Draft Guidance for Industry on Current Good Manufacturing Practice-Interim Guidance for Human Drug Compounding Outsourcing Facilities Under the Federal Food, Drug and Cosmetic Act; Availability, 37743-37747 [2014-15370]
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Federal Register / Vol. 79, No. 127 / Wednesday, July 2, 2014 / Notices
comments. Identify comments with the
docket number found in brackets in the
heading of this document. Received
comments may be seen in the Division
of Dockets Management between 9 a.m.
and 4 p.m., Monday through Friday, and
will be posted to the docket at https://
www.regulations.gov.
III. Electronic Access
Persons with access to the Internet
may obtain the document at either
https://www.fda.gov/Drugs/Guidance
ComplianceRegulatoryInformation/
Guidances/default.htm or https://
www.regulations.gov.
Dated: June 25, 2014.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2014–15372 Filed 7–1–14; 8:45 am]
BILLING CODE 4164–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2014–D–0779]
Draft Guidance for Industry on Current
Good Manufacturing Practice—Interim
Guidance for Human Drug
Compounding Outsourcing Facilities
Under the Federal Food, Drug and
Cosmetic Act; Availability
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice.
The Food and Drug
Administration (FDA) is announcing the
availability of a draft guidance for
industry entitled ‘‘Current Good
Manufacturing Practice—Interim
Guidance for Human Drug
Compounding Outsourcing Facilities
under Section 503B of the FD&C Act.’’
This draft guidance describes FDA’s
current expectations regarding
compliance with current good
manufacturing practice (CGMP)
requirements for facilities that
compound human drugs and register
with FDA as outsourcing facilities under
the Federal Food, Drug, and Cosmetic
Act (the FD&C Act), in accordance with
provisions added by the Drug Quality
and Security Act (DQSA). FDA is also
soliciting public input on specific
potential alternative approaches
regarding certain CGMP requirements.
These potential approaches are
explained in detail in the draft
guidance.
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SUMMARY:
Although you can comment on
any guidance at any time (see 21 CFR
10.115(g)(5)), to ensure that the Agency
DATES:
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considers your comment on this draft
guidance before it begins work on the
final version of the guidance, submit
either electronic or written comments
on the draft guidance by September 2,
2014.
ADDRESSES: Submit written requests for
single copies of the draft guidance to the
Division of Drug Information, Center for
Drug Evaluation and Research, Food
and Drug Administration, 10903 New
Hampshire Ave., Bldg. 51, Rm. 2201,
Silver Spring, MD 20993–0002. Send
one self-addressed adhesive label to
assist that office in processing your
requests. See the SUPPLEMENTARY
INFORMATION section for electronic
access to the draft guidance document.
Submit electronic comments on the
draft guidance to https://
www.regulations.gov. Submit written
comments to the Division of Dockets
Management (HFA–305), Food and Drug
Administration, 5630 Fishers Lane, Rm.
1061, Rockville, MD 20852.
FOR FURTHER INFORMATION CONTACT:
Brian Hasselbalch, Center for Drug
Evaluation and Research, Food and
Drug Administration, 10903 New
Hampshire Ave., Bldg. 51, Rm. 4364,
Silver Spring, MD 20993–0002, 301–
796–3279.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of
a draft guidance for industry entitled
‘‘Current Good Manufacturing PracticeInterim Guidance for Human Drug
Compounding Outsourcing Facilities
under Section 503B of the FD&C Act.’’
On November 27, 2013, President
Obama signed the DQSA (Public Law
113–54), which added section 503B to
the FD&C Act (21 U.S.C. 353b). Under
section 503B(b) of the FD&C Act, a
compounder can register as an
outsourcing facility with FDA. Drug
products compounded in a registered
outsourcing facility can qualify for
exemptions from the FDA approval
requirements in section 505 of the FD&C
Act (21 U.S.C. 355) and the requirement
to label products with adequate
directions for use under section
502(f)(1) of the FD&C Act (21 U.S.C.
352(f)(1)) if the requirements in section
503B are met. Outsourcing facilities will
be inspected by FDA and must comply
with other provisions of the FD&C Act,
including CGMP requirements under
section 501(a)(2)(B) (21 U.S.C.
