5700 Federal Register / Vol. 62, No. 25 / Thursday, February 6, 1997 / Proposed Rules

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

21 CFR Ch. I

[Docket No. 96N–0417]

RIN 0910–AA59

Current Good Manufacturing Practice

in Manufacturing, Packing, or Holding

Dietary Supplements

AGENCY: Food and Drug Administration,

HHS.

ACTION: Advance notice of proposed

rulemaking.

SUMMARY: The Food and Drug

Administration (FDA) is announcing

that it is considering whether to

institute rulemaking to develop current

good manufacturing practice (CGMP)

regulations for dietary supplements and

dietary supplement ingredients. FDA

solicits comments on whether it should

do so, and if it should, what constitutes

CGMP for these products. In issuing this

notice, FDA is responding to the section

of the Federal Food, Drug, and Cosmetic

Act (the act) that provides that the

Secretary of Health and Human Services

(the Secretary) may, by regulation,

prescribe good manufacturing practice

for dietary supplements and to a

submission from representatives of the

dietary supplement industry asking

FDA to consider a framework that the

industry had developed as a basis for

CGMP regulations. FDA is publishing

the industry submission and is asking

for public comment on the framework

that the submission presents. In

addition, FDA is requesting comment on

a number of other related issues.

DATES: Written comments by May 7,

1997.

ADDRESSES: Submit written comments

to the Dockets Management Branch

(HFA–305), Food and Drug

Administration, 12420 Parklawn Dr.,

rm. 1–23, Rockville, MD 20857.

FOR FURTHER INFORMATION CONTACT:

Robert J. Moore, Center for Food Safety

and Applied Nutrition (HFS–456), Food

and Drug Administration, 200 C St. SW.,

Washington, DC 20204, 202–205–4605.

SUPPLEMENTARY INFORMATION:

I. Background

On October 25, 1994, the Dietary

Supplement Health and Education Act

(the DSHEA) (Pub. L. 103–417) was

signed into law. The DSHEA, among

other things, amended the act by adding

section 402(g) (21 U.S.C. 342(g)), which

provides, in part, that:

The Secretary may by regulation prescribe

good manufacturing practices for dietary

supplements. Such regulations shall be

modeled after current good manufacturing

practice regulations for food and may not

impose standards for which there is no

current and generally available analytical

methodology. No standard of current good

manufacturing practice may be imposed

unless such standard is included in a

regulation promulgated after notice and

opportunity for comment in accordance with

chapter 5 of title 5, United States Code.

While section 402(g) of the act does not

require that the Secretary (and by

delegation, FDA) adopt regulations that

prescribe CGMP, a significant segment

of the dietary supplement industry has

told the agency that such regulations

would be helpful for ensuring that

dietary supplements are safe for their

intended use.

On November 20, 1995,

representatives of the dietary

supplement industry submitted to FDA

a suggested outline for the development

of CGMP regulations for dietary

supplements. FDA evaluated the outline

and determined that it provided an

extremely useful starting point should

FDA decide to proceed to rulemaking to

adopt such regulations. However, the

agency recognizes that the first question

that must be addressed is whether there

is a need for such regulations or

whether part 110 (21 CFR part 110)

continues to be adequate. The agency

also recognizes that if it decides that

there is a need for CGMP regulations,

certain issues were not addressed in the

submission, and that other interested

parties, such as consumers, segments of

the industry not represented by the

manufacturers and trade associations

who submitted the outline, and the

health care community, should have an

opportunity to provide comment before

the agency developed a proposal.

Therefore, the agency is issuing this

notice to solicit comments and other

information on whether it should

propose new CGMP regulations for

dietary supplements and, if it should,

what those regulations should include.

Based on the submission and the

comments that the agency receives in

response to this notice, FDA will

consider whether to develop a proposed

rule that is designed to establish CGMP

that will ensure that dietary

supplements are produced under

conditions that will result in a safe and

properly labeled product but that does

not impose any unnecessary burden on

the industry.

II. The Industry Submission

A. Introduction

On November 30, 1995, FDA met with

representatives of the dietary

supplement industry at their request

(Ref. 1). At that meeting, the industry

representatives submitted a document

that outlined suggested CGMP for

dietary supplements (Ref. 2). The

objectives of the CGMP, as stated by the

industry representatives, are to ensure

that consumers are provided with

dietary supplement products that: (1)

Are safe and not adulterated or

misbranded; (2) have the identity and

provide the quantity of dietary

ingredients declared in labeling; and (3)

meet the quality specifications that the

supplement is represented to meet. The

industry submission was patterned after

the CGMP for food regulation contained

in part 110, but also contained

requirements beyond those in part 110

that the industry representatives stated

that they ‘‘consider essential to the

manufacture of safe and properly

labeled dietary supplements.’’ FDA is

publishing the industry suggested

dietary supplements CGMP and

soliciting comments from industry,

consumers, and other interested parties

on the need for dietary supplement

CGMP regulations and on the

requirements that should be included in

such regulations.

B. The Industry Draft

The text of the industry suggested

dietary supplements CGMP follows:

Good Manufacturing Practices (GMP’s) for

Dietary Supplements: Statement of Purpose

This document describes Good

Manufacturing Practices to be followed in the

manufacturing and control operations for

dietary supplements and dietary ingredients.

The objective of these Good Manufacturing

Practices is to assure that consumers are

provided with safe dietary supplement

products which are not adulterated or

misbranded, which have the identity and

provide the quantity of dietary ingredients

declared in labeling, and which meet the

quality specifications that the supplement is

represented to meet.

The Food, Drug, and Cosmetic Act defines

dietary supplements in section 201(ff).

Dietary supplements include a broad

spectrum of product forms and a broad

spectrum of dietary ingredients. Dietary

ingredients may include vitamins; minerals;

herbs or other botanicals; amino acids; other

dietary substances used to supplement the

diet; and concentrates, metabolites,

constituents, extracts, or combinations of

these. Product forms include tablets,

capsules, softgels, gelcaps, liquids, and other

forms including—under some conditions—

conventional food forms. These Good

Manufacturing Practices are intended to

encompass all of these types of products. In

some cases, judgment may be required in

determining the applicability of a specific

provision to a particular product or class of

products.

Dietary supplements in the physical form

of conventional food shall comply with these
Federal Register / Vol. 62, No. 25 / Thursday, February 6, 1997 / Proposed Rules 5701

Good Manufacturing Practices and with

applicable food GMP’s. For example, if they

are thermally processed low-acid products

packaged in hermetically sealed containers,

they shall also comply with the applicable

GMP’s covering that product category.

These Good Manufacturing Practices are

modeled after good manufacturing practices

for foods. Provisions have been adopted,

modified, or expanded as appropriate,

considering the special requirements

applicable to the manufacture of dietary

supplements and dietary ingredients. There

is no desire or intent to impose on dietary

supplements the type of documentation and

validation currently required in the

manufacture of pharmaceutical products,

where it would be inappropriate or

unnecessary to ensure safe and unadulterated

products. Dietary supplements are classified

as foods, and the Good Manufacturing

Practices applicable to them are similar to

those generally applicable to other foods.

Proposed Supplement GMP

Definitions

The definitions and interpretations of

terms in section 201 of the Federal Food,

Drug, and Cosmetic Act (the act) are

applicable to such terms when used in this

part. The following definitions shall also

apply:

(a) ‘‘Adequate’’ means that which is

needed to accomplish the intended purpose

in keeping with good public health practice.

(b) ‘‘Batch or Lot’’ means a specific

quantity of a finished product or other

material that is intended to have uniform

character and quality, within specified limits,

and is produced according to a single

manufacturing order during the same cycle of

manufacture.

