Agency Information Collection Activities; Submission for Office of Management and Budget Review; Comment Request; Current Good Manufacturing Practice Regulations for Finished Pharmaceuticals, 10117-10121 [2015-03881]
Download as PDF
<![CDATA[
asabaliauskas on DSK5VPTVN1PROD with NOTICES
Federal Register / Vol. 80, No. 37 / Wednesday, February 25, 2015 / Notices
the Executive Order and subject to
review by the Office of Management and
Budget (OMB). Section 3(f) of Executive
Order 12866 defines a ‘‘significant
regulatory action’’ as an action likely to
result in a rule that may—
(1) Have an annual effect on the
economy of $100 million or more, or
adversely affect a sector of the economy,
productivity, competition, jobs, the
environment, public health or safety, or
State, local, or tribal governments or
communities in a material way (also
referred to as an ‘‘economically
significant’’ rule);
(2) Create serious inconsistency or
otherwise interfere with an action taken
or planned by another agency;
(3) Materially alter the budgetary
impacts of entitlement grants, user fees,
or loan programs or the rights and
obligations of recipients thereof; or
(4) Raise novel legal or policy issues
arising out of legal mandates, the
President’s priorities, or the principles
stated in the Executive Order.
This proposed regulatory action is not
a significant regulatory action subject to
review by OMB under section 3(f) of
Executive Order 12866.
We have also reviewed this regulatory
action under Executive Order 13563,
which supplements and explicitly
reaffirms the principles, structures, and
definitions governing regulatory review
established in Executive Order 12866.
To the extent permitted by law,
Executive Order 13563 requires that an
agency—
(1) Propose or adopt regulations only
upon a reasoned determination that
their benefits justify their costs
(recognizing that some benefits and
costs are difficult to quantify);
(2) Tailor its regulations to impose the
least burden on society, consistent with
obtaining regulatory objectives and
taking into account—among other things
and to the extent practicable—the costs
of cumulative regulations;
(3) In choosing among alternative
regulatory approaches, select those
approaches that maximize net benefits
(including potential economic,
environmental, public health and safety,
and other advantages; distributive
impacts; and equity);
(4) To the extent feasible, specify
performance objectives, rather than the
behavior or manner of compliance a
regulated entity must adopt; and
(5) Identify and assess available
alternatives to direct regulation,
including economic incentives—such as
user fees or marketable permits—to
encourage the desired behavior, or
provide information that enables the
public to make choices.
VerDate Sep<11>2014
18:05 Feb 24, 2015
Jkt 235001
Executive Order 13563 also requires
an agency ‘‘to use the best available
techniques to quantify anticipated
present and future benefits and costs as
accurately as possible.’’ The Office of
Information and Regulatory Affairs of
OMB has emphasized that these
techniques may include ‘‘identifying
changing future compliance costs that
might result from technological
innovation or anticipated behavioral
changes.’’
We are issuing this proposed priority
only upon a reasoned determination
that its benefits would justify its costs.
In choosing among alternative
regulatory approaches, we selected
those approaches that would maximize
net benefits. Based on the analysis that
follows, the Department believes that
this proposed priority is consistent with
the principles in Executive Order 13563.
We also have determined that this
regulatory action would not unduly
interfere with State, local, and tribal
governments in the exercise of their
governmental functions.
In accordance with both Executive
Orders, the Department has assessed the
potential costs and benefits, both
quantitative and qualitative, of this
regulatory action. The potential costs
are those resulting from statutory
requirements and those we have
determined as necessary for
administering the Department’s
programs and activities.
The benefits of the Disability and
Rehabilitation Research Projects and
Centers Program have been well
established over the years. Projects
similar to one envisioned by the
proposed priority have been completed
successfully, and the proposed priority
would generate new knowledge through
research. The new DRRP would
generate, disseminate, and promote the
use of new information that would
improve accessibility of the built
environment for individuals with
disabilities.
Intergovernmental Review: This
program is not subject to Executive
Order 12372.
Electronic Access to This Document:
The official version of this document is
the document published in the Federal
Register. Free Internet access to the
official edition of the Federal Register
and the Code of Federal Regulations is
available via the Federal Digital System
at: www.gpo.gov/fdsys. At this site you
can view this document, as well as all
other documents of this Department
published in the Federal Register, in
text or Adobe Portable Document
Format (PDF). To use PDF you must
have Adobe Acrobat Reader, which is
available free at the site.
