Agency Information Collection Activities; Submission for Office of Management and Budget Review; Comment Request; Current Good Manufacturing Practice Regulations for Finished Pharmaceuticals, 60052-60055 [2011-24991]
Download as PDF
<![CDATA[
60052
Federal Register / Vol. 76, No. 188 / Wednesday, September 28, 2011 / Notices
ANNUAL BURDEN ESTIMATES
Number of
respondents
Instrument
State Council on Developmental Disabilities Program Performance Report ..
55
Estimated Total Annual Burden
Hours: 7,590.
In compliance with the requirements
of Section 506(c)(2)(A) of the Paperwork
Reduction Act of 1995, the
Administration for Children and
Families is soliciting public comment
on the specific aspects of the
information collection described above.
Copies of the proposed collection of
information can be obtained and
comments may be forwarded by writing
to the Administration for Children and
Families, Office of Planning, Research
and Evaluation, 370 L’Enfant
Promenade, SW., Washington, DC
20447, Attn: ACF Reports Clearance
Officer. E-mail address:
infocollection@acf.hhs.gov. All requests
should be identified by the title of the
information collection.
The Department specifically requests
comments on: (a) Whether the proposed
collection of information is necessary
for the proper performance of the
functions of the agency, including
whether the information shall have
practical utility; (b) the accuracy of the
agency’s estimate of the burden of the
proposed collection of information; (c)
the quality, utility, and clarity of the
information to be collected; and (d)
ways to minimize the burden
information to be collected; and (d)
ways to minimize the burden of the
collection of information on
respondents, including through the use
of automated collection techniques or
other forms of information technology.
Consideration will be given to
comments and suggestions submitted
within 60 days of this publication.
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Robert Sargis,
Reports Clearance Officer.
FOR FURTHER INFORMATION CONTACT:
[FR Doc. 2011–24967 Filed 9–27–11; 8:45 am]
sroberts on DSK5SPTVN1PROD with NOTICES
BILLING CODE 4184–01–P
Food and Drug Administration
[Docket No. FDA–2011–N–0362]
Agency Information Collection
Activities; Submission for Office of
Management and Budget Review;
Comment Request; Current Good
Manufacturing Practice Regulations for
Finished Pharmaceuticals
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice.
The Food and Drug
Administration (FDA) is announcing
that a proposed collection of
information has been submitted to the
Office of Management and Budget
(OMB) for review and clearance under
the Paperwork Reduction Act of 1995.
SUMMARY:
Fax written comments on the
collection of information by October 28,
2011.
DATES:
To ensure that comments on
the information collection are received,
OMB recommends that written
comments be faxed to the Office of
Information and Regulatory Affairs,
OMB, Attn: FDA Desk Officer, Fax: 202–
395–7285, or e-mailed to
oira_submission@omb.eop.gov. All
comments should be identified with the
OMB control number 0910–0139. Also
include the FDA docket number found
in brackets in the heading of this
document.
ADDRESSES:
Juanmanuel Vilela, Office of
Information Management, Food and
Drug Administration, 1350 Piccard Dr.,
PI50–400B, Rockville, MD 20850, 301–
796–7651,
juanmanuel.vilela@fda.hhs.gov.
In
compliance with 44 U.S.C. 3507, FDA
has submitted the following proposed
collection of information to OMB for
review and clearance.
SUPPLEMENTARY INFORMATION:
VerDate Mar<15>2010
19:59 Sep 27, 2011
Jkt 223001
PO 00000
Frm 00056
Fmt 4703
Sfmt 4703
Number of
responses per
respondent
1
Average
burden hours
per response
138
Total burden
hours
7,590
Current Good Manufacturing Practice
Regulations for Finished
Pharmaceuticals—21CFR Parts 210 and
211 (OMB Control No. 0910–0139)—
Extension
Under Section 501(a)(2)(B) of the
Federal Food, Drug, and Cosmetic Act
(the FD&C Act) (21 U.S.C. 351(a)(2)(B)),
a drug is 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 Current Good
Manufacturing Practices (CGMPs) to
ensure that such drug meets the
requirements of the FD&C 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.
The FDA has the authority under
Section 701(a) of the FD&C Act
(21 U.S.C. 371(a)) to issue regulations
for the efficient enforcement of the
FD&C 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.
