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1、美国GMP英文版 21 Code of Federal Regulations Parts 210 and 211 Part 210 - CURRENT GOOD MANUFACTURING PRACTICE IN MANUFACTURING, PROCESSING, PACKING, OR HOLDING OF DRUGS; GENERAL Part 211 - CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS Part 210 - CURRENT GOOD MANUFACTURING PRACTI

2、CE IN MANUFACTURING, PROCESSING, PACKING, OR HOLDING OF DRUGS; GENERAL Sec. 210.1 Status of current good manufacturing practice regulations. 210.2 Applicability of current good manufacturing practice regulations. 210.3 Definitions. AUTHORITY: Secs. 201, 501, 502, 505, 506, 507, 512, 701, 704 of

3、 the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321, 351, 352, 355, 356, 357, 360b, 371, 374). SOURCE: 43 FR 45076, Sept. 29, 1978, unless otherwise noted. ?210.1 Status of current good manufacturing practice regulations. (a) The regulations set forth in this part and in Parts 211 through 22

4、6 of this chapter contain the minimum current good manufacturing practice for methods to be used in, and the facilities or controls to be used for, the manufacture, processing, packing, or holding of a drug to assure that such drug meets the requirements of the act as to safety, and has the identity

5、 and strength and meets the quality and purity characteristics that it purports or is represented to possess. (b) The failure to comply with any regulation set forth in this part and in Parts 211 through 226 of this chapter in the manufacture, processing, packing, or holding of a drug shall render

6、such drug to be adulterated under section 501(a)(2)(B) of the act and such drug, as well as the person who is responsible for the failure to comply, shall be subject to regulatory action. ?210.2 Applicability of current good manufacturing practice regulations. (a) The regulations in this part and

7、in Parts 211 through 226 of this chapter as they may pertain to a drug and in Parts 600 through 680 of this chapter as they may pertain to a biological product for human use, shall be considered to supplement, not supersede, each other, unless the regulations explicitly provide otherwise. In the eve

8、nt that it is impossible to comply with all applicable regulations in these parts, the regulations specifically applicable to the drug in question shall supersede the more general. (b) If a person engages in only some operations subject to the regulations in this part and in Parts 211 through 226 a

9、nd Parts 600 through 680 of this chapter, and not in others, that person need only comply with those regulations applicable to the operations in which he or she is engaged. ?210.3 Definitions. (a) The definitions and interpretations contained in section 201 of the act shall be applicable to such

10、terms when used in this part and in Parts 211 through 226 of this chapter. (b) The following definitions of terms apply to this part and to Parts 211 through 226 of this chapter. (1) Act means the Federal Food, Drug, and Cosmetic Act, as amended (21 U.S.C. 301 et seq.). (2) Batch means a specific

11、 quantity of a drug 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. (3) Component means any ingredient intended for use in the manufacture of a drug pro

12、duct, including those that may not appear in such drug product. (4) Drug product means a finished dosage form, for example, tablet, capsule, solution, etc., that contains an active drug ingredient generally, but not necessarily, in association with inactive ingredients. The term also includes a fin

13、ished dosage form that does not contain an active ingredient but is intended to be used as a placebo. (5) Fiber means any particulate contaminant with a length at least three times greater than its width. (6) Non-fiber-releasing filter means any filter, which after any appropriate pretreatment suc

14、h as washing or flushing, will not release fibers into the component or drug product that is being filtered. All filters composed of asbestos are deemed to be fiber-releasing filters. (7) Active ingredient means any component that is intended to furnish pharmacological activity or other direct effe

15、ct in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body of man or other animals. The term includes those components that may undergo chemical change in the manufacture of the drug product and be present in the drug product in

16、 a modified form intended to furnish the specified activity or effect. (8) Inactive ingredient means any component other than an ``active ingredient.'' (9) In-process material means any material fabricated, compounded, blended, or derived by chemical reaction that is produced for, and used in, the

17、 preparation of the drug product. (10) Lot means a batch, or a specific identified portion of a batch, having uniform character and quality within specified limits; or, in the case of a drug product produced by continuous process, it is a specific identified amount produced in a unit of time or qua