351(a)(2)(B)).
Under section 501(a)(2)(B) of the
FD&C Act, a drug is deemed to be
adulterated if it is not produced in
accordance with CGMP. FDA’s
regulations regarding CGMP
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37743
requirements for the preparation of drug
products have been established in 21
CFR parts 210 and 211. FDA intends to
issue more specific CGMP regulations
for outsourcing facilities. Until final
regulations are issued, this draft
guidance describes FDA’s expectations
regarding outsourcing facilities and the
CGMP requirements in parts 210 and
211 during this interim period. This
draft guidance reflects FDA’s intent to
recognize the differences between
compounding outsourcing facilities and
conventional drug manufacturers, and
to tailor CGMP requirements to the
nature of the specific compounding
operations conducted by outsourcing
facilities while maintaining the
minimum standards necessary to protect
patients from the risks of contaminated
or otherwise substandard compounded
drug products. This draft guidance is
only applicable to drugs compounded in
accordance with section 503B of the
FD&C Act.
FDA intends to focus its inspectional
and enforcement efforts on those aspects
of compounding operations that pose
the highest risk to patient safety. In
particular, the primary focus of this
draft guidance is on those aspects of
part 211 that relate to sterility assurance
of sterile drug products and the safety
of compounded drug products more
generally, with respect to strength (e.g.,
subpotency, superpotency), and labeling
or drug product mix-ups.
II. Specific Request for Comments and
Information
In addition to comments on the draft
guidance generally, FDA is requesting
comments and related supporting
information on the following specific
issues: (1) alternative approaches that
would enable an outsourcing facility to
have confidence in the quality of
incoming components from sources
used by multiple outsourcing facilities
without each individual outsourcing
facility having to conduct periodic
laboratory testing to confirm the
information in the third-party supplier’s
certificate of analysis and (2) alternative
approaches that would minimize the
need for outsourcing facilities to
establish an in-house laboratory while
providing confidence about the
accuracy of testing performed by a third
party used by more than one
outsourcing facility. FDA has described
these potential alternative approaches in
the draft guidance and is seeking public
comment on these and any other
alternative approaches.
This draft guidance is being issued
consistent with FDA’s good guidance
practices regulation (21 CFR 10.115).
The draft guidance, when finalized, will
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represent the Agency’s current thinking
on ‘‘Current Good Manufacturing
Practice-Interim Guidance for Human
Drug Compounding Outsourcing
Facilities under Section 503B of the
FD&C Act.’’ It does not create or confer
any rights for or on any person and does
not operate to bind FDA or the public.
An alternative approach may be used if
such approach satisfies the
requirements of the applicable statutes
and regulations.
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III. Comments
Interested persons may submit
electronic comments regarding this
document to https://
www.regulations.gov, or written
comments to the Division of Dockets
Management (see ADDRESSES). It is only
necessary to send one set of comments.
Identify comments with the docket
number found in brackets in the
heading of this document. Received
comments may be seen in the Division
of Dockets Management between 9 a.m.
and 4 p.m., Monday through Friday, and
will be posted to the docket at https://
www.regulations.gov.
IV. Paperwork Reduction Act of 1995
This draft guidance contains
information collection provisions that
are subject to review by the Office of
Management and Budget (OMB) under
the Paperwork Reduction Act of 1995
(the PRA) (44 U.S.C. 3501–3520). The
title, description, and respondent
description of the information collection
are given under this section with an
estimate of the annual recordkeeping,
third-party disclosure, and reporting
burdens. Included in the estimate is the
time for reviewing instructions,
searching existing data sources,
gathering and maintaining the data
needed, and completing and reviewing
the collection of information.
We invite comments on these topics:
(1) Whether the proposed collection of
information is necessary for the proper
performance of FDA’s functions,
including whether the information will
have practical utility; (2) the accuracy of
FDA’s estimate of the burden of the
proposed collection of information,
including the validity of the
methodology and assumptions used; (3)
ways to enhance the quality, utility, and
clarity of the information to be
collected; and (4) ways to minimize the
burden of the collection of information
on respondents, including through the
use of automated collection techniques,
when appropriate, and other forms of
information technology.