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
CGMP 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 § 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 one year after the
expiration date of the batch and, for
certain OTC drugs, three years after
distribution of the batch (§ 211.180(a)).
E:\FR\FM\28SEN1.SGM
28SEN1
sroberts on DSK5SPTVN1PROD with NOTICES
Federal Register / Vol. 76, No. 188 / Wednesday, September 28, 2011 / Notices
Records for all components, drug
product containers, closures, and
labeling are required to be maintained
for at least one year after the expiration
date and three years for certain OTC
products (§ 211.180(b)).
All part 211 records must be readily
available for authorized inspections
during the retention period
(§ 211.180(c)), and such records may be
retained either as original records or as
true copies (§ 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 (§ 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; provisions for a review
of complaints, recalls, returned or
salvaged drug products; and
investigations conducted under
§ 211.192 for each drug product.
The specific recordkeeping
requirements provided in table 1 of this
document are as follows:
Section 211.34—Consultants advising
on the manufacture, processing,
packing, or holding of drug products
must have sufficient education, training,
and experience to advise on the subject
for which they are retained. Records
must be maintained stating the name,
address, and qualifications of any
consultants and the type of service they
provide.
Section 211.67(c)—Records must be
kept of maintenance, cleaning,
sanitizing, and inspection as specified
in §§ 211.180 and 211.182.
Section 211.68—Appropriate controls
must be exercised over computer or
related systems to assure that changes in
master production and control records
or other records are instituted only by
authorized personnel.
Section 211.68(a)—Records must be
maintained of calibration checks,
inspections, and computer or related
VerDate Mar<15>2010
18:20 Sep 27, 2011
Jkt 223001
system programs for automatic,
mechanical, and electronic equipment.
Section 211.68(b)—All appropriate
controls must be exercised over all
computers or related systems and
control data systems to assure that
changes in master production and
control records or other records are
instituted only by authorized persons.
Section 211.72—Filters for liquid
filtration used in the manufacture,
processing, or packing of injectable drug
products intended for human use must
not release fibers into such products.
Section 211.80(d)—Each container or
grouping of containers for components
or drug product containers or closures
must be identified with a distinctive
code for each lot in each shipment
received. This code must be used in
recording the disposition of each lot.
Each lot must be appropriately
identified as to its status.
Section 211.100(b)—Written
production and process control
procedures must be followed in the
execution of the various production and
process control functions and must be
documented at the time of performance.
Any deviation from the written
procedures must be recorded and
justified.
Section 211.105(b)—Major equipment
must be identified by a distinctive
identification number or code that must
be recorded in the batch production
record to show the specific equipment
used in the manufacture of each batch
of a drug product. In cases where only
one of a particular type of equipment
exists in a manufacturing facility, the
name of the equipment may be used in
lieu of a distinctive identification
number or code.
Section 211.122(c)—Records must be
maintained for each shipment received
of each different labeling and packaging
material indicating receipt,
examination, or testing.
Section 211.130(e)—Inspection of
packaging and labeling facilities must be
made immediately before use to assure
that all drug products have been
removed from previous operations.
Inspection must also be made to assure
that packaging and labeling materials
not suitable for subsequent operations
have been removed. Results of
inspection must be documented in the
batch production records.
Section 211.132(c)—Certain retail
packages of OTC drug products must
bear a statement that is prominently
placed so consumers are alerted to the
specific tamper-evident feature of the
package. The labeling statement is
required to be so placed that it will be
unaffected if the tamper-resistant feature
of the package is breached or missing.
PO 00000
Frm 00057
Fmt 4703
Sfmt 4703
60053
If the tamper-evident feature chosen is
one that uses an identifying
characteristic, that characteristic is
required to be referred to in the labeling
statement.
Section 211.132(d)—A request for an
exemption from packaging and labeling
requirements by a manufacturer or
packer is required to be submitted in the
form of a citizen petition under 21 CFR
10.30.
Section 211.137—Requirements
regarding product expiration dating and
compliance with 21 CFR 201.17 are set
forth.
Section 211.160(a)—The
establishment of any specifications,
standards, sampling plans, test
procedures, or other laboratory control
mechanisms, including any change in
such specifications, standards, sampling
plans, test procedures, or other
laboratory control mechanisms, must be
drafted by the appropriate
organizational unit and reviewed and
approved by the quality control unit.
These requirements must be followed
and documented at the time of
performance. Any deviation from the
written specifications, standards,
sampling plans, test procedures, or
other laboratory control mechanisms
must be recorded and justified.
