List of Subjects

21 CFR Part 111

Dietary foods, Drugs, Foods, Packaging and containers.

Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, FDA is
amending 21 CFR chapter I part 111 as set forth below:

PART 111‑‑CURRENT GOOD MANUFACTURING PRACTICE IN MANUFACTURING,
PACKAGING, LABELING, OR HOLDING OPERATIONS FOR DIETARY SUPPLEMENTS

1\. The authority citation for part 111 is revised to read as follows:

Authority: 21 U.S.C. 321, 342, 343, 371, 374, 381, 393; 42 U.S.C. 264.

2\. The part heading for part 111 is revised as set forth above.

3\. Add new subpart A to part 111 to read as follows:

Subpart A‑‑General Provisions

§ 111.1 Who Is Subject to These Regulations?

§ 111.3 What Definitions Apply to This Part?

§ 111.5 Do Other Statutory Provisions and Regulations Apply?

[§ 111.1 Who Is Subject to These Regulations?]{.underline}

\(a\) Except as provided by paragraph (b) of this section, you are
subject to these regulations if you manufacture, package, label, or hold
a dietary supplement, including:

\(1\) A dietary supplement you manufacture but that is packaged or
labeled by another person; and

\(2\) A dietary supplement imported or offered for import in any State
or Territory of the United States, the District of Columbia, or the
Commonwealth of Puerto Rico.

\(b\) The requirements pertaining to holding dietary supplements do not
apply to you if you are holding those dietary supplements at a retail
establishment for the sole purpose of direct retail sale to individual
consumers. A retail establishment does not include a warehouse or other
storage facility for a retailer or a warehouse or other storage facility
that sells directly to individual consumers.

[§ 111.3 What Definitions Apply to This Part?]{.underline}

The definitions and interpretations of terms in section 201 of the
Federal Food, Drug, and Cosmetic Act (the act) apply to such terms when
used in these regulations. For the purpose of these regulations, the
following definitions also apply:

**Actual yield** means the quantity that is actually produced at any
appropriate step of manufacture or packaging of a particular dietary
supplement.

**Batch** means a specific quantity of a dietary supplement that is
uniform, that is intended to meet specifications for identity, purity,
strength, and composition, and that is produced during a specified time
period according to a single manufacturing record during the same cycle
of manufacture.

**Batch number, lot number, or control number** means any distinctive
group of letters, numbers, or symbols, or any combination of them, from
which the complete history of the manufacturing, packaging, labeling,
and/or holding of a batch or lot of dietary supplements can be
determined.

**Component** means any substance intended for use in the manufacture of
a dietary supplement, including those that may not appear in the
finished batch of the dietary supplement. Component includes dietary
ingredients (as described in section 201(ff) of the act) and other
ingredients.

**Contact surface** means any surface that contacts a component or
dietary supplement, and those surfaces from which drainage onto the
component or dietary supplement, or onto surfaces that contact the
component or dietary supplement, occurs during the normal course of
operations. Examples of contact surfaces include containers, utensils,
tables, contact surfaces of equipment, and packaging.

**Ingredient** means any substance that is used in the manufacture of a
dietary supplement and that is intended to be present in the finished
batch of the dietary supplement. An ingredient includes, but is not
necessarily limited to, a dietary ingredient as defined in section
201(ff) of the act.

**In-process material** means any material that is fabricated,
compounded, blended, ground, extracted, sifted, sterilized, derived by
chemical reaction, or processed in any other way for use in the
manufacture of a dietary supplement.

**Lot** means a batch, or a specific identified portion of a batch, that
is uniform and that is intended to meet specifications for identity,
purity, strength, and composition; or, in the case of a dietary
supplement produced by continuous process, a specific identified amount
produced in a specified unit of time or quantity in a manner that is
uniform and that is intended to meet specifications for identity,
purity, strength, and composition.

**Microorganisms** means yeasts, molds, bacteria, viruses, and other
similar microscopic organisms having public health or sanitary concern.
This definition includes species that:

\(1\) May have public health significance;

\(2\) May cause a component or dietary supplement to decompose;

\(3\) Indicate that the component or dietary supplement is contaminated
with filth; or

\(4\) Otherwise may cause the component or dietary supplement to be
adulterated.

**Must** is used to state a requirement.

**Pest** means any objectionable insect or other animal including birds,
rodents, flies, mites, and larvae.

**Physical plant** means all or any part of a building or facility used
for or in connection with manufacturing, packaging, labeling, or holding
a dietary supplement.

**Product complaint** means any communication that contains any
allegation, written, electronic, or oral, expressing concern, for any
reason, with the quality of a dietary supplement, that could be related
to current good manufacturing practice. Examples of product complaints
are: foul odor, off taste, illness or injury, disintegration time, color
variation, tablet size or size variation, under-filled container,
foreign material in a dietary supplement container, improper packaging,
mislabeling, or dietary supplements that are superpotent, subpotent, or
contain the wrong ingredient, or contain a drug or other contaminant
(e.g., bacteria, pesticide, mycotoxin, glass, lead).

**Quality** means that the dietary supplement consistently meets the
established specifications for identity, purity, strength, and
composition, and limits on contaminants, and has been manufactured,
packaged, labeled, and held under conditions to prevent adulteration
under sections 402(a)(1), (a)(2), (a)(3), and (a)(4) of the act.

**Quality control** means a planned and systematic operation or
procedure for ensuring the quality of a dietary supplement. **Quality
control** **personnel** means any person, persons, or group, within or
outside of your organization, who you designate to be responsible for
your quality control operations.

**Representative sample** means a sample that consists of an adequate
number of units that are drawn based on rational criteria, such as
random sampling, and that are intended to ensure that the sample
accurately portrays the material being sampled.

**Reprocessing** means using, in the manufacture of a dietary
supplement, clean, uncontaminated components or dietary supplements that
have been previously removed from manufacturing and that have been made
suitable for use in the manufacture of a dietary supplement.

**Reserve sample** means a representative sample of product that is held
for a designated period of time.

**Sanitize** means to adequately treat cleaned equipment, containers,
utensils, or any other cleaned contact surface by a process that is
effective in destroying vegetative cells of microorganisms of public
health significance, and in substantially reducing numbers of other
microorganisms, but without adversely affecting the product or its
safety for the consumer.

**Theoretical yield** means the quantity that would be produced at any
appropriate step of manufacture or packaging of a particular dietary
supplement, based upon the quantity of components or packaging to be
used, in the absence of any loss or error in actual production.

**Water activity** (a~w~) is a measure of the free moisture in a
component or dietary supplement and is the quotient of the water vapor
pressure of the substance divided by the vapor pressure of pure water at
the same temperature.

**We** means the U.S. Food and Drug Administration (FDA).

**You** means a person who manufactures, packages, labels, or holds
dietary supplements.

[§ 111.5 Do Other Statutory Provisions and Regulations
Apply?]{.underline}

In addition to these regulations, you must comply with other applicable
statutory provisions and regulations under the act related to dietary
supplements.

4\. Add §§ 111.8 through 111.14 to newly added subpart B to read as
follows:

Subpart B\--Personnel

§ 111.8 What Are the Requirements Under This Subpart for Written
Procedures?

§ 111.10 What Requirements Apply for Preventing Microbial Contamination
From Sick or Infected Personnel and for Hygienic Practices?

§ 111.12 What Personnel Qualification Requirements Apply?

§ 111.13 What Supervisor Requirements Apply?

§ 111.14 Under This Subpart, What Records Must You Make and Keep?

Subpart B -- Personnel

[§ 111.8 What Are the Requirements Under This Subpart for Written
Procedures?]{.underline}

You must establish and follow written procedures for fulfilling the
requirements of this subpart.

[§ 111.10 What Requirements Apply for Preventing Microbial Contamination
From Sick or Infected Personnel and for Hygienic Practices?]{.underline}

\(a\) Preventing microbial contamination. You must take measures to
exclude from any operations any person who might be a source of
microbial contamination, due to a health condition, where such
contamination may occur, of any material, including components, dietary
supplements, and contact surfaces used in the manufacture, packaging,
labeling, or holding of a dietary supplement. Such measures include the
following:

\(1\) Excluding from working in any operations that may result in
contamination any person who, by medical examination, the person's
acknowledgement, or supervisory observation, is shown to have, or
appears to have, an illness, infection, open lesion, or any other
abnormal source of microbial contamination, that could result in
microbial contamination of components, dietary supplements, or contact
surfaces, until the health condition no longer exists; 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
result in microbial contamination of any components, dietary
supplements, or any contact surface.

\(b\) Hygienic practices. If you work in an operation during which
adulteration of the component, dietary supplement, or contact surface
could occur, you must use hygienic practices to the extent necessary to
protect against such contamination of components, dietary supplements,
or contact surfaces. These hygienic practices include:

\(1\) Wearing outer garments in a manner that protects against the
contamination of components, dietary supplements, or any contact
surface;

\(2\) Maintaining adequate personal cleanliness;

\(3\) Washing hands thoroughly (and sanitizing if necessary to protect
against contamination with microorganisms) in an adequate hand-washing
facility:

\(i\) Before starting work; and

\(ii\) At any time when the hands may have become soiled or
contaminated;

\(4\) Removing all unsecured jewelry and other objects that might fall
into components, dietary supplements, equipment, or packaging, and
removing hand jewelry that cannot be adequately sanitized during periods
in which components or dietary supplements are manipulated by hand. If
hand jewelry cannot be removed, it must be covered by material that is
maintained in an intact, clean, and sanitary condition and that
effectively protects against contamination of components, dietary
supplements, or contact surfaces;

\(5\) Maintaining gloves used in handling components or dietary
supplements in an intact, clean, and sanitary condition. The gloves must
be of an impermeable material;

\(6\) Wearing, where appropriate, in an effective manner, hair nets,
caps, beard covers, or other effective hair restraints;

\(7\) Not storing clothing or other personal belongings in areas where
components, dietary supplements, or any contact surfaces are exposed or
where contact surfaces are washed;

\(8\) Not eating food, chewing gum, drinking beverages, or using tobacco
products in areas where components, dietary supplements, or any contact
surfaces are exposed, or where contact surfaces are washed; and

\(9\) Taking any other precautions necessary to protect against the
contamination of components, dietary supplements, or contact surfaces
with microorganisms, filth, or any other extraneous materials, including
perspiration, hair, cosmetics, tobacco, chemicals, and medicines applied
to the skin.

[§ 111.12 What Personnel Qualification Requirements Apply?]{.underline}

\(a\) You must have qualified employees who manufacture, package, label,
or hold dietary supplements.

\(b\) You must identify who is responsible for your quality control
operations. Each person who is identified to perform quality control
operations must be qualified to do so and have distinct and separate
responsibilities related to performing such operations from those
responsibilities that the person otherwise has when not performing such
operations.

\(c\) Each person engaged in manufacturing, packaging, labeling, or
holding, or in performing any quality control operations, must have the
education, training, or experience to perform the person's assigned
functions.

[§ 111.13 What Supervisor Requirements Apply?]{.underline}

\(a\) You must assign qualified personnel to supervise the
manufacturing, packaging, labeling, or holding of dietary supplements.

\(b\) Each supervisor whom you use must be qualified by education,
training, or experience to supervise.

[§ 111.14 Under This Subpart, What Records Must You Make and
Keep?]{.underline}

\(a\) You must make and keep records required under this subpart in
accordance with Subpart P.

\(b\) You must make and keep the following records:

\(1\) Written procedures for fulfilling the requirements of this
subpart; and

\(2\) Documentation of training, including the date of the training, the
type of training, and the person(s) trained.

