | level for a    |                |                |
|                  | food is based  |                |                |
|                  | on its water   |                |                |
|                  | activity       |                |                |
|                  | (a~w~). An     |                |                |
|                  | a~w~ will be   |                |                |
|                  | considered     |                |                |
|                  | safe for food  |                |                |
|                  | if adequate    |                |                |
|                  | data are       |                |                |
|                  | available that |                |                |
|                  | demonstrate    |                |                |
|                  | that the food  |                |                |
|                  | at or below    |                |                |
|                  | the given a~w~ |                |                |
|                  | will not       |                |                |
|                  | support growth |                |                |
|                  | of undesirable |                |                |
|                  | m              |                |                |
|                  | icroorganisms. |                |                |
+------------------+----------------+----------------+----------------+
|                  | \(o\) Sanitize | \(t\)          | [Sanitiz       |
|                  | means to       | \"Sanitize\"   | e]{.underline} |
|                  | adequately     | means to       | means to       |
|                  | treat          | adequately     | adequately     |
|                  | food-contact   | treat          | treat          |
|                  | surfaces by a  | equipment,     | equipment,     |
|                  | process that   | containers or  | containers,    |
|                  | is effective   | utensils by a  | utensils, or   |
|                  | in destroying  | process that   | any other      |
|                  | vegetative     | is effective   | dietary        |
|                  | cells of       | in destroying  | product        |
|                  | microorganisms | vegetative     | contact        |
|                  | of public      | cells of       | surface by     |
|                  | health         | microorganisms | applying       |
|                  | significance,  | of public      | cumulative     |
|                  | and in         | health         | heat or        |
|                  | substantially  | significance,  | chemicals on   |
|                  | reducing       | and in         | cleaned food   |
|                  | numbers of     | substantially  | contact        |
|                  | other          | reducing       | surfaces that  |
|                  | undesirable    | numbers of     | when evaluated |
|                  | m              | other          | for efficacy,  |
|                  | icroorganisms, | undesirable    | yield a        |
|                  | but without    | m              | reduction of 5 |
|                  | adversely      | icroorganisms, | logs, which is |
|                  | affecting the  | but without    | equal to       |
|                  | product or its | adversely      | 99.999 percent |
|                  | safety for the | affecting the  | reduction, of  |
|                  | consumer.      | product or its | representative |
|                  |                | safety for the | disease        |
|                  |                | consumer.      | microorganisms |
|                  |                |                | of public      |
|                  |                |                | health         |
|                  |                |                | significance   |
|                  |                |                | and            |
|                  |                |                | substantially  |
|                  |                |                | reduce the     |
|                  |                |                | numbers of     |
|                  |                |                | other          |
|                  |                |                | undesirable    |
|                  |                |                | m              |
|                  |                |                | icroorganisms, |
|                  |                |                | but without    |
|                  |                |                | adversely      |
|                  |                |                | affecting the  |
|                  |                |                | product or its |
|                  |                |                | safety for the |
|                  |                |                | consumer.      |
+------------------+----------------+----------------+----------------+
|                  | \(q\) Should   | \(v\)          |                |
|                  | is used to     | \"Should\" is  |                |
|                  | state          | used to state  |                |
|                  | recommended or | recommended or |                |
|                  | advisory       | advisory       |                |
|                  | procedures or  | procedures or  |                |
|                  | identify       | identify       |                |
|                  | recommended    | recommended    |                |
|                  | equipment.     | equipment.     |                |
+------------------+----------------+----------------+----------------+
| \(16\)           |                |                |                |
| *Strength*       |                |                |                |
| means:           |                |                |                |
|                  |                |                |                |
| \(i\) The        |                |                |                |
| concentration of |                |                |                |
| the drug         |                |                |                |
| substance (for   |                |                |                |
| example,         |                |                |                |
| weight/weight,   |                |                |                |
| weight/volume,   |                |                |                |
| or unit          |                |                |                |
| dose/volume      |                |                |                |
| basis), and/or   |                |                |                |
|                  |                |                |                |
| \(ii\) The       |                |                |                |
| potency, that    |                |                |                |
| is, the          |                |                |                |
| therapeutic      |                |                |                |
| activity of the  |                |                |                |
| drug product as  |                |                |                |
| indicated by     |                |                |                |
| appropriate      |                |                |                |
| laboratory tests |                |                |                |
| or by adequately |                |                |                |
| developed and    |                |                |                |
| controlled       |                |                |                |
| clinical data    |                |                |                |
| (expressed, for  |                |                |                |
| example, in      |                |                |                |
| terms of units   |                |                |                |
| by reference to  |                |                |                |
| a standard).     |                |                |                |
+------------------+----------------+----------------+----------------+
| \(17\)           |                |                | [Theoretical   |
| *Theoretical     |                |                | yiel           |
| yield* means the |                |                | d]{.underline} |
| quantity that    |                |                | means the      |
| would be         |                |                | quantity that  |
| produced at any  |                |                | would be       |
| appropriate      |                |                | produced at    |
| phase of         |                |                | any            |
| manufacture,     |                |                | appropriate    |
| processing, or   |                |                | step of        |
| packing of a     |                |                | manufacture or |
| particular drug  |                |                | packaging of a |
| product, based   |                |                | particular     |
| upon the         |                |                | dietary        |
| quantity of      |                |                | ingredient or  |
| components to be |                |                | dietary        |
| used, in the     |                |                | supplement,    |
| absence of any   |                |                | based upon the |
| loss or error in |                |                | quantity of    |
| actual           |                |                | components or  |
| production.      |                |                | packaging to   |
|                  |                |                | be used; in    |
|                  |                |                | the absence of |
|                  |                |                | any loss or    |
|                  |                |                | error in       |
|                  |                |                | actual         |
|                  |                |                | production.    |
+------------------+----------------+----------------+----------------+
|                  | \(r\) Water    | \(w\) \"Water  | [Water         |
|                  | activity       | activity       | activity       |
|                  | (a~w~) is a    | (a~w~)\" is a  | (a~w~          |
|                  | measure of the | measure of the | )]{.underline} |
|                  | free moisture  | free moisture  | is a measure   |
|                  | in a food and  | in a dietary   | of the free    |
|                  | is the         | ingredient or  | moisture in a  |
|                  | quotient of    | dietary        | component,     |
|                  | the water      | supplement and | dietary        |
|                  | vapor pressure | is the         | ingredient, or |
|                  | of the         | quotient of    | dietary        |
|                  | substance      | the water      | supplement and |
|                  | divided by the | vapor pressure | is the         |
|                  | vapor pressure | of the         | quotient of    |
|                  | of pure water  | substance      | the water      |
|                  | at the same    | divided by the | vapor pressure |
|                  | temperature.   | vapor pressure | of the         |
|                  |                | of pure water  | substance      |
|                  |                | at the same    | divided by the |
|                  |                | temperature.   | vapor pressure |
|                  |                |                | of pure water  |
|                  |                |                | at the same    |
|                  |                |                | temperature.   |
+------------------+----------------+----------------+----------------+
|                  |                | [W             |                |
|                  |                | e]{.underline} |                |
|                  |                | means the      |                |
|                  |                | United States  |                |
|                  |                | Food and Drug  |                |
|                  |                | Administration |                |
|                  |                | (FDA).         |                |
+------------------+----------------+----------------+----------------+
|                  |                | [Yo            |                |
|                  |                | u]{.underline} |                |
|                  |                | means a person |                |
|                  |                | who            |                |
|                  |                | manufactures,  |                |
|                  |                | packages, or   |                |
|                  |                | holds dietary  |                |
|                  |                | ingredients or |                |
|                  |                | dietary        |                |
|                  |                | supplements.   |                |
+------------------+----------------+----------------+----------------+
|                  |                | **§ 111.5 [Do  |                |
|                  |                | other          |                |
|                  |                | statutory      |                |
|                  |                | provisions and |                |
|                  |                | regulations    |                |
|                  |                | apply?]        |                |
|                  |                | {.underline}** |                |
|                  |                |                |                |
|                  |                | In addition to |                |
|                  |                | the            |                |
|                  |                | regulations in |                |
|                  |                | this part, you |                |
|                  |                | must comply    |                |
|                  |                | with other     |                |
|                  |                | applicable     |                |
|                  |                | statutory      |                |
|                  |                | provisions and |                |
|                  |                | regulations    |                |
|                  |                | under the act  |                |
|                  |                | related to the |                |
|                  |                | manufacturing, |                |
|                  |                | packaging, or  |                |
|                  |                | holding of     |                |
|                  |                | dietary        |                |
|                  |                | ingredients or |                |
|                  |                | dietary        |                |
|                  |                | supplements.   |                |
+------------------+----------------+----------------+----------------+
|                  | **¶110.19      | #              |                |
|                  | Exclusions**   | ### Exclusions |                |
|                  |                |                |                |
|                  | \(a\) The      | The following  |                |
|                  | following      | operations are |                |
|                  | operations are | not subject to |                |
|                  | not subject to | this part:     |                |
|                  | this part:     | Establishments |                |
|                  | Establishments | engaged solely |                |
|                  | engaged solely | in the         |                |
|                  | in the         | harvesting,    |                |
|                  | harvesting,    | storage, or    |                |
|                  | storage, or    | distribution   |                |
|                  | distribution   | of one or more |                |
|                  | of one or more | \"raw          |                |
|                  | \"raw          | agricultural   |                |
|                  | agricultural   | commodities,\" |                |
|                  | commodities,\" | as defined in  |                |
|                  | as defined in  | section 201(r) |                |
|                  | section 201(r) | of the act,    |                |
|                  | of the act,    | which are      |                |
|                  | which are      | ordinarily     |                |
|                  | ordinarily     | cleaned,       |                |
|                  | cleaned,       | prepared,      |                |
|                  | prepared,      | treated, or    |                |
|                  | treated, or    | otherwise      |                |
|                  | otherwise      | processed      |                |
|                  | processed      | before being   |                |
|                  | before being   | marketed to    |                |
|                  | marketed to    | the consuming  |                |
|                  | the consuming  | public.**§     |                |
|                  | public.        | 111.6          |                |
|                  |                | [Exclusions]{  |                |
|                  | \(b\) FDA,     | .underline}.** |                |
|                  | however, will  | The            |                |
|                  | issue special  | regulations in |                |
|                  | regulations if | this part do   |                |
|                  | it is          | not apply to a |                |
|                  | necessary to   | person engaged |                |
|                  | cover these    | solely in      |                |
|                  | excluded       | activities     |                |
|                  | operations.    | related to the |                |
|                  |                | harvesting,    |                |
|                  |                | storage, or    |                |
|                  |                | distribution   |                |
|                  |                | of raw         |                |
|                  |                | agricultural   |                |
|                  |                | commodities    |                |
|                  |                | that will be   |                |
|                  |                | incorporated   |                |
|                  |                | into a dietary |                |
|                  |                | ingredient or  |                |
|                  |                | dietary        |                |
|                  |                | supplement by  |                |
|                  |                | other persons. |                |
+------------------+----------------+----------------+----------------+
| ## § 21          | **110.10       | **Personnel**  | Subpart        |
| 1.28 Personnel r | Personnel**    |                | B\--Personnel  |
| esponsibilities. |                | The plant      |                |
|                  | The plant      | management     | [§ 111.10 What |
| \(d\) Any person | management     | shall take all | microbial      |
| shown at any     | shall take all | reasonable     | contamination  |
| time (either by  | reasonable     | measures and   | and hygiene    |
| medical          | measures and   | precautions to | requirements   |
| examination or   | precautions to | assure the     | apply          |
| supervisory      | ensure the     | following:     | ?]{.underline} |
| observation) to  | following:     |                |                |
| have an apparent |                | \(a\) Disease  | \(a\)          |
| illness or open  | \(a\) Disease  | control. Any   | [Microbial     |
| lesions that may | control. Any   | person who, by | contamination  |
| adversely affect | person who, by | medical        | .]{.underline} |
| the safety or    | medical        | examination or | You must take  |
| quality of drug  | examination or | supervisory    | measures to    |
| products shall   | supervisory    | observation,   | exclude from   |
| be excluded from | observation,   | is shown to    | any operations |
| direct contact   | is shown to    | have, or       | any person who |
| with components, | have, or       | appears to     | might be a     |
| drug product     | appears to     | have, an       | source of      |
| containers,      | have, an       | illness, open  | microbial      |
| closures,        | illness, open  | lesion,        | contamination  |
| in-process       | lesion,        | including      | of any         |
| materials, and   | including      | boils, sores,  | material       |
| drug products    | boils, sores,  | or infected    | including      |
| until the        | or infected    | wounds, or any | components,    |
| condition is     | wounds, or any | other abnormal | dietary        |
| corrected or     | other abnormal | source of      | ingredients,   |
| determined by    | source of      | microbial      | dietary        |
| competent        | microbial      | contamination  | supplements,   |
| medical          | contamination  | by which there | and contact    |
| personnel not to | by which there | is a           | surfaces used  |
| jeopardize the   | is a           | reasonable     | in the         |
| safety or        | reasonable     | possibility of | manufacture,   |
| quality of drug  | possibility of | an in-process  | packaging, or  |
| products. All    | food,          | or finished    | holding of a   |
| personnel shall  | food-contact   | dietary        | dietary        |
| be instructed to | surfaces, or   | product        | ingredient or  |
| report to        | food-packaging | becoming       | a dietary      |
| supervisory      | materials      | adulterated,   | supplement.    |
| personnel any    | becoming       | or processing  | Such measures  |
| health           | contaminated,  | equipment,     | include, but   |
| conditions that  | shall be       | utensils or    | are not        |
| may have an      | excluded from  | packaging      | limited to,    |
| adverse effect   | any operations | materials      | the following: |
| on drug          | which may be   | becoming       |                |
| products.        | expected to    | contaminated,  | \(1\)          |
|                  | result in such | shall be       | Excluding any  |
|                  | contamination  | excluded from  | person who, by |
|                  | until the      | any operations | medical        |
|                  | condition is   | which may be   | examination or |
|                  | corrected.     | expected to    | supervisory    |
|                  | Personnel      | result in such | observation,   |
|                  | shall be       | adulteration   | is shown to    |
|                  | instructed to  | or             | have, or       |
|                  | report such    | contamination  | appears to     |
|                  | health         | until the      | have an        |
|                  | conditions to  | condition is   | illness, open  |
|                  | their          | corrected.     | lesion, or any |
|                  | supervisors.   | Personnel      | other abnormal |
|                  |                | shall be       | source of      |
|                  |                | instructed to  | microbial      |
|                  |                | report such    | contamination, |
|                  |                | health         | which may be   |
|                  |                | conditions to  | expected to    |
|                  |                | their          | result in      |
|                  |                | supervisors.   | microbial      |
|                  |                |                | contamination  |
|                  |                |                | of components, |
|                  |                |                | dietary        |
|                  |                |                | ingredients,   |
|                  |                |                | dietary        |
|                  |                |                | supplements,   |
|                  |                |                | or contact,    |
|                  |                |                | surfaces, from |
|                  |                |                | working in any |
|                  |                |                | operations     |
|                  |                |                | until the      |
|                  |                |                | condition is   |
|                  |                |                | corrected; and |
|                  |                |                |                |
|                  |                |                | \(2\)          |
|                  |                |                | Instructing    |
|                  |                |                | your employees |
|                  |                |                | to notify      |
|                  |                |                | their          |
|                  |                |                | supervisor(s)  |
|                  |                |                | if they have   |
|                  |                |                | or if there is |
|                  |                |                | a reasonable   |
|                  |                |                | possibility    |
|                  |                |                | that they have |
|                  |                |                | a health       |
|                  |                |                | condition,     |
|                  |                |                | described in   |
|                  |                |                | paragraph (a)  |
|                  |                |                | (1) of this    |
|                  |                |                | section that   |
|                  |                |                | could          |
|                  |                |                | contaminate    |
|                  |                |                | any            |
|                  |                |                | components,    |
|                  |                |                | dietary        |
|                  |                |                | ingredients,   |
|                  |                |                | dietary        |
|                  |                |                | supplements,   |
|                  |                |                | or any contact |
|                  |                |                | surface.       |
+------------------+----------------+----------------+----------------+
|                  | \(b\)          | \(b\)          | \(b\)          |
|                  | Cleanliness.   | Cleanliness.   | [Hygienic      |
|                  | All persons    | All persons    | Practices      |
|                  | working in     | working in     | .]{.underline} |
|                  | direct contact | direct contact | If you work in |
|                  | with food,     | with raw       | operations     |
|                  | food-contact   | materials,     | during which   |
|                  | surfaces, and  | in-process or  | adulteration   |
|                  | food-packaging | finished       | of the         |
|                  | materials      | dietary        | component,     |
|                  | shall conform  | products,      | dietary        |
|                  | to hygienic    | processing     | ingredients,   |
|                  | practices      | equipment,     | dietary        |
|                  | while on duty  | utensils or    | supplement, or |
|                  | to the extent  | packaging      | contact        |
|                  | necessary to   | materials      | surface may    |
|                  | protect        | shall conform  | occur, you     |
|                  | against        | to hygienic    | must use       |
|                  | contamination  | practices      | hygienic       |
|                  | of food. The   | while on duty  | practices to   |
|                  | methods for    | to the extent  | the extent     |
|                  | maintaining    | necessary to   | necessary to   |
|                  | cleanliness    | protect        | protect        |
|                  | include, but   | against        | against        |
|                  | are not        | adulteration   | contamination  |
|                  | limited to:    | or             | of components, |
|                  |                | contamination  | dietary        |
|                  |                | of such        | ingredients,   |
|                  |                | materials. The | dietary        |
|                  |                | methods for    | supplements,   |
|                  |                | maintaining    | or contact     |
|                  |                | cleanliness    | surfaces. The  |
|                  |                | include, but   | hygienic       |
|                  |                | are not        | practices      |
|                  |                | limited to:    | include, but   |
|                  |                |                | are not        |
|                  |                |                | limited to:    |
+------------------+----------------+----------------+----------------+
| \(a\) Personnel  | \(1\) Wearing  | \(1\) Wearing  | \(1\) Wearing  |
| engaged in the   | outer garments | outer garments | outer garments |
| manufacture,     | suitable to    | suitable to    | in a manner    |
| processing,      | the operation  | the operation  | that protects  |
| packing, or      | in a manner    | in a manner    | against the    |
| holding of a     | that protects  | that protects  | contamination  |
| drug product     | against the    | against the    | of components, |
| shall wear clean | contamination  | adulteration   | dietary        |
| clothing         | of food,       | of in-process  | ingredients,   |
| appropriate for  | food-contact,  | or finished    | dietary        |
| the duties they  | surfaces or    | dietary        | supplements,   |
| perform...       | food-packaging | products, or   | or any contact |
|                  | materials.     | contamination  | surface;       |
|                  |                | of processing  |                |
|                  |                | equipment,     |                |
|                  |                | utensils or    |                |
|                  |                | packaging      |                |
|                  |                | materials.     |                |
+------------------+----------------+----------------+----------------+
| \(b\) Personnel  | \(2\)          | \(2\)          | \(2\)          |
| shall practice   | Maintaining    | Maintaining    | Maintaining    |
| good sanitation  | adequate       | adequate       | adequate       |
| and health       | personal       | personal       | personal,      |
| habits.          | cleanliness    | cleanliness.   | cleanliness;   |
+------------------+----------------+----------------+----------------+
|                  | \(3\) Washing  | \(3\) Washing  | \(3\) Washing  |
|                  | hands          | hands          | hands          |
|                  | thoroughly     | thoroughly     | thoroughly     |
|                  | (and           | (and           | (and,          |
|                  | sanitizing if  | sanitizing if  | sanitizing if  |
|                  | necessary to   | necessary to   | necessary to   |
|                  | protect        | protect        | protect        |
|                  | against        | against        | against        |
|                  | contamination  | contamination  | contamination  |
|                  | with           | with           | with           |
|                  | undesirable    | undesirable    | m              |
|                  | m              | m              | icroorganisms) |
|                  | icroorganisms) | icroorganisms) | in an adequate |
|                  | in an adequate | in an adequate | hand-washing   |
|                  | hand-washing   | hand-washing   | facility:      |
|                  | facility       | facility       |                |
|                  | before         | before         | \(i\) Before   |
|                  | starting work, | starting work, | starting work; |
|                  | after each     | after each     | and            |
|                  | absence from   | absence from   |                |
|                  | the work       | the work       | \(ii\) At any  |
|                  | station, and   | station, and   | time when the  |
|                  | at any other   | at any other   | hands may have |
|                  | time when the  | time when the  | become soiled  |
|                  | hands may have | hands may have | or             |
|                  | become soiled  | become soiled  | contaminated;  |
|                  | or             | or             |                |
|                  | contaminated.  | contaminated.  |                |
+------------------+----------------+----------------+----------------+
|                  | \(4\) Removing | \(4\) Removing | \(4\) Removing |
|                  | all unsecured  | all unsecured  | all unsecured  |
|                  | jewelry and    | jewelry and    | jewelry and    |
|                  | other objects  | other objects  | other objects  |
|                  | that might     | that might     | that might     |
|                  | fall into      | fall into raw  | fall into      |
|                  | food,          | materials,     | components,    |
|                  | equipment, or  | in-process or  | dietary        |
|                  | containers,    | finished       | ingredients,   |
|                  | and removing   | dietary        | dietary        |
|                  | hand jewelry   | product,       | supplements,   |
|                  | that cannot be | equipment, or  | equipment, or  |
|                  | adequately     | containers,    | packaging, and |
|                  | sanitized      | and removing   | removing hand  |
|                  | during periods | hand jewelry   | jewelry that   |
|                  | in which food  | that cannot be | cannot be      |
|                  | is manipulated | adequately     | adequately     |
|                  | by hand. If    | sanitized      | sanitized      |
|                  | such hand      | during periods | during periods |
|                  | jewelry cannot | in which       | in which       |
|                  | be removed, it | in-process or  | components,    |
|                  | may be covered | finished       | dietary        |
|                  | by material    | product is     | ingredients,   |
|                  | which can be   | manipulated by | or dietary     |
|                  | maintained in  | hand. If such  | supplements    |
|                  | an intact,     | hand jewelry   | are            |
|                  | clean, and     | cannot be      | manipulated by |
|                  | sanitary       | removed, it    | hand. If hand  |
|                  | condition and  | may be covered | jewelry cannot |
|                  | which          | by material    | be removed, it |
|                  | effectively    | which can be   | must be        |
|                  | protects       | maintained in  | covered by     |
|                  | against the    | an intact,     | material that  |
|                  | contamination  | clean, and     | is maintained  |
|                  | by these       | sanitary       | in an intact,  |
|                  | objects of the | condition and  | clean, and     |
|                  | food,          | which          | sanitary       |
|                  | food-contact   | effectively    | condition and  |
|                  | surfaces, or   | protects       | that           |
|                  | food-packaging | against the    | effectively    |
|                  | materials.     | adulteration   | protects       |
|                  |                | of dietary     | against        |
|                  |                | products or    | contamination  |
|                  |                | contamination  | of components, |
|                  |                | of processing  | dietary        |
|                  |                | equipment,     | ingredients,   |
|                  |                | utensils or    | dietary        |
|                  |                | packaging      | supplements,   |
|                  |                | materials.     | or contact     |
|                  |                |                | surfaces;      |
+------------------+----------------+----------------+----------------+
|                  | \(5\)          | \(5\)          | \(5\)          |
|                  | Maintaining    | Maintaining    | Maintaining    |
|                  | gloves, if     | gloves, if     | gloves used in |
|                  | they are used  | they are used  | handling       |
|                  | in food        | in in-process  | components,    |
|                  | handling, in   | or finished    | dietary        |
|                  | an intact,     | product        | ingredients,   |
|                  | clean, and     | handling, in   | or dietary     |
|                  | sanitary       | an intact,     | supplements in |
|                  | condition. The | clean, and     | an intact,     |
|                  | gloves should  | sanitary       | clean, and     |
|                  | be of an       | condition. The | sanitary       |
|                  | impermeable    | gloves should  | condition. The |
|                  | material.      | be of a        | gloves must be |
|                  |                | material that  | of an          |
|                  |                | adequately     | impermeable    |
|                  |                | protects the   | material;      |
|                  |                | product from   |                |
|                  |                | contamination. |                |
+------------------+----------------+----------------+----------------+
| (a)...Protective | \(6\) Wearing, | \(6\) Wearing, | \(6\) Wearing, |
| apparel, such as | where          | where          | where          |
| head, face,      | appropriate,   | appropriate,   | appropriate,   |
| hand, and arm    | in an          | in an          | in an          |
| coverings, shall | effective      | effective      | effective      |
| be worn as       | manner, hair   | manner, hair   | manner,        |
| necessary to     | nets,          | nets, caps,    | hairnets,      |
| protect drug     | headbands,     | beard covers,  | caps, beard    |
| products from    | caps, beard    | or other       | covers, or     |
| contamination.   | covers, or     | effective hair | other          |
|                  | other          | restraints.    | effective hair |
|                  | effective hair |                | restraints;    |
|                  | restraints.    |                |                |
+------------------+----------------+----------------+----------------+
|                  | \(7\) Storing  | \(7\) Storing  | \(7\) Not      |
|                  | clothing or    | clothing or    | storing        |
|                  | other personal | other personal | clothing or    |
|                  | belongings in  | belongings in  | other personal |
|                  | areas other    | areas other    | belongings in  |
|                  | than where     | than where     | areas where    |
|                  | food is        | in-process or  | components,    |
|                  | exposed or     | finished       | dietary        |
|                  | where          | product is     | ingredients,   |
|                  | equipment or   | exposed or     | or dietary     |
|                  | utensils are   | where          | supplements or |
|                  | washed.        | processing     | any contact    |
|                  |                | equipment or   | surfaces are   |
|                  |                | utensils are   | exposed or     |
|                  |                | washed.        | where contact  |
|                  |                |                | surfaces are   |
|                  |                |                | washed;        |
+------------------+----------------+----------------+----------------+
|                  | \(8\)          | \(8\)          | \(8\) Not      |
|                  | Confining the  | Confining the  | eating food,   |
|                  | following to   | following to   | chewing gum,   |
|                  | areas other    | areas other    | drinking       |
|                  | than where     | than where     | beverages and  |
|                  | food may be    | in-process or  | using tobacco  |
|                  | exposed or     | finished       | products in    |
|                  | where          | product may be | areas, where   |
|                  | equipment or   | stored or      | components,    |
|                  | utensils are   | exposed, or    | dietary        |
|                  | washed: eating | where          | ingredients,   |
|                  | food, chewing  | processing     | dietary        |
|                  | gum, drinking  | equipment or   | supplements,   |
|                  | beverages, or  | utensils are   | or any contact |
|                  | using tobacco. | washed: eating | surfaces are   |
|                  |                | food, chewing  | exposed, or    |
|                  |                | gum, drinking  | where contact  |
|                  |                | beverages, or  | surfaces are   |
|                  |                | using tobacco. | washed; and    |
+------------------+----------------+----------------+----------------+
|                  | \(9\) Taking   | \(9\) Taking   | \(9\) Taking   |
|                  | any other      | any other      | any other      |
|                  | necessary      | necessary      | precautions    |
|                  | precautions to | precautions to | necessary to   |
|                  | protect        | protect        | protect        |
|                  | against        | against        | against the    |
|                  | contamination  | adulteration   | contamination  |
|                  | of food,       | of raw         | of components, |
|                  | food-contact,  | materials,     | dietary        |
|                  | surfaces, or   | in-process or  | ingredients,   |
|                  | food-packaging | finished       | dietary        |
|                  | materials with | product, or    | supplements,   |
|                  | m              | contamination  | or contact     |
|                  | icro-organisms | of processing  | surfaces with  |
|                  | or foreign     | equipment,     | m              |
|                  | substances     | utensils or    | icroorganisms, |
|                  | including, but | packaging      | filth, or any  |
|                  | not limited    | materials with | other          |
|                  | to,            | m              | extraneous     |
|                  | perspiration,  | icro-organisms | materials,     |
|                  | hair,          | or foreign     | including, but |
|                  | cosmetics,     | substances     | not limited    |
|                  | tobacco,       | including, but | to,            |
|                  | chemicals, and | not limited    | perspiration,  |
|                  | medicines      | to,            | hair,          |
|                  | applied to the | perspiration,  | cosmetics,     |
|                  | skin.          | hair,          | tobacco,       |
|                  |                | cosmetics,     | chemicals, and |
|                  |                | tobacco,       | medicines      |
|                  |                | chemicals, and | applied to the |
|                  |                | medicines      | skin.          |
|                  |                | applied to the |                |
|                  |                | skin.          |                |
+------------------+----------------+----------------+----------------+
| \(c\) Only       |                |                |                |
| personnel        |                |                |                |
| authorized by    |                |                |                |
| supervisory      |                |                |                |
| personnel shall  |                |                |                |
| enter those      |                |                |                |
| areas of the     |                |                |                |
| buildings and    |                |                |                |
| facilities       |                |                |                |
| designated as    |                |                |                |
| limited-access   |                |                |                |
| areas.           |                |                |                |
+------------------+----------------+----------------+----------------+
| ## §             | \(c\)          | \(c\)          | **§ 111.12     |
| 211.25 Personnel | Education and  | Education and  | [What          |
|  qualifications. | training.      | training. Each | personnel      |
|                  | Personnel      | person engaged | qualification  |
| \(a\) Each       | responsible    | in the         | requirements   |
| person engaged   | for            | manufacture of | apply?]        |
| in the           | identifying    | a dietary      | {.underline}** |
| manufacture,     | sanitation     | product should |                |
| processing,      | failures or    | have the       | \(a\) You must |
| packing, or      | food           | proper         | have qualified |
| holding of a     | contamination  | education,     | employees to   |
| drug product     | should have a  | training, and  | manufacture,   |
| shall have       | background of  | experience (or | package, or    |
| education,       | education or   | any            | hold dietary   |
| training, and    | experience, or | combination    | ingredients or |
| experience, or   | a combination  | thereof)       | dietary        |
| any combination  | thereof, to    | needed to      | supplements;   |
| thereof, to      | provide a      | perform the    | and            |
| enable that      | level of       | assigned       |                |
| person to        | competency     | functions.     | \(b\) Each     |
| perform the      | necessary for  | Training       | person engaged |
| assigned         | production of  | should be in   | in             |
| functions.       | clean and safe | the particular | manufacturing, |
| Training shall   | food. Food     | operation(s)   | packaging, or  |
| be in the        | handlers and   | that the       | holding must   |
| particular       | supervisors    | employee       | have the       |
| operations that  | should receive | performs as    | training and   |
| the employee     | appropriate    | they relate to | experience to  |
| performs and in  | training in    | the            | perform the    |
| current good     | proper food    | employee\'s    | person\'s      |
| manufacturing    | handling       | functions.     | duties.        |
| practice         | techniques and | Appropriate    |                |
| (including the   | f              | documentation  |                |
| current good     | ood-protection | of training    |                |
| manufacturing    | principles and | shall be       |                |
| practice         | should be      | retained by    |                |
| regulations in   | informed of    | the            |                |
| this chapter and | the danger of  | manufacturer.  |                |
| written          | poor personal  |                |                |
| procedures       | hygiene and    |                |                |
| required by      | insanitary     |                |                |
| these            | practices.     |                |                |
| regulations) as  |                |                |                |
| they relate to   |                |                |                |
| the employee\'s  |                |                |                |
| functions.       |                |                |                |
| Training in      |                |                |                |
| current good     |                |                |                |
| manufacturing    |                |                |                |
| practice shall   |                |                |                |
| be conducted by  |                |                |                |
| qualified        |                |                |                |
| individuals on a |                |                |                |
| continuing basis |                |                |                |
| and with         |                |                |                |
| sufficient       |                |                |                |
| frequency to     |                |                |                |
| assure that      |                |                |                |
| employees remain |                |                |                |
| familiar with    |                |                |                |
| CGMP             |                |                |                |
| requirements     |                |                |                |
| applicable to    |                |                |                |
| them.            |                |                |                |
+------------------+----------------+----------------+----------------+
| \(b\) Each       | \(d\)          | d\)            | **§ 111.13     |
| person           | Supervision.   | Supervision.   | [What          |
| responsible for  | Responsibility | Responsibility | supervisor     |
| supervising the  | for assuring   | for assuring   | requirements   |
| manufacture,     | compliance by  | compliance by  | apply?]        |
| processing,      | all personnel  | all personnel  | {.underline}** |
| packing, or      | with all       | with all       |                |
| holding of a     | requirements   | requirements   | \(a\) You must |
| drug product     | of this part   | of this part   | assign         |
| shall have the   | shall be       | shall be       | qualified      |
| education,       | clearly        | clearly        | personnel to   |
| training, and    | assigned to    | assigned to    | supervise the  |
| experience, or   | competent      | qualified      | manufacturing, |
| any combination  | supervisory    | personnel with | packaging, or  |
| thereof, to      | personnel.     | proper         | holding of     |
| perform assigned |                | education,     | dietary        |
| functions in     |                | training and   | ingredients    |
| such a manner as |                | experience (or | and dietary    |
| to provide       |                | any            | supplements.   |
| assurance that   |                | combination    |                |
| the drug product |                | thereof).      | \(b\) You and  |
| has the safety,  |                |                | the            |
| identity,        |                |                | supervisors    |
| strength,        |                |                | you use must   |
| quality, and     |                |                | be qualified   |
| purity that it   |                |                | by training    |
| purports or is   |                |                | and experience |
| represented to   |                |                | to supervise.  |
| possess.         |                |                |                |
+------------------+----------------+----------------+----------------+
| \(c\) There      |                |                |                |
| shall be an      |                |                |                |
| adequate number  |                |                |                |
| of qualified     |                |                |                |
| personnel to     |                |                |                |
| perform and      |                |                |                |
| supervise the    |                |                |                |
| manufacture,     |                |                |                |
| processing,      |                |                |                |
| packing, or      |                |                |                |
| holding of each  |                |                |                |
| drug product.    |                |                |                |
+------------------+----------------+----------------+----------------+
| ## § 211         |                |                |                |
| .34 Consultants. |                |                |                |
|                  |                |                |                |
| Consultants      |                |                |                |
| advising on the  |                |                |                |
| manufacture,     |                |                |                |
| processing,      |                |                |                |
| packing, or      |                |                |                |
| holding of drug  |                |                |                |
| products shall   |                |                |                |
| have sufficient  |                |                |                |
| education,       |                |                |                |
| training, and    |                |                |                |
| experience, or   |                |                |                |
| any combination  |                |                |                |
| thereof, to      |                |                |                |
| advise on the    |                |                |                |
| subject for      |                |                |                |
| which they are   |                |                |                |
| retained.        |                |                |                |
| Records shall be |                |                |                |
| maintained       |                |                |                |
| stating the      |                |                |                |
| name, address,   |                |                |                |
| and              |                |                |                |
| qualifications   |                |                |                |
| of any           |                |                |                |
| consultants and  |                |                |                |
| the type of      |                |                |                |
| service they     |                |                |                |
| provide.         |                |                |                |
+------------------+----------------+----------------+----------------+
| ## § 21          | **¶110.35      | **Sanitation   | ###            |
| 1.56 Sanitation. | Sanitary       | of Buildings   |  Subpart C\--P |
|                  | operations.**  | and            | hysical Plant  |
| \(a\) Any        |                | Facilities**   |                |
| building used in | \(a\) General  |                | **§ 111.15     |
| the manufacture, | maintenance.   | \(a\) General  | [What          |
| processing,      | Buildings,     | maintenance.   | sanitation     |
| packing, or      | fixtures, and  | Buildings,     | requirements   |
| holding of a     | other physical | fixtures, and  | apply to your  |
| drug product     | facilities of  | other physical | physical       |
| shall be         | the plant      | facilities of  | plant?]        |
| maintained in a  | shall be       | the plant      | {.underline}** |
| clean and        | maintained in  | shall be       |                |
| sanitary         | a sanitary     | maintained in  | \(a\)          |
| condition. Any   | condition and  | a sanitary     | [Physical      |
| such building    | shall be kept  | condition and  | plant          |
| shall be free of | in repair      | shall be kept  | facilities     |
| infestation by   | sufficient to  | in repair      | ]{.underline}. |
| rodents, birds,  | prevent food   | sufficient to  |                |
| insects, and     | from becoming  | prevent raw    | \(1\) You must |
| other vermin     | adulterated    | materials,     | maintain your  |
| (other than      | within the     | in-process or  | physical plant |
| laboratory       | meaning of the | finished       | in a clean and |
| animals). Trash  | act\....       | dietary        | sanitary       |
| and organic      |                | products from  | condition; and |
| waste matter     |                | becoming       |                |
| shall be held    |                | adulterated    | \(2\) You must |
| and disposed of  |                | within the     | keep your      |
| in a timely and  |                | meaning of the | physical plant |
| sanitary manner. |                | act.           | in repair      |
|                  |                |                | sufficient to  |
| **§ 211.58       |                |                | prevent        |
| Maintenance.**   |                |                | components,    |
|                  |                |                | dietary        |
| Any building     |                |                | ingredients,   |
| used in the      |                |                | dietary        |
| manufacture,     |                |                | supplements or |
| processing,      |                |                | contact        |
| packing, or      |                |                | surfaces from  |
| holding of a     |                |                | becoming       |
| drug product     |                |                | contaminated.  |
| shall be         |                |                |                |
| maintained in a  |                |                |                |
| good state of    |                |                |                |
| repair.          |                |                |                |
+------------------+----------------+----------------+----------------+
| ## § 21          |                |                |                |
| 1.56 Sanitation. |                |                |                |
|                  |                |                |                |
| \(b\) There      |                |                |                |
| shall be written |                |                |                |
| procedures       |                |                |                |
| assigning        |                |                |                |
| responsibility   |                |                |                |
| for sanitation   |                |                |                |
| and describing   |                |                |                |
| in sufficient    |                |                |                |
| detail the       |                |                |                |
| cleaning         |                |                |                |
| schedules,       |                |                |                |
| methods,         |                |                |                |
| equipment, and   |                |                |                |
| materials to be  |                |                |                |
| used in cleaning |                |                |                |
| the buildings    |                |                |                |
| and facilities;  |                |                |                |
| such written     |                |                |                |
| procedures shall |                |                |                |
| be followed.     |                |                |                |
+------------------+----------------+----------------+----------------+
|                  | \(b\)          | \(b\) Cleaning | \(b\)          |
|                  | Substances     | and sanitizing | [Cleaning      |
|                  | used in        | materials.     | compounds.     |
|                  | cleaning and   |                | sanitizing     |
|                  | sanitizing;    | \(1\) Cleaning | agents. and    |
|                  | storage of     | compounds and  | pesticides     |
|                  | toxic          | sanitizing     | .]{.underline} |
|                  | materials.     | agents used in |                |
|                  |                | cleaning and   | \(1\) You must |
|                  | \(1\) Cleaning | sanitizing     | use cleaning   |
|                  | compounds and  | procedures     | compounds and  |
|                  | sanitizing     | shall be free  | sanitizing     |
|                  | agents used in | from           | agents that    |
|                  | cleaning and   | undesirable    | are free from  |
|                  | sanitizing     | microorganisms | microorganisms |
|                  | procedures     | and shall be   | of public      |
|                  | shall be free  | safe and       | health         |
|                  | from           | adequate under | significance   |
|                  | undesirable    | the conditions | and safe and   |
|                  | microorganisms | of use.        | adequate under |
|                  | and shall be   |                | the conditions |
|                  | safe and       |                | of use.        |
|                  | adequate under |                |                |
|                  | the conditions |                |                |
|                  | of use.        |                |                |
+------------------+----------------+----------------+----------------+
|                  | ...Compliance  | ...Compliance  |                |
|                  | with this      | with this      |                |
|                  | requirement    | requirement    |                |
|                  | may be         | may be         |                |
|                  | verified by    | verified by    |                |
|                  | any effective  | any effective  |                |
|                  | means          | means          |                |
|                  | including      | including      |                |
|                  | purchase of    | purchase of    |                |
|                  | these          | these          |                |
|                  | substances     | substances     |                |
|                  | under a        | under a        |                |
|                  | supplier\'s    | supplier\'s    |                |
|                  | guarantee or   | guarantee or   |                |
|                  | certification, | certification, |                |
|                  | or examination | or examination |                |
|                  | of these       | of these       |                |
|                  | substances for | substances for |                |
|                  | contamination. | contamination. |                |
+------------------+----------------+----------------+----------------+
|                  | Only the       | Only the       | \(2\) You must |
|                  | following      | following      | not use or     |
|                  | toxic          | toxic          | hold toxic     |
|                  | materials may  | materials may  | materials in a |
|                  | be used or     | be used or     | physical plant |
|                  | stored in a    | stored in a    | in which       |
|                  | plant where    | plant where    | contact        |
|                  | food is        | product is     | surfaces,      |
|                  | processed or   | processed or   | components,    |
|                  | exposed:       | exposed:       | dietary        |
|                  |                |                | ingredients,   |
|                  | (i) Those      | > \(i\) Those  | or dietary     |
|                  |     required   | > required to  | supplements    |
|                  |     to         | > maintain     | are            |
|                  |     maintain   | > clean and    | manufactured   |
|                  |     clean and  | > sanitary     | or exposed,    |
|                  |     sanitary   | > conditions;  | unless those   |
|                  |                | >              | materials are  |
|                  |    conditions; | > \(ii\) Those | necessary:\    |
|                  |                | > necessary    | (i) To         |
|                  | (ii) Those     | > for use in   | maintain clean |
|                  |      necessary | > laboratory   | and sanitary   |
|                  |      for use   | > testing      | conditions;    |
|                  |      in        | > procedures;  |                |
|                  |                | >              | \(ii\) For use |
|                  |     laboratory | > \(iii\)      | in, laboratory |
|                  |      testing   | > Those        | testing        |
|                  |                | > necessary    | procedures;    |
|                  |    procedures; | > for plant    |                |
|                  |                | > and          | \(iii\) For    |
|                  | \(iii\) Those  | > equipment    | maintaining or |
|                  | necessary for  | > maintenance  | operating the  |
|                  | plant and      | > and          | physical plant |
|                  | equipment      | > operation;   | or equipment;  |
|                  | maintenance    | > and          | or             |
|                  | and operation; | >              |                |
|                  | and            | > \(iv\) Those | \(iv\) For use |
|                  |                | > necessary    | in the         |
|                  | \(iv\) Those   | > for use in   | plant\'s       |
|                  | necessary for  | > the plant\'s | operations.    |
|                  | use in the     | > operations.  |                |
|                  | plant\'s       |                |                |
|                  | operations.    |                |                |
+------------------+----------------+----------------+----------------+
| ## § 211         | \(2\) Toxic    | \(2\) Toxic    | \(3\) You must |
| .56 Sanitation.  | cleaning       | cleaning       | identify and   |
|                  | compounds,     | compounds,     | hold toxic     |
| \(c\) There      | sanitizing     | sanitizing     | cleaning       |
| shall be written | agents, and    | agents, and    | compounds,     |
| procedures for   | pesticide      | pesticide      | sanitizing     |
| use of suitable  | chemicals      | chemicals      | agents,        |
| rodenticides,    | shall be       | shall be       | pesticides,    |
| insecticides,    | identified,    | identified,    | and pesticide  |
| fungicides,      | held, and      | used, held,    | chemicals in a |
| fumigating       | stored in a    | and stored in  | manner that    |
| agents, and      | manner that    | a manner that  | protects       |
| cleaning and     | protects       | protects       | against        |
| sanitizing       | against        | against        | contamination  |
| agents. Such     | contamination  | adulteration   | of components, |
| written          | of food,       | of raw         | dietary        |
| procedures shall | food-contact   | materials,     | ingredients,   |
| be designed to   | surfaces, or   | in-process or  | dietary        |
| prevent the      | food-packaging | finished       | supplements,   |
| contamination of | materials.     | product, or    | or contact     |
| equipment,       |                | contamination  | surfaces.      |
| components, drug |                | of processing  |                |
| product          |                | equipment or   |                |
| containers,      |                | packaging      |                |
| closures,        |                | materials.     |                |
| packaging,       |                |                |                |
| labeling         |                |                |                |
| materials, or    |                |                |                |
| drug products    |                |                |                |
| and shall be     |                |                |                |
| followed.        |                |                |                |
+------------------+----------------+----------------+----------------+
| Rodenticides,    | All relevant   | All relevant   |                |
| insecticides,    | regulations    | regulations    |                |
| and fungicides   | promulgated by | promulgated by |                |
| shall not be     | other Federal, | other Federal, |                |
| used unless      | State, and     | State, and     |                |
| registered and   | local          | local          |                |
| used in          | government     | government     |                |
| accordance with  | agencies for   | agencies for   |                |
| the Federal      | the            | the            |                |
| Insecticide,     | application,   | application,   |                |
| Fungicide, and   | use or holding | use or holding |                |
| Rodenticide Act  | of these       | of these       |                |
| (7 U.S.C. 135).  | products       | products       |                |
|                  | should be      | should be      |                |
|                  | followed.      | followed.      |                |
|                  |                | Rodenticides,  |                |
|                  |                | insecticides,  |                |
|                  |                | and fungicides |                |
|                  |                | should be      |                |
|                  |                | registered and |                |
|                  |                | used in        |                |
|                  |                | accordance     |                |
|                  |                | with the       |                |
|                  |                | Federal        |                |
|                  |                | Insecticide,   |                |
|                  |                | Fungicide, and |                |
|                  |                | Rodenticide    |                |
|                  |                | Act.           |                |
+------------------+----------------+----------------+----------------+
| \(d\) Sanitation |                |                |                |
| procedures shall |                |                |                |
| apply to work    |                |                |                |
| performed by     |                |                |                |
| contractors or   |                |                |                |
| temporary        |                |                |                |
| employees as     |                |                |                |
| well as work     |                |                |                |
| performed by     |                |                |                |
| full-time        |                |                |                |
| employees during |                |                |                |
| the ordinary     |                |                |                |
| course of        |                |                |                |
| operations.      |                |                |                |
+------------------+----------------+----------------+----------------+
|                  | \(c\) Pest     | \(c\) Pest     | \(c\) [Pest    |
|                  | control. No    | control. No    | control        |
|                  | pests shall be | pests shall be | .]{.underline} |
|                  | allowed in any | allowed in any |                |
|                  | area of a food | area of a      | \(1\) You must |
|                  | plant. Guard   | dietary        | not allow      |
|                  | or guide dogs  | product        | animals or     |
|                  | may be allowed | manufacturing  | pests in any   |
|                  | in some areas  | plant.         | area of your   |
|                  | of a plant if  | Effective      | physical       |
|                  | the presence   | measures shall | plant. Guard   |
|                  | of the dogs is | be taken to    | or guide dogs  |
|                  | unlikely to    | exclude pests  | are allowed in |
|                  | result in      | from the       | some areas of  |
|                  | contamination  | processing     | your physical  |
|                  | of food,       | areas and to   | plant if the   |
|                  | food-contact   | protect        | presence of    |
|                  | surfaces, or   | against the    | the dogs will  |
|                  | food-packaging | adulteration   | not result in  |
|                  | materials.     | of product on  | contamination  |
|                  | Effective      | the premises   | of components, |
|                  | measures shall | by pests. The  | dietary        |
|                  | be taken to    | use of         | ingredients,   |
|                  | exclude pests  | insecticides   | dietary        |
|                  | from the       | or             | supplements,   |
|                  | processing     | rodenticides   | or contact     |
|                  | areas and to   | is permitted   | surfaces;      |
|                  | protect        | only under     |                |
|                  | against the    | precautions    | \(2\) You must |
|                  | contamination  | and            | take effective |
|                  | of food on the | restrictions   | measures to    |
|                  | premises by    | that will      | exclude pests  |
|                  | pests. The use | protect        | from the       |
|                  | of             | against the    | physical plant |
|                  | insecticides   | adulteration   | and to protect |
|                  | or             | of raw         | against        |
|                  | rodenticides   | materials,     | contamination  |
|                  | is permitted   | in-process or  | of components, |
|                  | only under     | finished       | dietary        |
|                  | precautions    | product, or    | ingredients,   |
|                  | and            | contamination  | dietary        |
|                  | restrictions   | of processing  | supplements,   |
|                  | that will      | equipment,     | and contact    |
|                  | protect        | utensils or    | surfaces on    |
|                  | against the    | packaging      | the premises   |
|                  | contamination  | materials.     | by pests; and  |
|                  | of food,       |                |                |
|                  | food-contact   |                | \(3\) You must |
|                  | surfaces, and  |                | not use        |
|                  | food-packaging |                | insecticides,  |
|                  | materials.     |                | fumigants,     |
|                  |                |                | fungicides or  |
|                  |                |                | rodenticides,  |
|                  |                |                | unless you     |
|                  |                |                | take           |
|                  |                |                | precautions to |
|                  |                |                | protect        |
|                  |                |                | against the    |
|                  |                |                | contamination  |
|                  |                |                | of components, |
|                  |                |                | dietary        |
|                  |                |                | ingredients,   |
|                  |                |                | dietary        |
|                  |                |                | supplements,   |
|                  |                |                | or contact     |
|                  |                |                | surfaces.      |
+------------------+----------------+----------------+----------------+
| ## §             | **¶110.37      | \(d\) Water    | \(d\) [Water   |
| 211.48 Plumbing. | Sanitary       | supply.        | supply         |
|                  | facilities and | Potable water  | .]{.underline} |
| \(a\) Potable    | controls.**    | at a suitable  |                |
| water shall be   |                | temperature,   | \(1\) You must |
| supplied under   | Each plant     | and under      | provide water  |
| continuous       | shall be       | pressure as    | that is safe   |
| positive         | equipped with  | needed, shall  | and of         |
| pressure in a    | adequate       | be provided in | adequate       |
| plumbing system  | sanitary       | all areas      | sanitary       |
| free of defects  | facilities and | where required | quality, at    |
| that could       | accommodations | for the        | suitable       |
| contribute       | including, but | processing of  | temperatures,  |
| contamination to | not limited    | dietary        | and under      |
| any drug         | to:            | products, for  | pressure as    |
| product. Potable |                | the cleaning   | needed, in all |
| water shall meet | \(a\) Water    | of processing  | areas where    |
| the standards    | supply. The    | equipment,     | water is       |
| prescribed in    | water supply   | utensils, and  | necessary for: |
| the              | shall be       | packaging      |                |
| Environmental    | sufficient for | materials, or  | \(i\)          |
| Protection       | the operations | for employee   | Manufacturing  |
| Agency\'s        | intended and   | sanitary       | dietary        |
| Primary Drinking | shall be       | facilities.    | ingredients or |
| Water            | derived from   | Any water that | dietary        |
| Regulations set  | an adequate    | contacts       | supplements;   |
| forth in 40 CFR  | source. Any    | in-process or  |                |
| part 141. Water  | water that     | finished       | \(ii\) Making  |
| not meeting such | contacts food  | dietary        | ice that comes |
| standards shall  | or             | products,      | in contact     |
| not be permitted | food-contact   | utensils or    | with           |
| in the potable   | surfaces shall | processing     | components,    |
| water system.    | be safe and of | equipment      | dietary        |
|                  | adequate       | shall meet the | ingredients,   |
|                  | sanitary       | standards      | dietary        |
|                  | quality.       | prescribed in  | supplements or |
|                  | Running water  | the            | contact        |
|                  | at a suitable  | Environmental  | surfaces;      |
|                  | temperature,   | Protection     |                |
|                  | and under      | Agency\'s      | \(iii\)        |
|                  | pressure as    | Primary        | Cleaning any   |
|                  | needed, shall  | Drinking Water | surface; and   |
|                  | be provided in | Regulations    |                |
|                  | all areas      | (40 CFR Part   | \(iv\)         |
|                  | where required | 141).          | Employee       |
|                  | for the        |                | bathrooms and  |
|                  | processing of  |                | hand-washing   |
|                  | food, for the  |                | facilities.    |
|                  | cleaning of    |                |                |
|                  | equipment,     |                | \(2\) Water    |
|                  | utensils, and  |                | that contacts  |
|                  | food-packaging |                | components,    |
|                  | materials, or  |                | dietary        |
|                  | for employee   |                | ingredients,   |
|                  | sanitary       |                | dietary        |
|                  | facilities.    |                | supplements,   |
|                  |                |                | or any contact |
|                  |                |                | surface must   |
|                  |                |                | at a minimum   |
|                  |                |                | comply with    |
|                  |                |                | the National   |
|                  |                |                | Primary        |
|                  |                |                | Drinking Water |
|                  |                |                | regulations    |
|                  |                |                | prescribed by  |
|                  |                |                | the            |
|                  |                |                | Environmental  |
|                  |                |                | Protection     |
|                  |                |                | Agency under   |
|                  |                |                | 40 CFR part    |
|                  |                |                | 141 and any    |
|                  |                |                | state and      |
|                  |                |                | local          |
|                  |                |                | government     |
|                  |                |                | requirements;  |
|                  |                |                |                |
|                  |                |                | \(3\) You must |
|                  |                |                | have           |
|                  |                |                | documentation  |
|                  |                |                | or otherwise   |
|                  |                |                | be able to     |
|                  |                |                | show that      |
|                  |                |                | water that     |
|                  |                |                | contacts       |
|                  |                |                | components,    |
|                  |                |                | dietary        |
|                  |                |                | ingredients,   |
|                  |                |                | dietary        |
|                  |                |                | supplements,   |
|                  |                |                | or any contact |
|                  |                |                | surface meets  |
|                  |                |                | the            |
|                  |                |                | requirements   |
|                  |                |                | in paragraph   |
|                  |                |                | (d) (2) of     |
|                  |                |                | this section.  |
+------------------+----------------+----------------+----------------+
| \(b\) Drains     | \(b\)          | \(e\)          | \(e\)          |
| shall be of      | Plumbing.      | Plumbing.      | [Plumbing      |
| adequate size    | Plumbing shall | Plumbing shall | .]{.underline} |
| and, where       | be of adequate | be of adequate | The plumbing   |
| connected        | size and       | size and       | in your        |
| directly to a    | design and     | design and     | physical plant |
| sewer, shall be  | adequately     | adequately     | must be of an  |
| provided with an | installed and  | installed and  | adequate size  |
| air break or     | maintained to: | maintained to: | and design and |
| other mechanical |                |                | be adequately  |
| device to        | \(1\) Carry    | \(1\) Carry    | installed and  |
| prevent          | sufficient     | sufficient     | maintained to: |
| back-siphonage.  | quantities of  | quantities of  |                |
|                  | water to       | water to       | \(1\) Carry    |
|                  | required       | required       | sufficient     |
|                  | locations      | locations      | amounts of     |
|                  | throughout the | throughout the | water to       |
|                  | plant.         | plant.         | required       |
|                  |                |                | locations      |
|                  | \(2\) Properly | \(2\) Properly | throughout the |
|                  | convey sewage  | convey sewage  | physical       |
|                  | and liquid     | and liquid     | plant;         |
|                  | disposable     | disposable     |                |
|                  | waste from the | waste from the | \(2\) Properly |
|                  | plant.         | plant.         | convey sewage  |
|                  |                |                | and liquid     |
|                  | \(3\) Avoid    | \(3\) Avoid    | disposable     |
|                  | constituting a | constituting a | waste from     |
|                  | source of      | source of      | your physical  |
|                  | contamination  | adulteration   | plant;         |
|                  | to food, water | to product, or |                |
|                  | supplies,      | contamination  | \(3\) Avoid    |
|                  | equipment, or  | of water       | being a source |
|                  | utensils or    | supplies,      | of             |
|                  | creating an    | processing     | contamination  |
|                  | unsanitary     | equipment, or  | to components, |
|                  | condition.     | utensils or    | dietary        |
|                  |                | creating an    | ingredients,   |
|                  | \(4\) Provide  | unsanitary     | dietary        |
|                  | adequate floor | condition.     | supplements,   |
|                  | drainage in    |                | water          |
|                  | all areas      | \(4\) Provide  | supplies, or   |
|                  | where floors   | adequate floor | any contact    |
|                  | are subject to | drainage or    | surface, or    |
|                  | flooding-type  | other          | creating an    |
|                  | cleaning or    | appropriate    | unsanitary     |
|                  | where normal   | means of water | condition;     |
|                  | operations     | removal in all |                |
|                  | release or     | areas where    | \(4\) Provide  |
|                  | discharge      | floors are     | adequate floor |
|                  | water or other | subject to     | drainage in    |
|                  | liquid waste   | flooding-type  | all areas      |
|                  | on the floor.  | cleaning or    | where floors   |
|                  |                | where normal   | are subject to |
|                  | \(5\) Provide  | operations     | flooding-type  |
|                  | that there is  | release or     | cleaning or    |
|                  | not backflow   | discharge      | where normal   |
|                  | from, or       | water or other | operations     |
|                  | cr             | liquid waste   | release or     |
|                  | oss-connection | on the floor.  | discharge      |
|                  | between,       |                | water or other |
|                  | piping systems | \(5\) Provide  | liquid waste   |
|                  | that discharge | that there is  | on the floor;  |
|                  | waste water or | not backflow   | and            |
|                  | sewage and     | from, or       |                |
|                  | piping systems | cr             | \(5\) Not      |
|                  | that carry     | oss-connection | allow backflow |
|                  | water for food | between,       | from, or cross |
|                  | or food        | piping systems | connection     |
|                  | manufacturing. | that discharge | between,       |
|                  |                | waste water or | piping systems |
|                  |                | sewage and     | that discharge |
|                  |                | piping systems | waste water or |
|                  |                | that carry     | sewage and     |
|                  |                | water used for | piping systems |
|                  |                | the            | that carry     |
|                  |                | manufacture of | water used for |
|                  |                | dietary        | manufacturing  |
|                  |                | products.      | dietary        |
|                  |                |                | ingredients or |
|                  |                |                | dietary        |
|                  |                |                | supplements,   |
|                  |                |                | for cleaning   |
|                  |                |                | contact        |
|                  |                |                | surfaces, or   |
|                  |                |                | for use in     |
|                  |                |                | bathrooms or   |
|                  |                |                | hand-washing   |
|                  |                |                | facilities.    |
+------------------+----------------+----------------+----------------+
| ## § 211.50 Se   | \(c\) Sewage   | \(f\) Sewage   | \(f\) [Sewage  |
| wage and refuse. | disposal.      | disposal.      | disposal       |
|                  | Sewage         | Sewage         | ]{.underline}. |
| Sewage, trash,   | disposal shall | disposal shall | You must       |
| and other refuse | be made into   | be made into   | dispose of     |
| in and from the  | an adequate    | an adequate    | sewage into an |
| building and     | sewerage       | sewerage       | adequate       |
| immediate        | system or      | system or      | sewage system  |
| premises shall   | disposed of    | disposed of    | or through     |
| be disposed of   | through other  | through other  | other adequate |
| in a safe and    | adequate       | adequate       | means.         |
| sanitary manner. | means.         | means.         |                |
+------------------+----------------+----------------+----------------+
| ## § 211.5       | \(d\) Toilet   | \(g\) Toilet   | \(g\)          |
| 2 Washing and to | facilities.    | facilities.    | [Bathrooms     |
| ilet facilities. | Each plant     | Each plant     | .]{.underline} |
|                  | shall provide  | shall provide  | You must       |
| Adequate washing | its employees  | its employees  | provide your   |
| facilities shall | with adequate, | with adequate, | employees with |
| be provided,     | readily        | readily        | adequate,      |
| including hot    | accessible     | accessible     | readily        |
| and cold water,  | toilet         | toilet         | accessible     |
| soap or          | facilities.    | facilities.    | bathrooms. The |
| detergent, air   | Compliance     | Compliance     | bathrooms must |
| driers or        | with this      | with this      | be kept clean  |
| single-service   | requirement    | requirement    | and must not   |
| towels, and      | may be         | may be         | become a       |
| clean toilet     | accomplished   | accomplished   | potential      |
| facilities       | by:            | by:            | source of\     |
| easily           |                |                | contamination  |
| accessible to    | \(1\)          | \(1\)          | to components, |
| working areas.   | Maintaining    | Maintaining    | dietary        |
|                  | the facilities | the facilities | ingredients,   |
|                  | in a sanitary  | in a sanitary  | dietary        |
|                  | condition.     | condition.     | supplements,   |
|                  |                |                | or contact     |
|                  | \(2\) Keeping  | \(2\) Keeping  | surfaces. You  |
|                  | the facilities | the facilities | must:          |
|                  | in good repair | in good repair |                |
|                  | at all times.  | at all times.  | \(1\) Keep the |
|                  |                |                | bathrooms in   |
|                  | \(3\)          | \(3\)          | good repair at |
|                  | Providing      | Providing      | all times;     |
|                  | self-closing   | self-closing   |                |
|                  | doors.         | doors.         | \(2\) Provide  |
|                  |                |                | self-closing   |
|                  | \(4\)          | \(4\)          | doors; and     |
|                  | Providing      | Providing      |                |
|                  | doors that do  | doors that do  | \(3\) Provide  |
|                  | not open into  | not open into  | doors that do  |
|                  | areas where    | areas where    | not open into  |
|                  | food is        | dietary        | areas where    |
|                  | exposed to     | product is     | components,    |
|                  | airborne       | exposed to     | dietary        |
|                  | contamination, | airborne       | ingredients,   |
|                  | except where   | contamination, | dietary        |
|                  | alternate      | except where   | supplements,   |
|                  | means have     | alternate      | or contact     |
|                  | been taken to  | means have     | surfaces are   |
|                  | protect        | been taken to  | exposed to     |
|                  | against such   | protect        | airborne       |
|                  | contamination  | against such   | contamination  |
|                  | (such as       | contamination  | except where   |
|                  | double doors   | (such as       | alternate      |
|                  | or positive    | double doors   | means have     |
|                  | air-flow       | or positive    | been taken to  |
|                  | systems).      | air-flow       | protect        |
|                  |                | systems).      | against        |
|                  |                |                | contamination  |
|                  |                |                | (such as       |
|                  |                |                | double doors   |
|                  |                |                | or positive    |
|                  |                |                | airflow        |
|                  |                |                | systems).      |
+------------------+----------------+----------------+----------------+
|                  | \(e\)          | \(h\)          | \(h\)          |
|                  | Hand-washing   | Hand-washing   | [Hand-washing  |
|                  | facilities.    | facilities.    | facilities     |
|                  | Hand-washing   | Hand-washing   | ]{.underline}. |
|                  | facilities     | facilities     | You must       |
|                  | shall be       | shall be       | provide        |
|                  | adequate and   | adequate and   | hand-washing   |
|                  | convenient and | convenient and | facilities     |
|                  | be furnished   | be furnished   | that are       |
|                  | with running   | with running   | adequate,      |
|                  | water at a     | water at a     | convenient,    |
|                  | suitable       | suitable       | and furnish    |
|                  | temperature.   | temperature.   | running water  |
|                  | Compliance     | Compliance     | at a suitable  |
|                  | with this      | with this      | temperature.   |
|                  | requirement    | requirement    | You must do    |
|                  | may be         | may be         | this by        |
|                  | accomplished   | accomplished   | providing:     |
|                  | by providing:  | by providing:  |                |
|                  |                |                | \(1\)          |
|                  | \(1\)          | \(1\)          | Hand-washing   |
|                  | Hand-washing   | Hand-washing   | and, where     |
|                  | and, where     | and, where     | appropriate,   |
|                  | appropriate,   | appropriate,   | h              |
|                  | h              | h              | and-sanitizing |
|                  | and-sanitizing | and-sanitizing | facilities at  |
|                  | facilities at  | facilities at  | each location  |
|                  | each location  | each location  | in your        |
|                  | in the plant   | in the plant   | physical plant |
|                  | where good     | where good     | where good     |
|                  | sanitary       | sanitary       | hygienic       |
|                  | practices      | practices      | practices      |
|                  | require        | require        | require        |
|                  | employees to   | employees to   | employees to   |
|                  | wash and/or    | wash and/or    | wash or to     |
|                  | sanitize their | sanitize their | sanitize or    |
|                  | hands.         | hands.         | both wash and  |
|                  |                |                | sanitize their |
|                  | \(2\)          | \(2\)          | hands;         |
|                  | Effective      | Effective      |                |
|                  | hand-cleaning  | hand-cleaning  | \(2\)          |
|                  | and sanitizing | and sanitizing | Effective      |
|                  | preparations.  | preparations.  | hand-cleaning  |
|                  |                |                | and sanitizing |
|                  | \(3\) Sanitary | \(3\) Air      | preparations;  |
|                  | towel service  | driers,        |                |
|                  | or suitable    | sanitary towel | \(3\) Air      |
|                  | drying         | service or     | driers,        |
|                  | devices.       | suitable       | sanitary towel |
|                  |                | drying         | service, such  |
|                  | \(4\) Devices  | devices.       | as disposable  |
|                  | or fixtures,   |                | paper towels,  |
|                  | such as water  | \(4\) Devices  | or other       |
|                  | control        | or fixtures,   | suitable       |
|                  | valves, so     | such as water  | drying         |
|                  | designed and   | control        | devices;       |
|                  | constructed to | valves, so     |                |
|                  | protect        | designed and   | \(4\) Devices  |
|                  | against        | constructed to | or fixtures,   |
|                  | r              | protect        | such as water  |
|                  | econtamination | against        | control        |
|                  | of clean,      | r              | valves,        |
|                  | sanitized      | econtamination | designed and   |
|                  | hands.         | of clean,      | constructed to |
|                  |                | sanitized      | protect        |
|                  | \(5\) Readily  | hands.         | against        |
|                  | understandable |                | r              |
|                  | signs          | \(5\) Readily  | econtamination |
|                  | directing      | understandable | of clean,      |
|                  | employees      | signs          | sanitized      |
|                  | handling       | directing      | hands;         |
|                  | unprotected    | employees      |                |
|                  | food,          | handling       | \(5\) Signs    |
|                  | unprotected    | unprotected    | that are easy  |
|                  | food-packaging | product,       | to understand  |
|                  | materials,     | packaging      | and are posted |
|                  | food-contact   | materials,     | throughout the |
|                  | surfaces to    | utensils or    | physical plant |
|                  | wash and,      | processing     | that direct    |
|                  | where          | equipment to   | employees      |
|                  | appropriate,   | wash and,      | handling       |
|                  | sanitize their | where          | components,    |
|                  | hands before   | appropriate,   | dietary        |
|                  | they start     | sanitize their | ingredients,   |
|                  | work, after    | hands before   | dietary        |
|                  | each absence   | they start     | supplements,   |
|                  | from post of   | work, after    | or contact     |
|                  | duty, and when | each absence   | surfaces to    |
|                  | their hands    | from post of   | wash and,      |
|                  | may have       | duty, and when | where          |
|                  | become soiled  | their hands    | appropriate,   |
