1、TITLE 21-FOOD AND DRUGSCHAPTER I-FOOD AND DRUG ADMINISTRATIONDEPARTMENT OF HEALTH AND HUMAN SERVICES SUBCHAPTER B-FOOD FOR HUMAN CONSUMPTION PART 111 CURRENT GOOD MANUFACTURING PRACTICE IN MANUFACTURING, PACKAGING, LABELING, OR HOLDING OPERATIONS FOR DIETARY SUPPLEMENTSCode of Federal RegulationsTit
2、le 21, Volume 2Revised as of April 1, 2008CITE: 21CFR111Subpart A-General Provisions Sec. 111.1 Who is subject to this part? (a) Except as provided by paragraph (b) of this section, you are subject to this part if you manufacture, package, label, or hold a dietary supplement, including:(1) A dietary
3、 supplement you manufacture but that is packaged or labeled by another person; and(2) A dietary supplement imported or offered for import in any State or territory of the United States, the District of Columbia, or the Commonwealth of Puerto Rico.(b) The requirements pertaining to holding dietary su
4、pplements do not apply to you if you are holding those dietary supplements at a retail establishment for the sole purpose of direct retail sale to individual consumers. A retail establishment does not include a warehouse or other storage facility for a retailer or a warehouse or other storage facili
5、ty that sells directly to individual consumers.Sec. 111.3 What definitions apply to this part? The definitions and interpretations of terms in section 201 of the Federal Food, Drug, and Cosmetic Act (the act) apply to such terms when used in this part. For the purpose of this part, the following def
6、initions also apply:Actual yield means the quantity that is actually produced at any appropriate step of manufacture or packaging of a particular dietary supplement.Batch means a specific quantity of a dietary supplement that is uniform, that is intended to meet specifications for identity, purity,
7、strength, and composition, and that is produced during a specified time period according to a single manufacturing record during the same cycle of manufacture.Batch number, lot number, or control number means any distinctive group of letters, numbers, or symbols, or any combination of them, from whi
8、ch the complete history of the manufacturing, packaging, labeling, and/or holding of a batch or lot of dietary supplements can be determined.Component means any substance intended for use in the manufacture of a dietary supplement, including those that may not appear in the finished batch of the die
9、tary supplement. Component includes dietary ingredients (as described in section 201(ff) of the act) and other ingredients.Contact surface means any surface that contacts a component or dietary supplement, and those surfaces from which drainage onto the component or dietary supplement, or onto surfa
10、ces that contact the component or dietary supplement, occurs during the normal course of operations. Examples of contact surfaces include containers, utensils, tables, contact surfaces of equipment, and packaging.Ingredient means any substance that is used in the manufacture of a dietary supplement
11、and that is intended to be present in the finished batch of the dietary supplement. An ingredient includes, but is not necessarily limited to, a dietary ingredient as defined in section 201(ff) of the act.In-process material means any material that is fabricated, compounded, blended, ground, extract
12、ed, sifted, sterilized, derived by chemical reaction, or processed in any other way for use in the manufacture of a dietary supplement.Lot means a batch, or a specific identified portion of a batch, that is uniform and that is intended to meet specifications for identity, purity, strength, and compo
13、sition; or, in the case of a dietary supplement produced by continuous process, a specific identified amount produced in a specified unit of time or quantity in a manner that is uniform and that is intended to meet specifications for identity, purity, strength, and composition.Microorganisms means y
14、easts, molds, bacteria, viruses, and other similar microscopic organisms having public health or sanitary concern. This definition includes species that:(1) May have public health significance;(2) May cause a component or dietary supplement to decompose;(3) Indicate that the component or dietary sup
15、plement is contaminated with filth; or(4) Otherwise may cause the component or dietary supplement to be adulterated.Must is used to state a requirement.Pest means any objectionable insect or other animal including birds, rodents, flies, mites, and larvae.Physical plant means all or any part of a bui
16、lding or facility used for or in connection with manufacturing, packaging, labeling, or holding a dietary supplement.Product complaint means any communication that contains any allegation, written, electronic, or oral, expressing concern, for any reason, with the quality of a dietary supplement, tha
17、t could be related to current good manufacturing practice. Examples of product complaints are: Foul odor, off taste, illness or injury, disintegration time, color variation, tablet size or size variation, under-filled container, foreign material in a dietary supplement container, improper packaging,
