[Federal Register Volume 63, Number 247 (Thursday, December 24, 1998)] [Notices] [Pages 71291-71294] From the Federal Register Online via the Government Publishing Office [www.gpo.gov] [FR Doc No: 98-34114] ----------------------------------------------------------------------- DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. 98N-1110] Agency Information Collection Activities: Proposed Collection; Comment Request; CGMP Regulations for Finished Pharmaceuticals AGENCY: Food and Drug Administration, HHS. ACTION: Notice. ----------------------------------------------------------------------- SUMMARY: The Food and Drug Administration (FDA) is announcing an opportunity for public comment on the proposed collection of certain information by the agency. Under the Paperwork Reduction Act of 1995 (the PRA), Federal agencies are required to publish notice in the Federal Register concerning each proposed collection of information, including each proposed reinstatement of an existing collection of information, and to allow 60 days for public comment in response to the notice. This notice solicits comments on information collection provisions relating to the regulation of FDA's current good manufacturing practices (CGMP's) and related regulations for finished pharmaceuticals. DATES: Submit written comments on the collection of information by February 22, 1999. ADDRESSES: Submit written comments on the collection of information to the Dockets Management Branch (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. All comments should be identified with the docket number found in brackets in the heading of this document. FOR FURTHER INFORMATION CONTACT: Karen L. Nelson, Office of Information Resources Management (HFA-250), Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857, 301-827-1482. SUPPLEMENTARY INFORMATION: Under the PRA (44 U.S.C. 3501-3520), Federal agencies must obtain approval from the Office of Management and Budget (OMB) for each collection of information they conduct or sponsor. ``Collection of information'' is defined in 44 U.S.C. 3502(3) and 5 CFR 1320.3(c) and includes agency requests or requirements that members of the public submit reports, keep records, or provide information to a third party. Section 3506(c)(2)(A) of the PRA (44 U.S.C. 3506(c)(2)(A)) requires Federal agencies to provide a 60-day notice in the Federal Register concerning each proposed collection of information, including each proposed reinstatement of an existing collection of information, before submitting the collection to OMB for approval. To comply with this requirement, FDA is publishing notice of the proposed collection of information listed below. With respect to the following collection of information, FDA invites comments on: (1) Whether the proposed collection of information is necessary for the proper performance of FDA's functions, including whether the information will have practical utility; (2) the accuracy of FDA's estimate of the burden of the proposed collection of information, including the validity of the methodology and assumptions used; (3) ways to enhance the quality, utility, and clarity of the information to be collected; and (4) ways to minimize the burden of the collection of information on respondents, including through the use of automated collection techniques, when appropriate, and other forms of information technology. [[Page 71292]] CGMP Regulations for Finished Pharmaceuticals--Parts 210 and 211 (21 CFR Parts 210 and 211) (OMB Control Number 0910-0139)-- Reinstatement Under section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (the act) (21 U.S.C. 351(a)(2)(B)), a drug is deemed to be adulterated if the methods used in, or the facilities or controls used for, its manufacture, processing, packing, or holding do not conform to or are not operated or administered in conformity with CGMP's to ensure that such drug meets the requirements of the act as to safety and has the identity and strength, and meets the quality and purity characteristics, which it purports or is represented to possess. FDA has the authority under section 701(a) of the act (21 U.S.C. 371(a)) to issue regulations for the efficient enforcement of the act regarding CGMP procedures for manufacturing, processing, and holding drugs and drug products. The CGMP regulations help ensure that drug products meet the statutory requirements for safety and have their purported or represented identity, strength, quality, and purity characteristics. The information collection requirements in the CGMP regulations provide FDA with the necessary information to perform its duty to protect public health and safety. Although CGMP must be current in the industry, a practice need not be widely prevalent providing such practice is both feasible and valuable in ensuring drug quality. CGMP requirements establish accountability in the manufacturing and processing of drug products, provide for meaningful FDA inspections, and enable manufacturers to improve the quality