18、ntity in a manner that assures its having uniform character and quality within specified limits. (11) Lot number, control number, or batch number means any distinctive combination of letters, numbers, or symbols, or any combination of them, from which the complete history of the manufacture, proces

19、sing, packing, holding, and distribution of a batch or lot of drug product or other material can be determined. (12) Manufacture, processing, packing, or holding of a drug product includes packaging and labeling operations, testing, and quality control of drug products. (13) The term medicated fee

20、d means any Type B or Type C medicated feed as defined in 558.3 of this chapter. The feed contains one or more drugs as defined in section 201(g) of the act. The manufacture of medicated feeds is subject to the requirements of Part 225 of this chapter. (14) The term medicated premix means a Type A

21、medicated article as defined in 558.3 of this chapter. The article contains one or more drugs as defined in section 201(g) of the act. The manufacture of medicated premixes is subject to the requirements of Part 226 of this chapter. (15) Quality control unit means any person or organizational eleme

22、nt designated by the firm to be responsible for the duties relating to quality control. (16) Strength means: (I) The concentration of the drug substance (for example, weight/weight, weight/volume, or unit dose/volume basis), and/or (ii) The potency, that is, the therapeutic activity of the drug p

23、roduct as indicated by appropriate laboratory tests or by adequately developed and controlled clinical data (expressed, for example, in terms of units by reference to a standard). (17) Theoretical yield means the quantity that would be produced at any appropriate phase of manufacture, processing, o

24、r packing of a particular drug product, based upon the quantity of components to be used, in the absence of any loss or error in actual production. (18) Actual yield means the quantity that is actually produced at any appropriate phase of manufacture, processing, or packing of a particular drug pro

25、duct. (19) Percentage of theoretical yield means the ratio of the actual yield (at any appropriate phase of manufacture, processing, or packing of a particular drug product) to the theoretical yield (at the same phase), stated as a percentage. (20) Acceptance criteria means the product specificati

26、ons and acceptance/rejection criteria, such as acceptable quality level and unacceptable quality level, with an associated sampling plan, that are necessary for making a decision to accept or reject a lot or batch (or any other convenient subgroups of manufactured units). (21) Representative sample

27、 means a sample that consists of a number of units that are drawn based on rational criteria such as random sampling and intended to assure that the sample accurately portrays the material being sampled. (22) Gang-printed labeling means labeling derived from a sheet of material on which more than o

28、ne item of labeling is printed. [43 FR 45076, Sept. 29, 1978, as amended at 51 FR 7389, Mar. 3, 1986; 58 FR 41353, Aug. 3, 1993] EFFECTIVE DATE NOTE: At 58 FR 41353, Aug. 8, 1993, 210.3 was amended by adding paragraph (b)(22) effective Aug. 3, 1994. Part 211 -CURRENT GOOD MANUFACTURING PRACTICE

29、 FOR FINISHED PHARMACEUTICALS (21 CFR Part 211 As of April, 1996) Authority: Secs. 201, 501, 502, 505, 506, 507, 512, 701, 704 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321, 351, 352, 355, 356, 357, 360b, 371, 374). Source: 43 FR 45077, Sept. 29, 1978, unless otherwise noted. PAR

30、T 211 - CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS Subpart A - General Provisions Sec. 211.1 Scope 211.3 Definitions Subpart B - Organization and Personnel 211.22 Responsibilities of quality control unit. 211.25 Personnel Qualifications. 211.28 Personnel responsibilitie

31、s. 211.34 Consultants. Subpart C - Buildings and Facilities 211.42 Design and construction features. 211.44 Lighting. 211.46 Ventilation, air filtration, air heating and cooling. 211.48 Plumbing. 211.50 Sewage and refuse. 211.52 Washing and toilet facilities. 211.56 Sanitation. 211.58 Main

32、tenance Subpart D - Equipment 211.63 Equipment design, size, and location. 211.65 Equipment construction. 211.67 Equipment cleaning and maintenance. 211.68 Automatic, mechanical, and electronic equipment. 211.72 Filters. Subpart E - Control of Components and Drug Product Containers and Closur

33、es 211.80 General requirements. 211.82 Receipt and storage of untested components, drug product containers, and closures. 211.84 Testing and approval or rejection of components, drug product containers, and closures. 211.86 Use of approved components, drug product containers, and closures. 211.