Section 211.165(e)—The accuracy,
sensitivity, specificity, and
reproducibility of test methods
employed by a firm must be established
and documented. Such validation and
documentation may be accomplished in
accordance with § 211.194(a)(2).
Section 211.166(c)—Homeopathic
drug product requirements are set forth.
Section 211.173—Animals used in
testing components, in-process
materials, or drug products for
compliance with established
specifications must be maintained and
controlled in a manner that assures their
suitability for their intended use. They
must be identified, and adequate
records must be maintained showing the
history of their use.
Section 211.180(e)—Written records
required by part 211 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. Written
procedures must be established and
followed for such evaluations and must
include provisions for a representative
number of batches, whether approved or
unapproved or rejected, and a review of
complaints, recalls, returned or salvaged
drug products, and investigations
conducted under § 211.192 for each
drug product.
E:\FR\FM\28SEN1.SGM
28SEN1
sroberts on DSK5SPTVN1PROD with NOTICES
60054
Federal Register / Vol. 76, No. 188 / Wednesday, September 28, 2011 / Notices
Section 211.180(f)—Procedures must
be established to assure that the
responsible officials of the firm, if they
are not personally involved in or
immediately aware of such actions, are
notified in writing of any investigations,
conducted under § 211.198, 211.204, or
211.208, any recalls, reports of
inspectional observations issued, or any
regulatory actions relating to good
manufacturing practices brought by
FDA.
Section 211.182—Specifies
requirements for equipment cleaning
records and the use log.
Section 211.184—Specifies
requirements for component, drug
product container, closure, and labeling
records.
Section 211.186—Specifies master
production and control records
requirements.
Section 211.188—Specifies batch
production and control records
requirement.
Section 211.192—Specifies the
information that must be maintained on
the investigation of discrepancies found
in the review of all drug product
production and control records by the
quality control staff.
Section 211.194—Explains and
describes laboratory records that must
be retained.
Section 211.196—Specifies the
information that must be included in
records on the distribution of the drug.
Section 211.198—Specifies and
describes the handling of all complaint
files received by the applicant.
Section 211.204—Specifies that
records be maintained of returned and
salvaged drug products and describes
the procedures involved.
Written procedures, referred to here
as standard operating procedures
(SOPs), 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 information collection impact of
SOPs results from their creation.
Thereafter, SOPs need to be periodically
updated. A combined estimate for
routine maintenance of SOPs is
provided in table 1 of this document.
The 25 SOP provisions under Part 211
in the combined maintenance estimate
include:
Section 211.22(d)—Responsibilities
and procedures of the quality control
unit;
Section 211.56(b)—Sanitation
procedures;
Section 211.56(c)—Use of suitable
rodenticides, insecticides, fungicides,
VerDate Mar<15>2010
18:20 Sep 27, 2011
Jkt 223001
fumigating agents, and cleaning and
sanitizing agents;
Section 211.67(b)—Cleaning and
maintenance of equipment;
Section 211.68(a)—Proper
performance of automatic, mechanical,
and electronic equipment;
Section 211.80(a)—Receipt,
identification, storage, handling,
sampling, testing, and approval or
rejection of components and drug
product containers or closures;
Section 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;
Section 211.100(a)—Production and
process control;
Section 211.110(a)—Sampling and
testing of in-process materials and drug
products;
Section 211.113(a)—Prevention of
objectionable microorganisms in drug
products not required to be sterile;
Section 211.113(b)—Prevention of
microbiological contamination of drug
products purporting to be sterile,
including validation of any sterilization
process;
Section 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;
Section 211.122(a)—Receipt,
identification, storage, handling,
sampling, examination and/or testing of
labeling and packaging materials;
Section 211.125(f)—Control
procedures for the issuance of labeling;
Section 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, and 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;
Section 211.142—Warehousing;
Section 211.150—Distribution of drug
products;
Section 211.160—Laboratory controls;
Section 211.165(c)—Testing and
release for distribution;
Section 211.166(a)—Stability testing;
Section 211.167—Special testing
requirements;
Section 211.180(f)—Notification of
responsible officials of investigations,
recalls, reports of inspectional
observations, and any regulatory actions
relating to good manufacturing practice;
Section 211.198(a)—Written and oral
complaint procedures, including quality
PO 00000
Frm 00058
Fmt 4703
Sfmt 4703
control unit review of any complaint
involving specifications failures, and
serious and unexpected adverse drug
experiences;
Section 211.204—Holding, testing,
and reprocessing of returned drug
products; and
Section 211.208—Drug product
salvaging.