PO 00000
Frm 00074
Fmt 4703
Sfmt 4703
10117
You may also access documents of the
Department published in the Federal
Register by using the article search
feature at: www.federalregister.gov.
Specifically, through the advanced
search feature at this site, you can limit
your search to documents published by
the Department.
Dated: February 19, 2015.
Kathy Greenlee,
Administrator.
[FR Doc. 2015–03888 Filed 2–24–15; 8:45 am]
BILLING CODE 4154–01–P
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.
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 March 27,
2015.
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 emailed 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.
SUMMARY:
FDA
PRA Staff, Office of Operations, Food
and Drug Administration, 8455
Colesville Rd., COLE–14526, Silver
Spring, MD 20993–0002, PRAStaff@
fda.hhs.gov.
FOR FURTHER INFORMATION CONTACT:
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:
E:\FR\FM\25FEN1.SGM
25FEN1
asabaliauskas on DSK5VPTVN1PROD with NOTICES
10118
Federal Register / Vol. 80, No. 37 / Wednesday, February 25, 2015 / Notices
Current Good Manufacturing Practice
Regulations for Finished
Pharmaceuticals—21 CFR Parts 210
and 211 (OMB Control Number 0910–
0139)
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 1 year after the
expiration date of the batch and, for
certain over-the-counter (OTC) drugs, 3
years after distribution of the batch
(§ 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 (§ 211.180(b)).
All part 211 records must be readily
available for authorized inspections
during the retention period
VerDate Sep<11>2014
18:05 Feb 24, 2015
Jkt 235001
(§ 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 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
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.
PO 00000
Frm 00075
Fmt 4703
Sfmt 4703
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
E:\FR\FM\25FEN1.SGM
25FEN1
asabaliauskas on DSK5VPTVN1PROD with NOTICES
Federal Register / Vol. 80, No. 37 / Wednesday, February 25, 2015 / Notices
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.
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—Stability testing
program for drug products.
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.
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
VerDate Sep<11>2014
18:05 Feb 24, 2015
Jkt 235001
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. 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
PO 00000
Frm 00076
Fmt 4703
Sfmt 4703
10119
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
E:\FR\FM\25FEN1.SGM
25FEN1
10120
Federal Register / Vol. 80, No. 37 / Wednesday, February 25, 2015 / Notices
and 680) reference certain CGMP
regulations in part 211: §§ 610.12(g),
610.13(a)(2), 610.18(d), 680.2(f), and
680.3(f). In table 1, 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, 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 November
10, 2014 (79 FR 66724), FDA published
a 60-day notice requesting public
comment on the proposed collection of
information. No comments were
received.
FDA estimates the burden of this
collection of information as follows:
TABLE 1—ESTIMATED ANNUAL RECORDKEEPING BURDEN 1
asabaliauskas on DSK5VPTVN1PROD with NOTICES
21 CFR Section
Number of
recordkeepers
SOP Maintenance ....................
New startup SOPs ...................
211.34—Consultants ................
211.67(c)—Equipment cleaning
and maintenance.
211.68—Changes in master
production and control
records or other records.
211.68(a)—Automatic, mechanical, and electronic
equipment.
211.68(b)—Computer or related systems.
211.72—Filters .........................
211.80(d)—Components and
drug product containers or
closures.
211.100(b)—Production and
process controls.
211.105(b)—Equipment identification.
211.122(c)—Labeling and
packaging material.
211.130(e)—Labeling and
packaging facilities.
211.132(c)—Tamper-evident
packaging.
211.132(d)—Tamper-evident
packaging.
211.137—Expiration dating ......
211.160(a)—Laboratory controls.
211.165(e)—Test methodology
211.166—Stability testing ........
211.173—Laboratory animals ..
211.180(e)—Production, control, and distribution records.
211.180(f)—Procedures for notification of regulatory actions.
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 production
and control records.
211.192—Discrepancies in
drug product production and
control records.
211.194—Laboratory records ..
211.196—Distribution records
211.198—Compliant files .........
211.204—Returned drug products.