34、87 Retesting of approved components, drug product containers and closures. 211.89 Rejected components, drug product containers, and closures. 211.94 Drug product containers and closures. Subpart F - Production and Process Controls 211.100 Written procedures; deviations. 211.101 Charge-in of com

35、ponents. 211.103 Calculation of yield. 211.105 Equipment identification. 211.110 Sampling and testing of in-process materials and drug products. 211.111 Time limitations on production. 211.113 Control of microbiological contamination. 211.115 Reprocessing. Subpart G - Packaging and Labeling C

36、ontrol 211.122 Materials examination and usage criteria. 211.125 Labeling issuance. 211.130 Packaging and labeling operations. 211.132 Tamper-resistant packaging requirements for over-the-counter human drug products. 211.134 Drug product inspection. 211.137 Expiration dating. Subpart H - Hold

37、ing and Distribution 211.142 Warehousing procedures. 211.150 Distribution procedures. Subpart I - Laboratory Controls 211.160 General requirements. 211.165 Testing and release for distribution. 211.166 Stability testing. 211.167 Special testing requirements. 211.170 Reserve samples. 211.173

38、 Laboratory animals. 211.176 Penicillin contamination. Subpart J - Records and Reports 211.180 General requirements. 211.182 Equipment cleaning and use log. 211.184 Component, drug product container, closure, and labeling records. 211.186 Master production and control records. 211.188 Batch p

39、roduction and control records. 211.192 Production record review. 211.194 Laboratory records. 211.196 Distribution records. 211.198 Complaint files. Subpart K - Returned and Salvaged Drug Products 211.204 Returned drug products. 211.208 Drug product salvaging. Subpart A-General Provisions ?

40、211.1 Scope (a) The regulations in this part contain the minimum current good manufacturing practice for preparation of drug products for administration to humans or animals. (b) The current good manufacturing practice regulations in this chapter, as they pertain to drug products, and in parts 60

41、0 through 680 of this chapter, as they pertain to biological products for human use, shall be considered to supplement, not supersede, the regulations in this part unless the regulations explicitly provide otherwise. In the event it is impossible to comply with applicable regulations both in this pa

42、rt and in other parts of this chapter or in parts 600 through 680 of this chapter, the regulation specifically applicable to the drug product in question shall supersede the regulation in this part. (c) Pending consideration of a proposed exemption, published in the Federal Register of September 2

43、9, 1978, the requirements in this part shall not be enforced for OTC drug products if the products and all their ingredients are ordinarily marketed and consumed as human foods, and which products may also fall within the legal definition of drugs by virtue of their intended use. Therefore, until fu

44、rther notice, regulations under part 110 of this chapter, and where applicable, parts 113 to 129 of this chapter, shall be applied in determining whether these OTC drug products that are also foods are manufactured, processed, packed, or held under current good manufacturing practice. ?211.3 Defin

45、itions. The definitions set forth in ?210.3 of this chapter apply in this part. Subpart B-Organization and Personnel ?211.22 Responsibilities of quality control unit. (a) There shall be a quality control unit that shall have the responsibility and authority to approve or reject all components,

46、drug product containers, closures, in-process materials, packaging material, labeling, and drug products, and the authority to review production records to assure that no errors have occurred or, if errors have occurred, that they have been fully investigated. The quality control unit shall be respo

47、nsible for approving or rejecting drug products manufactured, processed, packed, or held under contract by another company. (b) Adequate laboratory facilities for the testing and approval (or rejection) of components, drug product containers, closures, packaging materials, in-process materials, and

48、 drug products shall be available to the quality control unit. (c) The quality control unit shall have the responsibility for approving or rejecting all procedures or specifications impacting on the identity, strength, quality, and purity of the drug product. (d) The responsibilities and procedure

49、s applicable to the quality control unit shall be in writing; such written procedures shall be followed. ?211.25 Personnel qualifications. (a) Each person engaged in the manufacture, processing, packing, or holding of a drug product shall have education, training, and experience, or any combinati