In addition, the following regulations
in parts 610 and 680 (21 CFR Parts 610
and 680) reference certain CGMP
regulations in part 211: §§ 610.12(h),
610.13(a)(2), 610.18(d), 680.2(f), and
680.3(f). In table 1 of this document, the
burden associated with the information
collection requirements in these
regulations is included in the burden
estimates under §§ 211.165, 211.167,
211.188, and 211.194, as appropriate.
Although 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 startup
firms that will need to create SOPs. As
provided in table 1 of this document,
FDA is assuming that approximately
100 firms will have to create up to 25
SOPs for a total of 2,500 records, and
the Agency estimates that it will take 20
hours per recordkeeper to create 25 new
SOPs for a total of 50,000 hours.
In the Federal Register of May 31,
2011 (76 FR 31342), FDA published a
60-day notice requesting public
comment on the proposed collection of
information. FDA received one
comment that pertained to the
information collection.
The comment, from a plasma protein
therapies association, stated that data
from their association members may be
higher than FDA’s estimates and
provided some examples of differences
between their numbers and FDA’s
estimates. The comment stated that
table 1 in the notice provides averages,
but does not give data range. The
comment requested that FDA provide
data ranges so they could better assess
if their members’ high data are factored
into the Agency’s averages.
The burden estimates in the 60-day
notice were compiled by FDA personnel
(including field personnel who visit
sites and review records) familiar with
the records and the time it takes to
assemble and maintain these records.
The estimates are not expressed in
ranges of data. The burden estimates are
published every 3 years in the Federal
Register to give the public an
opportunity to comment on the
accuracy of the estimates. We appreciate
that the comment informed us that their
actual data differed from our estimates.
However, for us to consider revising our
estimates, we request that the comment
E:\FR\FM\28SEN1.SGM
28SEN1
Federal Register / Vol. 76, No. 188 / Wednesday, September 28, 2011 / Notices
provide to the docket specific proposals
on what the burden estimates should be
for their members for the CFR sections
and headings in table 1 of this notice.
60055
FDA estimates the burden of this
collection of information as follows:
TABLE 1—ESTIMATED ANNUAL RECORDKEEPING BURDEN 1
Number of
recordkeepers
21 CFR Section
SOP maintenance (See list of 25 SOPs in the SUPPLEMENTARY INFORMATION section of this document)
New startup SOPs .............................................................
211.34 ................................................................................
211.67(c) ............................................................................
211.68 ................................................................................
211.68(a) ............................................................................
211.68(b) ............................................................................
211.72 ................................................................................
211.80(d) ............................................................................
211.100(b) ..........................................................................
211.105(b) ..........................................................................
211.122(c) ..........................................................................
211.130(e) ..........................................................................
211.132(c) ..........................................................................
211.132(d) ..........................................................................
211.137 ..............................................................................
211.160(a) ..........................................................................
211.165(e) ..........................................................................
211.166(c) ..........................................................................
211.173 ..............................................................................
211.180(e) ..........................................................................
211.180(f) ...........................................................................
211.182 ..............................................................................
211.184 ..............................................................................
211.186 ..............................................................................
211.188 ..............................................................................
211.192 ..............................................................................
211.194 ..............................................................................
211.196 ..............................................................................
211.198 ..............................................................................
211.204 ..............................................................................
4,184
100
4,184
4,184
4,184
4,184
4,184
4,184
4,184
4, 184
4,184
4,184
4,184
1,698
1,698
4,184
4,184
4,184
4,184
1.077
4,184
4,184
4,184
4,184
4,184
4,184
4,184
4,184
4,184
4,184
4,184
Total ............................................................................
........................