VerDate Sep<11>2014
18:05 Feb 24, 2015
Number of records
per recordkeeper
4,360
100
4,360
4,360
Total annual
records
1
25
Average burden per
recordkeeping
Total hours
50
4,360
2500
1,090
218,000
25 ............................................
20 ............................................
.5 (30 minutes) ........................
.25 (15 minutes) ......................
109,000
50,000
545
54,500
4,360
2
8,720
1 ..............................................
8,720
4,360
10
43,600
.5 (30 minutes) ........................
21,800
4,360
5
21,800
.25 (15 minutes) ......................
5,450
1,090
1,090
1 ..............................................
.10 (6 minutes) ........................
1,090
109
13,080
2 ..............................................
26,160
1,090
.25 (15 minutes) ......................
273
.25
4,360
4,360
.25
.25
4,360
3
4,360
.25
4,360
50
218,000
.25 (15 minutes) ......................
54,500
4,360
50
218,000
.25 (15 minutes) ......................
54,500
1,769
20
35,380
.5 (30 minutes) ........................
17,690
354
.5 (30 minutes) ........................
177
21,800
8,720
.5 (30 minutes) ........................
1 ..............................................
10,900
8,720
1,769
.2
4,360
4,360
5
2
4,360
4,360
1,077
4,360
1
2
1
.2
4,360
8,720
1,077
872
1 ..............................................
.5 (30 minutes) ........................
.25 (15 minutes) ......................
.25 (15 minutes) ......................
4,360
4,360
269
218
4,360
.2
872
1 ..............................................
872
4,360
8,720
.25 (15 minutes) ......................
2,180
4,360
3
13,080
.5 (30 minutes) ........................
6,540
4,360
10
43,600
2 ..............................................
87,200
4,360
25
109,000
2 ..............................................
218,000
4,360
2
8,720
1 ..............................................
8,720
4,360
4,360
4,360
4,360
Jkt 235001
2
25
25
5
10
109,000
109,000
21,800
43,600
.5 (30 minutes) ........................
.25 (15 minutes) ......................
1 ..............................................
.5 (30 minutes) ........................
54,500
27,250
21,800
21,800
PO 00000
Frm 00077
Fmt 4703
Sfmt 4703
E:\FR\FM\25FEN1.SGM
25FEN1
Federal Register / Vol. 80, No. 37 / Wednesday, February 25, 2015 / Notices
10121
TABLE 1—ESTIMATED ANNUAL RECORDKEEPING BURDEN 1—Continued
Number of
recordkeepers
Total ..................................
1 There
Number of records
per recordkeeper
Total annual
records
Average burden per
recordkeeping
............................
21 CFR Section
..............................
............................
..................................................
Premarket Notification for a New
Dietary Ingredient—21 CFR 190.6
(OMB Control Number 0910–0330)—
Extension
[FR Doc. 2015–03881 Filed 2–24–15; 8:45 am]
BILLING CODE 4164–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2013–N–0878]
Agency Information Collection
Activities; Submission for Office of
Management and Budget Review;
Comment Request; Premarket
Notification for a New Dietary
Ingredient
Food and Drug Administration,
HHS.
ACTION:
Notice.
The Food and Drug
Administration (FDA or we) 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
(the PRA).
DATES: Fax written comments on the
collection of information by March 27,
2015.
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 emailed to oira_
submission@omb.eop.gov. All
comments should be identified with the
OMB control number 0910–0330. Also
include the FDA docket number found
in brackets in the heading of this
document.
FOR FURTHER INFORMATION CONTACT: FDA
PRA Staff, Office of Operations, Food
and Drug Administration, 8455
Colesville Rd., COLE—14526, Silver
Spring, MD 20993–0002, PRAStaff@
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.
SUMMARY:
asabaliauskas on DSK5VPTVN1PROD with NOTICES
882,203
are no capital costs or operating and maintenance costs associated with this collection of information.
Dated: February 19, 2015.
Leslie Kux,
Associate Commissioner for Policy.