of drug products over time. The recordkeeping requirements also serve preventive and remedial purposes and provide crucial information if it is necessary to recall a drug product. The general requirements for recordkeeping under part 211 (21 CFR part 211) are set forth in Sec. 211.180. Any production, control, or distribution record associated with a batch and required to be maintained in compliance with part 211 must be retained for at least 1 year after the expiration date of the batch and, for certain OTC drugs, 3 years after distribution of the batch (Sec. 211.180(a)). Records for all components, drug product containers, closures, and labeling are required to be maintained for at least 1 year after the expiration date and 3 years for certain OTC products (Sec. 211.180(b)). All part 211 records must be readily available for authorized inspections during the retention period (Sec. 211.180(c)), and such records may be retained either as original records or as true copies (Sec. 211.180(d)). In addition, 21 CFR 11.2(a) provides that ``For records required to be maintained but not submitted to the agency, persons may use electronic records in lieu of paper records or electronic signatures in lieu of traditional signatures, in whole or in part, provided that the requirements of this part are met.'' To the extent this electronic option is used, the burden of maintaining paper records should be substantially reduced as should any review of such records. In order to facilitate improvements and corrective actions, records must be maintained so that data can be used for evaluating, at least annually, the quality standards of each drug product to determine the need for changes in drug product specifications or manufacturing or control procedures (Sec. 211.180(e)). Written procedures for these evaluations are to be established and include provisions for a review of a representative number of batches and, where applicable, records associated with the batch, and provisions for a review of complaints, recalls, returned or salvaged drug products, and investigations conducted under Sec. 211.192 for each drug product. Written procedures, referred to here as standard operating procedures (SOP's), are required for many part 211 records. The current SOP requirements were initially provided in a final rule published in the Federal Register of September 29, 1978 (43 FR 45014), and are now an integral and familiar part of the drug manufacturing process. The major paperwork impact of SOP's results from their creation. Thereafter, SOP's need to be periodically updated. A combined estimate is provided below for routine maintenance of SOP's. Estimates for specific recordkeeping requirements are listed individually. The 25 SOP provisions under part 211 in the combined maintenance estimate include: (1) Sec. 211.22(d) (responsibilities and procedures of the quality control unit); (2) Sec. 211.56(b) (sanitation procedures); (3) Sec. 211.56(c) (use of suitable rodenticides, insecticides, fungicides, fumigating agents, and cleaning and sanitizing agents); (4) Sec. 211.67(b) (cleaning and maintenance of equipment); (5) Sec. 211.68(a) (proper performance of automatic, mechanical, and electronic equipment); (6) Sec. 211.80(a) (receipt, identification, storage, handling, sampling, testing, approval or rejection of components and drug product containers or closures); (7) Sec. 211.94(d) (standards or specifications, methods of testing, and methods of cleaning, sterilizing, and processing to remove pyrogenic properties for drug product containers and closures); (8) Sec. 211.100(a) (production and process control); (9) Sec. 211.110(a) (sampling and testing of in-process materials and drug products); (10) Sec. 211.113(a) (prevention of objectionable microorganisms in drug products not required to be sterile); (11) Sec. 211.113(b) (prevention of microbiological contamination of drug products purporting to be sterile, including validation of any sterilization process); (12) Sec. 211.115(a) (system for reprocessing batches that do not conform to standards or specifications, to insure that reprocessed batches conform with all established standards, specifications, and characteristics); (13) Sec. 211.122(a) (receipt, identification, storage, handling, sampling, examination and/or testing of labeling and packaging materials); (14) Sec. 211.125(f) (control procedures for the issuance of labeling); (15) Sec. 211.130 (packaging and label operations, prevention of mixup and cross contamination, identification and handling of filed drug product containers that are set aside and held in unlabeled condition, identification of the drug product with a lot or control number that permits determination of the history of the manufacture and control of the batch); (16) Sec. 211.142 (warehousing); (17) Sec. 211.150 (distribution of drug products); (18) Sec. 211.160 (laboratory controls); (19) Sec. 211.165(c) (testing and release for distribution); (20) Sec. 211.166(a) (stability