5\. Add §§ 111.15 through 111.23 to newly added subpart C to read as
follows:

Subpart C\--Physical Plant and Grounds

§ 111.15 What Sanitation Requirements Apply to Your physical Plant?

§ 111.16 What Are the Requirements Under This Subpart for Written
Procedures?

§ 111.20 What Design and Construction Requirements Apply to Your
Physical Plant?

§ 111.23 Under This Subpart, What Records Must You Make and Keep?

Subpart C\--Physical Plant and Grounds

[§ 111.15 What Sanitation Requirements Apply to Your Physical
Plant]{.underline} [and Grounds?]{.underline}

\(a\) [Grounds.]{.underline} You must keep the grounds of your physical
plant in a condition that protects against the contamination of
components, dietary supplements, or contact surfaces. The methods for
adequate ground maintenance include:

\(1\) Properly storing equipment, removing litter and waste, and cutting
weeds or grass within the immediate vicinity of the physical plant so
that it does not attract pests, harbor pests, or provide pests a place
for breeding;

\(2\) Maintaining roads, yards, and parking lots so that they do not
constitute a source of contamination in areas where components, dietary
supplements, or contact surfaces are exposed;

\(3\) Adequately draining areas that may contribute to the contamination
of components, dietary supplements, or contact surfaces by seepage,
filth or any other extraneous materials, or by providing a breeding
place for pests;

\(4\) Adequately operating systems for waste treatment and disposal so
that they do not constitute a source of contamination in areas where
components, dietary supplements, or contact surfaces are exposed; and

\(5\) If your plant grounds are bordered by grounds not under your
control, and if those other grounds are not maintained in the manner
described in this section, you must exercise care in the plant by
inspection, extermination, or other means to exclude pests, dirt, and
filth or any other extraneous materials that may be a source of
contamination.

\(b\) Physical plant facilities. (1) You must maintain your physical
plant in a clean and sanitary condition; and

\(2\) You must maintain your physical plant in repair sufficient to
prevent components, dietary supplements, or contact surfaces from
becoming contaminated.

\(c\) Cleaning compounds, sanitizing agents, pesticides, and other toxic
materials. (1) You must use cleaning compounds and sanitizing agents
that are free from microorganisms of public health significance and that
are safe and adequate under the conditions of use.

\(2\) You must not use or hold toxic materials in a physical plant in
which components, dietary supplements, or contact surfaces are
manufactured or exposed, unless those materials are necessary:

\(i\) To maintain clean and sanitary conditions;

\(ii\) For use in laboratory testing procedures;

\(iii\) For maintaining or operating the physical plant or equipment; or

\(iv\) For use in the plant's operations.

\(3\) You must identify and hold cleaning compounds, sanitizing agents,
pesticides, pesticide chemicals, and other toxic materials in a manner
that protects against contamination of components, dietary supplements,
or contact surfaces.

\(d\) [Pest control.]{.underline} (1) You must not allow animals or
pests in any area of your physical plant. Guard or guide dogs are
allowed in some areas of your physical plant if the presence of the dogs
will not result in contamination of components, dietary supplements, or
contact surfaces;

\(2\) You must take effective measures to exclude pests from the
physical plant and to protect against contamination of components,
dietary supplements, and contact surfaces on the premises by pests; and

\(3\) You must not use insecticides, fumigants, fungicides, or
rodenticides, unless you take precautions to protect against the
contamination of components, dietary supplements, or contact surfaces.

\(e\) [Water supply.]{.underline} (1) You must provide water that is
safe and sanitary, at suitable temperatures, and under pressure as
needed, for all uses where water does not become a component of the
dietary supplement.

\(2\) Water that is used in a manner such that the water may become a
component of the dietary supplement, e.g., when such water contacts
components, dietary supplements, or any contact surface, must, at a
minimum, comply with applicable Federal, State, and local requirements
and not contaminate the dietary supplement.

\(f\) Plumbing. The plumbing in your physical plant must be of an
adequate size and design and be adequately installed and maintained to:

\(1\) Carry sufficient amounts of water to required locations throughout
the physical plant;

\(2\) Properly convey sewage and liquid disposable waste from your
physical plant;

\(3\) Avoid being a source of contamination to components, dietary
supplements, water supplies, or any contact surface, or creating an
unsanitary condition;

\(4\) Provide adequate floor drainage in all areas where floors are
subject to flooding-type cleaning or where normal operations release or
discharge water or other liquid waste on the floor; and

\(5\) Not allow backflow from, or cross connection between, piping
systems that discharge waste water or sewage and piping systems that
carry water used for manufacturing dietary supplements, for cleaning
contact surfaces, or for use in bathrooms or hand-washing facilities.

\(g\) [Sewage disposal.]{.underline} You must dispose of sewage into an
adequate sewage system or through other adequate means.

\(h\) [Bathrooms.]{.underline} You must provide your employees with
adequate, readily accessible bathrooms. The bathrooms must be kept clean
and must not be a potential source of contamination to components,
dietary supplements, or contact surfaces.

\(i\) [Hand-washing facilities.]{.underline} You must provide
hand-washing facilities that are designed to ensure that an employee's
hands are not a source of contamination of components, dietary
supplements, or any contact surface, by providing facilities that are
adequate, convenient, and furnish running water at a suitable
temperature.

\(j\) [Trash disposal.]{.underline} You must convey, store, and dispose
of trash to:

\(1\) Minimize the development of odors;

\(2\) Minimize the potential for the trash to attract, harbor, or become
a breeding place for pests;

\(3\) Protect against contamination of components, dietary supplements,
any contact surface, water supplies, and grounds surrounding your
physical plant; and

\(4\) Control hazardous waste to prevent contamination of components,
dietary supplements, and contact surfaces.

\(k\) [Sanitation supervisors.]{.underline} You must assign one or more
employees to supervise overall sanitation. Each of these supervisors
must be qualified by education, training, or experience to develop and
supervise sanitation procedures.

[§ 111.16 What Are the Requirements Under This Subpart for Written
Procedures?]{.underline}

You must establish and follow written procedures for cleaning the
physical plant and for pest control.

[§ 111.20 What Design and Construction Requirements Apply to Your
Physical Plant?]{.underline}

Any physical plant you use in the manufacture, packaging, labeling, or
holding of dietary supplements must:

\(a\) Be suitable in size, construction, and design to facilitate
maintenance, cleaning, and sanitizing operations;

\(b\) Have adequate space for the orderly placement of equipment and
holding of materials as is necessary for maintenance, cleaning, and
sanitizing operations and to prevent contamination and mix-ups of
components and dietary supplements during manufacturing, packaging,
labeling, or holding;

\(c\) Permit the use of proper precautions to reduce the potential for
mix-ups or contamination of components, dietary supplements, or contact
surfaces, with microorganisms, chemicals, filth, or other extraneous
material. Your physical plant must have, and you must use, separate or
defined areas of adequate size or other control systems, such as
computerized inventory controls or automated systems of separation, to
prevent contamination and mix-ups of components and dietary supplements
during the following operations:

\(1\) Receiving, identifying, holding, and withholding from use,
components, dietary supplements, packaging, and labels that will be used
in or during the manufacturing, packaging, labeling, or holding of
dietary supplements;

\(2\) Separating, as necessary, components, dietary supplements,
packaging, and labels that are to be used in manufacturing from
components, dietary supplements, packaging, or labels that are awaiting
material review and disposition decision, reprocessing, or are awaiting
disposal after rejection;

\(3\) Separating the manufacturing, packaging, labeling, and holding of
different product types including different types of dietary supplements
and other foods, cosmetics, and pharmaceutical products;

\(4\) Performing laboratory analyses and holding laboratory supplies and
samples;

\(5\) Cleaning and sanitizing contact surfaces;

\(6\) Packaging and label operations; and

\(7\) Holding components or dietary supplements.

\(d\) Be designed and constructed in a manner that prevents
contamination of components, dietary supplements, or contact surfaces.

\(1\) The design and construction must include:

\(i\) Floors, walls, and ceilings that can be adequately cleaned and
kept clean and in good repair;

\(ii\) Fixtures, ducts, and pipes that do not contaminate components,
dietary supplements, or contact surfaces by dripping or other leakage,
or condensate;

\(iii\) Adequate ventilation or environmental control equipment such as
airflow systems, including filters, fans, and other air-blowing
equipment, that minimize odors and vapors (including steam and noxious
fumes) in areas where they may contaminate components, dietary
supplements, or contact surfaces;

\(iv\) Equipment that controls temperature and humidity, when such
equipment is necessary to ensure the quality of the dietary supplement;
and

\(v\) Aisles or working spaces between equipment and walls that are
adequately unobstructed and of adequate width to permit all persons to
perform their duties and to protect against contamination of components,
dietary supplements, or contact surfaces with clothing or personal
contact.

\(2\) When fans and other air-blowing equipment are used, such fans and
equipment must be located and operated in a manner that minimizes the
potential for microorganisms and particulate matter to contaminate
components, dietary supplements, or contact surfaces;

\(e\) Provide adequate light in:

\(1\) All areas where components or dietary supplements are examined,
processed, or held;

\(2\) All areas where contact surfaces are cleaned; and

\(3\) Hand-washing areas, dressing and locker rooms, and bathrooms.

\(f\) Use safety-type light bulbs, fixtures, skylights, or other glass
or glass-like materials when the light bulbs, fixtures, skylights or
other glass or glass-like materials are suspended over exposed
components or dietary supplements in any step of preparation, unless
your physical plant is otherwise constructed in a manner that will
protect against contamination of components or dietary supplements in
case of breakage of glass or glass-like materials.

\(g\) Provide effective protection against contamination of components
and dietary supplements in bulk fermentation vessels, by, for example:

\(1\) Use of protective coverings;

\(2\) Placement in areas where you can eliminate harborages for pests
over and around the vessels;

\(3\) Placement in areas where you can check regularly for pests, pest
infestation, filth or any other extraneous materials; and

\(4\) Use of skimming equipment.

\(h\) Use adequate screening or other protection against pests, where
necessary.

[§ 111.23 Under This Subpart, What Records Must You Make and
Keep?]{.underline}

\(a\) You must make and keep records required under this subpart in
accordance with subpart P.

\(b\) You must make and keep records of the written procedures for
cleaning the physical plant and for pest control.

\(c\) You must make and keep records that show that water, when used in
a manner such that the water may become a component of the dietary
supplement, meets the requirements of § 111.15(e)(2).

6\. Add §§ 111.25 through 111.35 to newly added subpart D to read as
follows:

Subpart D\--Equipment and Utensils

§ 111.25 What Are the Requirements Under This Subpart for Written
Procedures?

§ 111.27 What Requirements Apply to the Equipment and Utensils That You
Use?

§ 111.30 What Requirements Apply to Automated, Mechanical, or Electronic
Equipment?

§ 111.35 Under This Subpart, What Records Must You Make and Keep?

Subpart D\--Equipment and Utensils

[§ 111.25 What Are the Requirements Under This Subpart for Written
Procedures?]{.underline}

You must establish and follow written procedures for fulfilling the
requirements of this subpart, including written procedures for:

\(a\) Calibrating instruments and controls that you use in manufacturing
or testing a component or dietary supplement;

\(b\) Calibrating, inspecting, and checking automated, mechanical, and
electronic equipment; and

\(c\) Maintaining, cleaning, and sanitizing, as necessary, all
equipment, utensils, and any other contact surfaces that are used to
manufacture, package, label, or hold components or dietary supplements.

[§ 111.27 What Requirements Apply to the Equipment and
Utensils]{.underline} [That You Use?]{.underline}

\(a\) You must use equipment and utensils that are of appropriate
design, construction, and workmanship to enable them to be suitable for
their intended use and to be adequately cleaned and properly maintained.