(c) ‘‘Blanching’’ means a prepackaging heat

treatment of a dietary product for a sufficient

time and at a sufficient temperature to

partially or completely inactivate the

naturally occurring enzymes and to effect

other physical or biochemical changes in the

product.

(d) ‘‘Composition’’ means, as appropriate:

(1) the identity of a dietary ingredient or

dietary supplement, and

(2) the concentration of a dietary ingredient

(e.g., weight or other unit of use/weight

or volume), or the potency or activity of

one or more dietary ingredients, as

indicated by appropriate procedures.

(e) ‘‘Dietary ingredient’’ means an

ingredient intended for use or used in a

dietary supplement that is:

(1) a vitamin,

(2) a mineral,

(3) an herb or other botanical,

(4) an amino acid,

(5) a dietary substance for use by man to

supplement the diet by increasing the

total dietary intake, or

(6) a concentrate, metabolite, constituent,

extract, or combination of any of the

foregoing ingredients.

(f) ‘‘Dietary product’’ means either a

dietary ingredient or dietary supplement as

defined in this Part.

(g) ‘‘Dietary supplement’’ means dietary

supplement as defined in section 201(ff) of

the act.

(h) ‘‘In-process material’’ means any

material fabricated, compounded, blended,

ground, extracted, sifted, sterilized, derived

by chemical reaction or processed in any

other way that is produced for, and used in,

the preparation of a dietary product.

(i) ‘‘Lot’’ means ‘‘batch’’ as defined in this

part.

(j) ‘‘Lot number’’ means any distinctive

combination of letters, numbers, or symbols,

or any combination of them from which the

complete history of the manufacture,

processing, packing, holding, and

distribution of a batch or lot of a finished

dietary ingredient, dietary supplement or

other material can be determined.

(k) ‘‘Manufacture’’ or ‘‘manufacturing’’

includes all operations associated with the

production of dietary products, including

packaging and labeling operations, testing,

and quality control of a dietary ingredient or

dietary supplement.

(l) ‘‘Microorganisms’’ means yeasts, molds,

bacteria, and viruses and includes, but is not

limited to, species having public health

significance. The term ‘‘undesirable

microorganisms’’ includes those

microorganisms that are of public health

significance, that subject food to

decomposition, that indicate that a dietary

ingredient or dietary supplement is

contaminated with filth, or that otherwise

may cause a dietary product to be adulterated

within the meaning of the act. Occasionally

in these regulations, the adjective

‘‘microbial’’ is used instead of using an

adjectival phrase containing the word

microorganism.

(m) ‘‘Pest’’ refers to any objectionable

animals or insects including, but not limited

to, bird, rodents, flies, and larvae.

(n) ‘‘Plant’’ means the building or facility

or parts thereof, used for or in connection

with the manufacturing, packaging, labeling,

or holding of a dietary product.

(o) ‘‘Quality control operation’’ means a

planned and systematic procedure for taking

all actions necessary to prevent a dietary

product from being adulterated within the

meaning of the act.

(p) ‘‘Quality control unit’’ means any

person or organizational element designated

by the firm to be responsible for the duties

relating to quality control operations.

(q) ‘‘Raw material’’ means any ingredient

intended for use in the manufacture of a

dietary ingredient or dietary supplement,

including those that may not appear in such

finished product.

(r) ‘‘Representable sample’’ means a sample

that consists of a number of units that are

drawn based on rational criteria, such as

random sampling, and is intended to assure

that the sample accurately portrays the

material being sampled.

(s) ‘‘Rework’’ means clean, unadulterated

material that has been removed from

processing for reasons other than insanitary

conditions or that has been successfully

reconditioned by reprocessing and that is

suitable for use in the manufacture of a

dietary product.

(t) ‘‘Sanitize’’ means to adequately treat

equipment, containers, or utensils by a

process that is effective in destroying

vegetative cells of microorganisms of public

health significance, and in substantially

reducing numbers of other undesirable

microorganisms, but without adversely

affecting the product or its safety for the

consumer.

(u) ‘‘Shall’’ is used to state mandatory

requirements.

(v) ‘‘Should’’ is used to state recommended

or advisory procedures or identify

recommended equipment.

(w) ‘‘Water activity (aw)’’ is a measure of

the free moisture in a dietary ingredient 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.

Personnel

The plant management shall take all

reasonable measures and precautions to

assure the following:

(a) Disease control. Any person who, by

medical examination or supervisory

observation, is shown to have, or appears to

have, an illness, open lesion, including boils,

sores, or infected wounds, or any other

abnormal source of microbial contamination

by which there is a reasonable possibility of

an in-process or finished dietary product

becoming adulterated, or processing

equipment, utensils or packaging materials

becoming contaminated, shall be excluded

from any operations which may be expected

to result in such adulteration or

contamination until the condition is

corrected. Personnel shall be instructed to

report such health conditions to their

supervisors.

(b) Cleanliness. All persons working in

direct contact with raw materials, in-process

or finished dietary products, processing

equipment, utensils or packaging materials

shall conform to hygienic practices while on

duty to the extent necessary to protect against

adulteration or contamination of such

materials. The methods for maintaining

cleanliness include, but are not limited to:

(1) Wearing outer garments suitable to the

operation in a manner that protects

against the adulteration of in-process or

finished dietary products, or

contamination of processing equipment,

utensils or packaging materials.

(2) Maintaining adequate personal

cleanliness.

(3) Washing hands thoroughly (and

sanitizing if necessary to protect against

contamination with undesirable

microorganisms) in an adequate handwashing facility before starting work,

after each absence from the work station,

and at any other time when the hands

may have become soiled or

contaminated.

(4) Removing all unsecured jewelry and

other objects that might fall into raw

materials, in-process or finished dietary

product, equipment, or containers, and

removing hand jewelry that cannot be

adequately sanitized during periods in

which in-process or finished product is

manipulated by hand. If such hand

jewelry cannot be removed, it may be

covered by material which can be

maintained in an intact, clean, and

sanitary condition and which effectively
5702 Federal Register / Vol. 62, No. 25 / Thursday, February 6, 1997 / Proposed Rules

protects against the adulteration of

dietary products or contamination of

processing equipment, utensils or

packaging materials.

(5) Maintaining gloves, if they are used inprocess or finished product handling, in

an intact, clean, and sanitary condition.

The gloves should be of a material that

adequately protects the product from

contamination.

(6) Wearing, where appropriate, in an

effective manner, hair nets, caps, beard

covers, or other effective hair restraints.

(7) Storing clothing or other personal

belongings in areas other than where inprocess or finished product is exposed or

where processing equipment or utensils

are washed.

(8) Confining the following to areas other

than where in-process or finished

product may be stored or exposed, or

where processing equipment or utensils

are washed: eating food, chewing gum,

drinking beverages, or using tobacco.

(9) Taking any other necessary precautions

to protect against adulteration of raw

materials, in-process or finished product,

or contamination of processing

equipment, utensils or packaging

materials with micro-organisms or

foreign substances including, but not

limited to, perspiration, hair, cosmetics,

tobacco, chemicals, and medicines

applied to the skin.

(c) Education and training. Each person

engaged in the manufacture of a dietary

product should have the proper education,

training, and experience (or any combination

thereof) needed to perform the assigned

functions. Training should be in the

particular operation(s) that the employee

performs as they relate to the employee’s

functions. Appropriate documentation of

training shall be retained by the

manufacturer.

(d) Supervision. Responsibility for assuring

compliance by all personnel with all

requirements of this part shall be clearly

assigned to qualified personnel with proper

education, training and experience (or any

combination thereof).