AGENCY:
Total hours
VerDate Sep<11>2014
18:05 Feb 24, 2015
Jkt 235001
Section 413(a) of the Federal Food,
Drug, and Cosmetic Act (the FD&C Act)
(21 U.S.C. 350b(a)) provides that at least
75 days before the introduction or
delivery for introduction into interstate
commerce of a dietary supplement that
contains a new dietary ingredient, the
manufacturer or distributor of the
dietary supplement or of the new
dietary ingredient is to submit to us (as
delegate for the Secretary of Health and
Human Services) information upon
which the manufacturer or distributor
has based its conclusion that a dietary
supplement containing the new dietary
ingredient will reasonably be expected
to be safe. FDA’s implementing
regulation, 21 CFR 190.6, requires this
information to be submitted to the
Office of Nutrition, Labeling, and
Dietary Supplements (ONLDS) in the
form of a notification. Under § 190.6(b),
the notification must include the
following: (1) The name and complete
address of the manufacturer or
distributor, (2) the name of the new
dietary ingredient, (3) a description of
the dietary supplement(s) that contain
the new dietary ingredient, including
the level of the new dietary ingredient
in the dietary supplement and the
dietary supplement’s conditions of use,
(4) the history of use or other evidence
of safety establishing that the new
dietary ingredient will reasonably be
expected to be safe when used under the
conditions recommended or suggested
in the labeling of the dietary
supplement, and (5) the signature of a
responsible person designated by the
manufacturer or distributor.
These premarket notification
requirements are designed to enable us
to monitor the introduction into the
marketplace of new dietary ingredients
and dietary supplements that contain
new dietary ingredients, in order to
protect consumers from ingredients and
products whose safety is unknown. We
use the information collected in new
dietary ingredient notifications to
evaluate the safety of new dietary
ingredients in dietary supplements and
to support regulatory action against
PO 00000
Frm 00078
Fmt 4703
Sfmt 4703
ingredients and products that are
potentially unsafe.
We are developing an electronic
portal that interested persons will be
able to use to electronically submit their
notifications to ONLDS via FDA Unified
Registration and Listing System
(FURLS). Firms that prefer to submit a
paper notification in a format of their
own choosing will still have the option
to do so, however. Form FDA 3880
prompts a submitter to input the
elements of a new dietary ingredient
notification (NDIN) in a standard format
and helps the submitter organize its
NDIN to focus on the information
needed for our safety review. Safety
information will be submitted via a
supplemental form entitled ‘‘New
Dietary Ingredient (NDI) Safety
Information.’’ This form provides a
standard format to describe the history
of use or other evidence of safety on
which the manufacturer or distributor
bases its conclusion that the new dietary
ingredient will be reasonably expected
to be safe under the conditions of use
recommended or suggested in the
labeling of the dietary supplement, as
well as related identity information that
is necessary to demonstrate safety by
showing that the new dietary ingredient
and dietary supplement(s) that are the
subject of the notification are the same
or similar to the ingredients and
products for which safety data and
information have been provided. Draft
screenshots of Form FDA 3880 and the
supplemental safety information form
are available for comment at https://
www.fda.gov/Food/Dietary
Supplements/NewDietaryIngredients
NotificationProcess/ucm356620.htm.
Description of Respondents: The
respondents to this collection of
information are manufacturers and
distributors in the dietary supplement
industry; specifically, firms that
manufacture or distribute new dietary
ingredients or dietary supplements that
contain a new dietary ingredient.
In the Federal Register of November
14, 2014 (79 FR 68275), we published a
60-day notice requesting public
comment on the proposed extension of
this collection of information. We
received three comments in response to
the notice. Two of the comments were
unrelated to the PRA, and therefore we
did not consider them.
E:\FR\FM\25FEN1.SGM
25FEN1
]]>Agencies
[Federal Register Volume 80, Number 37 (Wednesday, February 25, 2015)]
[Notices]
[Pages 10117-10121]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2015-03881]
-----------------------------------------------------------------------
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 March
27, 2015.
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 emailed 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: FDA PRA Staff, Office of Operations,
Food and Drug Administration, 8455 Colesville Rd., COLE-14526, Silver
Spring, MD 20993-0002, PRAStaff@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.
[[Page 10118]]
Current Good Manufacturing Practice Regulations for Finished
Pharmaceuticals--21 CFR Parts 210 and 211 (OMB Control Number 0910-
0139)
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 1
year after the expiration date of the batch and, for certain over-the-
counter (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; 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 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
[[Page 10119]]
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.