\(1\) Equipment and utensils include the following:

\(i\) 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 automated, mechanical, or electronic systems.

\(2\) You must use equipment and utensils of appropriate design and
construction so that use will not result in the contamination of
components or dietary supplements with:

\(i\) Lubricants;

\(ii\) Fuel;

\(iii\) Coolants;

\(iv\) Metal or glass fragments;

\(v\) Filth or any other extraneous material;

\(vi\) Contaminated water; or

\(vii\) Any other contaminants.

\(3\) All equipment and utensils you use must be:

\(i\) Installed and maintained to facilitate cleaning the equipment,
utensils, and all adjacent spaces;

\(ii\) Corrosion-resistant if the equipment or utensils contact
components or dietary supplements;

\(iii\) Made of nontoxic materials;

\(iv\) Designed and constructed to withstand the environment in which
they are used, the action of components or dietary supplements, and, if
applicable, cleaning compounds and sanitizing agents; and

\(v\) Maintained to protect components and dietary supplements from
being contaminated by any source.

\(4\) Equipment and utensils you use must have seams that are smoothly
bonded or maintained to minimize accumulation of dirt, filth, organic
material, particles of components or dietary supplements, or any other
extraneous materials or contaminants.

\(5\) Each freezer, refrigerator, and other cold storage compartment you
use to hold components or dietary supplements:

\(i\) Must be fitted with an indicating thermometer,
temperature-measuring device, or temperature-recording device that
indicates and records, or allows for recording by hand, the temperature
accurately within the compartment; and

\(ii\) Must have an automated device for regulating temperature or an
automated alarm system to indicate a significant temperature change in a
manual operation.

\(6\) Instruments or controls used in the manufacturing, packaging,
labeling, or holding of a dietary supplement, and instruments or
controls that you use to measure, regulate, or record temperatures,
hydrogen-ion concentration (pH), water activity, or other conditions, to
control or prevent the growth of microorganisms or other contamination
must be:

\(i\) Accurate and precise;

\(ii\) Adequately maintained; and

\(iii\) Adequate in number for their designated uses.

\(7\) Compressed air or other gases you introduce mechanically into or
onto a component, dietary supplement, or contact surface or that you use
to clean any contact surface must be treated in such a way that the
component, dietary supplement, or contact surface is not contaminated.

\(b\) You must calibrate instruments and controls you use in
manufacturing or testing a component or dietary supplement. You must
calibrate:

\(1\) Before first use;

\(2\) At the frequency specified in writing by the manufacturer of the
instrument and control; or

\(3\) At routine intervals or as otherwise necessary to ensure the
accuracy and precision of the instrument and control.

\(c\) You must repair or replace instruments or controls that cannot be
adjusted to agree with the reference standard.

\(d\) You must maintain, clean, and sanitize, as necessary, all
equipment, utensils, and any other contact surfaces used to manufacture,
package, label, or hold components or dietary supplements.

\(1\) Equipment and utensils must be taken apart as necessary for
thorough maintenance, cleaning, and sanitizing.

\(2\) You must ensure that all contact surfaces, used for manufacturing
or holding low-moisture components or dietary supplements, are in a dry
and sanitary condition when in use. When the surfaces are wet-cleaned,
they must be sanitized, when necessary, and thoroughly dried before
subsequent use.

\(3\) If you use wet processing during manufacturing, you must clean and
sanitize all contact surfaces, as necessary, to protect against the
introduction of microorganisms into components or dietary supplements.
When cleaning and sanitizing is necessary, you must clean and sanitize
all contact surfaces before use and after any interruption during which
the contact surface may have become contaminated. If you use contact
surfaces in a continuous production operation or in consecutive
operations involving different batches of the same dietary supplement,
you must adequately clean and sanitize the contact surfaces, as
necessary.

\(4\) You must clean surfaces that do not come into direct contact with
components or dietary supplements as frequently as necessary to protect
against contaminating components or dietary supplements.

\(5\) Single-service articles (such as utensils intended for one-time
use, paper cups, and paper towels) must be:

\(i\) Stored in appropriate containers; and

\(ii\) Handled, dispensed, used, and disposed of in a manner that
protects against contamination of components, dietary supplements, or
any contact surface.

\(6\) Cleaning compounds and sanitizing agents must be adequate for
their intended use and safe under their conditions of use;

\(7\) You must store cleaned and sanitized portable equipment and
utensils that have contact surfaces in a location and manner that
protects them from contamination.

[§ 111.30 What Requirements Apply to Automated, Mechanical, or
Electronic Equipment?]{.underline}

For any automated, mechanical, or electronic equipment that you use to
manufacture, package, label, or hold a dietary supplement, you must:

\(a\) Design or select equipment to ensure that dietary supplement
specifications are consistently met;

\(b\) Determine the suitability of the equipment by ensuring that your
equipment is capable of operating satisfactorily within the operating
limits required by the process;

\(c\) Routinely calibrate, inspect, or check the equipment to ensure
proper performance. Your quality control personnel must periodically
review these calibrations, inspections, or checks;

\(d\) Establish and use appropriate controls for automated, mechanical,
and electronic equipment (including software for a computer controlled
process) to ensure that any changes to the manufacturing, packaging,
labeling, holding, or other operations are approved by quality control
personnel and instituted only by authorized personnel; and

\(e\) Establish and use appropriate controls to ensure that the
equipment functions in accordance with its intended use. These controls
must be approved by quality control personnel.

[§ 111.35 Under This Subpart, What Records Must You Make and
Keep?]{.underline}

\(a\) You must make and keep records required under this subpart in
accordance with subpart P.

\(b\) You must make and keep the following records:

\(1\) Written procedures for fulfilling the requirements of this
subpart, including written procedures for:

\(i\) Calibrating instruments and controls that you use in manufacturing
or testing a component or dietary supplement;

\(ii\) Calibrating, inspecting, and checking automated, mechanical, and
electronic equipment; and

\(iii\) Maintaining, cleaning, and sanitizing, as necessary, all
equipment, utensils, and any other contact surfaces that are used to
manufacture, package, label, or hold components or dietary supplements;

\(2\) Documentation, in individual equipment logs, of the date of the
use, maintenance, cleaning, and sanitizing of equipment, unless such
documentation is kept with the batch record;

\(3\) Documentation of any calibration, each time the calibration is
performed, for instruments and controls that you use in manufacturing or
testing a component or dietary supplement. In your documentation, you
must:

\(i\) Identify the instrument or control calibrated;

\(ii\) Provide the date of calibration;

\(iii\) Identify the reference standard used including the certification
of accuracy of the known reference standard and a history of
recertification of accuracy;

\(iv\) Identify the calibration method used, including appropriate
limits for accuracy and precision of instruments and controls when
calibrating;

\(v\) Provide the calibration reading or readings found;

\(vi\) Identify the recalibration method used, and reading or readings
found, if accuracy or precision or both accuracy and precision limits
for instruments and controls were not met; and

\(vii\) Include the initials of the person who performed the calibration
and any recalibration.

\(4\) Written records of calibrations, inspections, and checks of
automated, mechanical, and electronic equipment;

\(5\) Backup file(s) of current software programs (and of outdated
software that is necessary to retrieve records that you are required to
keep in accordance with subpart P, when current software is not able to
retrieve such records) and of data entered into computer systems that
you use to manufacture, package, label, or hold dietary supplements.

\(i\) Your backup file (e.g., a hard copy of data you have entered,
diskettes, tapes, microfilm, or compact disks) must be an exact and
complete record of the data you entered.

\(ii\) You must keep your backup software programs and data secure from
alterations, inadvertent erasures, or loss; and

\(6\) Documentation of the controls that you use to ensure that
equipment functions in accordance with its intended use.

8\. Add §§ 111.55 through 111.95 to newly added subpart E to read as
follows:

Subpart E -- Requirement to Establish

a Production and Process Control System

§ 111.55 What Are the Requirements to Implement a Production and Process
Control System?

§ 111.60 What Are the Design Requirements for the Production and Process
Control System?

§ 111.65 What Are the Requirements For Quality Control Operations?

§ 111.70 What Specifications Must You Establish?

§ 111.73 What is Your Responsibility for Determining Whether Established
Specifications Are Met?

§ 111.75 What Must You do to Determine Whether Specifications are Met?

§ 111.77 What Must You do if Established Specifications are Not Met?

§ 111.80 What Representative Samples Must You Collect?

§ 111.83 What Are the Requirements for Reserve Samples?

§ 111.87 Who Conducts a Material Review and Makes a Disposition
Decision?

§ 111.90 What Requirements Apply to Treatment, In-process Adjustments,
and Reprocessing When There is a Deviation or Unanticipated Occurrence
or When a Specification Established in Accordance with § 111.70 is not
Met?

§ 111.95 Under This Subpart, What Records Must You Make and Keep?

Subpart E -- Requirement to Establish

a Production and Process Control System

[§ 111.55 What Are the Requirements to Implement a Production and
Process Control System?]{.underline}

You must implement a system of production and process controls that
covers all stages of manufacturing, packaging, labeling, and holding of
the dietary supplement to ensure the quality of the dietary supplement
and that the dietary supplement is packaged and labeled as specified in
the master manufacturing record.

[§ 111.60 What Are the Design Requirements for the Production and
Process Control System?]{.underline}

\(a\) Your production and in-process control system must be designed to
ensure that the dietary supplement is manufactured, packaged, labeled,
and held in a manner that will ensure the quality of the dietary
supplement and that the dietary supplement is packaged and labeled as
specified in the master manufacturing record; and

\(b\) The production and in-process control system must include all
requirements of subparts E through L of this part and must be reviewed
and approved by quality control personnel.

[§ 111.65 What Are the Requirements For]{.underline} [Quality Control
Operations?]{.underline}

You must implement quality control operations in your manufacturing,
packaging, labeling, and holding operations for producing the dietary
supplement to ensure the quality of the dietary supplement and that the
dietary supplement is packaged and labeled as specified in the master
manufacturing record.

[§ 111.70 What Specifications Must You Establish?]{.underline}

\(a\) You must establish a specification for any point, step, or stage
in the manufacturing process where control is necessary to ensure the
quality of the dietary supplement and that the dietary supplement is
packaged and labeled as specified in the master manufacturing record.

\(b\) For each component that you use in the manufacture of a dietary
supplement, you must establish component specifications as follows:

\(1\) You must establish an identity specification;

\(2\) You must establish component specifications that are necessary to
ensure that specifications for the purity, strength and composition of
dietary supplements manufactured using the components are met; and

\(3\) You must establish limits on those types of contamination that may
adulterate or may lead to adulteration of the finished batch of the
dietary supplement to ensure the quality of the dietary supplement.

\(c\) For the in-process production:

\(1\) You must establish in-process specifications for any point, step,
or stage in the master manufacturing record where control is necessary
to help ensure that specifications are met for the identity, purity,
strength, and composition of the dietary supplements and, as necessary,
for limits on those types of contamination that may adulterate or may
lead to adulteration of the finished batch of the dietary supplement;

\(2\) You must provide adequate documentation of your basis for why
meeting the in-process specifications, in combination with meeting
component specifications, will help ensure that the specifications are
met for the identity, purity, strength, and composition of the dietary
supplements and for limits on those types of contamination that may
adulterate or may lead to adulteration of the finished batch of the
dietary supplement; and

\(3\) Quality control personnel must review and approve the
documentation that you provide under paragraph (c)(2) of this section.

\(d\) You must establish specifications for dietary supplement labels
(label specifications) and for packaging that may come in contact with
dietary supplements (packaging specifications). Packaging that may come
into contact with dietary supplements must be safe and suitable for its
intended use and must not be reactive or absorptive or otherwise affect
the safety or quality of the dietary supplement.