Exclusions

The following operations are not subject to

this part: Establishments engaged solely in

the harvesting, storage, or distribution of one

or more ‘‘raw agricultural commodities,’’ as

defined in section 201(r) of the act, which are

ordinarily cleaned, prepared, treated, or

otherwise processed before being marketed to

the consuming public.

Plant and Grounds

(a) Grounds. The grounds about a dietary

product manufacturing plant under the

control of the operator shall be kept in a

condition that will protect against the

adulteration of dietary products. The

methods for adequate maintenance of

grounds include, but are not limited to:

(1) Properly storing equipment, removing

litter and waste, and cutting weeds or

grass within the immediate vicinity of

the plant buildings or structures that

may constitute an attractant, breeding

place, or harborage for pests.

(2) Maintaining roads, yards, and parking

lots so that they do not constitute a

source of adulteration in areas where

product is exposed.

(3) Adequately draining areas that may

contribute to product adulteration by

seepage, foot-borne filth, or providing a

breeding place for pests.

(4) Operating systems for waste treatment

and disposal in an adequate manner so

that they do not constitute a source of

adulteration in areas where product is

exposed. If the plant grounds are

bordered by grounds not under the

operator’s control and not maintained in

the manner described in paragraph (a)(1)

through (3) of this section, care shall be

exercised in the plant by inspection,

extermination, or other means to exclude

pests, dirt, and filth that may be a source

of product adulteration.

(b) Plant construction and design. Plant

buildings and structures shall be suitable in

size, construction. and design to facilitate

maintenance, cleaning and sanitary

operations for dietary product manufacturing

purposes and to prevent mixups between

different raw materials and products. The

plant and facilities shall:

(1) Provide sufficient space for such

placement of equipment and storage of

materials as is necessary for the

prevention of mixups, maintenance of

sanitary operations and the production

of safe dietary products.

(2) Permit the taking of proper precautions

to reduce the potential for mixups or

adulteration of in-process or finished

dietary product, or contamination of

processing equipment, utensils or

packaging materials with

microorganisms, chemicals, filth, or

other extraneous material. The potential

for mixups and product adulteration may

be reduced by adequate product safety

controls and operating practices or

effective design, including the separation

of operations in which contamination is

likely to occur, by one or more of the

following means: Location, time,

partition, air flow, enclosed systems, or

other effective means.

(3) Permit the taking of proper precautions

to protect dietary ingredients or dietary

supplements in outdoor bulk

fermentation vessels by any effective

means, including:

(i) Using protective coverings.

(ii) Controlling areas over and around the

vessels to eliminate harborages for pests.

(iii) Checking on a regular basis for pests

and pest infestation.

(iv) Skimming the fermentation vessels, as

necessary.

(4) Be constructed in such a manner that

floors, walls, and ceilings may be

adequately cleaned and kept clean and

kept in good repair; that drip or

condensate from fixtures, ducts and

pipes does not adulterate raw materials,

in-process or finished dietary products,

or contaminate product containers,

utensils or packaging materials; and that

aisles or working spaces are provided

between equipment and walls and are

adequately unobstructed and of adequate

width to permit employees to perform

their duties and to protect against

adulterating in-process or finished

product, or contaminating processing

equipment with clothing or personal

contact.

(5) Provide adequate lighting in handwashing areas, dressing and locker

rooms, and toilet rooms and in all areas

where product is examined, processed,

or stored and where equipment or

utensils are cleaned; and provide safetytype light bulbs, fixtures, sky-lights, or

other glass suspended over exposed

product in any step of preparation or

otherwise protect against product

adulteration in case of glass breakage.

(6) Provide adequate ventilation or control

equipment to maintain adequate control

over microorganisms, dust, humidity,

and temperature, when appropriate, for

the manufacture of dietary products; to

minimize odors and vapors (including

steam and noxious fumes) in areas where

they may adulterate dietary products;

and locate and operate fans and other

air-blowing equipment in a manner that

minimizes the potential for adulterating

raw materials, in-process or finished

dietary products, or contaminating

processing equipment, utensils or

packaging materials.

(7) Provide, where necessary, adequate

screening or other protection against

pests.

Sanitation of Buildings and Facilities

(a) General maintenance. Buildings,

fixtures, and other physical facilities of the

plant shall be maintained in a sanitary

condition and shall be kept in repair

sufficient to prevent raw materials, inprocess or finished dietary products from

becoming adulterated within the meaning of

the act.

(b) Cleaning and sanitizing materials.

(1) Cleaning compounds and sanitizing

agents used in cleaning and sanitizing

procedures shall be free from

undesirable microorganisms and shall be

safe and adequate under the conditions

of use. Compliance with this

requirement may be verified by any

effective means including purchase of

these substances under a supplier’s

guarantee or certification, or examination

of these substances for contamination.

Only the following toxic materials may

be used or stored in a plant where

product is processed or exposed:

(i) Those required to maintain clean and

sanitary conditions;

(ii) Those necessary for use in laboratory

testing procedures;

(iii) Those necessary for plant and

equipment maintenance and operation;

and

(iv) Those necessary for use in the plant’s

operations.

(2) Toxic cleaning compounds, sanitizing

agents, and pesticide chemicals shall be

identified, used, held, and stored in a

manner that protects against adulteration

of raw materials, in-process or finished

product, or contamination of processing

equipment or packaging materials. All
Federal Register / Vol. 62, No. 25 / Thursday, February 6, 1997 / Proposed Rules 5703

relevant regulations promulgated by

other Federal, State, and local

government agencies for the application,

use or holding of these products should

be followed. Rodenticides, insecticides,

and fungicides should be registered and

used in accordance with the Federal

Insecticide, Fungicide, and Rodenticide

Act.

(c) Pest control. No pests shall be allowed

in any area of a dietary product

manufacturing plant. Effective measures shall

be taken to exclude pests from the processing

areas and to protect against the adulteration

of product on the premises by pests. The use

of insecticides or rodenticides is permitted

only under precautions and restrictions that

will protect against the adulteration of raw

materials, in-process or finished product, or

contamination of processing equipment,

utensils or packaging materials.

(d) Water supply. Potable water at a

suitable temperature, and under pressure as

needed, shall be provided in all areas where

required for the processing of dietary

products, for the cleaning of processing

equipment, utensils, and packaging

materials, or for employee sanitary facilities.

Any water that contacts in-process or

finished dietary products, utensils or

processing equipment shall meet the

standards prescribed in the Environmental

Protection Agency’s Primary Drinking Water

Regulations (40 CFR part 141).

(e) Plumbing. Plumbing shall be of

adequate size and design and adequately

installed and maintained to:

(1) Carry sufficient quantities of water to

required locations throughout the plant.

(2) Properly convey sewage and liquid

disposable waste from the plant.

(3) Avoid constituting a source of

adulteration to product, or

contamination of water supplies,

processing equipment, or utensils or

creating an unsanitary condition.

(4) Provide adequate floor drainage or other

appropriate means of water removal 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.

(5) Provide that there is not backflow from,

or crossconnection between, piping

systems that discharge waste water or

sewage and piping systems that carry

water used for the manufacture of dietary

products.

(f) Sewage disposal. Sewage disposal shall

be made into an adequate sewerage system or

disposed of through other adequate means.

(g) Toilet facilities. Each plant shall

provide its employees with adequate, readily

accessible toilet facilities. Compliance with

this requirement may be accomplished by:

(1) Maintaining the facilities in a sanitary

condition.

(2) Keeping the facilities in good repair at

all times.

(3) Providing self-closing doors.

(4) Providing doors that do not open into

areas where dietary product is exposed

to airborne contamination, except where

alternate means have been taken to

protect against such contamination (such

as double doors or positive air-flow

systems).