Number of
records per
recordkeeper
1 There
Total annual
records
1
25
Average
burden per
recordkeeping
(in hours) 2
Total
hours
.25
50
2
10
5
.25
.25
3
.25
50
50
20
.2
5
2
1
2
1
.2
.2
2
3
10
25
2
25
25
5
10
4,184
2500
1,046
209,200
8,368
41,840
20,920
1,046
1,046
12,552
1,046
209,200
209,200
33,960
340
20,920
8,368
4,184
8,368
1,077
837
837
8,368
12,552
41,840
104,600
8,368
104,600
104,600
20,920
41,840
25
20
30/60
15/60
1
30/60
15/60
1
6/60
2
15/60
15/60
15/60
30/60
30/60
30/60
1
1
30/60
15/60
15/60
1
15/60
30/60
2
2
1
30/60
15/60
1
30/60
104,600
50,000
523
52,300
8,368
20,920
5,230
1,046
105
25,104
262
52,300
52,300
16,980
170
10,460
8,368
4,184
4,184
269
209
837
2,092
6,276
83,680
209,200
8,368
52,300
26,150
20,920
20,920
..........................
........................
........................
848,625
are no capital costs or operating and maintenance costs associated with this collection of information.
estimates of less than 1 hour are expressed as a fraction of an hour in the format ‘‘[number of minutes per response]/60’’.
2 Burden
Dated: September 22, 2011.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2011–24991 Filed 9–27–11; 8:45 am]
BILLING CODE 4160–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
sroberts on DSK5SPTVN1PROD with NOTICES
[Docket No. FDA–2011–D–0212]
Draft Guidance for Industry:
Applications for Premarket Review of
New Tobacco Products; Availability;
Agency Information Collection
Activities; Proposed Collection;
Comment Request
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice.
VerDate Mar<15>2010
18:20 Sep 27, 2011
Jkt 223001
The Food and Drug
Administration (FDA) is announcing the
availability of a draft guidance for
industry entitled ‘‘Applications for
Premarket Review of New Tobacco
Products.’’ The draft guidance is
intended to assist persons submitting
applications for new tobacco products
under the Federal Food, Drug, and
Cosmetic Act (the FD&C Act), as
amended by the Family Smoking
Prevention and Tobacco Control Act
(Tobacco Control Act). The draft
guidance explains, among other things,
for new tobacco product applications,
who submits, when and how to submit,
what information the FD&C Act requires
applicants to submit, and what
information FDA recommends that
applicants submit.
SUMMARY:
Although you can comment on
any guidance at any time (see 21 CFR
10.115(g)(5)), to ensure that the Agency
considers your comment on this draft
DATES:
PO 00000
Frm 00059
Fmt 4703
Sfmt 4703
guidance before it begins work on the
final version of the guidance, submit
written or electronic comments on the
draft guidance by December 27, 2011.
Submit electronic
comments on the draft guidance,
including comments on the proposed
collection of information, to https://
www.regulations.gov.
Submit written comments on the draft
guidance, including comments
regarding the proposed collection of
information, to the Division of Dockets
Management (HFA–305), Food and Drug
Administration, 5630 Fishers Lane, rm.
1061, Rockville, MD 20852.
Submit written requests for single
copies of the draft guidance document
entitled ‘‘Applications for Premarket
Review of New Tobacco Products’’ to
the Center for Tobacco Products, Food
and Drug Administration, 9200
Corporate Blvd., Rockville, MD 20850–
3229. Send one self-addressed adhesive
ADDRESSES:
E:\FR\FM\28SEN1.SGM
28SEN1
]]>Agencies
[Federal Register Volume 76, Number 188 (Wednesday, September 28, 2011)]
[Notices]
[Pages 60052-60055]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2011-24991]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2011-N-0362]
Agency Information Collection Activities; Submission for Office
of Management and Budget Review; Comment Request; Current Good
Manufacturing Practice Regulations for Finished Pharmaceuticals
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA) is announcing that a
proposed collection of information has been submitted to the Office of
Management and Budget (OMB) for review and clearance under the
Paperwork Reduction Act of 1995.
DATES: Fax written comments on the collection of information by October
28, 2011.
ADDRESSES: To ensure that comments on the information collection are
received, OMB recommends that written comments be faxed to the Office
of Information and Regulatory Affairs, OMB, Attn: FDA Desk Officer,
Fax: 202-395-7285, or e-mailed to oira_submission@omb.eop.gov. All
comments should be identified with the OMB control number 0910-0139.
Also include the FDA docket number found in brackets in the heading of
this document.
FOR FURTHER INFORMATION CONTACT: Juanmanuel Vilela, Office of
Information Management, Food and Drug Administration, 1350 Piccard Dr.,
PI50-400B, Rockville, MD 20850, 301-796-7651,
juanmanuel.vilela@fda.hhs.gov.