\(e\) For each dietary supplement that you manufacture you must
establish product specifications for the identity, purity, strength, and
composition of the finished batch of the dietary supplement, and for
limits on those types of contamination that may adulterate, or that may
lead to adulteration of, the finished batch of the dietary supplement to
ensure the quality of the dietary supplement.

\(f\) If you receive a product from a supplier for packaging or labeling
as a dietary supplement (and for distribution rather than for return to
the supplier), you must establish specifications to provide sufficient
assurance that the product you receive is adequately identified and is
consistent with your purchase order.

\(g\) You must establish specifications for the packaging and labeling
of the finished packaged and labeled dietary supplements, including
specifications that ensure that you used the specified packaging and
that you applied the specified label.

[§ 111.73 What is Your Responsibility for Determining Whether
Established Specifications are Met?]{.underline}

You must determine whether the specifications you establish under §
111.70 are met.

[§ 111.75 What must You do to Determine Whether Specifications are
Met?]{.underline}

\(a\) Before you use a component, you must:

\(1\) Conduct at least one appropriate test or examination to verify the
identity of any component that is a dietary ingredient; and

\(2\) Confirm the identity of other components and determine whether
other applicable component specifications established in accordance with
§ 111.70(b) are met. To do so, you must either:

\(i\) Conduct appropriate tests or examinations; or

\(ii\) Rely on a certificate of analysis from the supplier of the
component that you receive, provided that:

\(A\) You first qualify the supplier by establishing the reliability of
the supplier's certificate of analysis through confirmation of the
results of the supplier's tests or examinations;

\(B\) The certificate of analysis includes a description of the test or
examination method(s) used, limits of the test or examinations, and
actual results of the tests or examinations;

\(C\) You maintain documentation of how you qualified the supplier;

\(D\) You periodically re-confirm the supplier's certificate of
analysis; and

\(E\) Your quality control personnel review and approve the
documentation setting forth the basis for qualification (and
re-qualification) of any supplier.

\(b\) You must monitor the in-process points, steps, or stages where
control is necessary to ensure the quality of the finished batch of
dietary supplement to:

\(1\) Determine whether the in-process specifications are met; and

\(2\) Detect any deviation or unanticipated occurrence that may result
in a failure to meet specifications.

\(c\) For a subset of finished dietary supplement batches that you
identify through a sound statistical sampling plan (or for every
finished batch), you must verify that your finished batch of the dietary
supplement meets product specifications for identity, purity, strength,
composition, and for limits on those types of contamination that may
adulterate or that may lead to adulteration of the finished batch of the
dietary supplement. To do so:

\(1\) You must select one or more established specifications for
identity, purity, strength, composition, and the limits on those types
of contamination that may adulterate or that may lead to adulteration of
the dietary supplement that, if tested or examined on the finished
batches of the dietary supplement, would verify that the production and
process control system is producing a dietary supplement that meets all
product specifications (or only those product specifications not
otherwise exempted from this provision by quality control personnel
under paragraph (d) of this section);

\(2\) You must conduct appropriate tests or examinations to determine
compliance with the specifications selected in paragraph (c)(1) of this
section;

\(3\) You must provide adequate documentation of your basis for
determining compliance with the specification(s) selected under
paragraph (c)(1) of this section, through the use of appropriate tests
or examinations conducted under paragraph (c)(2) of this section, will
ensure that your finished batch of the dietary supplement meets all
product specifications for identity, purity, strength, and composition,
and the limits on those types of contamination that may adulterate, or
that may lead to the adulteration of, the dietary supplement; and

\(4\) Your quality control personnel must review and approve the
documentation that you provide under paragraph (c)(3) of this section.

(d)(1) You may exempt one or more product specifications from
verification requirements in paragraph (c)(1) of this section if you
determine and document that the specifications you select under
paragraph (c)(1) of this section for determination of compliance with
specifications are not able to verify that the production and process
control system is producing a dietary supplement that meets the exempted
product specification and there is no scientifically valid method for
testing or examining such exempted product specification at the finished
batch stage. In such a case, you must document why, for example, any
component and in-process testing, examination, or monitoring, and any
other information, will ensure that such exempted product specification
is met without verification through periodic testing of the finished
batch; and

\(2\) Your quality control personnel must review and approve the
documentation that you provide under paragraph (d)(1) of this section.

\(e\) Before you package or label a product that you receive for
packaging or labeling as a dietary supplement (and for distribution
rather than for return to the supplier), you must visually examine the
product and have documentation to determine whether the specifications
that you established under § 111.70 (f) are met.

(f)(1) Before you use packaging, you must, at a minimum, conduct a
visual identification of the containers and closures and review the
supplier's invoice, guarantee, or certification to determine whether the
packaging specifications are met; and

\(2\) Before you use labels, you must, at a minimum, conduct a visual
examination of the label and review the supplier's invoice, guarantee,
or certification to determine whether label specifications are met.

\(g\) You must, at a minimum, conduct a visual examination of the
packaging and labeling of the finished packaged and labeled dietary
supplements to determine whether you used the specified packaging and
applied the specified label.

(h)(1) You must ensure that the tests and examinations that you use to
determine whether the specifications are met are appropriate,
scientifically valid methods.

\(2\) The tests and examinations that you use must include at least one
of the following:

\(i\) Gross organoleptic analysis;

\(ii\) Macroscopic analysis;

\(iii\) Microscopic analysis;

\(iv\) Chemical analysis; or

\(v\) Other scientifically valid methods.

\(i\) You must establish corrective action plans for use when an
established specification is not met.

[§ 111.77 What Must You Do if Established Specifications are not
Met?]{.underline}

\(a\) For specifications established under § 111.70(a), (b)(2), (b)(3),
(c), (d), (e), and (g) that you do not meet, quality control personnel,
in accordance with the requirements in subpart F of this part, must
reject the component, dietary supplement, package or label unless such
personnel approve a treatment, an in-process adjustment, or reprocessing
that will ensure the quality of the finished dietary supplement and that
the dietary supplement is packaged and labeled as specified in the
master manufacturing record. No finished batch of dietary supplements
may be released for distribution unless it complies with § 111.123(b).

\(b\) For specifications established under § 111.70(b)(1) that you do
not meet, quality control personnel must reject the component and the
component must not be used in manufacturing the dietary supplement.

\(c\) For specifications established under § 111.70(f) that you do not
meet, quality control personnel must reject the product and the product
may not be packaged or labeled for distribution as a dietary supplement.

[§ 111.80 What Representative Samples Must You Collect?]{.underline}

The representative samples that you must collect include:

\(a\) Representative samples of each unique lot of components,
packaging, and labels that you use to determine whether the components,
packaging, and labels meet specifications established in accordance with
§ 111.70(b) and (d), and as applicable, § 111.70(a) (and, when you
receive components, packaging, or labels from a supplier, representative
samples of each unique shipment, and of each unique lot within each
unique shipment);

\(b\) Representative samples of in-process materials for each
manufactured batch 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, strength, and composition of
dietary supplements to determine whether the in-process materials meet
specifications established in accordance with § 111.70(c), and as
applicable, § 111.70(a);

\(c\) Representative samples of a subset of finished batches of each
dietary supplement that you manufacture, which you identify through a
sound statistical sampling plan (or otherwise every finished batch),
before releasing for distribution to verify that the finished batch of
dietary supplement meets product specifications established in
accordance with § 111.70(e), and as applicable, § 111.70(a);

\(d\) Representative samples of each unique shipment, and of each unique
lot within each unique shipment, of product that you receive for
packaging or labeling as a dietary supplement (and for distribution
rather than for return to the supplier) to determine whether the
received product meets specifications established in accordance with §
111.70(f), and as applicable, § 111.70(a); and

\(e\) Representative samples of each lot of packaged and labeled dietary
supplements to determine whether the packaging and labeling of the
finished packaged and labeled dietary supplements meet specifications
established in accordance with § 111.70(g), and as applicable,
§ 111.70(a).

[§ 111.83 What Are the Requirements for Reserve Samples?]{.underline}

\(a\) You must collect and hold reserve samples of each lot of packaged
and labeled dietary supplements that you distribute.

\(b\) The reserve samples must:

\(1\) Be held using the same container-closure system in which the
packaged and labeled dietary supplement is distributed, or if
distributing dietary supplements to be packaged and labeled, using a
container-closure system that provides essentially the same
characteristics to protect against contamination or deterioration as the
one in which it is distributed for packaging and labeling elsewhere;

\(2\) Be identified with the batch, lot, or control number;

\(3\) Be retained for one year past the shelf life date (if shelf life
dating is used), or for 2 years from the date of distribution of the
last batch of dietary supplements associated with the reserve sample,
for use in appropriate investigations; and

\(4\) Consist of at least twice the quantity necessary for all tests or
examinations to determine whether or not the dietary supplement meets
product specifications.

[§ 111.87 Who Conducts a Material Review and Makes a Disposition
Decision?]{.underline}

Quality control personnel must conduct all required material reviews and
make all required disposition decisions.

[§ 111.90 What Requirements Apply to Treatments, In-process Adjustments,
and Reprocessing When There is a Deviation or Unanticipated Occurrence
or When a Specification Established in Accordance with § 111.70 is not
Met?]{.underline}

\(a\) You must not reprocess a rejected dietary supplement treat or
provide an in-process adjustment to a component, packaging, or label to
make it suitable for use in the manufacture of a dietary supplement
unless:

\(1\) quality control personnel conduct a material review and make a
disposition decision to approve the reprocessing, treatment, or
in-process adjustment; and

\(2\) the reprocessing, treatment, or in-process adjustment is permitted
by § 111.77;

\(b\) You must not reprocess any dietary supplement, treat or provide an
in-process adjustment to a component to make it suitable for use in the
manufacture of a dietary supplement, unless:

\(1\) quality control personnel conduct a material review and make a
disposition decision that is based on a scientifically valid reason and
approves the reprocessing, treatment, or in-process adjustment; and

\(2\) the reprocessing, treatment or in-process adjustment is permitted
by § 111.77;

\(c\) Any batch of dietary supplement that is reprocessed, that contains
components that you have treated, or to which you have made in-process
adjustments to make them suitable for use in the manufacture of the
dietary supplement must be approved by quality control personnel and
comply with § 111.123(b) before releasing for distribution.

[§ 111.95 Under This Subpart, What Records Must You Make and
Keep?]{.underline}

\(a\) You must make and keep records required under this subpart in
accordance with subpart P.

\(b\) Under this subpart, you must make and keep the following records:

\(1\) The specifications established;

\(2\) Documentation of your qualification of a supplier for the purpose
of relying on the supplier's certificate of analysis;

\(3\) Documentation for why meeting in-process specifications, in
combination with meeting component specifications, helps ensure that the
dietary supplement meets the specifications for identity, purity,
strength, and composition; and for limits on those types of
contamination that may adulterate or may lead to adulteration of the
finished batch of the dietary supplement; and

\(4\) Documentation for why the results of appropriate tests or
examinations for the product specifications selected under §
111.75(c)(1) ensure that the dietary supplement meets all product
specifications;

\(5\) Documentation for why any component and in-process testing,
examination, or monitoring, and any other information, will ensure that
a product specification that is exempted under § 111.75(d) is met
without verification through periodic testing of the finished batch,
including documentation that the selected specifications tested or
examined under § 111.75 (c)(1) are not able to verify that the
production and process control system is producing a dietary supplement
that meets the exempted product specification and there is no
scientifically valid method for testing or examining such exempted
product specification at the finished batch stage.

9\. Add §§ 111.103 through 111.140 to newly added subpart F to read as
follows:

Subpart F - Production and Process Control System:

Requirements for Quality Control

§ 111.103 What Are the Requirements Under This Subpart for Written
Procedures?