(h) Hand-washing facilities. Hand-washing

facilities shall be adequate and convenient

and be furnished with running water at a

suitable temperature. Compliance with this

requirement may be accomplished by

providing:

(1) Hand-washing and, where appropriate,

hand-sanitizing facilities at each location

in the plant where good sanitary

practices require employees to wash

and/or sanitize their hands.

(2) Effective hand-cleaning and sanitizing

preparations.

(3) Air driers, sanitary towel service or

suitable drying devices.

(4) Devices or fixtures, such as water

control valves, so designed and

constructed to protect against

recontamination of clean, sanitized

hands.

(5) Readily understandable signs directing

employees handling unprotected

product, packaging materials, utensils or

processing equipment to wash and,

where appropriate, sanitize their hands

before they start work, after each absence

from post of duty, and when their hands

may have become soiled or

contaminated. These signs may be

posted in the processing room(s) and in

all other areas where employees may

handle such products, materials, utensils

or equipment.

(6) Refuse receptacles that are constructed

and maintained in a manner that protects

against adulteration of dietary products.

(i) Rubbish disposal. Rubbish shall be so

conveyed, stored, and disposed of as to

minimize the development of odor, minimize

the potential for the waste becoming an

attractant and harborage or breeding place for

pests, and protect against adulteration of raw

materials, in-process or finished dietary

products, or contamination of utensils,

processing equipment, water supplies, and

ground surfaces.

(j) Supervision. Overall sanitation of the

plant shall be under the supervision of one

or more individuals qualified by education,

experience and training (or any combination

thereof) assigned responsibility for assuring

that sanitation procedures are accomplished.

Equipment and Utensils

(a) Design and construction.

(1) All plant equipment and utensils shall

be so designed and of such material and

workmanship as to be adequately

cleanable, and shall be properly

maintained.

(2) The design, construction and use of

equipment and utensils shall preclude

the adulteration of raw materials,

packaging materials, in-process materials

or finished product with lubricants, fuel,

metal fragments, contaminated water, or

any other contaminants.

(3) All equipment should be so installed

and maintained as to facilitate the

cleaning of the equipment and of all

adjacent spaces. Processing equipment

and utensils shall be corrosion-resistant

when in contact with raw materials, inprocess or finished dietary product. They

shall be made of nontoxic materials and

designed to withstand the environment

of their intended use and the action of

dietary products, and, if applicable,

cleaning compounds and sanitizing

agents. Processing equipment and

utensils shall be maintained to protect

dietary products from being adulterated

by any source.

(4) Seams on utensils and processing

equipment shall be smoothly bonded or

maintained so as to minimize

accumulation of product, dirt, and

organic matter and thus minimize the

opportunity for growth of

microorganisms.

(5) Equipment that is in the manufacturing

or product handling area and that does

not come into contact with a dietary

product shall be so constructed that it

can be kept in a clean condition.

(6) Holding, conveying, and manufacturing

systems, including gravimetric,

pneumatic, closed, and automated

systems, shall be of a design and

construction that enables them to be

maintained in an appropriate clean

condition.

(7) Each freezer and cold storage

compartment used to store and hold a

dietary product capable of supporting

growth of microorganisms shall be fitted

with an indicating thermometer,

temperature-measuring device, or

temperature-recording device so

installed as to show the temperature

accurately within the compartment, and

should be fitted with an automatic

control for regulating temperature or

with an automatic alarm system to

indicate a significant temperature change

in a manual operation.

(8) Instruments and controls used in the

manufacture, processing, packing or

holding dietary products, including

instruments and controls used for

measuring, regulating, or recording

temperatures, pH, acidity, water activity,

or other conditions that control or

prevent the growth of undesirable

microorganisms in such products shall

be accurate and adequately maintained,

and adequate in number for their

designated uses.

(9) Compressed air or other gases

mechanically introduced into a dietary

product or used to clean equipment or

utensils shall be treated in such a way

that dietary ingredients or dietary

supplements are not adulterated.

(b) Sanitation of equipment and utensils.

(1) Cleaning and sanitizing of utensils and

equipment shall be conducted in a

manner that protects against adulteration

of raw materials, in-process or finished

dietary product, processing equipment,

utensils or packaging materials.

(2) All utensils and processing equipment

shall be cleaned as frequently as

necessary to protect against product

adulteration.

(3) Utensils and processing equipment

used for manufacturing or holding of dry

dietary products shall be in a dry,

sanitary condition at the time of use.

When the surfaces are wet-cleaned, they

shall, when necessary, be sanitized and

thoroughly dried before subsequent use.
5704 Federal Register / Vol. 62, No. 25 / Thursday, February 6, 1997 / Proposed Rules

(4) In wet processing, when cleaning is

necessary to protect against the

introduction of microorganisms into a

dietary product, all utensils and

processing equipment shall be cleaned

and sanitized as appropriate before use

and after any interruption during which

the utensils or processing equipment

may have become contaminated. Where

equipment and utensils are used in a

continuous production operation or in

back-to-back operations involving

different batches of the same products,

the utensils and product-contact surfaces

of the equipment shall be cleaned and

sanitized as appropriate.

(5) Nonproduct-contact surfaces of

equipment should be cleaned as

frequently as necessary to protect against

product adulteration.

(6) Single-service articles (such as utensils

intended for one-time use, paper cups,

and paper towels) should be stored in

appropriate containers and shall be

handled, dispensed, used, and disposed

of in a manner that protects against

adulteration of dietary products, and

contamination of utensils and processing

equipment.

(7) Sanitizing agents shall be adequate and

safe under conditions of use. Any

facility, procedure, or machine is

acceptable for cleaning and sanitizing

equipment and utensils if it is

established that the facility, procedure,

or machine will routinely render

equipment and utensils clean and

provide adequate cleaning and sanitizing

treatment.

(8) Cleaned and sanitized portable

equipment with product-contact surfaces

and utensils should be stored in a

location and manner that protects

product-contact surfaces from

contamination.

(9) Equipment and utensils and finished

product containers shall be maintained

in an acceptable condition through

appropriate cleaning and sanitizing, as

necessary. Insofar as necessary,

equipment shall be taken apart for

thorough cleaning.

(10) Written procedures shall be

established and followed for cleaning

and maintaining equipment and utensils

used in the manufacture of dietary

products.

(11) A written record of major equipment

cleaning and use shall be maintained in

individual equipment logs that show the

date, product and lot number of each

batch processed. The persons performing

the cleaning shall record in the log that

the work was performed. Entries in the

log should be in chronological order.

(12) Equipment, containers, and utensils

used to convey, hold, or store raw

materials, in-process material, rework, or

finished product shall be constructed,

handled, and maintained during

manufacturing or storage in a manner

that protects against contamination.

Quality Control and Laboratory Operations

Appropriate quality control operations

shall be employed to assure that dietary

products conform to appropriate standards of

purity, quality and composition, and that

packaging materials are safe and suitable for

their intended purpose.

(a) Quality control unit.

(1) There shall be a quality control unit

that has the responsibility and authority

to:

(i) Approve or reject all procedures,

specifications, controls, tests and

examinations, or deviations from them,

that impact the purity, quality and

composition of a dietary ingredient or

dietary supplement;

(ii) Approve or reject all raw materials,

packaging materials labeling, and

finished dietary products, including

products manufactured. processed,

packed, or held under contract by

another company, based on adequate

determination of conformance to

established specifications; and

(iii) Assure that completed production

records are reviewed as appropriate.

Quality control shall be responsible for

evaluation of errors committed in the

manufacture of a product and shall have

the final authority to determine if the

error may be corrected in such manner

that the product can be approved for

distribution or must be destroyed. Such

evaluations and their resolution must be

documented and maintained with and/or

cross referenced in the batch production

record.