|                  | or             | may have       | to sanitize    |
|                  | contaminated.  | become soiled  | their hands    |
|                  | These signs    | or             | before they    |
|                  | may be posted  | contaminated.  | start work,    |
|                  | in the         | These signs    | after each     |
|                  | processing     | may be posted  | absence from   |
|                  | room(s) and in | in the         | their duty     |
|                  | all other      | processing     | station, and   |
|                  | areas where    | room(s) and in | when their     |
|                  | employees may  | all other      | hands may have |
|                  | handle such    | areas where    | become soiled  |
|                  | food,          | employees may  | or             |
|                  | materials, or  | handle such    | contaminated;  |
|                  | surfaces.      | products,      | and            |
|                  |                | materials,     |                |
|                  | \(6\) Refuse   | utensils or    | \(6\) Trash    |
|                  | receptacles    | equipment.     | bins that are  |
|                  | that are       |                | constructed    |
|                  | constructed    | \(6\) Refuse   | and maintained |
|                  | and maintained | receptacles    | in a manner to |
|                  | in a manner    | that are       | protect        |
|                  | that protects  | constructed    | against        |
|                  | against        | and maintained | r              |
|                  | contamination  | in a manner    | econtamination |
|                  | of food.       | that protects  | of hands and   |
|                  |                | against        | contamination  |
|                  |                | adulteration   | of components, |
|                  |                | of dietary     | dietary        |
|                  |                | products.      | ingredients;   |
|                  |                |                | dietary        |
|                  |                |                | supplements,   |
|                  |                |                | or any contact |
|                  |                |                | surface.       |
+------------------+----------------+----------------+----------------+
|                  | \(f\) Rubbish  | \(i\) Rubbish  | \(i\) [Trash   |
|                  | and offal      | disposal.      | disposal       |
|                  | disposal.      | Rubbish shall  | .]{.underline} |
|                  | Rubbish and    | be so          | You must       |
|                  | any offal      | conveyed,      | convey, store, |
|                  | shall be so    | stored, and    | and dispose of |
|                  | conveyed,      | disposed of as | trash to:      |
|                  | stored, and    | to minimize    |                |
|                  | disposed of as | the            | \(1\) Minimize |
|                  | to minimize    | development of | the            |
|                  | the            | odor, minimize | development of |
|                  | development of | the potential  | odor;          |
|                  | odor, minimize | for the waste  |                |
|                  | the potential  | becoming an    | \(2\) Minimize |
|                  | for the waste  | attractant and | the potential  |
|                  | becoming an    | harborage or   | for the trash  |
|                  | attractant and | breeding place | to attract,    |
|                  | harborage or   | for pests, and | harbor, or     |
|                  | breeding place | protect        | become a       |
|                  | for pests, and | against        | breeding place |
|                  | protect        | adulteration   | for pests;     |
|                  | against        | of raw         |                |
|                  | contamination  | materials,     | \(3\) Protect  |
|                  | of food,       | in-process or  | against        |
|                  | food-contact   | finished       | contamination  |
|                  | surfaces,      | dietary        | of components, |
|                  | water          | products, or   | dietary        |
|                  | supplies, and  | contamination  | ingredients,   |
|                  | ground         | of utensils,   | dietary        |
|                  | surfaces.      | processing     | supplements,   |
|                  |                | equipment,     | any contact    |
|                  |                | water          | surface, water |
|                  |                | supplies, and  | supplies, and  |
|                  |                | ground         | grounds        |
|                  |                | surfaces.      | surrounding    |
|                  |                |                | your physical  |
|                  |                |                | plant; and     |
|                  |                |                |                |
|                  |                |                | \(4\) Control  |
|                  |                |                | hazardous      |
|                  |                |                | waste to       |
|                  |                |                | prevent        |
|                  |                |                | contamination  |
|                  |                |                | of components, |
|                  |                |                | dietary        |
|                  |                |                | ingredients,   |
|                  |                |                | dietary        |
|                  |                |                | supplements,   |
|                  |                |                | and contact    |
|                  |                |                | surfaces.      |
+------------------+----------------+----------------+----------------+
|                  | ¶110.80        | \(j\)          | \(j\)          |
|                  | Processes and  | Supervision.   | [Sanitation    |
|                  | controls.      | Overall        | supervisors    |
|                  |                | sanitation of  | .]{.underline} |
|                  | \...Overall    | the plant      | You must       |
|                  | sanitation of  | shall be under | assign one or  |
|                  | the plant      | the            | more employees |
|                  | shall be under | supervision of | to supervise   |
|                  | the            | one or more    | overall        |
|                  | supervision of | individuals    | sanitation.    |
|                  | one or more    | qualified by   | These          |
|                  | competent      | education,     | supervisors    |
|                  | individuals    | experience and | must be        |
|                  | assigned       | training (or   | qualified by   |
|                  | responsibility | any            | training and   |
|                  | for this       | combination    | experience to  |
|                  | function\...   | thereof)       | develop and    |
|                  |                | assigned       | supervise      |
|                  |                | responsibility | sanitation     |
|                  |                | for assuring   | procedures.    |
|                  |                | that           |                |
|                  |                | sanitation     |                |
|                  |                | procedures are |                |
|                  |                | accomplished.  |                |
+------------------+----------------+----------------+----------------+
|                  | **Subpart      | #### Pla       |                |
|                  | B\--Buildings  | nt and Grounds |                |
|                  | and            |                |                |
|                  | Facilities**   | \(a\) Grounds. |                |
|                  |                | The grounds    |                |
|                  | **¶110.20      | about a        |                |
|                  | Plant and      | dietary        |                |
|                  | grounds.**     | product        |                |
|                  |                | manufacturing  |                |
|                  | \(a\) Grounds. | plant under    |                |
|                  | The grounds    | the control of |                |
|                  | about a food   | the operator   |                |
|                  | plant under    | shall be kept  |                |
|                  | the control of | in a condition |                |
|                  | the operator   | that will      |                |
|                  | shall be kept  | protect        |                |
|                  | in a condition | against the    |                |
|                  | that will      | adulteration   |                |
|                  | protect        | of dietary     |                |
|                  | against the    | products. The  |                |
|                  | contamination  | methods for    |                |
|                  | of food. The   | adequate       |                |
|                  | methods for    | maintenance of |                |
|                  | adequate       | grounds        |                |
|                  | maintenance of | include, but   |                |
|                  | grounds        | are not        |                |
|                  | include, but   | limited to:    |                |
|                  | are not        |                |                |
|                  | limited to:    | \(1\) Properly |                |
|                  |                | storing        |                |
|                  | \(1\) Properly | equipment,     |                |
|                  | storing        | removing       |                |
|                  | equipment,     | litter and     |                |
|                  | removing       | waste, and     |                |
|                  | litter and     | cutting weeds  |                |
|                  | waste, and     | or grass       |                |
|                  | cutting weeds  | within the     |                |
|                  | or grass       | immediate      |                |
|                  | within the     | vicinity of    |                |
|                  | immediate      | the plant      |                |
|                  | vicinity of    | buildings or   |                |
|                  | the plant      | structures     |                |
|                  | buildings or   | that may       |                |
|                  | structures     | constitute an  |                |
|                  | that may       | attractant,    |                |
|                  | constitute an  | breeding       |                |
|                  | attractant,    | place, or      |                |
|                  | breeding       | harborage for  |                |
|                  | place, or      | pests.         |                |
|                  | harborage for  |                |                |
|                  | pests.         | \(2\)          |                |
|                  |                | Maintaining    |                |
|                  | \(2\)          | roads, yards,  |                |
|                  | Maintaining    | and parking    |                |
|                  | roads, yards,  | lots so that   |                |
|                  | and parking    | they do not    |                |
|                  | lots so that   | constitute a   |                |
|                  | they do not    | source of      |                |
|                  | constitute a   | adulteration   |                |
|                  | source of      | in areas where |                |
|                  | contamination  | product is     |                |
|                  | in areas where | exposed.       |                |
|                  | food is        |                |                |
|                  | exposed.       | \(3\)          |                |
|                  |                | Adequately     |                |
|                  | \(3\)          | draining areas |                |
|                  | Adequately     | that may       |                |
|                  | draining areas | contribute to  |                |
|                  | that may       | product        |                |
|                  | contribute     | adulteration   |                |
|                  | contamination  | by seepage,    |                |
|                  | to food by     | foot-borne     |                |
|                  | seepage,       | filth, or      |                |
|                  | foot-borne     | providing a    |                |
|                  | filth, or      | breeding place |                |
|                  | providing a    | for pests.     |                |
|                  | breeding place |                |                |
|                  | for pests.     | \(4\)          |                |
|                  |                | Operating      |                |
|                  | \(4\)          | systems for    |                |
|                  | Operating      | waste          |                |
|                  | systems for    | treatment and  |                |
|                  | waste          | disposal in an |                |
|                  | treatment and  | adequate       |                |
|                  | disposal in an | manner so that |                |
|                  | adequate       | they do not    |                |
|                  | manner so that | constitute a   |                |
|                  | they do not    | source of      |                |
|                  | constitute a   | adulteration   |                |
|                  | source of      | in areas where |                |
|                  | contamination  | product is     |                |
|                  | in areas where | exposed. If    |                |
|                  | food is        | the plant      |                |
|                  | exposed. If    | grounds are    |                |
|                  | the plant      | bordered by    |                |
|                  | grounds are    | grounds not    |                |
|                  | bordered by    | under the      |                |
|                  | grounds not    | operator\'s    |                |
|                  | under the      | control and    |                |
|                  | operator\'s    | not maintained |                |
|                  | control and    | in the manner  |                |
|                  | not maintained | described in   |                |
|                  | in the manner  | paragraph      |                |
|                  | described in   | (a)(1) through |                |
|                  | paragraph      | (3) of this    |                |
|                  | (a)(1) through | section, care  |                |
|                  | (3) of this    | shall be       |                |
|                  | section, care  | exercised in   |                |
|                  | shall be       | the plant by   |                |
|                  | exercised in   | inspection,    |                |
|                  | the plant by   | extermination, |                |
|                  | inspection,    | or other means |                |
|                  | extermination, | to exclude     |                |
|                  | or other means | pests, dirt,   |                |
|                  | to exclude     | and filth that |                |
|                  | pests, dirt,   | may be a       |                |
|                  | and filth that | source of      |                |
|                  | may be a       | product        |                |
|                  | source of food | adulteration.  |                |
|                  | contamination. |                |                |
+------------------+----------------+----------------+----------------+
| ## § 211.42 D    | \(b\) Plant    | \(b\) Plant    | **§ 111.20     |
| esign and constr | construction   | construction   | [What design   |
| uction features. | and design.    | and design.    | and            |
|                  |                | Plant          | construction   |
| \(a\) Any        | Plant          | buildings and  | requirements   |
| building or      | buildings and  | structures     | apply to your  |
| buildings used   | structures     | shall be       | physical       |
| in the           | shall be       | suitable in    | plant?]        |
| manufacture,     | suitable in    | size,          | {.underline}** |
| processing,      | size,          | construction,  |                |
| packing, or      | construction,  | and design to  | Any physical   |
| holding of a     | and design to  | facilitate     | plant you use  |
| drug product     | facilitate     | maintenance,   | in the         |
| shall be of      | maintenance    | cleaning and   | manufacture,   |
| suitable size,   | and sanitary   | sanitary       | packaging, or  |
| construction and | operations for | operations for | holding of     |
| location to      | food           | dietary        | dietary        |
| facilitate       | -manufacturing | product        | ingredients or |
| cleaning,        | purposes. The  | manufacturing  | dietary        |
| maintenance, and | plant and      | purposes and   | supplements    |
| proper           | facilities     | to prevent     | must:          |
| operations.      | shall:         | mixups between |                |
|                  |                | different raw  | \(a\) Be       |
|                  |                | materials and  | suitable in    |
|                  |                | products. The  | size,          |
|                  |                | plant and      | construction,  |
|                  |                | facilities     | and design to  |
|                  |                | shall:         | facilitate     |
|                  |                |                | maintenance,   |
|                  |                |                | cleaning, and  |
|                  |                |                | sanitizing     |
|                  |                |                | operations;    |
+------------------+----------------+----------------+----------------+
| \(b\) Any such   | \(1\) Provide  | \(1\) Provide  | \(b\) Have     |
| building shall   | sufficient     | sufficient     | adequate space |
| have adequate    | space for such | space for such | for the        |
| space for the    | placement of   | placement of   | orderly        |
| orderly          | equipment and  | equipment and  | placement of   |
| placement of     | storage of     | storage of     | equipment and  |
| equipment and    | materials as   | materials as   | holding        |
| materials to     | is necessary   | is necessary   | materials as   |
| prevent mixups   | for the        | for the        | is necessary   |
| between          | maintenance of | prevention of  | for            |
| different        | sanitary       | mixups,        | maintenance,   |
| components, drug | operations and | maintenance of | cleaning, and  |
| product          | the production | sanitary       | sanitizing     |
| containers,      | of safe food.  | operations and | operations and |
| closures,        |                | the production | to prevent     |
| labeling,        |                | of safe        | contamination  |
| in-process       |                | dietary        | and mixups of  |
| materials, or    |                | products.      | components,    |
| drug products,   |                |                | dietary        |
| and to prevent   |                |                | ingredients,   |
| contamination.   |                |                | and dietary    |
| The flow of      |                |                | supplements    |
| components, drug |                |                | during         |
| product          |                |                | manufacturing, |
| containers,      |                |                | packaging, or  |
| closures,        |                |                | holding;       |
| labeling,        |                |                |                |
| in-process       |                |                |                |
| materials, and   |                |                |                |
| drug products    |                |                |                |
| through the      |                |                |                |
| building or      |                |                |                |
| buildings shall  |                |                |                |
| be designed to   |                |                |                |
| prevent          |                |                |                |
| contamination.   |                |                |                |
+------------------+----------------+----------------+----------------+
| \(c\) Operations | \(2\) Permit   | \(2\) Permit   | \(c\) Permit   |
| shall be         | the taking of  | the taking of  | the use of     |
| performed within | proper         | proper         | proper         |
| specifically     | precautions to | precautions to | precautions to |
| defined areas of | reduce the     | reduce the     | reduce the     |
| adequate size.   | potential for  | potential for  | potential for  |
| There shall be   | contamination  | mixups or      | mixups or      |
| separate or      | of food,       | adulteration   | contamination  |
| defined areas or | food-contact   | of in-process  | of components, |
| such other       | surfaces, or   | or finished    | dietary        |
| control systems  | food-packaging | dietary        | ingredients,   |
| for the firm\'s  | materials with | product, or    | dietary        |
| operations as    | m              | contamination  | supplements,   |
| are necessary to | icroorganisms, | of processing  | or contact     |
| prevent          | chemicals,     | equipment,     | surfaces, with |
| contamination or | filth, or      | utensils or    | m              |
| mixups during    | other          | packaging      | icroorganisms, |
| the course of    | extraneous     | materials with | chemicals,     |
| the following    | material.      | m              | filth, or      |
| procedures:      | \...The        | icroorganisms, | ot             |
|                  | potential for  | chemicals,     | her-extraneous |
| \(1\) Receipt,   | contamination  | filth, or      | material. Your |
| identification,  | may be reduced | other          | physical plant |
| storage, and     | by adequate    | extraneous     | must have and  |
| withholding from | food safety    | material. The  | you must use   |
| use of           | controls and   | potential for  | separate or    |
| components, drug | operating      | mixups and     | defined areas  |
| product          | practices or   | product        | of adequate    |
| containers,      | effective      | adulteration   | size or other  |
| closures, and    | design,        | may be reduced | control        |
| labeling,        | including the  | by adequate    | systems, such  |
| pending the      | separation of  | product safety | as             |
| appropriate      | operations in  | controls and   | computerized   |
| sampling,        | which          | operating      | inventory      |
| testing, or      | contamination  | practices or   | controls or    |
| examination by   | is likely to   | effective      | automated      |
| the quality      | occur, by one  | design,        | systems of     |
| control unit     | or more of the | including the  | separation, to |
| before release   | following      | separation of  | prevent        |
| for              | means:         | operations in  | contamination  |
| manufacturing or | location,      | which          | and mixups of  |
| packaging;       | time,          | contamination  | components,    |
|                  | partition, air | is likely to   | dietary        |
| \(2\) Holding    | flow, enclosed | occur, by one  | ingredients,   |
| rejected         | systems, or    | or more of the | and dietary    |
| components, drug | other          | following      | supplements    |
| product          | effective      | means:         | during the     |
| containers,      | means.         | location,      | following      |
| closures, and    |                | time,          | operations:    |
| labeling before  |                | partition, air |                |
| disposition;     |                | flow, enclosed | \(1\)          |
|                  |                | systems, or    | Receiving,     |
| \(3\) Storage of |                | other          | identifying,   |
| released         |                | effective      | holding, and   |
| components, drug |                | means.         | withholding    |
| product          |                |                | from use,      |
| containers,      |                |                | components,    |
| closures, and    |                |                | dietary        |
| labeling;        |                |                | ingredients,   |
|                  |                |                | dietary        |
| \(4\) Storage of |                |                | supplements,   |
| in-process       |                |                | packaging, and |
| materials;       |                |                | labels that    |
|                  |                |                | will be used   |
| \(5\)            |                |                | in or during   |
| Manufacturing    |                |                | the            |
| and processing   |                |                | manufacturing, |
| operations;      |                |                | packaging, or  |
|                  |                |                | holding of     |
| \(6\) Packaging  |                |                | dietary        |
| and labeling     |                |                | ingredients    |
| operations;      |                |                | and dietary    |
|                  |                |                | supplements;   |
| \(7\) Quarantine |                |                |                |
| storage before   |                |                | \(2\)          |
| release of drug  |                |                | Separating, as |
| products;        |                |                | necessary,     |
|                  |                |                | components,    |
| \(8\) Storage of |                |                | dietary        |
| drug products    |                |                | ingredients,   |
| after release;   |                |                | dietary        |
|                  |                |                | supplements,   |
| \(9\) Control    |                |                | packaging, and |
| and laboratory   |                |                | labels, that   |
| operations;      |                |                | are to be used |
|                  |                |                | from           |
| \(10\) Aseptic   |                |                | components,    |
| processing,      |                |                | dietary        |
| which includes   |                |                | ingredients,   |
| as appropriate:  |                |                | dietary        |
|                  |                |                | supplements,   |
| > \(i\) Floors,  |                |                | packaging, or  |
| > walls, and     |                |                | labels that    |
| > ceilings of    |                |                | are awaiting   |
| > smooth, hard   |                |                | material       |
| > surfaces that  |                |                | review and     |
| > are easily     |                |                | disposition    |
| > cleanable;     |                |                | decision,      |
| >                |                |                | reprocessing,  |
| > \(ii\)         |                |                | or are         |
| > Temperature    |                |                | awaiting       |
| > and humidity   |                |                | disposal after |
| > controls;      |                |                | rejection;     |
| >                |                |                |                |
| > \(iii\) An air |                |                | \(3\)          |
| > supply         |                |                | Separating the |
| > filtered       |                |                | manufacturing, |
| > through        |                |                | packaging, and |
| >                |                |                | holding of     |
|  high-efficiency |                |                | different      |
| > particulate    |                |                | product types  |
| > air filters    |                |                | including, but |
| > under positive |                |                | not limited    |
| > pressure,      |                |                | to, different  |
| > regardless of  |                |                | types of       |
| > whether flow   |                |                | dietary        |
| > is laminar or  |                |                | ingredients,   |
| > nonlaminar;    |                |                | dietary        |
| >                |                |                | supplements    |
| > \(iv\) A       |                |                | and other      |
| > system for     |                |                | foods,         |
| > monitoring     |                |                | cosmetics, and |
| > environmental  |                |                | pharmaceutical |
| > conditions;    |                |                | products;      |
| >                |                |                |                |
| > \(v\) A system |                |                | \(4\)          |
| > for cleaning   |                |                | Performing     |
| > and            |                |                | laboratory     |
| > disinfecting   |                |                | analyses and   |
| > the room and   |                |                | holding        |
| > equipment to   |                |                | laboratory     |
| > produce        |                |                | supplies and   |
| > aseptic        |                |                | samples;       |
| > conditions;    |                |                |                |
| >                |                |                | \(5\) Cleaning |
| > \(vi\) A       |                |                | and sanitizing |
| > system for     |                |                | contact        |
| > maintaining    |                |                | surfaces;      |
| > any equipment  |                |                |                |
| > used to        |                |                | \(6\)          |
| > control the    |                |                | Packaging and  |
| > aseptic        |                |                | label          |
| > conditions.    |                |                | operations;    |
|                  |                |                | and            |
|                  |                |                |                |
|                  |                |                | \(7\) Holding  |
|                  |                |                | dietary        |
|                  |                |                | ingredients or |
|                  |                |                | dietary        |
|                  |                |                | supplements.   |
+------------------+----------------+----------------+----------------+
| \(c\) (10)       | \(4\) Be       | \(4\) Be       | \(d\) Be       |
| Aseptic          | constructed in | constructed in | designed and   |
| processing,      | such a manner  | such a manner  | constructed in |
| which includes   | that floors,   | that floors,   | a manner that  |
| as appropriate:  | walls, and     | walls, and     | prevents       |
|                  | ceilings may   | ceilings may   | contamination  |
| \(i\) Floors,    | be adequately  | be adequately  | of components, |
| walls, and       | cleaned and    | cleaned and    | dietary        |
| ceilings of      | kept clean and | kept clean and | ingredients,   |
| smooth, hard     | kept in good   | kept in good   | dietary        |
| surfaces that    | repair; that   | repair; that   | supplements,   |
| are easily       | drip or        | drip or        | or contact     |
| cleanable;       | condensate     | condensate     | surfaces. The  |
|                  | from fixtures, | from fixtures, | design and     |
|                  | ducts and      | ducts and      | construction   |
|                  | pipes does not | pipes does not | must include,  |
|                  | contaminate    | adulterate raw | but not be     |
|                  | food,          | materials,     | limited to:    |
|                  | food-contact   | in-process or  |                |
|                  | surfaces, or   | finished       | \(1\) Floors,  |
|                  | food-packaging | dietary        | Walls, and     |
|                  | materials; ... | products, or   | ceilings that  |
|                  |                | contaminate    | are of smooth  |
|                  |                | product        | and hard       |
|                  |                | containers,    | surfaces that  |
|                  |                | utensils or    | can be         |
|                  |                | packaging      | adequately     |
|                  |                | materials; ... | cleaned and    |
|                  |                |                | kept clean and |
|                  |                |                | in good        |
|                  |                |                | repair;        |
|                  |                |                |                |
|                  |                |                | \(2\)          |
|                  |                |                | Fixtures,      |
|                  |                |                | ducts, and     |
|                  |                |                | pipes that do  |
|                  |                |                | not            |
|                  |                |                | contaminate    |
|                  |                |                | components,    |
|                  |                |                | dietary        |
|                  |                |                | ingredients,   |
|                  |                |                | dietary        |
|                  |                |                | supplements,   |
|                  |                |                | or contact     |
|                  |                |                | surfaces by    |
|                  |                |                | dripping or    |
|                  |                |                | condensate;    |
+------------------+----------------+----------------+----------------+
| \(d\) Operations |                |                |                |
| relating to the  |                |                |                |
| manufacture,     |                |                |                |
| processing, and  |                |                |                |
| packing of       |                |                |                |
| penicillin shall |                |                |                |
| be performed in  |                |                |                |
| facilities       |                |                |                |
| separate from    |                |                |                |
| those used for   |                |                |                |
| other drug       |                |                |                |
| products for     |                |                |                |
| human use.       |                |                |                |
+------------------+----------------+----------------+----------------+
| ##               | \(6\) Provide  | \(6\) Provide  | \(3\) Adequate |
|   § 211.46 Venti | adequate       | adequate       | ventilation or |
| lation, air filt | ventilation or | ventilation or | environmental  |
| ration, air heat | control        | control        | control        |
| ing and cooling. | equipment to   | equipment to   | equipment such |
|                  | minimize odors | maintain       | as air flow    |
| \(a\) Adequate   | and vapors     | adequate       | systems,       |
| ventilation      | (including     | control over   | including      |
| shall be         | steam and      | m              | filters, fans, |
| provided.        | noxious fumes) | icroorganisms, | and other      |
|                  | in areas where | dust,          | air-blowing    |
| \(b\) Equipment  | they may       | humidity, and  | equipment,     |
| for adequate     | contaminate    | temperature,   | that minimize  |
| control over air | food; and      | when           | odors and      |
| pressure,        | locate and     | appropriate,   | vapors         |
| micro-organisms, | operate fans   | for the        | (including     |
| dust, humidity,  | and other      | manufacture of | steam and      |
| and temperature  | air-blowing    | dietary        | noxious fumes) |
| shall be         | equipment in a | products; to   | in areas where |
| provided when    | manner that    | minimize odors | they may       |
| appropriate for  | minimizes the  | and vapors     | contaminate    |
| the manufacture, | potential for  | (including     | components,    |
| processing,      | contaminating  | steam and      | dietary        |
| packing, or      | food,          | noxious fumes) | ingredients,   |
| holding of a     | food-packaging | in areas where | dietary        |
| drug product.    | materials, and | they may       | supplements,   |
|                  | food-contact   | adulterate     | or contact     |
| \(c\) Air        | surfaces.      | dietary        | surfaces;      |
| filtration       |                | products; and  |                |
| systems,         |                | locate and     | \(4\) Fans and |
| including        |                | operate fans   | other          |
| prefilters and   |                | and other      | air-blowing    |
| particulate      |                | air-blowing    | equipment      |
| matter air       |                | equipment in a | located and    |
| filters, shall   |                | manner that    | operated in a  |
| be used when     |                | minimizes the  | manner that    |
| appropriate on   |                | potential for  | minimizes the  |
| air supplies to  |                | adulterating   | potential for  |
| production       |                | raw materials, | microorganisms |
| areas. If air is |                | in-process or  | and            |
| recirculated to  |                | finished       | particulate    |
| production       |                | dietary        | matter to      |
| areas, measures  |                | products, or   | contaminate    |
| shall be taken   |                | contaminating  | components,    |
| to control       |                | processing     | dietary        |
| recirculation of |                | equipment,     | ingredients,   |
| dust from        |                | utensils or    | dietary        |
| production. In   |                | packaging      | supplements,   |
| areas where air  |                | materials.     | or contact     |
| contamination    |                |                | surfaces;      |
| occurs during    |                |                |                |
| production,      |                |                | \(5\)          |
| there shall be   |                |                | Equipment that |
| adequate exhaust |                |                | controls       |
| systems or other |                |                | temperature    |
| systems adequate |                |                | and humidity;  |
| to control       |                |                | and            |
| contaminants.    |                |                |                |
|                  |                |                |                |
| \(d\)            |                |                |                |
| Air-handling     |                |                |                |
| systems for the  |                |                |                |
| manufacture,     |                |                |                |
| processing, and  |                |                |                |
| packing of       |                |                |                |
| penicillin shall |                |                |                |
| be completely    |                |                |                |
| separate from    |                |                |                |
| those for other  |                |                |                |
| drug products    |                |                |                |
| for human use.   |                |                |                |
+------------------+----------------+----------------+----------------+
|                  | (4)...and that | (4)...and that | \(6\) Aisles   |
|                  | aisles or      | aisles or      | or working     |
|                  | working spaces | working spaces | spaces between |
|                  | are provided   | are provided   | equipment and  |
|                  | between        | between        | walls that are |
|                  | equipment and  | equipment and  | adequately     |
|                  | walls and are  | walls and are  | unobstructed   |
|                  | adequately     | adequately     | and of         |
|                  | unobstructed   | unobstructed   | adequate width |
|                  | and of         | and of         | to permit all  |
|                  | adequate width | adequate width | persons to     |
|                  | to permit      | to permit      | perform their  |
|                  | employees to   | employees to   | duties and to  |
|                  | perform their  | perform their  | protect        |
|                  | duties and to  | duties and to  | against        |
|                  | protect        | protect        | contamination  |
|                  | against        | against        | of components, |
|                  | contaminating  | adulterating   | dietary        |
|                  | food or        | in-process or  | ingredients,   |
|                  | food-contact   | finished       | dietary        |
|                  | surfaces with  | product, or    | supplements,   |
|                  | clothing or    | contaminating  | or contact     |
|                  | personal       | processing     | surfaces with  |
|                  | contact.       | equipment with | clothing or    |
|                  |                | clothing or    | personal       |
|                  |                | personal       | contact.       |
|                  |                | contact.       |                |
+------------------+----------------+----------------+----------------+
| ## §             | \(5\) Provide  | \(5\) Provide  | \(e\) Provide  |
| 211.44 Lighting. | adequate       | adequate       | adequate light |
|                  | lighting in    | lighting in    | in:            |
| Adequate         | hand-washing   | hand-washing   |                |
| lighting shall   | areas,         | areas,         | \(1\) All      |
| be provided in   | dressing and   | dressing and   | areas where    |
| all areas.       | locker rooms,  | locker rooms,  | components,    |
|                  | and toilet     | and toilet     | dietary        |
|                  | rooms and in   | rooms and in   | ingredients,   |
|                  | all areas      | all areas      | or dietary     |
|                  | where food is  | where product  | supplements    |
|                  | examined,      | is examined,   | are examined,  |
|                  | processed, or  | processed, or  | processed, or  |
|                  | stored and     | stored and     | held;          |
|                  | where          | where          |                |
|                  | equipment or   | equipment or   | \(2\) All      |
|                  | utensils are   | utensils are   | areas where    |
|                  | cleaned; and   | cleaned; and   | contact        |
|                  | ...            | ...            | surfaces are   |
|                  |                |                | cleaned; and   |
|                  |                |                |                |
|                  |                |                | \(3\)          |
|                  |                |                | Hand-washing   |
|                  |                |                | areas,         |
|                  |                |                | dressing and   |
|                  |                |                | locker rooms,  |
|                  |                |                | and bathrooms. |
+------------------+----------------+----------------+----------------+
|                  | (5)...provide  | (5)...provide  | \(f\) Use      |
|                  | safety-type    | safety-type    | safety-type    |
|                  | light bulbs,   | light bulbs,   | light bulbs,   |
|                  | fixtures,      | fixtures,      | fixtures,      |
|                  | sky-lights, or | sky-lights, or | skylights, or  |
|                  | other glass    | other glass    | other glass    |
|                  | suspended over | suspended over | that is        |
|                  | exposed food   | exposed        | suspended over |
|                  | in any step of | product in any | exposed        |
|                  | preparation or | step of        | components,    |
|                  | otherwise      | preparation or | dietary        |
|                  | protect        | otherwise      | ingredients,   |
|                  | against food   | protect        | or dietary     |
|                  | contamination  | against        | supplements in |
|                  | in case of     | product        | any step of    |
|                  | glass          | adulteration   | preparation,   |
|                  | breakage.      | in case of     | unless         |
|                  |                | glass          | otherwise      |
|                  |                | breakage.      | constructed in |
|                  |                |                | a manner that  |
|                  |                |                | will protect   |
|                  |                |                | against        |
|                  |                |                | contamination  |
|                  |                |                | of components, |
|                  |                |                | dietary        |
|                  |                |                | ingredients,   |
|                  |                |                | or dietary     |
|                  |                |                | supplements in |
|                  |                |                | case of glass  |
|                  |                |                | breakage.      |
+------------------+----------------+----------------+----------------+
|                  | \(3\) Permit   | \(3\) Permit   | \(g\) Provide  |
|                  | the taking of  | the taking of  | protection by  |
|                  | proper         | proper         | any effective  |
|                  | precautions to | precautions to | means against  |
|                  | protect food   | protect        | contamination  |
|                  | in outdoor     | dietary        | of components, |
|                  | bulk           | ingredients or | dietary        |
|                  | fermentation   | dietary        | ingredients,   |
|                  | vessels by any | supplements in | and dietary    |
|                  | effective      | outdoor bulk   | supplements in |
|                  | means,         | fermentation   | bulk           |
|                  | including:     | vessels by any | fermentation   |
|                  |                | effective      | vessels,       |
|                  | (i) Using      | means,         | including      |
|                  |     protective | including:     | consideration  |
|                  |     coverings. |                | of:            |
|                  |                | (i) Using      |                |
|                  | (i             |     protective | \(1\) Use of   |
|                  | i) Controlling |     coverings. | protective     |
|                  |      areas     |                | coverings;     |
|                  |      over and  | (i             |                |
|                  |      around    | i) Controlling | \(2\)          |
|                  |      the       |      areas     | Placement in   |
|                  |      vessels   |      over and  | areas where    |
|                  |      to        |      around    | you can        |
|                  |      eliminate |      the       | eliminate      |
|                  |                |      vessels   | harborages for |
|                  |     harborages |      to        | pests over and |
|                  |      for       |      eliminate | around the     |
|                  |      pests.    |                | vessels;       |
|                  |                |     harborages |                |
|                  | (iii) Checking |      for       | \(3\)          |
|                  |       on a     |      pests.    | Placement in   |
|                  |       regular  |                | areas where    |
|                  |       basis    | (iii) Checking | you can check  |
|                  |       for      |       on a     | regularly for  |
|                  |       pests    |       regular  | pests, pest    |
|                  |       and pest |       basis    | infestation,   |
|                  |                |       for      | filth or any   |
|                  |   infestation. |       pests    | other          |
|                  |                |       and pest | extraneous     |
|                  | (iv) Skimming  |                | materials; and |
|                  |      the       |   infestation. |                |
|                  |                |                | \(4\) Use of   |
|                  |   fermentation | (iv) Skimming  | skimming       |
|                  |      vessels,  |      the       | equipment.     |
|                  |      as        |                |                |
|                  |                |   fermentation |                |
|                  |     necessary. |      vessels,  |                |
|                  |                |      as        |                |
|                  |                |                |                |
|                  |                |     necessary. |                |
+------------------+----------------+----------------+----------------+
|                  | \(7\) Provide, | \(7\) Provide, | \(h\) Use      |
|                  | where          | where          | adequate       |
|                  | necessary,     | necessary,     | screening or   |
|                  | adequate       | adequate       | other          |
|                  | screening or   | screening or   | protection     |
|                  | other          | other          | against pests, |
|                  | protection     | protection     | where          |
|                  | against pests. | against pests. | necessary.     |
+------------------+----------------+----------------+----------------+
| #                | ##### Subpart  | **Equipment    | **Subpart      |
| # § 211.63 Equip |  C---Equipment | and Utensils** | D\--Equipment  |
| ment design, siz |                |                | and Utensils** |
| e, and location. | **¶110.40      | **(a) Design   |                |
|                  | Equipment and  | and            | **§ 111.25     |
| Equipment used   | utensils.**    | c              | [What          |
| in the           |                | onstruction.** | requirements   |
| manufacture,     | \(a\) All      |                | apply to the   |
| processing,      | plant          | \(1\) All      | equipment and  |
| packing, or      | equipment and  | plant          | utensils you   |
| holding of a     | utensils shall | equipment and  | use?           |
| drug product     | be so designed | utensils shall | ]              |
| shall be of      | and of such    | be so designed | {.underline}** |
| appropriate      | material and   | and of such    |                |
| design, adequate | workmanship as | material and   | \(a\) (1) You  |
| size, and        | to be          | workmanship as | must use       |
| suitably located | adequately     | to be          | equipment and  |
| to facilitate    | cleanable, and | adequately     | utensils that  |
| operations for   | shall be       | cleanable, and | are of         |
| its intended use | properly       | shall be       | appropriate    |
| and for its      | maintained.    | properly       | design,        |
| cleaning and     |                | maintained.    | construction,  |
| maintenance.     | \(d\) Holding, |                | and            |
|                  | conveying, and | \(6\) Holding, | workmanship to |
|                  | manufacturing  | conveying, and | enable them to |
|                  | systems,       | manufacturing  | be suitable    |
|                  | including      | systems,       | for their      |
|                  | gravimetric,   | including      | intended use   |
|                  | pneumatic,     | gravimetric,   | and to be      |
|                  | closed, and    | pneumatic,     | adequately     |
|                  | automated      | closed, and    | cleaned and    |
|                  | systems, shall | automated      | properly       |
|                  | be of a design | systems, shall | maintained.    |
|                  | and            | be of a design | Equipment and  |
|                  | construction   | and            | utensils       |
|                  | that enables   | construction   | include, but   |
|                  | them to be     | that enables   | are not        |
|                  | maintained in  | them to be     | limited to,    |
|                  | an appropriate | maintained in  | the following: |
|                  | sanitary       | an appropriate |                |
|                  | condition.     | clean          | \(i\)          |
|                  |                | condition.     | Equipment used |
|                  |                |                | to hold or     |
|                  |                |                | convey;        |
|                  |                |                |                |
|                  |                |                | \(ii\)         |
|                  |                |                | Equipment used |
|                  |                |                | to measure;    |
|                  |                |                |                |
|                  |                |                | \(iii\)        |
|                  |                |                | Equipment      |
|                  |                |                | using          |
|                  |                |                | compressed air |
|                  |                |                | or gas;        |
|                  |                |                |                |
|                  |                |                | iv\) Equipment |
|                  |                |                | used to carry  |
|                  |                |                | out processes  |
|                  |                |                | in closed      |
|                  |                |                | pipes and      |
|                  |                |                | vessels; and   |
|                  |                |                |                |
|                  |                |                | \(v\)          |
|                  |                |                | Equipment used |
|                  |                |                | in automatic,  |
|                  |                |                | mechanical, or |
|                  |                |                | electronic     |
|                  |                |                | systems.       |
+------------------+----------------+----------------+----------------+
| ##               | The design,    | \(2\) The      | \(2\) You must |
| § 211.65 Equipme | construction,  | design,        | use equipment  |
| nt construction. | and use of     | construction   | and utensils   |
|                  | equipment and  | and use of     | of appropriate |
| \(a\) Equipment  | utensils shall | equipment and  | design and     |
| shall be         | preclude the   | utensils shall | construction   |
| constructed so   | adulteration   | preclude the   | so that use    |
| that surfaces    | of food with   | adulteration   | will not       |
| that contact     | lubricants,    | of raw         | result in the  |
| components,      | fuel, metal    | materials,     | contamination  |
| in-process       | fragments,     | packaging      | of components, |
| materials, or    | contaminated   | materials,     | dietary        |
| drug products    | water, or any  | in-process     | ingredients,   |
| shall not be     | other          | materials or   | or dietary\    |
| reactive,        | contaminants.  | finished       | supplements    |
| additive, or     |                | product with   | with:          |
| absorptive so as |                | lubricants,    |                |
| to alter the     |                | fuel, metal    | \(i\)          |
| safety,          |                | fragments,     | Lubricants;    |
| identity,        |                | contaminated   |                |
| strength,        |                | water, or any  | \(ii\) Fuel;   |
| quality, or      |                | other          |                |
| purity of the    |                | contaminants.  | \(iii\)        |
| drug product     |                |                | Coolants;      |
| beyond the       |                |                |                |
| official or      |                |                | \(iv\) Metal   |
| other            |                |                | or glass       |
| established      |                |                | fragments;     |
| requirements.    |                |                |                |
|                  |                |                | \(v\) Filth or |
| \(b\) Any        |                |                | any other      |
| substances       |                |                | extraneous     |
| required for     |                |                | material;      |
| operation, such  |                |                |                |
| as lubricants or |                |                | \(vi\)         |
| coolants, shall  |                |                | Contaminated   |
| not come into    |                |                | water; or      |
| contact with     |                |                |                |
| components, drug |                |                | \(vii\) Any    |
| product          |                |                | other          |
| containers,      |                |                | contaminants.  |
| closures,        |                |                |                |
| in-process       |                |                |                |
| materials, or    |                |                |                |
| drug products so |                |                |                |
| as to alter the  |                |                |                |
| safety,          |                |                |                |
| identity,        |                |                |                |
| strength,        |                |                |                |
| quality, or      |                |                |                |
| purity of the    |                |                |                |
| drug product     |                |                |                |
| beyond the       |                |                |                |
| official or      |                |                |                |
| other            |                |                |                |
| established      |                |                |                |
| requirements.    |                |                |                |
+------------------+----------------+----------------+----------------+
|                  | All equipment  | \(3\) All      | \(3\) All      |
|                  | should be so   | equipment      | equipment and  |
|                  | installed and  | should be so   | utensils you   |
|                  | maintained as  | installed and  | use must be:   |
|                  | to facilitate  | maintained as  |                |
|                  | the cleaning   | to facilitate  | \(i\)          |
|                  | of the         | the cleaning   | Installed and  |
|                  | equipment and  | of the         | maintained to  |
|                  | of all         | equipment and  | facilitate     |
|                  | adjacent       | of all         | cleaning the   |
|                  | spaces.        | adjacent       | equipment,     |
|                  | Food-contact   | spaces.        | utensils, and  |
|                  | surfaces shall | Processing     | all adjacent   |
|                  | be             | equipment and  | spaces;        |
|                  | corro          | utensils shall |                |
|                  | sion-resistant | be             | \(ii\)         |
|                  | when in        | corro          | Corro          |
|                  | contact with   | sion-resistant | sion-resistant |
|                  | food. They     | when in        | if the         |
|                  | shall be made  | contact with   | equipment or   |
|                  | of nontoxic    | raw materials, | utensils       |
|                  | materials and  | in-process or  | contact        |
|                  | designed to    | finished       | components,    |
|                  | withstand the  | dietary        | dietary        |
|                  | environment of | product. They  | ingredients,   |
|                  | their intended | shall be made  | or dietary     |
|                  | use and the    | of nontoxic    | supplements;   |
|                  | action of      | materials and  |                |
|                  | food, and, if  | designed to    | \(iii\) Made   |
|                  | applicable,    | withstand the  | of nontoxic    |
|                  | cleaning       | environment of | materials;     |
|                  | compounds and  | their intended |                |
|                  | sanitizing     | use and the    | \(iv\)         |
|                  | agents.        | action of      | Designed and   |
|                  | Food-contact   | dietary        | constructed to |
|                  | surfaces shall | products, and, | withstand the  |
|                  | be maintained  | if applicable, | environment of |
|                  | to protect     | cleaning       | their intended |
|                  | food from      | compounds and  | use, the       |
|                  | being          | sanitizing     | action of      |
|                  | contaminated   | agents.        | components,    |
|                  | by any source, | Processing     | dietary        |
|                  | including      | equipment and  | ingredients,   |
|                  | unlawful       | utensils shall | or dietary     |
|                  | indirect food  | be maintained  | supplements,   |
|                  | additives.     | to protect     | and, if        |
|                  |                | dietary        | applicable,    |
|                  | \....(7)       | products from  | cleaning       |
|                  | Equipment,     | being          | compounds and  |
|                  | containers,    | adulterated by | sanitizing     |
|                  | and utensils   | any source.    | agents; and    |
|                  | used to        |                |                |
|                  | convey, hold,  | \(12\)         | \(v\)          |
|                  | or store raw   | Equipment,     | Maintained to  |
|                  | materials,     | containers,    | protect        |
|                  | wo             | and utensils   | components,    |
|                  | rk-in-process, | used to        | dietary        |
|                  | rework, or     | convey, hold,  | ingredients,   |
|                  | food shall be  | or store raw   | and dietary    |
|                  | constructed,   | materials,     | supplements    |
|                  | handled, and   | in-process     | from being     |
|                  | maintained     | material,      | contaminated   |
|                  | during         | rework, or     | by any source. |
|                  | manufacturing  | finished       |                |
|                  | or storage in  | product shall  |                |
|                  | a manner that  | be             |                |
|                  | protects       | constructed,   |                |
|                  | against        | handled, and   |                |
|                  | cont           | maintained     |                |
|                  | amination\.... | during         |                |
|                  |                | manufacturing  |                |
|                  |                | or storage in  |                |
|                  |                | a manner that  |                |
|                  |                | protects       |                |
|                  |                | against        |                |
|                  |                | contamination. |                |
+------------------+----------------+----------------+----------------+
|                  | \(b\) Seams on | \(4\) Seams on | \(4\)          |
|                  | food-contact   | utensils and   | Equipment and  |
|                  | surfaces shall | processing     | utensils you   |
|                  | be smoothly    | equipment      | use must have  |
|                  | bonded or      | shall be       | seams that are |
|                  | maintained so  | smoothly       | smoothly       |
|                  | as to minimize | bonded or      | bonded or      |
|                  | accumulation   | maintained so  | maintained to  |
|                  | of food        | as to minimize | minimize       |
|                  | particles,     | accumulation   | accumulation   |
|                  | dirt, and      | of product,    | of component,  |
|                  | organic matter | dirt, and      | dietary        |
|                  | and thus       | organic matter | ingredient, or |
|                  | minimize the   | and thus       | dietary        |
|                  | opportunity    | minimize the   | supplement     |
|                  | for growth of  | opportunity    | particles,     |
|                  | m              | for growth of  | dirt, filth,   |
|                  | icroorganisms. | m              | organic        |
|                  |                | icroorganisms. | material, or   |
|                  |                |                | any extraneous |
|                  |                |                | materials or   |
|                  |                |                | contaminants   |
|                  |                |                | to minimize    |
|                  |                |                | the            |
|                  |                |                | opportunity    |
|                  |                |                | for growth of  |
|                  |                |                | m              |
|                  |                |                | icroorganisms. |
+------------------+----------------+----------------+----------------+
|                  | \(c\)          | \(5\)          |                |
|                  | Equipment that | Equipment that |                |
|                  | is in the      | is in the      |                |
|                  | manufacturing  | manufacturing  |                |
|                  | or             | or product     |                |
|                  | food-handling  | handling area  |                |
|                  | area and that  | and that does  |                |
|                  | does not come  | not come into  |                |
|                  | into contact   | contact with a |                |
|                  | with food      | dietary        |                |
|                  | shall be so    | product shall  |                |
|                  | constructed    | be so          |                |
|                  | that it can be | constructed    |                |
|                  | kept in a      | that it can be |                |
|                  | clean          | kept in a      |                |
|                  | condition.     | clean          |                |
|                  |                | condition.     |                |
+------------------+----------------+----------------+----------------+
|                  | \(e\) Each     | \(7\) Each     | \(5\) Each     |
|                  | freezer and    | freezer and    | freezer and    |
|                  | cold storage   | cold storage   | cold storage   |
|                  | compartment    | compartment    | compartment    |
|                  | used to store  | used to store  | you use to     |
|                  | and hold food  | and hold a     | hold           |
|                  | capable of     | dietary        | components,    |
|                  | supporting     | product        | dietary        |
|                  | growth of      | capable of     | ingredients,   |
|                  | microorganisms | supporting     | or dietary     |
|                  | shall be       | growth of      | supplements:   |
|                  | fitted with an | microorganisms |                |
|                  | indicating     | shall be       | \(i\) Must be  |
|                  | thermometer,   | fitted with an | fitted with an |
|                  | tempera        | indicating     | indicating     |
|                  | ture-measuring | thermometer,   | thermometer,   |
|                  | device, or     | tempera        | tempera        |
|                  | tempera        | ture-measuring | ture-measuring |
|                  | ture-recording | device, or     | device, or     |
|                  | device so      | tempera        | tempera        |
|                  | installed as   | ture-recording | ture-recording |
|                  | to show the    | device so      | device that    |
|                  | temperature    | installed as   | shows the      |
|                  | accurately     | to show the    | temperature    |
|                  | within the     | temperature    | accurately     |
|                  | compartment,   | accurately     | within the     |
|                  | and should be  | within the     | compartment;   |
|                  | fitted with an | compartment,   | and            |
|                  | automatic      | and should be  |                |
|                  | control for    | fitted with an | \(ii\) Must    |
|                  | regulating     | automatic      | have an        |
|                  | temperature or | control for    | automatic      |
|                  | with an        | regulating     | device for     |
|                  | automatic      | temperature or | regulating     |
|                  | alarm system   | with an        | temperature or |
|                  | to indicate a  | automatic      | an automatic   |
|                  | significant    | alarm system   | alarm system   |
|                  | temperature    | to indicate a  | to indicate a  |
|                  | change in a    | significant    | significant    |
|                  | manual         | temperature    | temperature    |
|                  | operation.     | change in a    | change in a    |
|                  |                | manual         | manual         |
|                  |                | operation.     | operation.     |
+------------------+----------------+----------------+----------------+
|                  | \(f\)          | \(8\)          | \(6\)          |
|                  | Instruments    | Instruments    | Instruments or |
|                  | and controls   | and controls   | controls used  |
|                  | used for       | used in the    | in the         |
|                  | measuring,     | manufacture,   | manufacturing, |
|                  | regulating, or | processing,    | packaging, or  |
|                  | recording      | packing or     | holding of a   |
|                  | temperatures,  | holding        | dietary        |
|                  | pH, acidity,   | dietary        | ingredient or  |
|                  | water          | products,      | dietary        |
|                  | activity, or   | including      | supplement,    |
|                  | other          | instruments    | including but  |
|                  | conditions     | and controls   | not limited    |
|                  | that control   | used for       | to,            |
|                  | or prevent the | measuring,     | instruments or |
|                  | growth of      | regulating, or | controls you   |
|                  | undesirable    | recording      | use to         |
|                  | microorganisms | temperatures,  | measure,       |
|                  | in food shall  | pH, acidity,   | regulate, or   |
|                  | be accurate    | water          | record         |
|                  | and adequately | activity, or   | temperatures,  |
|                  | maintained,    | other          | hydrogen ion   |
|                  | and adequate   | conditions     | concentration  |
|                  | in number for  | that control   | (pH), water    |
|                  | their          | or prevent the | activity, or   |
|                  | designated     | growth of      | other          |
|                  | uses.          | undesirable    | conditions     |
|                  |                | microorganisms | that control   |
|                  |                | in such        | or prevent the |
|                  |                | products shall | growth of      |
|                  |                | be accurate    | microorganisms |
|                  |                | and adequately | or other       |
|                  |                | maintained,    | contamination  |
|                  |                | and adequate   | must be:       |
|                  |                | in number for  |                |
|                  |                | their          | \(i\) Accurate |
|                  |                | designated     | and precise;   |
|                  |                | uses.          |                |
|                  |                |                | \(ii\)         |
|                  |                |                | Adequately     |
|                  |                |                | maintained;    |
|                  |                |                | and            |
|                  |                |                |                |
|                  |                |                | \(iii\)        |
|                  |                |                | Adequate in    |
|                  |                |                | number for     |
|                  |                |                | their          |
|                  |                |                | designated     |
|                  |                |                | uses.          |
+------------------+----------------+----------------+----------------+
|                  | \(g\)          | \(9\)          | \(7\)          |
|                  | Compressed air | Compressed air | Compressed air |
|                  | or other gases | or other gases | or other gases |
|                  | mechanically   | mechanically   | you introduce  |
|                  | introduced     | introduced     | mechanically   |
|                  | into food or   | into a dietary | into or onto a |
|                  | used to clean  | product or     | component,     |
|                  | food-contact   | used to clean  | dietary        |
|                  | surfaces or    | equipment or   | ingredient,    |
|                  | equipment      | utensils shall | dietary        |
|                  | shall be       | be treated in  | supplement, or |
|                  | treated in     | such a way     | contact        |
|                  | such a way     | that dietary   | surface or     |
|                  | that food is   | ingredients or | that you use   |
|                  | not            | dietary        | to clean any   |
|                  | contaminated   | supplements    | contact        |
|                  | with unlawful  | are not        | surface must   |
|                  | indirect food  | adulterated.   | be treated in  |
|                  | additives.     |                | such a way     |
|                  |                |                | that the       |
|                  |                |                | component,     |
|                  |                |                | dietary        |
|                  |                |                | ingredient,    |
|                  |                |                | dietary        |
|                  |                |                | supplement, or |
|                  |                |                | contact        |
|                  |                |                | surface is not |
|                  |                |                | contaminated.  |
+------------------+----------------+----------------+----------------+
|                  |                |                | (b)(l) You     |
|                  |                |                | must calibrate |
|                  |                |                | instruments    |
|                  |                |                | and controls   |
|                  |                |                | you use in     |
|                  |                |                | manufacturing  |
|                  |                |                | or testing a   |
|                  |                |                | component,     |
|                  |                |                | dietary        |
|                  |                |                | ingredient, or |
|                  |                |                | dietary        |
|                  |                |                | supplement.    |
|                  |                |                |                |
|                  |                |                | \(2\) You must |
|                  |                |                | calibrate      |
|                  |                |                | before first   |
|                  |                |                | use; and       |
|                  |                |                |                |
|                  |                |                | \(i\) As       |
|                  |                |                | specified in   |
|                  |                |                | writing by the |
|                  |                |                | manufacturer   |
|                  |                |                | of the         |
|                  |                |                | instrument and |
|                  |                |                | control, or    |
|                  |                |                |                |
|                  |                |                | \(ii\) At      |
|                  |                |                | routine        |
|                  |                |                | intervals or   |
|                  |                |                | as otherwise   |
|                  |                |                | necessary to   |
|                  |                |                | ensure the     |
|                  |                |                | accuracy and   |
|                  |                |                | precision of   |
|                  |                |                | the instrument |
|                  |                |                | and control.   |
+------------------+----------------+----------------+----------------+
| **§ 211.160      |                |                | \(c\) You      |
| General          |                |                | must:          |
| requirements.**  |                |                |                |
|                  |                |                | \(1\)          |
| Laboratory       |                |                | Establish a    |
| controls shall   |                |                | written        |
| include:         |                |                | procedure for  |
|                  |                |                | calibrating    |
| \(4\) The        |                |                | instruments    |
| calibration of   |                |                | and controls   |
| instruments,     |                |                | you use in     |
| apparatus,       |                |                | manufacturing  |
| gauges, and      |                |                | or testing a   |
| recording        |                |                | component,     |
| devices at       |                |                | dietary        |
| suitable         |                |                | ingredient, or |
| intervals in     |                |                | dietary        |
| accordance with  |                |                | supplement and |
| an established   |                |                | document that  |
| written program  |                |                | the written    |
| containing       |                |                | procedure was  |
| specific         |                |                | followed each  |
| directions,      |                |                | time a         |
| schedules,       |                |                | calibration is |
| limits for       |                |                | performed, or  |
| accuracy and     |                |                |                |
| precision, and   |                |                | \(2\)          |
| provisions for   |                |                | Document, at   |
| remedial action  |                |                | the time of    |
| in the event     |                |                | performance    |
| accuracy and/or  |                |                | that the       |
| precision limits |                |                | instrument and |
| are not met.     |                |                | control        |
| Instruments,     |                |                | calibration    |
| apparatus,       |                |                | established in |
| gauges, and      |                |                | accordance     |
| recording        |                |                | with this      |
| devices not      |                |                | section was    |
| meeting          |                |                | performed.     |
| established      |                |                |                |
| specifications   |                |                |                |
| shall not be     |                |                |                |
| used.            |                |                |                |
+------------------+----------------+----------------+----------------+
|                  |                |                | \(d\) You must |
|                  |                |                | identify the   |
|                  |                |                | following for  |
|                  |                |                | calibrating    |
|                  |                |                | instruments    |
|                  |                |                | and controls   |
|                  |                |                | in any written |
|                  |                |                | procedure or   |
|                  |                |                | at the time of |
|                  |                |                | performance:   |
|                  |                |                |                |
|                  |                |                | \(1\) The      |
|                  |                |                | instrument or  |
|                  |                |                | control        |
|                  |                |                | calibrated;    |
|                  |                |                |                |
|                  |                |                | \(2\) The date |
|                  |                |                | of             |
|                  |                |                | calibration;   |
|                  |                |                |                |
|                  |                |                | \(3\) The      |
|                  |                |                | reference      |
|                  |                |                | standard used  |
|                  |                |                | including the  |
|                  |                |                | certification  |
|                  |                |                | of accuracy of |
|                  |                |                | the known      |
|                  |                |                | reference      |
|                  |                |                | standard and a |
|                  |                |                | history of     |
|                  |                |                | r              |
|                  |                |                | ecertification |
|                  |                |                | of accuracy;   |
|                  |                |                |                |
|                  |                |                | \(4\) The      |
|                  |                |                | calibration    |
|                  |                |                | method used    |
|                  |                |                | including      |
|                  |                |                | appropriate    |
|                  |                |                | limits for     |
|                  |                |                | accuracy and   |
|                  |                |                | precision of   |
|                  |                |                | instruments    |
|                  |                |                | and controls   |
|                  |                |                | when           |
|                  |                |                | calibrating;   |
|                  |                |                |                |
|                  |                |                | \(5\) The      |
|                  |                |                | calibration    |
|                  |                |                | reading or     |
|                  |                |                | readings       |
|                  |                |                | found; and     |
|                  |                |                |                |
|                  |                |                | \(6\) The      |
|                  |                |                | recalibration  |
|                  |                |                | method used if |
|                  |                |                | accuracy or    |
|                  |                |                | precision or   |
|                  |                |                | both accuracy  |
|                  |                |                | and precision  |
|                  |                |                | limits for     |
|                  |                |                | instruments    |
|                  |                |                | and controls   |
|                  |                |                | were not met;  |
|                  |                |                | and            |
|                  |                |                |                |
|                  |                |                | \(7\) The      |
|                  |                |                | initials of    |
|                  |                |                | the person who |
|                  |                |                | performed the  |
|                  |                |                | calibration.   |
+------------------+----------------+----------------+----------------+
|                  |                |                | \(d\) You must |
|                  |                |                | repair or      |
|                  |                |                | replace        |
|                  |                |                | instruments or |
|                  |                |                | controls that  |
|                  |                |                | cannot be      |
|                  |                |                | adjusted to    |
|                  |                |                | agree with the |
|                  |                |                | reference      |
|                  |                |                | standard.      |
+------------------+----------------+----------------+----------------+
| ## § 211.67 Equ  | **¶110.80(b)   | \(b\)          | (e)(1) You     |
| ipment cleaning  | Manufacturing  | Sanitation of  | must maintain, |
| and maintenance. | operations.**  | equipment and  | clean, and     |
|                  |                | utensils.      | sanitize as    |
| \(a\) Equipment  | \(1\)          |                | necessary, all |
| and utensils     | Equipment and  | \(9\)          | equipment,     |
| shall be         | utensils and   | Equipment and  | utensils, and  |
| cleaned,         | finished food  | utensils and   | any other      |
| maintained, and  | containers     | finished       | contact        |
| sanitized at     | shall be       | product        | surfaces that  |
| appropriate      | maintained in  | containers     | are used to    |
| intervals to     | an acceptable  | shall be       | manufacture,   |
| prevent          | condition      | maintained in  | package, or    |
| malfunctions or  | through        | an acceptable  | hold           |
| contamination    | appropriate    | condition      | components,    |
| that would alter | cleaning and   | through        | dietary        |
| the safety,      | sanitizing, as | appropriate    | ingredients,   |
| identity,        | necessary.     | cleaning and   | or dietary     |
| strength,        | Insofar as     | sanitizing, as | supplements.   |
| quality, or      | necessary,     | necessary.     | Equipment and  |
| purity of the    | equipment      | Insofar as     | utensils must  |
| drug product     | shall be taken | necessary,     | be taken apart |
| beyond the       | apart for      | equipment      | as necessary   |
| official or      | thorough       | shall be taken | for thorough   |
| other            | cleaning\....  | apart for      | maintenance,   |
| established      |                | thorough       | cleaning, and  |
| requirements.    | **¶110.35      | cleaning.      | sanitizing.    |
|                  | Sanitary       |                |                |
|                  | operations.**  | \(1\) Cleaning | \(2\) You must |
|                  |                | and sanitizing | ensure that    |
|                  | \(a\) General  | of utensils    | all contact    |
|                  | maintenance.   | and equipment  | surfaces used  |
|                  |                | shall be       | for            |
|                  | \....Cleaning  | conducted in a | manufacturing  |
|                  | and sanitizing | manner that    | or holding of  |
|                  | of utensils    | protects       | low-moisture   |
|                  | and equipment  | against        | components,    |
|                  | shall be       | adulteration   | dietary        |
|                  | conducted in a | of raw         | ingredients,   |
|                  | manner that    | materials,     | or dietary     |
|                  | protects       | in-process or  | supplements    |
|                  | against        | finished       | are in a dry   |
|                  | contamination  | dietary        | and sanitary   |
|                  | of food,       | product,       | condition at   |
|                  | food-contact   | processing     | the time of    |
|                  | surfaces, or   | equipment,     | use. When the  |
|                  | food-packaging | utensils or    | surfaces are   |
|                  | materials\.... | packaging      | wet-cleaned,   |
|                  |                | materials.     | they must be   |
|                  | \(d\)          |                | sanitized,     |
|                  | Sanitation of  | \(2\) All      | when           |
|                  | food-contact   | utensils and   | necessary, and |
|                  | surfaces. All  | processing     | thoroughly     |
|                  | food-contact   | equipment      | dried before   |
|                  | surfaces,      | shall be       | subsequent     |
|                  | including      | cleaned as     | use.           |
|                  | utensils and   | frequently as  |                |
|                  | food-contact   | necessary to   |                |
|                  | surfaces of    | protect        |                |
|                  | equipment,     | against        |                |
|                  | shall be       | product        |                |
|                  | cleaned as     | adulteration.  |                |
|                  | frequently as  |                |                |
|                  | necessary to   | \(3\) Utensils |                |
|                  | protect        | and processing |                |
|                  | against        | equipment used |                |
|                  | contamination  | for            |                |
|                  | of food.       | manufacturing  |                |
|                  |                | or holding of  |                |
|                  | \(1\)          | dry dietary    |                |
|                  | Food-contact   | products shall |                |
|                  | surfaces used  | be in a dry,   |                |
|                  | for            | sanitary       |                |
|                  | manufacturing  | condition at   |                |
|                  | or holding     | the time of    |                |
|                  | low-moisture   | use. When the  |                |
|                  | food shall be  | surfaces are   |                |
|                  | in a dry,      | wet-cleaned,   |                |
|                  | sanitary       | they shall,    |                |
|                  | condition at   | when           |                |
|                  | the time of    | necessary, be  |                |
|                  | use. When the  | sanitized and  |                |
|                  | surfaces are   | thoroughly     |                |
|                  | wet-cleaned,   | dried before   |                |
|                  | they shall,    | subsequent     |                |
|                  | when           | use.           |                |
|                  | necessary, be  |                |                |
|                  | sanitized and  |                |                |
|                  | thoroughly     |                |                |
|                  | dried before   |                |                |
|                  | subsequent     |                |                |
|                  | use.           |                |                |
+------------------+----------------+----------------+----------------+
|                  | \(2\) In wet   | \(4\) In wet   | \(3\) If you   |
|                  | processing,    | processing,    | use wet        |
|                  | when cleaning  | when cleaning  | processing     |
|                  | is necessary   | is necessary   | during         |
|                  | to protect     | to protect     | manufacturing, |
|                  | against the    | against the    | you must clean |
|                  | introduction   | introduction   | and sanitize   |
|                  | of             | of             | all contact    |
|                  | microorganisms | microorganisms | surfaces, as   |
|                  | into food, all | into a dietary | necessary, to  |
|                  | food-contact   | product, all   | protect        |
|                  | surfaces shall | utensils and   | against the    |
|                  | be cleaned and | processing     | introduction   |
|                  | sanitized      | equipment      | of             |
|                  | before use and | shall be       | microorganisms |
|                  | after any      | cleaned and    | into           |
|                  | interruption   | sanitized as   | components,    |
|                  | during which   | appropriate    | dietary        |
|                  | the            | before use and | ingredients,   |
|                  | food-contact   | after any      | or dietary     |
|                  | surfaces may   | interruption   | supplements.   |
|                  | have become    | during which   | When cleaning  |
|                  | contaminated.  | the utensils   | and sanitizing |
|                  | Where          | or processing  | is necessary,  |
|                  | equipment and  | equipment may  | you must clean |
|                  | utensils are   | have become    | and sanitize   |
|                  | used in a      | contaminated.  | all contact    |
|                  | continuous     | Where          | surfaces       |
|                  | production     | equipment and  | before use and |
|                  | operation. the | utensils are   | after any      |
|                  | utensils and   | used in a      | interruption   |
|                  | food-contact   | continuous     | during which   |
|                  | surfaces of    | production     | the contact    |
|                  | the equipment  | operation or   | surface may    |
|                  | shall be       | in             | have become    |
|                  | cleaned and    | back-to-back   | contaminated.  |
|                  | sanitized as   | operations     | If you use     |
|                  | necessary.     | involving      | contact        |
|                  |                | different      | surfaces in a  |
|                  |                | batches of the | continuous     |
|                  |                | same products, | production     |
|                  |                | the utensils   | operation or   |
|                  |                | and            | in             |
|                  |                | p              | back-to-back   |
|                  |                | roduct-contact | operations     |
|                  |                | surfaces of    | involving      |
|                  |                | the equipment  | different      |
|                  |                | shall be       | batches of the |
|                  |                | cleaned and    | same dietary   |
|                  |                | sanitized as   | ingredient or  |
|                  |                | appropriate.   | dietary        |
|                  |                |                | supplement,    |
|                  |                |                | you must clean |
|                  |                |                | and sanitize   |
|                  |                |                | the contact    |
|                  |                |                | surfaces as    |
|                  |                |                | necessary.     |
+------------------+----------------+----------------+----------------+
|                  | \(3\)          | \(5\)          | \(4\) You must |
|                  | No             | Non-p          | clean surfaces |
|                  | n-food-contact | roduct-contact | that do not    |
|                  | surfaces of    | surfaces of    | touch          |
|                  | equipment used | equipment      | components,    |
|                  | in the         | should be      | dietary        |
|                  | operation of   | cleaned as     | ingredients,   |
|                  | food plants    | frequently as  | or dietary     |
|                  | should be      | necessary to   | supplements as |
|                  | cleaned as     | protect        | frequently as  |
|                  | frequently as  | against        | necessary to   |
|                  | necessary to   | product        | protect        |
|                  | protect        | adulteration.  | against        |
|                  | against        |                | contaminating  |