50、on thereof, to enable that person to perform the assigned functions. Training shall be in the particular operations that the employee performs and in current good manufacturing practice (including the current good manufacturing practice regulations in this chapter and written procedures required by

51、these regulations) as they relate to the employee's functions. Training in current good manufacturing practice shall be conducted by qualified individuals on a continuing basis and with sufficient frequency to assure that employees remain familiar with CGMP requirements applicable to them. (b) Each

52、 person responsible for supervising the manufacture, processing, packing, or holding of a drug product shall have the education, training, and experience, or any combination thereof, to perform assigned functions in such a manner as to provide assurance that the drug product has the safety, identity

53、, strength, quality, and purity that it purports or is represented to possess. (c) There shall be an adequate number of qualified personnel to perform and supervise the manufacture, processing, packing, or holding of each drug product. ?211.28 Personnel responsibilities. (a) Personnel engaged in

54、the manufacture, processing, packing, or holding of a drug product shall wear clean clothing appropriate for the duties they perform. Protective apparel, such as head, face, hand, and arm coverings, shall be worn as necessary to protect drug products from contamination. (b) Personnel shall practice

55、 good sanitation and health habits. (c) Only personnel authorized by supervisory personnel shall enter those areas of the buildings and facilities designated as limited-access areas. (d) Any person shown at any time (either by medical examination or supervisory observation) to have an apparent ill

56、ness or open lesions that may adversely affect the safety or quality of drug products shall be excluded from direct contact with components, drug product containers, closures, in-process materials, and drug products until the condition is corrected or determined by competent medical personnel not to

57、 jeopardize the safety or quality of drug products. All personnel shall be instructed to report to supervisory personnel any health conditions that may have an adverse effect on drug products. ?211.34 Consultants. Consultants advising on the manufacture, processing, packing, or holding of drug pr

58、oducts shall have sufficient education, training, and experience, or any combination thereof, to advise on the subject for which they are retained. Records shall be maintained stating the name, address, and qualifications of any consultants and the type of service they provide. Subpart C-Buildings

59、 and Facilities ?211.42 Design and construction features. (a) Any building or buildings used in the manufacture, processing, packing, or holding of a drug product shall be of suitable size, construction and location to facilitate cleaning, maintenance, and proper operations. (b) Any such build

60、ing shall have adequate space for the orderly placement of equipment and materials to prevent mixups between different components, drug product containers, closures, labeling, in-process materials, or drug products, and to prevent contamination. The flow of components, drug product containers, closu

61、res, labeling, in-process materials, and drug products through the building or buildings shall be designed to prevent contamination. (c) Operations shall be performed within specifically defined areas of adequate size. There shall be separate or defined areas for the firm's operations to prevent c

62、ontamination or mixups as follows: (1) Receipt, identification, storage, and withholding from use of components, drug product containers, closures, and labeling, pending the appropriate sampling, testing, or examination by the quality control unit before release for manufacturing or packaging; (2)

63、 Holding rejected components, drug product containers, closures, and labeling before disposition; (3) Storage of released components, drug product containers, closures, and labeling; (4) Storage of in-process materials; (5) Manufacturing and processing operations; (6) Packaging and labeling op

64、erations; (7) Quarantine storage before release of drug products; (8) Storage of drug products after release; (9) Control and laboratory operations; (10) Aseptic processing, which includes as appropriate: (I) Floors, walls, and ceilings of smooth, hard surfaces that are easily cleanable; (ii)

65、Temperature and humidity controls; (iii) An air supply filtered through high-efficiency particulate air filters under positive pressure, regardless of whether flow is laminar or nonlaminar; (iv) A system for monitoring environmental conditions; (v) A system for cleaning and disinfecting the room

66、and equipment to produce aseptic conditions; (vi) A system for maintaining any equipment used to control the aseptic conditions. (d) Operations relating to the manufacture, processing, and packing of penicillin shall be performed in facilities separate from those used for other drug products for human use. [43 FR 45077, Sept. 29, 1978, as amended at 60 FR 4091, Jan. 20, 1995] ?211.44 Lighting. Adequate lighting shall be provided in all areas. ?211.46 Ventilation, air filtration, air heat