(2) Adequate laboratory facilities should be

available, as needed, to the quality

control unit.

(3) The responsibilities and procedures

applicable to the quality control unit

shall be established in writing and

followed.

(b) Laboratory records. Laboratory records

shall be maintained and shall include

complete data derived from all specified

tests.

(c) Expiration dating.

(1) Whenever a dietary ingredient or

dietary supplement bears an expiration

date, such date shall be supported by

data and rationale to reasonably assure

that the product meets established

specifications at the expiration date.

(2) Appropriate accelerated stability

studies or data from similar product

formulations may be used for an initial

determination of shelf life. Product shelf

life shall be confirmed and may be

extended on the basis of real time studies

on product stored under labeled storage

conditions.

Production and Process Controls

(a) Master production and control records.

(1) To assure uniformity from batch to

batch, a master production and control

record shall be prepared for the

manufacture of each dietary ingredient

and dietary supplement, and shall be

reviewed and approved by the quality

control unit.

(2) Master production and control records

shall include, as appropriate.

(i) A complete list of raw materials used in

the manufacture of a dietary product,

designated by names or codes

sufficiently specific to indicate any

special quality characteristic(s).

(ii) An accurate statement of the weight or

measure of each raw material used in the

manufacture of a dietary product. Each

batch shall be formulated with the intent

to provide not less than 100 percent of

each claimed dietary ingredient.

(iii) For dietary supplements, the name and

weight or measure of each dietary

ingredient per unit or portion or per unit

of weight or measure of the supplement.

(iv) A statement concerning any calculated

excess of dietary ingredient contained in

a dietary supplement.

(v) A statement of the total weight or

measure of any dietary supplement unit.

(vi) A statement of theoretical weight or

measure of a dietary ingredient or dietary

supplement expected at the conclusion

of manufacture, including the maximum

and minimum percentages of theoretical

yield beyond which investigation is

required.

(vii) A description of the product

container(s), closure(s), and other

packaging materials, including positive

identification of all labeling used.

(viii) Manufacturing and control

instructions, designed to assure that the

dietary product has the purity,

composition, and quality it is

represented to possess.

(b) Batch production and control records.

(1) Individual batch production and

control records shall be prepared and

followed for each batch of dietary

product produced and shall include

complete information relating to the

production and control of each batch.

(2) These records shall be an accurate

reproduction of the appropriate master

production and control record and shall

include documentation that each

significant step in the manufacture,

processing, packing, or holding of the

batch was accomplished, including:

(i) Dates;

(ii) Identity of individual major equipment

and lines used;

(iii) Specific identification, including lot

number, of each raw material or inprocess material used;

(iv) Weight or measure of each raw

material used in the course of

processing;

(v) Quality control results;

(vi) Inspection of the packaging and

labeling area;

(vii) A statement of the actual yield at the

conclusion of manufacture and a

statement of the percentage of theoretical

yield, as appropriate;

(viii) Label control records, including

specimens, copies, or records of all

labels used;

(ix) Description of product containers and

closures used; and

(x) Any special notes of investigations or

deviations from the described process.

(3) Any deviation from written, approved

specifications, standards, test

procedures, or other laboratory control

mechanisms shall be recorded and

justified.

(c) Handling and storage of raw materials,

in-process materials and rework.
Federal Register / Vol. 62, No. 25 / Thursday, February 6, 1997 / Proposed Rules 5705

(1) Raw materials, in-process materials and

rework shall be inspected and segregated

or otherwise handled as necessary to

ascertain that they are clean and suitable

for processing into dietary products and

shall be stored under conditions that will

protect against adulteration and

minimize deterioration.

Containers of raw materials should be

inspected on receipt to assure that their

condition has not contributed to the

adulteration or deterioration of the

contents.

Liquid or dry raw materials and other

ingredients received and stored in bulk

form shall be held in a manner that

protects against contamination.

(2) Raw agricultural materials that contain

soil or other contaminants shall be

washed or cleaned as necessary. Water

used for washing, rinsing, or conveying

raw agricultural materials shall be safe

and of adequate sanitary quality.

Notwithstanding the general requirement

for potable water, water may be reused

for washing, rinsing, or conveying raw

agricultural materials, if it does not

increase the level of contamination of the

such materials.

(3) Raw materials, in-process materials,

and rework shall be held in bulk, or in

containers designed and constructed so

as to protect against adulteration and

shall be held at such temperature and

relative humidity and in such a manner

as to prevent a dietary ingredient or

dietary supplement from becoming

adulterated within the meaning of the

act. Material scheduled for rework shall

be identified as such.

(4) Frozen raw materials and other

ingredients shall be kept frozen. If

thawing is required prior to use, it shall

be done in a manner that prevents the

raw materials and other ingredients from

becoming adulterated within the

meaning of the act.

(5) Written procedures shall be established

and followed describing the receipt,

identification, examination, handling,

sampling, testing and approval or

rejection of raw materials.

(6) Each lot of raw material shall be

identified with a distinctive lot number

and shall be appropriately controlled

according to its status (e.g., quarantined,

approved, rejected).

(7) Raw material samples shall be

examined and tested as follows:

(i) Each lot of raw material, in-process

material, and rework that is liable to

adulteration with filth, insect infestation,

or other visually evident extraneous

material shall be examined against

established specifications for such

adulteration, and shall comply with any

applicable Food and Drug

Administration regulations and

guidelines. In lieu of such examination

by the manufacturer, a guarantee or

certification of examination may be

accepted from the supplier of a

component provided that the

manufacturer establishes the reliability

of the supplier’s examination.

(ii) Each lot of a raw material that is liable

to microbiological contamination that is

objectionable in view of its intended use

shall be subjected to microbiological

tests before use. Raw materials shall

either not contain levels of

microorganisms that may produce food

poisoning or other disease in humans, or

they shall be otherwise treated during

manufacturing operations so that they no

longer contain levels that would cause

the product to be adulterated within the

meaning of the act. In lieu of such testing

by the manufacturer, a guarantee or

certification of analysis may be accepted

from the supplier of a component

provided that the manufacturer

establishes the reliability of the

supplier’s analyses.

(iii) Raw materials and other ingredients

susceptible to adulteration with aflatoxin

or other natural toxins shall comply with

current Food and Drug Administration

regulations, guidelines, and action levels

for poisonous or deleterious substances

before these materials or ingredients are

incorporated into a finished dietary

ingredient or dietary supplement.

Compliance with this requirement may

be accomplished by analyzing these

materials and ingredients for aflatoxins

and other natural toxins or, in lieu of

such testing by the manufacturer, a

guarantee or certification of analysis may

be accepted from the supplier of a

component provided that the

manufacturer establishes the reliability

of the supplier’s analyses.

(iv) Each lot of raw material shall undergo

at least one test by the manufacturer to

verify its identity. Such tests may

include any appropriate test with

sufficient specificity to determine

identity, including chemical and

laboratory tests, gross organoleptic

analysis, microscopic identification, or

analysis of constituent markers.

(v) Each lot of raw material shall be tested

for conformity with all other established

specifications. In lieu of such testing by

the manufacturer, a guarantee or

certification of analysis may be accepted

from the supplier of a component

provided that the manufacturer

establishes the reliability of the

supplier’s analyses.

(8) Approved raw materials shall be rotated

so that the oldest approved stock is used

first. Deviation from this requirement is

permitted if such deviation is temporary

and appropriate.

(9) Raw materials shall be retested or

reexamined and approved or rejected by

the quality control after a specified time

in storage or after exposure to air, heat,

or other conditions that are likely to

adversely affect the purity, quality, or

composition of the raw material.