|                  | contamination  |                | components,    |
|                  | of food.       |                | dietary        |
|                  |                |                | ingredients,   |
|                  |                |                | or dietary     |
|                  |                |                | supplements.   |
+------------------+----------------+----------------+----------------+
|                  | \(4\)          | \(6\)          | \(5\)          |
|                  | Single-service | Single-service | Single-service |
|                  | articles (such | articles (such | articles (such |
|                  | as utensils    | as utensils    | as utensils    |
|                  | intended for   | intended for   | intended for   |
|                  | one-time use,  | one-time use,  | one-time use,  |
|                  | paper cups,    | paper cups,    | paper cups,    |
|                  | and paper      | and paper      | and paper      |
|                  | towels) should | towels) should | towels) must   |
|                  | be stored in   | be stored in   | be:            |
|                  | appropriate    | appropriate    |                |
|                  | containers and | containers and | \(i\) Stored   |
|                  | shall be       | shall be       | in appropriate |
|                  | handled,       | handled,       | containers;    |
|                  | dispensed,     | dispensed,     | and            |
|                  | used, and      | used, and      |                |
|                  | disposed of in | disposed of in | \(ii\)         |
|                  | a manner that  | a manner that  | Handled,       |
|                  | protects       | protects       | dispensed,     |
|                  | against        | against        | used, and      |
|                  | contamination  | adulteration   | disposed of in |
|                  | of food or     | of dietary     | a manner that  |
|                  | food-contact   | products, and  | protects       |
|                  | surfaces.      | contamination  | against        |
|                  |                | of utensils    | contamination  |
|                  |                | and processing | of components, |
|                  |                | equipment.     | dietary        |
|                  |                |                | ingredients,   |
|                  |                |                | dietary        |
|                  |                |                | supplements,   |
|                  |                |                | or any contact |
|                  |                |                | surface.       |
+------------------+----------------+----------------+----------------+
|                  | \(5\)          | \(7\)          | \(6\) Cleaning |
|                  | Sanitizing     | Sanitizing     | compounds and  |
|                  | agents shall   | agents shall   | sanitizing     |
|                  | be adequate    | be adequate    | agents must be |
|                  | and safe under | and safe under | adequate for   |
|                  | conditions of  | conditions of  | intended use   |
|                  | use. Any       | use. Any       | and safe under |
|                  | facility,      | facility,      | condition of   |
|                  | procedure, or  | procedure, or  | use;           |
|                  | machine is     | machine is     |                |
|                  | acceptable for | acceptable for |                |
|                  | cleaning and   | cleaning and   |                |
|                  | sanitizing     | sanitizing     |                |
|                  | equipment and  | equipment and  |                |
|                  | utensils if it | utensils if it |                |
|                  | is established | is established |                |
|                  | that the       | that the       |                |
|                  | facility,      | facility,      |                |
|                  | procedure, or  | procedure, or  |                |
|                  | machine will   | machine will   |                |
|                  | routinely      | routinely      |                |
|                  | render         | render         |                |
|                  | equipment and  | equipment and  |                |
|                  | utensils clean | utensils clean |                |
|                  | and provide    | and provide    |                |
|                  | adequate       | adequate       |                |
|                  | cleaning and   | cleaning and   |                |
|                  | sanitizing     | sanitizing     |                |
|                  | treatment.     | treatment.     |                |
+------------------+----------------+----------------+----------------+
|                  | \(e\) Storage  | \(8\) Cleaned  | \(7\) You must |
|                  | and handling   | and sanitized  | store cleaned  |
|                  | of cleaned     | portable       | and sanitized  |
|                  | portable       | equipment with | portable       |
|                  | equipment and  | p              | equipment and  |
|                  | utensils.      | roduct-contact | utensils that  |
|                  | Cleaned and    | surfaces and   | have contact   |
|                  | sanitized      | utensils       | surfaces in a  |
|                  | portable       | should be      | location and   |
|                  | equipment with | stored in a    | manner that    |
|                  | food-contact   | location and   | protects them  |
|                  | surfaces and   | manner that    | from           |
|                  | utensils       | protects       | contamination. |
|                  | should be      | p              |                |
|                  | stored in a    | roduct-contact |                |
|                  | location and   | surfaces from  |                |
|                  | manner that    | contamination. |                |
|                  | protects       |                |                |
|                  | food-contact   |                |                |
|                  | surfaces from  |                |                |
|                  | contamination. |                |                |
+------------------+----------------+----------------+----------------+
| \(b\) Written    |                | \(10\) Written |                |
| procedures shall |                | procedures     |                |
| be established   |                | shall be       |                |
| and followed for |                | established    |                |
| cleaning and     |                | and followed   |                |
| maintenance of   |                | for cleaning   |                |
| equipment,       |                | and            |                |
| including        |                | maintaining    |                |
| utensils, used   |                | equipment and  |                |
| in the           |                | utensils used  |                |
| manufacture,     |                | in the         |                |
| processing,      |                | manufacture of |                |
| packing, or      |                | dietary        |                |
| holding of a     |                | products.      |                |
| drug product.    |                |                |                |
| These procedures |                |                |                |
| shall include,   |                |                |                |
| but are not      |                |                |                |
| necessarily      |                |                |                |
| limited to, the  |                |                |                |
| following:       |                |                |                |
|                  |                |                |                |
| \(1\) Assignment |                |                |                |
| of               |                |                |                |
| responsibility   |                |                |                |
| for cleaning and |                |                |                |
| maintaining      |                |                |                |
| equipment;       |                |                |                |
|                  |                |                |                |
| \(2\)            |                |                |                |
| Maintenance and  |                |                |                |
| cleaning         |                |                |                |
| schedules,       |                |                |                |
| including, where |                |                |                |
| appropriate,     |                |                |                |
| sanitizing       |                |                |                |
| schedules;       |                |                |                |
|                  |                |                |                |
| \(3\) A          |                |                |                |
| description in   |                |                |                |
| sufficient       |                |                |                |
| detail of the    |                |                |                |
| methods,         |                |                |                |
| equipment, and   |                |                |                |
| materials used   |                |                |                |
| in cleaning and  |                |                |                |
| maintenance      |                |                |                |
| operations, and  |                |                |                |
| the methods of   |                |                |                |
| disassembling    |                |                |                |
| and reassembling |                |                |                |
| equipment as     |                |                |                |
| necessary to     |                |                |                |
| assure proper    |                |                |                |
| cleaning and     |                |                |                |
| maintenance;     |                |                |                |
|                  |                |                |                |
| \(4\) Removal or |                |                |                |
| obliteration of  |                |                |                |
| previous batch   |                |                |                |
| identification;  |                |                |                |
|                  |                |                |                |
| \(5\) Protection |                |                |                |
| of clean         |                |                |                |
| equipment from   |                |                |                |
| contamination    |                |                |                |
| prior to use;    |                |                |                |
|                  |                |                |                |
| \(6\) Inspection |                |                |                |
| of equipment for |                |                |                |
| cleanliness      |                |                |                |
| immediately      |                |                |                |
| before use.      |                |                |                |
|                  |                |                |                |
| \(c\) Records    |                |                |                |
| shall be kept of |                |                |                |
| maintenance,     |                |                |                |
| cleaning,        |                |                |                |
| sanitizing, and  |                |                |                |
| inspection as    |                |                |                |
| specified in     |                |                |                |
| §§211.180        |                |                |                |
| and211.182.      |                |                |                |
+------------------+----------------+----------------+----------------+
|                  |                |                | \(f\) You must |
|                  |                |                | keep           |
|                  |                |                | calibration    |
|                  |                |                | records as     |
|                  |                |                | required by    |
|                  |                |                | this section   |
|                  |                |                | in accordance  |
|                  |                |                | with §         |
|                  |                |                | 111.125.       |
+------------------+----------------+----------------+----------------+
| ## § 211.68      |                |                | **§ 111.30     |
| Automatic, mecha |                |                | [What          |
| nical, and elect |                |                | requirements   |
| ronic equipment. |                |                | apply to       |
|                  |                |                | automatic,     |
| \(a\) Automatic, |                |                | mechanical, or |
| mechanical, or   |                |                | electronic     |
| electronic       |                |                | equipment?     |
| equipment or     |                |                | ]              |
| other types of   |                |                | {.underline}** |
| equipment,       |                |                |                |
| including        |                |                | \(a\) When you |
| computers, or    |                |                | use automatic, |
| related systems  |                |                | mechanical, or |
| that will        |                |                | electronic     |
| perform a        |                |                | equipment to   |
| function         |                |                | manufacture,   |
| satisfactorily,  |                |                | package,       |
| may be used in   |                |                | label, and     |
| the manufacture, |                |                | hold a dietary |
| processing,      |                |                | ingredient or  |
| packing, and     |                |                | dietary        |
| holding of a     |                |                | supplement,    |
| drug product.    |                |                | you must:      |
|                  |                |                |                |
|                  |                |                | \(1\) Design   |
|                  |                |                | or select      |
|                  |                |                | equipment to   |
|                  |                |                | ensure that    |
|                  |                |                | dietary        |
|                  |                |                | ingredient or  |
|                  |                |                | dietary        |
|                  |                |                | supplement     |
|                  |                |                | specifications |
|                  |                |                | are            |
|                  |                |                | consistently   |
|                  |                |                | achieved and   |
|                  |                |                |                |
|                  |                |                | \(2\)          |
|                  |                |                | Determine the  |
|                  |                |                | suitability of |
|                  |                |                | your equipment |
|                  |                |                | by ensuring    |
|                  |                |                | that your      |
|                  |                |                | equipment is   |
|                  |                |                | capable of     |
|                  |                |                | operating      |
|                  |                |                | satisfactorily |
|                  |                |                | within the     |
|                  |                |                | operating      |
|                  |                |                | limits         |
|                  |                |                | required by    |
|                  |                |                | the process.   |
+------------------+----------------+----------------+----------------+
| If such          |                |                | \(b\) For any  |
| equipment is so  |                |                | automatic,     |
| used, it shall   |                |                | mechanical, or |
| be routinely     |                |                | electronic     |
| calibrated,      |                |                | equipment you  |
| inspected, or    |                |                | use, you must: |
| checked          |                |                |                |
| according to a   |                |                | \(1\)          |
| written program  |                |                | Routinely      |
| designed to      |                |                | calibrate,     |
| assure proper    |                |                | inspect, or    |
| performance....  |                |                | check to       |
|                  |                |                | ensure proper  |
| \(b\)            |                |                | performance.   |
| Appropriate      |                |                | Your quality   |
| controls shall   |                |                | control unit   |
| be exercised     |                |                | must approve   |
| over computer or |                |                | these          |
| related systems  |                |                | calibrations,  |
| to assure that   |                |                | inspections,   |
| changes in       |                |                | or checks;     |
| master           |                |                |                |
| production and   |                |                | \(2\) Make and |
| control records  |                |                | keep written   |
| or other records |                |                | records of     |
| are instituted   |                |                | equipment      |
| only by          |                |                | calibrations,  |
| authorized       |                |                | inspections,   |
| personnel. Input |                |                | or checks;     |
| to and output    |                |                |                |
| from the         |                |                | \(3\)          |
| computer or      |                |                | Establish and  |
| related system   |                |                | use            |
| of formulas or   |                |                | appropriate    |
| other records or |                |                | controls, to   |
| data shall be    |                |                | ensure that    |
| checked for      |                |                | your quality   |
| accuracy. The    |                |                | control unit   |
| degree and       |                |                | approves       |
| frequency of     |                |                | changes in the |
| input/output     |                |                | master         |
| verification     |                |                | manufacturing  |
| shall be based   |                |                | record, batch  |
| on the           |                |                | control        |
| complexity and   |                |                | records,       |
| reliability of   |                |                | packaging      |
| the computer or  |                |                | operations and |
| related system.  |                |                | label          |
| A backup file of |                |                | operations, or |
| data entered     |                |                | changes to     |
| into the         |                |                | other          |
| computer or      |                |                | operations     |
| related system   |                |                | related to the |
| shall be         |                |                | equipment that |
| maintained       |                |                | you use and    |
| except where     |                |                | that only      |
| certain data,    |                |                | authorized     |
| such as          |                |                | personnel      |
| calculations     |                |                | institute the  |
| performed in     |                |                | changes;       |
| connection with  |                |                |                |
| laboratory       |                |                | \(4\)          |
| analysis, are    |                |                | Establish and  |
| eliminated by    |                |                | use            |
| computerization  |                |                | appropriate    |
| or other         |                |                | controls to    |
| automated        |                |                | ensure that    |
| processes. In    |                |                | the equipment  |
| such instances a |                |                | functions in   |
| written record   |                |                | accordance     |
| of the program   |                |                | with its       |
| shall be         |                |                | intended use.  |
| maintained along |                |                | These controls |
| with appropriate |                |                | must be        |
| validation data. |                |                | approved by    |
| Hard copy or     |                |                | your quality   |
| alternative      |                |                | control unit;  |
| systems, such as |                |                | and            |
| duplicates,      |                |                |                |
| tapes, or        |                |                | \(5\) Make and |
| microfilm,       |                |                | keep backup    |
| designed to      |                |                | file(s) of     |
| assure that      |                |                | software       |
| backup data are  |                |                | programs and   |
| exact and        |                |                | of data        |
| complete and     |                |                | entered into   |
| that it is       |                |                | your computer  |
| secure from      |                |                | system. Your   |
| alteration,      |                |                | backup file    |
| inadvertent      |                |                | (e.g., a hard  |
| erasures, or     |                |                | copy of data   |
| loss shall be    |                |                | you have       |
| maintained.      |                |                | entered,       |
|                  |                |                | diskettes,     |
|                  |                |                | tapes,         |
|                  |                |                | microfilm, or  |
|                  |                |                | compact disks) |
|                  |                |                | must be an     |
|                  |                |                | exact and      |
|                  |                |                | complete       |
|                  |                |                | record of the  |
|                  |                |                | data you       |
|                  |                |                | entered. You   |
|                  |                |                | must keep your |
|                  |                |                | backup         |
|                  |                |                | software       |
|                  |                |                | programs and   |
|                  |                |                | data secure    |
|                  |                |                | from           |
|                  |                |                | alterations,   |
|                  |                |                | inadvertent    |
|                  |                |                | erasures, or   |
|                  |                |                | equipment      |
|                  |                |                | loss.          |
+------------------+----------------+----------------+----------------+
| \(a\)            |                |                | \(c\) You must |
| \...Written      |                |                | keep           |
| records of those |                |                | automatic,     |
| calibration      |                |                | mechanical, or |
| checks and       |                |                | electronic     |
| inspections      |                |                | equipment      |
| shall be         |                |                | records        |
| maintained.      |                |                | required by    |
|                  |                |                | this section   |
|                  |                |                | in accordance  |
|                  |                |                | with §         |
|                  |                |                | 111.125.       |
+------------------+----------------+----------------+----------------+
| ## §             |                |                |                |
|  211.72 Filters. |                |                |                |
|                  |                |                |                |
| Filters for      |                |                |                |
| liquid           |                |                |                |
| filtration used  |                |                |                |
| in the           |                |                |                |
| manufacture,     |                |                |                |
| processing, or   |                |                |                |
| packing of       |                |                |                |
| injectable drug  |                |                |                |
| products         |                |                |                |
| intended for     |                |                |                |
| human use shall  |                |                |                |
| not release      |                |                |                |
| fibers into such |                |                |                |
| products.        |                |                |                |
| Fiber-releasing  |                |                |                |
| filters may not  |                |                |                |
| be used in the   |                |                |                |
| manufacture,     |                |                |                |
| processing, or   |                |                |                |
| packing of these |                |                |                |
| injectable drug  |                |                |                |
| products unless  |                |                |                |
| it is not        |                |                |                |
| possible to      |                |                |                |
| manufacture such |                |                |                |
| drug products    |                |                |                |
| without the use  |                |                |                |
| of such filters. |                |                |                |
| If use of a      |                |                |                |
| fiber-releasing  |                |                |                |
| filter is        |                |                |                |
| necessary, an    |                |                |                |
| additional       |                |                |                |
| non              |                |                |                |
| -fiber-releasing |                |                |                |
| filter of 0.22   |                |                |                |
| micron maximum   |                |                |                |
| mean porosity    |                |                |                |
| (0.45 micron if  |                |                |                |
| the              |                |                |                |
| manufacturing    |                |                |                |
| conditions so    |                |                |                |
| dictate) shall   |                |                |                |
| subsequently be  |                |                |                |
| used to reduce   |                |                |                |
| the content of   |                |                |                |
| particles in the |                |                |                |
| injectable drug  |                |                |                |
| product. Use of  |                |                |                |
| an               |                |                |                |
| asb              |                |                |                |
| estos-containing |                |                |                |
| filter, with or  |                |                |                |
| without          |                |                |                |
| subsequent use   |                |                |                |
| of a specific    |                |                |                |
| non              |                |                |                |
| -fiber-releasing |                |                |                |
| filter, is       |                |                |                |
| permissible only |                |                |                |
| upon submission  |                |                |                |
| of proof to the  |                |                |                |
| appropriate      |                |                |                |
| bureau of the    |                |                |                |
| Food and Drug    |                |                |                |
| Administration   |                |                |                |
| that use of a    |                |                |                |
| non              |                |                |                |
| -fiber-releasing |                |                |                |
| filter will, or  |                |                |                |
| is likely to,    |                |                |                |
| compromise the   |                |                |                |
| safety or        |                |                |                |
| effectiveness of |                |                |                |
| the injectable   |                |                |                |
| drug product.    |                |                |                |
+------------------+----------------+----------------+----------------+
|                  |                |                | **Subpart      |
|                  |                |                | E\--Production |
|                  |                |                | and Process    |
|                  |                |                | Controls**     |
|                  |                |                |                |
|                  |                |                | **§ 111.35     |
|                  |                |                | [What          |
|                  |                |                | production and |
|                  |                |                | process        |
|                  |                |                | controls must  |
|                  |                |                | you            |
|                  |                |                | use?]          |
|                  |                |                | {.underline}** |
|                  |                |                |                |
|                  |                |                | \(a\) You must |
|                  |                |                | implement a    |
|                  |                |                | system of      |
|                  |                |                | production and |
|                  |                |                | process        |
|                  |                |                | controls that  |
|                  |                |                | covers all     |
|                  |                |                | stages of      |
|                  |                |                | manufacturing, |
|                  |                |                | packaging,     |
|                  |                |                | labeling, and  |
|                  |                |                | holding of the |
|                  |                |                | dietary        |
|                  |                |                | ingredients    |
|                  |                |                | and dietary    |
|                  |                |                | supplements.   |
|                  |                |                |                |
|                  |                |                | \(b\) Your     |
|                  |                |                | production and |
|                  |                |                | in-process     |
|                  |                |                | control system |
|                  |                |                | must be        |
|                  |                |                | designed to    |
|                  |                |                | ensure that    |
|                  |                |                | the dietary    |
|                  |                |                | ingredient or  |
|                  |                |                | dietary        |
|                  |                |                | supplement is  |
|                  |                |                | manufactured,  |
|                  |                |                | packaged, and  |
|                  |                |                | held in a      |
|                  |                |                | manner that    |
|                  |                |                | will prevent   |
|                  |                |                | adulteration   |
|                  |                |                | of the dietary |
|                  |                |                | ingredient or  |
|                  |                |                | dietary        |
|                  |                |                | supplement.    |
|                  |                |                | The production |
|                  |                |                | and in-process |
|                  |                |                | control system |
|                  |                |                | must include   |
|                  |                |                | all            |
|                  |                |                | requirements   |
|                  |                |                | of this        |
|                  |                |                | subpart and    |
|                  |                |                | must be        |
|                  |                |                | reviewed and   |
|                  |                |                | approved by    |
|                  |                |                | the quality    |
|                  |                |                | control unit.  |
+------------------+----------------+----------------+----------------+
|                  |                |                | \(c\) You must |
|                  |                |                | use a quality  |
|                  |                |                | control unit   |
|                  |                |                | in your        |
|                  |                |                | manufacturing, |
|                  |                |                | packaging, and |
|                  |                |                | label          |
|                  |                |                | operations for |
|                  |                |                | producing the  |
|                  |                |                | dietary        |
|                  |                |                | ingredient or  |
|                  |                |                | dietary        |
|                  |                |                | supplement to  |
|                  |                |                | ensure that    |
|                  |                |                | these          |
|                  |                |                | operations are |
|                  |                |                | performed in a |
|                  |                |                | manner that    |
|                  |                |                | prevents       |
|                  |                |                | adulteration   |
|                  |                |                | and ensures    |
|                  |                |                | that the       |
|                  |                |                | dietary        |
|                  |                |                | ingredient or  |
|                  |                |                | dietary        |
|                  |                |                | supplement     |
|                  |                |                | meets          |
|                  |                |                | specifications |
|                  |                |                | for identity,  |
|                  |                |                | purity,        |
|                  |                |                | quality,       |
|                  |                |                | strength, and  |
|                  |                |                | composition.   |
+------------------+----------------+----------------+----------------+
|                  |                |                | \(d\) Any      |
|                  |                |                | substance,     |
|                  |                |                | other than a   |
|                  |                |                | \"dietary      |
|                  |                |                | ingredient\"   |
|                  |                |                | within the     |
|                  |                |                | meaning of     |
|                  |                |                | section        |
|                  |                |                | 201(ff) of the |
|                  |                |                | Federal Food,  |
|                  |                |                | Drug; and      |
|                  |                |                | Cosmetic Act   |
|                  |                |                | (the act), the |
|                  |                |                | intended use   |
|                  |                |                | of which       |
|                  |                |                | results or may |
|                  |                |                | reasonably be  |
|                  |                |                | expected to    |
|                  |                |                | result,        |
|                  |                |                | directly or    |
|                  |                |                | indirectly, in |
|                  |                |                | its becoming a |
|                  |                |                | component or   |
|                  |                |                | otherwise      |
|                  |                |                | affecting the  |
|                  |                |                | c              |
|                  |                |                | haracteristics |
|                  |                |                | of the dietary |
|                  |                |                | ingredient or  |
|                  |                |                | dietary        |
|                  |                |                | supplement     |
|                  |                |                | must be:       |
|                  |                |                |                |
|                  |                |                | \(1\)          |
|                  |                |                | Authorized for |
|                  |                |                | use as a food  |
|                  |                |                | additive under |
|                  |                |                | section 409 of |
|                  |                |                | the act; or    |
|                  |                |                |                |
|                  |                |                | \(2\)          |
|                  |                |                | Authorized by  |
|                  |                |                | a prior        |
|                  |                |                | sanction       |
|                  |                |                | consistent     |
|                  |                |                | with §         |
|                  |                |                | 170.3(l) of    |
|                  |                |                | this chapter;  |
|                  |                |                | or             |
|                  |                |                |                |
|                  |                |                | \(3\) If used  |
|                  |                |                | as a color     |
|                  |                |                | additive,      |
|                  |                |                | subject to a   |
|                  |                |                | listing that,  |
|                  |                |                | by the terms   |
|                  |                |                | of that        |
|                  |                |                | listing,       |
|                  |                |                | includes the   |
|                  |                |                | use in a       |
|                  |                |                | dietary        |
|                  |                |                | supplement; or |
|                  |                |                |                |
|                  |                |                | \(4\)          |
|                  |                |                | Generally      |
|                  |                |                | recognized as  |
|                  |                |                | safe (GRAS)    |
|                  |                |                | for use in a   |
|                  |                |                | dietary        |
|                  |                |                | ingredient or  |
|                  |                |                | dietary        |
|                  |                |                | supplement.    |
|                  |                |                | Any claim that |
|                  |                |                | a substance is |
|                  |                |                | GRAS, other    |
|                  |                |                | than a dietary |
|                  |                |                | ingredient     |
|                  |                |                | within the     |
|                  |                |                | meaning of     |
|                  |                |                | section        |
|                  |                |                | 201(ff) of the |
|                  |                |                | act, must be   |
|                  |                |                | supported by a |
|                  |                |                | citation to    |
|                  |                |                | the agency\'s  |
|                  |                |                | regulations or |
|                  |                |                | by an          |
|                  |                |                | explanation    |
|                  |                |                | for why there  |
|                  |                |                | is general     |
|                  |                |                | recognition of |
|                  |                |                | safety of the  |
|                  |                |                | use of the     |
|                  |                |                | substance in a |
|                  |                |                | dietary        |
|                  |                |                | ingredient or  |
|                  |                |                | dietary        |
|                  |                |                | supplement;    |
|                  |                |                | and            |
|                  |                |                |                |
|                  |                |                | \(5\) Must     |
|                  |                |                | comply with    |
|                  |                |                | all other      |
|                  |                |                | applicable     |
|                  |                |                | statutory and  |
|                  |                |                | regulatory     |
|                  |                |                | requirements   |
|                  |                |                | under the act  |
+------------------+----------------+----------------+----------------+
| ##               |                |                | \(e\) You must |
|  § 211.160 Gener |                |                | establish a    |
| al requirements. |                |                | specification  |
|                  |                |                | for any point, |
| \(b\) Laboratory |                |                | step, or stage |
| controls shall   |                |                | in the         |
| include the      |                |                | manufacturing  |
| establishment of |                |                | process where  |
| scientifically   |                |                | control is     |
| sound and        |                |                | necessary to   |
| appropriate      |                |                | prevent        |
| specifications,  |                |                | adulteration.  |
| standards,       |                |                | Specifications |
| sampling plans,  |                |                | must be        |
| and test         |                |                | established    |
| procedures       |                |                | for:           |
| designed to      |                |                |                |
| assure that      |                |                | \(1\) The      |
| components, drug |                |                | identity,      |
| product          |                |                | purity,        |
| containers,      |                |                | quality,       |
| closures,        |                |                | strength, and  |
| in-process       |                |                | composition of |
| materials,       |                |                | components,    |
| labeling, and    |                |                | dietary        |
| drug products    |                |                | ingredients,   |
| conform to       |                |                | or dietary     |
| appropriate      |                |                | supplements    |
| standards of     |                |                | that you       |
| identity,        |                |                | receive;       |
| strength,        |                |                |                |
| quality, and     |                |                | \(2\) The      |
| purity.          |                |                | in-process     |
| Laboratory       |                |                | controls in    |
| controls shall   |                |                | the master     |
| include:         |                |                | manufacturing  |
|                  |                |                | record where   |
| \(1\)            |                |                | control is     |
| Determination of |                |                | necessary to   |
| conformance to   |                |                | ensure the     |
| appropriate      |                |                | identity,      |
| written          |                |                | purity,        |
| specifications   |                |                | quality,       |
| for the          |                |                | strength, and  |
| acceptance of    |                |                | composition of |
| each lot within  |                |                | dietary        |
| each shipment of |                |                | ingredients or |
| components, drug |                |                | dietary        |
| product          |                |                | supplements;   |
| containers,      |                |                |                |
| closures, and    |                |                | \(3\) The      |
| labeling used in |                |                | identity,      |
| the manufacture, |                |                | purity,        |
| processing,      |                |                | quality,       |
| packing, or      |                |                | strength, and  |
| holding of drug  |                |                | composition of |
| products. The    |                |                | the dietary    |
| specifications   |                |                | ingredient or  |
| shall include a  |                |                | dietary        |
| description of   |                |                | supplement     |
| the sampling and |                |                | that you       |
| testing          |                |                | manufacture;   |
| procedures used. |                |                | and            |
| Samples shall be |                |                |                |
| representative   |                |                |                |
| and adequately   |                |                |                |
| identified. Such |                |                |                |
| procedures shall |                |                |                |
| also require     |                |                |                |
| appropriate      |                |                |                |
| retesting of any |                |                |                |
| component, drug  |                |                |                |
| product          |                |                |                |
| container, or    |                |                |                |
| closure that is  |                |                |                |
| subject to       |                |                |                |
| deterioration.   |                |                |                |
|                  |                |                |                |
| \(2\)            |                |                |                |
| Determination of |                |                |                |
| conformance to   |                |                |                |
| written          |                |                |                |
| specifications   |                |                |                |
| and a            |                |                |                |
| description of   |                |                |                |
| sampling and     |                |                |                |
| testing          |                |                |                |
| procedures for   |                |                |                |
| in-process       |                |                |                |
| materials. Such  |                |                |                |
| samples shall be |                |                |                |
| representative   |                |                |                |
| and properly     |                |                |                |
| identified.      |                |                |                |
|                  |                |                |                |
| \(3\)            |                |                |                |
| Determination of |                |                |                |
| conformance to   |                |                |                |
| written          |                |                |                |
| descriptions of  |                |                |                |
| sampling         |                |                |                |
| procedures and   |                |                |                |
| appropriate      |                |                |                |
| specifications   |                |                |                |
| for drug         |                |                |                |
| products. Such   |                |                |                |
| samples shall be |                |                |                |
| representative   |                |                |                |
| and properly     |                |                |                |
| identified.      |                |                |                |
+------------------+----------------+----------------+----------------+
| #                |                |                | \(4\) The      |
| # § 211.94 Drug  |                |                | dietary        |
| product containe |                |                | ingredient or  |
| rs and closures. |                |                | dietary        |
|                  |                |                | supplement     |
| \(a\) Drug       |                |                | labels and the |
| product          |                |                | packaging that |
| containers and   |                |                | may come in    |
| closures shall   |                |                | contact with   |
| not be reactive, |                |                | dietary        |
| additive, or     |                |                | ingredients    |
| absorptive so as |                |                | and dietary    |
| to alter the     |                |                | supplements.   |
| safety,          |                |                | The packaging  |
| identity,        |                |                | must be safe   |
| strength,        |                |                | and suitable   |
| quality, or      |                |                | for its        |
| purity of the    |                |                | intended use   |
| drug beyond the  |                |                | and comply     |
| official or      |                |                | with all other |
| established      |                |                | applicable     |
| requirements.    |                |                | statutory and  |
|                  |                |                | regulatory     |
| \(b\) Container  |                |                | requirements   |
| closure systems  |                |                | under the act  |
| shall provide    |                |                | and must not   |
| adequate         |                |                | be reactive or |
| protection       |                |                | absorptive so  |
| against          |                |                | as to affect   |
| foreseeable      |                |                | the safety of  |
| external factors |                |                | the dietary    |
| in storage and   |                |                | ingredient and |
| use that can     |                |                | dietary        |
| cause            |                |                | supplement.    |
| deterioration or |                |                |                |
| contamination of |                |                |                |
| the drug         |                |                |                |
| product.         |                |                |                |
|                  |                |                |                |
| \(c\) Drug       |                |                |                |
| product          |                |                |                |
| containers and   |                |                |                |
| closures shall   |                |                |                |
| be clean and,    |                |                |                |
| where indicated  |                |                |                |
| by the nature of |                |                |                |
| the drug,        |                |                |                |
| sterilized and   |                |                |                |
| processed to     |                |                |                |
| remove pyrogenic |                |                |                |
| properties to    |                |                |                |
| assure that they |                |                |                |
| are suitable for |                |                |                |
| their intended   |                |                |                |
| use.             |                |                |                |
|                  |                |                |                |
| \(d\) Standards  |                |                |                |
| or               |                |                |                |
| specifications,  |                |                |                |
| methods of       |                |                |                |
| testing, and,    |                |                |                |
| where indicated, |                |                |                |
| methods of       |                |                |                |
| cleaning,        |                |                |                |
| sterilizing, and |                |                |                |
| processing to    |                |                |                |
| remove pyrogenic |                |                |                |
| properties shall |                |                |                |
| be written and   |                |                |                |
| followed for     |                |                |                |
| drug product     |                |                |                |
| containers and   |                |                |                |
| closures.        |                |                |                |
+------------------+----------------+----------------+----------------+
| ## § 211.110     |                |                | \(f\) You must |
|  Sampling and te |                |                | monitor the    |
| sting of in-proc |                |                | in-process     |
| ess materials an |                |                | control        |
| d drug products. |                |                | points, steps, |
|                  |                |                | or stages to   |
| \(a\) To assure  |                |                | ensure that    |
| batch uniformity |                |                | specifications |
| and integrity of |                |                | established    |
| drug products,   |                |                | under          |
| written          |                |                | paragraph (e)  |
| procedures shall |                |                | of this        |
| be established   |                |                | section are    |
| and followed     |                |                | met and to     |
| that describe    |                |                | detect any     |
| the in-process   |                |                | unanticipated  |
| controls, and    |                |                | occurrence     |
| tests, or        |                |                | that may       |
| examinations to  |                |                | result in      |
| be conducted on  |                |                | adulteration;  |
| appropriate      |                |                |                |
| samples of       |                |                |                |
| in-process       |                |                |                |
| materials of     |                |                |                |
| each batch. Such |                |                |                |
| control          |                |                |                |
| procedures shall |                |                |                |
| be established   |                |                |                |
| to monitor the   |                |                |                |
| output and to    |                |                |                |
| validate the     |                |                |                |
| performance of   |                |                |                |
| those            |                |                |                |
| manufacturing    |                |                |                |
| processes that   |                |                |                |
| may be           |                |                |                |
| responsible for  |                |                |                |
| causing          |                |                |                |
| variability in   |                |                |                |
| the              |                |                |                |
| characteristics  |                |                |                |
| of in-process    |                |                |                |
| material and the |                |                |                |
| drug product.    |                |                |                |
| Such control     |                |                |                |
| procedures shall |                |                |                |
| include, but are |                |                |                |
| not limited to,  |                |                |                |
| the following,   |                |                |                |
| where            |                |                |                |
| appropriate:     |                |                |                |
|                  |                |                |                |
| \(1\) Tablet or  |                |                |                |
| capsule weight   |                |                |                |
| variation;       |                |                |                |
|                  |                |                |                |
| \(2\)            |                |                |                |
| Disintegration   |                |                |                |
| time;            |                |                |                |
|                  |                |                |                |
| \(3\) Adequacy   |                |                |                |
| of mixing to     |                |                |                |
| assure           |                |                |                |
| uniformity and   |                |                |                |
| homogeneity;     |                |                |                |
|                  |                |                |                |
| \(4\)            |                |                |                |
| Dissolution time |                |                |                |
| and rate;        |                |                |                |
|                  |                |                |                |
| \(5\) Clarity,   |                |                |                |
| completeness, or |                |                |                |
| pH of solutions. |                |                |                |
|                  |                |                |                |
| \(b\) Valid      |                |                |                |
| in-process       |                |                |                |
| specifications   |                |                |                |
| for such         |                |                |                |
| characteristics  |                |                |                |
| shall be         |                |                |                |
| consistent with  |                |                |                |
| drug product     |                |                |                |
| final            |                |                |                |
| specifications   |                |                |                |
| and shall be     |                |                |                |
| derived from     |                |                |                |
| previous         |                |                |                |
| acceptable       |                |                |                |
| process average  |                |                |                |
| and process      |                |                |                |
| variability      |                |                |                |
| estimates where  |                |                |                |
| possible and     |                |                |                |
| determined by    |                |                |                |
| the application  |                |                |                |
| of suitable      |                |                |                |
| statistical      |                |                |                |
| procedures where |                |                |                |
| appropriate.     |                |                |                |
| Examination and  |                |                |                |
| testing of       |                |                |                |
| samples shall    |                |                |                |
| assure that the  |                |                |                |
| drug product and |                |                |                |
| in-process       |                |                |                |
| material conform |                |                |                |
| to               |                |                |                |
| specifications.  |                |                |                |
|                  |                |                |                |
| \(c\) In-process |                |                |                |
| materials shall  |                |                |                |
| be tested for    |                |                |                |
| identity,        |                |                |                |
| strength,        |                |                |                |
| quality, and     |                |                |                |
| purity as        |                |                |                |
| appropriate, and |                |                |                |
| approved or      |                |                |                |
| rejected by the  |                |                |                |
| quality control  |                |                |                |
| unit, during the |                |                |                |
| production       |                |                |                |
| process, e.g.,   |                |                |                |
| at commencement  |                |                |                |
| or completion of |                |                |                |
| significant      |                |                |                |
| phases or after  |                |                |                |
| storage for long |                |                |                |
| periods.         |                |                |                |
|                  |                |                |                |
| \(d\) Rejected   |                |                |                |
| in-process       |                |                |                |
| materials shall  |                |                |                |
| be identified    |                |                |                |
| and controlled   |                |                |                |
| under a          |                |                |                |
| quarantine       |                |                |                |
| system designed  |                |                |                |
| to prevent their |                |                |                |
| use in           |                |                |                |
| manufacturing or |                |                |                |
| processing       |                |                |                |
| operations for   |                |                |                |
| which they are   |                |                |                |
| unsuitable.      |                |                |                |
+------------------+----------------+----------------+----------------+
| **§ 211.84       |                | \(7\) (iv)     | \(g\) You must |
| Testing and      |                | Each lot of    | ensure,        |
| approval or      |                | raw material   | through        |
| rejection of     |                | shall undergo  | testing or     |
| components, drug |                | at least one   | examination,   |
| product          |                | test by the    | that each      |
| containers, and  |                | manufacturer   | specification  |
| closures.**      |                | to verify its  | that you       |
|                  |                | identity. Such | established    |
| \(d\) Samples    |                | tests may      | under          |
| shall be         |                | include any    | paragraph (e)  |
| examined and     |                | appropriate    | of this        |
| tested as        |                | test with      | section is     |
| follows:         |                | sufficient     | met. Specific  |
|                  |                | specificity to | testing        |
| \(1\) At least   |                | determine      | requirements   |
| one test shall   |                | identity,      | are as         |
| be conducted to  |                | including      | follows:       |
| verify the       |                | chemical and   |                |
| identity of each |                | laboratory     | \(1\) You must |
| component of a   |                | tests, gross   | test each      |
| drug product.    |                | organoleptic   | finished batch |
| Specific         |                | analysis,      | of the dietary |
| identity tests,  |                | microscopic    | ingredient or  |
| if they exist,   |                | i              | dietary        |
| shall be used.   |                | dentification, | supplement     |
|                  |                | or analysis of | produced       |
| \(2\) Each       |                | constituent    | before         |
| component shall  |                | markers.       | releasing for  |
| be tested for    |                |                | distribution   |
| conformity with  |                | \(11\) Written | to determine   |
| all appropriate  |                | procedures     | whether        |
| written          |                | shall be       | established    |
| specifications   |                | established    | specifications |
| for purity,      |                | and followed   | for identity,  |
| strength, and    |                | that describe  | purity,        |
| quality. In lieu |                | appropriate    | quality,       |
| of such testing  |                | tests, and/or  | strength, and  |
| by the           |                | examinations   | composition    |
| manufacturer, a  |                | to be          | are met        |
| report of        |                | conducted that | provided that  |
| analysis may be  |                | may be         | there are      |
| accepted from    |                | necessary to   | scientifically |
| the supplier of  |                | assure the     | valid          |
| a component,     |                | purity,        | analytical     |
| provided that at |                | composition    | methods        |
| least one        |                | and quality of | available to   |
| specific         |                | the finished   | conduct such   |
| identity test is |                | product.       | testing.       |
| conducted on     |                |                |                |
| such component   |                |                | \(2\) For any  |
| by the           |                |                | specification  |
| manufacturer,    |                |                | for identity,  |
| and provided     |                |                | purity,        |
| that the         |                |                | quality,       |
| manufacturer     |                |                | strength, or   |
| establishes the  |                |                | composition    |
| reliability of   |                |                | for which you  |
| the supplier\'s  |                |                | document       |
| analyses through |                |                | cannot be      |
| appropriate      |                |                | tested on the  |
| validation of    |                |                | finished batch |
| the supplier\'s  |                |                | of a dietary   |
| test results at  |                |                | ingredient or  |
| appropriate      |                |                | dietary        |
| intervals.       |                |                | supplement,    |
|                  |                |                | because there  |
| \(4\) When       |                |                | is no          |
| appropriate,     |                |                | scientifically |
| components shall |                |                | valid          |
| be               |                |                | analytical     |
| microscopically  |                |                | method         |
| examined.        |                |                | available for  |
|                  |                |                | such testing,  |
| ##               |                |                | then you must: |
|  § 211.165 Testi |                |                |                |
| ng and release f |                |                | \(i\) Perform  |
| or distribution. |                |                | testing on     |
|                  |                |                | each shipment  |
| \(a\) For each   |                |                | lot of         |
| batch of drug    |                |                | components,    |
| product, there   |                |                | dietary        |
| shall be         |                |                | ingredients or |
| appropriate      |                |                | dietary        |
| laboratory       |                |                | supplements    |
| determination of |                |                | received to    |
| satisfactory     |                |                | determine      |
| conformance to   |                |                | whether such   |
| final            |                |                | specification  |
| specifications   |                |                | is met; and    |
| for the drug     |                |                |                |
| product,         |                |                | \(ii\) Perform |
| including the    |                |                | testing        |
| identity and     |                |                | in-process in  |
| strength of each |                |                | accordance     |
| active           |                |                | with the       |
| ingredient,      |                |                | master         |
| prior to         |                |                | manufacturing  |
| release. Where   |                |                | record where   |
| sterility and/or |                |                | control is     |
| pyrogen testing  |                |                | necessary to   |
| are conducted on |                |                | ensure the     |
| specific batches |                |                | identity,      |
| of shortlived    |                |                | purity,        |
| radio            |                |                | quality,       |
| pharmaceuticals, |                |                | strength, and  |
| such batches may |                |                | composition of |
| be released      |                |                | dietary        |
| prior to         |                |                | ingredients or |
| completion of    |                |                | dietary        |
| sterility and/or |                |                | supplements;   |
| pyrogen testing, |                |                | and            |
| provided such    |                |                |                |
| testing is       |                |                | \(3\) Your     |
| completed as     |                |                | quality        |
| soon as          |                |                | control unit   |
| possible.        |                |                | must determine |
|                  |                |                | when finished  |
| \(b\) There      |                |                | batch testing  |
| shall be         |                |                | cannot be      |
| appropriate      |                |                | completed for  |
| laboratory       |                |                | any            |
| testing, as      |                |                | specification  |
| necessary, of    |                |                | on the         |
| each batch of    |                |                | identity,      |
| drug product     |                |                | purity,        |
| required to be   |                |                | quality,       |
| free of          |                |                | strength, and  |
| objectionable    |                |                | composition of |
| microorganisms.  |                |                | dietary        |
|                  |                |                | ingredients or |
| \(c\) Any        |                |                | dietary        |
| sampling and     |                |                | supplements.   |
| testing plans    |                |                |                |
| shall be         |                |                |                |
| described in     |                |                |                |
| written          |                |                |                |
| procedures that  |                |                |                |
| shall include    |                |                |                |
| the method of    |                |                |                |
| sampling and the |                |                |                |
| number of units  |                |                |                |
| per batch to be  |                |                |                |
| tested; such     |                |                |                |
| written          |                |                |                |
| procedure shall  |                |                |                |
| be followed.     |                |                |                |
|                  |                |                |                |
| \(d\) Acceptance |                |                |                |
| criteria for the |                |                |                |
| sampling and     |                |                |                |
| testing          |                |                |                |
| conducted by the |                |                |                |
| quality control  |                |                |                |
| unit shall be    |                |                |                |
| adequate to      |                |                |                |
| assure that      |                |                |                |
| batches of drug  |                |                |                |
| products meet    |                |                |                |
| each appropriate |                |                |                |
| specification    |                |                |                |
| and appropriate  |                |                |                |
| statistical      |                |                |                |
| quality control  |                |                |                |
| criteria as a    |                |                |                |
| condition for    |                |                |                |
| their approval   |                |                |                |
| and release. The |                |                |                |
| statistical      |                |                |                |
| quality control  |                |                |                |
| criteria shall   |                |                |                |
| include          |                |                |                |
| appropriate      |                |                |                |
| acceptance       |                |                |                |
| levels and/or    |                |                |                |
| appropriate      |                |                |                |
| rejection        |                |                |                |
| levels.          |                |                |                |
+------------------+----------------+----------------+----------------+
| > \(e\) The      |                |                | \(h\) You must |
| > accuracy,      |                |                | use an         |
| > sensitivity,   |                |                | appropriate    |
| > specificity,   |                |                | test or        |
| > and            |                |                | examination to |
| >                |                |                | determine      |
|  reproducibility |                |                | whether your   |
| > of test        |                |                | specifications |
| > methods        |                |                | are met. An    |
| > employed by    |                |                | appropriate    |
| > the firm shall |                |                | test is one    |
| > be established |                |                | that is a      |
| > and            |                |                | scientifically |
| > documented.    |                |                | valid          |
| > Such           |                |                | analytical     |
| > validation and |                |                | method.        |
| > documentation  |                |                |                |
| > may be         |                |                |                |
| > accomplished   |                |                |                |
| > in accordance  |                |                |                |
| > with           |                |                |                |
| >                |                |                |                |
|  §211.194(a)(2). |                |                |                |
+------------------+----------------+----------------+----------------+
|                  |                |                | \(i\) You      |
|                  |                |                | must:          |
|                  |                |                |                |
|                  |                |                | \(1\)          |
|                  |                |                | Establish      |
|                  |                |                | corrective     |
|                  |                |                | action plans   |
|                  |                |                | for use when   |
|                  |                |                | an established |
|                  |                |                | specification  |
|                  |                |                | is not met;    |
|                  |                |                |                |
|                  |                |                | \(2\) Review   |
|                  |                |                | the results of |
|                  |                |                | the monitoring |
|                  |                |                | required by    |
|                  |                |                | this section   |
|                  |                |                | and conduct a  |
|                  |                |                | material       |
|                  |                |                | review of any  |
|                  |                |                | component,     |
|                  |                |                | dietary        |
|                  |                |                | ingredient,    |
|                  |                |                | dietary        |
|                  |                |                | supplement,    |
|                  |                |                | packaging or   |
|                  |                |                | label for      |
|                  |                |                | which you      |
|                  |                |                | establish a    |
|                  |                |                | specification  |
|                  |                |                | that is not    |
|                  |                |                | met, or any    |
|                  |                |                | unanticipated  |
|                  |                |                | occurrence     |
|                  |                |                | that           |
|                  |                |                | adulterates or |
|                  |                |                | could result   |
|                  |                |                | in             |
|                  |                |                | adulteration   |
|                  |                |                | of the         |
|                  |                |                | component,     |
|                  |                |                | dietary        |
|                  |                |                | ingredient,    |
|                  |                |                | dietary        |
|                  |                |                | supplement,    |
|                  |                |                | packaging, or  |
|                  |                |                | label; and     |
|                  |                |                |                |
|                  |                |                | \(3\) Make a   |
|                  |                |                | material       |
|                  |                |                | disposition    |
|                  |                |                | decision for   |
|                  |                |                | any component, |
|                  |                |                | dietary        |
|                  |                |                | ingredient,    |
|                  |                |                | dietary        |
|                  |                |                | supplement,    |
|                  |                |                | packaging, or  |
|                  |                |                | label:         |
|                  |                |                |                |
|                  |                |                | \(i\) If a     |
|                  |                |                | component,     |
|                  |                |                | dietary        |
|                  |                |                | ingredient,    |
|                  |                |                | dietary        |
|                  |                |                | supplement,    |
|                  |                |                | packaging, or  |
|                  |                |                | label fails to |
|                  |                |                | meet           |
|                  |                |                | s              |
|                  |                |                | pecifications; |
|                  |                |                |                |
|                  |                |                | \(ii\) If any  |
|                  |                |                | step           |
|                  |                |                | established in |
|                  |                |                | the master     |
|                  |                |                | manufacturing  |
|                  |                |                | record is not  |
|                  |                |                | completed;     |
|                  |                |                |                |
|                  |                |                | \(iii\) If     |
|                  |                |                | there is any   |
|                  |                |                | unanticipated  |
|                  |                |                | occurrence     |
|                  |                |                | during the     |
|                  |                |                | manufacturing  |
|                  |                |                | operations     |
|                  |                |                | that           |
|                  |                |                | adulterates or |
|                  |                |                | may lead to    |
|                  |                |                | adulteration   |
|                  |                |                | of the         |
|                  |                |                | component,     |
|                  |                |                | dietary        |
|                  |                |                | ingredient,    |
|                  |                |                | dietary        |
|                  |                |                | supplement,    |
|                  |                |                | packaging, or  |
|                  |                |                | label;         |
|                  |                |                |                |
|                  |                |                | \(iv\) If      |
|                  |                |                | calibration of |
|                  |                |                | an instrument, |
|                  |                |                | or control     |
|                  |                |                | suggests a     |
|                  |                |                | problem that   |
|                  |                |                | may have       |
|                  |                |                | caused batches |
|                  |                |                | of, a dietary  |
|                  |                |                | ingredient or  |
|                  |                |                | dietary        |
|                  |                |                | supplement to  |
|                  |                |                | become         |
|                  |                |                | adulterated;   |
|                  |                |                | or             |
|                  |                |                |                |
|                  |                |                | \(v\) If a     |
|                  |                |                | dietary        |
|                  |                |                | ingredient or  |
|                  |                |                | dietary        |
|                  |                |                | supplement is  |
|                  |                |                | returned.      |
+------------------+----------------+----------------+----------------+
| \(f\) Drug       | **¶110.80      | \(3\) All      | \(4\) For any  |
| products failing | Processes and  | product that   | deviation, or  |
| to meet          | controls.**    | has become     | unanticipated  |
| established      |                | contaminated   | occurrence     |
| standards or     | All food that  | to the extent  | which resulted |
| specifications   | has become     | that it is     | in or could    |
| and any other    | contaminated   | adulterated    | lead to        |
| relevant quality | to the extent  | within the     | adulteration   |
| control criteria | that it is     | meaning of the | of the         |
| shall be         | adulterated    | act shall be   | component,     |
| rejected.        | within the     | rejected, or   | dietary        |
| Reprocessing may | meaning of the | if             | ingredient,    |
| be performed.    | act shall be   | permissible,   | dietary        |
| Prior to         | rejected, or   | treated or     | supplement,    |
| acceptance and   | if             | processed to   | packaging, or  |
| use, reprocessed | permissible,   | eliminate the  | label          |
| material must    | treated or     | contamination. |                |
| meet appropriate | processed to   |                | \(i\) You must |
| standards,       | eliminate the  |                | reject the     |
| specifications,  | contamination. |                | component,     |
| and any other    |                |                | dietary        |
| relevant         |                |                | ingredient,    |
| critieria.       |                |                | dietary        |
|                  |                |                | supplement,    |
| **§ 211.84       |                |                | packaging, or  |
| Testing and      |                |                | label unless   |
| approval or      |                |                | the quality    |
| rejection of     |                |                | control unit   |
| components, drug |                |                | determines     |
| product          |                |                | that           |
| containers, and  |                |                | in-process     |
| closures.**      |                |                | adjustments    |
|                  |                |                | are possible   |
| \(e\) Any lot of |                |                | to correct the |
| components, drug |                |                | deviation or   |
| product          |                |                | occurrence;    |
| containers, or   |                |                |                |
| closures that    |                |                | \(ii\) You     |
| meets the        |                |                | must not       |
| appropriate      |                |                | reprocess a    |
| written          |                |                | rejected       |
| specifications   |                |                | component,     |
| of identity,     |                |                | dietary        |
| strength,        |                |                | ingredient, or |
| quality, and     |                |                | dietary        |
| purity and       |                |                | supplement     |
| related tests    |                |                | unless         |
| under paragraph  |                |                | approved by    |
| (d) of this      |                |                | the quality    |
| section may be   |                |                | control unit;  |
| approved and     |                |                | and            |
| released for     |                |                |                |
| use. Any lot of  |                |                | \(iii\) You    |
| such material    |                |                | must not       |
| that does not    |                |                | reprocess any  |
| meet such        |                |                | component,     |
| specifications   |                |                | dietary        |
| shall be         |                |                | ingredient or  |
| rejected         |                |                | dietary        |
|                  |                |                | supplement if  |
|                  |                |                | it is rejected |
|                  |                |                | because of     |
|                  |                |                | contamination  |
|                  |                |                | with           |
|                  |                |                | microorganisms |
|                  |                |                | or other       |
|                  |                |                | contaminants,  |
|                  |                |                | such as heavy  |
|                  |                |                | metals;        |
+------------------+----------------+----------------+----------------+
|                  |                |                | \(5\) Have     |
|                  |                |                | your quality   |
|                  |                |                | control unit   |
|                  |                |                | review and     |
|                  |                |                | approve any    |
|                  |                |                | material       |
|                  |                |                | review and     |
|                  |                |                | disposition    |
|                  |                |                | decision       |
|                  |                |                | described in   |
|                  |                |                | paragraphs (i) |
|                  |                |                | (2) and (i)    |
|                  |                |                | (3) of this    |
|                  |                |                | section.       |
+------------------+----------------+----------------+----------------+
|                  |                |                | \(j\) The      |
|                  |                |                | person who     |
|                  |                |                | conducts the   |
|                  |                |                | material       |
|                  |                |                | review and     |
|                  |                |                | makes the      |
|                  |                |                | disposition    |
|                  |                |                | decision must, |
|                  |                |                | at the time of |
|                  |                |                | performance,   |
|                  |                |                | document every |
|                  |                |                | material       |
|                  |                |                | review and     |
|                  |                |                | disposition    |
|                  |                |                | decision in    |
|                  |                |                | paragraph (i)  |
|                  |                |                | of this        |
|                  |                |                | section. The   |
|                  |                |                | documentation  |
|                  |                |                | must be        |
|                  |                |                | included in    |
|                  |                |                | the            |
|                  |                |                | appropriate    |
|                  |                |                | batch          |
|                  |                |                | production     |
|                  |                |                | record and     |
|                  |                |                | must:          |
|                  |                |                |                |
|                  |                |                | \(1\) Identify |
|                  |                |                | the specific   |
|                  |                |                | deviation from |
|                  |                |                | the            |
|                  |                |                | specification  |
|                  |                |                | or the         |
|                  |                |                | unanticipated  |
|                  |                |                | occurrence;    |
|                  |                |                |                |
|                  |                |                | \(2\) Describe |
|                  |                |                | your           |