SUPPLEMENTARY INFORMATION: In compliance with 44 U.S.C. 3507, FDA has
submitted the following proposed collection of information to OMB for
review and clearance.
Current Good Manufacturing Practice Regulations for Finished
Pharmaceuticals--21CFR Parts 210 and 211 (OMB Control No. 0910-0139)--
Extension
Under Section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic
Act (the FD&C Act) (21 U.S.C. 351(a)(2)(B)), a drug is 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 Current Good
Manufacturing Practices (CGMPs) to ensure that such drug meets the
requirements of the FD&C 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.
The FDA has the authority under Section 701(a) of the FD&C Act (21
U.S.C. 371(a)) to issue regulations for the efficient enforcement of
the FD&C 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. 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 CGMP 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
one year after the expiration date of the batch and, for certain OTC
drugs, three years after distribution of the batch (Sec. 211.180(a)).
[[Page 60053]]
Records for all components, drug product containers, closures, and
labeling are required to be maintained for at least one year after the
expiration date and three 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; provisions for a review of complaints,
recalls, returned or salvaged drug products; and investigations
conducted under Sec. 211.192 for each drug product.
The specific recordkeeping requirements provided in table 1 of this
document are as follows:
Section 211.34--Consultants advising on the manufacture,
processing, packing, or holding of drug products must have sufficient
education, training, and experience to advise on the subject for which
they are retained. Records must be maintained stating the name,
address, and qualifications of any consultants and the type of service
they provide.
Section 211.67(c)--Records must be kept of maintenance, cleaning,
sanitizing, and inspection as specified in Sec. Sec. 211.180 and
211.182.
Section 211.68--Appropriate controls must be exercised over
computer or related systems to assure that changes in master production
and control records or other records are instituted only by authorized
personnel.
Section 211.68(a)--Records must be maintained of calibration
checks, inspections, and computer or related system programs for
automatic, mechanical, and electronic equipment.
Section 211.68(b)--All appropriate controls must be exercised over
all computers or related systems and control data systems to assure
that changes in master production and control records or other records
are instituted only by authorized persons.
Section 211.72--Filters for liquid filtration used in the
manufacture, processing, or packing of injectable drug products
intended for human use must not release fibers into such products.
Section 211.80(d)--Each container or grouping of containers for
components or drug product containers or closures must be identified
with a distinctive code for each lot in each shipment received. This
code must be used in recording the disposition of each lot. Each lot
must be appropriately identified as to its status.
Section 211.100(b)--Written production and process control
procedures must be followed in the execution of the various production
and process control functions and must be documented at the time of
performance. Any deviation from the written procedures must be recorded
and justified.
Section 211.105(b)--Major equipment must be identified by a
distinctive identification number or code that must be recorded in the
batch production record to show the specific equipment used in the
manufacture of each batch of a drug product. In cases where only one of
a particular type of equipment exists in a manufacturing facility, the
name of the equipment may be used in lieu of a distinctive
identification number or code.
Section 211.122(c)--Records must be maintained for each shipment
received of each different labeling and packaging material indicating
receipt, examination, or testing.
Section 211.130(e)--Inspection of packaging and labeling facilities
must be made immediately before use to assure that all drug products
have been removed from previous operations. Inspection must also be
made to assure that packaging and labeling materials not suitable for
subsequent operations have been removed. Results of inspection must be
documented in the batch production records.
Section 211.132(c)--Certain retail packages of OTC drug products
must bear a statement that is prominently placed so consumers are
alerted to the specific tamper-evident feature of the package. The
labeling statement is required to be so placed that it will be
unaffected if the tamper-resistant feature of the package is breached
or missing. If the tamper-evident feature chosen is one that uses an
identifying characteristic, that characteristic is required to be
referred to in the labeling statement.
Section 211.132(d)--A request for an exemption from packaging and
labeling requirements by a manufacturer or packer is required to be
submitted in the form of a citizen petition under 21 CFR 10.30.
Section 211.137--Requirements regarding product expiration dating
and compliance with 21 CFR 201.17 are set forth.
Section 211.160(a)--The establishment of any specifications,
standards, sampling plans, test procedures, or other laboratory control
mechanisms, including any change in such specifications, standards,
sampling plans, test procedures, or other laboratory control
mechanisms, must be drafted by the appropriate organizational unit and
reviewed and approved by the quality control unit. These requirements
must be followed and documented at the time of performance. Any
deviation from the written specifications, standards, sampling plans,
test procedures, or other laboratory control mechanisms must be
recorded and justified.