(10) Rejected raw materials, shall be

identified and controlled under a system

that prevents their use in manufacturing

or processing operations for which they

are unsuitable.

(d) Manufacturing operations.

(1) All operations in the receiving,

inspecting, transporting, segregating,

preparing, manufacturing, packaging,

and storing of dietary products shall be

conducted in accordance with adequate

sanitation principles.

(2) All reasonable precautions shall be

taken to assure that production

procedures do not contribute

adulteration from any source. Chemical,

microbial, or extraneous-material testing

procedures shall be used where

necessary to identify sanitation failures

or possible product adulteration.

(3) All product that has become

contaminated to the extent that it is

adulterated within the meaning of the act

shall be rejected, or if permissible,

treated or processed to eliminate the

contamination.

(4) All product manufacturing, including

packaging and storage, shall be

conducted under such conditions and

controls as are necessary to minimize the

potential for the growth of

microorganisms, or for the adulteration

of raw materials, in-process materials

and finished product.

(5) Measures such as sterilizing,

irradiating, pasteurizing, freezing,

refrigerating, controlling pH or

controlling water activity (aw) that are

taken to destroy or prevent the growth of

undesirable microorganisms, particularly

those of public health significance, shall

be adequate under the conditions of

manufacture, handling, and distribution

to prevent dietary products from being

adulterated within the meaning of the

act.

(6) Work-in-process shall be handled in a

manner that protects against

adulteration.

(7) Effective measures shall be taken to

protect finished dietary ingredients and

dietary supplements from adulteration

by raw materials, in-process materials or

refuse. When raw materials, in-process

materials or refuse are unprotected, they

shall not be handled simultaneously in

a receiving, loading, or shipping area if

that handling could result in adulterated

dietary products. Dietary ingredients and

dietary supplements transported by

conveyor shall be protected against

adulteration as necessary.

(8) All raw material containers,

compounding and storage containers,

processing lines and major equipment

used during the production of a batch

shall be properly identified at all times

to indicate their contents and when

necessary, the phase of processing of the

batch.

(9) Effective measures shall be taken as

necessary to protect against the inclusion

of metal or other extraneous material in

product. Compliance with this

requirement may be accomplished by

using sieves, traps, magnets, electronic

metal detectors, or other suitable

effective means.

(10) Dietary products, raw materials, and

in-process materials that are rejected or

adulterated within the meaning of the act

shall be identified, stored and disposed

of in a manner that protects against the

adulteration of other products.

(11) Written procedures shall be

established and followed that describe
5706 Federal Register / Vol. 62, No. 25 / Thursday, February 6, 1997 / Proposed Rules

appropriate tests, and/or examinations to

be conducted that may be necessary to

assure the purity, composition, and

quality of the finished product.

(12) Written procedures shall be

established and followed prescribing the

method for reprocessing batches or

operational start-up materials that do not

conform to finished goods standards or

specifications. Finished goods

manufactured using such materials shall

meet all established purity, composition,

and quality standards.

(13) Mechanical manufacturing steps such

as cutting, sorting, inspecting, shredding,

drying, grinding, blending, and sifting

shall be performed so as to protect

dietary ingredients and dietary

supplements against adulteration.

Compliance with this requirement may

be accomplished by providing adequate

physical protection of dietary products

from contact with adulterants. Protection

may be provided by adequate cleaning

and sanitizing of all processing

equipment between each manufacturing

step.

(14) Heat blanching, when required in the

preparation of a dietary product, should

be effected by heating the product to the

required temperature, holding it at this

temperature for the required time, and

then either rapidly cooling the material

or passing it to subsequent

manufacturing without delay.

Thermophilic growth and contamination

in blanchers should be minimized by the

use of adequate operating temperatures

and by periodic cleaning. Where the

blanched product is washed prior to

filling, potable water shall be used.

(15) Intermediate or dehydrated dietary

products that rely on the control of water

activity (aw) for preventing the growth of

undesirable microorganisms shall be

processed to and maintained at a safe

moisture level. Compliance with this

requirement may be accomplished by

any effective means, including

employment of one or more of the

following practices:

(i) Monitoring the water activity (aw) of the

material.

(ii) Controlling the soluble solids-water

ratio in finished product.

(iii) Protecting finished product from

moisture pickup, by use of a moisture

barrier or by other means, so that the

water activity (aw) of the product does

not increase to an unsafe level.

(16) Dietary ingredients and dietary

supplements that rely principally on the

control of pH for preventing the growth

of undesirable microorganisms shall be

monitored and maintained at an

appropriate pH. Compliance with this

requirement may be accomplished by

any effective means, including

employment of one or more of the

following practices:

(i) Monitoring the pH of raw materials, in

process material, and finished product.

(ii) Controlling the amount of acid added

to the product.

(17) When ice is used in contact with

dietary products, it shall be made from

potable water, and shall be used only if

it has been manufactured in accordance

with current good manufacturing

practice as outlined in 21 CFR part 110.

(e) Packaging and labeling operations.

(1) Filling, assembling, packaging, and

other operations shall be performed in

such a way that dietary products are

protected against adulteration.

Compliance with this requirement may

be accomplished by any effective means,

including:

(i) Adequate cleaning and sanitizing of all

filling and packaging equipment,

utensils, and product containers, as

appropriate.

(ii) Using materials for product containers

and packaging materials that are safe and

suitable.

(iii) Providing physical protection from

adulteration, particularly airborne

contamination.

(iv) Using sanitary handling procedures.

(2) Written procedures shall be established

and followed describing in sufficient

detail the control procedures employed

for the receipt, storage, handling,

sampling, examination, and/or testing

that may be necessary to assure the

identity of labeling and the appropriate

identity, cleanliness and quality

characteristics of packaging materials for

dietary products.

(3) For dietary supplements, labels and

other labeling materials for each different

product type, strength, or quantity of

contents shall be stored separately with

suitable identification.

(4) Obsolete labels, labeling, and other

packaging materials for dietary products

shall be destroyed.

(5) Written procedures shall be established

and followed to assure that correct

labels, labeling, and packaging materials

are issued and used for dietary products.

(6) Dietary ingredient and dietary

supplement packages shall be identified

with a lot number that permits

determination of the history of the

manufacture and control of the batch.

(7) Packaged and labeled dietary

supplements shall be examined to

provide assurance that containers and

packages in the lot have the correct label

and lot number. Products not meeting

specifications shall be rejected by the

quality control unit.

Warehousing, Distribution and PostDistribution Procedures

(a) Storage and distribution.

(1) Storage and transportation of finished

product shall be under conditions that

will protect product against physical,

chemical, and microbial adulteration as

well as against deterioration of the

product and the container.

(2) Adequate distribution records shall be

maintained and retained by the

manufacturer at least 1 year beyond

expected product shelf life, whereby an

effective product recall can be achieved

should one become necessary.

(b) Reserve samples. An appropriately

identified reserve sample that is

representative of each batch of a dietary

product should be retained and stored under

conditions consistent with the product

labeling until at least 1 year after the

expiration date, or if no expiration date is

identified on the product, for at least 3 years

after the date of manufacture. The reserve

sample should be stored in the same

immediate container-closure system in which

the finished product is marketed or in one

that provides similar protection. The reserve

sample shall consist of at least twice the

quantity necessary to perform all the required

tests.

(c) Records retention.

(1) Any laboratory, production, control or

distribution record specifically

associated with a batch of product shall

be retained for at least 1 year after the

expiration date of the batch, or if no

expiration date is identified on the

product, for at least 3 years after the date

of manufacture.