Title: Guidance for Industry, Current
Good Manufacturing Practice—Interim
Guidance for Human Drug
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Compounding Outsourcing Facilities
under Section 503B of the FD&C Act.
Description: The draft guidance
describes FDA’s expectations regarding
compliance with CGMP requirements
for facilities that register with FDA as
outsourcing facilities under section
503B of the FD&C Act. The primary
focus of the draft guidance is on sterility
assurance of sterile products and the
safety of compounded drug products
with respect to strength (e.g.,
subpotency, superpotency), and labeling
or drug product mix-ups. OMB has
already approved the information
collection (recordkeeping) contained in
FDA’s CGMP regulations in part 211
(OMB control number 0910–0139). FDA
believes that much of the recordkeeping
burden that would result from the draft
guidance is already incurred by
outsourcing facilities in the normal
course of their business activities. Thus,
the burden estimates for these ‘‘usual
and customary’’ business practices are
not included in the calculation of
burden that follows (see 5 CFR
1320.3(b)(2).
The draft guidance contains the
following collections of information
under the PRA:
1. Facility Design
The draft guidance describes those
elements of facility design of
outsourcing facilities that are
considered critical to assuring the
quality of compounded sterile drug
products at those facilities. For example,
the draft guidance states that sterile
drugs should be produced only in ISO
5 or better air quality, and that the ISO
5 zone or critical area must be qualified
(i.e., shown to meet the specifications).
In section III.A, the draft guidance lists
certain studies and tests which should
be successfully performed for
outsourcing facilities, and states that the
results of these studies and tests should
be documented.
We estimate that annually a total of
approximately 50 outsourcing facilities 1
(‘‘No. of Recordkeepers’’ in table 1, row
1) will individually document
approximately 20 studies and tests
(‘‘Total Annual Records’’ in table 1, row
1) that are critical to assuring the quality
of compounded sterile drug products.
1 This is an estimate of the number of facilities
that will register as outsourcing facilities in fiscal
year 2014 (which runs from October 1, 2013 to
September 30, 2014). As of April 30, 2014, 40
facilities had registered as outsourcing facilities,
and on average, 2 facilities have registered each
month for the past 3 months, but these estimates are
highly uncertain. Annual establishment fees will be
assessed for each outsourcing facility registered on
or after October 1, 2014. It is unknown how many
facilities will remain as registered outsourcing
facilities once these fees take effect.
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We also estimate that preparing and
maintaining each record as described in
the draft guidance will take on average
approximately 1.5 hours for each record
(‘‘Average Burden per Recordkeeping’’
in table 1, row 1).
2. Control Systems and Procedures for
Maintaining Suitable Facilities
The draft guidance describes certain
controls, procedures, and
documentation that should be
established and followed for
maintaining suitable facilities and to
prevent contamination and mix-ups
during the course of aseptic operations
at outsourcing facilities. Procedures
must be established that assign
responsibility for and describe cleaning
schedules, methods, equipment, and
materials. In addition, the guidance
describes that procedures should ensure
recording of instances when there is a
loss of positive pressure in the clean
room during production.
We estimate that annually a total of
approximately 50 outsourcing facilities
(‘‘No. of Recordkeepers’’ in table 1, row
2) will individually establish and
maintain approximately 3 records
(procedures and documentation) for
maintaining suitable outsourcing
facilities (‘‘Total Annual Records’’ in
table 1, row 2). We also estimate that
preparing and maintaining each record
as described in section III.B of the draft
guidance will take on average
approximately 5 hours for each record
(‘‘Average Burden per Recordkeeping’’
in table 1, row 2).
3. Environmental and Personnel
Monitoring
Under the draft guidance, procedures
for environmental and personnel
monitoring in the aseptic processing
area for viable, nonviable, and total
particulate matter should be established
and followed in outsourcing facilities.
The procedures should include
establishing the validity of the
microbiological media, including the
preparation, sterilization, and growth
potential of the media used in
performing tests.