Section 211.165(e)--The accuracy, sensitivity, specificity, and
reproducibility of test methods employed by a firm must be established
and documented. Such validation and documentation may be accomplished
in accordance with Sec. 211.194(a)(2).
Section 211.166(c)--Homeopathic drug product requirements are set
forth.
Section 211.173--Animals used in testing components, in-process
materials, or drug products for compliance with established
specifications must be maintained and controlled in a manner that
assures their suitability for their intended use. They must be
identified, and adequate records must be maintained showing the history
of their use.
Section 211.180(e)--Written records required by part 211 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. Written procedures must be established and followed for
such evaluations and must include provisions for a representative
number of batches, whether approved or unapproved or rejected, and a
review of complaints, recalls, returned or salvaged drug products, and
investigations conducted under Sec. 211.192 for each drug product.
[[Page 60054]]
Section 211.180(f)--Procedures must be established to assure that
the responsible officials of the firm, if they are not personally
involved in or immediately aware of such actions, are notified in
writing of any investigations, conducted under Sec. 211.198, 211.204,
or 211.208, any recalls, reports of inspectional observations issued,
or any regulatory actions relating to good manufacturing practices
brought by FDA.
Section 211.182--Specifies requirements for equipment cleaning
records and the use log.
Section 211.184--Specifies requirements for component, drug product
container, closure, and labeling records.
Section 211.186--Specifies master production and control records
requirements.
Section 211.188--Specifies batch production and control records
requirement.
Section 211.192--Specifies the information that must be maintained
on the investigation of discrepancies found in the review of all drug
product production and control records by the quality control staff.
Section 211.194--Explains and describes laboratory records that
must be retained.
Section 211.196--Specifies the information that must be included in
records on the distribution of the drug.
Section 211.198--Specifies and describes the handling of all
complaint files received by the applicant.
Section 211.204--Specifies that records be maintained of returned
and salvaged drug products and describes the procedures involved.
Written procedures, referred to here as standard operating
procedures (SOPs), 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 information collection impact of SOPs results from their
creation. Thereafter, SOPs need to be periodically updated. A combined
estimate for routine maintenance of SOPs is provided in table 1 of this
document. The 25 SOP provisions under Part 211 in the combined
maintenance estimate include:
Section 211.22(d)--Responsibilities and procedures of the quality
control unit;
Section 211.56(b)--Sanitation procedures;
Section 211.56(c)--Use of suitable rodenticides, insecticides,
fungicides, fumigating agents, and cleaning and sanitizing agents;
Section 211.67(b)--Cleaning and maintenance of equipment;
Section 211.68(a)--Proper performance of automatic, mechanical, and
electronic equipment;
Section 211.80(a)--Receipt, identification, storage, handling,
sampling, testing, and approval or rejection of components and drug
product containers or closures;
Section 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;
Section 211.100(a)--Production and process control;
Section 211.110(a)--Sampling and testing of in-process materials
and drug products;
Section 211.113(a)--Prevention of objectionable microorganisms in
drug products not required to be sterile;
Section 211.113(b)--Prevention of microbiological contamination of
drug products purporting to be sterile, including validation of any
sterilization process;
Section 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;
Section 211.122(a)--Receipt, identification, storage, handling,
sampling, examination and/or testing of labeling and packaging
materials;
Section 211.125(f)--Control procedures for the issuance of
labeling;
Section 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, and 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;
Section 211.142--Warehousing;
Section 211.150--Distribution of drug products;
Section 211.160--Laboratory controls;
Section 211.165(c)--Testing and release for distribution;
Section 211.166(a)--Stability testing;
Section 211.167--Special testing requirements;
Section 211.180(f)--Notification of responsible officials of
investigations, recalls, reports of inspectional observations, and any
regulatory actions relating to good manufacturing practice;
Section 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;
Section 211.204--Holding, testing, and reprocessing of returned
drug products; and
Section 211.208--Drug product salvaging.
In addition, the following regulations in parts 610 and 680 (21 CFR
Parts 610 and 680) reference certain CGMP regulations in part 211:
Sec. Sec. 610.12(h), 610.13(a)(2), 610.18(d), 680.2(f), and 680.3(f).