§ 111.105 What Must Quality Control Personnel Do?

§ 111.110 What Quality Control Operations Are Required for Laboratory
Operations Associated With the Production and Process Control System?

§ 111.113 What Quality Control Operations Are Required for a Material
Review and Disposition Decision?

§ 111.117 What Quality Control Operations Are Required For Equipment,
Instruments, and Controls?

§ 111.120 What Quality Control Operations are Required for Components,
Packaging, and Labels Before Use in the Manufacture of a Dietary
Supplement?

§ 111.123 What Quality Control Operations Are Required for the Master
Manufacturing Record, the Batch Production Record, and Manufacturing
Operations?

§ 111.127 What Quality Control Operations Are Required for Packaging and
Labeling Operations?

§ 111.130 What Quality Control Operations Are Required for Returned
Dietary Supplements?

§ 111.135 What Quality Control Operations Are Required for Product
Complaints?

§ 111.140 Under This Subpart, What Records Must You Make and Keep?

Subpart F - Production and Process Control System:

Requirements for Quality Control

[§ 111.103 What Are the Requirements Under This Subpart for Written
Procedures?]{.underline}

You must establish and follow written procedures for the
responsibilities of the quality control operations, including written
procedures for conducting a material review and making a disposition
decision, and for approving or rejecting any reprocessing.

[§ 111.105 What Must]{.underline} [Quality Control Personnel
Do?]{.underline}

Quality control personnel must ensure that your manufacturing,
packaging, labeling, and holding operations ensure the quality of the
dietary supplement and that the dietary supplement is packaged and
labeled as specified in the master manufacturing record. To do so,
quality control personnel must perform operations that include:

\(a\) Approving or rejecting all processes, specifications, written
procedures, controls, tests, and examinations, and deviations from or
modifications to them, that may affect the identity, purity, strength,
or composition of a dietary supplement;

\(b\) Reviewing and approving the documentation setting forth the basis
for qualification of any supplier;

\(c\) Reviewing and approving the documentation setting forth the basis
for why meeting in-process specifications, in combination with meeting
component specifications, will help ensure that the identity, purity,
strength, and composition of the dietary supplement are met;

\(d\) Reviewing and approving the documentation setting forth the basis
for why the results of appropriate tests or examinations for each
product specification selected under § 111.75(c)(1) will ensure that the
finished batch of the dietary supplement meets product specifications;

\(e\) Reviewing and approving the basis and the documentation for why
any product specification is exempted from the verification requirements
in § 111.75(c)(1), and for why any component and in-process testing,
examination, or monitoring, or other methods will ensure that such
exempted product specification is met without verification through
periodic testing of the finished batch;

\(f\) Ensuring that required representative samples are collected;

\(g\) Ensuring that required reserve samples are collected and held;

\(h\) Determining whether all specifications established under §
111.70(a) are met; and

\(i\) Performing other operations required under this subpart.

[§ 111.110 What Quality Control Operations Are Required for Laboratory
Operations Associated With the Production and Process Control
System?]{.underline}

Quality control operations for laboratory operations associated with the
production and process control system must include:

\(a\) Reviewing and approving all laboratory control processes
associated with the production and process control system;

\(b\) Ensuring that all tests and examinations required under § 111.75
are conducted; and

\(c\) Reviewing and approving the results of all tests and examinations
required under § 111.75.

[§ 111.113 What Quality Control Operations Are Required for a Material
Review and Disposition Decision?]{.underline}

\(a\) Quality control personnel must conduct a material review and make
a disposition decision if:

\(1\) A specification established in accordance with § 111.70 is not
met;

\(2\) A batch deviates from the master manufacturing record, including
when any step established in the master manufacturing record is not
completed and including any deviation from specifications;

\(3\) There is any unanticipated occurrence during the manufacturing
operations that adulterates or may lead to adulteration of the
component, dietary supplement, or packaging, or could lead to the use of
a label not specified in the master manufacturing record;

\(4\) Calibration of an instrument or control suggests a problem that
may have resulted in a failure to ensure the quality of a batch or
batches of a dietary supplement; or

\(5\) A dietary supplement is returned.

\(b\) (1) When there is a deviation or unanticipated occurrence during
the production and in-process control system that results in or could
lead to adulteration of a component, dietary supplement, or packaging,
or could lead to the use of a label not specified in the master
manufacturing record, quality control personnel must reject the
component, dietary supplement, packaging, or label unless it approves a
treatment, an in-process adjustment, or reprocessing to correct the
applicable deviation or occurrence.

\(2\) When a specification established in accordance with § 111.70 is
not met, quality control personnel must reject the component, dietary
supplement, package or label, unless quality control personnel approve a
treatment, an in-process adjustment, or reprocessing, as permitted in §
111.77.

\(c\) The person who conducts a material review and makes the
disposition decision must, at the time of performance, document that
material review and disposition decision.

[§ 111.117 What Quality Control Operations Are Required for Equipment,
Instruments, and Controls?]{.underline}

Quality control operations for equipment, instruments, and controls must
include:

\(a\) Reviewing and approving all processes for calibrating instruments
and controls;

\(b\) Periodically reviewing all records for calibration of instruments
and controls;

\(c\) Periodically reviewing all records for calibrations, inspections,
and checks of automated, mechanical, or electronic equipment; and

\(d\) Reviewing and approving controls to ensure that automated,
mechanical, or electronic equipment functions in accordance with its
intended use.

[§ 111.120 What Quality Control Operations Are Required for Components,
Packaging, and Labels Before Use in the Manufacture of a Dietary
Supplement?]{.underline}

Quality control operations for components, packaging, and labels before
use in the manufacture of a dietary supplement must include:

\(a\) Reviewing all receiving records for components, packaging, and
labels;

\(b\) Determining whether all components, packaging, and labels conform
to specifications established under § 111.70 (b) and (d);

\(c\) Conducting any required material review and making any required
disposition decision;

\(d\) Approving or rejecting any treatment and in-process adjustments of
components, packaging, or labels to make them suitable for use in the
manufacture of a dietary supplement; and

\(e\) Approving, and releasing from quarantine, all components,
packaging, and labels before they are used.

[§ 111.123 What Quality Control Operations Are Required for the Master
Manufacturing Record, the Batch Production Record, and Manufacturing
Operations?]{.underline}

\(a\) Quality control operations for the master manufacturing record,
the batch production record, and manufacturing operations must include:

\(1\) Reviewing and approving all master manufacturing records and all
modifications to the master manufacturing records;

\(2\) Reviewing and approving all batch production-related records;

\(3\) Reviewing all monitoring required under subpart E;

\(4\) Conducting any required material review and making any required
disposition decision;

\(5\) Approving or rejecting any reprocessing;

\(6\) Determining whether all in-process specifications established in
accordance with § 111.70(c) are met;

\(7\) Determining whether each finished batch conforms to product
specifications established in accordance with § 111.70(e); and

\(8\) Approving and releasing, or rejecting, each finished batch for
distribution, including any reprocessed finished batch.

\(b\) Quality control personnel must not approve and release for
distribution:

\(1\) any batch of dietary supplement for which any component in the
batch does not meet its identity specification;

\(2\) any batch of dietary supplement, including any reprocessed batch,
that does not meet all product specifications established in accordance
with § 111.70(e);

\(3\) any batch of dietary supplement, including any reprocessed batch,
that has not been manufactured, packaged, labeled, and held under
conditions to prevent adulteration under sections 402(a)(1), (a)(2),
(a)(3), and (a)(4) of the act: and

\(4\) any product received from a supplier for packaging or labeling as
a dietary supplement (and for distribution rather than for return to the
supplier) for which sufficient assurance is not provided to adequately
identify the product and to determine that the product is consistent
with your purchase order.

[§ 111.127 What Quality Control Operations Are Required for Packaging
and Labeling Operations?]{.underline}

Quality control operations for packaging and labeling operations must
include:

\(a\) Reviewing the results of any visual examination and documentation
to ensure that specifications established under § 111.70(f) are met for
all products that you receive for packaging and labeling as a dietary
supplement (and for distribution rather than for return to the
supplier);

\(b\) Approving, and releasing from quarantine, all products that you
receive for packaging or labeling as a dietary supplement (and for
distribution rather than for return to the supplier) before they are
used for packaging or labeling;

\(c\) Reviewing and approving all records for packaging and label
operations;

\(d\) Determining whether the finished packaged and labeled dietary
supplement conforms to specifications established in accordance with §
111.70(g);

\(e\) Conducting any required material review and making any required
disposition decision;

\(f\) Approving or rejecting any repackaging of a packaged dietary
supplement;

\(g\) Approving or rejecting any relabeling of a packaged and labeled
dietary supplement; and

\(h\) Approving for release, or rejecting, any packaged and labeled
dietary supplement (including a repackaged or relabeled dietary
supplement) for distribution.

[§ 111.130 What Quality Control Operations Are Required for Returned
Dietary Supplements?]{.underline}

Quality control operations for returned dietary supplements must
include:

\(a\) Conducting any required material review and making any required
disposition decision; including

\(1\) Determining whether tests or examination are necessary to
determine compliance with product specifications established in
accordance with § 111.70(e); and

\(2\) Reviewing the results of any tests or examinations that are
conducted to determine compliance with product specifications
established in accordance with § 111.70(e);

\(b\) Approving or rejecting any salvage and redistribution of any
returned dietary supplement;

\(c\) Approving or rejecting any reprocessing of any returned dietary
supplement; and

\(d\) Determining whether the reprocessed dietary supplement meets
product specifications and either approving for release, or rejecting,
any returned dietary supplement that is reprocessed.

[§ 111.135 What Quality Control Operations Are Required for Product
Complaints?]{.underline}

Quality control operations for product complaints must include reviewing
and approving decisions about whether to investigate a product complaint
and reviewing and approving the findings and follow-up action of any
investigation performed.

[§ 111.140 Under This Subpart, What Records Must You Make and
Keep?]{.underline}

\(a\) You must make and keep the records required under this subpart in
accordance with subpart P.

\(b\) You must make and keep the following records:

\(1\) Written procedures for the responsibilities of the quality control
operations, including written procedures for conducting a material
review and making a disposition decision and written procedures for
approving or rejecting any reprocessing;

\(2\) Written documentation, at the time of performance, that quality
control personnel performed the review, approval, or rejection
requirements by recording the following:

\(i\) Date that the review, approval, or rejection was performed; and

\(ii\) Signature of the person performing the review, approval, or
rejection; and

\(3\) Documentation of any material review and disposition decision and
follow-up. Such documentation must be included in the appropriate batch
production record and must include:

\(i\) Identification of the specific deviation or the unanticipated
occurrence;

\(ii\) Description of your investigation into the cause of the deviation
from the specification or the unanticipated occurrence;

\(iii\) Evaluation of whether or not the deviation or unanticipated
occurrence has resulted in or could lead to a failure to ensure the
quality of the dietary supplement or a failure to package and label the
dietary supplement as specified in the master manufacturing record;

\(iv\) Identification of the action(s) taken to correct, and prevent a
recurrence of, the deviation or the unanticipated occurrence;

\(v\) Explanation of what you did with the component, dietary
supplement, packaging, or label;

\(vi\) A scientifically valid reason for any reprocessing of a dietary
supplement that is rejected or any treatment or in-process adjustment of
a component that is rejected; and

\(vii\) The signature of the individual(s) designated to perform the
quality control operation, who conducted the material review and made
the disposition decision, and of each qualified individual who provides
information relevant to that material review and disposition decision.