|                  |                |                | investigation  |
|                  |                |                | into the cause |
|                  |                |                | of the         |
|                  |                |                | deviation from |
|                  |                |                | the            |
|                  |                |                | specification  |
|                  |                |                | or the         |
|                  |                |                | unanticipated  |
|                  |                |                | occurrence;    |
|                  |                |                |                |
|                  |                |                | \(3\) Evaluate |
|                  |                |                | whether or not |
|                  |                |                | the deviation  |
|                  |                |                | from the       |
|                  |                |                | specification  |
|                  |                |                | or             |
|                  |                |                | unanticipated  |
|                  |                |                | occurrence has |
|                  |                |                | resulted in or |
|                  |                |                | could lead to  |
|                  |                |                | adulteration;  |
|                  |                |                |                |
|                  |                |                | \(4\) Identify |
|                  |                |                | the action(s)  |
|                  |                |                | taken to       |
|                  |                |                | correct and    |
|                  |                |                | prevent a      |
|                  |                |                | recurrence of  |
|                  |                |                | the deviation  |
|                  |                |                | or the         |
|                  |                |                | unanticipated  |
|                  |                |                | occurrence;    |
|                  |                |                | and            |
|                  |                |                |                |
|                  |                |                | \(5\) Discuss  |
|                  |                |                | what you did   |
|                  |                |                | with the       |
|                  |                |                | component,     |
|                  |                |                | dietary        |
|                  |                |                | ingredient,    |
|                  |                |                | dietary        |
|                  |                |                | supplement,    |
|                  |                |                | packaging, or  |
|                  |                |                | label.         |
+------------------+----------------+----------------+----------------+
| **§ 211.84       | \(4\) Raw      | \(7\) Raw      | \(k\) You must |
| Testing and      | materials,     | material       | test or        |
| approval or      | other          | samples shall  | examine        |
| rejection of     | ingredients,   | be examined    | components,    |
| components, drug | and rework     | and tested as  | dietary        |
| product          | susceptible to | follows:       | ingredients,   |
| containers, and  | contamination  |                | and dietary    |
| closures.**      | with pests,    | \(i\) Each lot | supplements    |
|                  | undesirable    | of raw         | for those      |
| \(d\) Samples    | m              | material,      | types of       |
| shall be         | icroorganisms, | in-process     | contamination  |
| examined and     | or extraneous  | material and   | that may       |
| tested as        | material shall | rework that is | adulterate or  |
| follows:         | comply with    | liable to      | may lead to    |
|                  | applicable     | adulteration   | adulteration.  |
| \(6\) Each lot   | Food and Drug  | with filth,    | You must use   |
| of a component,  | Administration | insect         | an appropriate |
| drug product     | regulations,   | infestation or | scientifically |
| container, or    | guidelines,    | other visually | valid method   |
| closure that is  | and defect     | evident        | for the test   |
| liable to        | action levels  | extraneous     | or             |
| microbiological  | for natural or | material shall | examination.   |
| contamination    | unavoidable    | be examined    | The types of   |
| that is          | defects if a   | against        | contamination  |
| objectionable in | manufacturer   | established    | include, but   |
| view of its      | wishes to use  | specifications | are not        |
| intended use     | the materials  | for such       | limited to,    |
| shall be         | in             | adulteration,  | the following: |
| subjected to     | manufacturing  | and shall      |                |
| microbiological  | food.          | comply with    | \(1\) Filth,   |
| tests before     | Compliance     | any applicable | insects, or    |
| use.             | with this      | Food and Drug  | other          |
|                  | requirement    | Administration | extraneous     |
|                  | may be         | regulations,   | material;      |
|                  | verified by    | and            |                |
|                  | any effective  | guidelines. In | \(2\)          |
|                  | means,         | lieu of such   | M              |
|                  | including      | examination by | icroorganisms; |
|                  | purchasing the | the            | and            |
|                  | materials      | manufacturer,  |                |
|                  | under a        | a guarantee or | \(3\) Toxic    |
|                  | supplier\'s    | certification  | substances.    |
|                  | guarantee or   | of examination |                |
|                  | certification, | may be         | \(l\) Tests in |
|                  | or examination | accepted from  | accordance     |
|                  | of these       | the supplier   | with this      |
|                  | materials for  | of a component | section must   |
|                  | contamination. | provided that  | include at     |
|                  |                | the            | least, one of  |
|                  |                | manufacturer   | the following: |
|                  |                | establishes    |                |
|                  |                | the            | \(1\) Gross    |
|                  |                | reliability of | organoleptic   |
|                  |                | the            | analysis;      |
|                  |                | supplier\'s    |                |
|                  |                | examination.   | \(2\)          |
|                  |                |                | Microscopic    |
|                  |                | \(ii\) Each    | analysis;      |
|                  |                | lot of a raw   |                |
|                  |                | material that  | \(3\) Chemical |
|                  |                | is liable to   | analysis; or   |
|                  |                | m              |                |
|                  |                | icrobiological | \(4\) Other    |
|                  |                | contamination  | appropriate    |
|                  |                | that is        | test.          |
|                  |                | objectionable  |                |
|                  |                | in view of its |                |
|                  |                | intended use   |                |
|                  |                | shall be       |                |
|                  |                | subjected to   |                |
|                  |                | m              |                |
|                  |                | icrobiological |                |
|                  |                | tests before   |                |
|                  |                | use. Raw       |                |
|                  |                | materials      |                |
|                  |                | shall either   |                |
|                  |                | not contain    |                |
|                  |                | levels of      |                |
|                  |                | microorganisms |                |
|                  |                | that may       |                |
|                  |                | produce food   |                |
|                  |                | poisoning or   |                |
|                  |                | other disease  |                |
|                  |                | in humans, or  |                |
|                  |                | they shall be  |                |
|                  |                | otherwise      |                |
|                  |                | treated during |                |
|                  |                | manufacturing  |                |
|                  |                | operations so  |                |
|                  |                | that they no   |                |
|                  |                | longer contain |                |
|                  |                | levels that    |                |
|                  |                | would cause    |                |
|                  |                | the product to |                |
|                  |                | be adulterated |                |
|                  |                | within the     |                |
|                  |                | meaning of the |                |
|                  |                | act. In lieu   |                |
|                  |                | of such        |                |
|                  |                | testing by the |                |
|                  |                | manufacturer,  |                |
|                  |                | a guarantee or |                |
|                  |                | certification  |                |
|                  |                | of analysis    |                |
|                  |                | may be         |                |
|                  |                | accepted from  |                |
|                  |                | the supplier   |                |
|                  |                | of a component |                |
|                  |                | provided that  |                |
|                  |                | the            |                |
|                  |                | manufacturer   |                |
|                  |                | establishes    |                |
|                  |                | the            |                |
|                  |                | reliability of |                |
|                  |                | the            |                |
|                  |                | supplier\'s    |                |
|                  |                | analyses.      |                |
+------------------+----------------+----------------+----------------+
|                  | \(3\) Raw      | \(iii\) Raw    |                |
|                  | materials and  | materials and  |                |
|                  | other          | other          |                |
|                  | ingredients    | ingredients    |                |
|                  | susceptible to | susceptible to |                |
|                  | contamination  | adulteration   |                |
|                  | with aflatoxin | with aflatoxin |                |
|                  | or other       | or other       |                |
|                  | natural toxins | natural toxins |                |
|                  | shall comply   | shall comply   |                |
|                  | with current   | with current   |                |
|                  | Food and Drug  | Food and Drug  |                |
|                  | Administration | Administration |                |
|                  | regulations,   | regulations,   |                |
|                  | guidelines,    | guidelines,    |                |
|                  | and action     | and action     |                |
|                  | levels for     | levels for     |                |
|                  | poisonous or   | poisonous or   |                |
|                  | deleterious    | deleterious    |                |
|                  | substances     | substances     |                |
|                  | before these   | before these   |                |
|                  | materials or   | materials or   |                |
|                  | ingredients    | ingredients    |                |
|                  | are            | are            |                |
|                  | incorporated   | incorporated   |                |
|                  | into finished  | into a         |                |
|                  | food.          | finished       |                |
|                  | Compliance     | dietary        |                |
|                  | with this      | ingredient or  |                |
|                  | requirement    | dietary        |                |
|                  | may be         | supplement.    |                |
|                  | accomplished   | Compliance     |                |
|                  | by purchasing  | with this      |                |
|                  | raw materials  | requirement    |                |
|                  | and other      | may be         |                |
|                  | ingredients    | accomplished   |                |
|                  | under a        | by analyzing   |                |
|                  | supplier\'s    | these          |                |
|                  | guarantee or   | materials and  |                |
|                  | certification, | ingredients    |                |
|                  | or may be      | for aflatoxins |                |
|                  | verified by    | and other      |                |
|                  | analyzing      | natural toxins |                |
|                  | these          | or, in lieu of |                |
|                  | materials and  | such testing   |                |
|                  | ingredients    | by the         |                |
|                  | for aflatoxins | manufacturer,  |                |
|                  | and other      | a guarantee or |                |
|                  | natural        | certification  |                |
|                  | toxins.        | of analysis    |                |
|                  |                | may be         |                |
|                  |                | accepted from  |                |
|                  |                | the supplier   |                |
|                  |                | of a component |                |
|                  |                | provided that  |                |
|                  |                | the            |                |
|                  |                | manufacturer   |                |
|                  |                | establishes    |                |
|                  |                | the            |                |
|                  |                | reliability of |                |
|                  |                | the            |                |
|                  |                | supplier\'s    |                |
|                  |                | analyses.      |                |
+------------------+----------------+----------------+----------------+
|                  |                | \(b\)          | \(m\) You must |
|                  |                | Laboratory     | record results |
|                  |                | records.       | of all testing |
|                  |                |                | and            |
|                  |                | Laboratory     | examinations   |
|                  |                | records shall  | performed in   |
|                  |                | be maintained  | accordance     |
|                  |                | and shall      | with this      |
|                  |                | include        | section. If a  |
|                  |                | complete data  | test or        |
|                  |                | derived from   | examination is |
|                  |                | all specified  | performed on a |
|                  |                | tests.         | batch          |
|                  |                |                | production you |
|                  |                |                | must record    |
|                  |                |                | the test or    |
|                  |                |                | examination    |
|                  |                |                | result in the  |
|                  |                |                | batch          |
|                  |                |                | production     |
|                  |                |                | record in      |
|                  |                |                | accordance     |
|                  |                |                | with §         |
|                  |                |                | 111.50(c)      |
|                  |                |                | (10). Your     |
|                  |                |                | records must   |
|                  |                |                | document       |
|                  |                |                | whether the    |
|                  |                |                | testing and    |
|                  |                |                | examination    |
|                  |                |                | demonstrates   |
|                  |                |                | that           |
|                  |                |                | specifications |
|                  |                |                | are met.       |
+------------------+----------------+----------------+----------------+
| ##               |                |                | \(n\) For any  |
|                  |                |                | specification  |
|                  |                |                | that is not    |
|                  |                |                | met, you must  |
|                  |                |                | conduct a      |
|                  |                |                | material       |
|                  |                |                | review and     |
|                  |                |                | disposition    |
|                  |                |                | decision under |
|                  |                |                | paragraph (i)  |
|                  |                |                | of this        |
|                  |                |                | section.       |
+------------------+----------------+----------------+----------------+
| **§ 211.194      |                |                | \(o\) You must |
| Laboratory       |                |                | make and       |
| records.**       |                |                | retain         |
|                  |                |                | records, in    |
| \(a\) Laboratory |                |                | accordance     |
| records shall    |                |                | with §         |
| include complete |                |                | 111.125, to    |
| data derived     |                |                | ensure that    |
| from all tests   |                |                | you follow the |
| necessary to     |                |                | requirements   |
| assure           |                |                | of this        |
| compliance with  |                |                | section. The   |
| established      |                |                | records must   |
| specifications   |                |                | include, but   |
| and standards,   |                |                | are not        |
| including        |                |                | limited to:    |
| examinations and |                |                |                |
| assays, as       |                |                | \(1\) The      |
| follows:         |                |                | specifications |
|                  |                |                | established;   |
| \(1\) A          |                |                |                |
| description of   |                |                | \(2\) The      |
| the sample       |                |                | actual results |
| received for     |                |                | obtained       |
| testing with     |                |                | during the     |
| identification   |                |                | monitoring     |
| of source (that  |                |                | operation;     |
| is, location     |                |                |                |
| from where       |                |                | \(3\) Any      |
| sample was       |                |                | deviation from |
| obtained),       |                |                | specifications |
| quantity, lot    |                |                | and any        |
| number or other  |                |                | unanticipated  |
| distinctive      |                |                | occurrences;   |
| code, date       |                |                |                |
| sample was       |                |                | \(4\) Any      |
| taken, and date  |                |                | corrective     |
| sample was       |                |                | actions taken; |
| received for     |                |                |                |
| testing.         |                |                | \(5\) The      |
|                  |                |                | disposition    |
| \(2\) A          |                |                | decisions and  |
| statement of     |                |                | follow-up; and |
| each method used |                |                |                |
| in the testing   |                |                | \(6\) The      |
| of the sample.   |                |                | identity of    |
| The statement    |                |                | the individual |
| shall indicate   |                |                | qualified by   |
| the location of  |                |                | training and   |
| data that        |                |                | experience who |
| establish that   |                |                | investigated   |
| the methods used |                |                | any deviation  |
| in the testing   |                |                | from           |
| of the sample    |                |                | s              |
| meet proper      |                |                | pecifications) |
| standards of     |                |                | or             |
| accuracy and     |                |                | unanticipated  |
| reliability as   |                |                | occurrence and |
| applied to the   |                |                | the identity   |
| product tested.  |                |                | of the         |
| (If the method   |                |                | individual     |
| employed is in   |                |                | from the       |
| the current      |                |                | quality        |
| revision of the  |                |                | control unit   |
| United States    |                |                | who reviewed   |
| Pharmacopeia,    |                |                | the results of |
| National         |                |                | that           |
| Formulary,       |                |                | investigation. |
| Association of   |                |                |                |
| Official         |                |                |                |
| Analytical       |                |                |                |
| Chemists, Book   |                |                |                |
| of Methods,2 or  |                |                |                |
| in other         |                |                |                |
| recognized       |                |                |                |
| standard         |                |                |                |
| references, or   |                |                |                |
| is detailed in   |                |                |                |
| an approved new  |                |                |                |
| drug application |                |                |                |
| and the          |                |                |                |
| referenced       |                |                |                |
| method is not    |                |                |                |
| modified, a      |                |                |                |
| statement        |                |                |                |
| indicating the   |                |                |                |
| method and       |                |                |                |
| reference will   |                |                |                |
| suffice). The    |                |                |                |
| suitability of   |                |                |                |
| all testing      |                |                |                |
| methods used     |                |                |                |
| shall be         |                |                |                |
| verified under   |                |                |                |
| actual           |                |                |                |
| conditions of    |                |                |                |
| use.             |                |                |                |
|                  |                |                |                |
| 2Copies may be   |                |                |                |
| obtained from:   |                |                |                |
| Association of   |                |                |                |
| Official         |                |                |                |
| Analytical       |                |                |                |
| Chemists, 2200   |                |                |                |
| Wilson Blvd.,    |                |                |                |
| Suite 400,       |                |                |                |
| Arlington, VA    |                |                |                |
| 22201-3301.      |                |                |                |
|                  |                |                |                |
| \(3\) A          |                |                |                |
| statement of the |                |                |                |
| weight or        |                |                |                |
| measure of       |                |                |                |
| sample used for  |                |                |                |
| each test, where |                |                |                |
| appropriate.     |                |                |                |
|                  |                |                |                |
| \(4\) A complete |                |                |                |
| record of all    |                |                |                |
| data secured in  |                |                |                |
| the course of    |                |                |                |
| each test,       |                |                |                |
| including all    |                |                |                |
| graphs, charts,  |                |                |                |
| and spectra from |                |                |                |
| laboratory       |                |                |                |
| instrumentation, |                |                |                |
| properly         |                |                |                |
| identified to    |                |                |                |
| show the         |                |                |                |
| specific         |                |                |                |
| component, drug  |                |                |                |
| product          |                |                |                |
| container,       |                |                |                |
| closure,         |                |                |                |
| in-process       |                |                |                |
| material, or     |                |                |                |
| drug product,    |                |                |                |
| and lot tested.  |                |                |                |
|                  |                |                |                |
| \(5\) A record   |                |                |                |
| of all           |                |                |                |
| calculations     |                |                |                |
| performed in     |                |                |                |
| connection with  |                |                |                |
| the test,        |                |                |                |
| including units  |                |                |                |
| of measure,      |                |                |                |
| conversion       |                |                |                |
| factors, and     |                |                |                |
| equivalency      |                |                |                |
| factors.         |                |                |                |
|                  |                |                |                |
| \(6\) A          |                |                |                |
| statement of the |                |                |                |
| results of tests |                |                |                |
| and how the      |                |                |                |
| results compare  |                |                |                |
| with established |                |                |                |
| standards of     |                |                |                |
| identity,        |                |                |                |
| strength,        |                |                |                |
| quality, and     |                |                |                |
| purity for the   |                |                |                |
| component, drug  |                |                |                |
| product          |                |                |                |
| container,       |                |                |                |
| closure,         |                |                |                |
| in-process       |                |                |                |
| material, or     |                |                |                |
| drug product     |                |                |                |
| tested.          |                |                |                |
|                  |                |                |                |
| \(7\) The        |                |                |                |
| initials or      |                |                |                |
| signature of the |                |                |                |
| person who       |                |                |                |
| performs each    |                |                |                |
| test and the     |                |                |                |
| date(s) the      |                |                |                |
| tests were       |                |                |                |
| performed.       |                |                |                |
|                  |                |                |                |
| \(8\) The        |                |                |                |
| initials or      |                |                |                |
| signature of a   |                |                |                |
| second person    |                |                |                |
| showing that the |                |                |                |
| original records |                |                |                |
| have been        |                |                |                |
| reviewed for     |                |                |                |
| accuracy,        |                |                |                |
| completeness,    |                |                |                |
| and compliance   |                |                |                |
| with established |                |                |                |
| standards.       |                |                |                |
+------------------+----------------+----------------+----------------+
| \(b\) Complete   |                |                |                |
| records shall be |                |                |                |
| maintained of    |                |                |                |
| any modification |                |                |                |
| of an            |                |                |                |
| established      |                |                |                |
| method employed  |                |                |                |
| in testing. Such |                |                |                |
| records shall    |                |                |                |
| include the      |                |                |                |
| reason for the   |                |                |                |
| modification and |                |                |                |
| data to verify   |                |                |                |
| that the         |                |                |                |
| modification     |                |                |                |
| produced results |                |                |                |
| that are at      |                |                |                |
| least as         |                |                |                |
| accurate and     |                |                |                |
| reliable for the |                |                |                |
| material being   |                |                |                |
| tested as the    |                |                |                |
| established      |                |                |                |
| method.          |                |                |                |
|                  |                |                |                |
| \(c\) Complete   |                |                |                |
| records shall be |                |                |                |
| maintained of    |                |                |                |
| any testing and  |                |                |                |
| standardization  |                |                |                |
| of laboratory    |                |                |                |
| reference        |                |                |                |
| standards,       |                |                |                |
| reagents, and    |                |                |                |
| standard         |                |                |                |
| solutions.       |                |                |                |
|                  |                |                |                |
| \(d\) Complete   |                |                |                |
| records shall be |                |                |                |
| maintained of    |                |                |                |
| the periodic     |                |                |                |
| calibration of   |                |                |                |
| laboratory       |                |                |                |
| instruments,     |                |                |                |
| apparatus,       |                |                |                |
| gauges, and      |                |                |                |
| recording        |                |                |                |
| devices required |                |                |                |
| by               |                |                |                |
| §211.160(b)(4).  |                |                |                |
|                  |                |                |                |
| ## (e) Comp      |                |                |                |
| lete records sha |                |                |                |
| ll be maintained |                |                |                |
|  of all stabilit |                |                |                |
| y testing perfor |                |                |                |
| med in accordanc |                |                |                |
| e with §211.166. |                |                |                |
+------------------+----------------+----------------+----------------+
|                  | **Subpart      | **Quality      | **§ 111.37     |
|                  | E\--Production | Control and    | [What          |
|                  | and Process    | Laboratory     | requirements   |
|                  | Controls**     | Operations**   | apply to       |
|                  |                |                | quality        |
|                  | **¶110.80      | Appropriate    | control?       |
|                  | Processes and  | quality        | ]              |
|                  | controls.**    | control        | {.underline}** |
|                  |                | operations     |                |
|                  | \              | shall be       | \(a\) You must |
|                  | ...Appropriate | employed to    | use a quality  |
|                  | quality        | assure that    | control unit   |
|                  | control        | dietary        | to ensure that |
|                  | operations     | products       | your           |
|                  | shall be       | conform to     | manufacturing, |
|                  | employed to    | appropriate    | packaging,     |
|                  | ensure that    | standards of   | label, and     |
|                  | food is        | purity,        | holding        |
|                  | suitable for   | quality and    | operations in  |
|                  | human          | composition,   | the production |
|                  | consumption    | and that       | of dietary     |
|                  | and that       | packaging      | ingredients    |
|                  | food-packaging | materials are  | and dietary    |
|                  | materials are  | safe and       | supplements    |
|                  | safe and       | suitable for   | are performed  |
|                  | suitable\...   | their intended | in a manner    |
|                  |                | purpose.       | that prevents  |
|                  |                |                | adulteration   |
|                  |                |                | and            |
|                  |                |                | misbranding,   |
|                  |                |                | including      |
|                  |                |                | ensuring that  |
|                  |                |                | dietary        |
|                  |                |                | ingredients    |
|                  |                |                | and dietary    |
|                  |                |                | supplements    |
|                  |                |                | meet           |
|                  |                |                | specifications |
|                  |                |                | for identity,  |
|                  |                |                | purity,        |
|                  |                |                | quality,       |
|                  |                |                | strength, and  |
|                  |                |                | composition.   |
+------------------+----------------+----------------+----------------+
| **§ 211.22       |                | \(a\) Quality  | \(b\) Your     |
| Responsibilities |                | control unit.  | quality        |
| of quality       |                |                | control unit   |
| control unit.**  |                | \(1\) There    | must do the    |
|                  |                | shall be a     | following:     |
| \(a\) There      |                | quality        |                |
| shall be a       |                | control unit   | \(1\) Approve  |
| quality control  |                | that has the   | or reject all  |
| unit that shall  |                | responsibility | processes,     |
| have the         |                | and authority  | s              |
| responsibility   |                | to:            | pecifications, |
| and authority to |                |                | controls,      |
| approve or       |                | (i) Approve or | tests, and     |
| reject all       |                |     reject all | examinations,  |
| components, drug |                |                | and deviations |
| product          |                |    procedures, | from or        |
| containers,      |                |     s          | modifications  |
| closures,        |                | pecifications, | to them, that  |
| in-process       |                |     controls,  | may affect the |
| materials,       |                |     tests and  | identity,      |
| packaging        |                |                | purity,        |
| material,        |                |  examinations, | quality,       |
| labeling, and    |                |     or         | strength, and  |
| drug products,   |                |     deviations | composition of |
| and the          |                |     from them, | a dietary      |
| authority to     |                |     that       | ingredient or  |
| review           |                |     impact the | dietary        |
| production       |                |     purity,    | supplement;    |
| records to       |                |     quality    |                |
| assure that no   |                |     and        | \(2\)          |
| errors have      |                |                | Determine      |
| occurred or, if  |                |    composition | whether all    |
| errors have      |                |     of a       | components,    |
| occurred, that   |                |     dietary    | dietary        |
| they have been   |                |     ingredient | ingredients    |
| fully            |                |     or dietary | dietary        |
| investigated.    |                |                | supplements,   |
| The quality      |                |    supplement; | packaging, and |
| control unit     |                |     and        | labels conform |
| shall be         |                |                | to             |
| responsible for  |                | (ii) Approve   | s              |
| approving or     |                |      or reject | pecifications; |
| rejecting drug   |                |      all raw   |                |
| products         |                |                | \(3\) Approve  |
| manufactured,    |                |     materials, | or reject all  |
| processed,       |                |      packaging | components,    |
| packed, or held  |                |                | dietary        |
| under contract   |                |     materials, | ingredients,   |
| by another       |                |      labeling, | dietary        |
| company.         |                |      and       | supplements,   |
|                  |                |      finished  | packaging and  |
| \(c\) The        |                |      dietary   | labels;        |
| quality control  |                |      products, |                |
| unit shall have  |                |      including | \(4\) Review   |
| the              |                |      products  | and approve    |
| responsibility   |                |                | all master     |
| for approving or |                |  manufactured, | manufacturing  |
| rejecting all    |                |                | records and    |
| procedures or    |                |     processed, | all            |
| specifications   |                |      packed,   | modifications  |
| impacting on the |                |      or held   | to the master  |
| identity,        |                |      under     | manufacturing  |
| strength,        |                |      contract  | records;       |
| quality, and     |                |      by        |                |
| purity of the    |                |      another   | \(5\) Review   |
| drug product.    |                |      company,  | and approve    |
|                  |                |      based on  | all batch      |
| **§ 211.160      |                |      adequate  | prod           |
| General          |                |                | uction-related |
| requirements.**  |                |  determination | records which  |
|                  |                |      of        | include, but   |
| \(a\) The        |                |                | are not        |
| establishment of |                |    conformance | limited to,    |
| any              |                |      to        | cro            |
| specifications,  |                |                | ss-referencing |
| standards,       |                |    established | receiving and  |
| sampling plans,  |                |      s         | batch          |
| test procedures, |                | pecifications; | production     |
| or other         |                |      and       | records,       |
| laboratory       |                |                | approval of a  |
| control          |                | (iii) Assure   | material       |
| mechanisms       |                |       that     | review and     |
| required by this |                |                | disposition    |
| subpart,         |                |      completed | decision,      |
| including any    |                |                | approval for   |
| change in such   |                |     production | reprocessing,  |
| specifications,  |                |       records  | and reject all |
| standards,       |                |       are      | components,    |
| sampling plans,  |                |       reviewed | dietary        |
| test procedures, |                |       as       | ingredients    |
| or other         |                |                | packaging, and |
| laboratory       |                |   appropriate. | labels;        |
| control          |                |       Quality  | approve all    |
| mechanisms,      |                |       control  | master         |
| shall be drafted |                |       shall be | manufacturing  |
| by the           |                |                | records and    |
| appropriate      |                |    responsible | the master     |
| organizational   |                |       for      | manufacturing  |
| unit and         |                |                | records;       |
| reviewed and     |                |     evaluation | approval for   |
| approved by the  |                |       of       | releasing for  |
| quality control  |                |       errors   | distribution;  |
| unit. The        |                |                |                |
| requirements in  |                |      committed | \(6\) Review   |
| this subpart     |                |       in the   | and approve    |
| shall be         |                |                | all processes  |
| followed and     |                |    manufacture | for            |
| shall be         |                |       of a     | calibrating    |
| documented at    |                |       product  | instruments or |
| the time of      |                |       and      | controls;      |
| performance. Any |                |       shall    |                |
| deviation from   |                |       have the | \(7\) Review   |
| the written      |                |       final    | all records    |
| specifications,  |                |                | for            |
| standards,       |                |      authority | calibration of |
| sampling plans,  |                |       to       | instruments,   |
| test procedures, |                |                | apparatus,     |
| or other         |                |      determine | gauges, and    |
| laboratory       |                |       if the   | recording      |
| control          |                |       error    | devices;       |
| mechanisms shall |                |       may be   |                |
| be recorded and  |                |                | \(8\) Review   |
| justified.       |                |      corrected | all records    |
|                  |                |       in such  | for equipment  |
|                  |                |       manner   | calibrations,  |
|                  |                |       that the | inspections,   |
|                  |                |       product  | and checks;    |
|                  |                |       can be   |                |
|                  |                |       approved | \(9\) Review   |
|                  |                |       for      | and approve    |
|                  |                |                | all laboratory |
|                  |                |   distribution | control        |
|                  |                |       or must  | processes, and |
|                  |                |       be       | testing        |
|                  |                |                | results;       |
|                  |                |     destroyed. |                |
|                  |                |       Such     | \(10\) Review  |
|                  |                |                | and approve    |
|                  |                |    evaluations | all packaging  |
|                  |                |       and      | and label      |
|                  |                |       their    | records which  |
|                  |                |                | include, but   |
|                  |                |     resolution | are not        |
|                  |                |       must be  | limited to,    |
|                  |                |                | cro            |
|                  |                |     documented | ss-referencing |
|                  |                |       and      | receiving and  |
|                  |                |                | batch          |
|                  |                |     maintained | production     |
|                  |                |       with     | records,       |
|                  |                |       and/or   | approval for   |
|                  |                |       cr       | repackaging    |
|                  |                | oss-referenced | and            |
|                  |                |       in the   | relabeling,    |
|                  |                |       batch    | and approval   |
|                  |                |                | for releasing  |
|                  |                |     production | for            |
|                  |                |       record.  | distribution;  |
+------------------+----------------+----------------+----------------+
| **§ 211.84       |                |                | \(11\) Collect |
| Testing and      |                |                | representative |
| approval or      |                |                | samples of:    |
| rejection of     |                |                |                |
| components, drug |                |                | \(i\) Each     |
| product          |                |                | shipment lot   |
| containers, and  |                |                | of components, |
| closures.**      |                |                | dietary        |
|                  |                |                | ingredients,   |
| \(b\)            |                |                | dietary        |
| Representative   |                |                | supplements,   |
| samples of each  |                |                | packaging, and |
| shipment of each |                |                | labels         |
| lot shall be     |                |                | received to    |
| collected for    |                |                | determine      |
| testing or       |                |                | whether the    |
| examination. The |                |                | component,     |
| number of        |                |                | dietary        |
| containers to be |                |                | ingredient,    |
| sampled, and the |                |                | dietary        |
| amount of        |                |                | supplement,    |
| material to be   |                |                | packaging, or  |
| taken from each  |                |                | labels meet    |
| container, shall |                |                | s              |
| be based upon    |                |                | pecifications; |
| appropriate      |                |                |                |
| criteria such as |                |                |                |
| statistical      |                |                |                |
| criteria for     |                |                |                |
| component        |                |                |                |
| variability,     |                |                |                |
| confidence       |                |                |                |
| levels, and      |                |                |                |
| degree of        |                |                |                |
| precision        |                |                |                |
| desired, the     |                |                |                |
| past quality     |                |                |                |
| history of the   |                |                |                |
| supplier, and    |                |                |                |
| the quantity     |                |                |                |
| needed for       |                |                |                |
| analysis and     |                |                |                |
| reserve where    |                |                |                |
| required by      |                |                |                |
| §211.170.        |                |                |                |
|                  |                |                |                |
| \(c\) Samples    |                |                |                |
| shall be         |                |                |                |
| collected in     |                |                |                |
| accordance with  |                |                |                |
| the following    |                |                |                |
| procedures:      |                |                |                |
|                  |                |                |                |
| \(1\) The        |                |                |                |
| containers of    |                |                |                |
| components       |                |                |                |
| selected shall   |                |                |                |
| be cleaned where |                |                |                |
| necessary, by    |                |                |                |
| appropriate      |                |                |                |
| means.           |                |                |                |
|                  |                |                |                |
| \(2\) The        |                |                |                |
| containers shall |                |                |                |
| be opened,       |                |                |                |
| sampled, and     |                |                |                |
| resealed in a    |                |                |                |
| manner designed  |                |                |                |
| to prevent       |                |                |                |
| contamination of |                |                |                |
| their contents   |                |                |                |
| and              |                |                |                |
| contamination of |                |                |                |
| other            |                |                |                |
| components, drug |                |                |                |
| product          |                |                |                |
| containers, or   |                |                |                |
| closures.        |                |                |                |
|                  |                |                |                |
| \(3\) Sterile    |                |                |                |
| equipment and    |                |                |                |
| aseptic sampling |                |                |                |
| techniques shall |                |                |                |
| be used when     |                |                |                |
| necessary.       |                |                |                |
|                  |                |                |                |
| \(4\) If it is   |                |                |                |
| necessary to     |                |                |                |
| sample a         |                |                |                |
| component from   |                |                |                |
| the top, middle, |                |                |                |
| and bottom of    |                |                |                |
| its container,   |                |                |                |
| such sample      |                |                |                |
| subdivisions     |                |                |                |
| shall not be     |                |                |                |
| composited for   |                |                |                |
| testing.         |                |                |                |
|                  |                |                |                |
| \(5\) Sample     |                |                |                |
| containers shall |                |                |                |
| be identified so |                |                |                |
| that the         |                |                |                |
| following        |                |                |                |
| information can  |                |                |                |
| be determined:   |                |                |                |
| name of the      |                |                |                |
| material         |                |                |                |
| sampled, the lot |                |                |                |
| number, the      |                |                |                |
| container from   |                |                |                |
| which the sample |                |                |                |
| was taken, the   |                |                |                |
| date on which    |                |                |                |
| the sample was   |                |                |                |
| taken, and the   |                |                |                |
| name of the      |                |                |                |
| person who       |                |                |                |
| collected the    |                |                |                |
| sample.          |                |                |                |
|                  |                |                |                |
| ## (6)           |                |                |                |
|  Containers from |                |                |                |
|  which samples h |                |                |                |
| ave been taken s |                |                |                |
| hall be marked t |                |                |                |
| o show that samp |                |                |                |
| les have been re |                |                |                |
| moved from them. |                |                |                |
+------------------+----------------+----------------+----------------+
|                  |                |                | \(ii\) In      |
|                  |                |                | process        |
|                  |                |                | materials at   |
|                  |                |                | points, steps, |
|                  |                |                | or stages, in  |
|                  |                |                | the            |
|                  |                |                | manufacturing  |
|                  |                |                | process as     |
|                  |                |                | specified in   |
|                  |                |                | the, master    |
|                  |                |                | manufacturing  |
|                  |                |                | record where   |
|                  |                |                | control is     |
|                  |                |                | necessary to   |
|                  |                |                | ensure the     |
|                  |                |                | identity,      |
|                  |                |                | purity,        |
|                  |                |                | quality,       |
|                  |                |                | strength, and  |
|                  |                |                | composition of |
|                  |                |                | dietary        |
|                  |                |                | ingredients or |
|                  |                |                | dietary        |
|                  |                |                | supplements;   |
|                  |                |                |                |
|                  |                |                | \(iii\) Each   |
|                  |                |                | batch of       |
|                  |                |                | dietary        |
|                  |                |                | ingredient or  |
|                  |                |                | dietary        |
|                  |                |                | supplement     |
|                  |                |                | manufactured   |
|                  |                |                | to determine,  |
|                  |                |                | before         |
|                  |                |                | releasing for  |
|                  |                |                | distribution,  |
|                  |                |                | whether the    |
|                  |                |                | dietary        |
|                  |                |                | ingredient or  |
|                  |                |                | dietary        |
|                  |                |                | supplement     |
|                  |                |                | meets its      |
|                  |                |                | specifications |
|                  |                |                | for identity,  |
|                  |                |                | purity,        |
|                  |                |                | quality,       |
|                  |                |                | strength, and  |
|                  |                |                | composition;   |
|                  |                |                | and            |
|                  |                |                |                |
|                  |                |                | \(iv\) Each    |
|                  |                |                | batch of       |
|                  |                |                | packaged and   |
|                  |                |                | labeled        |
|                  |                |                | dietary        |
|                  |                |                | ingredients or |
|                  |                |                | dietary        |
|                  |                |                | supplements to |
|                  |                |                | determine that |
|                  |                |                | you used the   |
|                  |                |                | packaging      |
|                  |                |                | specified in   |
|                  |                |                | the master     |
|                  |                |                | manufacturing  |
|                  |                |                | record and     |
|                  |                |                | applied the    |
|                  |                |                | label          |
|                  |                |                | specified in   |
|                  |                |                | the master     |
|                  |                |                | manufacturing  |
|                  |                |                | record.        |
+------------------+----------------+----------------+----------------+
|                  |                |                | \(12\) Keep    |
|                  |                |                | the reserve    |
|                  |                |                | samples for 3  |
|                  |                |                | years from the |
|                  |                |                | date of        |
|                  |                |                | manufacture    |
|                  |                |                | for use in     |
|                  |                |                | appropriate    |
|                  |                |                | investigations |
|                  |                |                | including, but |
|                  |                |                | not limited    |
|                  |                |                | to, consumer   |
|                  |                |                | complaint      |
|                  |                |                | investigations |
|                  |                |                | to determine,  |
|                  |                |                | for example,   |
|                  |                |                | whether the    |
|                  |                |                | dietary        |
|                  |                |                | ingredient or  |
|                  |                |                | dietary        |
|                  |                |                | supplement     |
|                  |                |                | associated     |
|                  |                |                | with a         |
|                  |                |                | consumer       |
|                  |                |                | complaint      |
|                  |                |                | failed to meet |
|                  |                |                | any of its     |
|                  |                |                | specifications |
|                  |                |                | for identity,  |
|                  |                |                | purity,        |
|                  |                |                | quality,       |
|                  |                |                | strength, and  |
|                  |                |                | composition.   |
|                  |                |                | The reserve    |
|                  |                |                | samples must:  |
|                  |                |                |                |
|                  |                |                | \(i\) Be       |
|                  |                |                | identified     |
|                  |                |                | with the batch |
|                  |                |                | or lot number; |
|                  |                |                | and            |
|                  |                |                |                |
|                  |                |                | \(ii\) Consist |
|                  |                |                | of at least    |
|                  |                |                | twice the      |
|                  |                |                | quantity       |
|                  |                |                | necessary for  |
|                  |                |                | tests.         |
+------------------+----------------+----------------+----------------+
|                  |                |                | \(13\) Perform |
|                  |                |                | appropriate    |
|                  |                |                | tests and      |
|                  |                |                | examinations   |
|                  |                |                | of:            |
|                  |                |                |                |
|                  |                |                | \(i\)          |
|                  |                |                | Components,    |
|                  |                |                | dietary        |
|                  |                |                | ingredients,   |
|                  |                |                | dietary        |
|                  |                |                | supplements,   |
|                  |                |                | packaging, and |
|                  |                |                | labels         |
|                  |                |                | received to    |
|                  |                |                | ensure that    |
|                  |                |                | they meet      |
|                  |                |                | s              |
|                  |                |                | pecifications; |
|                  |                |                |                |
|                  |                |                | \(ii\) Dietary |
|                  |                |                | ingredient and |
|                  |                |                | dietary        |
|                  |                |                | supplement     |
|                  |                |                | batch          |
|                  |                |                | production at  |
|                  |                |                | points, steps, |
|                  |                |                | or stages      |
|                  |                |                | identified in  |
|                  |                |                | the master     |
|                  |                |                | manufacturing  |
|                  |                |                | record where   |
|                  |                |                | control is     |
|                  |                |                | necessary to   |
|                  |                |                | prevent        |
|                  |                |                | adulteration;  |
|                  |                |                |                |
|                  |                |                | \(iii\)        |
|                  |                |                | Dietary        |
|                  |                |                | ingredients    |
|                  |                |                | and dietary    |
|                  |                |                | supplements    |
|                  |                |                | that you       |
|                  |                |                | manufacture to |
|                  |                |                | ensure that    |
|                  |                |                | they meet      |
|                  |                |                | s              |
|                  |                |                | pecifications; |
|                  |                |                | and            |
|                  |                |                |                |
|                  |                |                | \(iv\)         |
|                  |                |                | Packaged and   |
|                  |                |                | labeled        |
|                  |                |                | dietary        |
|                  |                |                | ingredients    |
|                  |                |                | and dietary    |
|                  |                |                | supplements to |
|                  |                |                | ensure that    |
|                  |                |                | you used the   |
|                  |                |                | packaging      |
|                  |                |                | specified in   |
|                  |                |                | the master     |
|                  |                |                | manufacturing  |
|                  |                |                | record and you |
|                  |                |                | applied the    |
|                  |                |                | label          |
|                  |                |                | specified in   |
|                  |                |                | the master     |
|                  |                |                | manufacturing  |
|                  |                |                | record.        |
+------------------+----------------+----------------+----------------+
|                  |                |                | \(14\) Review  |
|                  |                |                | and approve    |
|                  |                |                | all material   |
|                  |                |                | review and     |
|                  |                |                | disposition    |
|                  |                |                | decisions; and |
+------------------+----------------+----------------+----------------+
|                  |                |                | \(15\) Approve |
|                  |                |                | the            |
|                  |                |                | reprocessing   |
|                  |                |                | or             |
|                  |                |                | distribution   |
|                  |                |                | of returned    |
|                  |                |                | dietary        |
|                  |                |                | ingredients or |
|                  |                |                | dietary        |
|                  |                |                | supplements.   |
+------------------+----------------+----------------+----------------+
|                  |                |                | \(c\) Your     |
|                  |                |                | quality        |
|                  |                |                | control unit   |
|                  |                |                | must establish |
|                  |                |                | and maintain   |
|                  |                |                | documentation  |
|                  |                |                | at the time of |
|                  |                |                | performance    |
|                  |                |                | that it        |
|                  |                |                | performed the  |
|                  |                |                | review,        |
|                  |                |                | approval, or   |
|                  |                |                | rejection      |
|                  |                |                | requirements   |
|                  |                |                | of this        |
|                  |                |                | section by     |
|                  |                |                | recording the  |
|                  |                |                | following:     |
|                  |                |                |                |
|                  |                |                | \(1\) Date the |
|                  |                |                | required       |
|                  |                |                | review,        |
|                  |                |                | approval, or   |
|                  |                |                | rejection was  |
|                  |                |                | performed; and |
|                  |                |                |                |
|                  |                |                | \(2\)          |
|                  |                |                | Signature of   |
|                  |                |                | the person     |
|                  |                |                | performing the |
|                  |                |                | requirement.   |
+------------------+----------------+----------------+----------------+
| **§ 211.22       |                | \(3\) The      |                |
| Responsibilities |                | re             |                |
| of quality       |                | sponsibilities |                |
| control unit.**  |                | and procedures |                |
|                  |                | applicable to  |                |
| \(d\) The        |                | the quality    |                |
| responsibilities |                | control unit   |                |
| and procedures   |                | shall be       |                |
| applicable to    |                | established in |                |
| the quality      |                | writing and    |                |
| control unit     |                | followed.      |                |
| shall be in      |                |                |                |
| writing; such    |                |                |                |
| written          |                |                |                |
| procedures shall |                |                |                |
| be followed.     |                |                |                |
+------------------+----------------+----------------+----------------+
|                  |                |                | \(d\) You must |
|                  |                |                | keep quality   |
|                  |                |                | control        |
|                  |                |                | records in     |
|                  |                |                | accordance     |
|                  |                |                | with §         |
|                  |                |                | 111.125.       |
+------------------+----------------+----------------+----------------+
| **§ 211.137      |                | \(c\)          |                |
| Expiration       |                | Expiration     |                |
| dating.**        |                | dating.        |                |
|                  |                |                |                |
| \(a\) To assure  |                | \(1\) Whenever |                |
| that a drug      |                | a dietary      |                |
| product meets    |                | ingredient or  |                |
| applicable       |                | dietary        |                |
| standards of     |                | supplement     |                |
| identity,        |                | bears an       |                |
| strength,        |                | expiration     |                |
| quality, and     |                | date, such     |                |
| purity at the    |                | date shall be  |                |
| time of use, it  |                | supported by   |                |
| shall bear an    |                | data and       |                |
| expiration date  |                | rationale to   |                |
| determined by    |                | reasonably     |                |
| appropriate      |                | assure that    |                |
| stability        |                | the product    |                |
| testing          |                | meets          |                |
| described in     |                | established    |                |
| §211.166.        |                | specifications |                |
|                  |                | at the         |                |
| \(b\) Expiration |                | expiration     |                |
| dates shall be   |                | date.          |                |
| related to any   |                |                |                |
| storage          |                |                |                |
| conditions       |                |                |                |
| stated on the    |                |                |                |
| labeling, as     |                |                |                |
| determined by    |                |                |                |
| stability        |                |                |                |
| studies          |                |                |                |
| described in     |                |                |                |
| §211.166.        |                |                |                |
|                  |                |                |                |
| \(c\) If the     |                |                |                |
| drug product is  |                |                |                |
| to be            |                |                |                |
| reconstituted at |                |                |                |
| the time of      |                |                |                |
| dispensing, its  |                |                |                |
| labeling shall   |                |                |                |
| bear expiration  |                |                |                |
| information for  |                |                |                |
| both the         |                |                |                |
| reconstituted    |                |                |                |
| and              |                |                |                |
| unreconstituted  |                |                |                |
| drug products.   |                |                |                |
|                  |                |                |                |
| \(d\) Expiration |                |                |                |
| dates shall      |                |                |                |
| appear on        |                |                |                |
| labeling in      |                |                |                |
| accordance with  |                |                |                |
| the requirements |                |                |                |
| of §201.17 of    |                |                |                |
| this chapter.    |                |                |                |
+------------------+----------------+----------------+----------------+
| \(e\)            |                |                |                |
| Homeopathic drug |                |                |                |
| products shall   |                |                |                |
| be exempt from   |                |                |                |
| the requirements |                |                |                |
| of this section. |                |                |                |
|                  |                |                |                |
| \(f\) Allergenic |                |                |                |
| extracts that    |                |                |                |
| are labeled \"No |                |                |                |
| U.S. Standard of |                |                |                |
| Potency\" are    |                |                |                |
| exempt from the  |                |                |                |
| requirements of  |                |                |                |
| this section.    |                |                |                |
|                  |                |                |                |
| \(g\) New drug   |                |                |                |
| products for     |                |                |                |
| investigational  |                |                |                |
| use are exempt   |                |                |                |
| from the         |                |                |                |
| requirements of  |                |                |                |
| this section,    |                |                |                |
| provided that    |                |                |                |
| they meet        |                |                |                |
| appropriate      |                |                |                |
| standards or     |                |                |                |
| specifications   |                |                |                |
| as demonstrated  |                |                |                |
| by stability     |                |                |                |
| studies during   |                |                |                |
| their use in     |                |                |                |
| clinical         |                |                |                |
| investigations.  |                |                |                |
| Where new drug   |                |                |                |
| products for     |                |                |                |
| investigational  |                |                |                |
| use are to be    |                |                |                |
| reconstituted at |                |                |                |
| the time of      |                |                |                |
| dispensing,      |                |                |                |
| their labeling   |                |                |                |
| shall bear       |                |                |                |
| expiration       |                |                |                |
| information for  |                |                |                |
| the              |                |                |                |
| reconstituted    |                |                |                |
| drug product.    |                |                |                |
|                  |                |                |                |
| \(h\) Pending    |                |                |                |
| consideration of |                |                |                |
| a proposed       |                |                |                |
| exemption,       |                |                |                |
| published in the |                |                |                |
| Federal Register |                |                |                |
| of September 29, |                |                |                |
| 1978, the        |                |                |                |
| requirements in  |                |                |                |
| this section     |                |                |                |
| shall not be     |                |                |                |
| enforced for     |                |                |                |
| human OTC drug   |                |                |                |
| products if      |                |                |                |
| their labeling   |                |                |                |
| does not bear    |                |                |                |
| dosage           |                |                |                |
| limitations and  |                |                |                |
| they are stable  |                |                |                |
| for at least 3   |                |                |                |
| years as         |                |                |                |
| supported by     |                |                |                |
| appropriate      |                |                |                |
| stability data.  |                |                |                |
+------------------+----------------+----------------+----------------+
| **§ 211.166      |                | \(2\)          |                |
| Stability        |                | Appropriate    |                |
| testing.**       |                | accelerated    |                |
|                  |                | stability      |                |
| \(a\) There      |                | studies or     |                |
| shall be a       |                | data from      |                |
| written testing  |                | similar        |                |
| program designed |                | product        |                |
| to assess the    |                | formulations   |                |
| stability        |                | may be used    |                |
| characteristics  |                | for an initial |                |
| of drug          |                | determination  |                |
| products. The    |                | of shelf life. |                |
| results of such  |                | Product shelf  |                |
| stability        |                | life shall be  |                |
| testing shall be |                | confirmed and  |                |
| used in          |                | may be         |                |
| determining      |                | extended on    |                |
| appropriate      |                | the basis of   |                |
| storage          |                | real time      |                |
| conditions and   |                | studies on     |                |
| expiration       |                | product stored |                |
| dates. The       |                | under labeled  |                |
| written program  |                | storage        |                |
| shall be         |                | conditions.    |                |
| followed and     |                |                |                |
| shall include:   |                |                |                |
|                  |                |                |                |
| \(1\) Sample     |                |                |                |
| size and test    |                |                |                |
| intervals based  |                |                |                |
| on statistical   |                |                |                |
| criteria for     |                |                |                |
| each attribute   |                |                |                |
| examined to      |                |                |                |
| assure valid     |                |                |                |
| estimates of     |                |                |                |
| stability;       |                |                |                |
|                  |                |                |                |
| \(2\) Storage    |                |                |                |
| conditions for   |                |                |                |
| samples retained |                |                |                |
| for testing;     |                |                |                |
|                  |                |                |                |
| \(3\) Reliable,  |                |                |                |
| meaningful, and  |                |                |                |
| specific test    |                |                |                |
| methods;         |                |                |                |
|                  |                |                |                |
| \(4\) Testing of |                |                |                |
| the drug product |                |                |                |
| in the same      |                |                |                |
| c                |                |                |                |
| ontainer-closure |                |                |                |
| system as that   |                |                |                |
| in which the     |                |                |                |
| drug product is  |                |                |                |
| marketed;        |                |                |                |
|                  |                |                |                |
| \(5\) Testing of |                |                |                |
| drug products    |                |                |                |
| for              |                |                |                |
| reconstitution   |                |                |                |
| at the time of   |                |                |                |
| dispensing (as   |                |                |                |
| directed in the  |                |                |                |
| labeling) as     |                |                |                |
| well as after    |                |                |                |
| they are         |                |                |                |
| reconstituted.   |                |                |                |
|                  |                |                |                |
| \(b\) An         |                |                |                |
| adequate number  |                |                |                |
| of batches of    |                |                |                |
| each drug        |                |                |                |
| product shall be |                |                |                |
| tested to        |                |                |                |
| determine an     |                |                |                |
| appropriate      |                |                |                |
| expiration date  |                |                |                |
| and a record of  |                |                |                |
| such data shall  |                |                |                |
| be maintained.   |                |                |                |
| Accelerated      |                |                |                |
| studies,         |                |                |                |
| combined with    |                |                |                |
| basic stability  |                |                |                |
| information on   |                |                |                |
| the components,  |                |                |                |
| drug products,   |                |                |                |
| and              |                |                |                |
| c                |                |                |                |
| ontainer-closure |                |                |                |
| system, may be   |                |                |                |
| used to support  |                |                |                |
| tentative        |                |                |                |
| expiration dates |                |                |                |
| provided full    |                |                |                |
| shelf life       |                |                |                |
| studies are not  |                |                |                |
| available and    |                |                |                |
| are being        |                |                |                |
| conducted. Where |                |                |                |
| data from        |                |                |                |
| accelerated      |                |                |                |
| studies are used |                |                |                |
| to project a     |                |                |                |
| tentative        |                |                |                |
| expiration date  |                |                |                |
| that is beyond a |                |                |                |
| date supported   |                |                |                |
| by actual shelf  |                |                |                |
| life studies,    |                |                |                |
| there must be    |                |                |                |
| stability        |                |                |                |
| studies          |                |                |                |
| conducted,       |                |                |                |
| including drug   |                |                |                |
| product testing  |                |                |                |
| at appropriate   |                |                |                |
| intervals, until |                |                |                |
| the tentative    |                |                |                |
| expiration date  |                |                |                |
| is verified or   |                |                |                |
| the appropriate  |                |                |                |
| expiration date  |                |                |                |
| determined.      |                |                |                |
+------------------+----------------+----------------+----------------+
| \(c\) For        |                |                |                |
| homeopathic drug |                |                |                |
| products, the    |                |                |                |
| requirements of  |                |                |                |
| this section are |                |                |                |
| as follows:      |                |                |                |
|                  |                |                |                |
| \(1\) There      |                |                |                |
| shall be a       |                |                |                |
| written          |                |                |                |
| assessment of    |                |                |                |
| stability based  |                |                |                |
| at least on      |                |                |                |
| testing or       |                |                |                |
| examination of   |                |                |                |
| the drug product |                |                |                |
| for              |                |                |                |
| compatibility of |                |                |                |
| the ingredients, |                |                |                |
| and based on     |                |                |                |
| marketing        |                |                |                |
| experience with  |                |                |                |
| the drug product |                |                |                |
| to indicate that |                |                |                |
| there is no      |                |                |                |
| degradation of   |                |                |                |
| the product for  |                |                |                |
| the normal or    |                |                |                |
| expected period  |                |                |                |
| of use.          |                |                |                |
|                  |                |                |                |
| \(2\) Evaluation |                |                |                |
| of stability     |                |                |                |
| shall be based   |                |                |                |
| on the same      |                |                |                |
| c                |                |                |                |
| ontainer-closure |                |                |                |
| system in which  |                |                |                |
| the drug product |                |                |                |
| is being         |                |                |                |
| marketed.        |                |                |                |
|                  |                |                |                |
| \(d\) Allergenic |                |                |                |
| extracts that    |                |                |                |
| are labeled \"No |                |                |                |