In table 1 of this document, the burden associated with the information
collection requirements in these regulations is included in the burden
estimates under Sec. Sec. 211.165, 211.167, 211.188, and 211.194, as
appropriate.
Although 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 startup firms that will need to create
SOPs. As provided in table 1 of this document, FDA is assuming that
approximately 100 firms will have to create up to 25 SOPs for a total
of 2,500 records, and the Agency estimates that it will take 20 hours
per recordkeeper to create 25 new SOPs for a total of 50,000 hours.
In the Federal Register of May 31, 2011 (76 FR 31342), FDA
published a 60-day notice requesting public comment on the proposed
collection of information. FDA received one comment that pertained to
the information collection.
The comment, from a plasma protein therapies association, stated
that data from their association members may be higher than FDA's
estimates and provided some examples of differences between their
numbers and FDA's estimates. The comment stated that table 1 in the
notice provides averages, but does not give data range. The comment
requested that FDA provide data ranges so they could better assess if
their members' high data are factored into the Agency's averages.
The burden estimates in the 60-day notice were compiled by FDA
personnel (including field personnel who visit sites and review
records) familiar with the records and the time it takes to assemble
and maintain these records. The estimates are not expressed in ranges
of data. The burden estimates are published every 3 years in the
Federal Register to give the public an opportunity to comment on the
accuracy of the estimates. We appreciate that the comment informed us
that their actual data differed from our estimates. However, for us to
consider revising our estimates, we request that the comment
[[Page 60055]]
provide to the docket specific proposals on what the burden estimates
should be for their members for the CFR sections and headings in table
1 of this notice.
FDA estimates the burden of this collection of information as
follows:
Table 1--Estimated Annual Recordkeeping Burden 1
----------------------------------------------------------------------------------------------------------------
Average burden
Number of Number of Total annual per
21 CFR Section recordkeepers records per records recordkeeping Total hours
recordkeeper (in hours) 2
----------------------------------------------------------------------------------------------------------------
SOP maintenance (See list of 25 4,184 1 4,184 25 104,600
SOPs in the SUPPLEMENTARY
INFORMATION section of this
document)......................
New startup SOPs................ 100 25 2500 20 50,000
211.34.......................... 4,184 .25 1,046 30/60 523
211.67(c)....................... 4,184 50 209,200 15/60 52,300
211.68.......................... 4,184 2 8,368 1 8,368
211.68(a)....................... 4,184 10 41,840 30/60 20,920
211.68(b)....................... 4,184 5 20,920 15/60 5,230
211.72.......................... 4,184 .25 1,046 1 1,046
211.80(d)....................... 4,184 .25 1,046 6/60 105
211.100(b)...................... 4, 184 3 12,552 2 25,104
211.105(b)...................... 4,184 .25 1,046 15/60 262
211.122(c)...................... 4,184 50 209,200 15/60 52,300
211.130(e)...................... 4,184 50 209,200 15/60 52,300
211.132(c)...................... 1,698 20 33,960 30/60 16,980
211.132(d)...................... 1,698 .2 340 30/60 170
211.137......................... 4,184 5 20,920 30/60 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 30/60 4,184
211.173......................... 1.077 1 1,077 15/60 269
211.180(e)...................... 4,184 .2 837 15/60 209
211.180(f)...................... 4,184 .2 837 1 837
211.182......................... 4,184 2 8,368 15/60 2,092
211.184......................... 4,184 3 12,552 30/60 6,276
211.186......................... 4,184 10 41,840 2 83,680
211.188......................... 4,184 25 104,600 2 209,200
211.192......................... 4,184 2 8,368 1 8,368
211.194......................... 4,184 25 104,600 30/60 52,300
211.196......................... 4,184 25 104,600 15/60 26,150
211.198......................... 4,184 5 20,920 1 20,920
211.204......................... 4,184 10 41,840 30/60 20,920
-------------------------------------------------------------------------------
Total....................... .............. .............. .............. .............. 848,625
----------------------------------------------------------------------------------------------------------------
1 There are no capital costs or operating and maintenance costs associated with this collection of information.
2 Burden estimates of less than 1 hour are expressed as a fraction of an hour in the format ``[number of minutes
per response]/60''.
Dated: September 22, 2011.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2011-24991 Filed 9-27-11; 8:45 am]
BILLING CODE 4160-01-P