10\. Add §§ 111.153 through 111.180 to newly added subpart G to read as
follows:

Subpart G -- Production and Process Control System:

Requirements for Components, Packaging, and Labels and for

Product that You Receive for Packaging or Labeling

as a Dietary Supplement

§ 111.153 What Are the Requirements Under This Subpart for Written
Procedures?

§ 111.155 What Requirements Apply to Components of Dietary Supplements?

§ 111.160 What Requirements Apply to Packaging and Labels Received?

§ 111.165 What Requirements Apply to a Product Received for Packaging or
Labeling as a Dietary Supplement (and for distribution rather than for
return to the supplier)?

§ 111.170 What Requirements Apply to Rejected Components, Packaging, and
Labels, and to Rejected Products That are Received for Packaging or
Labeling as a Dietary Supplement?

§ 111.180 Under This Subpart, What Records Must You Make and Keep?

Subpart G -- Production and Process Control System:

Requirements for Components, Packaging, and Labels and for

Product that You Receive for Packaging or Labeling

as a Dietary Supplement

[§ 111.153 What Are the Requirements Under This Subpart for Written
Procedures?]{.underline}

You must establish and follow written procedures for fulfilling the
requirements of this subpart.

[§ 111.155 What Requirements Apply to Components of Dietary
Supplements?]{.underline}

\(a\) You must visually examine each immediate container or grouping of
immediate containers in a shipment that you receive for appropriate
content label, container damage, or broken seals to determine whether
the container condition may have resulted in contamination or
deterioration of the components;

\(b\) You must visually examine the supplier's invoice, guarantee, or
certification in a shipment you receive to ensure the components are
consistent with your purchase order;

\(c\) You must quarantine components before you use them in the
manufacture of a dietary supplement until:

\(1\) You collect representative samples of each unique lot of
components (and, for components that you receive, of each unique
shipment, and of each unique lot within each unique shipment);

\(2\) Quality control personnel review and approve the results of any
tests or examinations conducted on components; and

\(3\) Quality control personnel approve the components for use in the
manufacture of a dietary supplement, including approval of any treatment
(including in-process adjustments) of components to make them suitable
for use in the manufacture of a dietary supplement, and releases them
from quarantine.

(d)(1) You must identify each unique lot within each unique shipment of
components that you receive and any lot of components that you produce
in a manner that allows you to trace the lot to the supplier, the date
received, the name of the component, the status of the component (e.g.,
quarantined, approved, or rejected); and to the dietary supplement that
you manufactured and distributed.

\(2\) You must use this unique identifier whenever you record the
disposition of each unique lot within each unique shipment of components
that you receive and any lot of components that you produce.

\(e\) You must hold components under conditions that will protect
against contamination and deterioration, and avoid mixups.

[§ 111.160 What Requirements Apply to Packaging and Labels
Received?]{.underline}

\(a\) You must visually examine each immediate container or grouping of
immediate containers in a shipment for appropriate content label,
container damage, or broken seals to determine whether the container
condition may have resulted in contamination or deterioration of the
packaging and labels.

\(b\) You must visually examine the supplier's invoice, guarantee, or
certification in a shipment to ensure that the packaging or labels are
consistent with your purchase order.

\(c\) You must quarantine packaging and labels before you use them in
the manufacture of a dietary supplement until:

\(1\) You collect representative samples of each unique shipment, and of
each unique lot within each unique shipment, of packaging and labels
and, at a minimum, conduct a visual identification of the immediate
containers and closures;

\(2\) Quality control personnel review and approve the results of any
tests or examinations conducted on the packaging and labels; and

\(3\) Quality control personnel approve the packaging and labels for use
in the manufacture of a dietary supplement and release them from
quarantine.

(d)(1) You must identify each unique lot within each unique shipment of
packaging and labels in a manner that allows you to trace the lot to the
supplier, the date received, the name of the packaging and label, the
status of the packaging and label (e.g., quarantined, approved, or
rejected); and to the dietary supplement that you distributed; and

\(2\) You must use this unique identifier whenever you record the
disposition of each unique lot within each unique shipment of packaging
and labels.

\(e\) You must hold packaging and labels under conditions that will
protect against contamination and deterioration, and avoid mixups.

[§ 111.165 What Requirements Apply to a Product Received for Packaging
or Labeling as a Dietary Supplement (and for distribution rather than
for return to the supplier)?]{.underline}

\(a\) You must visually examine each immediate container or grouping of
immediate containers in a shipment of product that you receive for
packaging or labeling as a dietary supplement (and for distribution
rather than for return to the supplier) for appropriate content label,
container damage, or broken seals to determine whether the container
condition may have resulted in contamination or deterioration of the
received product.

\(b\) You must visually examine the supplier's invoice, guarantee, or
certification in a shipment of the received product to ensure that the
received product is consistent with your purchase order.

\(c\) You must quarantine the received product until:

\(1\) You collect representative samples of each unique shipment, and of
each unique lot within each unique shipment, of received product;

\(2\) Quality control personnel review and approve the documentation to
determine whether the received product meets the specifications that you
established under § 111.70(f); and

\(3\) Quality control personnel approve the received product for
packaging or labeling as a dietary supplement and release the received
product from quarantine.

(d)(1) You must identify each unique lot within each unique shipment of
received product in a manner that allows you to trace the lot to the
supplier, the date received, the name of the received product, the
status of the received product (e.g., quarantined, approved, or
rejected), and to the product that you packaged or labeled and
distributed as a dietary supplement.

\(2\) You must use this unique identifier whenever you record the
disposition of each unique lot within each unique shipment of the
received product.

\(e\) You must hold the received product under conditions that will
protect against contamination and deterioration, and avoid mixups.

[§ 111.170 What Requirements Apply to Rejected Components, Packaging,
and Labels, and to Rejected Products Received for Packaging or Labeling
as a Dietary Supplement?]{.underline}

You must clearly identify, hold, and control under a quarantine system
for appropriate disposition any component, packaging, and label, and any
product that you receive for packaging or labeling as a dietary
supplement (and for distribution rather than for return to the
supplier), that is rejected and unsuitable for use in manufacturing,
packaging, or labeling operations.

[§ 111.180 Under This Subpart, What Records Must You Make and
Keep?]{.underline}

\(a\) You must make and keep records required under this subpart in
accordance with subpart P.

\(b\) You must make and keep the following records:

\(1\) Written procedures for fulfilling the requirements of this
subpart.

\(2\) Receiving records (including records such as certificates of
analysis, suppliers' invoices, and suppliers' guarantees) for
components, packaging, and labels and for products that you receive for
packaging or labeling as a dietary supplement (and for distribution
rather than for return to the supplier); and

\(3\) Documentation that the requirements of this subpart were met.

\(i\) The person who performs the required operation must document, at
the time of performance, that the required operation was performed.

\(ii\) The documentation must include:

\(A\) The date that the components, packaging, labels, or products that
you receive for packaging or labeling as a dietary supplement were
received;

\(B\) The initials of the person performing the required operation;

\(C\) The results of any tests or examinations conducted on components,
packaging or labels, and of any visual examination of product that you
receive for packaging or labeling as a dietary supplement; and

\(D\) Any material review and disposition decision conducted on
components, packaging, labels, or products that you receive for
packaging or labeling as a dietary supplement.

11\. Add §§ 111.205 through 111.210 to newly added subpart H to read as
follows:

Subpart H -- Production and Process Control System:

Requirements for the Master Manufacturing Record

§ 111.205 What is the Requirement to Establish a Master Manufacturing
Record?

§ 111.210 What Must the Master Manufacturing Record Include?

Subpart H -- Production and Process Control System:

Requirements for the Master Manufacturing Record

[§ 111.205 What is The Requirement to Establish a Master Manufacturing
Record?]{.underline}

\(a\) You must prepare and follow a written master manufacturing record
for each unique formulation of dietary supplement that you manufacture,
and for each batch size, to ensure uniformity in the finished batch from
batch to batch.

\(b\) The master manufacturing record must:

\(1\) Identify specifications for the points, steps, or stages in the
manufacturing process where control is necessary to ensure the quality
of the dietary supplement and that the dietary supplement is packaged
and labeled as specified in the master manufacturing record; and

\(2\) Establish controls and procedures to ensure that each batch of
dietary supplement that you manufacture meets the specifications
identified in accordance with paragraph (b)(1) of this section.

\(c\) You must make and keep master manufacturing records in accordance
with Subpart P.

[§ 111.210 What Must the Master Manufacturing Record
Include?]{.underline}

The master manufacturing record must include:

\(a\) The name of the dietary supplement to be manufactured and the
strength, concentration, weight, or measure of each dietary ingredient
for each batch size;

\(b\) A complete list of components to be used;

\(c\) An accurate statement of the weight or measure of each component
to be used;

\(d\) The identity and weight or measure of each dietary ingredient that
will be declared on the Supplement Facts label and the identity of each
ingredient that will be declared on the ingredients list of the dietary
supplement;

\(e\) A statement of any intentional overage amount of a dietary
ingredient;

\(f\) A statement of theoretical yield of a manufactured dietary
supplement expected at each point, step, or stage of the manufacturing
process where control is needed to ensure the quality of the dietary
supplement, and the expected yield when you finish manufacturing the
dietary supplement, including the maximum and minimum percentages of
theoretical yield beyond which a deviation investigation of a batch is
necessary and material review is conducted and disposition decision is
made;

\(g\) A description of packaging and a representative label, or a
cross-reference to the physical location of the actual or representative
label;

\(h\) Written instructions, including the following:

\(1\) Specifications for each point, step, or stage in the manufacturing
process where control is necessary to ensure the quality of the dietary
supplement and that the dietary supplement is packaged and labeled as
specified in the master manufacturing record;

\(2\) Procedures for sampling and a cross-reference to procedures for
tests or examinations;

\(3\) Specific actions necessary to perform and verify points, steps, or
stages in the manufacturing process where control is necessary to ensure
the quality of the dietary supplement and that the dietary supplement is
packaged and labeled as specified in the master manufacturing record.

\(i\) Such specific actions must include verifying the weight or measure
of any component and verifying the addition of any component; and

\(ii\) For manual operations, such specific actions must include:

\(A\) One person weighing or measuring a component and another person
verifying the weight or measure; and

\(B\) One person adding the component and another person verifying the
addition.

\(4\) Special notations and precautions to be followed; and

\(5\) Corrective action plans for use when a specification is not met.

12\. Add §§ 111.255 through 111.260 to newly added subpart I to read as
follows:

Subpart I -- Production and Process Control System:

Requirements for the Batch Production Record

§ 111.255 What is the Requirement to Establish a Batch Production
Record?

§ 111.260 What Must the Batch Record Include?

Subpart I -- Production and Process Control System:

Requirements for the Batch Production Record

[§ 111.255 What is the Requirement to Establish a Batch Production
Record?]{.underline}

\(a\) You must prepare a batch production record every time you
manufacture a batch of a dietary supplement;

\(b\) Your batch production record must include complete information
relating to the production and control of each batch;

\(c\) Your batch production record must accurately follow the
appropriate master manufacturing record and you must perform each step
in the production of the batch; and

\(d\) You must make and keep batch production records in accordance with
subpart P.

