[Federal Register Volume 62, Number 25 (Thursday, February 6, 1997)]
[Proposed Rules]
[Pages 5700-5709]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-3014]



[[Page 5699]]

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Part IV





Department of Health and Human Services





_______________________________________________________________________



Food and Drug Administration



_______________________________________________________________________



21 CFR Ch. I



Current Good Manufacturing Practice in Manufacturing, Packing, or 
Holding Dietary Supplements; Proposed Rule

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

[[Page 5700]]



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.

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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

[[Page 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 (a<INF>w)'' 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 hand-washing 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

[[Page 5702]]

protects against the adulteration of dietary products or 
contamination of processing equipment, utensils or packaging 
materials.
    (5) Maintaining gloves, if they are used in-process 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 in-process 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 hand-washing 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 safety-type 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, in-
process 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

[[Page 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, in-process 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.

[[Page 5704]]

    (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 in-process 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.

[[Page 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 (a<INF>w) 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

[[Page 5706]]

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 (a<INF>w) for preventing the growth of 
undesirable microorganisms shall be processed to and maintained at a 
safe moisture level. Compliance with this requirement may be 
accomplished by any effective means, including employment of one or 
more of the following practices:
    (i) Monitoring the water activity (a<INF>w) 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 
(a<INF>w) 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 Post-Distribution 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

[[Page 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 (Sec. 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

[[Page 5708]]

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)

[[Page 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