We estimate that annually a total of
approximately 50 outsourcing facilities
(‘‘No. of Recordkeepers’’ in table 1, row
3) will individually establish
approximately 1,200 environmental and
personnel monitoring procedures and
records to document test results (‘‘Total
Annual Records’’ in table 1, row 3) for
the aseptic processing areas. We also
estimate that preparing and maintaining
the environmental and personnel
monitoring procedures as described in
section III.C of the draft guidance will
take on average approximately 0.25
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hours for each record (‘‘Average Burden
per Recordkeeping’’ in table 1, row 3).
4. Equipment, Containers, and Closures
Procedures and documentation
should be established and maintained
for testing compounding equipment and
containers and closures to ensure the
quality of compounded drug products at
outsourcing facilities.
We estimate that annually a total of
approximately 50 outsourcing facilities
(‘‘No. of Recordkeepers’’ in table 1, row
4) will individually establish and
maintain approximately 1,000
procedures and documentation for
testing equipment, containers, and
closures (‘‘Total Annual Records’’ in
table 1, row 4) in the aseptic processing
areas. We also estimate that preparing
and maintaining these procedures and
documentation as described in section
III.D of the draft guidance will take on
average approximately 0.25 hours for
each record (‘‘Average Burden per
Recordkeeping’’ in table 1, row 4).
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5. Components
Procedures should be established and
records maintained concerning the
source and quality of components such
as raw materials or ingredients used in
producing compounded sterile drug
products at outsourcing facilities.
We estimate that annually a total of
approximately 50 outsourcing facilities
(‘‘No. of Recordkeepers’’ in table 1, row
5) will individually establish and
maintain approximately 240 records of
testing to ensure the quality of
components used in producing
compounded drugs, as recommended in
section III.E of the draft guidance
(‘‘Total Annual Records’’ in table 1, row
5). We also estimate that preparing and
maintaining these records will take on
average approximately 4 hours for each
record (‘‘Average Burden per
Recordkeeping’’ in table 1, row 5).
6. Production and Process Controls
Production and process
documentation and procedures, such as
batch records, must be established to
assure the quality of compounded
sterile drug products at outsourcing
facilities. Training on aseptic technique,
cleanroom behavior, gowning, and
procedures covering aseptic
manufacturing area operations must be
established. Sterilization validation of
operations (e.g., holding vessels, filling
equipment, lyophilizer) and periodic
verification activities and results must
be documented.
We estimate that annually a total of
approximately 50 outsourcing facilities
(‘‘No. of Recordkeepers’’ in table 1, row
6) will individually establish and
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maintain approximately 5,000 records
pertaining to production and process
controls, such as validation procedures
and training, to assure the quality of
compounded sterile drug products
(‘‘Total Annual Records’’ in table 1, row
6). We also estimate that preparing and
maintaining these records, as described
in section III.F of the draft guidance,
will take on average approximately 0.25
hours for each record (‘‘Average Burden
per Recordkeeping’’ in table 1, row 6).
We also estimate that annually, a total
of approximately 10 outsourcing
facilities (‘‘No. of Respondents’’ in table
3) will individually submit to FDA 1
notification of the test results for any
compounded drug product that fails to
meet a sterility criterion (‘‘Total Annual
Responses’’ in table 3). Preparing and
submitting this information will take
approximately 5 hours per notification
(‘‘Average Burden per Response’’ in
table 3).
7. Release Testing
8. Laboratory Controls
Each laboratory used to conduct
testing of components, in-process
materials, and finished drug products
for outsourcing facilities must follow
written procedures for the conduct of
each test and document the results,
establish sampling and testing
procedures to ensure that components,
in-process materials, and drug products
conform to the product specifications,
and keep complete records of all tests
performed to ensure compliance with
established specifications and
standards, including examinations and
assays.
We estimate that annually a total of
approximately 50 outsourcing facilities
(‘‘No. of Recordkeepers’’ in table 1, row
8) will individually establish and
maintain approximately 1,000
laboratory records as described in
section III.H of the draft guidance
(‘‘Total Annual Records’’ in table 1, row
8). We also estimate that preparing and
maintaining these records will take on
average approximately 0.5 hours for
each record (‘‘Average Burden per
Recordkeeping’’ in table 1, row 8).