| U.S. Standard of |                |                |                |
| Potency\" are    |                |                |                |
| exempt from the  |                |                |                |
| requirements of  |                |                |                |
| this section.    |                |                |                |
+------------------+----------------+----------------+----------------+
| **§ 211.167      |                |                |                |
| Special testing  |                |                |                |
| requirements.**  |                |                |                |
|                  |                |                |                |
| \(a\) For each   |                |                |                |
| batch of drug    |                |                |                |
| product          |                |                |                |
| purporting to be |                |                |                |
| sterile and/or   |                |                |                |
| pyrogen-free,    |                |                |                |
| there shall be   |                |                |                |
| appropriate      |                |                |                |
| laboratory       |                |                |                |
| testing to       |                |                |                |
| determine        |                |                |                |
| conformance to   |                |                |                |
| such             |                |                |                |
| requirements.    |                |                |                |
| The test         |                |                |                |
| procedures shall |                |                |                |
| be in writing    |                |                |                |
| and shall be     |                |                |                |
| followed.        |                |                |                |
|                  |                |                |                |
| \(b\) For each   |                |                |                |
| batch of         |                |                |                |
| ophthalmic       |                |                |                |
| ointment, there  |                |                |                |
| shall be         |                |                |                |
| appropriate      |                |                |                |
| testing to       |                |                |                |
| determine        |                |                |                |
| conformance to   |                |                |                |
| specifications   |                |                |                |
| regarding the    |                |                |                |
| presence of      |                |                |                |
| foreign          |                |                |                |
| particles and    |                |                |                |
| harsh or         |                |                |                |
| abrasive         |                |                |                |
| substances. The  |                |                |                |
| test procedures  |                |                |                |
| shall be in      |                |                |                |
| writing and      |                |                |                |
| shall be         |                |                |                |
| followed.        |                |                |                |
|                  |                |                |                |
| \(c\) For each   |                |                |                |
| batch of         |                |                |                |
| co               |                |                |                |
| ntrolled-release |                |                |                |
| dosage form,     |                |                |                |
| there shall be   |                |                |                |
| appropriate      |                |                |                |
| laboratory       |                |                |                |
| testing to       |                |                |                |
| determine        |                |                |                |
| conformance to   |                |                |                |
| the              |                |                |                |
| specifications   |                |                |                |
| for the rate of  |                |                |                |
| release of each  |                |                |                |
| active           |                |                |                |
| ingredient. The  |                |                |                |
| test procedures  |                |                |                |
| shall be in      |                |                |                |
| writing and      |                |                |                |
| shall be         |                |                |                |
| followed.        |                |                |                |
+------------------+----------------+----------------+----------------+
| **§ 211.82       | **¶110.80 (a)  | \(c\) Handling | **§ 111.40     |
| Receipt and      | Raw materials  | and storage of | [What          |
| storage of       | and other      | raw materials, | requirements   |
| untested         | ingredients.** | in-process     | apply to       |
| components, drug |                | materials and  | components,    |
| product          | \...Containers | rework.        | dietary        |
| containers, and  | and carriers   |                | ingredients.   |
| closures.**      | of raw         | ...Containers  | dietary        |
|                  | materials      | of raw         | supplements,   |
| \(a\) Upon       | should be      | materials      | packaging, and |
| receipt and      | inspected on   | should be      | labels you     |
| before           | receipt to     | inspected on   | receive?]      |
| acceptance, each | ensure that    | receipt to     | {.underline}** |
| container or     | their          | assure that    |                |
| grouping of      | condition has  | their          | \(a\) For      |
| containers of    | not            | condition has  | components,    |
| components, drug | contributed to | not            | dietary        |
| product          | the            | contributed to | ingredients,   |
| containers, and  | contamination  | the            | or dietary     |
| closures shall   | or             | adulteration   | supplements    |
| be examined      | deterioration  | or             | you receive,   |
| visually for     | of food.       | deterioration  | you must:      |
| appropriate      |                | of the         |                |
| labeling as to   |                | contents.      | \(1\) Visually |
| contents,        |                |                | examine each   |
| container damage |                | \(2\) Written  | container or   |
| or broken seals, |                | procedures     | grouping of    |
| and              |                | shall be       | containers in  |
| contamination.   |                | established    | a shipment for |
|                  |                | and followed   | appropriate    |
| \(b\)            |                | describing in  | content label, |
| Components, drug |                | sufficient     | container,     |
| product          |                | detail the     | damage, or     |
| containers, and  |                | control        | broken seals   |
| closures shall   |                | procedures     | to determine   |
| be stored under  |                | employed for   | whether the    |
| quarantine until |                | the receipt,   | container      |
| they have been   |                | storage,       | condition has  |
| tested or        |                | handling,      | resulted in    |
| examined, as     |                | sampling,      | contamination  |
| appropriate, and |                | examination,   | or             |
| released.        |                | and/or testing | deterioration  |
| Storage within   |                | that may be    | of the         |
| the area shall   |                | necessary to   | components,    |
| conform to the   |                | assure the     | dietary        |
| requirements of  |                | identity of    | ingredients,   |
| §211.80.         |                | labeling and   | or dietary     |
|                  |                | the            | supplement;    |
| **§ 211.84       |                | appropriate    |                |
| Testing and      |                | identity,      |                |
| approval or      |                | cleanliness    |                |
| rejection of     |                | and quality    |                |
| components, drug |                | c              |                |
| product          |                | haracteristics |                |
| containers, and  |                | of packaging   |                |
| closures.**      |                | materials for  |                |
|                  |                | dietary        |                |
| \(d\) (5) Each   |                | products.      |                |
| lot of a         |                |                |                |
| component, drug  |                |                |                |
| product          |                |                |                |
| container, or    |                |                |                |
| closure that is  |                |                |                |
| liable to        |                |                |                |
| contamination    |                |                |                |
| with filth,      |                |                |                |
| insect           |                |                |                |
| infestation, or  |                |                |                |
| other extraneous |                |                |                |
| adulterant shall |                |                |                |
| be examined      |                |                |                |
| against          |                |                |                |
| established      |                |                |                |
| specifications   |                |                |                |
| for such         |                |                |                |
| contamination.   |                |                |                |
+------------------+----------------+----------------+----------------+
|                  |                |                | \(2\) Visually |
|                  |                |                | examine the    |
|                  |                |                | supplier's     |
|                  |                |                | invoice,       |
|                  |                |                | guarantee, or  |
|                  |                |                | certification  |
|                  |                |                | to ensure that |
|                  |                |                | the            |
|                  |                |                | components,    |
|                  |                |                | dietary        |
|                  |                |                | ingredients,   |
|                  |                |                | or dietary     |
|                  |                |                | supplements    |
|                  |                |                | are consistent |
|                  |                |                | with your      |
|                  |                |                | purchase order |
|                  |                |                | and perform    |
|                  |                |                | testing, as    |
|                  |                |                | needed, to     |
|                  |                |                | determine      |
|                  |                |                | whether        |
|                  |                |                | specifications |
|                  |                |                | are met.       |
+------------------+----------------+----------------+----------------+
| **§ 211.84       |                |                | \(3\)          |
| Testing and      |                |                | Quarantine     |
| approval or      |                |                | components,    |
| rejection of     |                |                | dietary        |
| components, drug |                |                | ingredients,   |
| product          |                |                | or dietary     |
| containers, and  |                |                | supplements    |
| closures.**      |                |                | until your     |
|                  |                |                | quality        |
| \(a\) Each lot   |                |                | control unit   |
| of components,   |                |                | reviews the    |
| drug product     |                |                | supplier's     |
| containers, and  |                |                | invoice,       |
| closures shall   |                |                | guarantee, or  |
| be withheld from |                |                | certification  |
| use until the    |                |                | and performs   |
| lot has been     |                |                | testing, as    |
| sampled, tested, |                |                | needed, of a   |
| or examined, as  |                |                | representative |
| appropriate, and |                |                | sample to      |
| released for use |                |                | determine that |
| by the quality   |                |                | specifications |
| control unit.    |                |                | are met. If    |
|                  |                |                | specifications |
|                  |                |                | are not met,   |
|                  |                |                | you must       |
|                  |                |                | conduct a      |
|                  |                |                | material       |
|                  |                |                | review and     |
|                  |                |                | make a         |
|                  |                |                | disposition    |
|                  |                |                | decision. Your |
|                  |                |                | quality        |
|                  |                |                | control unit   |
|                  |                |                | must approve   |
|                  |                |                | and release    |
|                  |                |                | the            |
|                  |                |                | components,    |
|                  |                |                | dietary        |
|                  |                |                | ingredients,   |
|                  |                |                | and dietary    |
|                  |                |                | supplements    |
|                  |                |                | from           |
|                  |                |                | quarantine     |
|                  |                |                | before you use |
|                  |                |                | them;          |
+------------------+----------------+----------------+----------------+
| **§ 211.80       |                | \(6\) Each lot | \(4\) Identify |
| General          |                | of raw         | each lot of    |
| requirements.**  |                | material shall | components,    |
|                  |                | be identified  | dietary        |
| \(d\) Each       |                | with a         | ingredients,   |
| container or     |                | distinctive    | or dietary     |
| grouping of      |                | lot number and | supplements in |
| containers for   |                | shall be       | a shipment in  |
| components or    |                | appropriately  | a manner that  |
| drug product     |                | controlled     | allows you to  |
| containers, or   |                | according to   | trace the      |
| closures shall   |                | its status     | shipment to    |
| be identified    |                | (e.g.          | the supplier,  |
| with a           |                | quarantined,   | the date       |
| distinctive code |                | approved,      | received, the  |
| for each lot in  |                | rejected).     | name of the    |
| each shipment    |                |                | component or   |
| received. This   |                |                | dietary        |
| code shall be    |                |                | supplement,    |
| used in          |                |                | and the status |
| recording the    |                |                | (e.g.,         |
| disposition of   |                |                | quarantined,   |
| each lot. Each   |                |                | approved, or   |
| lot shall be     |                |                | rejected) and  |
| appropriately    |                |                | to trace the   |
| identified as to |                |                | shipment lot   |
| its status       |                |                | to the dietary |
| (i.e.,           |                |                | ingredient or  |
| quarantined,     |                |                | dietary        |
| approved, or     |                |                | supplement     |
| rejected).       |                |                | manufactured   |
|                  |                |                | and            |
|                  |                |                | distributed.   |
|                  |                |                | You must use   |
|                  |                |                | this unique    |
|                  |                |                | identifier     |
|                  |                |                | whenever you   |
|                  |                |                | record the     |
|                  |                |                | disposition of |
|                  |                |                | each shipment  |
|                  |                |                | lot received;  |
|                  |                |                | and            |
+------------------+----------------+----------------+----------------+
| \(b\) Components | **¶110.80 (a)  | \(1\) Raw      | \(5\) Hold     |
| and drug product | Raw materials  | materials,     | components,    |
| containers and   | and other      | in-process     | dietary        |
| closures shall   | ingredients.** | materials and  | ingredients,   |
| at all times be  |                | rework shall   | or dietary     |
| handled and      | \(1\) Raw      | be inspected   | supplements    |
| stored in a      | materials and  | and segregated | under          |
| manner to        | other          | or otherwise   | conditions     |
| prevent          | ingredients    | handled as     | that will      |
| contamination.   | shall be       | necessary to   | protect        |
|                  | inspected and  | ascertain that | against        |
| \(c\) Bagged or  | segregated or  | they are clean | contamination, |
| boxed components | otherwise      | and suitable   | deterioration, |
| of drug product  | handled as     | for processing | and avoid      |
| containers, or   | necessary to   | into dietary   | mixups.        |
| closures shall   | ascertain that | products and   |                |
| be stored off    | they are clean | shall be       |                |
| the floor and    | and suitable   | stored under   |                |
| suitably spaced  | for processing | conditions     |                |
| to permit        | into food and  | that will      |                |
| cleaning and     | shall be       | protect        |                |
| inspection.      | stored under   | against        |                |
|                  | conditions     | adulteration   |                |
|                  | that will      | and minimize   |                |
|                  | protect        | deterioration. |                |
|                  | against        |                |                |
|                  | contamination  | (1)...Liquid   |                |
|                  | and minimize   | or dry raw     |                |
|                  | deterioration. | materials and  |                |
|                  |                | other          |                |
|                  | \(7\) Liquid   | ingredients    |                |
|                  | or dry raw     | received and   |                |
|                  | materials and  | stored in bulk |                |
|                  | other          | form shall be  |                |
|                  | ingredients    | held in a      |                |
|                  | received and   | manner that    |                |
|                  | stored in bulk | protects       |                |
|                  | form shall be  | against        |                |
|                  | held in a      | contamination. |                |
|                  | manner that    |                |                |
|                  | protects       | \(3\) Raw      |                |
|                  | against        | materials,     |                |
|                  | contamination. | in-process     |                |
|                  |                | materials, and |                |
|                  | \(5\) Raw      | rework shall   |                |
|                  | materials,     | be held in     |                |
|                  | other          | bulk, or in    |                |
|                  | ingredients,   | containers     |                |
|                  | and rework     | designed and   |                |
|                  | shall be held  | constructed so |                |
|                  | in bulk, or in | as to protect  |                |
|                  | containers     | against        |                |
|                  | designed and   | adulteration   |                |
|                  | constructed so | and shall be   |                |
|                  | as to protect  | held at such   |                |
|                  | against        | temperature    |                |
|                  | contamination  | and relative   |                |
|                  | and shall be   | humidity and   |                |
|                  | held at such   | in such a      |                |
|                  | temperature    | manner as to   |                |
|                  | and relative   | prevent a      |                |
|                  | humidity and   | dietary        |                |
|                  | in such a      | ingredient or  |                |
|                  | manner as to   | dietary        |                |
|                  | prevent the    | supplement     |                |
|                  | food from      | from becoming  |                |
|                  | becoming       | adulterated    |                |
|                  | adulterated    | within the     |                |
|                  | within the     | meaning of the |                |
|                  | meaning of the | act. Material  |                |
|                  | act. Material  | scheduled for  |                |
|                  | scheduled for  | rework shall   |                |
|                  | rework shall   | be identified  |                |
|                  | be identified  | as such.       |                |
|                  | as such.       |                |                |
+------------------+----------------+----------------+----------------+
|                  | \(6\) Frozen   | \(4\) Frozen   |                |
|                  | raw materials  | raw materials  |                |
|                  | and other      | and other      |                |
|                  | ingredients    | ingredients    |                |
|                  | shall be kept  | shall be kept  |                |
|                  | frozen. If     | frozen. If     |                |
|                  | thawing is     | thawing is     |                |
|                  | required prior | required prior |                |
|                  | to use, it     | to use, it     |                |
|                  | shall be done  | shall be done  |                |
|                  | in a manner    | in a manner    |                |
|                  | that prevents  | that prevents  |                |
|                  | the raw        | the raw        |                |
|                  | materials and  | materials and  |                |
|                  | other          | other          |                |
|                  | ingredients    | ingredients    |                |
|                  | from becoming  | from becoming  |                |
|                  | adulterated    | adulterated    |                |
|                  | within the     | within the     |                |
|                  | meaning of the | meaning of the |                |
|                  | act.           | act.           |                |
+------------------+----------------+----------------+----------------+
| **§ 211.80       |                | \(5\) Written  |                |
| General          |                | procedures     |                |
| requirements.**  |                | shall be       |                |
|                  |                | established    |                |
| \(a\) There      |                | and followed   |                |
| shall be written |                | describing the |                |
| procedures       |                | receipt,       |                |
| describing in    |                | i              |                |
| sufficient       |                | dentification, |                |
| detail the       |                | examination,   |                |
| receipt,         |                | handling,      |                |
| identification,  |                | sampling,      |                |
| storage,         |                | testing and    |                |
| handling,        |                | approval or    |                |
| sampling,        |                | rejection of   |                |
| testing, and     |                | raw materials. |                |
| approval or      |                |                |                |
| rejection of     |                |                |                |
| components and   |                |                |                |
| drug product     |                |                |                |
| containers and   |                |                |                |
| closures; such   |                |                |                |
| written          |                |                |                |
| procedures shall |                |                |                |
| be followed.     |                |                |                |
+------------------+----------------+----------------+----------------+
| **§ 211.82       |                |                | \(b\) For      |
| Receipt and      |                |                | packaging and  |
| storage of       |                |                | labels you     |
| untested         |                |                | receive, you   |
| components, drug |                |                | must:          |
| product          |                |                |                |
| containers, and  |                |                | \(1\) Visually |
| closures.**      |                |                | examine each   |
|                  |                |                | container or   |
| \(a\) Upon       |                |                | grouping of    |
| receipt and      |                |                | containers in  |
| before           |                |                | a shipment for |
| acceptance, each |                |                | appropriate    |
| container or     |                |                | content label, |
| grouping of      |                |                | container      |
| containers of    |                |                | damage, or     |
| components, drug |                |                | broken seals   |
| product          |                |                | to determine   |
| containers, and  |                |                | whether the    |
| closures shall   |                |                | container      |
| be examined      |                |                | condition has  |
| visually for     |                |                | resulted in    |
| appropriate      |                |                | contamination  |
| labeling as to   |                |                | or             |
| contents,        |                |                | deterioration  |
| container damage |                |                | of the         |
| or broken seals, |                |                | packaging and  |
| and              |                |                | labels;        |
| contamination.   |                |                |                |
|                  |                |                |                |
| \(b\)            |                |                |                |
| Components, drug |                |                |                |
| product          |                |                |                |
| containers, and  |                |                |                |
| closures shall   |                |                |                |
| be stored under  |                |                |                |
| quarantine until |                |                |                |
| they have been   |                |                |                |
| tested or        |                |                |                |
| examined, as     |                |                |                |
| appropriate, and |                |                |                |
| released.        |                |                |                |
| Storage within   |                |                |                |
| the area shall   |                |                |                |
| conform to the   |                |                |                |
| requirements of  |                |                |                |
| §211.80.         |                |                |                |
|                  |                |                |                |
| **§ 211.84       |                |                |                |
| Testing and      |                |                |                |
| approval or      |                |                |                |
| rejection of     |                |                |                |
| components, drug |                |                |                |
| product          |                |                |                |
| containers, and  |                |                |                |
| closures.**      |                |                |                |
|                  |                |                |                |
| \(d\) (5) Each   |                |                |                |
| lot of a         |                |                |                |
| component, drug  |                |                |                |
| product          |                |                |                |
| container, or    |                |                |                |
| closure that is  |                |                |                |
| liable to        |                |                |                |
| contamination    |                |                |                |
| with filth,      |                |                |                |
| insect           |                |                |                |
| infestation, or  |                |                |                |
| other extraneous |                |                |                |
| adulterant shall |                |                |                |
| be examined      |                |                |                |
| against          |                |                |                |
| established      |                |                |                |
| specifications   |                |                |                |
| for such         |                |                |                |
| contamination.   |                |                |                |
+------------------+----------------+----------------+----------------+
| \(d\) (3)        |                |                | \(2\)          |
| Containers and   |                |                | Quarantine     |
| closures shall   |                |                | packaging and  |
| be tested for    |                |                | labels until   |
| conformance with |                |                | your quality   |
| all appropriate  |                |                | control unit   |
| written          |                |                | tests or       |
| procedures. In   |                |                | examines a     |
| lieu of such     |                |                | representative |
| testing by the   |                |                | sample to      |
| manufacturer, a  |                |                | determine that |
| certificate of   |                |                | specifications |
| testing may be   |                |                | are met. You   |
| accepted from    |                |                | must conduct   |
| the supplier,    |                |                | at least a     |
| provided that at |                |                | visual         |
| least a visual   |                |                | identification |
| identification   |                |                | on the         |
| is conducted on  |                |                | containers and |
| such             |                |                | closures. If   |
| con              |                |                | specifications |
| tainers/closures |                |                | are not met,   |
| by the           |                |                | you must       |
| manufacturer and |                |                | conduct a      |
| provided that    |                |                | material       |
| the manufacturer |                |                | review and     |
| establishes the  |                |                | make a         |
| reliability of   |                |                | disposition    |
| the supplier\'s  |                |                | decision. Your |
| test results     |                |                | quality        |
| through          |                |                | control unit   |
| appropriate      |                |                | must approve   |
| validation of    |                |                | and release    |
| the supplier\'s  |                |                | packaging and  |
| test results at  |                |                | labels from    |
| appropriate      |                |                | quarantine     |
| intervals.       |                |                | before you use |
|                  |                |                | them;          |
+------------------+----------------+----------------+----------------+
| **§ 211.80       |                |                | \(3\) Identify |
| General          |                |                | each shipment  |
| requirements.**  |                |                | lot of         |
|                  |                |                | packaging and  |
| \(d\) Each       |                |                | labels in a    |
| container or     |                |                | manner that    |
| grouping of      |                |                | allows you to  |
| containers for   |                |                | trace the      |
| components or    |                |                | shipment lot   |
| drug product     |                |                | to the         |
| containers, or   |                |                | supplier, the  |
| closures shall   |                |                | date received, |
| be identified    |                |                | the name of    |
| with a           |                |                | the packaging  |
| distinctive code |                |                | and label and  |
| for each lot in  |                |                | the status     |
| each shipment    |                |                | (e.g.,         |
| received. This   |                |                | quarantined,   |
| code shall be    |                |                | approved, or   |
| used in          |                |                | rejected) and  |
| recording the    |                |                | to trace the   |
| disposition of   |                |                | shipment lot   |
| each lot. Each   |                |                | to the dietary |
| lot shall be     |                |                | ingredient or  |
| appropriately    |                |                | dietary        |
| identified as to |                |                | supplement     |
| its status       |                |                | manufactured   |
| (i.e.,           |                |                | and            |
| quarantined,     |                |                | distributed.   |
| approved, or     |                |                | You must use   |
| rejected).       |                |                | this unique    |
|                  |                |                | identifier     |
|                  |                |                | whenever you   |
|                  |                |                | record the     |
|                  |                |                | disposition of |
|                  |                |                | each shipment  |
|                  |                |                | lot received;  |
|                  |                |                | and            |
+------------------+----------------+----------------+----------------+
| \(b\) Components |                |                | \(4\) Hold     |
| and drug product |                |                | packaging and  |
| containers and   |                |                | labels under   |
| closures shall   |                |                | conditions     |
| at all times be  |                |                | that will      |
| handled and      |                |                | protect        |
| stored in a      |                |                | against        |
| manner to        |                |                | contamination, |
| prevent          |                |                | deterioration, |
| contamination.   |                |                | and avoid      |
|                  |                |                | mixups.        |
| \(c\) Bagged or  |                |                |                |
| boxed components |                |                |                |
| of drug product  |                |                |                |
| containers, or   |                |                |                |
| closures shall   |                |                |                |
| be stored off    |                |                |                |
| the floor and    |                |                |                |
| suitably spaced  |                |                |                |
| to permit        |                |                |                |
| cleaning and     |                |                |                |
| inspection.      |                |                |                |
+------------------+----------------+----------------+----------------+
| ## § 2           |                |                |                |
| 11.122 Materials |                |                |                |
|  examination and |                |                |                |
|  usage criteria. |                |                |                |
|                  |                |                |                |
| \(a\) There      |                |                |                |
| shall be written |                |                |                |
| procedures       |                |                |                |
| describing in    |                |                |                |
| sufficient       |                |                |                |
| detail the       |                |                |                |
| receipt,         |                |                |                |
| identification,  |                |                |                |
| storage,         |                |                |                |
| handling,        |                |                |                |
| sampling,        |                |                |                |
| examination,     |                |                |                |
| and/or testing   |                |                |                |
| of labeling and  |                |                |                |
| packaging        |                |                |                |
| materials; such  |                |                |                |
| written          |                |                |                |
| procedures shall |                |                |                |
| be followed.     |                |                |                |
| Labeling and     |                |                |                |
| packaging        |                |                |                |
| materials shall  |                |                |                |
| be               |                |                |                |
| representatively |                |                |                |
| sampled, and     |                |                |                |
| examined or      |                |                |                |
| tested upon      |                |                |                |
| receipt and      |                |                |                |
| before use in    |                |                |                |
| packaging or     |                |                |                |
| labeling of a    |                |                |                |
| drug product.    |                |                |                |
|                  |                |                |                |
| \(b\) Any        |                |                |                |
| labeling or      |                |                |                |
| packaging        |                |                |                |
| materials        |                |                |                |
| meeting          |                |                |                |
| appropriate      |                |                |                |
| written          |                |                |                |
| specifications   |                |                |                |
| may be approved  |                |                |                |
| and released for |                |                |                |
| use. Any         |                |                |                |
| labeling or      |                |                |                |
| packaging        |                |                |                |
| materials that   |                |                |                |
| do not meet such |                |                |                |
| specifications   |                |                |                |
| shall be         |                |                |                |
| rejected to      |                |                |                |
| prevent their    |                |                |                |
| use in           |                |                |                |
| operations for   |                |                |                |
| which they are   |                |                |                |
| unsuitable.      |                |                |                |
|                  |                |                |                |
| \(c\) Records    |                |                |                |
| shall be         |                |                |                |
| maintained for   |                |                |                |
| each shipment    |                |                |                |
| received of each |                |                |                |
| different        |                |                |                |
| labeling and     |                |                |                |
| packaging        |                |                |                |
| material         |                |                |                |
| indicating       |                |                |                |
| receipt,         |                |                |                |
| examination or   |                |                |                |
| testing, and     |                |                |                |
| whether accepted |                |                |                |
| or rejected.     |                |                |                |
+------------------+----------------+----------------+----------------+
| ## § 211.184 C   |                |                | \(c\) (1) The  |
| omponent, drug p |                |                | person who     |
| roduct container |                |                | performs the   |
| , closure, and l |                |                | component,     |
| abeling records. |                |                | dietary        |
|                  |                |                | ingredient,    |
| These records    |                |                | dietary        |
| shall include    |                |                | supplement,    |
| the following:   |                |                | packaging, or  |
|                  |                |                | label          |
| \(a\) The        |                |                | requirements   |
| identity and     |                |                | of this        |
| quantity of each |                |                | section must   |
| shipment of each |                |                | document, at   |
| lot of           |                |                | the time of    |
| components, drug |                |                | performance,   |
| product          |                |                | that the       |
| containers,      |                |                | requirements   |
| closures, and    |                |                | were followed. |
| labeling; the    |                |                | The            |
| name of the      |                |                | documentation  |
| supplier; the    |                |                | must include,  |
| supplier\'s lot  |                |                | but not be     |
| number(s) if     |                |                | limited to:    |
| known; the       |                |                |                |
| receiving code   |                |                | \(i\) The date |
| as specified in  |                |                | that the       |
| §211.80; and the |                |                | components,    |
| date of receipt. |                |                | dietary        |
| The name and     |                |                | ingredients,   |
| location of the  |                |                | dietary        |
| prime            |                |                | supplements,   |
| manufacturer, if |                |                | packaging, or  |
| different from   |                |                | labels were    |
| the supplier,    |                |                | received;      |
| shall be listed  |                |                |                |
| if known.        |                |                | \(ii\) The     |
|                  |                |                | signature of   |
| \(b\) The        |                |                | the person     |
| results of any   |                |                | performing the |
| test or          |                |                | requirement;   |
| examination      |                |                |                |
| performed        |                |                | \(iii\) Any    |
| (including those |                |                | test results;  |
| performed as     |                |                | and            |
| required by      |                |                |                |
| §211.82(a),      |                |                | \(iv\) Any     |
| §211.84(d), or   |                |                | material       |
| §211.122(a)) and |                |                | review and     |
| the conclusions  |                |                | disposition    |
| derived          |                |                | decision you   |
| therefrom.       |                |                | conducted in   |
|                  |                |                | accordance     |
| \(c\) An         |                |                | with           |
| individual       |                |                | §111.35(i) and |
| inventory record |                |                | disposition of |
| of each          |                |                | any rejected   |
| component, drug  |                |                | material under |
| product          |                |                | S 111.74.      |
| container, and   |                |                |                |
| closure and, for |                |                | \(2\) You must |
| each component,  |                |                | keep           |
| a reconciliation |                |                | component,     |
| of the use of    |                |                | dietary        |
| each lot of such |                |                | supplement,    |
| component. The   |                |                | packaging, and |
| inventory record |                |                | label          |
| shall contain    |                |                | receiving      |
| sufficient       |                |                | records in     |
| information to   |                |                | accordance     |
| allow            |                |                | with §         |
| determination of |                |                | 111.125.       |
| any batch or lot |                |                |                |
| of drug product  |                |                |                |
| associated with  |                |                |                |
| the use of each  |                |                |                |
| component, drug  |                |                |                |
| product          |                |                |                |
| container, and   |                |                |                |
| closure.         |                |                |                |
|                  |                |                |                |
| \(d\)            |                |                |                |
| Documentation of |                |                |                |
| the examination  |                |                |                |
| and review of    |                |                |                |
| labels and       |                |                |                |
| labeling for     |                |                |                |
| conformity with  |                |                |                |
| established      |                |                |                |
| specifications   |                |                |                |
| in accord with   |                |                |                |
| §§211.122(c)     |                |                |                |
| and211.130(c).   |                |                |                |
|                  |                |                |                |
| \(e\) The        |                |                |                |
| disposition of   |                |                |                |
| rejected         |                |                |                |
| components, drug |                |                |                |
| product          |                |                |                |
| containers,      |                |                |                |
| closure, and     |                |                |                |
| labeling.        |                |                |                |
+------------------+----------------+----------------+----------------+
| ##               |                | **Production   | **§ 111.45     |
| § 211.186 Master |                | and Process    | [What          |
|  production and  |                | Controls**     | requirements   |
| control records. |                |                | apply to       |
|                  |                | \(a\) Master   | establishing a |
| \(a\) To assure  |                | production and | master         |
| uniformity from  |                | control        | manufacturing  |
| batch to batch,  |                | records.       | record?]       |
| master           |                |                | {.underline}** |
| production and   |                | \(1\) To       |                |
| control records  |                | assure         | \(a\) You must |
| for each drug    |                | uniformity     | prepare and    |
| product,         |                | from batch to  | follow a       |
| including each   |                | batch, a       | written master |
| batch size       |                | master         | manufacturing  |
| thereof, shall   |                | production and | record for     |
| be prepared,     |                | control record | each type of   |
| dated, and       |                | shall be       | dietary        |
| signed (full     |                | prepared for   | ingredient or  |
| signature,       |                | the            | dietary        |
| handwritten) by  |                | manufacture of | supplement     |
| one person and   |                | each dietary   | that you       |
| independently    |                | ingredient and | manufacture    |
| checked, dated,  |                | dietary        | and for each   |
| and signed by a  |                | supplement,    | batch size to  |
| second person.   |                | ...            | ensure         |
| The preparation  |                |                | uniformity     |
| of master        |                |                | from batch to  |
| production and   |                |                | batch. The     |
| control records  |                |                | master         |
| shall be         |                |                | manufacturing  |
| described in a   |                |                | record must:   |
| written          |                |                |                |
| procedure and    |                |                | \(1\) Identify |
| such written     |                |                | specifications |
| procedure shall  |                |                | for the        |
| be followed.     |                |                | points, steps, |
|                  |                |                | or stages in   |
|                  |                |                | the            |
|                  |                |                | manufacturing  |
|                  |                |                | process where  |
|                  |                |                | control is     |
|                  |                |                | necessary to   |
|                  |                |                | prevent        |
|                  |                |                | adulteration;  |
|                  |                |                | and            |
|                  |                |                |                |
|                  |                |                | \(2\)          |
|                  |                |                | Establish      |
|                  |                |                | controls and   |
|                  |                |                | procedures to  |
|                  |                |                | ensure that    |
|                  |                |                | each batch of  |
|                  |                |                | dietary        |
|                  |                |                | ingredient or  |
|                  |                |                | dietary        |
|                  |                |                | supplement     |
|                  |                |                | manufactured   |
|                  |                |                | meets those    |
|                  |                |                | s              |
|                  |                |                | pecifications. |
+------------------+----------------+----------------+----------------+
| \(b\) Master     |                | > Master       | \(b\) The      |
| production and   |                | > production   | master         |
| control records  |                | > and control  | manufacturing  |
| shall include:   |                | > records      | record must    |
|                  |                | > shall        | include the    |
| \(1\) The name   |                | > include, as  | following      |
| and strength of  |                | > appropriate: | information:   |
| the product and  |                |                |                |
| a description of |                |                | \(1\) The name |
| the dosage form; |                |                | of the dietary |
|                  |                |                | ingredient or  |
|                  |                |                | dietary        |
|                  |                |                | supplement to  |
|                  |                |                | be             |
|                  |                |                | manufactured   |
|                  |                |                | and the        |
|                  |                |                | strength,      |
|                  |                |                | concentration, |
|                  |                |                | weight, or     |
|                  |                |                | measure of     |
|                  |                |                | each dietary   |
|                  |                |                | ingredient for |
|                  |                |                | each batch     |
|                  |                |                | size;          |
+------------------+----------------+----------------+----------------+
| \(3\) A complete |                | > \(i\) A      | \(2\) A        |
| list of          |                | > complete     | complete list  |
| components       |                | > list of raw  | of components  |
| designated by    |                | > materials    | to be used;    |
| names or codes   |                | > used in the  |                |
| sufficiently     |                | > manufacture  |                |
| specific to      |                | > of a dietary |                |
| indicate any     |                | > product,     |                |
| special quality  |                | > designated   |                |
| characteristic;  |                | > by names or  |                |
|                  |                | > codes        |                |
|                  |                | > sufficiently |                |
|                  |                | > specific to  |                |
|                  |                | > indicate any |                |
|                  |                | > special      |                |
|                  |                | > quality      |                |
|                  |                | > char         |                |
|                  |                | acteristic(s). |                |
+------------------+----------------+----------------+----------------+
| \(4\) An         |                | > \(ii\) An    | \(3\) An       |
| accurate         |                | > accurate     | accurate       |
| statement of the |                | > statement of | statement of   |
| weight or        |                | > the weight   | the weight or  |
| measure of each  |                | > or measure   | measure of     |
| component, using |                | > of each raw  | each component |
| the same weight  |                | > material     | to be used;    |
| system (metric,  |                | > used in the  |                |
| avoirdupois, or  |                | > manufacture  |                |
| apothecary) for  |                | > of a dietary |                |
| each component.  |                | > product.     |                |
| Reasonable       |                | > Each batch   |                |
| variations may   |                | > shall be     |                |
| be permitted,    |                | > formulated   |                |
| however, in the  |                | > with the     |                |
| amount of        |                | > intent to    |                |
| components       |                | > provide not  |                |
| necessary for    |                | > less than    |                |
| the preparation  |                | > 100 percent  |                |
| in the dosage    |                | > of each      |                |
| form, provided   |                | > claimed      |                |
| they are         |                | > dietary      |                |
| justified in the |                | > ingredient.  |                |
| master           |                |                |                |
| production and   |                |                |                |
| control records; |                |                |                |
|                  |                |                |                |
| ## §             |                |                |                |
| 211.101 Charge-i |                |                |                |
| n of components. |                |                |                |
|                  |                |                |                |
| \(a\) The batch  |                |                |                |
| shall be         |                |                |                |
| formulated with  |                |                |                |
| the intent to    |                |                |                |
| provide not less |                |                |                |
| than 100 percent |                |                |                |
| of the labeled   |                |                |                |
| or established   |                |                |                |
| amount of active |                |                |                |
| ingredient.      |                |                |                |
+------------------+----------------+----------------+----------------+
| ##               |                | > \(iii\) For  | \(4\) The      |
| § 211.186 Master |                | > dietary      | identity and,  |
|  production and  |                | > supplements, | weight or      |
| control records. |                | > the name and | measure of     |
|                  |                | > weight or    | each dietary   |
| \(b\) (2) The    |                | > measure of   | ingredient     |
| name and weight  |                | > each dietary | that will be   |
| or measure of    |                | > ingredient   | declared on    |
| each active      |                | > per unit or  | the Supplement |
| ingredient per   |                | > portion or   | Facts label    |
| dosage unit or   |                | > per unit of  | and the        |
| per unit of      |                | > weight or    | identity of    |
| weight or        |                | > measure of   | each           |
| measure of the   |                | > the          | ingredient     |
| drug product,    |                | > supplement.  | that will be   |
| and a statement  |                |                | declared on    |
| of the total     |                |                | the            |
| weight or        |                |                | ingredients    |
| measure of any   |                |                | list of the    |
| dosage unit;     |                |                | dietary        |
|                  |                |                | supplement in  |
|                  |                |                | compliance     |
|                  |                |                | with section   |
|                  |                |                | 403(s) of the  |
|                  |                |                | Federal Food,  |
|                  |                |                | Drug, and      |
|                  |                |                | Cosmetic Act;  |
+------------------+----------------+----------------+----------------+
| \(5\) A          |                | > \(iv\) A     | \(5\) A        |
| statement        |                | > statement    | statement that |
| concerning any   |                | > concerning   | explains any   |
| calculated       |                | > any          | intentional    |
| excess of        |                | > calculated   | excess amount  |
| component;       |                | > excess of    | of a dietary   |
|                  |                | > dietary      | ingredient;    |
|                  |                | > ingredient   |                |
|                  |                | > contained in |                |
|                  |                | > a dietary    |                |
|                  |                | > supplement.  |                |
+------------------+----------------+----------------+----------------+
|                  |                | > \(v\) A      |                |
|                  |                | > statement of |                |
|                  |                | > the total    |                |
|                  |                | > weight or    |                |
|                  |                | > measure of   |                |
|                  |                | > any dietary  |                |
|                  |                | > supplement   |                |
|                  |                | > unit.        |                |
+------------------+----------------+----------------+----------------+
| \(6\) A          |                | > \(vi\) A     | \(6\) A        |
| statement of     |                | > statement of | statement of   |
| theoretical      |                | > theoretical  | theoretical    |
| weight or        |                | > weight or    | yield of a     |
| measure at       |                | > measure of a | manufactured   |
| appropriate      |                | > dietary      | dietary        |
| phases of        |                | > ingredient   | ingredient or  |
| processing;      |                | > or dietary   | dietary        |
|                  |                | > supplement   | supplement     |
| \(7\) A          |                | > expected at  | expected at    |
| statement of     |                | > the          | each point,    |
| theoretical      |                | > conclusion   | step, or stage |
| yield, including |                | > of           | of the         |
| the maximum and  |                | > manufacture, | manufacturing  |
| minimum          |                | > including    | process where  |
| percentages of   |                | > the maximum  | control is     |
| theoretical      |                | > and minimum  | needed to      |
| yield beyond     |                | > percentages  | prevent        |
| which            |                | > of           | adulteration,  |
| investigation    |                | > theoretical  | and the        |
| according to     |                | > yield beyond | expected yield |
| §211.192 is      |                | > which        | when you       |
| required;        |                | >              | finish         |
|                  |                |  investigation | manufacturing  |
|                  |                | > is required. | the dietary    |
|                  |                |                | ingredient or  |
|                  |                |                | dietary        |
|                  |                |                | supplement,    |
|                  |                |                | including the  |
|                  |                |                | maximum and    |
|                  |                |                | minimum        |
|                  |                |                | percentages of |
|                  |                |                | theoretical    |
|                  |                |                | yield beyond   |
|                  |                |                | which a        |
|                  |                |                | deviation      |
|                  |                |                | investigation  |
|                  |                |                | of a batch is  |
|                  |                |                | performed and  |
|                  |                |                | material       |
|                  |                |                | review is      |
|                  |                |                | conducted and  |
|                  |                |                | disposition    |
|                  |                |                | decision is    |
|                  |                |                | made;          |
+------------------+----------------+----------------+----------------+
| \(8\) A          |                | > \(vii\) A    | \(7\) A        |
| description of   |                | > description  | description of |
| the drug product |                | > of the       | packaging and  |
| containers,      |                | > product      | a copy of the  |
| closures, and    |                | >              | label to be    |
| packaging        |                |  container(s), | used; and      |
| materials,       |                | > closure(s),  |                |
| including a      |                | > and other    |                |
| specimen or copy |                | > packaging    |                |
| of each label    |                | > materials,   |                |
| and all other    |                | > including    |                |
| labeling signed  |                | > positive     |                |
| and dated by the |                | >              |                |
| person or        |                | identification |                |
| persons          |                | > of all       |                |
| responsible for  |                | > labeling     |                |
| approval of such |                | > used.        |                |
| labeling;        |                |                |                |
+------------------+----------------+----------------+----------------+
| \(9\) Complete   |                | \(viii\)       | \(8\) Written  |
| manufacturing    |                | Manufacturing  | instructions   |
| and control      |                | and control    | including, but |
| instructions,    |                | instructions,  | not limited    |
| sampling and     |                | designed to    | to, the        |
| testing          |                | assure that    | following:     |
| procedures,      |                | the dietary    |                |
| specifications,  |                | product has    | \(i\)          |
| special          |                | the purity,    | Specifications |
| notations, and   |                | composition    | for each       |
| precautions to   |                | and quality it | point, step,   |
| be followed.     |                | is represented | or stage in    |
|                  |                | to possess.    | manufacturing  |
|                  |                |                | the dietary    |
|                  |                |                | ingredient or  |
|                  |                |                | dietary        |
|                  |                |                | supplement     |
|                  |                |                | necessary to   |
|                  |                |                | prevent        |
|                  |                |                | adulteration;  |
|                  |                |                |                |
|                  |                |                | \(ii\)         |
|                  |                |                | Sampling and   |
|                  |                |                | testing        |
|                  |                |                | procedures;    |
|                  |                |                |                |
|                  |                |                | \(iii\)        |
|                  |                |                | Specific       |
|                  |                |                | actions        |
|                  |                |                | necessary to   |
|                  |                |                | perform and    |
|                  |                |                | verify points, |
|                  |                |                | steps, or      |
|                  |                |                | stages,        |
|                  |                |                | necessary to   |
|                  |                |                | meet           |
|                  |                |                | specifications |
|                  |                |                | and otherwise  |
|                  |                |                | prevent        |
|                  |                |                | adulteration,  |
|                  |                |                | including, but |
|                  |                |                | not limited    |
|                  |                |                | to, one person |
|                  |                |                | weighing or    |
|                  |                |                | measuring a    |
|                  |                |                | component and  |
|                  |                |                | another person |
|                  |                |                | verifying the  |
|                  |                |                | weight or      |
|                  |                |                | measure and    |
|                  |                |                | one person     |
|                  |                |                | adding the     |
|                  |                |                | component and  |
|                  |                |                | another person |
|                  |                |                | verifying the  |
|                  |                |                | addition;      |
|                  |                |                |                |
|                  |                |                | \(iv\) Special |
|                  |                |                | notations and  |
|                  |                |                | precautions to |
|                  |                |                | be followed;   |
|                  |                |                | and            |
|                  |                |                |                |
|                  |                |                | \(v\)          |
|                  |                |                | Corrective     |
|                  |                |                | action plans   |
|                  |                |                | for use when a |
|                  |                |                | specification  |
|                  |                |                | is not met.    |
+------------------+----------------+----------------+----------------+
|                  |                | \(a\) (1) ...  | \(c\) You must |
|                  |                | and shall be   | have the       |
|                  |                | reviewed and   | quality        |
|                  |                | approved by    | control unit   |
|                  |                | the quality    | review and     |
|                  |                | control unit.  | approve each   |
|                  |                |                | master         |
|                  |                |                | manufacturing  |
|                  |                |                | record and any |
|                  |                |                | modifications  |
|                  |                |                | to a master    |
|                  |                |                | manufacturing  |
|                  |                |                | record.        |
+------------------+----------------+----------------+----------------+
|                  |                |                | \(d\) You must |
|                  |                |                | keep master    |
|                  |                |                | manufacturing  |
|                  |                |                | records in     |
|                  |                |                | accordance     |
|                  |                |                | with §         |
|                  |                |                | 111.125.       |
+------------------+----------------+----------------+----------------+
| ##               |                | \(b\) Batch    | **§ 111.50     |
|  § 211.188 Batch |                | production and | [What          |
|  production and  |                | control        | requirements   |
| control records. |                | records.       | apply to       |
|                  |                |                | establishing a |
| Batch production |                | \(1\)          | batch          |
| and control      |                | Individual     | production     |
| records shall be |                | batch          | record?]       |
| prepared for     |                | production and | {.underline}** |
| each batch of    |                | control        |                |
| drug product     |                | records shall  | \(a\) You must |
| produced and     |                | be prepared    | prepare a      |
| shall include    |                | and followed   | batch          |
| complete         |                | for each batch | production     |
| information      |                | of dietary     | record every   |
| relating to the  |                | product        | time you       |
| production and   |                | produced and   | manufacture a  |
| control of each  |                | shall include  | batch of a     |
| batch.           |                | complete       | dietary        |
|                  |                | information    | ingredient or  |
|                  |                | relating to    | dietary        |
|                  |                | the production | supplement and |
|                  |                | and control of | the batch      |
|                  |                | each batch.    | production     |
|                  |                |                | record must    |
|                  |                |                | include        |
|                  |                |                | complete       |
|                  |                |                | information    |
|                  |                |                | relating to    |
|                  |                |                | the production |
|                  |                |                | and control of |
|                  |                |                | each batch.    |
+------------------+----------------+----------------+----------------+
| ## § 211.1       |                | \(2\) These    | \(b\) Your     |
| 88 Batch product |                | records shall  | batch          |
| ion and control  |                | be an accurate | production     |
| records. (Cont.) |                | reproduction   | record must    |
|                  |                | of the         | accurately     |
| These records    |                | appropriate    | follow the     |
| shall include:   |                | master         | appropriate    |
|                  |                | production and | master         |
| \(a\) An         |                | control record | manufacturing  |
| accurate         |                | and shall      | record and you |
| reproduction of  |                | include        | must perform   |
| the appropriate  |                | documentation  | each step in   |
| master           |                | that each      | producing the  |
| production or    |                | significant    | batch.         |
| control record,  |                | step in the    |                |
| checked for      |                | manufacture,   | \(c\) The      |
| accuracy, dated, |                | processing,    | batch          |
| and signed;      |                | packing, or    | production     |
|                  |                | holding of the | record must    |
| \(b\)            |                | batch was      | include, but   |
| Documentation    |                | accomplished,  | is not limited |
| that each        |                | including:     | to, the        |
| significant step |                |                | following      |
| in the           |                |                | information:   |
| manufacture,     |                |                |                |
| processing,      |                |                |                |
| packing, or      |                |                |                |
| holding of the   |                |                |                |
| batch was        |                |                |                |
| accomplished,    |                |                |                |
| including:       |                |                |                |
+------------------+----------------+----------------+----------------+
|                  |                |                | \(1\) The      |
|                  |                |                | batch, lot, or |
|                  |                |                | control        |
|                  |                |                | number,        |
+------------------+----------------+----------------+----------------+
| \(1\) Dates;     |                | > \(i\) Dates; | \(2\)          |
|                  |                |                | Documentation  |
|                  |                |                | at the time of |
|                  |                |                | performance,   |
|                  |                |                | showing the    |
|                  |                |                | date on which  |
|                  |                |                | each step of   |
|                  |                |                | the master     |
|                  |                |                | manufacturing  |
|                  |                |                | record was     |
|                  |                |                | performed, and |
|                  |                |                | the initials   |
|                  |                |                | of the persons |
|                  |                |                | performing     |
|                  |                |                | each step,     |
|                  |                |                | including but  |
|                  |                |                | not limited    |
|                  |                |                | to:            |
|                  |                |                |                |
|                  |                |                | \(i\) The      |
|                  |                |                | person         |
|                  |                |                | responsible    |
|                  |                |                | for weighing   |
|                  |                |                | or measuring   |
|                  |                |                | each component |
|                  |                |                | used in the    |
|                  |                |                | batch; and     |
|                  |                |                |                |
|                  |                |                | \(ii\) The     |
|                  |                |                | person         |
|                  |                |                | responsible    |
|                  |                |                | for adding the |
|                  |                |                | component to   |
|                  |                |                | the batch.     |
+------------------+----------------+----------------+----------------+
| \(2\) Identity   |                | > \(ii\)       | \(3\) The      |
| of individual    |                | > Identity of  | identity of    |
| major equipment  |                | > individual   | equipment and  |
| and lines used;  |                | > major        | processing     |
|                  |                | > equipment    | lines used in  |
|                  |                | > and lines    | producing the  |
|                  |                | > used;        | batch;         |
+------------------+----------------+----------------+----------------+
| **§ 211.182      |                | ### Equipmen   | 4\) The date   |
| Equipment        |                | t and Utensils | and time of    |
| cleaning and use |                |                | the            |
| log.**           |                | \(b\)          | maintenance,   |
|                  |                | Sanitation of  | cleaning, and  |
| A written record |                | equipment and  | sanitizing of  |
| of major         |                | utensils.      | the equipment  |
| equipment        |                |                | and processing |
| cleaning,        |                | \(11\) A       | lines used in  |
| maintenance      |                | written record | producing the  |
| (except routine  |                | of major       | batch;         |
| maintenance such |                | equipment      |                |
| as lubrication   |                | cleaning and   |                |
| and              |                | use shall be   |                |
| adjustments),    |                | maintained in  |                |
| and use shall be |                | individual     |                |
| included in      |                | equipment logs |                |
| individual       |                | that show the  |                |
| equipment logs   |                | date, product  |                |
| that show the    |                | and lot number |                |
| date, time,      |                | of each batch  |                |
| product, and lot |                | processed. The |                |
| number of each   |                | persons        |                |
| batch processed. |                | performing the |                |
| If equipment is  |                | cleaning shall |                |
| dedicated to     |                | record in the  |                |
| manufacture of   |                | log that the   |                |
| one product,     |                | work was       |                |
| then individual  |                | performed.     |                |
| equipment logs   |                | Entries in the |                |
| are not          |                | log should be  |                |
| required,        |                | in             |                |
| provided that    |                | chronological  |                |
| lots or batches  |                | order.         |                |
| of such product  |                |                |                |
| follow in        |                |                |                |
| numerical order  |                |                |                |
| and are          |                |                |                |
| manufactured in  |                |                |                |
| numerical        |                |                |                |
| sequence. In     |                |                |                |
| cases where      |                |                |                |
| dedicated        |                |                |                |
| equipment is     |                |                |                |
| employed, the    |                |                |                |
| records of       |                |                |                |
| cleaning,        |                |                |                |
| maintenance, and |                |                |                |
| use shall be     |                |                |                |
| part of the      |                |                |                |
| batch record.    |                |                |                |
| The persons      |                |                |                |
| performing and   |                |                |                |
| double-checking  |                |                |                |
| the cleaning and |                |                |                |
| maintenance      |                |                |                |
| shall date and   |                |                |                |
| sign or initial  |                |                |                |
| the log          |                |                |                |
| indicating that  |                |                |                |
| the work was     |                |                |                |
| performed.       |                |                |                |
| Entries in the   |                |                |                |
| log shall be in  |                |                |                |
| chronological    |                |                |                |
| order.           |                |                |                |
+------------------+----------------+----------------+----------------+
| **§ 211.188      |                | > \(vi\)       |                |
| Batch production |                | > Inspection   |                |
| and control      |                | > of the       |                |
| records.         |                | > packaging    |                |
| (Cont.)**        |                | > and labeling |                |
|                  |                | > area;        |                |
| \(6\) Inspection |                |                |                |
| of the packaging |                |                |                |
| and labeling     |                |                |                |
| area before and  |                |                |                |
| after use;       |                |                |                |
+------------------+----------------+----------------+----------------+
| \(3\) Specific   |                | > \(iii\)      | \(5\) The      |
| identification   |                | > Specific     | shipment lot   |
| of each batch of |                | > i            | unique         |
| component or     |                | dentification, | identifier of  |
| in-process       |                | > including    | each           |
| material used;   |                | > lot number,  | component,     |
|                  |                | > of each raw  | dietary        |
|                  |                | > material or  | ingredient,    |
|                  |                | > in-process   | dietary        |
|                  |                | > material     | supplement,    |
|                  |                | > used;        | packaging, and |
|                  |                |                | label used;    |
+------------------+----------------+----------------+----------------+
| \(4\) Weights    |                | > \(iv\)       | \(6\) The      |
| and measures of  |                | > Weight or    | identity and   |
| components used  |                | > measure of   | weight or      |
| in the course of |                | > each raw     | measure of     |
| processing;      |                | > material     | each component |
|                  |                | > used in the  | used;          |
|                  |                | > course of    |                |
|                  |                | > processing;  |                |
+------------------+----------------+----------------+----------------+
| \(11\)           |                |                | \(7\) The      |
| Identification   |                |                | initials at    |
| of the persons   |                |                | the time of    |
| performing and   |                |                | performance or |
| directly         |                |                | at the         |
| supervising or   |                |                | completion of  |
| checking each    |                |                | the batch of   |
| significant step |                |                | the person     |
| in the           |                |                | responsible    |
| operation;       |                |                | for verifying  |
|                  |                |                | the weight or  |
|                  |                |                | measure of     |
|                  |                |                | each component |
|                  |                |                | used in the    |
|                  |                |                | batch;         |
+------------------+----------------+----------------+----------------+
| \(11\)           |                |                | \(8\) The      |
| Identification   |                |                | initials at    |
| of the persons   |                |                | the time of    |
| performing and   |                |                | performance or |
| directly         |                |                | at the         |
| supervising or   |                |                | completion of  |
| checking each    |                |                | the batch of   |
| significant step |                |                | the person     |
| in the           |                |                | responsible    |
| operation;       |                |                | for verifying  |
|                  |                |                | the addition   |
|                  |                |                | of components  |
|                  |                |                | to the batch;  |
+------------------+----------------+----------------+----------------+
| \(7\) A          |                | > \(vii\) A    | \(9\) A        |
| statement of the |                | > statement of | statement of   |
| actual yield and |                | > the actual   | the actual     |
| a statement of   |                | > yield at the | yield and a    |
| the percentage   |                | > conclusion   | statement of   |
| of theoretical   |                | > of           | the percentage |
| yield at         |                | > manufacture  | of theoretical |
| appropriate      |                | > and a        | yield at       |
| phases of        |                | > statement of | appropriate    |
| processing;      |                | > the          | phases of      |
|                  |                | > percentage   | processing;    |
| ##               |                | > of           |                |
|  § 211.103 Calcu |                | > theoretical  |                |
| lation of yield. |                | > yield, as    |                |
|                  |                | > appropriate; |                |
| Actual yields    |                |                |                |
| and percentages  |                |                |                |
| of theoretical   |                |                |                |
| yield shall be   |                |                |                |
| determined at    |                |                |                |
| the conclusion   |                |                |                |
| of each          |                |                |                |
| appropriate      |                |                |                |
| phase of         |                |                |                |
| manufacturing,   |                |                |                |
| processing,      |                |                |                |
| packaging, or    |                |                |                |
| holding of the   |                |                |                |
| drug product.    |                |                |                |
| Such             |                |                |                |
| calculations     |                |                |                |
| shall be         |                |                |                |
| performed by one |                |                |                |
| person and       |                |                |                |
| independently    |                |                |                |
| verified by a    |                |                |                |
| second person.   |                |                |                |
+------------------+----------------+----------------+----------------+
| **§ 211.188      |                | > \(v\)        | \(10\) The     |
| Batch production |                | > Quality      | actual test    |
| and control      |                | > control      | results for    |
| records.         |                | > results;     | any testing    |
| (Cont.)**        |                |                | performed      |
|                  |                |                | during the     |
| \(5\) In-process |                |                | batch          |
| and laboratory   |                |                | production;    |
| control results; |                |                |                |
+------------------+----------------+----------------+----------------+
|                  |                |                | \(11\)         |
|                  |                |                | Documentation  |
|                  |                |                | that the       |
|                  |                |                | dietary        |
|                  |                |                | ingredient and |
|                  |                |                | dietary        |
|                  |                |                | supplement     |
|                  |                |                | meets          |
|                  |                |                | s              |
|                  |                |                | pecifications; |
+------------------+----------------+----------------+----------------+
| \(8\) Complete   |                | > \(viii\)     | \(12\) Copies  |
| labeling control |                | > Label        | of all         |
| records,         |                | > control      | container      |
| including        |                | > records,     | labels used    |
| specimens or     |                | > including    | and the        |
| copies of all    |                | > specimens,   | results of     |
| labeling used;   |                | > copies or    | examinations   |
|                  |                | > records of   | conducted      |
|                  |                | > all labels   | during the     |
|                  |                | > used;        | label          |
|                  |                |                | operation to   |
|                  |                |                | ensure that    |
|                  |                |                | the containers |
|                  |                |                | have the       |
|                  |                |                | correct label; |
+------------------+----------------+----------------+----------------+
| \(9\)            |                | > \(ix\)       |                |
| Description of   |                | > Description  |                |
| drug product     |                | > of product   |                |
| containers and   |                | > containers   |                |
| closures;        |                | > and closures |                |
|                  |                | > used;        |                |
+------------------+----------------+----------------+----------------+
| \(12\) Any       |                | > \(x\) Any    | \(13\) Any     |
| investigation    |                | > special      | documented     |
| made according   |                | > notes of     | material       |
| to §211.192.     |                | >              | review and     |
|                  |                | investigations | disposition    |
|                  |                | > or           | decision in    |
|                  |                | > deviations   | accordance     |
|                  |                | > from the     | with §         |