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--Stability testing program for drug products.
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.
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. 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
[[Page 10120]]
and 680) reference certain CGMP regulations in part 211: Sec. Sec.
610.12(g), 610.13(a)(2), 610.18(d), 680.2(f), and 680.3(f). In table 1,
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, 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 November 10, 2014 (79 FR 66724), FDA
published a 60-day notice requesting public comment on the proposed
collection of information. No comments were received.
FDA estimates the burden of this collection of information as
follows:
Table 1--Estimated Annual Recordkeeping Burden \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
Number of Number of records Total annual Average burden per
21 CFR Section recordkeepers per recordkeeper records recordkeeping Total hours
--------------------------------------------------------------------------------------------------------------------------------------------------------
SOP Maintenance.............................. 4,360 1 4,360 25.............................. 109,000
New startup SOPs............................. 100 25 2500 20.............................. 50,000
211.34--Consultants.......................... 4,360 .25 1,090 .5 (30 minutes)................. 545
211.67(c)--Equipment cleaning and maintenance 4,360 50 218,000 .25 (15 minutes)................ 54,500
211.68--Changes in master production and 4,360 2 8,720 1............................... 8,720
control records or other records.
211.68(a)--Automatic, mechanical, and 4,360 10 43,600 .5 (30 minutes)................. 21,800
electronic equipment.
211.68(b)--Computer or related systems....... 4,360 5 21,800 .25 (15 minutes)................ 5,450
211.72--Filters.............................. 4,360 .25 1,090 1............................... 1,090
211.80(d)--Components and drug product 4,360 .25 1,090 .10 (6 minutes)................. 109
containers or closures.
211.100(b)--Production and process controls.. 4,360 3 13,080 2............................... 26,160
211.105(b)--Equipment identification......... 4,360 .25 1,090 .25 (15 minutes)................ 273
211.122(c)--Labeling and packaging material.. 4,360 50 218,000 .25 (15 minutes)................ 54,500
211.130(e)--Labeling and packaging facilities 4,360 50 218,000 .25 (15 minutes)................ 54,500
211.132(c)--Tamper-evident packaging......... 1,769 20 35,380 .5 (30 minutes)................. 17,690
211.132(d)--Tamper-evident packaging......... 1,769 .2 354 .5 (30 minutes)................. 177
211.137--Expiration dating................... 4,360 5 21,800 .5 (30 minutes)................. 10,900
211.160(a)--Laboratory controls.............. 4,360 2 8,720 1............................... 8,720
211.165(e)--Test methodology................. 4,360 1 4,360 1............................... 4,360
211.166--Stability testing................... 4,360 2 8,720 .5 (30 minutes)................. 4,360
211.173--Laboratory animals.................. 1,077 1 1,077 .25 (15 minutes)................ 269
211.180(e)--Production, control, and 4,360 .2 872 .25 (15 minutes)................ 218
distribution records.
211.180(f)--Procedures for notification of 4,360 .2 872 1............................... 872
regulatory actions.
211.182--Equipment cleaning and use log...... 4,360 2 8,720 .25 (15 minutes)................ 2,180
211.184--Component, drug product container, 4,360 3 13,080 .5 (30 minutes)................. 6,540
closure, and labeling records.
211.186--Master production and control 4,360 10 43,600 2............................... 87,200
records.
211.188--Batch production and control records 4,360 25 109,000 2............................... 218,000
211.192--Discrepancies in drug product 4,360 2 8,720 1............................... 8,720
production and control records.
211.194--Laboratory records.................. 4,360 25 109,000 .5 (30 minutes)................. 54,500
211.196--Distribution records................ 4,360 25 109,000 .25 (15 minutes)................ 27,250
211.198--Compliant files..................... 4,360 5 21,800 1............................... 21,800
211.204--Returned drug products.............. 4,360 10 43,600 .5 (30 minutes)................. 21,800
----------------------------------------------------------------------------------------------------------
[[Page 10121]]
Total.................................... ................ ................. ................ ................................ 882,203
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.
Dated: February 19, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-03881 Filed 2-24-15; 8:45 am]
BILLING CODE 4164-01-P