Compounded drug products produced
at outsourcing facilities must be tested
to determine whether they meet final
product specifications prior to release
for distribution, and procedures for final
release testing must be established and
followed.
We estimate that annually a total of
approximately 50 outsourcing facilities
(‘‘No. of Recordkeepers’’ in table 1, row
7) will individually establish and
maintain approximately 240 records
pertaining to final release testing of
compounded drug products, including
release testing procedures and
documentation (‘‘Total Annual
Records’’ in table 1, row 7). We also
estimate that preparing and maintaining
these records, as described in section
III.G of the draft guidance, will take on
average approximately 4 hours for each
record (‘‘Average Burden per
Recordkeeping’’ in table 1, row 7).
If sterility testing is not completed
prior to release under certain conditions
described in section III.G of the draft
guidance, procedures must be
established that specify that if the
product fails to meet a criterion for
sterility, all healthcare and other
facilities that received the product must
be immediately notified of the test
results and provided with any
appropriate information and
recommendations to aid in the
treatment of patients; the notification
must be documented; and FDA must be
notified in writing.
We estimate that annually a total of
approximately 10 outsourcing facilities
(‘‘No. of Respondents’’ in table 2, row 1)
will individually send approximately 1
notification of test results to all
healthcare and other facilities that
received the compounded drug product
and provide them with any appropriate
information and recommendations to
aid in the treatment of patients (‘‘Total
Annual Disclosures’’ in table 2, row 1).
We also estimate that preparing and
sending each notification will take
approximately 5 hours (‘‘Average
Burden per Disclosure’’ in table 2, row
1).
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9. Stability/Expiration Dating
Stability testing is used to ensure that
a drug product will retain its quality (in
particular, strength) and remain sterile
through the labeled expiration date. The
draft guidance recommends that
procedures established by outsourcing
facilities for assessing the stability of
drug products should include: (1) using
stability-indicating test methods that are
reliable, meaningful and specific; (2)
evaluating samples of the drug product
in the same container closure system in
which the drug product will be
marketed; (3) evaluating samples for
stability that are representative of the lot
or batch from which they were obtained
and are stored under suitable
conditions; and (4) testing to evaluate
antimicrobial effectiveness (resistance to
antimicrobial contamination) for drug
products labeled or intended to be
multiple dose.
We estimate that annually a total of
approximately 50 outsourcing facilities
(‘‘No. of Recordkeepers’’ in table 1, row
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9) will individually establish and
maintain approximately 90 procedures
for stability studies to determine an
expiration date (‘‘Total Annual
Records’’ in table 1, row 9) for
compounded drug products. We also
estimate that preparing and maintaining
these procedures as described in section
III.I of the draft guidance will take
approximately 5 hours for each record
(‘‘Average Burden per Recordkeeping’’
in table 1, row 9).
10. Packaging and Labels
Packaging of sterile drugs must ensure
the sterility and integrity of the product
until it is administered to a patient, and
product labels must contain required
information and labeling operations
must include controls to prevent mixups. Procedures should be established
by outsourcing facilities for packaging
and labeling operations for compounded
sterile drug products, including the
following: (1) The container, closure,
and packaging systems should provide
adequate protection against foreseeable
external factors in storage, shipment,
and use that can cause contamination or
deterioration; (2) packaging records
should include specimens of all labels
used; procedures should be established
for issuance of labels, examination of
issued labels, reconciliation of used
labels to prevent mix-ups; (3) there
should be physical/spatial separation
between different labeling and
packaging operations to prevent mixups; and (4) controls should be
established that assure proper
identification of any filled containers of
sterile products that are stored
unlabeled for any period of time.
We estimate that annually a total of
approximately 50 outsourcing facilities
(‘‘No. of Recordkeepers’’ in table 1, row
10) will individually establish and
maintain approximately 20 procedures
and records for packaging operations
and labels (‘‘Total Annual Records’’ in
table 1, row 10) for compounded drug
products. We also estimate that
preparing and maintaining these
procedures and records as described in
section III.J of the draft guidance will
take approximately 5.5 hours for each
record (‘‘Average Burden per
Recordkeeping’’ in table 1, row 10).