|                  |                | > described    | 111.35(j); and |
|                  |                | > process.     |                |
+------------------+----------------+----------------+----------------+
|                  |                |                | \(14\)         |
|                  |                |                | Signature of   |
|                  |                |                | the quality    |
|                  |                |                | control unit   |
|                  |                |                | to document    |
|                  |                |                | batch          |
|                  |                |                | production     |
|                  |                |                | record review  |
|                  |                |                | and any        |
|                  |                |                | approval for   |
|                  |                |                | reprocessing   |
|                  |                |                | or             |
|                  |                |                | repackaging.   |
+------------------+----------------+----------------+----------------+
| \(10\) Any       |                |                |                |
| sampling         |                |                |                |
| performed;       |                |                |                |
+------------------+----------------+----------------+----------------+
| \(13\) Results   |                |                |                |
| of examinations  |                |                |                |
| made in          |                |                |                |
| accordance with  |                |                |                |
| §211.134.        |                |                |                |
+------------------+----------------+----------------+----------------+
| ## § 211.111     |                |                |                |
|  Time limitation |                |                |                |
| s on production. |                |                |                |
|                  |                |                |                |
| When             |                |                |                |
| appropriate,     |                |                |                |
| time limits for  |                |                |                |
| the completion   |                |                |                |
| of each phase of |                |                |                |
| production shall |                |                |                |
| be established   |                |                |                |
| to assure the    |                |                |                |
| quality of the   |                |                |                |
| drug product.    |                |                |                |
| Deviation from   |                |                |                |
| established time |                |                |                |
| limits may be    |                |                |                |
| acceptable if    |                |                |                |
| such deviation   |                |                |                |
| does not         |                |                |                |
| compromise the   |                |                |                |
| quality of the   |                |                |                |
| drug product.    |                |                |                |
| Such deviation   |                |                |                |
| shall be         |                |                |                |
| justified and    |                |                |                |
| documented.      |                |                |                |
+------------------+----------------+----------------+----------------+
| ## § 2           |                | \(3\) Any      | \(d\) The      |
| 11.192 Productio |                | deviation from | quality        |
| n record review. |                | written,       | control unit   |
|                  |                | approved       | must review in |
| All drug product |                | s              | accordance     |
| production and   |                | pecifications, | with § 111.37  |
| control records, |                | standards,     | (b) (5) the    |
| including those  |                | test           | batch          |
| for packaging    |                | procedures or  | production     |
| and labeling,    |                | other          | record         |
| shall be         |                | laboratory     | established in |
| reviewed and     |                | control        | paragraph (c)  |
| approved by the  |                | mechanisms     | of this        |
| quality control  |                | shall be       | section.       |
| unit to          |                | recorded and   |                |
| determine        |                | justified.     | \(1\) If a     |
| compliance with  |                |                | batch deviates |
| all established, |                |                | from the       |
| approved written |                |                | master         |
| procedures       |                |                | manufacturing  |
| before a batch   |                |                | record,        |
| is released or   |                |                | including any  |
| distributed. Any |                |                | deviation from |
| unexplained      |                |                | s              |
| discrepancy      |                |                | pecifications, |
| (including a     |                |                | the quality    |
| percentage of    |                |                | control unit   |
| theoretical      |                |                | must conduct a |
| yield exceeding  |                |                | material       |
| the maximum or   |                |                | review and     |
| minimum          |                |                | make a         |
| percentages      |                |                | disposition    |
| established in   |                |                | decision and   |
| master           |                |                | record any     |
| production and   |                |                | decision in    |
| control records) |                |                | the batch      |
| or the failure   |                |                | production     |
| of a batch or    |                |                | record.        |
| any of its       |                |                |                |
| components to    |                |                | \(2\) The      |
| meet any of its  |                |                | quality        |
| specifications   |                |                | control unit   |
| shall be         |                |                | must not       |
| thoroughly       |                |                | approve and    |
| investigated,    |                |                | release for    |
| whether or not   |                |                | distribution   |
| the batch has    |                |                | any batch of   |
| already been     |                |                | dietary        |
| distributed. The |                |                | ingredient or  |
| investigation    |                |                | dietary        |
| shall extend to  |                |                | supplement     |
| other batches of |                |                | that does not  |
| the same drug    |                |                | meet all       |
| product and      |                |                | s              |
| other drug       |                |                | pecifications. |
| products that    |                |                |                |
| may have been    |                |                |                |
| associated with  |                |                |                |
| the specific     |                |                |                |
| failure or       |                |                |                |
| discrepancy. A   |                |                |                |
| written record   |                |                |                |
| of the           |                |                |                |
| investigation    |                |                |                |
| shall be made    |                |                |                |
| and shall        |                |                |                |
| include the      |                |                |                |
| conclusions and  |                |                |                |
| followup.        |                |                |                |
+------------------+----------------+----------------+----------------+
| ## § 211.100     |                |                | \(e\) The      |
|  Written procedu |                |                | quality        |
| res; deviations. |                |                | control unit   |
|                  |                |                | must document  |
| \(a\) There      |                |                | in accordance  |
| shall be written |                |                | with §         |
| procedures for   |                |                | 111.37(c) the  |
| production and   |                |                | review         |
| process control  |                |                | performed in   |
| designed to      |                |                | accordance     |
| assure that the  |                |                | with paragraph |
| drug products    |                |                | (d) of this    |
| have the         |                |                | section and it |
| identity,        |                |                | must be        |
| strength,        |                |                | documented at  |
| quality, and     |                |                | the time of    |
| purity they      |                |                | performance.   |
| purport or are   |                |                | The review and |
| represented to   |                |                | documentation  |
| possess. Such    |                |                | must include,  |
| procedures shall |                |                | but is not     |
| include all      |                |                | limited to,    |
| requirements in  |                |                | the following: |
| this subpart.    |                |                |                |
| These written    |                |                | \(1\) Review   |
| procedures,      |                |                | of component,  |
| including any    |                |                | dietary        |
| changes, shall   |                |                | ingredient,    |
| be drafted,      |                |                | and dietary    |
| reviewed, and    |                |                | supplement     |
| approved by the  |                |                | receiving      |
| appropriate      |                |                | records        |
| organizational   |                |                | including      |
| units and        |                |                | review of      |
| reviewed and     |                |                | testing and    |
| approved by the  |                |                | examination    |
| quality control  |                |                | results;       |
| unit.            |                |                |                |
|                  |                |                | \(2\)          |
| ##               |                |                | Identification |
|  (b) Written pro |                |                | of any         |
| duction and proc |                |                | deviation from |
| ess control proc |                |                | the master     |
| edures shall be  |                |                | manufacturing  |
| followed in the  |                |                | record that    |
| execution of the |                |                | may have       |
|  various product |                |                | caused a batch |
| ion and process  |                |                | or any of its  |
| control function |                |                | components to  |
| s and shall be d |                |                | fail to meet   |
| ocumented at the |                |                | specifications |
|  time of perform |                |                | identified in  |
| ance. Any deviat |                |                | the master     |
| ion from the wri |                |                | production     |
| tten procedures  |                |                | record;        |
| shall be recorde |                |                |                |
| d and justified. |                |                | \(3\) Records  |
|                  |                |                | of             |
|                  |                |                | i              |
|                  |                |                | nvestigations, |
|                  |                |                | conclusions,   |
|                  |                |                | and corrective |
|                  |                |                | actions        |
|                  |                |                | performed in   |
|                  |                |                | accordance     |
|                  |                |                | with paragraph |
|                  |                |                | (d) of this    |
|                  |                |                | section; and   |
|                  |                |                |                |
|                  |                |                | \(4\) The      |
|                  |                |                | identity of    |
|                  |                |                | the person     |
|                  |                |                | qualified by   |
|                  |                |                | training and   |
|                  |                |                | experience who |
|                  |                |                | performed the  |
|                  |                |                | investigation  |
|                  |                |                | in accordance  |
|                  |                |                | with paragraph |
|                  |                |                | (d) of this    |
|                  |                |                | section.       |
+------------------+----------------+----------------+----------------+
|                  |                |                | \(f\) You must |
|                  |                |                | not reprocess  |
|                  |                |                | a batch that   |
|                  |                |                | deviates from  |
|                  |                |                | the master     |
|                  |                |                | manufacturing  |
|                  |                |                | record unless  |
|                  |                |                | approved by    |
|                  |                |                | the quality    |
|                  |                |                | control unit.  |
|                  |                |                | You must not   |
|                  |                |                | reprocess a    |
|                  |                |                | dietary        |
|                  |                |                | ingredient or  |
|                  |                |                | dietary        |
|                  |                |                | supplement if  |
|                  |                |                | it is rejected |
|                  |                |                | because of     |
|                  |                |                | contamination  |
|                  |                |                | with           |
|                  |                |                | microorganisms |
|                  |                |                | of public      |
|                  |                |                | health         |
|                  |                |                | significance   |
|                  |                |                | or other       |
|                  |                |                | contaminants,  |
|                  |                |                | such as heavy  |
|                  |                |                | metals;        |
+------------------+----------------+----------------+----------------+
|                  |                |                | \(g\) Any      |
|                  |                |                | batch of       |
|                  |                |                | dietary        |
|                  |                |                | ingredient or  |
|                  |                |                | dietary        |
|                  |                |                | supplement     |
|                  |                |                | that is        |
|                  |                |                | reprocessed    |
|                  |                |                | must meet all  |
|                  |                |                | specifications |
|                  |                |                | for the batch  |
|                  |                |                | of dietary     |
|                  |                |                | ingredient or  |
|                  |                |                | dietary        |
|                  |                |                | supplement and |
|                  |                |                | be evaluated   |
|                  |                |                | and approved   |
|                  |                |                | by the quality |
|                  |                |                | control unit   |
|                  |                |                | before         |
|                  |                |                | releasing for  |
|                  |                |                | distribution.  |
|                  |                |                | The results of |
|                  |                |                | the            |
|                  |                |                | reevaluation   |
|                  |                |                | by the quality |
|                  |                |                | control unit   |
|                  |                |                | must be        |
|                  |                |                | documented in  |
|                  |                |                | the batch      |
|                  |                |                | production     |
|                  |                |                | record; and    |
+------------------+----------------+----------------+----------------+
| **§ 211.170      |                |                | \(h\) You must |
| Reserve          |                |                | collect        |
| samples.**       |                |                | representative |
|                  |                |                | reserve        |
| \(b\) An         |                |                | samples of     |
| appropriately    |                |                | each batch of  |
| identified       |                |                | dietary        |
| reserve sample   |                |                | ingredient or  |
| that is          |                |                | dietary        |
| representative   |                |                | supplement and |
| of each lot or   |                |                | keep the       |
| batch of drug    |                |                | reserve        |
| product shall be |                |                | samples for 3  |
| retained and     |                |                | years from the |
| stored under     |                |                | date of        |
| conditions       |                |                | manufacture    |
| consistent with  |                |                | for use in     |
| product          |                |                | appropriate    |
| labeling. The    |                |                | investigations |
| reserve sample   |                |                | including, but |
| shall be stored  |                |                | not limited    |
| in the same      |                |                | to, consumer   |
| immediate        |                |                | complaint      |
| c                |                |                | investigations |
| ontainer-closure |                |                | to determine   |
| system in which  |                |                | whether, for   |
| the drug product |                |                | example, the   |
| is marketed or   |                |                | dietary        |
| in one that has  |                |                | ingredient or  |
| essentially the  |                |                | dietary        |
| same             |                |                | supplement     |
| characteristics. |                |                | associated     |
| The reserve      |                |                | with a         |
| sample consists  |                |                | consumer       |
| of at least      |                |                | complaint      |
| twice the        |                |                | failed to meet |
| quantity         |                |                | any of its     |
| necessary to     |                |                | specifications |
| perform all the  |                |                | for identity,  |
| required tests,  |                |                | purity,        |
| except those for |                |                | quality,       |
| sterility and    |                |                | strength, and  |
| pyrogens...      |                |                | composition.   |
|                  |                |                |                |
| The retention    |                |                |                |
| time is as       |                |                |                |
| follows:         |                |                |                |
|                  |                |                |                |
| \(1\) For a drug |                |                |                |
| product other    |                |                |                |
| than those       |                |                |                |
| described in     |                |                |                |
| paragraphs (b)   |                |                |                |
| (2) and (3) of   |                |                |                |
| this section,    |                |                |                |
| the reserve      |                |                |                |
| sample shall be  |                |                |                |
| retained for 1   |                |                |                |
| year after the   |                |                |                |
| expiration date  |                |                |                |
| of the drug      |                |                |                |
| product.         |                |                |                |
|                  |                |                |                |
| \(3\) For an OTC |                |                |                |
| drug product     |                |                |                |
| that is exempt   |                |                |                |
| for bearing an   |                |                |                |
| expiration date  |                |                |                |
| under §211.137,  |                |                |                |
| the reserve      |                |                |                |
| sample must be   |                |                |                |
| retained for 3   |                |                |                |
| years after the  |                |                |                |
| lot or batch of  |                |                |                |
| drug product is  |                |                |                |
| distributed.     |                |                |                |
+------------------+----------------+----------------+----------------+
|                  |                |                | \(i\) You must |
|                  |                |                | keep batch     |
|                  |                |                | production     |
|                  |                |                | records in     |
|                  |                |                | accordance     |
|                  |                |                | with §         |
|                  |                |                | 111.125.       |
+------------------+----------------+----------------+----------------+
| **§ 211.22       |                | \(2\) Adequate | **§ 111.60     |
| Responsibilities |                | laboratory     | [What          |
| of quality       |                | facilities     | requirements   |
| control unit.**  |                | should be      | apply to       |
|                  |                | available, as  | laboratory     |
| \(b\) Adequate   |                | needed, to the | operations?]   |
| laboratory       |                | quality        | {.underline}** |
| facilities for   |                | control unit.  |                |
| the testing and  |                |                | \(a\) You must |
| approval (or     |                |                | use adequate   |
| rejection) of    |                |                | laboratory     |
| components, drug |                |                | facilities to  |
| product          |                |                | perform        |
| containers,      |                |                | whatever       |
| closures,        |                |                | testing and    |
| packaging        |                |                | examinations   |
| materials,       |                |                | are necessary  |
| in-process       |                |                | to determine   |
| materials, and   |                |                | that           |
| drug products    |                |                | components,    |
| shall be         |                |                | dietary        |
| available to the |                |                | ingredients,   |
| quality control  |                |                | and dietary    |
| unit.            |                |                | supplements    |
|                  |                |                | received meet  |
|                  |                |                | s              |
|                  |                |                | pecifications; |
|                  |                |                | that           |
|                  |                |                | specifications |
|                  |                |                | are met during |
|                  |                |                | in-process, as |
|                  |                |                | specified in   |
|                  |                |                | the master     |
|                  |                |                | manufacturing  |
|                  |                |                | record; and    |
|                  |                |                | that dietary   |
|                  |                |                | ingredients    |
|                  |                |                | and dietary    |
|                  |                |                | supplements    |
|                  |                |                | manufactured   |
|                  |                |                | meet           |
|                  |                |                | s              |
|                  |                |                | pecifications. |
+------------------+----------------+----------------+----------------+
|                  |                |                | (b)(1) You     |
|                  |                |                | must establish |
|                  |                |                | and follow     |
|                  |                |                | laboratory     |
|                  |                |                | control        |
|                  |                |                | processes that |
|                  |                |                | are approved   |
|                  |                |                | by the quality |
|                  |                |                | control unit.  |
|                  |                |                | Laboratory     |
|                  |                |                | control        |
|                  |                |                | processes must |
|                  |                |                | include, but   |
|                  |                |                | are not        |
|                  |                |                | limited to,    |
|                  |                |                | the following: |
|                  |                |                |                |
|                  |                |                | \(i\) Use of   |
|                  |                |                | criteria for   |
|                  |                |                | selecting      |
|                  |                |                | appropriate    |
|                  |                |                | examination    |
|                  |                |                | and testing    |
|                  |                |                | methods;       |
|                  |                |                |                |
|                  |                |                | \(ii\) Use of  |
|                  |                |                | criteria for   |
|                  |                |                | establishing   |
|                  |                |                | appropriate    |
|                  |                |                | s              |
|                  |                |                | pecifications; |
|                  |                |                | and            |
|                  |                |                |                |
|                  |                |                | \(iii\) Use of |
|                  |                |                | sampling plans |
|                  |                |                | for obtaining  |
|                  |                |                | representative |
|                  |                |                | samples of:    |
|                  |                |                |                |
|                  |                |                | \(A\)          |
|                  |                |                | Components,    |
|                  |                |                | dietary        |
|                  |                |                | ingredients,   |
|                  |                |                | and dietary    |
|                  |                |                | supplements    |
|                  |                |                | received to    |
|                  |                |                | determine      |
|                  |                |                | whether        |
|                  |                |                | specifications |
|                  |                |                | are met;       |
|                  |                |                |                |
|                  |                |                | \(B\)          |
|                  |                |                | In-process     |
|                  |                |                | materials      |
|                  |                |                | during the     |
|                  |                |                | batch          |
|                  |                |                | manufacturing  |
|                  |                |                | when testing   |
|                  |                |                | or examination |
|                  |                |                | is required in |
|                  |                |                | the master     |
|                  |                |                | manufacturing  |
|                  |                |                | record;        |
|                  |                |                |                |
|                  |                |                | \(C\) Each     |
|                  |                |                | batch of       |
|                  |                |                | dietary        |
|                  |                |                | ingredient or  |
|                  |                |                | dietary        |
|                  |                |                | supplement     |
|                  |                |                | manufactured   |
|                  |                |                | to determine   |
|                  |                |                | that the       |
|                  |                |                | dietary        |
|                  |                |                | ingredient or  |
|                  |                |                | dietary        |
|                  |                |                | supplement     |
|                  |                |                | meets          |
|                  |                |                | s              |
|                  |                |                | pecifications; |
|                  |                |                |                |
|                  |                |                | \(D\)          |
|                  |                |                | Packaging and  |
|                  |                |                | labels         |
|                  |                |                | received to    |
|                  |                |                | determine that |
|                  |                |                | he materials   |
|                  |                |                | meet           |
|                  |                |                | s              |
|                  |                |                | pecifications; |
|                  |                |                | and            |
|                  |                |                |                |
|                  |                |                | \(E\) Each     |
|                  |                |                | batch of       |
|                  |                |                | packaged and   |
|                  |                |                | labeled        |
|                  |                |                | dietary        |
|                  |                |                | ingredients or |
|                  |                |                | dietary        |
|                  |                |                | supplements to |
|                  |                |                | ensure that    |
|                  |                |                | the label      |
|                  |                |                | specified in   |
|                  |                |                | the master     |
|                  |                |                | manufacturing  |
|                  |                |                | record has     |
|                  |                |                | been applied.  |
|                  |                |                |                |
|                  |                |                | \(iv\) Use of  |
|                  |                |                | criteria for   |
|                  |                |                | selecting      |
|                  |                |                | standard       |
|                  |                |                | reference      |
|                  |                |                | materials used |
|                  |                |                | in performing  |
|                  |                |                | tests and      |
|                  |                |                | examinations;  |
|                  |                |                |                |
|                  |                |                | \(v\) Use of   |
|                  |                |                | appropriate    |
|                  |                |                | test method    |
|                  |                |                | validations;   |
|                  |                |                | and            |
|                  |                |                |                |
|                  |                |                | \(vi\) Use of  |
|                  |                |                | test methods   |
|                  |                |                | and,           |
|                  |                |                | examinations   |
|                  |                |                | in accordance  |
|                  |                |                | with           |
|                  |                |                | established    |
|                  |                |                | criteria,      |
|                  |                |                |                |
|                  |                |                | \(2\) The      |
|                  |                |                | person who     |
|                  |                |                | conducts the   |
|                  |                |                | testing and    |
|                  |                |                | examination at |
|                  |                |                | the time of    |
|                  |                |                | performance    |
|                  |                |                | must document  |
|                  |                |                | that           |
|                  |                |                | laboratory     |
|                  |                |                | examination    |
|                  |                |                | results.       |
|                  |                |                |                |
|                  |                |                | \(3\) You must |
|                  |                |                | keep           |
|                  |                |                | laboratory     |
|                  |                |                | examination    |
|                  |                |                | and testing    |
|                  |                |                | records in     |
|                  |                |                | accordance     |
|                  |                |                | with §         |
|                  |                |                | 111.125.       |
+------------------+----------------+----------------+----------------+
|                  |                |                | \(c\) You must |
|                  |                |                | verify that    |
|                  |                |                | the laboratory |
|                  |                |                | examination    |
|                  |                |                | and testing    |
|                  |                |                | methodologies  |
|                  |                |                | are            |
|                  |                |                | appropriate    |
|                  |                |                | for their      |
|                  |                |                | intended use.  |
+------------------+----------------+----------------+----------------+
|                  |                |                | \(d\) You must |
|                  |                |                | identify and   |
|                  |                |                | use the        |
|                  |                |                | appropriate    |
|                  |                |                | validated      |
|                  |                |                | testing method |
|                  |                |                | for each       |
|                  |                |                | established    |
|                  |                |                | specification  |
|                  |                |                | for which      |
|                  |                |                | testing is     |
|                  |                |                | required to    |
|                  |                |                | determine      |
|                  |                |                | whether the    |
|                  |                |                | specification  |
|                  |                |                | is met.        |
+------------------+----------------+----------------+----------------+
|                  |                |                | **§ 111.65     |
|                  |                |                | [What          |
|                  |                |                | requirements   |
|                  |                |                | apply to       |
|                  |                |                | manufacturing  |
|                  |                |                | operations?]   |
|                  |                |                | {.underline}** |
|                  |                |                |                |
|                  |                |                | \(a\) You must |
|                  |                |                | design or      |
|                  |                |                | select         |
|                  |                |                | manufacturing  |
|                  |                |                | processes to   |
|                  |                |                | ensure that    |
|                  |                |                | dietary        |
|                  |                |                | ingredient or  |
|                  |                |                | dietary        |
|                  |                |                | specifications |
|                  |                |                | are            |
|                  |                |                | consistently   |
|                  |                |                | achieved.      |
+------------------+----------------+----------------+----------------+
|                  | **¶110.80      | \(d\)          | \(b\) You must |
|                  | Processes and  | Manufacturing  | conduct all    |
|                  | controls.**    | operations.    | manufacturing  |
|                  |                |                | operations in  |
|                  | All operations | \(1\) All      | accordance     |
|                  | in the         | operations in  | with adequate  |
|                  | receiving,     | the receiving, | sanitation     |
|                  | inspecting,    | inspecting,    | principles.    |
|                  | transporting,  | transporting,  |                |
|                  | segregating,   | segregating,   |                |
|                  | preparing,     | preparing,     |                |
|                  | manufacturing, | manufacturing, |                |
|                  | packaging, and | packaging, and |                |
|                  | storing of     | storing of     |                |
|                  | food shall be  | dietary        |                |
|                  | conducted in   | products shall |                |
|                  | accordance     | be conducted   |                |
|                  | with adequate  | in accordance  |                |
|                  | sanitation     | with adequate  |                |
|                  | principles\... | sanitation     |                |
|                  |                | principles.    |                |
+------------------+----------------+----------------+----------------+
|                  | \...All        | \(2\) All      | \(c\) You must |
|                  | reasonable     | reasonable     | take all the   |
|                  | precautions    | precautions    | necessary      |
|                  | shall be taken | shall be taken | precautions    |
|                  | to ensure that | to assure that | during the     |
|                  | production     | production     | manufacture of |
|                  | procedures do  | procedures do  | a dietary      |
|                  | not contribute | not contribute | ingredient or  |
|                  | contamination  | adulteration   | dietary        |
|                  | from any       | from any       | supplement to  |
|                  | source.        | source.        | prevent        |
|                  | Chemical,      | Chemical,      | contamination  |
|                  | microbial, or  | microbial, or  | of components, |
|                  | extra          | extra          | dietary        |
|                  | neous-material | neous-material | ingredients,   |
|                  | testing        | testing        | or dietary     |
|                  | procedures     | procedures     | supplements.   |
|                  | shall be used  | shall be used  | These          |
|                  | where          | where          | precautions    |
|                  | necessary to   | necessary to   | include, but   |
|                  | identify       | identify       | are not        |
|                  | sanitation     | sanitation     | limited to:    |
|                  | failures or    | failures or    |                |
|                  | possible food  | possible       |                |
|                  | contamination. | product        |                |
|                  |                | adulteration.  |                |
+------------------+----------------+----------------+----------------+
| ## § 2           | **¶110.80(b)   | \(4\) All      | \(1\)          |
| 11.113 Control o | Manufacturing  | product        | Performing     |
| f microbiologica | operations.**  | manufacturing, | manufacturing  |
| l contamination. |                | including      | operations     |
|                  | \...(2) All    | packaging and  | under          |
| \(a\)            | food           | storage, shall | conditions and |
| Appropriate      | manufacturing, | be conducted   | controls that  |
| written          | including      | under such     | protect        |
| procedures,      | packaging and  | conditions and | against the    |
| designed to      | storage, shall | controls as    | potential for  |
| prevent          | be conducted   | are necessary  | growth of      |
| objectionable    | under such     | to minimize    | microorganisms |
| microorganisms   | conditions and | the potential  | and the        |
| in drug products | controls as    | for the growth | potential for  |
| not required to  | are necessary  | of             | contamination; |
| be sterile,      | to minimize    | m              |                |
| shall be         | the potential  | icroorganisms, |                |
| established and  | for the growth | or for the     |                |
| followed.        | of             | adulteration   |                |
|                  | m              | of raw         |                |
| \(b\)            | icroorganisms, | materials,     |                |
| Appropriate      | or for the     | in-process     |                |
| written          | contamination  | materials and  |                |
| procedures,      | of food.       | finished       |                |
| designed to      |                | product.       |                |
| prevent          |                |                |                |
| microbiological  |                |                |                |
| contamination of |                |                |                |
| drug products    |                |                |                |
| purporting to be |                |                |                |
| sterile, shall   |                |                |                |
| be established   |                |                |                |
| and followed.    |                |                |                |
| Such procedures  |                |                |                |
| shall include    |                |                |                |
| validation of    |                |                |                |
| any              |                |                |                |
| sterilization    |                |                |                |
| process.         |                |                |                |
+------------------+----------------+----------------+----------------+
|                  | (1)\...Raw     | \(2\) Raw      | \(2\) Washing  |
|                  | materials      | agricultural   | or cleaning    |
|                  | shall be       | materials that | components     |
|                  | washed or      | contain soil   | that contain   |
|                  | cleaned as     | or other       | soil or other  |
|                  | necessary to   | contaminants   | contaminants;  |
|                  | remove soil or | shall be       |                |
|                  | other          | washed or      |                |
|                  | contamination. | cleaned as     |                |
|                  |                | necessary.     |                |
+------------------+----------------+----------------+----------------+
|                  | (1)\...Water   | (2)... Water   | \(3\) Using    |
|                  | used for       | used for       | water that     |
|                  | washing,       | washing,       | meets the      |
|                  | rinsing, or    | rinsing, or    | National       |
|                  | conveying food | conveying raw  | Primary        |
|                  | shall be safe  | agricultural   | Drinking Water |
|                  | and of         | materials      | regulations    |
|                  | adequate       | shall be safe  | or, where      |
|                  | sanitary       | and of         | necessary,     |
|                  | quality. Water | adequate       | higher         |
|                  | may be reused  | sanitary       | sanitary       |
|                  | for washing,   | quality.       | quality and    |
|                  | rinsing, or    | N              | that complies  |
|                  | conveying food | otwithstanding | with all       |
|                  | if it does not | the general    | applicable     |
|                  | increase the   | requirement    | Federal,       |
|                  | level of       | for potable    | State, and     |
|                  | contamination  | water, water   | local          |
|                  | of the food.   | may be reused  | regulations    |
|                  |                | for washing,   | for water that |
|                  |                | rinsing, or    | is used in the |
|                  |                | conveying raw  | manufacturing  |
|                  |                | agricultural   | operation. If  |
|                  |                | materials if   | you reuse      |
|                  |                | it does not    | water that was |
|                  |                | increase the   | used to wash   |
|                  |                | level of       | components to  |
|                  |                | contamination  | remove soil or |
|                  |                | of the such    | contaminants,  |
|                  |                | materials.     | the reused     |
|                  |                |                | water must be  |
|                  |                |                | safe and of    |
|                  |                |                | adequate       |
|                  |                |                | sanitary       |
|                  |                |                | quality so     |
|                  |                |                | that it does   |
|                  |                |                | not become a   |
|                  |                |                | source of      |
|                  |                |                | contamination; |
+------------------+----------------+----------------+----------------+
|                  |                |                | \(4\)          |
|                  |                |                | Performing     |
|                  |                |                | chemical,      |
|                  |                |                | mi             |
|                  |                |                | crobiological, |
|                  |                |                | or other       |
|                  |                |                | testing as     |
|                  |                |                | necessary to   |
|                  |                |                | prevent the    |
|                  |                |                | use of         |
|                  |                |                | contaminated   |
|                  |                |                | components,    |
|                  |                |                | dietary        |
|                  |                |                | ingredients,   |
|                  |                |                | and dietary    |
|                  |                |                | supplements;   |
+------------------+----------------+----------------+----------------+
|                  | \(2\) Raw      | \(5\) Measures | \(5\)          |
|                  | materials and  | such as        | Sterilizing,   |
|                  | other          | sterilizing,   | pasteurizing,  |
|                  | ingredients    | irradiating,   | freezing,      |
|                  | shall either   | pasteurizing,  | refrigerating  |
|                  | not contain    | freezing,      | controlling    |
|                  | levels of      | refrigerating, | hydrogen-ion   |
|                  | microorganisms | controlling pH | concentration  |
|                  | that may       | or controlling | (pH),          |
|                  | produce food   | water activity | controlling    |
|                  | poisoning or   | (a~w~) that    | humidity,      |
|                  | other disease  | are taken to   | controlling    |
|                  | in humans, or  | destroy or     | water activity |
|                  | they shall be  | prevent the    | (A~w~), or     |
|                  | pasteurized or | growth of      | using any      |
|                  | otherwise      | undesirable    | other          |
|                  | treated during | m              | effective      |
|                  | manufacturing  | icroorganisms, | means to       |
|                  | operations so  | particularly   | remove,        |
|                  | that they no   | those of       | destroy, or    |
|                  | longer contain | public health  | prevent the    |
|                  | levels that    | significance,  | growth of      |
|                  | would cause    | shall be       | microorganisms |
|                  | the product to | adequate under | and prevent    |
|                  | be adulterated | the conditions | decomposition; |
|                  | within the     | of             |                |
|                  | meaning of the | manufacture,   |                |
|                  | act.           | handling, and  |                |
|                  | Compliance     | distribution   |                |
|                  | with this      | to prevent     |                |
|                  | requirement    | dietary        |                |
|                  | may be         | products from  |                |
|                  | verified by    | being          |                |
|                  | any effective  | adulterated    |                |
|                  | means,         | within the     |                |
|                  | including      | meaning of the |                |
|                  | purchasing raw | act.           |                |
|                  | materials and  |                |                |
|                  | other          | \(15\)         |                |
|                  | ingredients    | Intermediate   |                |
|                  | under a        | or dehydrated  |                |
|                  | supplier\'s    | dietary        |                |
|                  | guarantee or   | products that  |                |
|                  | certification. | rely on the    |                |
|                  |                | control of     |                |
|                  | One way to     | water activity |                |
|                  | comply with    | (a~w~) for     |                |
|                  | this           | preventing the |                |
|                  | requirement is | growth of      |                |
|                  | careful        | undesirable    |                |
|                  | monitoring of  | microorganisms |                |
|                  | physical       | shall be       |                |
|                  | factors such   | processed to   |                |
|                  | as time,       | and maintained |                |
|                  | temperature,   | at a safe      |                |
|                  | humidity,      | moisture       |                |
|                  | a~w~, pH,      | level.         |                |
|                  | pressure, flow | Compliance     |                |
|                  | rate, and      | with this      |                |
|                  | manufacturing  | requirement    |                |
|                  | operations     | may be         |                |
|                  | such as        | accomplished   |                |
|                  | freezing,      | by any         |                |
|                  | dehydration,   | effective      |                |
|                  | heat           | means,         |                |
|                  | processing,    | including      |                |
|                  | acidification, | employment of  |                |
|                  | and            | one or more of |                |
|                  | refrigeration  | the following  |                |
|                  | to ensure that | practices:     |                |
|                  | mechanical     |                |                |
|                  | breakdowns,    | (i) Monitoring |                |
|                  | time delays,   |     the water  |                |
|                  | temperature    |     activity   |                |
|                  | fluctuations,  |     (a~w~) of  |                |
|                  | and other      |     the        |                |
|                  | factors do not |     material.  |                |
|                  | contribute to  |                |                |
|                  | the            | (i             |                |
|                  | decomposition  | i) Controlling |                |
|                  | or             |      the       |                |
|                  | contamination  |      soluble   |                |
|                  | of food.       |                |                |
|                  |                |   solids-water |                |
|                  | \(4\) Measures |      ratio in  |                |
|                  | such as        |      finished  |                |
|                  | sterilizing,   |      product.  |                |
|                  | irradiating,   |                |                |
|                  | pasteurizing,  | (i             |                |
|                  | freezing,      | ii) Protecting |                |
|                  | refrigerating, |       finished |                |
|                  | controlling pH |       product  |                |
|                  | or controlling |       from     |                |
|                  | a~w~ that are  |       moisture |                |
|                  | taken to       |       pickup,  |                |
|                  | destroy or     |       by use   |                |
|                  | prevent the    |       of a     |                |
|                  | growth of      |       moisture |                |
|                  | undesirable    |       barrier  |                |
|                  | m              |       or by    |                |
|                  | icroorganisms, |       other    |                |
|                  | particularly   |       means,   |                |
|                  | those of       |       so that  |                |
|                  | public health  |       the      |                |
|                  | significance,  |       water    |                |
|                  | shall be       |       activity |                |
|                  | adequate under |       (a~w~)   |                |
|                  | the conditions |       of the   |                |
|                  | of             |       product  |                |
|                  | manufacture,   |       does not |                |
|                  | handling, and  |       increase |                |
|                  | distribution   |       to an    |                |
|                  | to prevent     |       unsafe   |                |
|                  | food from      |       level.   |                |
|                  | being          |                |                |
|                  | adulterated    |                |                |
|                  | within the     |                |                |
|                  | meaning of the |                |                |
|                  | act.           |                |                |
|                  |                |                |                |
|                  | \(14\) Food    |                |                |
|                  | such as, but   |                |                |
|                  | not limited    |                |                |
|                  | to, dry mixes, |                |                |
|                  | nuts,          |                |                |
|                  | intermediate   |                |                |
|                  | moisture food, |                |                |
|                  | and dehydrated |                |                |
|                  | food, that     |                |                |
|                  | relies on the  |                |                |
|                  | control of     |                |                |
|                  | a~w~ for       |                |                |
|                  | preventing the |                |                |
|                  | growth of      |                |                |
|                  | undesirable    |                |                |
|                  | microorganisms |                |                |
|                  | shall be       |                |                |
|                  | processed to   |                |                |
|                  | and maintained |                |                |
|                  | at a safe      |                |                |
|                  | moisture       |                |                |
|                  | level.         |                |                |
|                  | Compliance     |                |                |
|                  | with this      |                |                |
|                  | requirement    |                |                |
|                  | may be         |                |                |
|                  | accomplished   |                |                |
|                  | by any         |                |                |
|                  | effective      |                |                |
|                  | means,         |                |                |
|                  | including      |                |                |
|                  | employment of  |                |                |
|                  | one or more of |                |                |
|                  | the following  |                |                |
|                  | practices:     |                |                |
|                  |                |                |                |
|                  | (i) Monitoring |                |                |
|                  |     the a~w~   |                |                |
|                  |     of food.   |                |                |
|                  |                |                |                |
|                  | (i             |                |                |
|                  | i) Controlling |                |                |
|                  |      the       |                |                |
|                  |      soluble   |                |                |
|                  |                |                |                |
|                  |   solids-water |                |                |
|                  |      ratio in  |                |                |
|                  |      finished  |                |                |
|                  |      food.     |                |                |
|                  |                |                |                |
|                  | (i             |                |                |
|                  | ii) Protecting |                |                |
|                  |       finished |                |                |
|                  |       food     |                |                |
|                  |       from     |                |                |
|                  |       moisture |                |                |
|                  |       pickup,  |                |                |
|                  |       by use   |                |                |
|                  |       of a     |                |                |
|                  |       moisture |                |                |
|                  |       barrier  |                |                |
|                  |       or by    |                |                |
|                  |       other    |                |                |
|                  |       means,   |                |                |
|                  |       so that  |                |                |
|                  |       the a~w~ |                |                |
|                  |       of the   |                |                |
|                  |       food     |                |                |
|                  |       does not |                |                |
|                  |       increase |                |                |
|                  |       to an    |                |                |
|                  |       unsafe   |                |                |
|                  |       level.   |                |                |
+------------------+----------------+----------------+----------------+
|                  | \(15\) Food    | \(16\) Dietary |                |
|                  | such as, but   | ingredients    |                |
|                  | not limited    | and dietary    |                |
|                  | to, acid and   | supplements    |                |
|                  | acidified      | that rely      |                |
|                  | food, that     | principally on |                |
|                  | relies         | the control of |                |
|                  | principally on | pH for         |                |
|                  | the control of | preventing the |                |
|                  | pH for         | growth of      |                |
|                  | preventing the | undesirable    |                |
|                  | growth of      | microorganisms |                |
|                  | undesirable    | shall be       |                |
|                  | microorganisms | monitored and  |                |
|                  | shall be       | maintained at  |                |
|                  | monitored and  | an appropriate |                |
|                  | maintained at  | pH. Compliance |                |
|                  | a pH of 4.6 or | with this      |                |
|                  | below.         | requirement    |                |
|                  | Compliance     | may be         |                |
|                  | with this      | accomplished   |                |
|                  | requirement    | by any         |                |
|                  | may be         | effective      |                |
|                  | accomplished   | means,         |                |
|                  | by any         | including      |                |
|                  | effective      | employment of  |                |
|                  | means,         | one or more of |                |
|                  | including      | the following  |                |
|                  | employment of  | practices:     |                |
|                  | one or more of |                |                |
|                  | the following  | > \(i\)        |                |
|                  | practices:     | > Monitoring   |                |
|                  |                | > the pH of    |                |
|                  | (i) Monitoring | > raw          |                |
|                  |     the pH of  | > materials,   |                |
|                  |     raw        | > in process   |                |
|                  |     materials, | > material,    |                |
|                  |     food in    | > and finished |                |
|                  |     process,   | > product.     |                |
|                  |     and        | >              |                |
|                  |     finished   | > \(ii\)       |                |
|                  |     food.      | > Controlling  |                |
|                  |                | > the amount   |                |
|                  | (i             | > of acid      |                |
|                  | i) Controlling | > added to the |                |
|                  |      the       | > product      |                |
|                  |      amount of |                |                |
|                  |      acid or   |                |                |
|                  |      acidified |                |                |
|                  |      food      |                |                |
|                  |      added to  |                |                |
|                  |      low-acid  |                |                |
|                  |      food.     |                |                |
+------------------+----------------+----------------+----------------+
|                  | \(3\) Food     |                | \(6\) Holding  |
|                  | that can       |                | components,    |
|                  | support the    |                | dietary        |
|                  | rapid growth   |                | ingredients,   |
|                  | of undesirable |                | and dietary    |
|                  | mi             |                | supplements    |
|                  | cro-organisms, |                | that can       |
|                  | particularly   |                | support the    |
|                  | those of       |                | rapid growth   |
|                  | public health  |                | of             |
|                  | significance,  |                | microorganisms |
|                  | shall be held  |                | of public      |
|                  | in a manner    |                | health         |
|                  | that prevents  |                | significance   |
|                  | the food from  |                | in a manner    |
|                  | becoming       |                | that prevents  |
|                  | adulterated    |                | the            |
|                  | within the     |                | components,    |
|                  | meaning of the |                | dietary        |
|                  | act.           |                | ingredients,   |
|                  | Compliance     |                | and dietary    |
|                  | with this      |                | supplements    |
|                  | requirement    |                | from becoming  |
|                  | may be         |                | adulterated;   |
|                  | accomplished   |                |                |
|                  | by any         |                |                |
|                  | effective      |                |                |
|                  | means,         |                |                |
|                  | including:     |                |                |
|                  |                |                |                |
|                  | (              |                |                |
|                  | i) Maintaining |                |                |
|                  |                |                |                |
|                  |   refrigerated |                |                |
|                  |     foods at   |                |                |
|                  |     45°F       |                |                |
|                  |     (7.2°C) or |                |                |
|                  |     below as   |                |                |
|                  |                |                |                |
|                  |    appropriate |                |                |
|                  |     for the    |                |                |
|                  |     particular |                |                |
|                  |     food       |                |                |
|                  |     involved.  |                |                |
|                  |                |                |                |
|                  | (i             |                |                |
|                  | i) Maintaining |                |                |
|                  |      frozen    |                |                |
|                  |      foods in  |                |                |
|                  |      a frozen  |                |                |
|                  |      state.    |                |                |
|                  |                |                |                |
|                  | (ii            |                |                |
|                  | i) Maintaining |                |                |
|                  |       hot      |                |                |
|                  |       foods at |                |                |
|                  |       140°F    |                |                |
|                  |       (60°C)   |                |                |
|                  |       or       |                |                |
|                  |       above.   |                |                |
|                  |                |                |                |
|                  | (iv) Heat      |                |                |
|                  |      treating  |                |                |
|                  |      acid or   |                |                |
|                  |      acidified |                |                |
|                  |      foods to  |                |                |
|                  |      destroy   |                |                |
|                  |                |                |                |
|                  |     mesophilic |                |                |
|                  |      m         |                |                |
|                  | icro-organisms |                |                |
|                  |      when      |                |                |
|                  |      those     |                |                |
|                  |      foods are |                |                |
|                  |      to be     |                |                |
|                  |      held in   |                |                |
|                  |                |                |                |
|                  |   hermetically |                |                |
|                  |      sealed    |                |                |
|                  |                |                |                |
|                  |     containers |                |                |
|                  |      at        |                |                |
|                  |      ambient   |                |                |
|                  |                |                |                |
|                  |  temperatures. |                |                |
+------------------+----------------+----------------+----------------+
|                  |                |                | \(7\)          |
|                  |                |                | Identifying    |
|                  |                |                | and holding    |
|                  |                |                | any            |
|                  |                |                | components,    |
|                  |                |                | dietary        |
|                  |                |                | ingredients,   |
|                  |                |                | or dietary     |
|                  |                |                | supplements,   |
|                  |                |                | for which a    |
|                  |                |                | material       |
|                  |                |                | review and     |
|                  |                |                | disposition    |
|                  |                |                | decision is    |
|                  |                |                | required, in a |
|                  |                |                | manner that    |
|                  |                |                | protects the   |
|                  |                |                | components,    |
|                  |                |                | dietary        |
|                  |                |                | ingredients,   |
|                  |                |                | or dietary     |
|                  |                |                | supplements    |
|                  |                |                | against        |
|                  |                |                | contamination  |
|                  |                |                | and mixups;    |
+------------------+----------------+----------------+----------------+
|                  | \(10\)         | \(13\)         | \(8\)          |
|                  | Mechanical     | Mechanical     | Performing     |
|                  | manufacturing  | manufacturing  | mechanical     |
|                  | steps such as  | steps such as  | manufacturing  |
|                  | washing,       | cutting,       | steps (such as |
|                  | peeling,       | sorting,       | cutting,       |
|                  | trimming,      | inspecting,    | sorting,       |
|                  | cutting,       | shredding,     | inspecting,    |
|                  | sorting and    | drying,        | shredding,     |
|                  | inspecting,    | grinding,      | drying,        |
|                  | mashing,       | blending and   | grinding,      |
|                  | dewatering,    | sifting shall  | blending, and  |
|                  | cooling,       | be performed   | sifting) by    |
|                  | shredding,     | so as to       | any effective  |
|                  | extruding,     | protect        | means to       |
|                  | drying,        | dietary        | protect the    |
|                  | whipping,      | ingredients    | dietary        |
|                  | defatting, and | and dietary    | ingredients or |
|                  | forming shall  | supplements    | dietary        |
|                  | be performed   | against        | supplements    |
|                  | so as to       | adulteration.  | against        |
|                  | protect food   | Compliance     | contamination. |
|                  | against        | with this      | Such steps     |
|                  | contamination. | requirement    | must include   |
|                  | Compliance     | may be         | consideration  |
|                  | with this      | accomplished   | of:            |
|                  | requirement    | by providing   |                |
|                  | may be         | adequate       | \(i\) Cleaning |
|                  | accomplished   | physical       | and sanitizing |
|                  | by providing   | protection of  | contact        |
|                  | adequate       | dietary        | surfaces;      |
|                  | physical       | products from  |                |
|                  | protection of  | contact with   | \(ii\) Using   |
|                  | food from      | adulterants.   | temperature    |
|                  | contaminants   | Protection may | controls; and  |
|                  | that may drip, | be provided by |                |
|                  | drain, or be   | adequate       | \(iii\) Using  |
|                  | drawn into the | cleaning and   | time controls. |
|                  | food.          | sanitizing of  |                |
|                  | Protection may | all processing |                |
|                  | be provided by | equipment      |                |
|                  | adequate       | between each   |                |
|                  | cleaning and   | manufacturing  |                |
|                  | sanitizing of  | step.          |                |
|                  | all            |                |                |
|                  | food-contact   |                |                |
|                  | surfaces, and  |                |                |
|                  | by using time  |                |                |
|                  | and            |                |                |
|                  | temperature    |                |                |
|                  | controls at    |                |                |
|                  | and between    |                |                |
|                  | each           |                |                |
|                  | manufacturing  |                |                |
|                  | step.          |                |                |
+------------------+----------------+----------------+----------------+
|                  | \...(8)        | \(9\)          | \(9\) Using    |
|                  | Effective      | Effective      | effective      |
|                  | measures shall | measures shall | measures to    |
|                  | be taken to    | be taken as    | protect        |
|                  | protect        | necessary to   | against the    |
|                  | against the    | protect        | inclusion of   |
|                  | inclusion of   | against the    | metal or other |
|                  | metal or other | inclusion of   | foreign        |
|                  | extraneous     | metal or other | material in    |
|                  | material in    | extraneous     | components,    |
|                  | food.          | material in    | dietary        |
|                  | Compliance     | product.       | ingredients,   |
|                  | with this      | Compliance     | or dietary     |
|                  | requirement    | with this      | supplements.   |
|                  | may be         | requirement    | Compliance     |
|                  | accomplished   | may be         | with this      |
|                  | by using       | accomplished   | requirement    |
|                  | sieves, traps, | by using       | must include   |
|                  | magnets,       | sieves, traps, | consideration  |
|                  | electronic     | magnets,       | of the use of: |
|                  | metal          | electronic     |                |
|                  | detectors, or  | metal          | \(i\) Filters  |
|                  | other suitable | detectors, or  | or strainers;\ |
|                  | effective      | other suitable | (ii) Traps;\   |
|                  | means.         | effective      | (iii) Magnets; |
|                  |                | means.         | or\            |
|                  |                |                | (iv)           |
|                  |                |                | Electronic     |
|                  |                |                | metal          |
|                  |                |                | detectors.     |
+------------------+----------------+----------------+----------------+
| ## § 2           |                | \(8\) All raw  | \(10\)         |
| 11.105 Equipment |                | material       | Segregating    |
|  identification. |                | containers,    | and            |
|                  |                | compounding    | identifying    |
| \(a\) All        |                | and storage    | all containers |
| compounding and  |                | containers,    | for a specific |
| storage          |                | processing     | batch of       |
| containers,      |                | lines and      | dietary        |
| processing       |                | major          | ingredients or |
| lines, and major |                | equipment used | dietary        |
| equipment used   |                | during the     | supplements to |
| during the       |                | production of  | identify their |
| production of a  |                | a batch shall  | contents and,  |
| batch of a drug  |                | be properly    | where          |
| product shall be |                | identified at  | necessary, the |
| properly         |                | all times to   | phase of       |
| identified at    |                | indicate their | manufacturing; |
| all times to     |                | contents and   | and            |
| indicate their   |                | when           |                |
| contents and,    |                | necessary, the | \(11\)         |
| when necessary,  |                | phase of       | Identifying    |
| the phase of     |                | processing of  | all processing |
| processing of    |                | the batch.     | lines and      |
| the batch.       |                |                | major          |
|                  |                |                | equipment used |
| \(b\) Major      |                |                | during         |
| equipment shall  |                |                | manufacturing  |
| be identified by |                |                | to indicate    |
| a distinctive    |                |                | their contents |
| identification   |                |                | including the  |
| number or code   |                |                | name of the    |
| that shall be    |                |                | dietary        |
| recorded in the  |                |                | ingredient or  |
| batch production |                |                | dietary        |
| record to show   |                |                | supplement and |
| the specific     |                |                | the specific   |
| equipment used   |                |                | batch or lot   |
| in the           |                |                | number and,    |
| manufacture of   |                |                | when           |
| each batch of a  |                |                | necessary, the |
| drug product. In |                |                | phase of       |
| cases where only |                |                | manufacturing. |
| one of a         |                |                |                |
| particular type  |                |                |                |
| of equipment     |                |                |                |
| exists in a      |                |                |                |
| manufacturing    |                |                |                |
| facility, the    |                |                |                |
| name of the      |                |                |                |
| equipment may be |                |                |                |
| used in lieu of  |                |                |                |
| a distinctive    |                |                |                |
| identification   |                |                |                |
| number or code.  |                |                |                |
+------------------+----------------+----------------+----------------+
| ## § 211.1       | (9)\...If the  | \(12\) Written | \(d\) You must |
| 15 Reprocessing. | adulterated    | procedures     | conduct a      |
|                  | food is        | shall be       | material       |
| \(a\) Written    | capable of     | established    | review and     |
| procedures shall | being          | and followed   | make a         |
| be established   | reconditioned, | prescribing    | disposition    |
| and followed     | it shall be    | the method for | decision in    |
| prescribing a    | reconditioned  | reprocessing   | accordance     |
| system for       | using a method | batches or     | with §         |
| reprocessing     | that has been  | operational    | 111.35(i) for  |
| batches that do  | proven to be   | start-up       | any component, |
| not conform to   | effective or   | materials that | dietary        |
| standards or     | it shall be    | do not conform | ingredient, or |
| specifications   | reexamined and | to finished    | dietary        |
| and the steps to | found not to   | goods          | supplement     |
| be taken to      | be adulterated | standards or   | that fails to  |
| insure that the  | within the     | s              | meet           |
| reprocessed      | meaning of the | pecifications. | specifications |
| batches will     | act before     | Finished goods | or that is or  |
| conform with all | being          | manufactured   | may be         |
| established      | incorporated   | using such     | adulterated.   |
| standards,       | into other     | materials      | If the         |
| specifications,  | food.          | shall meet all | material       |
| and              |                | established    | review and     |
| characteristics. |                | purity,        | disposition    |
|                  |                | composition    | decision       |
| \(b\)            |                | and quality    | allows you to  |
| Reprocessing     |                | standards.     | reprocess the  |
| shall not be     |                |                | component,     |
| performed        |                |                | dietary        |
| without the      |                |                | ingredient, or |
| review and       |                |                | dietary        |
| approval of the  |                |                | supplement,    |
| quality control  |                |                | you must       |
| unit.            |                |                | retest or      |
|                  |                |                | reexamine the  |
|                  |                |                | component,     |
|                  |                |                | dietary        |
|                  |                |                | ingredient, or |
|                  |                |                | dietary        |
|                  |                |                | supplement to  |
|                  |                |                | ensure that it |
|                  |                |                | meets          |
|                  |                |                | specifications |
|                  |                |                | and is         |
|                  |                |                | approved by    |
|                  |                |                | the quality    |
|                  |                |                | control unit.  |
+------------------+----------------+----------------+----------------+
| ## § 211.86 Us   |                | \(8\) Approved |                |
| e of approved co |                | raw materials  |                |
| mponents, drug p |                | shall be       |                |
| roduct container |                | rotated so     |                |
| s, and closures. |                | that the       |                |
|                  |                | oldest         |                |
| Components, drug |                | approved stock |                |
| product          |                | is used first. |                |
| containers, and  |                | Deviation from |                |
| closures         |                | this           |                |
| approved for use |                | requirement is |                |
| shall be rotated |                | permitted if   |                |
| so that the      |                | such deviation |                |
| oldest approved  |                | is temporary   |                |
| stock is used    |                | and            |                |
| first. Deviation |                | appropriate.   |                |
| from this        |                |                |                |
| requirement is   |                |                |                |
| permitted if     |                |                |                |
| such deviation   |                |                |                |
| is temporary and |                |                |                |
| appropriate.     |                |                |                |
+------------------+----------------+----------------+----------------+
| ## §             |                | \(9\) Raw      |                |
|  211.87 Retestin |                | materials      |                |
| g of approved co |                | shall be       |                |
| mponents, drug p |                | retested or    |                |
| roduct container |                | reexamined and |                |
| s, and closures. |                | approved or    |                |
|                  |                | rejected by    |                |
| Components, drug |                | the quality    |                |
| product          |                | control after  |                |
| containers, and  |                | a specified    |                |
| closures shall   |                | time in        |                |
| be retested or   |                | storage or     |                |
| reexamined, as   |                | after exposure |                |
| appropriate, for |                | to air, heat,  |                |
| identity,        |                | or other       |                |
| strength,        |                | conditions     |                |
| quality, and     |                | that are       |                |
| purity and       |                | likely to      |                |
| approved or      |                | adversely      |                |
| rejected by the  |                | affect the     |                |
| quality control  |                | purity,        |                |
| unit in          |                | quality or     |                |
| accordance with  |                | composition of |                |
| §211.84 as       |                | the raw        |                |
| necessary, e.g., |                | material.      |                |
| after storage    |                |                |                |
| for long periods |                |                |                |
| or after         |                |                |                |
| exposure to air, |                |                |                |
| heat or other    |                |                |                |
| conditions that  |                |                |                |
| might adversely  |                |                |                |
| affect the       |                |                |                |
| component, drug  |                |                |                |
| product          |                |                |                |
| container, or    |                |                |                |
| closure.         |                |                |                |
+------------------+----------------+----------------+----------------+
|                  | \(11\) Heat    | \(14\) Heat    |                |
|                  | blanching,     | blanching,     |                |
|                  | when required  | when required  |                |
|                  | in the         | in the         |                |
|                  | preparation of | preparation of |                |
|                  | food, should   | a dietary      |                |
|                  | be effected by | product,       |                |
|                  | heating the    | should be      |                |
|                  | food to the    | effected by    |                |
|                  | required       | heating the    |                |
|                  | temperature,   | product to the |                |
|                  | holding it at  | required       |                |
|                  | this           | temperature,   |                |
|                  | temperature    | holding it at  |                |
|                  | for the        | this           |                |
|                  | required time, | temperature    |                |
|                  | and then       | for the        |                |
|                  | either rapidly | required time, |                |
|                  | cooling the    | and then       |                |
|                  | food or        | either rapidly |                |
|                  | passing it to  | cooling the    |                |
|                  | subsequent     | material or    |                |
|                  | manufacturing  | passing it to  |                |
|                  | without delay. | subsequent     |                |
|                  | Thermophilic   | manufacturing  |                |
|                  | growth and     | without delay. |                |
|                  | contamination  | Thermophilic   |                |
|                  | in blanchers   | growth and     |                |
|                  | should be      | contamination  |                |
|                  | minimized by   | in blanchers   |                |
|                  | the use of     | should be      |                |
|                  | adequate       | minimized by   |                |
|                  | operating      | the use of     |                |
|                  | temperatures   | adequate       |                |
|                  | and by         | operating      |                |
|                  | periodic       | temperatures   |                |
|                  | cleaning.      | and by         |                |
|                  | Where the      | periodic       |                |
|                  | blanched food  | cleaning.      |                |
|                  | is washed      | Where the      |                |
|                  | prior to       | blanched       |                |
|                  | filling, water | product is     |                |
|                  | used shall be  | washed prior   |                |
|                  | safe and of    | to filling,    |                |
|                  | adequate       | potable water  |                |
|                  | sanitary       | shall be used. |                |
|                  | quality.       |                |                |
+------------------+----------------+----------------+----------------+
|                  | \(12\)         |                |                |
|                  | Batters,       |                |                |
|                  | breading,      |                |                |
|                  | sauces,        |                |                |
|                  | gravies,       |                |                |
|                  | dressings, and |                |                |
|                  | other similar  |                |                |
|                  | preparations   |                |                |
|                  | shall be       |                |                |
|                  | treated or     |                |                |
|                  | maintained in  |                |                |
|                  | such a manner  |                |                |
|                  | that they are  |                |                |
|                  | protected      |                |                |
|                  | against        |                |                |
|                  | contamination. |                |                |
|                  | Compliance     |                |                |