18、 mislabeling, or dietary supplements that are superpotent, subpotent, or contain the wrong ingredient, or contain a drug or other contaminant (e.g., bacteria, pesticide, mycotoxin, glass, lead).Quality means that the dietary supplement consistently meets the established specifications for identity,
19、purity, strength, and composition, and limits on contaminants, and has been manufactured, packaged, labeled, and held under conditions to prevent adulteration under section 402(a)(1), (a)(2), (a)(3), and (a)(4) of the act.Quality control means a planned and systematic operation or procedure for ensu
20、ring the quality of a dietary supplement.Quality control personnel means any person, persons, or group, within or outside of your organization, who you designate to be responsible for your quality control operations.Representative sample means a sample that consists of an adequate number of units th
21、at are drawn based on rational criteria, such as random sampling, and that are intended to ensure that the sample accurately portrays the material being sampled.Reprocessing means using, in the manufacture of a dietary supplement, clean, uncontaminated components or dietary supplements that have bee
22、n previously removed from manufacturing and that have been made suitable for use in the manufacture of a dietary supplement.Reserve sample means a representative sample of product that is held for a designated period of time.Sanitize means to adequately treat cleaned equipment, containers, utensils,
23、 or any other cleaned contact surface by a process that is effective in destroying vegetative cells of microorganisms of public health significance, and in substantially reducing numbers of other microorganisms, but without adversely affecting the product or its safety for the consumer.Theoretical y
24、ield means the quantity that would be produced at any appropriate step of manufacture or packaging of a particular dietary supplement, based upon the quantity of components or packaging to be used, in the absence of any loss or error in actual production.Water activity (aw) is a measure of the free
25、moisture in a component or dietary supplement and is the quotient of the water vapor pressure of the substance divided by the vapor pressure of pure water at the same temperature.We means the U.S. Food and Drug Administration (FDA).You means a person who manufactures, packages, labels, or holds diet
26、ary supplements.Sec. 111.5 Do other statutory provisions and regulations apply? In addition to this part, you must comply with other applicable statutory provisions and regulations under the act related to dietary supplements.Subpart B-Personnel Sec. 111.8 What are the requirements under this subpar
27、t B for written procedures? You must establish and follow written procedures for fulfilling the requirements of this subpart.Sec. 111.10 What requirements apply for preventing microbial contamination from sick or infected personnel and for hygienic practices? (a)Preventing microbial contamination .
28、You must take measures to exclude from any operations any person who might be a source of microbial contamination, due to a health condition, where such contamination may occur, of any material, including components, dietary supplements, and contact surfaces used in the manufacture, packaging, label
29、ing, or holding of a dietary supplement. Such measures include the following:(1) Excluding from working in any operations that may result in contamination any person who, by medical examination, the persons acknowledgement, or supervisory observation, is shown to have, or appears to have, an illness
30、, infection, open lesion, or any other abnormal source of microbial contamination, that could result in microbial contamination of components, dietary supplements, or contact surfaces, until the health condition no longer exists; and(2) Instructing your employees to notify their supervisor(s) if the
31、y have or if there is a reasonable possibility that they have a health condition described in paragraph (a)(1) of this section that could result in microbial contamination of any components, dietary supplements, or any contact surface.(b)Hygienic practices . If you work in an operation during which
32、adulteration of the component, dietary supplement, or contact surface could occur, you must use hygienic practices to the extent necessary to protect against such contamination of components, dietary supplements, or contact surfaces. These hygienic practices include the following:(1) Wearing outer g
33、arments in a manner that protects against the contamination of components, dietary supplements, or any contact surface;(2) Maintaining adequate personal cleanliness;(3) Washing hands thoroughly (and sanitizing if necessary to protect against contamination with microorganisms) in an adequate hand-was
