45014 RULES AND REGULATIONS

1 In 45014 [4110-03] Title 21-Food and Drugs CHAPTER I-FOOD AND DRUG AD MINISTRATION DEPARTMENT OF HEALTH, EDUCATION, AND WEL FARE SUBCHAPTER C-DRUGS: GENERAL [Docket No. 75N-0339] HUMAN AND VETERINARY DRUGS Current Good Manufacturing Practice in Manufacture, Processing, Pack-Ing, or Holding AGENCY: Food and Drug Administra tion. ACTION: Final rule. SUMMARY: This document amendsthe FDA REGULATIONS that set forthcurrent good manufacturing practice(CGMP) for human and veterinarydrug products.

2 The amendmentsupdate present REGULATIONS in light ofcurrent technology for drug manufac turing and delineate requirementsmore specifically than do the presentregulations. Although some of the pro visions in these amendments representrequirements not specifically includedin the existing CGMP REGULATIONS , inmany instances the revisions are prac tices that have been considered implic it in the REGULATIONS or are at leastconsidered by most manufacturers tobe desirable- requirements for theirown the Federal Food. Drug, andCosmetic Act, a drug is deemed to beadulterated unless the methods used in its manufacture, processing.

3 Pack ing. and holding, and the facilities andcontrols used therefor, conform to cur rent good manufacturing practice sothat the drug meets the safety re quirements of the act and has the identity and strength and meets thequality and purity characteristics thatit is represented to have. The regula tions are being updated and mademore explicit, and therefore less sub ject to varylng interpretations, to assure that all members of the drugindustry are made aware of the levelof performance expected of them to bein compliance with the act. EFFECTIVE DATE: March FOR FURTHER INFORMATIONCONTACT: Clifford G.

4 Broker (HFD-323) (301 443-5307). or Robert J. Rice, Jr.,(HFD-30) (301-443-5220), Bureau of Drugs, Food and Drug Administra tion, Department of Health, Educa tion, and Welfare, 5600 FishersLane. Rockville, Md. 20857. RULES AND REGULATIONS SUPPLEMENTARY INFORMATION:In the FEDERAL REGISTER of February13. 1976 (41 FR 6878). the Commis sioner of Food and Drugs proposed torevise the CGMP REGULATIONS , Parts210 and 211 (21 CFR Parts 210 and211). issued under section 501(a)(2)(B)of the Federal Food, Drug, and C os metic Act (21 351(a)(2)(B)). toupdate them in light of current tech nology and to adopt more specific re quirements to assure the quality offinished drug products.

5 Because of thenature and extent of the proposed re visions, the Commissioner alloweduntil June 14, 1976, for interested per sons to submit Commissioner received com ments from 168 respondents totalingapproximately 2,000 pages. These com ments represent many interests - indi vidual consumers; nonprofit institu tions or associations: health-care de partments of hospitals, colleges, anduniversities: State and foreign health-care organizations; domestic and for eign drug manufacturers, distributors; consultants to thedrug industry; drug equipment manu facturers; and numerous trade andprofessional associations representingmanufacturers, repackers, distributors,consulting engineers, and profession als in the health-care general, the comments supportedthe Commissioner s concern for the availability of uniformly high qualitydrug products.

6 Consumers, in particu lar, expressed strong support for theproposed revisions, especially the pro visions for expiration dating of phar maceuticals. A majority of drug manu facturers agreed with many of the pro posed revisions, but objected to few manufacturers objected to mostof the Commissioner is pleased to notethat where differences existed, manyinterested persons furnished alterna tive wording and justification in sup-Port of such alternatives. The Com missioner has carefully consideredevery comment and all suggested al ternatives. The final regulation, setforth below, adopts a number of therecommendations submitted.

7 Certainother recommendatlons, not adoptedat this time, may be considered in anyfuture proposed the past several years, theFDA has issued a number of FEDERAL REGISTER documents relating toCGMP REGULATIONS , specifically Parts210 and 211. The following summarywill help clarify the status of thesevarious A proposal on returned and sal vaged drug products appeared in the IX. Buildings and Facilities (paragraphsFEDERAL REGISTER of January 16, 1975127 to 164). (40 FR 2822) and was reproposed as (paragraphs 165 to 198). (21 CFR ) in the FED-XI. Control of Components and DrugERAL REGISTER of February 13, 1976 ($! Product Containers and Closures (para-FR 6870).)

8 Comments on both propos-graphs 199 to 262). als were reviewed and considered in preparing the final REGULATIONS Setforth in Part 211 A proposal on CGMP regulationsfor human and veterinary drugs ap peared in the FEDERAL REGISTER ofFebruary 13, 1976 (41 FR 6878). Thatproposal is the basis for the subjectfinal REGULATIONS and included pro posed revisions in , , and Parts 210 and 211. and rev ocation of A final regulation in the FEDERAL REGISTER of April 23, 1978 (41 FR 16932) amended Part 211 (CGMP ) by eliminating reference toglass-fiber filters. It, therefore, elimi nated the need for further comments on the February 13, 1976, proposal re garding such filters because all refer ences to glass fiber-containing filterswould be deleted from the final regu A proposal on CGMP regulationsfor large volume parenteral drug prod ucts (LVP) for human use was pub lished the FEDERAL REGISTER ofJune 1.

9 1976 (41 FR 22202). The pro posal would add a new Part 212. Com ments were due by September 29. 1976and are under A request for comments and infor mation regarding small volume paren teral drug products (SVP) was pub lished in the FEDERAL REGISTER of June 1. 1976 (41 FR 222193. and the time for submitting comments was ex tended to October 29, 1976 by notice inthe FEDERAL REGISTER of September10, 1976 (41 FR 38540). Comments arebeing reviewed, and a specific proposalmay be published in the comments and recommenda tions regarding the January 16. 1975and February 13, 1976 proposals, theApril 23. 1976 amendment to the latterproposal, and the Commissioner s con clusions concerning them are set outbelow.)

10 TABLE OF CONTENTS FOR PREAMBLE I. General Comments (paragraphs 1 to12).II. Terminology and Language in these REGULATIONS (paragraphs 13 to 18).III. Amendments Regarding Placement ofExpiration Date on Drug Product Labels (paragraphs 19 to 27).IV. Amendments Regarding Drug Listing and Establishment Registration Require ments for Drug Product Salvaging Oper ations (paragraphs 28 to 32).V. Legal Status of CGMP REGULATIONS (paragraphs 33 to 41). VI. Applicability of CGMP REGULATIONS ;Exemptions (paragraphs 42 to 49).VII. Definitions (paragraphs 50 to 88). VIII. Organization and Personnel (para graphs 89 to 126).FEDERAL REGISTER, VOL.