|                  | with this      |                |                |
|                  | requirement    |                |                |
|                  | may be         |                |                |
|                  | accomplished   |                |                |
|                  | by any         |                |                |
|                  | effective      |                |                |
|                  | means,         |                |                |
|                  | including one  |                |                |
|                  | or more of the |                |                |
|                  | following:     |                |                |
|                  |                |                |                |
|                  | \(i\) Using    |                |                |
|                  | ingredients    |                |                |
|                  | free of        |                |                |
|                  | contamination. |                |                |
|                  |                |                |                |
|                  | \(ii\)         |                |                |
|                  | Employing      |                |                |
|                  | adequate heat  |                |                |
|                  | processes      |                |                |
|                  | where          |                |                |
|                  | applicable.    |                |                |
|                  |                |                |                |
|                  | \(iii\) Using  |                |                |
|                  | adequate time  |                |                |
|                  | and            |                |                |
|                  | temperature    |                |                |
|                  | controls.      |                |                |
|                  |                |                |                |
|                  | \(iv\)         |                |                |
|                  | Providing      |                |                |
|                  | adequate       |                |                |
|                  | physical       |                |                |
|                  | protection of  |                |                |
|                  | components     |                |                |
|                  | from           |                |                |
|                  | contaminants   |                |                |
|                  | that may drip, |                |                |
|                  | drain, or be   |                |                |
|                  | drawn to them. |                |                |
|                  |                |                |                |
|                  | \(v\) Cooling  |                |                |
|                  | to an adequate |                |                |
|                  | temperature    |                |                |
|                  | during         |                |                |
|                  | manufacturing. |                |                |
|                  |                |                |                |
|                  | \(vi\)         |                |                |
|                  | Disposing of   |                |                |
|                  | batters at     |                |                |
|                  | appropriate    |                |                |
|                  | intervals to   |                |                |
|                  | protect        |                |                |
|                  | against the    |                |                |
|                  | growth of      |                |                |
|                  | m              |                |                |
|                  | icroorganisms. |                |                |
+------------------+----------------+----------------+----------------+
|                  | \(16\) When    | \(17\) When    |                |
|                  | ice is used in | ice is used in |                |
|                  | contact with   | contact with   |                |
|                  | food, it shall | dietary        |                |
|                  | be made from   | products, it   |                |
|                  | water that is  | shall be made  |                |
|                  | safe and of    | from potable   |                |
|                  | adequate       | water, and     |                |
|                  | sanitary       | shall be used  |                |
|                  | quality, and   | only if it has |                |
|                  | shall be used  | been           |                |
|                  | only if it has | manufactured   |                |
|                  | been           | in accordance  |                |
|                  | manufactured   | with current   |                |
|                  | in accordance  | good           |                |
|                  | with current   | manufacturing  |                |
|                  | good           | practice as    |                |
|                  | manufacturing  | outlined in 21 |                |
|                  | practice as    | CFR Part 110.  |                |
|                  | outlined in    |                |                |
|                  | this part.     |                |                |
+------------------+----------------+----------------+----------------+
|                  | \(17\) Food    |                |                |
|                  | manufacturing  |                |                |
|                  | areas and      |                |                |
|                  | equipment used |                |                |
|                  | for            |                |                |
|                  | manufacturing  |                |                |
|                  | human food     |                |                |
|                  | should not be  |                |                |
|                  | used to        |                |                |
|                  | manufacture    |                |                |
|                  | nonhuman food  |                |                |
|                  | grade animal   |                |                |
|                  | food or        |                |                |
|                  | inedible       |                |                |
|                  | products,      |                |                |
|                  | unless there   |                |                |
|                  | is no          |                |                |
|                  | reasonable     |                |                |
|                  | possibility    |                |                |
|                  | for the        |                |                |
|                  | contamination  |                |                |
|                  | of the human   |                |                |
|                  | food.          |                |                |
+------------------+----------------+----------------+----------------+
| ## §             |                |                |                |
| 211.101 Charge-i |                |                |                |
| n of components. |                |                |                |
|                  |                |                |                |
| ##               |                |                |                |
|                  |                |                |                |
| Written          |                |                |                |
| production and   |                |                |                |
| control          |                |                |                |
| procedures shall |                |                |                |
| include the      |                |                |                |
| following, which |                |                |                |
| are designed to  |                |                |                |
| assure that the  |                |                |                |
| drug products    |                |                |                |
| produced have    |                |                |                |
| the identity,    |                |                |                |
| strength,        |                |                |                |
| quality, and     |                |                |                |
| purity they      |                |                |                |
| purport or are   |                |                |                |
| represented to   |                |                |                |
| possess:         |                |                |                |
|                  |                |                |                |
| \(b\) Components |                |                |                |
| for drug product |                |                |                |
| manufacturing    |                |                |                |
| shall be         |                |                |                |
| weighed,         |                |                |                |
| measured, or     |                |                |                |
| subdivided as    |                |                |                |
| appropriate. If  |                |                |                |
| a component is   |                |                |                |
| removed from the |                |                |                |
| original         |                |                |                |
| container to     |                |                |                |
| another, the new |                |                |                |
| container shall  |                |                |                |
| be identified    |                |                |                |
| with the         |                |                |                |
| following        |                |                |                |
| information:     |                |                |                |
|                  |                |                |                |
| \(1\) Component  |                |                |                |
| name or item     |                |                |                |
| code;            |                |                |                |
|                  |                |                |                |
| \(2\) Receiving  |                |                |                |
| or control       |                |                |                |
| number;          |                |                |                |
|                  |                |                |                |
| \(3\) Weight or  |                |                |                |
| measure in new   |                |                |                |
| container;       |                |                |                |
|                  |                |                |                |
| \(4\) Batch for  |                |                |                |
| which component  |                |                |                |
| was dispensed,   |                |                |                |
| including its    |                |                |                |
| product name,    |                |                |                |
| strength, and    |                |                |                |
| lot number.      |                |                |                |
|                  |                |                |                |
| \(c\) Weighing,  |                |                |                |
| measuring, or    |                |                |                |
| subdividing      |                |                |                |
| operations for   |                |                |                |
| components shall |                |                |                |
| be adequately    |                |                |                |
| supervised. Each |                |                |                |
| container of     |                |                |                |
| component        |                |                |                |
| dispensed to     |                |                |                |
| manufacturing    |                |                |                |
| shall be         |                |                |                |
| examined by a    |                |                |                |
| second person to |                |                |                |
| assure that:     |                |                |                |
|                  |                |                |                |
| \(1\) The        |                |                |                |
| component was    |                |                |                |
| released by the  |                |                |                |
| quality control  |                |                |                |
| unit;            |                |                |                |
|                  |                |                |                |
| \(2\) The weight |                |                |                |
| or measure is    |                |                |                |
| correct as       |                |                |                |
| stated in the    |                |                |                |
| batch production |                |                |                |
| records;         |                |                |                |
|                  |                |                |                |
| \(3\) The        |                |                |                |
| containers are   |                |                |                |
| properly         |                |                |                |
| identified.      |                |                |                |
|                  |                |                |                |
| \(d\) Each       |                |                |                |
| component shall  |                |                |                |
| be added to the  |                |                |                |
| batch by one     |                |                |                |
| person and       |                |                |                |
| verified by a    |                |                |                |
| second person.   |                |                |                |
+------------------+----------------+----------------+----------------+
| ## § 211.130 Pa  | \(13\)         | \(e\)          | **§ 111.70     |
| ckaging and labe | Filling,       | Packaging and  | [What          |
| ling operations. | assembling,    | labeling       | requirements   |
|                  | packaging, and | operations.    | apply to       |
| There shall be   | other          |                | packaging and  |
| written          | operations     | \(1\) Filling, | label          |
| procedures       | shall be       | assembling,    | operations?    |
| designed to      | performed in   | packaging, and | ]              |
| assure that      | such a way     | other          | {.underline}** |
| correct labels,  | that the food  | operations     |                |
| labeling, and    | is protected   | shall be       | \(a\) You must |
| packaging        | against        | performed in   | take necessary |
| materials are    | contamination. | such a way     | actions to     |
| used for drug    | Compliance     | that dietary   | ensure that    |
| products; such   | with this      | products are   | each packaging |
| written          | requirement    | protected      | container for  |
| procedures shall | may be         | against        | holding        |
| be followed.     | accomplished   | adulteration.  | dietary        |
| These procedures | by any         | Compliance     | ingredients or |
| shall            | effective      | with this      | dietary        |
| incorporate the  | means,         | requirement    | supplements    |
| following        | including:     | may be         | meets          |
| features:        |                | accomplished   | specifications |
|                  | (i) Use of a   | by any         | so that the    |
| \(a\) Prevention |     quality    | effective      | condition of   |
| of mixups and    |     control    | means,         | the packaging  |
| cro              |     operation  | including:     | container will |
| ss-contamination |     in which   |                | not            |
| by physical or   |     the        | (i) Adequate   | contaminate    |
| spatial          |     critical   |     cleaning   | your dietary   |
| separation from  |     control    |     and        | ingredients or |
| operations on    |     points are |     sanitizing | dietary        |
| other drug       |     identified |     of all     | supplements    |
| products.        |     and        |     filling    | nor cause them |
|                  |     controlled |     and        | to             |
| \(b\)            |     during     |     packaging  | deteriorate;   |
| Identification   |                |     equipment, |                |
| and handling of  | manufacturing. |     utensils   | \(b\) You must |
| filled drug      |                |     and        | fill,          |
| product          | (ii) Adequate  |     product    | assemble,      |
| containers that  |      cleaning  |                | package, and   |
| are set aside    |      and       |    containers, | perform other  |
| and held in      |                |     as         | related        |
| unlabeled        |     sanitizing |                | operations in  |
| condition for    |      of all    |   appropriate. | a way that     |
| future labeling  |                |                | protects your  |
| operations to    |   food-contact | (ii) Using     | dietary        |
| preclude         |      surfaces  |      materials | ingredients or |
| mislabeling of   |      and food  |      for       | dietary        |
| individual       |                |      product   | supplements    |
| containers,      |    containers. |                | against        |
| lots, or         |                |     containers | adulteration   |
| portions of      | (iii) Using    |      and       | and            |
| lots.            |                |      packaging | misbranding.   |
| Identification   |      materials |      materials | You must do    |
| need not be      |       for food |      that are  | this using any |
| applied to each  |                |      safe and  | effective      |
| individual       |     containers |      suitable. | means,         |
| container but    |       and      |                | including but  |
| shall be         |                | (              | not limited    |
| sufficient to    | food-packaging | iii) Providing | to, the        |
| determine name,  |                |       physical | following:     |
| strength,        |      materials |                |                |
| quantity of      |       that are |     protection | \(1\) Cleaning |
| contents, and    |       safe and |       from     | and sanitizing |
| lot or control   |                |                | all filling    |
| number of each   |      suitable, |  adulteration, | and packaging  |
| container.       |       as       |                | equipment,     |
|                  |       defined  |   particularly | utensils, and  |
| \(d\)            |       in       |       airborne | dietary        |
| Examination of   |                |                | ingredient or  |
| packaging and    |      ¶130.3(d) | contamination. | dietary        |
| labeling         |       of this  |                | supplement     |
| materials for    |       chapter. | (iv) Using     | containers, as |
| suitability and  |                |      sanitary  | appropriate;   |
| correctness      | (iv) Providing |      handling  |                |
| before packaging |      physical  |                | \(2\)          |
| operations, and  |                |    procedures. | Protecting     |
| documentation of |     protection |                | manufactured   |
| such examination |      from      |                | dietary        |
| in the batch     |                |                | ingredients    |
| production       | contamination, |                | and dietary    |
| record.          |                |                | supplements    |
|                  |   particularly |                | from           |
| \(e\) Inspection |      airborne  |                | contamination, |
| of the packaging |                |                | particularly   |
| and labeling     | contamination. |                | airborne       |
| facilities       |                |                | contamination; |
| immediately      | (v) Using      |                |                |
| before use to    |     sanitary   |                | \(3\) Using    |
| assure that all  |     handling   |                | sanitary       |
| drug products    |                |                | handling       |
| have been        |    procedures. |                | procedures;    |
| removed from     |                |                |                |
| previous         |                |                |                |
| operations.      |                |                |                |
| Inspection shall |                |                |                |
| also be made to  |                |                |                |
| assure that      |                |                |                |
| packaging and    |                |                |                |
| labeling         |                |                |                |
| materials not    |                |                |                |
| suitable for     |                |                |                |
| subsequent       |                |                |                |
| operations have  |                |                |                |
| been removed.    |                |                |                |
| Results of       |                |                |                |
| inspection shall |                |                |                |
| be documented in |                |                |                |
| the batch        |                |                |                |
| production       |                |                |                |
| records.         |                |                |                |
+------------------+----------------+----------------+----------------+
| ## § 2           |                | \(3\) For      | \(4\)          |
| 11.122 Materials |                | dietary        | Establishing   |
|  examination and |                | supplements,   | physical or    |
|  usage criteria. |                | labels and     | spatial        |
|                  |                | other labeling | separation of  |
| \(d\) Labels and |                | materials for  | packaging and  |
| other labeling   |                | each different | labels from    |
| materials for    |                | product type,  | operations on  |
| each different   |                | strength, or   | other dietary  |
| drug product,    |                | quantity of    | ingredients    |
| strength, dosage |                | contents shall | and dietary    |
| form, or         |                | be stored      | supplements to |
| quantity of      |                | separately     | prevent        |
| contents shall   |                | with suitable  | mixups;        |
| be stored        |                | i              |                |
| separately with  |                | dentification. |                |
| suitable         |                |                |                |
| identification.  |                |                |                |
| Access to the    |                |                |                |
| storage area     |                |                |                |
| shall be limited |                |                |                |
| to authorized    |                |                |                |
| personnel.       |                |                |                |
+------------------+----------------+----------------+----------------+
|                  |                |                | \(5\)          |
|                  |                |                | Identifying,   |
|                  |                |                | by any         |
|                  |                |                | effective      |
|                  |                |                | means, filled  |
|                  |                |                | dietary        |
|                  |                |                | ingredient or  |
|                  |                |                | dietary        |
|                  |                |                | supplement     |
|                  |                |                | containers     |
|                  |                |                | that are set   |
|                  |                |                | aside and held |
|                  |                |                | in unlabeled   |
|                  |                |                | condition for  |
|                  |                |                | future label   |
|                  |                |                | operations, to |
|                  |                |                | prevent        |
|                  |                |                | mixups;        |
+------------------+----------------+----------------+----------------+
| **§ 211.130      |                | \(6\) Dietary  | \(6\)          |
| Packaging and    |                | ingredient and | Identifying    |
| labeling         |                | dietary        | the dietary    |
| operations.**    |                | supplement     | ingredient or  |
|                  |                | packages shall | dietary        |
| \(c\)            |                | be identified  | supplement     |
| Identification   |                | with a lot     | with a batch,  |
| of the drug      |                | number that    | lot, or        |
| product with a   |                | permits        | control number |
| lot or control   |                | determination  | that can be    |
| number that      |                | of the history | used to        |
| permits          |                | of the         | determine the  |
| determination of |                | manufacture    | manufacturing  |
| the history of   |                | and control of | history and    |
| the manufacture  |                | the batch.     | control of the |
| and control of   |                |                | batch;         |
| the batch.       |                |                |                |
+------------------+----------------+----------------+----------------+
| ## §             |                | \(7\) Packaged | \(7\)          |
| 211.134 Drug pro |                | and labeled    | Examining a    |
| duct inspection. |                | dietary        | representative |
|                  |                | supplements    | sample of each |
| \(a\) Packaged   |                | shall be       | batch of the   |
| and labeled      |                | examined to    | packaged and   |
| products shall   |                | provide        | labeled        |
| be examined      |                | assurance that | dietary        |
| during finishing |                | containers and | ingredient or  |
| operations to    |                | packages in    | dietary        |
| provide          |                | the lot have   | supplement to  |
| assurance that   |                | the correct    | ensure that    |
| containers and   |                | label and lot  | the dietary    |
| packages in the  |                | number.        | ingredient or  |
| lot have the     |                | Products not   | dietary        |
| correct label.   |                | meeting        | supplement     |
|                  |                | specifications | meets          |
| \(b\) A          |                | shall be       | specifications |
| representative   |                | rejected by    | and that the   |
| sample of units  |                | the quality    | label          |
| shall be         |                | control unit.  | specified in   |
| collected at the |                |                | the master     |
| completion of    |                |                | manufacturing  |
| finishing        |                |                | record has     |
| operations and   |                |                | been applied;  |
| shall be         |                |                | and            |
| visually         |                |                |                |
| examined for     |                |                |                |
| correct          |                |                |                |
| labeling.        |                |                |                |
|                  |                |                |                |
| \(c\) Results of |                |                |                |
| these            |                |                |                |
| examinations     |                |                |                |
| shall be         |                |                |                |
| recorded in the  |                |                |                |
| batch production |                |                |                |
| or control       |                |                |                |
| records.         |                |                |                |
+------------------+----------------+----------------+----------------+
| ## § 2           |                | \(4\) Obsolete | \(8\) Suitably |
| 11.122 Materials |                | labels,        | disposing of   |
|  examination and |                | labeling, and  | labels and     |
|  usage criteria. |                | other          | other          |
|                  |                | packaging      | packaging for  |
| \(e\) Obsolete   |                | materials for  | dietary        |
| and outdated     |                | dietary        | ingredients or |
| labels,          |                | products shall | dietary        |
| labeling, and    |                | be destroyed.  | supplements    |
| other packaging  |                |                | that are       |
| materials shall  |                |                | obsolete or    |
| be destroyed.    |                |                | incorrect to   |
|                  |                |                | ensure that    |
|                  |                |                | they are not   |
|                  |                |                | used in any    |
|                  |                |                | future         |
|                  |                |                | packaging and  |
|                  |                |                | label          |
|                  |                |                | operations.    |
+------------------+----------------+----------------+----------------+
| \(f\) Use of     |                |                |                |
| gang-printed     |                |                |                |
| labeling for     |                |                |                |
| different drug   |                |                |                |
| products, or     |                |                |                |
| different        |                |                |                |
| strengths or net |                |                |                |
| contents of the  |                |                |                |
| same drug        |                |                |                |
| product, is      |                |                |                |
| prohibited       |                |                |                |
| unless the       |                |                |                |
| labeling from    |                |                |                |
| gang-printed     |                |                |                |
| sheets is        |                |                |                |
| adequately       |                |                |                |
| differentiated   |                |                |                |
| by size, shape,  |                |                |                |
| or color.        |                |                |                |
+------------------+----------------+----------------+----------------+
| \(g\) If cut     |                |                |                |
| labeling is      |                |                |                |
| used, packaging  |                |                |                |
| and labeling     |                |                |                |
| operations shall |                |                |                |
| include one of   |                |                |                |
| the following    |                |                |                |
| special control  |                |                |                |
| procedures:      |                |                |                |
|                  |                |                |                |
| \(1\) Dedication |                |                |                |
| of labeling and  |                |                |                |
| packaging lines  |                |                |                |
| to each          |                |                |                |
| different        |                |                |                |
| strength of each |                |                |                |
| different drug   |                |                |                |
| product;         |                |                |                |
|                  |                |                |                |
| \(2\) Use of     |                |                |                |
| appropriate      |                |                |                |
| electronic or    |                |                |                |
| e                |                |                |                |
| lectromechanical |                |                |                |
| equipment to     |                |                |                |
| conduct a        |                |                |                |
| 100-percent      |                |                |                |
| examination for  |                |                |                |
| correct labeling |                |                |                |
| during or after  |                |                |                |
| completion of    |                |                |                |
| finishing        |                |                |                |
| operations; or   |                |                |                |
|                  |                |                |                |
| \(3\) Use of     |                |                |                |
| visual           |                |                |                |
| inspection to    |                |                |                |
| conduct a        |                |                |                |
| 100-percent      |                |                |                |
| examination for  |                |                |                |
| correct labeling |                |                |                |
| during or after  |                |                |                |
| completion of    |                |                |                |
| finishing        |                |                |                |
| operations for   |                |                |                |
| hand-applied     |                |                |                |
| labeling. Such   |                |                |                |
| examination      |                |                |                |
| shall be         |                |                |                |
| performed by one |                |                |                |
| person and       |                |                |                |
| independently    |                |                |                |
| verified by a    |                |                |                |
| second person.   |                |                |                |
+------------------+----------------+----------------+----------------+
| \(h\) Printing   |                |                |                |
| devices on, or   |                |                |                |
| associated with, |                |                |                |
| manufacturing    |                |                |                |
| lines used to    |                |                |                |
| imprint labeling |                |                |                |
| upon the drug    |                |                |                |
| product unit     |                |                |                |
| label or case    |                |                |                |
| shall be         |                |                |                |
| monitored to     |                |                |                |
| assure that all  |                |                |                |
| imprinting       |                |                |                |
| conforms to the  |                |                |                |
| print specified  |                |                |                |
| in the batch     |                |                |                |
| production       |                |                |                |
| record.          |                |                |                |
+------------------+----------------+----------------+----------------+
|                  |                |                | \(c\) You must |
|                  |                |                | conduct a      |
|                  |                |                | material       |
|                  |                |                | review and     |
|                  |                |                | make a         |
|                  |                |                | disposition    |
|                  |                |                | decision of    |
|                  |                |                | any packaged   |
|                  |                |                | and labeled    |
|                  |                |                | dietary        |
|                  |                |                | ingredients or |
|                  |                |                | dietary        |
|                  |                |                | supplements    |
|                  |                |                | that do not    |
|                  |                |                | meet           |
|                  |                |                | s              |
|                  |                |                | pecifications. |
+------------------+----------------+----------------+----------------+
|                  |                |                | \(d\) You must |
|                  |                |                | only repackage |
|                  |                |                | or relabel     |
|                  |                |                | dietary        |
|                  |                |                | ingredients or |
|                  |                |                | dietary        |
|                  |                |                | supplements    |
|                  |                |                | after the      |
|                  |                |                | quality        |
|                  |                |                | control unit   |
|                  |                |                | has approved   |
|                  |                |                | and documented |
|                  |                |                | such           |
|                  |                |                | repackaging or |
|                  |                |                | relabeling.    |
+------------------+----------------+----------------+----------------+
|                  |                |                | \(e\) You must |
|                  |                |                | retest or      |
|                  |                |                | reexamine any  |
|                  |                |                | repackaged or  |
|                  |                |                | relabeled      |
|                  |                |                | dietary        |
|                  |                |                | ingredients or |
|                  |                |                | dietary        |
|                  |                |                | supplements.   |
|                  |                |                | They must meet |
|                  |                |                | all            |
|                  |                |                | specifications |
|                  |                |                | and the        |
|                  |                |                | quality        |
|                  |                |                | control unit   |
|                  |                |                | must approve   |
|                  |                |                | or reject      |
|                  |                |                | their release  |
|                  |                |                | for            |
|                  |                |                | distribution.  |
+------------------+----------------+----------------+----------------+
| ## § 211.125 La  |                | \(5\) Written  | \(f\) (1) You  |
| beling issuance. |                | procedures     | must control   |
|                  |                | shall be       | the issuance   |
| \(a\) Strict     |                | established    | and use of     |
| control shall be |                | and followed   | packaging, and |
| exercised over   |                | to assure that | labels and     |
| labeling issued  |                | correct        | reconciliation |
| for use in drug  |                | labels,        | of any         |
| product labeling |                | labeling, and  | issuance and   |
| operations.      |                | packaging      | use            |
|                  |                | materials are  | discrepancies; |
| \(b\) Labeling   |                | issued and     | and            |
| materials issued |                | used for       |                |
| for a batch      |                | dietary        | \(2\) You must |
| shall be         |                | products.      | examine,       |
| carefully        |                |                | before         |
| examined for     |                |                | packaging      |
| identity and     |                |                | operations,    |
| conformity to    |                |                | packaging and  |
| the labeling     |                |                | labels for     |
| specified in the |                |                | each batch of  |
| master or batch  |                |                | dietary        |
| production       |                |                | ingredient or  |
| records.         |                |                | dietary        |
|                  |                |                | supplement to  |
| \(c\) Procedures |                |                | ensure that    |
| shall be used to |                |                | the label and  |
| reconcile the    |                |                | packaging      |
| quantities of    |                |                | conform to the |
| labeling issued, |                |                | master         |
| used, and        |                |                | manufacturing  |
| returned, and    |                |                | record.        |
| shall require    |                |                |                |
| evaluation of    |                |                |                |
| discrepancies    |                |                |                |
| found between    |                |                |                |
| the quantity of  |                |                |                |
| drug product     |                |                |                |
| finished and the |                |                |                |
| quantity of      |                |                |                |
| labeling issued  |                |                |                |
| when such        |                |                |                |
| discrepancies    |                |                |                |
| are outside      |                |                |                |
| narrow preset    |                |                |                |
| limits based on  |                |                |                |
| historical       |                |                |                |
| operating data.  |                |                |                |
| Such             |                |                |                |
| discrepancies    |                |                |                |
| shall be         |                |                |                |
| investigated in  |                |                |                |
| accordance with  |                |                |                |
| §211.192.        |                |                |                |
| Labeling         |                |                |                |
| reconciliation   |                |                |                |
| is waived for    |                |                |                |
| cut or roll      |                |                |                |
| labeling if a    |                |                |                |
| 100-percent      |                |                |                |
| examination for  |                |                |                |
| correct labeling |                |                |                |
| is performed in  |                |                |                |
| accordance with  |                |                |                |
| §211.122(g)(2).  |                |                |                |
+------------------+----------------+----------------+----------------+
| \(d\) All excess |                |                |                |
| labeling bearing |                |                |                |
| lot or control   |                |                |                |
| numbers shall be |                |                |                |
| destroyed.       |                |                |                |
|                  |                |                |                |
| \(e\) Returned   |                |                |                |
| labeling shall   |                |                |                |
| be maintained    |                |                |                |
| and stored in a  |                |                |                |
| manner to        |                |                |                |
| prevent mixups   |                |                |                |
| and provide      |                |                |                |
| proper           |                |                |                |
| identification   |                |                |                |
|                  |                |                |                |
| \(f\) Procedures |                |                |                |
| shall be written |                |                |                |
| describing in    |                |                |                |
| sufficient       |                |                |                |
| detail the       |                |                |                |
| control          |                |                |                |
| procedures       |                |                |                |
| employed for the |                |                |                |
| issuance of      |                |                |                |
| labeling; such   |                |                |                |
| written          |                |                |                |
| procedures shall |                |                |                |
| be followed.     |                |                |                |
+------------------+----------------+----------------+----------------+
|                  |                |                | \(g\) The      |
|                  |                |                | person that    |
|                  |                |                | performs the   |
|                  |                |                | requirements   |
|                  |                |                | of this        |
|                  |                |                | section must   |
|                  |                |                | document at    |
|                  |                |                | the time of    |
|                  |                |                | performance    |
|                  |                |                | that the       |
|                  |                |                | requirements   |
|                  |                |                | are performed  |
|                  |                |                | including, but |
|                  |                |                | not limited    |
|                  |                |                | to,            |
|                  |                |                | documentation  |
|                  |                |                | in the         |
|                  |                |                | ba             |
|                  |                |                | tch-production |
|                  |                |                | record of:     |
|                  |                |                |                |
|                  |                |                | \(1\) The      |
|                  |                |                | identity and   |
|                  |                |                | quantity of    |
|                  |                |                | the packaging  |
|                  |                |                | and labels     |
|                  |                |                | used and       |
|                  |                |                | reconciliation |
|                  |                |                | of any         |
|                  |                |                | discrepancies  |
|                  |                |                | between        |
|                  |                |                | issuance and   |
|                  |                |                | use;           |
|                  |                |                |                |
|                  |                |                | \(2\) The      |
|                  |                |                | examination    |
|                  |                |                | conducted, in  |
|                  |                |                | accordance     |
|                  |                |                | with paragraph |
|                  |                |                | (b)(7) of this |
|                  |                |                | section;       |
|                  |                |                |                |
|                  |                |                | \(3\) The      |
|                  |                |                | conclusions    |
|                  |                |                | you reached    |
|                  |                |                | from retests   |
|                  |                |                | conducted in   |
|                  |                |                | accordance     |
|                  |                |                | with paragraph |
|                  |                |                | (e) of this    |
|                  |                |                | section; and   |
|                  |                |                |                |
|                  |                |                | \(4\) Any      |
|                  |                |                | material       |
|                  |                |                | reviews and    |
|                  |                |                | disposition    |
|                  |                |                | decisions for  |
|                  |                |                | packaging and  |
|                  |                |                | labels.        |
+------------------+----------------+----------------+----------------+
|                  |                |                | \(h\) You must |
|                  |                |                | keep packaging |
|                  |                |                | and label      |
|                  |                |                | operations     |
|                  |                |                | records        |
|                  |                |                | required under |
|                  |                |                | this section   |
|                  |                |                | in accordance  |
|                  |                |                | with §         |
|                  |                |                | 111.125.       |
+------------------+----------------+----------------+----------------+
| ##               |                |                |                |
|  § 211.132 Tampe |                |                |                |
| r-evident packag |                |                |                |
| ing requirements |                |                |                |
|  for over-the-co |                |                |                |
| unter (OTC) huma |                |                |                |
| n drug products. |                |                |                |
|                  |                |                |                |
| \(a\) *General.* |                |                |                |
| The Food and     |                |                |                |
| Drug             |                |                |                |
| Administration   |                |                |                |
| has the          |                |                |                |
| authority under  |                |                |                |
| the Federal      |                |                |                |
| Food, Drug, and  |                |                |                |
| Cosmetic Act     |                |                |                |
| (the act) to     |                |                |                |
| establish a      |                |                |                |
| uniform national |                |                |                |
| requirement for  |                |                |                |
| tamper-evident   |                |                |                |
| packaging of OTC |                |                |                |
| drug products    |                |                |                |
| that will        |                |                |                |
| improve the      |                |                |                |
| security of OTC  |                |                |                |
| drug packaging   |                |                |                |
| and help assure  |                |                |                |
| the safety and   |                |                |                |
| effectiveness of |                |                |                |
| OTC drug         |                |                |                |
| products. An OTC |                |                |                |
| drug product     |                |                |                |
| (except a        |                |                |                |
| dermatological,  |                |                |                |
| dentifrice,      |                |                |                |
| insulin, or      |                |                |                |
| lozenge product) |                |                |                |
| for retail sale  |                |                |                |
| that is not      |                |                |                |
| packaged in a    |                |                |                |
| tamper-resistant |                |                |                |
| package or that  |                |                |                |
| is not properly  |                |                |                |
| labeled under    |                |                |                |
| this section is  |                |                |                |
| adulterated      |                |                |                |
| under section    |                |                |                |
| 501 of the act   |                |                |                |
| or misbranded    |                |                |                |
| under section    |                |                |                |
| 502 of the act,  |                |                |                |
| or both.         |                |                |                |
+------------------+----------------+----------------+----------------+
| \(b\)            |                |                |                |
| *Requirements    |                |                |                |
| for              |                |                |                |
| tamper-evident   |                |                |                |
| package*.        |                |                |                |
|                  |                |                |                |
| \(1\) Each       |                |                |                |
| manufacturer and |                |                |                |
| packer who       |                |                |                |
| packages an OTC  |                |                |                |
| drug product     |                |                |                |
| (except a        |                |                |                |
| dermatological,  |                |                |                |
| dentifrice,      |                |                |                |
| insulin, or      |                |                |                |
| lozenge product) |                |                |                |
| for retail sale  |                |                |                |
| shall package    |                |                |                |
| the product in a |                |                |                |
| tamper-evident   |                |                |                |
| package, if this |                |                |                |
| product is       |                |                |                |
| accessible to    |                |                |                |
| the public while |                |                |                |
| held for sale. A |                |                |                |
| tamper-evident   |                |                |                |
| package is one   |                |                |                |
| having one or    |                |                |                |
| more indicators  |                |                |                |
| or barriers to   |                |                |                |
| entry which, if  |                |                |                |
| breached or      |                |                |                |
| missing, can     |                |                |                |
| reasonably be    |                |                |                |
| expected to      |                |                |                |
| provide visible  |                |                |                |
| evidence to      |                |                |                |
| consumers that   |                |                |                |
| tampering has    |                |                |                |
| occurred. To     |                |                |                |
| reduce the       |                |                |                |
| likelihood of    |                |                |                |
| successful       |                |                |                |
| tampering and to |                |                |                |
| increase the     |                |                |                |
| likelihood that  |                |                |                |
| consumers will   |                |                |                |
| discover if a    |                |                |                |
| product has been |                |                |                |
| tampered with,   |                |                |                |
| the package is   |                |                |                |
| required to be   |                |                |                |
| distinctive by   |                |                |                |
| design or by the |                |                |                |
| use of one or    |                |                |                |
| more indicators  |                |                |                |
| or barriers to   |                |                |                |
| entry that       |                |                |                |
| employ an        |                |                |                |
| identifying      |                |                |                |
| characteristic   |                |                |                |
| (e.g., a         |                |                |                |
| pattern, name,   |                |                |                |
| registered       |                |                |                |
| trademark, logo, |                |                |                |
| or picture). For |                |                |                |
| purposes of this |                |                |                |
| section, the     |                |                |                |
| term             |                |                |                |
| \"distinctive by |                |                |                |
| design\" means   |                |                |                |
| the packaging    |                |                |                |
| cannot be        |                |                |                |
| duplicated with  |                |                |                |
| commonly         |                |                |                |
| available        |                |                |                |
| materials or     |                |                |                |
| through commonly |                |                |                |
| available        |                |                |                |
| processes. A     |                |                |                |
| tamper-evident   |                |                |                |
| package may      |                |                |                |
| involve an       |                |                |                |
| imm              |                |                |                |
| ediate-container |                |                |                |
| and closure      |                |                |                |
| system or        |                |                |                |
| sec              |                |                |                |
| ondary-container |                |                |                |
| or carton system |                |                |                |
| or any           |                |                |                |
| combination of   |                |                |                |
| systems intended |                |                |                |
| to provide a     |                |                |                |
| visual           |                |                |                |
| indication of    |                |                |                |
| package          |                |                |                |
| integrity. The   |                |                |                |
| tamper-evident   |                |                |                |
| feature shall be |                |                |                |
| designed to and  |                |                |                |
| shall remain     |                |                |                |
| intact when      |                |                |                |
| handled in a     |                |                |                |
| reasonable       |                |                |                |
| manner during    |                |                |                |
| manufacture,     |                |                |                |
| distribution,    |                |                |                |
| and retail       |                |                |                |
| display.         |                |                |                |
|                  |                |                |                |
| \(2\) In         |                |                |                |
| addition to the  |                |                |                |
| tamper-evident   |                |                |                |
| packaging        |                |                |                |
| feature          |                |                |                |
| described in     |                |                |                |
| paragraph (b)(1) |                |                |                |
| of this section, |                |                |                |
| any two-piece,   |                |                |                |
| hard gelatin     |                |                |                |
| capsule covered  |                |                |                |
| by this section  |                |                |                |
| must be sealed   |                |                |                |
| using an         |                |                |                |
| acceptable       |                |                |                |
| tamper-evident   |                |                |                |
| technology.      |                |                |                |
+------------------+----------------+----------------+----------------+
| \(c\)            |                |                |                |
| *Labeling*.      |                |                |                |
|                  |                |                |                |
| \(1\) In order   |                |                |                |
| to alert         |                |                |                |
| consumers to the |                |                |                |
| specific         |                |                |                |
| tamper-evident   |                |                |                |
| feature(s) used, |                |                |                |
| each retail      |                |                |                |
| package of an    |                |                |                |
| OTC drug product |                |                |                |
| covered by this  |                |                |                |
| section (except  |                |                |                |
| ammonia inhalant |                |                |                |
| in crushable     |                |                |                |
| glass ampules,   |                |                |                |
| containers of    |                |                |                |
| compressed       |                |                |                |
| medical oxygen,  |                |                |                |
| or aerosol       |                |                |                |
| products that    |                |                |                |
| depend upon the  |                |                |                |
| power of a       |                |                |                |
| liquefied or     |                |                |                |
| compressed gas   |                |                |                |
| to expel the     |                |                |                |
| contents from    |                |                |                |
| the container)   |                |                |                |
| is required to   |                |                |                |
| bear a statement |                |                |                |
| that:            |                |                |                |
|                  |                |                |                |
| > \(i\)          |                |                |                |
| > Identifies all |                |                |                |
| > tamper-evident |                |                |                |
| > feature(s) and |                |                |                |
| > any capsule    |                |                |                |
| > sealing        |                |                |                |
| > technologies   |                |                |                |
| > used to comply |                |                |                |
| > with paragraph |                |                |                |
| > (b) of this    |                |                |                |
| > section;       |                |                |                |
| >                |                |                |                |
| > \(ii\) Is      |                |                |                |
| > prominently    |                |                |                |
| > placed on the  |                |                |                |
| > package; and   |                |                |                |
| >                |                |                |                |
| > \(iii\) Is so  |                |                |                |
| > placed that it |                |                |                |
| > will be        |                |                |                |
| > unaffected if  |                |                |                |
| > the            |                |                |                |
| > tamper-evident |                |                |                |
| > feature of the |                |                |                |
| > package is     |                |                |                |
| > breached or    |                |                |                |
| > missing.       |                |                |                |
|                  |                |                |                |
| \(2\) If the     |                |                |                |
| tamper-evident   |                |                |                |
| feature chosen   |                |                |                |
| to meet the      |                |                |                |
| requirements in  |                |                |                |
| paragraph (b) of |                |                |                |
| this section     |                |                |                |
| uses an          |                |                |                |
| identifying      |                |                |                |
| characteristic,  |                |                |                |
| that             |                |                |                |
| characteristic   |                |                |                |
| is required to   |                |                |                |
| be referred to   |                |                |                |
| in the labeling  |                |                |                |
| statement. For   |                |                |                |
| example, the     |                |                |                |
| labeling         |                |                |                |
| statement on a   |                |                |                |
| bottle with a    |                |                |                |
| shrink band      |                |                |                |
| could say \"For  |                |                |                |
| your protection, |                |                |                |
| this bottle has  |                |                |                |
| an imprinted     |                |                |                |
| seal around the  |                |                |                |
| neck.\"          |                |                |                |
+------------------+----------------+----------------+----------------+
| \(d\) *Request   |                |                |                |
| for exemptions   |                |                |                |
| from packaging   |                |                |                |
| and labeling     |                |                |                |
| requirements.* A |                |                |                |
| manufacturer or  |                |                |                |
| packer may       |                |                |                |
| request an       |                |                |                |
| exemption from   |                |                |                |
| the packaging    |                |                |                |
| and labeling     |                |                |                |
| requirements of  |                |                |                |
| this section. A  |                |                |                |
| request for an   |                |                |                |
| exemption is     |                |                |                |
| required to be   |                |                |                |
| submitted in the |                |                |                |
| form of a        |                |                |                |
| citizen petition |                |                |                |
| under §10.30 of  |                |                |                |
| this chapter and |                |                |                |
| should be        |                |                |                |
| clearly          |                |                |                |
| identified on    |                |                |                |
| the envelope as  |                |                |                |
| a \"Request for  |                |                |                |
| Exemption from   |                |                |                |
| the              |                |                |                |
| Tamper-Evident   |                |                |                |
| Packaging        |                |                |                |
| Rule.\" The      |                |                |                |
| petition is      |                |                |                |
| required to      |                |                |                |
| contain the      |                |                |                |
| following:       |                |                |                |
|                  |                |                |                |
| \(1\) The name   |                |                |                |
| of the drug      |                |                |                |
| product or, if   |                |                |                |
| the petition     |                |                |                |
| seeks an         |                |                |                |
| exemption for a  |                |                |                |
| drug class, the  |                |                |                |
| name of the drug |                |                |                |
| class, and a     |                |                |                |
| list of products |                |                |                |
| within that      |                |                |                |
| class.           |                |                |                |
|                  |                |                |                |
| \(2\) The        |                |                |                |
| reasons that the |                |                |                |
| drug product\'s  |                |                |                |
| compliance with  |                |                |                |
| the              |                |                |                |
| tamper-evident   |                |                |                |
| packaging or     |                |                |                |
| labeling         |                |                |                |
| requirements of  |                |                |                |
| this section is  |                |                |                |
| unnecessary or   |                |                |                |
| cannot be        |                |                |                |
| achieved.        |                |                |                |
|                  |                |                |                |
| \(3\) A          |                |                |                |
| description of   |                |                |                |
| alternative      |                |                |                |
| steps that are   |                |                |                |
| available, or    |                |                |                |
| that the         |                |                |                |
| petitioner has   |                |                |                |
| already taken,   |                |                |                |
| to reduce the    |                |                |                |
| likelihood that  |                |                |                |
| the product or   |                |                |                |
| drug class will  |                |                |                |
| be the subject   |                |                |                |
| of malicious     |                |                |                |
| adulteration.    |                |                |                |
|                  |                |                |                |
| \(4\) Other      |                |                |                |
| information      |                |                |                |
| justifying an    |                |                |                |
| exemption.       |                |                |                |
+------------------+----------------+----------------+----------------+
| \(e\) *OTC drug  |                |                |                |
| products subject |                |                |                |
| to approved new  |                |                |                |
| drug             |                |                |                |
| applications.*   |                |                |                |
| Holders of       |                |                |                |
| approved new     |                |                |                |
| drug             |                |                |                |
| applications for |                |                |                |
| OTC drug         |                |                |                |
| products are     |                |                |                |
| required under   |                |                |                |
| §314.70 of this  |                |                |                |
| chapter to       |                |                |                |
| provide the      |                |                |                |
| agency with      |                |                |                |
| notification of  |                |                |                |
| changes in       |                |                |                |
| packaging and    |                |                |                |
| labeling to      |                |                |                |
| comply with the  |                |                |                |
| requirements of  |                |                |                |
| this section.    |                |                |                |
| Changes in       |                |                |                |
| packaging and    |                |                |                |
| labeling         |                |                |                |
| required by this |                |                |                |
| regulation may   |                |                |                |
| be made before   |                |                |                |
| FDA approval, as |                |                |                |
| provided under   |                |                |                |
| §314.70(c) of    |                |                |                |
| this chapter.    |                |                |                |
| Manufacturing    |                |                |                |
| changes by which |                |                |                |
| capsules are to  |                |                |                |
| be sealed        |                |                |                |
| require prior    |                |                |                |
| FDA approval     |                |                |                |
| under §314.70(b) |                |                |                |
| of this chapter. |                |                |                |
+------------------+----------------+----------------+----------------+
| \(f\) *Poison    |                |                |                |
| Prevention       |                |                |                |
| Packaging Act of |                |                |                |
| 1970.* This      |                |                |                |
| section does not |                |                |                |
| affect any       |                |                |                |
| requirements for |                |                |                |
| \"special        |                |                |                |
| packaging\" as   |                |                |                |
| defined under    |                |                |                |
| §310.3(l) of     |                |                |                |
| this chapter and |                |                |                |
| required under   |                |                |                |
| the Poison       |                |                |                |
| Prevention       |                |                |                |
| Packaging Act of |                |                |                |
| 1970.            |                |                |                |
+------------------+----------------+----------------+----------------+
|                  |                |                | **§ 111.72     |
|                  |                |                | [What          |
|                  |                |                | requirements   |
|                  |                |                | apply to       |
|                  |                |                | packaging of   |
|                  |                |                | i              |
|                  |                |                | ron-containing |
|                  |                |                | dietary        |
|                  |                |                | supplements?]  |
|                  |                |                | {.underline}** |
|                  |                |                |                |
|                  |                |                | \(a\) The use  |
|                  |                |                | of iron and    |
|                  |                |                | iron salts as  |
|                  |                |                | iron sources   |
|                  |                |                | in dietary     |
|                  |                |                | supplements    |
|                  |                |                | offered in     |
|                  |                |                | solid oral     |
|                  |                |                | dosage form    |
|                  |                |                | (e.g., tablets |
|                  |                |                | or capsules),  |
|                  |                |                | and containing |
|                  |                |                | 30 milligrams  |
|                  |                |                | or more of     |
|                  |                |                | iron per       |
|                  |                |                | dosage unit,   |
|                  |                |                | is safe and in |
|                  |                |                | accordance     |
|                  |                |                | with current   |
|                  |                |                | good           |
|                  |                |                | manufacturing  |
|                  |                |                | practice only  |
|                  |                |                | when such      |
|                  |                |                | supplements    |
|                  |                |                | are packaged   |
|                  |                |                | in unit-dose   |
|                  |                |                | packaging.     |
|                  |                |                | ''Unitdose     |
|                  |                |                | packaging''    |
|                  |                |                | means a method |
|                  |                |                | of packaging a |
|                  |                |                | product into a |
|                  |                |                | nonreusable    |
|                  |                |                | container      |
|                  |                |                | designed to    |
|                  |                |                | hold a single  |
|                  |                |                | dosage unit    |
|                  |                |                | intended for   |
|                  |                |                | administration |
|                  |                |                | directly from  |
|                  |                |                | that           |
|                  |                |                | container,     |
|                  |                |                | irrespective   |
|                  |                |                | of whether the |
|                  |                |                | recommended    |
|                  |                |                | dose is one or |
|                  |                |                | more than one  |
|                  |                |                | of these       |
|                  |                |                | units. The     |
|                  |                |                | term ''dosage  |
|                  |                |                | unit'' means   |
|                  |                |                | the individual |
|                  |                |                | physical unit  |
|                  |                |                | of the product |
|                  |                |                | (e.g., tablets |
|                  |                |                | or capsules).  |
|                  |                |                | I              |
|                  |                |                | ron-containing |
|                  |                |                | dietary        |
|                  |                |                | supplements    |
|                  |                |                | that are       |
|                  |                |                | subject to     |
|                  |                |                | this           |
|                  |                |                | regulation are |
|                  |                |                | also subject   |
|                  |                |                | to             |
|                  |                |                | c              |
|                  |                |                | hild-resistant |
|                  |                |                | special        |
|                  |                |                | packaging      |
|                  |                |                | requirements   |
|                  |                |                | in 16 CFR      |
|                  |                |                | parts 1700,    |
|                  |                |                | 1701, and      |
|                  |                |                | 1702.          |
|                  |                |                |                |
|                  |                |                | (b)(1) Dietary |
|                  |                |                | supplements    |
|                  |                |                | offered in     |
|                  |                |                | solid oral     |
|                  |                |                | dosage form    |
|                  |                |                | (e.g., tablets |
|                  |                |                | or capsules),  |
|                  |                |                | and containing |
|                  |                |                | 30 milligrams  |
|                  |                |                | or more of     |
|                  |                |                | iron per       |
|                  |                |                | dosage unit,   |
|                  |                |                | are exempt     |
|                  |                |                | from the       |
|                  |                |                | provisions of  |
|                  |                |                | paragraph (a)  |
|                  |                |                | of this        |
|                  |                |                | section until  |
|                  |                |                | January 15,    |
|                  |                |                | 1998, if the   |
|                  |                |                | sole source of |
|                  |                |                | iron in the    |
|                  |                |                | dietary        |
|                  |                |                | supplement is  |
|                  |                |                | carbonyl iron  |
|                  |                |                | that meets the |
|                  |                |                | specifications |
|                  |                |                | of § 184.1375  |
|                  |                |                | of this        |
|                  |                |                | chapter.       |
|                  |                |                |                |
|                  |                |                | \(2\) If the   |
|                  |                |                | temporary      |
|                  |                |                | exemption is   |
|                  |                |                | not extended   |
|                  |                |                | or made        |
|                  |                |                | permanent,     |
|                  |                |                | such dietary   |
|                  |                |                | supplements    |
|                  |                |                | shall be in    |
|                  |                |                | compliance     |
|                  |                |                | with the       |
|                  |                |                | provisions of  |
|                  |                |                | paragraph (a)  |
|                  |                |                | of this        |
|                  |                |                | section on or  |
|                  |                |                | before July    |
|                  |                |                | 15,1998.       |
+------------------+----------------+----------------+----------------+
| ## § 21          | \(9\) Food,    | \(10\)         | **§ 111.74     |
| 1.89 Rejected co | raw materials, | Rejected raw   | [What          |
| mponents, drug p | and other      | materials,     | requirements   |
| roduct container | ingredients    | shall be       | apply to       |
| s, and closures. | that are       | identified and | rejected       |
|                  | adulterated    | controlled     | components,    |
| Rejected         | within the     | under a system | dietary        |
| components, drug | meaning of the | that prevents  | ingredients,   |
| product          | act shall be   | their use in   | dietary        |
| containers, and  | disposed of in | manufacturing  | supplements,   |
| closures shall   | a manner that  | or processing  | packaging, and |
| be identified    | protects       | operations for | labels?]       |
| and controlled   | against the    | which they are | {.underline}** |
| under a          | contamination  | unsuitable.    |                |
| quarantine       | of other       |                | You must       |
| system designed  | food\...       | \(10\) Dietary | clearly        |
| to prevent their |                | products, raw  | identify,      |
| use in           |                | materials, and | hold, and      |
| manufacturing or |                | in-process     | control under  |
| processing       |                | materials that | a quarantine   |
| operations for   |                | are rejected   | system any     |
| which they are   |                | or adulterated | component,     |
| unsuitable.      |                | within the     | dietary        |
|                  |                | meaning of the | ingredient,    |
|                  |                | act shall be   | dietary        |
|                  |                | identified,    | supplement,    |
|                  |                | stored and     | packaging, and |
|                  |                | disposed of in | label that is  |
|                  |                | a manner that  | rejected and   |
|                  |                | protects       | unsuitable for |
|                  |                | against the    | use in         |
|                  |                | adulteration   | manufacturing, |
|                  |                | of other       | packaging, or  |
|                  |                | products.      | label          |
|                  |                |                | operations.    |
+------------------+----------------+----------------+----------------+
| ## §             | **¶110.93      | **Warehousing, | **Subpart      |
|  211.142 Warehou | Warehousing    | Distribution   | F\--Holding    |
| sing procedures. | and            | and            | and            |
|                  | d              | Pos            | Distributing** |
| Written          | istribution.** | t-Distribution |                |
| procedures       |                | Procedures**   | **§ 111.80     |
| describing the   | Storage and    |                | [What          |
| warehousing of   | transportation | \(a\) Storage  | requirements   |
| drug products    | of finished    | and            | apply to       |
| shall be         | food shall be  | distribution.  | holding        |
| established and  | under          |                | components     |
| followed. They   | conditions     | \(1\) Storage  | dietary        |
| shall include:   | that will      | and            | ingredients,   |
|                  | protect food   | transportation | dietary        |
| \(a\) Quarantine | against        | of finished    | supplements,   |
| of drug products | physical,      | product shall  | packaging and  |
| before release   | chemical, and  | be under       | labels]{       |
| by the quality   | microbial      | conditions     | .underline}?** |
| control unit.    | contamination  | that will      |                |
|                  | as well as     | protect        | \(a\) You must |
| \(b\) Storage of | against        | product        | hold           |
| drug products    | deterioration  | against        | components,    |
| under            | of the food    | physical,      | dietary        |
| appropriate      | and the        | chemical, and  | ingredients,   |
| conditions of    | container.     | microbial      | and dietary    |
| temperature,     |                | adulteration   | supplements    |
| humidity, and    |                | as well as     | under          |
| light so that    |                | against        | appropriate    |
| the identity,    |                | deterioration  | conditions of  |
| strength,        |                | of the product | temperature,   |
| quality, and     |                | and the        | humidity, and  |
| purity of the    |                | container.     | light so that  |
| drug products    |                |                | the identity,  |
| are not          |                |                | purity,        |
| affected.        |                |                | quality,       |
|                  |                |                | strength, and  |
|                  |                |                | composition of |
|                  |                |                | the            |
|                  |                |                | components,    |
|                  |                |                | dietary        |
|                  |                |                | ingredients,   |
|                  |                |                | and dietary    |
|                  |                |                | supplements    |
|                  |                |                | are not        |
|                  |                |                | affected.      |
+------------------+----------------+----------------+----------------+
|                  |                |                | \(b\) You must |
|                  |                |                | hold packaging |
|                  |                |                | and labels     |
|                  |                |                | under          |
|                  |                |                | appropriate    |
|                  |                |                | conditions of  |
|                  |                |                | temperature,   |
|                  |                |                | humidity, and  |
|                  |                |                | light so that  |
|                  |                |                | the quality of |
|                  |                |                | the packaging  |
|                  |                |                | and labels are |
|                  |                |                | not affected.  |
+------------------+----------------+----------------+----------------+
|                  | \(6\)          | \(7\)          | \(c\) You must |
|                  | Effective      | Effective      | hold           |
|                  | measures shall | measures shall | components,    |
|                  | be taken to    | be taken to    | dietary        |
|                  | protect        | protect        | ingredients,   |
|                  | finished food  | finished       | dietary        |
|                  | from           | dietary        | supplements,   |
|                  | contamination  | ingredients    | packaging, and |
|                  | by raw         | and dietary    | labels under   |
|                  | materials,     | supplements    | conditions     |
|                  | other          | from           | that do not    |
|                  | ingredients,   | adulteration   | lead to the    |
|                  | or refuse.     | by raw         | mixup,         |
|                  | When raw       | materials,     | contamination, |
|                  | materials,     | in-process     | or             |
|                  | other          | materials or   | deterioration  |
|                  | ingredients,   | refuse. When   | of components, |
|                  | or refuse are  | raw materials, | dietary        |
|                  | unprotected,   | in-process     | ingredients,   |
|                  | they shall not | materials or   | dietary        |
|                  | be handled     | refuse are     | supplements,   |
|                  | simultaneously | unprotected,   | packaging, and |
|                  | in a           | they shall not | labels.        |
|                  | receiving,     | be handled     |                |
|                  | loading, or    | simultaneously |                |
|                  | shipping area  | in a           |                |
|                  | if that        | receiving,     |                |
|                  | handling could | loading, or    |                |
|                  | result in      | shipping area  |                |