[§ 111.260 What Must the Batch Record Include?]{.underline}

The batch production record must include:

\(a\) The batch, lot, or control number

> \(1\) of the finished batch of dietary supplement; and
>
> \(2\) that you assign in accordance with § 111.415(f) for:
>
> \(i\) each lot of packaged and labeled dietary supplement from the
> finished batch of dietary supplement;
>
> \(ii\) each lot of dietary supplement, from the finished batch of
> dietary supplement, that you distribute to another person for
> packaging or labeling;

\(b\) The identity of equipment and processing lines used in producing
the batch;

\(c\) The date and time of the maintenance, cleaning, and sanitizing of
the equipment and processing lines used in producing the batch, or a
cross-reference to records, such as individual equipment logs, where
this information is retained;

\(d\) The unique identifier that you assigned to each component (or,
when applicable, to a product that you receive from a supplier for
packaging or labeling as a dietary supplement), packaging, and label
used;

\(e\) The identity and weight or measure of each component used;

\(f\) A statement of the actual yield and a statement of the percentage
of theoretical yield at appropriate phases of processing;

\(g\) The actual results obtained during any monitoring operation;

\(h\) The results of any testing or examination performed during the
batch production, or a cross-reference to such results;

\(i\) Documentation that the finished dietary supplement meets
specifications established in accordance with § 111.70(e) and (g);

\(j\) Documentation, at the time of performance, of the manufacture of
the batch, including:

\(1\) The date on which each step of the master manufacturing record was
performed; and

\(2\) The initials of the persons performing each step, including:

\(i\) The initials of the person responsible for weighing or measuring
each component used in the batch;

\(ii\) The initials of the person responsible for verifying the weight
or measure of each component used in the batch;

\(iii\) The initials of the person responsible for adding the component
to the batch; and

\(iv\) The initials of the person responsible for verifying the addition
of components to the batch;

\(k\) Documentation, at the time of performance, of packaging and
labeling operations, including:

\(1\) The unique identifier that you assigned to packaging and labels
used, the quantity of the packaging and labels used, and, when label
reconciliation is required, reconciliation of any discrepancies between
issuance and use of labels;

\(2\) An actual or representative label, or a cross-reference to the
physical location of the actual or representative label specified in the
master manufacturing record; and

\(3\) The results of any tests or examinations conducted on packaged and
labeled dietary supplements (including repackaged or relabeled dietary
supplements), or a cross-reference to the physical location of such
results;

\(l\) Documentation at the time of performance that quality control
personnel:

\(1\) Reviewed the batch production record, including:

\(i\) Review of any monitoring operation required under subpart E; and

\(ii\) Review of the results of any tests and examinations, including
tests and examinations conducted on components, in-process materials,
finished batches of dietary supplements, and packaged and labeled
dietary supplements;

\(2\) Approved or rejected any reprocessing or repackaging; and

\(3\) Approved and released, or rejected, the batch for distribution,
including any reprocessed batch; and

\(4\) Approved and released, or rejected, the packaged and labeled
dietary supplement, including any repackaged or relabeled dietary
supplement.

\(m\) Documentation at the time of performance of any required material
review and disposition decision.

\(n\) Documentation at the time of performance of any reprocessing.

13\. Add §§ 111.303 through 111.325 to newly added subpart J to read as
follows:

Subpart J -- Production and Process Control System:

Requirements for Laboratory Operations

§ 111.303 What Are the Requirements Under This Subpart for Written
Procedures?

§ 111.310 What Are the Requirements for the Laboratory Facilities That
You Use?

§ 111.315 What Are the Requirements for Laboratory Control Processes?

§ 111.320 What Requirements Apply to Laboratory Methods for Testing and
Examination?

§ 111.325 Under This Subpart, What Records Must You Make and Keep?

Subpart J -- Production and Process Control System:

Requirements for Laboratory Operations

[§ 111.303 What Are the Requirements Under This Subpart for Written
Procedures?]{.underline}

You must establish and follow written procedures for laboratory
operations, including written procedures for the tests and examinations
that you conduct to determine whether specifications are met.

[§ 111.310 What Are the Requirements for the Laboratory
Facilities?]{.underline}

You must use adequate laboratory facilities to perform whatever testing
and examinations are necessary to determine whether:

\(a\) Components that you use meet specifications;

\(b\) In-process specifications are met as specified in the master
manufacturing record; and

\(c\) Dietary supplements that you manufacture meet specifications.

[§ 111.315 What Are the Requirements for Laboratory Control
Processes?]{.underline}

You must establish and follow laboratory control processes that are
reviewed and approved by quality control personnel, including the
following:

\(a\) Use of criteria for establishing appropriate specifications;

\(b\) Use of sampling plans for obtaining representative samples, in
accordance with Subpart E, of:

\(1\) Components, packaging, and labels;

\(2\) In-process materials;

\(3\) Finished batches of dietary supplements;

\(4\) Product that you receive for packaging or labeling as a dietary
supplement (and for distribution rather than for return to the
supplier); and

\(5\) Packaged and labeled dietary supplements.

\(c\) Use of criteria for selecting appropriate examination and testing
methods;

\(d\) Use of criteria for selecting standard reference materials used in
performing tests and examinations; and

\(e\) Use of test methods and examinations in accordance with
established criteria.

[§ 111.320 What Requirements Apply to Laboratory Methods for Testing and
Examination?]{.underline}

\(a\) You must verify that the laboratory examination and testing
methodologies are appropriate for their intended use.

\(b\) You must identify and use an appropriate scientifically valid
method for each established specification for which testing or
examination is required to determine whether the specification is met.

[§ 111.325 Under This Subpart, What Records Must You Make and
Keep?]{.underline}

\(a\) You must make and keep records required under this subpart in
accordance with Subpart P.

\(b\) You must make and keep the following records:

\(1\) Written procedures for laboratory operations, including written
procedures for the tests and examinations that you conduct to determine
whether specifications are met;

\(2\) Documentation that laboratory methodology established in
accordance with this subpart is followed.

\(i\) The person who conducts the testing and examination must document,
at the time of performance, that laboratory methodology established in
accordance with this subpart is followed.

\(ii\) The documentation for laboratory tests and examinations must
include the results of the testing and examination; and

14\. Add §§ 111.353 through 111.375 to newly added subpart K to read as
follows:

Subpart K -- Production and Process Control System:

Requirements for Manufacturing Operations

§ 111.353 What Are the Requirements Under This Subpart for Written
Procedures?

§ 111.355 What Are the Design Requirements for Manufacturing Operations?

§ 111.360 What Are the Requirements for Sanitation?

§ 111.365 What Precautions Must You Take to Prevent Contamination?

§ 111.370 What Requirements Apply to Rejected Dietary Supplements?

§ 111.375 Under This Subpart, What Records Must You Make and Keep?

Subpart K -- Production and Process Control System:

Requirements for Manufacturing Operations

[§ 111.353 What Are the Requirements Under This Subpart for Written
Procedures?]{.underline}

You must establish and follow written procedures for manufacturing
operations.

[§ 111.355 What Are the Design Requirements for Manufacturing
Operations?]{.underline}

You must design or select manufacturing processes to ensure that product
specifications are consistently met.

[§ 111.360 What Are the Requirements for Sanitation?]{.underline}

You must conduct all manufacturing operations in accordance with
adequate sanitation principles.

[§ 111.365 What Precautions Must You Take to Prevent
Contamination?]{.underline}

You must take all the necessary precautions during the manufacture of a
dietary supplement to prevent contamination of components or dietary
supplements. These precautions include:

\(a\) Performing manufacturing operations under conditions and controls
that protect against the potential for growth of microorganisms and the
potential for contamination;

\(b\) Washing or cleaning components that contain soil or other
contaminants;

\(c\) Using water that, at a minimum, complies with the applicable
Federal, State, and local requirements and does not contaminate the
dietary supplement when the water may become a component of the finished
batch of dietary supplement;

\(d\) Performing chemical, microbiological, or other testing, as
necessary to prevent the use of contaminated components;

\(e\) Sterilizing, pasteurizing, freezing, refrigerating, controlling
hydrogen-ion concentration (pH), controlling humidity, controlling water
activity (aw), or using any other effective means to remove, destroy, or
prevent the growth of microorganisms and prevent decomposition;

\(f\) Holding components and dietary supplements that can support the
rapid growth of microorganisms of public health significance in a manner
that prevents the components and dietary supplements from becoming
adulterated;

\(g\) Identifying and holding any components or dietary supplements, for
which a material review and disposition decision is required, in a
manner that protects components or dietary supplements that are not
under a material review against contamination and mix-ups with those
that are under a material review;

\(h\) Performing mechanical manufacturing steps (such as cutting,
sorting, inspecting, shredding, drying, grinding, blending, and sifting)
by any effective means to protect the dietary supplements against
contamination, by, for example:

\(1\) Cleaning and sanitizing contact surfaces;

\(2\) Using temperature controls; and

\(3\) Using time controls.

\(i\) Using effective measures to protect against the inclusion of metal
or other foreign material in components or dietary supplements, by, for
example:

\(1\) Filters or strainers;

\(2\) Traps;

\(3\) Magnets; or

\(4\) Electronic metal detectors.

\(j\) Segregating and identifying all containers for a specific batch of
dietary supplements to identify their contents and, when necessary, the
phase of manufacturing; and

\(k\) Identifying all processing lines and major equipment used during
manufacturing to indicate their contents, including the name of the
dietary supplement and the specific batch or lot number and, when
necessary, the phase of manufacturing.

[§ 111.370 What Requirements Apply to Rejected Dietary
Supplements?]{.underline}

You must clearly identify, hold, and control under a quarantine system
for appropriate disposition any dietary supplement that is rejected and
unsuitable for use in manufacturing, packaging, or labeling operations.

[§ 111.375 Under This Subpart, What Records Must You Make and
Keep?]{.underline}

\(a\) You must make and keep records required under this subpart in
accordance with subpart P.

\(b\) You must make and keep records of the written procedures for
manufacturing operations.

15\. Add §§ 111.403 through 111.430 to newly added subpart L to read as
follows:

Subpart L -- Production and Process Control System:

Requirements for Packaging and Labeling Operations

§ 111.403 What Are the Requirements Under This Subpart for Written
Procedures?

§ 111.410 What Requirements Apply to Packaging and Labels?

§ 111.415 What Requirements Apply to Filling, Assembling, Packaging,
Labeling, and Related Operations?

§ 111.420 What Requirements Apply to Repackaging and Relabeling?

§ 111.425 What Requirements Apply to a Packaged and Labeled Dietary
Supplement That is Rejected for Distribution?

§ 111.430 Under This Subpart, What Records Must You Make and Keep?

Subpart L -- Production and Process Control System:

Requirements for Packaging and Labeling Operations

[§ 111.403 What Are the Requirements Under This Subpart for Written
Procedures?]{.underline}

You must establish and follow written procedures for packaging and
labeling operations.

[§ 111.410 What Requirements Apply to Packaging and Labels?]{.underline}

\(a\) You must take necessary actions to determine whether packaging for
dietary supplements meets specifications so that the condition of the
packaging will ensure the quality of your dietary supplements;

\(b\) You must control the issuance and use of packaging and labels and
reconciliation of any issuance and use discrepancies. Label
reconciliation is not required for cut or rolled labels if a 100 percent
examination for correct labels is performed by appropriate electronic or
electromechanical equipment during or after completion of finishing
operations; and

\(c\) You must examine, before packaging and labeling operations,
packaging and labels for each batch of dietary supplement to determine
whether the packaging and labels conform to the master manufacturing
record; and

\(d\) You must be able to determine the complete manufacturing history
and control of the packaged and labeled dietary supplement through
distribution.

[§ 111.415 What Requirements Apply to Filling, Assembling, Packaging,
Labeling, and Related Operations?]{.underline}

You must fill, assemble, package, label, and perform other related
operations in a way that ensures the quality of the dietary supplement
and that the dietary supplement is packaged and labeled as specified in
the master manufacturing record. You must do this using any effective
means, including the following:

\(a\) Cleaning and sanitizing all filling and packaging equipment,
utensils, and dietary supplement packaging, as appropriate;

\(b\) Protecting manufactured dietary supplements from contamination,
particularly airborne contamination;

\(c\) Using sanitary handling procedures;

\(d\) Establishing physical or spatial separation of packaging and label
operations from operations on other components and dietary supplements
to prevent mix-ups;

\(e\) Identifying, by any effective means, filled dietary supplement
containers that are set aside and held in unlabeled condition for future
label operations, to prevent mix-ups;

\(f\) Assigning a batch, lot, or control number to:

\(1\) each lot of packaged and labeled dietary supplement from a
finished batch of dietary supplement; and,

\(2\) each lot of dietary supplement, from a finished batch of dietary
supplement, that you distribute to another person for packaging or
labeling.