(2) Raw material records shall be

maintained for at least 1 year after the

expiration date of the last batch of

product incorporating the raw material,

or if no expiration date is identified on

the product, for at least 3 years after the

date of manufacture of the finished

product.

(d) Complaint files.

(1) Written procedures describing the

handling of all written and oral

complaints regarding a dietary product

shall be established and followed. Such

procedures shall include provisions for

review by the quality control unit of any

complaint involving the possible failure

of a product to meet any of its

specifications and, for such products, a

determination as to the need for an

investigation.

(2) A written record of each complaint

shall be maintained, until at least 1 year

after the expiration date of the product,

or 1 year after the date that the complaint

was received, whichever is longer.

(3) The written record shall include, where

known: The name and description of the

product, lot number, name of

complainant, nature of complaint, and

reply to complainant, if any.

(4) Where an investigation is conducted,

the written record shall include the

findings of the investigation and

followup action taken.

(e) Returned products. Returned dietary

products shall be identified as such and held.

If the conditions under which returned

dietary products have been held, stored, or

shipped before or during their return, or if

the condition of the product, its container,

carton, or labeling as a result of storage or

shipping, casts doubt on the purity,

composition or quality of the product, the

returned product shall be destroyed unless

examination, testing, or other investigations

prove the product meets appropriate

standards of purity, composition, and

quality. A product may be reprocessed

provided the subsequent product meets

appropriate specifications. Records

pertaining to returned products that are

subsequently reprocessed and/or

redistributed shall be maintained and shall

include the name and description of the
Federal Register / Vol. 62, No. 25 / Thursday, February 6, 1997 / Proposed Rules 5707

product, lot number, reason for the return,

quantity returned, date of disposition, and

ultimate disposition of the returned product.

(f) Product salvaging. Dietary products that

have been subjected to improper storage

conditions including extremes in

temperature, humidity smoke, fumes,

pressure, age, or radiation due to natural

disasters, fires, accidents, or equipment

failures shall not be salvaged and returned to

the marketplace. Whenever there is a

question whether products have been

subjected to such conditions, salvaging

operations may be conducted only if there is:

(1) Evidence from laboratory tests that the

products meet all applicable standards of

purity, quality, and composition; and (2)

evidence from inspection of the premises that

the products and their associated packaging

were not subjected to improper storage

conditions as a result of the disaster or

accident. Records including name, lot

number, and disposition shall be maintained

for products subject to this section.

(g) Defect action levels.

(1) Some dietary ingredients and dietary

supplements, even when produced

under current good manufacturing

practice, contain natural or unavoidable

defects that at low levels are not

hazardous to health. The Food and Drug

Administration establishes maximum

levels for these defects in dietary

products produced under current good

manufacturing practice and uses these

levels in deciding whether to

recommend regulatory action.

(2) Defect action levels are established for

dietary products whenever it is

necessary and feasible to do so. These

levels are subject to change upon the

development of new technology or the

availability of new information.

(3) Compliance with defect action levels

does not excuse violation of the

requirement in section 402(a)(4) of the

act that dietary products not be prepared,

packed, or held under unsanitary

conditions or the requirements in this

part that dietary product manufacturers,

distributors, and holders shall observe

current good manufacturing practice.

Evidence indicating that such a violation

exists causes a dietary product to be

adulterated within the meaning of the

act, even though the amounts of natural

or unavoidable defects are lower than the

currently established defect action

levels. The manufacturer, distributor,

and holder of a dietary product shall at

all times utilize quality control

operations that reduce natural or

unavoidable defects to the lowest level

currently feasible.

(4) The mixing of a dietary ingredient or

dietary supplement containing defects

above the current defect action level

with another lot of dietary ingredient or

dietary supplement is not permitted and

renders the final product adulterated

within the meaning of the act, regardless

of the defect level of the final product.

(5) A compilation of the current defect

action levels for natural or unavoidable

defects in dietary products that present

no health hazard may be obtained upon

request from the Industry Programs

Branch (HFF–326), Center for Food

Safety and Applied Nutrition, Food and

Drug Administration, 200 C St. SW.,

Washington, DC 20204.

III. Economic Issues

FDA requests comment on and

descriptions of CGMP in the dietary

supplement industry. The agency seeks

information on how closely the current

practices of firms manufacturing dietary

supplements conform to the industry

submission, and on how costly it would

be to bring those practices into

conformity. The agency asks for

comments on whether there should be

new CGMP regulations, whether the

regulations should be mandatory or

voluntary, and, if mandatory, how long

it would take establishments to come

into compliance. Because FDA would

like to determine how current

manufacturing practices differ with

plant size, the agency particularly

requests comments from both small

businesses and large businesses.

The establishment of CGMP could

have effects on small businesses in the

dietary supplement industry. There are

several possible definitions of ‘‘small’’

that can be applied to dietary

supplements. Although the Small

Business Administration (SBA) does not

define small for the dietary supplement

industry, the industry’s products are

generally closest to foods and

botanicals. The SBA size standards for

small businesses are 500 or fewer

employees for food preparations, 750 or

fewer employees for botanical products,

and annual sales revenue less than $5

million for businesses that cannot be

classified into a specific industry. The

Nutrition Business Journal (August

1996) divides firms into large (annual

sales over $100 million), medium

(annual sales between $20 and $100

million), and small (annual sales under

$20 million). Under any of the possible

definitions, instituting CGMP’s for the

industry has the potential to affect a

significant number of small businesses.

FDA asks for comments on this matter.

IV. Summary and Request for

Comments

FDA asks for comments on the

regulatory framework presented in the

industry submission in section II. of this

document and the economic issues

discussed above. In addition, the agency

requests comments on the following

issues:

1. Is there a need to develop specific

defect action levels (DAL’s) for dietary

ingredients? While FDA has established

DAL’s for many food ingredients,

including botanical food ingredients,

these DAL’s reflect their use for specific

purposes, for example, the use of many

botanicals as spices, flavorings, or other

trace ingredients in foods. The DAL’s

are designed to provide reasonable

assurance of the safety and

wholesomeness of the ingredient when

it is present in the food supply in small

quantities. However, the use of a

botanical in a dietary supplement may

result in a much greater exposure to the

botanical ingredient for consumers

because the dietary supplement will be

consumed in greater amounts than if the

ingredient was in a food as a spice or

flavoring agent. Therefore, FDA

tentatively concludes that it would not

be appropriate to apply the current

DAL’s to dietary supplements, and the

agency requests comments that would

assist in developing DAL’s for dietary

supplements.

2. FDA requests comments on

appropriate testing requirements to

provide positive identification of dietary

ingredients, particularly plant materials,

used in dietary supplements. The

misidentification of dietary ingredients,

particularly plant materials, used in

dietary supplements may present a

significant public health and economic

concern. However, the analytical

methodology available for identifying

many dietary ingredients is limited.

Furthermore, section 402(g)(2) of the act

states that CGMP regulations may not

impose standards for which there is no

current and generally available

analytical methodology. FDA is asking

for comments on the technical and

scientific feasibility for the

identification of different types of

dietary ingredients. The agency also

solicits information on what constitutes

‘‘adequate testing’’ for identity of

different types of ingredients, and, in

the absence of testing, what types of

practices would be effective alternatives

to testing to ensure the identity of

different types of dietary ingredients.

3. FDA requests comments on

standards that should be met in

certifying that a dietary ingredient or

dietary supplement is not contaminated

with filth; that it is free of harmful

contaminants, pesticide residues, or

other impurities; that it is

microbiologically safe; and that it meets

specified quality and identity standards.