11. Quality Assurance Activities
A quality control unit must be
established by outsourcing facilities to
oversee various aspects of compounded
sterile drug production and to monitor
quality assurance. The responsibilities
of the quality control unit must be
established in procedures and should
include investigations and development
and oversight of appropriate corrective
actions and preventive actions
regarding: Rejected lots of finished
product, unexpected results or trends,
validation and stability failures, and
process deviations or equipment
malfunctions that involve critical
equipment. The quality control unit also
is responsible for ensuring that
sampling and testing are conducted to
ensure that appropriate specifications
are met, and for product complaint
handling.
We estimate that annually a total of
approximately 50 outsourcing facilities
(‘‘No. of Recordkeepers’’ in table 1, row
11) will individually establish
approximately 8 procedures on the
responsibilities of the quality control
unit (‘‘Total Annual Records’’ in table 1,
row 10) as described in section III.K of
the draft guidance. We also estimate that
preparing and maintaining these
procedures will take approximately 3
hours for each record (‘‘Average Burden
per Recordkeeping’’ in table 1, row 11).
The total estimated recordkeeping,
third party disclosure, and reporting
burdens for the draft guidance are as
follows:
TABLE 1—ESTIMATED ANNUAL RECORDKEEPING BURDEN 1
Number of
recordkeepers
Type of recordkeeping
Number of
records per
recordkeeper
Total annual
records
Average burden per recordkeeping
Total hours
Facility Design ...................................
Control Systems and Procedures
For Maintaining Suitable Facilities.
Environmental and Personnel Monitoring.
Equipment, Containers, and Closures.
Components ......................................
Production and Process Controls .....
Release Testing ................................
Laboratory Controls ..........................
Stability/Expiration Dating .................
Packaging and Labels ......................
Quality Assurance Activities .............
50
50
20
3
1,000
150
1.5 ....................................................
5 .......................................................
1,500
750
50
1,200
60,000
0.25 (15 minutes) .............................
15,000
50
1,000
50,000
0.25 (15 minutes) .............................
12,500
50
50
50
50
50
50
50
240
5,000
240
1,000
90
20
8
12,000
250,000
12,000
50,000
4,500
1,000
400
4 .......................................................
0.25 (15 minutes) .............................
4 .......................................................
0.5 (30 minutes) ...............................
5 .......................................................
5.5 ....................................................
3 .......................................................
48,000
62,500
48,000
25,000
22,500
5,500
1,200
Total ...........................................
50
8,821
441,050
...........................................................
242,450
1 There
are no capital costs or operating and maintenance costs associated with this collection of information.
TABLE 2—ESTIMATED ANNUAL THIRD-PARTY DISCLOSURE BURDEN 1
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Type of disclosure & proposed 21
CFR section
Number of
respondents
Frequency per
disclosure
Total annual
disclosures
Average burden per disclosure
Total hours
Notification that a compounded drug
product fails to meet a sterility criterion.
An expiration date is added to the
compounded drug product’s label.
10
1
10
5 .......................................................
50
50
540
27,000
0.25 (15 minutes) .............................
6,750
Total ...........................................
6,800
1 There
are no capital costs or operating and maintenance costs associated with this collection of information.
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TABLE 3—ESTIMATED ANNUAL REPORTING BURDEN 1
Number of respondents
Type of reporting
& proposed 21 CFR section
Number of responses per
respondent
10
1
Notification to FDA that a compounded drug product fails
to meet a sterility criterion ................................................
1 There
Dated: June 25, 2014.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2014–15370 Filed 7–1–14; 8:45 am]
BILLING CODE 4164–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2013–N–1525]
Bulk Drug Substances That May Be
Used To Compound Drug Products in
Accordance With Section 503A of the
Federal Food, Drug, and Cosmetic Act;
Revised Request for Nominations
Food and Drug Administration,
HHS.
Notice; revised request for
nominations.