34、hing facility:(i) Before starting work; and(ii) At any time when the hands may have become soiled or contaminated;(4) Removing all unsecured jewelry and other objects that might fall into components, dietary supplements, equipment, or packaging, and removing hand jewelry that cannot be adequately sa
35、nitized during periods in which components or dietary supplements are manipulated by hand. If hand jewelry cannot be removed, it must be covered by material that is maintained in an intact, clean, and sanitary condition and that effectively protects against contamination of components, dietary suppl
36、ements, or contact surfaces;(5) Maintaining gloves used in handling components or dietary supplements in an intact, clean, and sanitary condition. The gloves must be of an impermeable material;(6) Wearing, where appropriate, in an effective manner, hair nets, caps, beard covers, or other effective h
37、air restraints;(7) Not storing clothing or other personal belongings in areas where components, dietary supplements, or any contact surfaces are exposed or where contact surfaces are washed;(8) Not eating food, chewing gum, drinking beverages, or using tobacco products in areas where components, die
38、tary supplements, or any contact surfaces are exposed, or where contact surfaces are washed; and(9) Taking any other precautions necessary to protect against the contamination of components, dietary supplements, or contact surfaces with microorganisms, filth, or any other extraneous materials, inclu
39、ding perspiration, hair, cosmetics, tobacco, chemicals, and medicines applied to the skin.Sec. 111.12 What personnel qualification requirements apply? (a) You must have qualified employees who manufacture, package, label, or hold dietary supplements.(b) You must identify who is responsible for your
40、quality control operations. Each person who is identified to perform quality control operations must be qualified to do so and have distinct and separate responsibilities related to performing such operations from those responsibilities that the person otherwise has when not performing such operatio
41、ns.(c) Each person engaged in manufacturing, packaging, labeling, or holding, or in performing any quality control operations, must have the education, training, or experience to perform the persons assigned functions.Sec. 111.13 What supervisor requirements apply? (a) You must assign qualified pers
42、onnel to supervise the manufacturing, packaging, labeling, or holding of dietary supplements.(b) Each supervisor whom you use must be qualified by education, training, or experience to supervise.Sec. 111.14 Under this subpart B, what records must you make and keep? (a) You must make and keep records
43、 required under this subpart B in accordance with subpart P of this part.(b) You must make and keep the following records:(1) Written procedures for fulfilling the requirements of this subpart B; and(2) Documentation of training, including the date of the training, the type of training, and the pers
44、on(s) trained.Subpart C-Physical Plant and Grounds Sec. 111.15 What sanitation requirements apply to your physical plant and grounds? (a)Grounds . You must keep the grounds of your physical plant in a condition that protects against the contamination of components, dietary supplements, or contact su
45、rfaces. The methods for adequate ground maintenance include:(1) Properly storing equipment, removing litter and waste, and cutting weeds or grass within the immediate vicinity of the physical plant so that it does not attract pests, harbor pests, or provide pests a place for breeding;(2) Maintaining
46、 roads, yards, and parking lots so that they do not constitute a source of contamination in areas where components, dietary supplements, or contact surfaces are exposed;(3) Adequately draining areas that may contribute to the contamination of components, dietary supplements, or contact surfaces by s
47、eepage, filth or any other extraneous materials, or by providing a breeding place for pests;(4) Adequately operating systems for waste treatment and disposal so that they do not constitute a source of contamination in areas where components, dietary supplements, or contact surfaces are exposed; and(
48、5) If your plant grounds are bordered by grounds not under your control, and if those other grounds are not maintained in the manner described in this section, you must exercise care in the plant by inspection, extermination, or other means to exclude pests, dirt, and filth or any other extraneous m
49、aterials that may be a source of contamination.(b)Physical plant facilities . (1) You must maintain your physical plant in a clean and sanitary condition; and(2) You must maintain your physical plant in repair sufficient to prevent components, dietary supplements, or contact surfaces from becoming contaminated.(c)Cleaning compounds, sanitizing agents, pesticides, and other toxic materials . (1) You must use cleaning compounds and sanitizing agents that are free from microorganisms of public health significance and that are safe and adequate under the conditions of use.(2) You m