For food (§ 110.80), it is CGMP for a

manufacturer to accept certification

from a supplier that products do not

contain microorganisms or filth or other

foreign material that would adulterate

the product in lieu of direct testing or

evaluation of the raw materials or final

product. However, many ingredients

used in dietary supplements do not

have a history of food use in the United
5708 Federal Register / Vol. 62, No. 25 / Thursday, February 6, 1997 / Proposed Rules

States, and thus the potential for

contamination with microorganisms or

filth is unknown. The agency does not

have information that provides a basis

for it to determine whether certification

by a supplier provides adequate

assurance that a dietary ingredient is

what it purports to be and is not

adulterated. Therefore, the agency asks

for comments on whether a certification

will provide assurance that dietary

ingredients are not contaminated, or

whether specific testing requirements

are necessary and would effectively

ensure the safety and wholesomeness of

these products.

4. CGMP is intended to ensure that a

firm follows quality control and other

procedures necessary to ensure that a

food is safe for its intended use. It is

possible that a firm will develop

adequate standard operating procedures

and other mechanisms to achieve this

end, but that such procedures will not

be followed. The agency asks for

comments on whether there is a need

for CGMP to include requirements for

manufacturers to establish procedures to

document that the procedures

prescribed for the manufacture of a

dietary supplement are followed on a

continuing or day-to-day basis.

FDA is aware that no provision of part

110 deals with the establishment of

documentation that a manufacturer is

following established procedures

prescribed for the manufacture of a

dietary supplement, and that section

402(g) of the act states that any CGMP

regulations for dietary supplements are

to be modeled after the CGMP

regulations for food. However, FDA’s

tentative judgment is that section 402(g)

of the act does not preclude FDA from

adopting CGMP regulations for dietary

supplements that have no counterpart in

part 110 if there is an appropriate basis

for so doing. FDA requests comments on

this issue.

5. The agency asks for comments on

whether dietary supplement CGMP

should require that reports of injuries or

illnesses to a firm be evaluated by

competent medical authorities to

determine whether followup action is

necessary to protect the public health.

Many dietary supplements contain

pharmacologically active substances,

and some may contain potential

allergens that result in adverse events in

certain consumers. The presence of

pharmacologically active substances in

these products distinguishes them from

most other foods. Because of the

potential for serious injury or illness in

some persons from the consumption of

such substances, it may be necessary

that trained medical professionals,

rather than quality control or

nonmedical scientific/regulatory

personnel, evaluate all reported adverse

events associated with the use of a

specific substance and advise

responsible management of their

findings. FDA also asks for comments

on whether CGMP for dietary

supplements should contain a

requirement that a firm establish

procedures for determining whether a

reported injury constitutes a serious

problem, and what actions are to be

taken when serious problems are

identified.

FDA is aware that no provision of part

110 deals with followup to reports of

illness or injury, and that section 402(g)

of the act states that any CGMP

regulations for dietary supplements are

to be modeled after the CGMP

regulations for food. However, as stated

above, FDA’s tentative judgment is that

section 402(g) of the act does not

preclude FDA from adopting CGMP

regulations for dietary supplements that

have no counterpart in part 110 if there

is an appropriate basis for so doing.

6. FDA asks for comments on whether

CGMP for dietary supplements should

require that manufacturers establish

procedures to identify, evaluate, and

respond to potential safety concerns

with dietary ingredients. As discussed

above, many dietary ingredients have

little history of use in food in the United

States or of use in the amounts that

would be used in a dietary supplement.

Moreover, dietary ingredients are

excepted from the definition of ‘‘food

additive’’ in section 201(s)(6) of the act

(21 U.S.C. 321(s)(6)). In these

circumstances, it may be appropriate to

provide that CGMP requires that a

manufacturer critically evaluate the

available scientific information on the

safety of the dietary ingredients that it

intends to use in its products to assure

itself that those products will be safe.

FDA asks for comments on whether

such an evaluation is necessary, and, if

so, what elements need to be included

in such an evaluation and their relative

importance (e.g., the presence and

potency of pharmacologically active

substances, the presence of different

microorganisms, the presence of

different contaminants and impurities).

In addition, the agency asks for

comments on whether it should require

that such an evaluation be documented

in a firm’s records, and, if so, what type

of records would be adequate to

document that such an evaluation had

occurred.

7. The agency asks for comments on

whether specific controls are necessary

for computer controlled or assisted

operations. Many modern

manufacturing operations rely on

computers to ensure that proper

procedures are followed in the handling

and processing of ingredients and the

manufacture of food products. If such

equipment is used in the production of

dietary supplements, FDA requests

comment on how best to ensure that the

software programs and equipment used

to direct and monitor the manufacturing

process are properly designed, tested,

validated, and monitored.

8. The agency asks for comments on

whether certain, or all, of the

requirements for manufacturing and

handling dietary ingredients and dietary

supplements may be more effectively

addressed by a regulation based on the

principles of Hazard Analysis and

Critical Control Points (HACCP), rather

than the system outlined in the industry

submission. FDA has issued regulations

based on HACCP to ensure the safety of

other foods (i.e., seafood) (Ref. 3) and

has issued an advance notice of

proposed rulemaking on the

appropriateness of extending the

HACCP concept to other segments of the

food industry (Ref. 4). HACCP-based

requirements enable manufacturers to

develop and implement processes and

controls that are tailored to their

specific products and manufacturing

operations. Because of the wide variety

of dietary ingredients and dietary

supplements and because of the

heterogenous composition of the dietary

supplement industry, CGMP based on

the principles of HACCP may provide a

more flexible and less burdensome

regulatory framework for manufacturers

and distributors than the approach set

out in the industry submission.

9. The dietary supplement industry

includes a broad spectrum of firms that

conduct one or more distinct operations,

such as the manufacture or distribution

of raw dietary ingredients, the

manufacture of finished products, or

solely the distribution and sale of

finished products (manufactured by a

separate firm) at the wholesale or retail

level. Consequently, the dietary

supplement CGMP regulations may

need to address the distinctive

requirements of each of these segments

of the industry in order to effectively

ensure that dietary supplements are

what they are represented to be and are

safe for their intended use. The agency

asks for comments on whether broad

CGMP regulations will be adequate, or

whether it will be necessary to address

the operations of particular segments of

the dietary supplement industry.

VII. Comments

Interested persons may, on or before

May 7, 1997, submit to the Dockets

Management Branch (address above)
Federal Register / Vol. 62, No. 25 / Thursday, February 6, 1997 / Proposed Rules 5709

written comments regarding this

proposal. Two copies of any comments

are to be submitted, except that

individuals may submit one copy.

Comments are to be identified with the

docket number found in brackets in the

heading of this document. Received

comments may be seen in the office

above between 9 a.m. and 4 p.m.,

Monday through Friday.

VIII. References

The following references have been

placed on display in the Dockets

Management Branch (address above)

and may be seen by interested persons

between 9 a.m. and 4 p.m., Monday

through Friday.

1. Memorandum of Meeting, Center for

Food Safety and Applied Nutrition, Food and

Drug Administration, Washington, DC,

November 30, 1995.

2. Discussion Draft of GMP’s for Dietary

Supplements, submitted to the Food and

Drug Administration, November 21, 1995.

3. Food and Drug Administration,

‘‘Procedures for the Safe and Sanitary

Processing and Importing of Fish and Fishery

Products,’’ final rule, 60 FR 65096, December

18, 1995.

4. Food and Drug Administration, Food

and Safety Assurance Program;

‘‘Development of Hazard Analysis Critical

Control Points for the Food Industry,’’

proposed rule, 59 FR 39888, August 4, 1994.

Dated: December 11, 1996.

William B. Schultz,

Deputy Commissioner for Policy.

[FR Doc. 97–3014 Filed 2–5–97; 8:45 am]

BILLING CODE 4160–01–F