|                  | contaminated   | if that        |                |
|                  | food. Food     | handling could |                |
|                  | transported by | result in      |                |
|                  | conveyor shall | adulterated    |                |
|                  | be protected   | dietary        |                |
|                  | against        | products.      |                |
|                  | contamination  | Dietary        |                |
|                  | as necessary.  | ingredients    |                |
|                  |                | and dietary    |                |
|                  |                | supplements    |                |
|                  |                | transported by |                |
|                  |                | conveyor shall |                |
|                  |                | be protected   |                |
|                  |                | against        |                |
|                  |                | adulteration   |                |
|                  |                | as necessary.  |                |
+------------------+----------------+----------------+----------------+
|                  | \(5\)          | \(6\)          | **Sec. 111.82  |
|                  | W              | W              | [What          |
|                  | ork-in-process | ork-in-process | requirements   |
|                  | shall be       | shall be       | apply to       |
|                  | handled in a   | handled in a   | holding        |
|                  | manner that    | manner that    | in-process     |
|                  | protects       | protects       | material?]     |
|                  | against        | against        | {.underline}** |
|                  | contamination. | adulteration.  |                |
|                  |                |                | \(a\) You must |
|                  |                |                | identify and   |
|                  |                |                | hold           |
|                  |                |                | in-process     |
|                  |                |                | material under |
|                  |                |                | conditions     |
|                  |                |                | that will      |
|                  |                |                | protect them   |
|                  |                |                | against mixup, |
|                  |                |                | contamination, |
|                  |                |                | and            |
|                  |                |                | deterioration  |
+------------------+----------------+----------------+----------------+
|                  |                |                | \(b\) You must |
|                  |                |                | hold in        |
|                  |                |                | process        |
|                  |                |                | material under |
|                  |                |                | appropriate    |
|                  |                |                | conditions of  |
|                  |                |                | temperature,   |
|                  |                |                | humidity, and  |
|                  |                |                | light.         |
+------------------+----------------+----------------+----------------+
| ## § 211.170     |                |                | **§ 111.83     |
| Reserve samples. |                |                | [What          |
|                  |                |                | requirements   |
| \(a\) An         |                |                | apply to       |
| appropriately    |                |                | holding        |
| identified       |                |                | reserve        |
| reserve sample   |                |                | samples of     |
| that is          |                |                | components,    |
| representative   |                |                | dietary        |
| of each lot in   |                |                | ingredients    |
| each shipment of |                |                | and dietary    |
| each active      |                |                | supplements?]  |
| ingredient shall |                |                | {.underline}** |
| be retained. The |                |                |                |
| reserve sample   |                |                | \(a\) For any  |
| consists of at   |                |                | reserve        |
| least twice the  |                |                | samples of     |
| quantity         |                |                | components or  |
| necessary for    |                |                | dietary        |
| all tests        |                |                | ingredients    |
| required to      |                |                | you collect,   |
| determine        |                |                | you must hold  |
| whether the      |                |                | such reserve   |
| active           |                |                | samples in a   |
| ingredient meets |                |                | manner that    |
| its established  |                |                | protects       |
| specifications,  |                |                | against        |
| except for       |                |                | contamination  |
| sterility and    |                |                | and            |
| pyrogen testing. |                |                | deterioration: |
| The retention    |                |                |                |
| time is as       |                |                |                |
| follows:         |                |                |                |
|                  |                |                |                |
| \(1\) For an     |                |                |                |
| active           |                |                |                |
| ingredient in a  |                |                |                |
| drug product     |                |                |                |
| other than those |                |                |                |
| described in     |                |                |                |
| paragraphs (a)   |                |                |                |
| (2) and (3) of   |                |                |                |
| this section,    |                |                |                |
| the reserve      |                |                |                |
| sample shall be  |                |                |                |
| retained for 1   |                |                |                |
| year after the   |                |                |                |
| expiration date  |                |                |                |
| of the last lot  |                |                |                |
| of the drug      |                |                |                |
| product          |                |                |                |
| containing the   |                |                |                |
| active           |                |                |                |
| ingredient.      |                |                |                |
+------------------+----------------+----------------+----------------+
| \(2\) For an     |                |                |                |
| active           |                |                |                |
| ingredient in a  |                |                |                |
| radioactive drug |                |                |                |
| product, except  |                |                |                |
| for              |                |                |                |
| nonradioactive   |                |                |                |
| reagent kits,    |                |                |                |
| the reserve      |                |                |                |
| sample shall be  |                |                |                |
| retained for:    |                |                |                |
|                  |                |                |                |
| > \(i\) Three    |                |                |                |
| > months after   |                |                |                |
| > the expiration |                |                |                |
| > date of the    |                |                |                |
| > last lot of    |                |                |                |
| > the drug       |                |                |                |
| > product        |                |                |                |
| > containing the |                |                |                |
| > active         |                |                |                |
| > ingredient if  |                |                |                |
| > the expiration |                |                |                |
| > dating period  |                |                |                |
| > of the drug    |                |                |                |
| > product is 30  |                |                |                |
| > days or less;  |                |                |                |
| > or             |                |                |                |
| >                |                |                |                |
| > \(ii\) Six     |                |                |                |
| > months after   |                |                |                |
| > the expiration |                |                |                |
| > date of the    |                |                |                |
| > last lot of    |                |                |                |
| > the drug       |                |                |                |
| > product        |                |                |                |
| > containing the |                |                |                |
| > active         |                |                |                |
| > ingredient if  |                |                |                |
| > the expiration |                |                |                |
| > dating period  |                |                |                |
| > of the drug    |                |                |                |
| > product is     |                |                |                |
| > more than 30   |                |                |                |
| > days.          |                |                |                |
|                  |                |                |                |
| \(3\) For an     |                |                |                |
| active           |                |                |                |
| ingredient in an |                |                |                |
| OTC drug product |                |                |                |
| that is exempt   |                |                |                |
| from bearing an  |                |                |                |
| expiration date  |                |                |                |
| under §211.137,  |                |                |                |
| the reserve      |                |                |                |
| sample shall be  |                |                |                |
| retained for 3   |                |                |                |
| years after      |                |                |                |
| distribution of  |                |                |                |
| the last lot of  |                |                |                |
| the drug product |                |                |                |
| containing the   |                |                |                |
| active           |                |                |                |
| ingredient.      |                |                |                |
+------------------+----------------+----------------+----------------+
| \(b\) An         |                | \(b\) Reserve  | \(b\) You must |
| appropriately    |                | samples. An    | hold reserve   |
| identified       |                | appropriately  | samples of     |
| reserve sample   |                | identified     | dietary        |
| that is          |                | reserve sample | supplements in |
| representative   |                | that is        | a manner that  |
| of each lot or   |                | representative | protects       |
| batch of drug    |                | of each batch  | against        |
| product shall be |                | of a dietary   | contamination  |
| retained and     |                | product should | and            |
| stored under     |                | be retained    | deterioration. |
| conditions       |                | and stored     | This includes, |
| consistent with  |                | under          | but is not     |
| product          |                | conditions     | limited to:    |
| labeling. The    |                | consistent     |                |
| reserve sample   |                | with the       | \(1\) Holding  |
| shall be stored  |                | product        | the reserve    |
| in the same      |                | labeling until | samples under  |
| immediate        |                | at least one   | conditions of  |
| c                |                | year after the | use            |
| ontainer-closure |                | expiration     | recommended or |
| system in which  |                | date, or if no | suggested in   |
| the drug product |                | expiration     | the label of   |
| is marketed or   |                | date is        | the dietary    |
| in one that has  |                | identified on  | supplement     |
| essentially the  |                | the product,   | and, if no     |
| same             |                | for at least   | conditions of  |
| characteristics. |                | three years    | use are        |
| The reserve      |                | after the date | recommended or |
| sample consists  |                | of             | suggested in   |
| of at least      |                | manufacture.   | the label,     |
| twice the        |                | The reserve    | then under     |
| quantity         |                | sample should  | ordinary       |
| necessary to     |                | be stored in   | conditions of  |
| perform all the  |                | the same       | use; and       |
| required tests,  |                | immediate      |                |
| except those for |                | con            | \(2\) Using    |
| sterility and    |                | tainer-closure | the same       |
| pyrogens. Except |                | system in      | con            |
| for those for    |                | which the      | tainer-closure |
| drug products    |                | finished       | system in      |
| described in     |                | product is     | which the      |
| paragraph (b)(2) |                | marketed or in | dietary        |
| of this section, |                | one that       | supplement is  |
| reserve samples  |                | provides       | marketed or in |
| from             |                | similar        | one that       |
| representative   |                | protection.    | provides the   |
| sample lots or   |                | The reserve    | same level of  |
| batches selected |                | sample shall   | protection     |
| by acceptable    |                | consist of at  | against        |
| statistical      |                | least twice    | contamination  |
| procedures shall |                | the quantity   | or             |
| be examined      |                | necessary to   | deterioration. |
| visually at      |                | perform all    |                |
| least once a     |                | the required   |                |
| year for         |                | tests.         |                |
| evidence of      |                |                |                |
| deterioration    |                |                |                |
| unless visual    |                |                |                |
| examination      |                |                |                |
| would affect the |                |                |                |
| integrity of the |                |                |                |
| reserve sample.  |                |                |                |
| Any evidence of  |                |                |                |
| reserve sample   |                |                |                |
| deterioration    |                |                |                |
| shall be         |                |                |                |
| investigated in  |                |                |                |
| accordance with  |                |                |                |
| §211.192. The    |                |                |                |
| results of the   |                |                |                |
| examination      |                |                |                |
| shall be         |                |                |                |
| recorded and     |                |                |                |
| maintained with  |                |                |                |
| other stability  |                |                |                |
| data on the drug |                |                |                |
| product. Reserve |                |                |                |
| samples of       |                |                |                |
| compressed       |                |                |                |
| medical gases    |                |                |                |
| need not be      |                |                |                |
| retained. The    |                |                |                |
| retention time   |                |                |                |
| is as follows:   |                |                |                |
|                  |                |                |                |
| \(1\) For a drug |                |                |                |
| product other    |                |                |                |
| than those       |                |                |                |
| described in     |                |                |                |
| paragraphs (b)   |                |                |                |
| (2) and (3) of   |                |                |                |
| this section,    |                |                |                |
| the reserve      |                |                |                |
| sample shall be  |                |                |                |
| retained for 1   |                |                |                |
| year after the   |                |                |                |
| expiration date  |                |                |                |
| of the drug      |                |                |                |
| product.         |                |                |                |
|                  |                |                |                |
| \(3\) For an OTC |                |                |                |
| drug product     |                |                |                |
| that is exempt   |                |                |                |
| for bearing an   |                |                |                |
| expiration date  |                |                |                |
| under §211.137,  |                |                |                |
| the reserve      |                |                |                |
| sample must be   |                |                |                |
| retained for 3   |                |                |                |
| years after the  |                |                |                |
| lot or batch of  |                |                |                |
| drug product is  |                |                |                |
| distributed.     |                |                |                |
+------------------+----------------+----------------+----------------+
| \(2\) For a      |                |                |                |
| radioactive drug |                |                |                |
| product, except  |                |                |                |
| for              |                |                |                |
| nonradioactive   |                |                |                |
| reagent kits,    |                |                |                |
| the reserve      |                |                |                |
| sample shall be  |                |                |                |
| retained for:    |                |                |                |
|                  |                |                |                |
| > \(i\) Three    |                |                |                |
| > months after   |                |                |                |
| > the expiration |                |                |                |
| > date of the    |                |                |                |
| > drug product   |                |                |                |
| > if the         |                |                |                |
| > expiration     |                |                |                |
| > dating period  |                |                |                |
| > of the drug    |                |                |                |
| > product is 30  |                |                |                |
| > days or less;  |                |                |                |
| > or             |                |                |                |
| >                |                |                |                |
| > \(ii\) Six     |                |                |                |
| > months after   |                |                |                |
| > the expiration |                |                |                |
| > date of the    |                |                |                |
| > drug product   |                |                |                |
| > if the         |                |                |                |
| > expiration     |                |                |                |
| > dating period  |                |                |                |
| > of the drug    |                |                |                |
| > product is     |                |                |                |
| > more than 30   |                |                |                |
| > days.          |                |                |                |
+------------------+----------------+----------------+----------------+
| ## § 211.173 Lab |                |                |                |
| oratory animals. |                |                |                |
|                  |                |                |                |
| Animals used in  |                |                |                |
| testing          |                |                |                |
| components,      |                |                |                |
| in-process       |                |                |                |
| materials, or    |                |                |                |
| drug products    |                |                |                |
| for compliance   |                |                |                |
| with established |                |                |                |
| specifications   |                |                |                |
| shall be         |                |                |                |
| maintained and   |                |                |                |
| controlled in a  |                |                |                |
| manner that      |                |                |                |
| assures their    |                |                |                |
| suitability for  |                |                |                |
| their intended   |                |                |                |
| use. They shall  |                |                |                |
| be identified,   |                |                |                |
| and adequate     |                |                |                |
| records shall be |                |                |                |
| maintained       |                |                |                |
| showing the      |                |                |                |
| history of their |                |                |                |
| use.             |                |                |                |
+------------------+----------------+----------------+----------------+
| ## § 2           |                |                |                |
| 11.176 Penicilli |                |                |                |
| n contamination. |                |                |                |
|                  |                |                |                |
| If a reasonable  |                |                |                |
| possibility      |                |                |                |
| exists that a    |                |                |                |
| non-penicillin   |                |                |                |
| drug product has |                |                |                |
| been exposed to  |                |                |                |
| cro              |                |                |                |
| ss-contamination |                |                |                |
| with penicillin, |                |                |                |
| the              |                |                |                |
| non-penicillin   |                |                |                |
| drug product     |                |                |                |
| shall be tested  |                |                |                |
| for the presence |                |                |                |
| of penicillin.   |                |                |                |
| Such drug        |                |                |                |
| product shall    |                |                |                |
| not be marketed  |                |                |                |
| if detectable    |                |                |                |
| levels are found |                |                |                |
| when tested      |                |                |                |
| according to     |                |                |                |
| procedures       |                |                |                |
| specified in     |                |                |                |
| \`Procedures for |                |                |                |
| Detecting and    |                |                |                |
| Measuring        |                |                |                |
| Penicillin       |                |                |                |
| Contamination in |                |                |                |
| Drugs,\' which   |                |                |                |
| is incorporated  |                |                |                |
| by reference.    |                |                |                |
| Copies are       |                |                |                |
| available from   |                |                |                |
| the Division of  |                |                |                |
| Research and     |                |                |                |
| Testing          |                |                |                |
| (HFD-470),       |                |                |                |
| Center for Drug  |                |                |                |
| Evaluation and   |                |                |                |
| Research, Food   |                |                |                |
| and Drug         |                |                |                |
| Administration,  |                |                |                |
| 200 C St. SW.,   |                |                |                |
| Washington, DC   |                |                |                |
| 20204, or        |                |                |                |
| available for    |                |                |                |
| inspection at    |                |                |                |
| the Office of    |                |                |                |
| the Federal      |                |                |                |
| Register, 800    |                |                |                |
| North Capitol    |                |                |                |
| Street, NW.,     |                |                |                |
| suite 700,       |                |                |                |
| Washington, DC   |                |                |                |
| 20408.           |                |                |                |
+------------------+----------------+----------------+----------------+
| ## §             |                | \(e\) Returned | **§ 111.85     |
|  211.204 Returne |                | products.      | [What          |
| d drug products. |                | Returned       | requirements   |
|                  |                | dietary        | apply to       |
| Returned drug    |                | products shall | returned       |
| products shall   |                | be identified  | dietary        |
| be identified as |                | as such and    | ingredients or |
| such and held.   |                | held. If the   | dietary        |
| If the           |                | conditions     | supplements?]  |
| conditions under |                | under which    | {.underline}** |
| which returned   |                | returned       |                |
| drug products    |                | dietary        | \(a\) You must |
| have been held,  |                | products have  | identify and   |
| stored, or       |                | been held,     | quarantine     |
| shipped before   |                | stored, or     | returned       |
| or during their  |                | shipped before | dietary        |
| return, or if    |                | or during      | ingredients or |
| the condition of |                | their return,  | dietary        |
| the drug         |                | or if the      | supplements    |
| product, its     |                | condition of   | until the      |
| container,       |                | the product,   | quality        |
| carton, or       |                | its container, | control unit   |
| labeling, as a   |                | carton, or     | conducts a     |
| result of        |                | labeling as a  | material       |
| storage or       |                | result of      | review and     |
| shipping, casts  |                | storage or     | makes a        |
| doubt on the     |                | shipping,      | disposition    |
| safety,          |                | casts doubt on | decision.      |
| identity,        |                | the purity,    |                |
| strength,        |                | composition or | \(b\) You must |
| quality or       |                | quality of the | not salvage    |
| purity of the    |                | product, the   | returned       |
| drug product,    |                | returned       | dietary        |
| the returned     |                | product shall  | ingredients    |
| drug product     |                | be destroyed   | and dietary    |
| shall be         |                | unless         | supplements,   |
| destroyed unless |                | examination,   | unless:        |
| examination,     |                | testing or     |                |
| testing, or      |                | other          | \(1\) Evidence |
| other            |                | investigations | from their     |
| investigations   |                | prove the      | packaging (or, |
| prove the drug   |                | product meets  | if possible,   |
| product meets    |                | appropriate    | an inspection  |
| appropriate      |                | standards of   | of the         |
| standards of     |                | purity,        | premises,      |
| safety,          |                | composition    | where the      |
| identity,        |                | and quality. A | dietary        |
| strength,        |                | product may be | ingredients    |
| quality, or      |                | reprocessed    | and dietary    |
| purity. A drug   |                | provided the   | supplements    |
| product may be   |                | subsequent     | were held)     |
| reprocessed      |                | product meets  | indicates that |
| provided the     |                | appropriate    | the dietary    |
| subsequent drug  |                | s              | ingredients    |
| product meets    |                | pecifications. | and dietary    |
| appropriate      |                | Records        | supplements    |
| standards,       |                | pertaining to  | were not       |
| specifications,  |                | returned       | subjected to   |
| and              |                | products that  | improper       |
| characteristics. |                | are            | storage        |
| Records of       |                | subsequently   | conditions;    |
| returned drug    |                | reprocessed    | and            |
| products shall   |                | and/or         |                |
| be maintained    |                | redistributed  | \(2\) Tests    |
| and shall        |                | shall be       | demonstrate    |
| include the name |                | maintained and | that the       |
| and label        |                | shall include  | dietary        |
| potency of the   |                | the name and   | ingredients or |
| drug product     |                | description of | dietary        |
| dosage form, lot |                | the product,   | supplements    |
| number (or       |                | lot number,    | meet all       |
| control number   |                | reason for the | specifications |
| or batch         |                | return,        | for identity,  |
| number), reason  |                | quantity       | purity,        |
| for the return,  |                | returned, date | quality,       |
| quantity         |                | of             | strength, and  |
| returned, date   |                | disposition,   | composition.   |
| of disposition,  |                | and ultimate   |                |
| and ultimate     |                | disposition of | \(c\) You must |
| disposition of   |                | the returned   | destroy or     |
| the returned     |                | product.       | suitably       |
| drug product. If |                |                | dispose of the |
| the reason for a |                | \(f\) Product  | returned       |
| drug product     |                | salvaging.     | dietary        |
| being returned   |                | Dietary        | ingredients or |
| implicates       |                | products that  | dietary        |
| associated       |                | have been      | supplements if |
| batches, an      |                | subjected to   | such dietary   |
| appropriate      |                | improper       | ingredients or |
| investigation    |                | storage        | dietary        |
| shall be         |                | conditions     | supplements do |
| conducted in     |                | including      | not meet       |
| accordance with  |                | extremes in    | specifications |
| the requirements |                | temperature,   | for identity,  |
| of §211.192.     |                | humidity,      | purity,        |
| Procedures for   |                | smoke, fumes,  | quality,       |
| the holding,     |                | pressure, age, | strength, and  |
| testing, and     |                | or radiation   | composition,   |
| reprocessing of  |                | due to natural | unless the     |
| returned drug    |                | disasters,     | quality        |
| products shall   |                | fires,         | control unit   |
| be in writing    |                | accidents, or  | conducts a     |
| and shall be     |                | equipment      | material       |
| followed.        |                | failures shall | review and     |
|                  |                | not be         | makes a        |
| ## §             |                | salvaged and   | disposition    |
|  211.208 Drug pr |                | returned to    | decision to    |
| oduct salvaging. |                | the            | allow          |
|                  |                | marketplace.   | reprocessing.  |
| Drug products    |                | Whenever there |                |
| that have been   |                | is a question  | \(d\) If the   |
| subjected to     |                | whether        | reason for a   |
| improper storage |                | products have  | dietary        |
| conditions       |                | been subjected | ingredient or  |
| including        |                | to such        | a dietary      |
| extremes in      |                | conditions,    | supplement     |
| temperature,     |                | salvaging      | being returned |
| humidity, smoke, |                | operations may | implicates     |
| fumes, pressure, |                | be conducted   | associated     |
| age, or          |                | only if there  | batches, you   |
| radiation due to |                | is (a)         | must conduct   |
| natural          |                | evidence from  | an             |
| disasters,       |                | laboratory     | investigation  |
| fires,           |                | tests that the | of your        |
| accidents, or    |                | products meet  | manufacturing  |
| equipment        |                | all applicable | processes and  |
| failures shall   |                | standards of   | those other    |
| not be salvaged  |                | purity,        | batches to     |
| and returned to  |                | quality and    | determine      |
| the marketplace. |                | composition,   | compliance     |
| Whenever there   |                | and (b)        | with           |
| is a question    |                | evidence from  | s              |
| whether drug     |                | inspection of  | pecifications. |
| products have    |                | the premises   |                |
| been subjected   |                | that the       | \(e\) You must |
| to such          |                | products and   | establish and  |
| conditions,      |                | their          | keep records   |
| salvaging        |                | associated     | for this       |
| operations may   |                | packaging were | section on the |
| be conducted     |                | not subjected  | material       |
| only if there is |                | to improper    | review and     |
| (a) evidence     |                | storage        | disposition    |
| from laboratory  |                | conditions as  | decision and   |
| tests and assays |                | a result of    | any testing    |
| (including       |                | the disaster   | conducted to   |
| animal feeding   |                | or accident.   | determine      |
| studies where    |                | Records        | compliance     |
| applicable) that |                | including      | with           |
| the drug         |                | name, lot      | established    |
| products meet    |                | number, and    | specifications |
| all applicable   |                | disposition    | in the master  |
| standards of     |                | shall be       | manufacturing  |
| identity,        |                | maintained for | record for the |
| strength,        |                | products       | type of        |
| quality, and     |                | subject to     | dietary        |
| purity and (b)   |                | this section.  | ingredient or  |
| evidence from    |                |                | dietary        |
| inspection of    |                |                | supplement     |
| the premises     |                |                | that was       |
| that the drug    |                |                | returned.      |
| products and     |                |                |                |
| their associated |                |                | \(f\) You must |
| packaging were   |                |                | keep returned  |
| not subjected to |                |                | dietary        |
| improper storage |                |                | ingredient and |
| conditions as a  |                |                | dietary        |
| result of the    |                |                | supplement     |
| disaster or      |                |                | records in     |
| accident.        |                |                | accordance     |
| Organoleptic     |                |                | with §         |
| examinations     |                |                | 111.125.       |
| shall be         |                |                |                |
| acceptable only  |                |                |                |
| as supplemental  |                |                |                |
| evidence that    |                |                |                |
| the drug         |                |                |                |
| products meet    |                |                |                |
| appropriate      |                |                |                |
| standards of     |                |                |                |
| identity,        |                |                |                |
| strength,        |                |                |                |
| quality, and     |                |                |                |
| purity. Records  |                |                |                |
| including name,  |                |                |                |
| lot number, and  |                |                |                |
| disposition      |                |                |                |
| shall be         |                |                |                |
| maintained for   |                |                |                |
| drug products    |                |                |                |
| subject to this  |                |                |                |
| section.         |                |                |                |
+------------------+----------------+----------------+----------------+
|                  |                |                | **§ 111.90     |
|                  |                |                | [What          |
|                  |                |                | requirements   |
|                  |                |                | apply to       |
|                  |                |                | distributing   |
|                  |                |                | dietary        |
|                  |                |                | ingredients or |
|                  |                |                | dietary        |
|                  |                |                | supplements?]  |
|                  |                |                | {.underline}** |
|                  |                |                |                |
|                  |                |                | Distribution   |
|                  |                |                | of dietary     |
|                  |                |                | ingredients    |
|                  |                |                | and dietary    |
|                  |                |                | supplements    |
|                  |                |                | must be under  |
|                  |                |                | conditions     |
|                  |                |                | that will      |
|                  |                |                | protect the    |
|                  |                |                | dietary        |
|                  |                |                | ingredients    |
|                  |                |                | and dietary    |
|                  |                |                | supplements    |
|                  |                |                | against        |
|                  |                |                | contamination  |
|                  |                |                | and            |
|                  |                |                | deterioration. |
+------------------+----------------+----------------+----------------+
| ## §             |                |                |                |
| 211.150 Distribu |                |                |                |
| tion procedures. |                |                |                |
|                  |                |                |                |
| Written          |                |                |                |
| procedures shall |                |                |                |
| be established,  |                |                |                |
| and followed,    |                |                |                |
| describing the   |                |                |                |
| distribution of  |                |                |                |
| drug products.   |                |                |                |
| They shall       |                |                |                |
| include:         |                |                |                |
|                  |                |                |                |
| \(a\) A          |                |                |                |
| procedure        |                |                |                |
| whereby the      |                |                |                |
| oldest approved  |                |                |                |
| stock of a drug  |                |                |                |
| product is       |                |                |                |
| distributed      |                |                |                |
| first. Deviation |                |                |                |
| from this        |                |                |                |
| requirement is   |                |                |                |
| permitted if     |                |                |                |
| such deviation   |                |                |                |
| is temporary and |                |                |                |
| appropriate.     |                |                |                |
+------------------+----------------+----------------+----------------+
| \(b\) A system   |                | \(2\) Adequate |                |
| by which the     |                | distribution   |                |
| distribution of  |                | records shall  |                |
| each lot of drug |                | be maintained  |                |
| product can be   |                | and retained   |                |
| readily          |                | by the         |                |
| determined to    |                | manufacturer   |                |
| facilitate its   |                | at least one   |                |
| recall if        |                | year beyond    |                |
| necessary.       |                | expected       |                |
|                  |                | product shelf  |                |
| **§ 211.196      |                | life, whereby  |                |
| Distribution     |                | an effective   |                |
| records.**       |                | product recall |                |
|                  |                | can be         |                |
| Distribution     |                | achieved       |                |
| records shall    |                | should one     |                |
| contain the name |                | become         |                |
| and strength of  |                | necessary.     |                |
| the product and  |                |                |                |
| description of   |                |                |                |
| the dosage form, |                |                |                |
| name and address |                |                |                |
| of the           |                |                |                |
| consignee, date  |                |                |                |
| and quantity     |                |                |                |
| shipped, and lot |                |                |                |
| or control       |                |                |                |
| number of the    |                |                |                |
| drug product.    |                |                |                |
| For compressed   |                |                |                |
| medical gas      |                |                |                |
| products,        |                |                |                |
| distribution     |                |                |                |
| records are not  |                |                |                |
| required to      |                |                |                |
| contain lot or   |                |                |                |
| control numbers. |                |                |                |
+------------------+----------------+----------------+----------------+
| ## § 211.198     |                | \(d\)          | **Subpart      |
| Complaint files. |                | Complaint      | G\--Consumer   |
|                  |                | files.         | Complaints**   |
| \(a\) Written    |                |                |                |
| procedures       |                | \(1\) Written  | **§ 111.95     |
| describing the   |                | procedures     | [What          |
| handling of all  |                | describing the | requirements   |
| written and oral |                | handling of    | apply to       |
| complaints       |                | all written    | consumer       |
| regarding a drug |                | and oral       | complaints?]   |
| product shall be |                | complaints     | {.underline}** |
| established and  |                | regarding a    |                |
| followed. Such   |                | dietary        | \(a\) A        |
| procedures shall |                | product shall  | qualified      |
| include          |                | be established | person must    |
| provisions for   |                | and followed.  | review all     |
| review by the    |                | Such           | consumer       |
| quality control  |                | procedures     | complaints to  |
| unit, of any     |                | shall include  | determine      |
| complaint        |                | provisions for | whether the    |
| involving the    |                | review by the  | consumer       |
| possible failure |                | quality        | complaint      |
| of a drug        |                | control unit   | involves a     |
| product to meet  |                | of any         | possible       |
| any of its       |                | complaint      | failure of a   |
| specifications   |                | involving the  | dietary        |
| and, for such    |                | possible       | ingredient or  |
| drug products, a |                | failure of a   | dietary        |
| determination as |                | product to     | supplement to  |
| to the need for  |                | meet any of    | meet any of    |
| an investigation |                | its            | its            |
| in accordance    |                | specifications | s              |
| with §211.192.   |                | and, for such  | pecifications, |
| Such procedures  |                | products, a    | or any other   |
| shall include    |                | determination  | requirements   |
| provisions for   |                | as to the need | of this part,  |
| review to        |                | for an         | including      |
| determine        |                | investigation. | those          |
| whether the      |                |                | specifications |
| complaint        |                |                | and other      |
| represents a     |                |                | requirements   |
| serious and      |                |                | that, if not   |
| unexpected       |                |                | met, may       |
| adverse drug     |                |                | result in a    |
| experience which |                |                | possible risk  |
| is required to   |                |                | of illness or  |
| be reported to   |                |                | injury.        |
| the Food and     |                |                |                |
| Drug             |                |                | \(b\) Your     |
| Administration   |                |                | quality        |
| in accordance    |                |                | control unit   |
| with §310.305 of |                |                | must review    |
| this chapter.    |                |                | all consumer   |
|                  |                |                | complaints     |
|                  |                |                | involving the  |
|                  |                |                | possible       |
|                  |                |                | failure of a   |
|                  |                |                | dietary        |
|                  |                |                | ingredient or  |
|                  |                |                | dietary        |
|                  |                |                | supplement to  |
|                  |                |                | meet any of    |
|                  |                |                | its            |
|                  |                |                | s              |
|                  |                |                | pecifications, |
|                  |                |                | or any other   |
|                  |                |                | requirements   |
|                  |                |                | of this part,  |
|                  |                |                | including      |
|                  |                |                | those-         |
|                  |                |                | specifications |
|                  |                |                | and other      |
|                  |                |                | requirements   |
|                  |                |                | that, if not   |
|                  |                |                | met, may       |
|                  |                |                | result in a    |
|                  |                |                | possible risk  |
|                  |                |                | of illness or  |
|                  |                |                | injury, to     |
|                  |                |                | determine      |
|                  |                |                | whether there  |
|                  |                |                | is a need to   |
|                  |                |                | investigate    |
|                  |                |                | the consumer   |
|                  |                |                | complaint.     |
|                  |                |                |                |
|                  |                |                | \(c\) Your     |
|                  |                |                | quality        |
|                  |                |                | control unit   |
|                  |                |                | must           |
|                  |                |                | investigate a  |
|                  |                |                | consumer       |
|                  |                |                | complaint when |
|                  |                |                | there is a     |
|                  |                |                | reasonable     |
|                  |                |                | possibility of |
|                  |                |                | a relationship |
|                  |                |                | between the    |
|                  |                |                | quality of a   |
|                  |                |                | dietary        |
|                  |                |                | supplement and |
|                  |                |                | an adverse     |
|                  |                |                | event.         |
|                  |                |                |                |
|                  |                |                | \(d\) Your     |
|                  |                |                | quality        |
|                  |                |                | control        |
|                  |                |                | unit\'s        |
|                  |                |                | investigation  |
|                  |                |                | of a consumer  |
|                  |                |                | complaint must |
|                  |                |                | include the    |
|                  |                |                | batch records  |
|                  |                |                | associated     |
|                  |                |                | with the       |
|                  |                |                | dietary        |
|                  |                |                | ingredient or  |
|                  |                |                | dietary        |
|                  |                |                | supplement     |
|                  |                |                | involved in    |
|                  |                |                | the consumer   |
|                  |                |                | complaint.     |
|                  |                |                | Your quality   |
|                  |                |                | control unit   |
|                  |                |                | must extend    |
|                  |                |                | the            |
|                  |                |                | investigation  |
|                  |                |                | to other       |
|                  |                |                | batches of     |
|                  |                |                | dietary        |
|                  |                |                | ingredients or |
|                  |                |                | dietary        |
|                  |                |                | supplements    |
|                  |                |                | that may have  |
|                  |                |                | been           |
|                  |                |                | associated     |
|                  |                |                | with an        |
|                  |                |                | adverse event. |
+------------------+----------------+----------------+----------------+
| \(b\) A written  |                | \(2\) A        | \(e\) You must |
| record of each   |                | written record | make and keep  |
| complaint shall  |                | of each        | a written      |
| be maintained in |                | complaint      | record of      |
| a file           |                | shall be       | every consumer |
| designated for   |                | maintained,    | complaint that |
| drug product     |                | until at least | is related to  |
| complaints. The  |                | 1 year after   | good           |
| file regarding   |                | the expiration | manufacturing  |
| such drug        |                | date of the    | practices. For |
| product          |                | product, or 1  | the purposes   |
| complaints shall |                | year after the | of the         |
| be maintained at |                | date that the  | regulations in |
| the              |                | complaint was  | this part, a   |
| establishment    |                | received,      | consumer       |
| where the drug   |                | whichever is   | complaint      |
| product involved |                | longer.        | about product  |
| was              |                |                | quality may or |
| manufactured,    |                | \(4\) Where an | may not        |
| processed, or    |                | investigation  | include        |
| packed, or such  |                | is conducted,  | concerns about |
| file may be      |                | the written    | a possible     |
| maintained at    |                | record shall   | hazard, to     |
| another facility |                | include the    | health.        |
| if the written   |                | findings of    | However, a     |
| records in such  |                | the            | consumer       |
| files are        |                | investigation  | complaint does |
| readily          |                | and follow-up  | not include an |
| available for    |                | action taken.  | adverse event, |
| inspection at    |                |                | illness, or    |
| that other       |                |                | injury related |
| facility.        |                |                | to the safety  |
| Written records  |                |                | of a           |
| involving a drug |                |                | particular     |
| product shall be |                |                | dietary        |
| maintained until |                |                | ingredient     |
| at least 1 year  |                |                | independent of |
| after the        |                |                | whether the    |
| expiration date  |                |                | product is     |
| of the drug      |                |                | produced under |
| product, or 1    |                |                | good           |
| year after the   |                |                | manufacturing  |
| date that the    |                |                | practices.     |
| complaint was    |                |                |                |
| received,        |                |                |                |
| whichever is     |                |                |                |
| longer. In the   |                |                |                |
| case of certain  |                |                |                |
| OTC drug         |                |                |                |
| products lacking |                |                |                |
| expiration       |                |                |                |
| dating because   |                |                |                |
| they meet the    |                |                |                |
| criteria for     |                |                |                |
| exemption under  |                |                |                |
| §211.137, such   |                |                |                |
| written records  |                |                |                |
| shall be         |                |                |                |
| maintained for 3 |                |                |                |
| years after      |                |                |                |
| distribution of  |                |                |                |
| the drug         |                |                |                |
| product.         |                |                |                |
+------------------+----------------+----------------+----------------+
| \(1\) The        |                | \(3\) The      | The consumer   |
| written record   |                | written record | complaint      |
| shall include    |                | shall include, | written record |
| the following    |                | where known:   | must include,  |
| information,     |                | the name and   | but is not     |
| where known: the |                | description of | limited to,    |
| name and         |                | the product,   | the following: |
| strength of the  |                | lot number,    |                |
| drug product,    |                | name of        | \(1\) The name |
| lot number, name |                | complainant,   | and            |
| of complainant,  |                | nature of      | description of |
| nature of        |                | complaint, and | the dietary    |
| complaint, and   |                | reply to       | ingredient or  |
| reply to         |                | complainant,   | dietary        |
| complainant.     |                | if any.        | supplement;    |
|                  |                |                |                |
|                  |                |                | \(2\) The      |
|                  |                |                | batch or lot   |
|                  |                |                | number of the  |
|                  |                |                | dietary        |
|                  |                |                | supplement, if |
|                  |                |                | available;     |
|                  |                |                |                |
|                  |                |                | \(3\) The name |
|                  |                |                | of the         |
|                  |                |                | complainant,   |
|                  |                |                | if available;  |
|                  |                |                |                |
|                  |                |                | \(4\) The      |
|                  |                |                | nature of the  |
|                  |                |                | complaint      |
|                  |                |                | including how  |
|                  |                |                | the consumer   |
|                  |                |                | used the       |
|                  |                |                | product;       |
|                  |                |                |                |
|                  |                |                | \(5\) The      |
|                  |                |                | reply to the   |
|                  |                |                | complainant if |
|                  |                |                | any; and       |
|                  |                |                |                |
|                  |                |                | \(6\) Findings |
|                  |                |                | of the         |
|                  |                |                | investigation  |
|                  |                |                | and follow-up  |
|                  |                |                | action taken   |
|                  |                |                | when an        |
|                  |                |                | investigation  |
|                  |                |                | is performed.  |
+------------------+----------------+----------------+----------------+
| \(2\) Where an   |                |                | (f)(1) The     |
| investigation    |                |                | person who     |
| under §211.192   |                |                | performs the   |
| is conducted,    |                |                | requirements   |
| the written      |                |                | in accordance  |
| record shall     |                |                | with this      |
| include the      |                |                | section must   |
| findings of the  |                |                | document at    |
| investigation    |                |                | the time of    |
| and followup.    |                |                | performance    |
| The record or    |                |                | that the       |
| copy of the      |                |                | requirement    |
| record of the    |                |                | was performed. |
| investigation    |                |                |                |
| shall be         |                |                | \(2\) You must |
| maintained at    |                |                | keep consumer  |
| the              |                |                | complaint      |
| establishment    |                |                | records in     |
| where the        |                |                | accordance     |
| investigation    |                |                | with §         |
| occurred in      |                |                | 111.125.       |
| accordance with  |                |                |                |
| §211.180(c).     |                |                |                |
|                  |                |                |                |
| \(3\) Where an   |                |                |                |
| investigation    |                |                |                |
| under §211.192   |                |                |                |
| is not           |                |                |                |
| conducted, the   |                |                |                |
| written record   |                |                |                |
| shall include    |                |                |                |
| the reason that  |                |                |                |
| an investigation |                |                |                |
| was found not to |                |                |                |
| be necessary and |                |                |                |
| the name of the  |                |                |                |
| responsible      |                |                |                |
| person making    |                |                |                |
| such a           |                |                |                |
| determination.   |                |                |                |
+------------------+----------------+----------------+----------------+
| ##               |                | \(c\) Records  | **Subpart      |
|  § 211.180 Gener |                | retention.     | H\--Records    |
| al requirements. |                |                | and            |
|                  |                | \(1\) Any      | R              |
| \(a\) Any        |                | laboratory,    | ecordkeeping** |
| production,      |                | production,    |                |
| control, or      |                | control or     | **§ 111.125    |
| distribution     |                | distribution   | [What          |
| record that is   |                | record         | requirements   |
| required to be   |                | specifically   | apply to       |
| maintained in    |                | associated     | r              |
| compliance with  |                | with a batch   | ecordkeeping?] |
| this part and is |                | of product     | {.underline}** |
| specifically     |                | shall be       |                |
| associated with  |                | retained for   | \(a\) You must |
| a batch of a     |                | at least one   | keep written   |
| drug product     |                | year after the | records        |
| shall be         |                | expiration     | required by    |
| retained for at  |                | date of the    | this part for  |
| least 1 year     |                | batch, or if   | 3 years beyond |
| after the        |                | no expiration  | the date of    |
| expiration date  |                | date is        | manufacture of |
| of the batch or, |                | identified on  | the last batch |
| in the case of   |                | the product,   | of dietary     |
| certain OTC drug |                | for at least   | ingredients or |
| products lacking |                | three years    | dietary        |
| expiration       |                | after the date | supplements    |
| dating because   |                | of             | associated     |
| they meet the    |                | manufacture.   | with those     |
| criteria for     |                |                | records.       |
| exemption under  |                | \(2\) Raw      |                |
| §211.137, 3      |                | material       |                |
| years after      |                | records shall  |                |
| distribution of  |                | be maintained  |                |
| the batch.       |                | for at least   |                |
|                  |                | one year after |                |
| \(b\) Records    |                | the expiration |                |
| shall be         |                | date of the    |                |
| maintained for   |                | last batch of  |                |
| all components,  |                | product        |                |
| drug product     |                | incorporating  |                |
| containers,      |                | the raw        |                |
| closures, and    |                | material, or   |                |
| labeling for at  |                | if no          |                |
| least 1 year     |                | expiration     |                |
| after the        |                | date is        |                |
| expiration date  |                | identified on  |                |
| or, in the case  |                | the product,   |                |
| of certain OTC   |                | for at least   |                |
| drug products    |                | three years    |                |
| lacking          |                | after the date |                |
| expiration       |                | of manufacture |                |
| dating because   |                | of the         |                |
| they meet the    |                | finished       |                |
| criteria for     |                | product.       |                |
| exemption under  |                |                |                |
| §211.137, 3      |                |                |                |
| years after      |                |                |                |
| distribution of  |                |                |                |
| the last lot of  |                |                |                |
| drug product     |                |                |                |
| incorporating    |                |                |                |
| the component or |                |                |                |
| using the        |                |                |                |
| container,       |                |                |                |
| closure, or      |                |                |                |
| labeling.        |                |                |                |
+------------------+----------------+----------------+----------------+
| \(c\) All        |                |                | \(b\) Records  |
| records required |                |                | required under |
| under this part, |                |                | this part must |
| or copies of     |                |                | be kept as     |
| such records,    |                |                | original       |
| shall be readily |                |                | records, as    |
| available for    |                |                | true copies    |
| authorized       |                |                | (such as       |
| inspection       |                |                | photocopies,   |
| during the       |                |                | microfilm,     |
| retention period |                |                | microfiche, or |
| at the           |                |                | other accurate |
| establishment    |                |                | reproductions  |
| where the        |                |                | of the         |
| activities       |                |                | original       |
| described in     |                |                | records), or   |
| such records     |                |                | as electronic  |
| occurred. These  |                |                | records. If    |
| records or       |                |                | you use        |
| copies thereof   |                |                | reduction      |
| shall be subject |                |                | techniques,    |
| to photocopying  |                |                | such as        |
| or other means   |                |                | microfilming,  |
| of reproduction  |                |                | you must make  |
| as part of such  |                |                | suitable       |
| inspection.      |                |                | reader and     |
| Records that can |                |                | photocopying   |
| be immediately   |                |                | equipment      |
| retrieved from   |                |                | readily        |
| another location |                |                | available to   |
| by computer or   |                |                | FDA. All       |
| other electronic |                |                | electronic     |
| means shall be   |                |                | records must   |
| considered as    |                |                | comply with    |
| meeting the      |                |                | part 11 of     |
| requirements of  |                |                | this chapter.  |
| this paragraph.  |                |                |                |
|                  |                |                | \(c\) You must |
| d\) Records      |                |                | have all       |
| required under   |                |                | records        |
| this part may be |                |                | required under |
| retained either  |                |                | this part, or  |
| as original      |                |                | copies of such |
| records or as    |                |                | records,       |
| true copies such |                |                | readily        |
| as photocopies,  |                |                | available      |
| microfilm,       |                |                | during the     |
| microfiche, or   |                |                | retention      |
| other accurate   |                |                | period for     |
| reproductions of |                |                | authorized     |
| the original     |                |                | inspection and |
| records. Where   |                |                | copying by FDA |
| reduction        |                |                | when           |
| techniques, such |                |                | requested.     |
| as microfilming, |                |                |                |
| are used,        |                |                |                |
| suitable reader  |                |                |                |
| and photocopying |                |                |                |
| equipment shall  |                |                |                |
| be readily       |                |                |                |
| available.       |                |                |                |
+------------------+----------------+----------------+----------------+
| \(e\) Written    |                |                |                |
| records required |                |                |                |
| by this part     |                |                |                |
| shall be         |                |                |                |
| maintained so    |                |                |                |
| that data        |                |                |                |
| therein can be   |                |                |                |
| used for         |                |                |                |
| evaluating, at   |                |                |                |
| least annually,  |                |                |                |
| the quality      |                |                |                |
| standards of     |                |                |                |
| each drug        |                |                |                |
| product to       |                |                |                |
| determine the    |                |                |                |
| need for changes |                |                |                |
| in drug product  |                |                |                |
| specifications   |                |                |                |
| or manufacturing |                |                |                |
| or control       |                |                |                |
| procedures.      |                |                |                |
| Written          |                |                |                |
| procedures shall |                |                |                |
| be established   |                |                |                |
| and followed for |                |                |                |
| such evaluations |                |                |                |
| and shall        |                |                |                |
| include          |                |                |                |
| provisions for:  |                |                |                |
|                  |                |                |                |
| \(1\) A review   |                |                |                |
| of a             |                |                |                |
| representative   |                |                |                |
| number of        |                |                |                |
| batches, whether |                |                |                |
| approved or      |                |                |                |
| rejected, and,   |                |                |                |
| where            |                |                |                |
| applicable,      |                |                |                |
| records          |                |                |                |
| associated with  |                |                |                |
| the batch.       |                |                |                |
|                  |                |                |                |
| \(2\) A review   |                |                |                |
| of complaints,   |                |                |                |
| recalls,         |                |                |                |
| returned or      |                |                |                |
| salvaged drug    |                |                |                |
| products, and    |                |                |                |
| investigations   |                |                |                |
| conducted under  |                |                |                |
| §211.192 for     |                |                |                |
| each drug        |                |                |                |
| product.         |                |                |                |
+------------------+----------------+----------------+----------------+
| \(f\) Procedures |                |                |                |
| shall be         |                |                |                |
| established to   |                |                |                |
| assure that the  |                |                |                |
| responsible      |                |                |                |
| officials of the |                |                |                |
| firm, if they    |                |                |                |
| are not          |                |                |                |
| personally       |                |                |                |
| involved in or   |                |                |                |
| immediately      |                |                |                |
| aware of such    |                |                |                |
| actions, are     |                |                |                |
| notified in      |                |                |                |
| writing of any   |                |                |                |
| investigations   |                |                |                |
| conducted under  |                |                |                |
| §§211.198,       |                |                |                |
| 211.204, or      |                |                |                |
| 211.208 of these |                |                |                |
| regulations, any |                |                |                |
| recalls, reports |                |                |                |
| of inspectional  |                |                |                |
| observations     |                |                |                |
| issued by the    |                |                |                |
| Food and Drug    |                |                |                |
| Administration,  |                |                |                |
| or any           |                |                |                |
| regulatory       |                |                |                |
| actions relating |                |                |                |
| to good          |                |                |                |
| manufacturing    |                |                |                |
| practices        |                |                |                |
| brought by the   |                |                |                |
| Food and Drug    |                |                |                |
| Administration   |                |                |                |
+------------------+----------------+----------------+----------------+
|                  | #####  Subp    | \(g\) Defect   |                |
|                  | art G\--Defect | Action Levels. |                |
|                  |  Action Levels |                |                |
|                  |                | \(1\) Some     |                |
|                  | **¶110.110**   | dietary        |                |
|                  | Natural or     | ingredients    |                |
|                  | unavoidable    | and dietary    |                |
|                  | defects in     | supplements,   |                |
|                  | food for human | even when      |                |
|                  | use that       | produced under |                |
|                  | present no     | current good   |                |
|                  | health hazard. | manufacturing  |                |
|                  |                | practice,      |                |
|                  | \(a\) Some     | contain        |                |
|                  | foods, even    | natural or     |                |
|                  | when produced  | unavoidable    |                |
|                  | under current  | defects that   |                |
|                  | good           | at low levels  |                |
|                  | manufacturing  | are not        |                |
|                  | practice,      | hazardous to   |                |
|                  | contain        | health. The    |                |
|                  | natural or     | Food and Drug  |                |
|                  | unavoidable    | Administration |                |
|                  | defects that   | establishes    |                |
|                  | at low levels  | maximum levels |                |
|                  | are not        | for these      |                |
|                  | hazardous to   | defects in     |                |
|                  | health. The    | dietary        |                |
|                  | Food and Drug  | products       |                |
|                  | Administration | produced under |                |
|                  | establishes    | current good   |                |
|                  | maximum levels | manufacturing  |                |
|                  | for these      | practice and   |                |
|                  | defects in     | uses these     |                |
|                  | foods produced | levels in      |                |
|                  | under current  | deciding       |                |
|                  | good           | whether to     |                |
|                  | manufacturing  | recommend      |                |
|                  | practice and   | regulatory     |                |
|                  | uses these     | action.        |                |
|                  | levels in      |                |                |
|                  | deciding       |                |                |
|                  | whether to     |                |                |
|                  | recommend      |                |                |
|                  | regulatory     |                |                |
|                  | action.        |                |                |
+------------------+----------------+----------------+----------------+
|                  | \(b\) Defect   | \(2\) Defect   |                |
|                  | action levels  | action levels  |                |
|                  | are            | are            |                |
|                  | established    | established    |                |
|                  | for foods      | for dietary    |                |
|                  | whenever it is | products       |                |
|                  | necessary and  | whenever it is |                |
|                  | feasible to do | necessary and  |                |
|                  | so. These      | feasible to do |                |
|                  | levels are     | so. These      |                |
|                  | subject to     | levels are     |                |
|                  | change upon    | subject to     |                |
|                  | the            | change upon    |                |
|                  | development of | the            |                |
|                  | new technology | development of |                |
|                  | or the         | new technology |                |
|                  | availability   | or the         |                |
|                  | of new         | availability   |                |
|                  | information.   | of new         |                |
|                  |                | information.   |                |
+------------------+----------------+----------------+----------------+
|                  |                |                | *PART          |
|                  |                |                | 112\--         |
|                  |                |                | RESTRICTIONS,. |
|                  |                |                | FQR SUBSTANCES |
|                  |                |                | USED IN        |
|                  |                |                | DIETARY        |
|                  |                |                | SUPPLEMENTS*   |
|                  |                |                |                |
|                  |                |                | **Subpart      |
|                  |                |                | A\--General    |
|                  |                |                | Provisions**   |
|                  |                |                | \[Reserved\]   |
|                  |                |                |                |
|                  |                |                | **Subpart      |
|                  |                |                | B\--New        |
|                  |                |                | Dietary**      |
|                  |                |                | *              |
|                  |                |                | *Ingredients** |
|                  |                |                | \[Reserved\]   |
|                  |                |                |                |
|                  |                |                | **Subpart      |
|                  |                |                | C\--Restricted |
|                  |                |                | Dietary**      |
|                  |                |                | *              |
|                  |                |                | *Ingredients** |
|                  |                |                | \[Reserved\]   |
+------------------+----------------+----------------+----------------+
|                  | \(c\)          | \(3\)          |                |
|                  | Compliance     | Compliance     |                |
|                  | with defect    | with defect    |                |
|                  | action levels  | action levels  |                |
|                  | does not       | does not       |                |
|                  | excuse         | excuse         |                |
|                  | violation of   | violation of   |                |
|                  | the            | the            |                |
|                  | requirement in | requirement in |                |
|                  | section        | section        |                |
|                  | 402(a)(4) of   | 402(a)(4) of   |                |
|                  | the act that   | the act that   |                |
|                  | food not be    | dietary        |                |
|                  | prepared,      | products not   |                |
|                  | packed, or     | be prepared,   |                |
|                  | held under     | packed, or     |                |
|                  | unsanitary     | held under     |                |
|                  | conditions or  | unsanitary     |                |
|                  | the            | conditions or  |                |
|                  | requirements   | the            |                |
|                  | in this part   | requirements   |                |
|                  | that food      | in this part   |                |
|                  | manufacturers, | that dietary   |                |
|                  | distributors,  | product        |                |
|                  | and holders    | manufacturers, |                |
|                  | shall observe  | distributors,  |                |
|                  | current good   | and holders    |                |
|                  | manufacturing  | shall observe  |                |
|                  | practice.      | current good   |                |
|                  | Evidence       | manufacturing  |                |
|                  | indicating     | practice.      |                |
|                  | that such a    | Evidence       |                |
|                  | violation      | indicating     |                |
|                  | exists causes  | that such a    |                |
|                  | the food to be | violation      |                |
|                  | adulterated    | exists causes  |                |
|                  | within the     | a dietary      |                |
|                  | meaning of the | product to be  |                |
|                  | act, even      | adulterated    |                |
|                  | though the     | within the     |                |
|                  | amounts of     | meaning of the |                |
|                  | natural or     | act, even      |                |
|                  | unavoidable    | though the     |                |
|                  | defects are    | amounts of     |                |
|                  | lower than the | natural or     |                |
|                  | currently      | unavoidable    |                |
|                  | established    | defects are    |                |
|                  | defect action  | lower than the |                |
|                  | levels. The    | currently      |                |
|                  | manufacturer,  | established    |                |
|                  | distributor,   | defect action  |                |
|                  | and holder of  | levels. The    |                |
|                  | food shall at  | manufacturer,  |                |
|                  | all times      | distributor,   |                |
|                  | utilize        | and holder of  |                |
|                  | quality        | a dietary      |                |
|                  | control        | product shall  |                |
|                  | operations     | at all times   |                |
|                  | that reduce    | utilize        |                |
|                  | natural or     | quality        |                |
|                  | unavoidable    | control        |                |
|                  | defects to the | operations     |                |
|                  | lowest level   | that reduce    |                |
|                  | currently      | natural or     |                |
|                  | feasible.      | unavoidable    |                |
|                  |                | defects to the |                |
|                  |                | lowest level   |                |
|                  |                | currently      |                |
|                  |                | feasible.      |                |
+------------------+----------------+----------------+----------------+
|                  | \(d\) The      | \(4\) The      |                |
|                  | mixing of a    | mixing of a    |                |
|                  | food           | dietary        |                |
|                  | containing     | ingredient or  |                |
|                  | defects above  | dietary        |                |
|                  | the current    | supplement     |                |
|                  | defect action  | containing     |                |
|                  | level with     | defects above  |                |
|                  | another lot of | the current    |                |
|                  | food is not    | defect action  |                |
|                  | permitted and  | level with     |                |
|                  | renders the    | another lot of |                |
|                  | final food     | dietary        |                |
|                  | adulterated    | ingredient or  |                |
|                  | within the     | dietary        |                |
|                  | meaning of the | supplement is  |                |
|                  | act,           | not permitted  |                |
|                  | regardless of  | and renders    |                |
|                  | the defect     | the final      |                |
|                  | level of the   | product        |                |
|                  | final food.    | adulterated    |                |
|                  |                | within the     |                |
|                  |                | meaning of the |                |
|                  |                | act,           |                |
|                  |                | regardless of  |                |
|                  |                | the defect     |                |
|                  |                | level of the   |                |
|                  |                | final product. |                |
+------------------+----------------+----------------+----------------+
|                  | \(e\) A        | \(5\) A        |                |
|                  | compilation of | compilation of |                |
|                  | the current    | the current    |                |
|                  | defect action  | defect action  |                |
|                  | levels for     | levels for     |                |
|                  | natural or     | natural or     |                |
|                  | unavoidable    | unavoidable    |                |
|                  | defects in     | defects in     |                |
|                  | food for human | dietary        |                |
|                  | use that       | products that  |                |
|                  | present no     | present no     |                |
|                  | health hazard  | health hazard  |                |
|                  | may be         | may be         |                |
|                  | obtained upon  | obtained upon  |                |
|                  | request from   | request from   |                |
|                  | the Industry   | the Industry   |                |
|                  | Programs       | Programs       |                |
|                  | Branch         | Branch         |                |
|                  | (HFF-326),     | (HFF-326),     |                |
|                  | Center for     | Center for     |                |
|                  | Food Safety    | Food Safety    |                |
|                  | and Applied    | and Applied    |                |
|                  | Nutrition,     | Nutrition,     |                |
|                  | Food and Drug  | Food and Drug  |                |
|                  | A              | A              |                |
|                  | dministration, | dministration, |                |
|                  | 200 C St. SW., | 200 C St. SW., |                |
|                  | Washington, DC | Washington, DC |                |
|                  | 20204.         | 20204.         |                |
+------------------+----------------+----------------+----------------+