testing); (21) Sec. 211.167 (special testing requirements); (22) Sec. 211.180(f) (notification of responsible officials of investigations, recalls, reports of inspectional observations, and any regulatory actions relating to good manufacturing practice); (23) Sec. 211.198(a) (written and oral complaint procedures, including quality control unit review of any complaint involving specifications failures, and serious and unexpected adverse drug experiences); (24) Sec. 211.204 (holding, testing, and reprocessing of returned drug products); and (25) Sec. 211.208 (drug product salvaging). The following burden estimates for routine maintenance and for specific recordkeeping requirements are based on FDA's institutional experience regarding creation and review of such procedures and similar recordkeeping requirements, and data provided by the Eastern Research Group (ERG) which is a consulting group hired by the FDA economics staff to prepare an economic [[Page 71293]] analysis of the potential economic impact of the May 3, 1996 (61 FR 20104), proposed rule. ERG prepared a report for FDA that estimated the recordkeeping burden for the proposed rule entitled ``Current Good Manufacturing Practice: Amendment of Certain Requirements for Finished Pharmaceuticals'' (61 FR 20104). This report provided information on the current number of establishments affected by FDA recordkeeping requirements and FDA has relied on these figures to estimate the number of establishments affected by part 211 recordkeeping provisions. ERG estimated that there are 1,077 establishments involved in pharmaceutical preparations, diagnostic substances, and biological products; 948 repackers or relabelers; and 2,159 medical gas establishments for a total estimate of 4,184 recordkeepers subject to CGMP recordkeeping requirements. ERG used a variety of sources to obtain its estimates including reports from the Department of Commerce and FDA registration files. The ERG report is available at the Dockets Management Branch (address above) under Docket No. 95N-0362. ERG also provided estimates on the burden involved in creating SOP's. While most of the CGMP provisions covered in this document were created many years ago, there will be some existing firms expanding into new manufacturing areas and start-up firms that will need to create SOP's. FDA is assuming that approximately 100 firms will have to create up to 25 SOP's for a total of 2,500 records, and the agency estimates that it will take 20 hours per recordkeeper to create 25 new SOP's for a total of 50,000 hours as a one-time burden. Annual SOP maintenance is estimated to involve 1 hour annually per SOP, totaling 25 hours annually per recordkeeper. The proposed rule revising part 211 CGMP requirements of May 3, 1996, would require additional SOP's. Cost estimates for those additional SOP's were included in the proposed rule, but are not included here. Any comments on those estimates will be evaluated in any final rule based on that proposal. FDA estimates the burden of this collection of information as follows: Table 1.--Estimated Annual Recordkeeping Burden1 ---------------------------------------------------------------------------------------------------------------- Annual 21 CFR Section No. of Frequency per Total Annual Hours per Total Hours Recordkeepers Recordkeeping Records Recordkeeper ---------------------------------------------------------------------------------------------------------------- SOP Maintenance (See previous list of 25 SOP's) 4,184 1 4,184 25 104,600 One-time Burden (New Start- up SOP's)2 100 25 2,500 20 50,000 211.34 4,184 .25 1,046 .5 523 211.67(c) 4,184 50 209,200 .25 52,300 211.68 4,184 2 8,368 1 8,368 211.68(a) 4,184 10 41,840 .5 20,920 211.68(b) 4,184 5 20,920 .25 5,230 211.72 4,184 .25 1,046 1 1,046 211.80(d) 4,184 .25 1,046 .1 105 211.100(b) 4,184 3 12,552 2 25,104 211.105(b) 4,184 .25 1,046 .25 262 211.122(c) 4,184 50 209,200 .25 52,300 211.130(e) 4,184 50 209,200 .25 52,300 211.132(c) 1,698 20 33,960 .5 16,980 211.132(d) 1,698 .2 340 .5 170 211.137 4,184 5 2,0920 .5 10,460 211.160(a) 4,184 2 8,368 1 8,368 211.165(e) 4,184 1 4,184 1 4,184 211.166(c) 4,184 2 8,368 .5 4,184 211.173 1,077 1 1,077 .25 269 211.180(e) 4,184 .2 837 .25 209 211.180(f) 4,184 .2 837 1 837 211.182 4,184 2 8,368 .25 2,092 211.184 4,184 3 12,552 .5 6,276 211.188 4,184 25 104,600 2 209,200 211.186 4,184 10 41,840 2 83,680 211.192 4,184 2 8,368 1 8,368 211.194 4,184 25 104,600 .5 52,300 211.196 4,184 25 104,600 .25 26,150 211.198 4,184 5 20,920 1 20,920 211.204 4,184 10 41,840 .5 20,920 Total 848,625 ---------------------------------------------------------------------------------------------------------------- \1\ There are no capital costs or operating and maintenance costs associated with this collection of information. \2\ This is a one-time burden. [[Page 71294]] Dated: December 15, 1998 William K. Hubbard, Associate Commissioner for Policy Coordination. [FR Doc. 98-34114 Filed 12-23-98; 8:45 am] BILLING CODE 4160-01-F