\(g\) Examining a representative sample of each batch of the packaged
and labeled dietary supplement to determine whether the dietary
supplement meets specifications established in accordance with §
111.70(g); and

\(h\) Suitably disposing of labels and packaging for dietary supplements
that are obsolete or incorrect to ensure that they are not used in any
future packaging and label operations.

[§ 111.420 What Requirements Apply to Repackaging and
Relabeling?]{.underline}

\(a\) You may repackage or relabel dietary supplements only after
quality control personnel have approved such repackaging or relabeling.

\(b\) You must examine a representative sample of each batch of
repackaged or relabeled dietary supplements to determine whether the
repackaged or relabeled dietary supplements meet all specifications
established in accordance with § 111.70(g).

\(c\) Quality control personnel must approve or reject each batch of
repackaged or relabeled dietary supplement prior to its release for
distribution.

[§ 111.425 What Requirements Apply to a Packaged and Labeled Dietary
Supplement That is Rejected for Distribution?]{.underline}

You must clearly identify, hold, and control under a quarantine system
for appropriate disposition any packaged and labeled dietary supplement
that is rejected for distribution.

[§ 111.430 Under This Subpart, What Records Must You Make and
Keep?]{.underline}

\(a\) You must make and keep records required under this subpart in
accordance with subpart P.

\(b\) You must make and keep records of the written procedures for
packaging and labeling operations.

16\. Add §§ 111.453 through 111.475 to newly added subpart M to read as
follows:

Subpart M - Holding and Distributing

§ 111.453 What Are the Requirements Under This Subpart for Written
Procedures?

§ 111.455 What Requirements Apply to Holding Components, Dietary
Supplements, Packaging, and Labels?

§ 111.460 What Requirements Apply to Holding In-process Material?

§ 111.465 What Requirements Apply to Holding Reserve Samples of Dietary
Supplements?

§ 111.470 What Requirements Apply to Distributing Dietary Supplements?

§ 111.475 Under This Subpart, What Records Must You Make and Keep?

Subpart M - Holding and Distributing

[§ 111.453 What Are the Requirements Under This Subpart for Written
Procedures?]{.underline}

You must establish and follow written procedures for holding and
distributing operations.

[§ 111.455 What Requirements Apply to Holding Components, Dietary
Supplements, Packaging, and Labels?]{.underline}

\(a\) You must hold components and dietary supplements under appropriate
conditions of temperature, humidity, and light so that the identity,
purity, strength, and composition of the components and dietary
supplements are not affected.

\(b\) You must hold packaging and labels under appropriate conditions so
that the packaging and labels are not adversely affected.

\(c\) You must hold components, dietary supplements, packaging, and
labels under conditions that do not lead to the mixup, contamination, or
deterioration of components, dietary supplements, packaging, and labels.

[§ 111.460 What Requirements Apply to Holding In-process
Material?]{.underline}

\(a\) You must identify and hold in-process material under conditions
that protect against mix-up, contamination, and deterioration.

\(b\) You must hold in-process material under appropriate conditions of
temperature, humidity, and light.

[§ 111.465 What Requirements Apply to Holding Reserve Samples of Dietary
Supplements?]{.underline}

\(a\) You must hold reserve samples of dietary supplements in a manner
that protects against contamination and deterioration. This includes:

\(1\) Holding the reserve samples under conditions consistent with
product labels or, if no storage conditions are recommended on the
label, under ordinary storage conditions; and

\(2\) Using the same container-closure system in which the packaged and
labeled dietary supplement is distributed, or if distributing dietary
supplements to be packaged and labeled, using a container-closure system
that provides essentially the same characteristics to protect against
contamination or deterioration as the one in which you distribute the
dietary supplement for packaging and labeling elsewhere.

\(b\) You must retain reserve samples for one year past the shelf life
date (if shelf life dating is used), or for 2 years from the date of
distribution of the last batch of dietary supplements associated with
the reserve samples, for use in appropriate investigations.

[§ 111.470 What Requirements Apply to Distributing Dietary
Supplements?]{.underline}

You must distribute dietary supplements under conditions that will
protect the dietary supplements against contamination and deterioration.

[§ 111.475 Under This Subpart, What Records Must You Make and
Keep?]{.underline}

\(a\) You must make and keep records required under this subpart in
accordance with Subpart P.

\(b\) You must make and keep the following records:

\(1\) Written procedures for holding and distributing operations; and

\(2\) Records of product distribution.

17\. Add §§ 111.503 through 111.535 to newly added subpart N to read as
follows:

Subpart N - Returned Dietary Supplements

§ 111.503 What Are the Requirements Under This Subpart for Written
Procedures?

§ 111.510 What Requirements Apply When a Returned Dietary Supplement is
Received?

§ 111.515 When Must a Returned Dietary Supplement Be Destroyed, or
Otherwise Suitably Disposed of?

§ 111.520 When May a Returned Dietary Supplement be Salvaged?

§ 111.525 What Requirements Apply to a Returned Dietary Supplement That
Quality Control Personnel Approve for Reprocessing?

§ 111.530 When Must an Investigation Be Conducted of Your Manufacturing
Processes and Other Batches?

§ 111.535 Under This Subpart, What Records Must You Make and Keep?

Subpart N - Returned Dietary Supplements

[§ 111.503 What Are the Requirements Under This Subpart for Written
Procedures?]{.underline}

You must establish and follow written procedures to fulfill the
requirements of this subpart.

[§ 111.510 What Requirements Apply When a Returned Dietary Supplement is
Received?]{.underline}

You must identify and quarantine returned dietary supplements until
quality control personnel conduct a material review and make a
disposition decision.

[§ 111.515 When Must a Returned Dietary Supplement Be Destroyed, or
Otherwise Suitably Disposed of?]{.underline}

\(a\) You must destroy, or otherwise suitably dispose of, any returned
dietary supplement unless the outcome of a material review and
disposition decision is that quality control personnel:

\(1\) Approve the salvage of the returned dietary supplement for
redistribution; or

\(2\) Approve the returned dietary supplement for reprocessing.

[§ 111.520 When May a Returned Dietary Supplement Be
Salvaged?]{.underline}

You may salvage a returned dietary supplement only if quality control
personnel conduct a material review and make a disposition decision to
allow the salvage.

[§ 111.525 What Requirements Apply to a Returned Dietary Supplement
That]{.underline} [Quality Control Personnel Approve for
Reprocessing?]{.underline}

\(a\) You must ensure that any returned dietary supplements that are
reprocessed meet all product specifications established in accordance
with § 111.70(e); and

\(b\) Quality control personnel must approve or reject the release for
distribution of any returned dietary supplement that is reprocessed.

[§ 111.530 When Must an Investigation Be Conducted of Your Manufacturing
Processes and Other Batches?]{.underline}

If the reason for a dietary supplement being returned implicates other
batches, you must conduct an investigation of your manufacturing
processes and each of those other batches to determine compliance with
specifications.

[§ 111.535 Under This Subpart, What Records Must You Make and
Keep?]{.underline}

\(a\) You must make and keep records required under this subpart in
accordance with Subpart P.

\(b\) You must make and keep the following records:

\(1\) Written procedures for fulfilling the requirements of this
subpart.

\(2\) Any material review and disposition decision on a returned dietary
supplement;

\(3\) The results of any testing or examination conducted to determine
compliance with product specifications established under § 111.70(e);
and,

\(4\) Documentation of the reevaluation by quality control personnel of
any dietary supplement that is reprocessed and the determination by
quality control personnel of whether the reprocessed dietary supplement
meets product specifications established in accordance with § 111.70(e).

18\. Add §§ 111.553 through 111.570 to newly added subpart O to read as
follows:

Subpart O - Product Complaints

§ 111.553 What Are the Requirements Under This Subpart for Written
Procedures?

§ 111.560 What requirements apply to the review and investigation of a
product complaint?

§ 111.570 Under This Subpart, What Records Must You Make and Keep?

Subpart O - Product Complaints

[§ 111.553 What Are the Requirements Under This Subpart for Written
Procedures?]{.underline}

You must establish and follow written procedures to fulfill the
requirements of this subpart.

[§ 111.560 What Requirements Apply to the Review and Investigation of a
Product Complaint?]{.underline}

\(a\) A qualified person must:

\(1\) Review all product complaints to determine whether the product
complaint involves a possible failure of a dietary supplement to meet
any of its specifications, or any other requirements of this part,
including those specifications and other requirements that, if not met,
may result in a risk of illness or injury; and

\(2\) Investigate any product complaint that involves a possible failure
of a dietary supplement to meet any of its specifications, or any other
requirements of this part, including those specifications and other
requirements that, if not met, may result in a risk of illness or
injury.

\(b\) Quality control personnel must review and approve decisions about
whether to investigate a product complaint and review and approve the
findings and follow-up action of any investigation performed.

\(c\) The review and investigation of the product complaint by a
qualified person, and the review by quality control personnel about
whether to investigate a product complaint, and the findings and
follow-up action of any investigation performed, must extend to all
relevant batches and records.

[§ 111.570 Under This Subpart, What Records Must You Make and
Keep?]{.underline}

\(a\) You must make and keep the records required under this subpart in
accordance with Subpart P.

\(b\) You must make and keep the following records:

\(1\) Written procedures for fulfilling the requirements of this
subpart.

\(2\) A written record of every product complaint that is related to
good manufacturing practice.

\(i\) The person who performs the requirements of this subpart must
document, at the time of performance, that the requirement was
performed.

\(ii\) The written record of the product complaint must include the
following:

\(A\) The name and description of the dietary supplement;

\(B\) The batch, lot, or control number of the dietary supplement, if
available;

\(C\) The date the complaint was received and the name, address, or
telephone number of the complainant, if available;

\(D\) The nature of the complaint including, if known, how the product
was used;

\(E\) The reply to the complainant, if any; and

\(F\) Findings of the investigation and follow-up action taken when an
investigation is performed.

19\. Add §§ 111.605 and 111.610 to newly added subpart P to read as
follows:

Subpart P - Records and Recordkeeping

§ 111.605 What Requirements Apply to the Records That You Make and Keep?

§ 111.610 What Records Must Be Made Available to FDA?

Subpart P - Records and Recordkeeping

[§ 111.605 What Requirements Apply to the Records You Make and
Keep?]{.underline}

\(a\) You must keep written records required by this part for one year
past the shelf life date, if shelf life dating is used, or 2 years
beyond the date of distribution of the last batch of dietary supplements
associated with those records.

\(b\) Records must be kept as original records, as true copies (such as
photocopies, microfilm, microfiche, or other accurate reproductions of
the original records), or as electronic records.

\(c\) All electronic records must comply with part 11 of this chapter.

[§ 111.610 What Records Must Be made Available to FDA?]{.underline}

\(a\) You must have all records required under this part, or copies of
such records, readily available during the retention period for
inspection and copying by FDA when requested.

\(b\) If you use reduction techniques, such as microfilming, you must
make suitable reader and photocopying equipment readily available to
FDA.

Dated: \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_

\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_

\[FR Doc. 05-????? Filed ??-??-05; 8:45 am\]

BILLING CODE 4160-01-S