[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]
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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.
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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
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Annual
21 CFR Section No. of Frequency per Total Annual Hours per Total Hours
Recordkeepers Recordkeeping Records Recordkeeper
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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
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\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