ACTION:
The Food and Drug
Administration (FDA or Agency) is
preparing to develop a list of bulk drug
substances (active ingredients) that may
be used to compound drug products in
accordance with section 503A of the
Federal Food, Drug, and Cosmetic Act
(the FD&C Act), although they are
neither the subject of a United States
Pharmacopeia (USP) or National
Formulary (NF) monograph nor
components of FDA-approved drugs. In
response to a notice published in the
Federal Register of December 4, 2013,
interested groups and individuals
previously nominated a wide variety of
substances for this list. However, many
of those nominations either were for a
substance that is already the subject of
a USP monograph or a component of an
FDA-approved drug, were not for bulk
drug substances used in compounding
as active ingredients, or did not include
sufficient information to justify
inclusion of the nominated substance on
the list. To improve the efficiency of the
process for developing the list of bulk
SUMMARY:
mstockstill on DSK4VPTVN1PROD with NOTICES
10
Average
burden per
response
Total hours
5
50
are no capital costs or operating and maintenance costs associated with this collection of information.
V. Electronic Access
Persons with access to the Internet
may obtain the document at either
https://www.fda.gov/Drugs/Guidance
ComplianceRegulatoryInformation/
Guidances/default.htm or https://
www.regulations.gov.
AGENCY:
Total annual
responses
VerDate Mar<15>2010
17:49 Jul 01, 2014
Jkt 232001
drug substances that may be used to
compound drug products under section
503A, FDA is providing more detailed
information on what it needs to evaluate
a nomination. Because the deadline for
nominations has passed, FDA is
reopening the nomination process so
that interested persons can submit
nominations of bulk drug substances
that are not the subject of a USP or NF
monograph or a component of an FDAapproved drug. Interested persons will
also have the opportunity to provide
adequate support to justify placement of
the substances on the list. Bulk drug
substances that were previously
nominated will not be further
considered unless they are renominated
and those nominations are adequately
supported. Substances that are already
eligible for use in compounding or that
are not adequately supported will not be
placed on the list.
DATES: Submit written or electronic
nominations for the bulk drug
substances list by September 30, 2014.
ADDRESSES: You may submit
nominations, identified by Docket No.
FDA–2013–N–1525, by any of the
following methods.
Electronic Submissions
Submit electronic nominations in the
following way:
• Federal eRulemaking Portal: https://
www.regulations.gov. Follow the
instructions for submitting ‘‘comments.’’
Written Submissions
Submit written nominations in the
following ways:
• Mail/Hand delivery/Courier (for
paper submissions): Division of Dockets
Management (HFA–305), Food and Drug
Administration, 5630 Fishers Lane, rm.
1061, Rockville, MD 20852.
Instructions: All submissions received
must include the Agency name and
Docket No. FDA–2013–N–1525 for this
request for nominations. All
nominations received may be posted
without change to https://
www.regulations.gov, including any
personal information provided. For
additional information on submitting
nominations, see the ‘‘Request for
Nominations’’ heading of the
PO 00000
Frm 00037
Fmt 4703
Sfmt 4703
SUPPLEMENTARY INFORMATION section of
this document.
Docket: For access to the docket to
read background documents or
nominations received, go to https://
www.regulations.gov and insert the
docket number, found in brackets in the
heading of this document, into the
‘‘Search’’ box and follow the prompts
and/or go to the Division of Dockets
Management, 5630 Fishers Lane, Rm.
1061, Rockville, MD 20852.
FOR FURTHER INFORMATION CONTACT:
Emily Helms Williams, Center for Drug
Evaluation and Research, Food and
Drug Administration, 10903 New
Hampshire Ave., Bldg. 51, Rm. 6280,
Silver Spring, MD 20993–0002, 301–
796–3381.
SUPPLEMENTARY INFORMATION:
I. Background
Section 503A of the FD&C Act (21
U.S.C. 353a) describes the conditions
under which a compounded drug
product may be entitled to an
exemption from certain sections of the
FD&C Act. Those conditions include
that the licensed pharmacist or licensed
physician compounds the drug product
using bulk drug substances that (1)
comply with the standards of an
applicable USP or NF monograph, if a
monograph exists, and the USP chapter
on pharmacy compounding; (2) if such
a monograph does not exist, are drug
substances that are components of drugs
approved by the Secretary; or (3) if such
a monograph does not exist and the
drug substance is not a component of a
drug approved by the Secretary, that
appear on a list developed by the
Secretary through regulations issued by
the Secretary under subsection (c) of
section 503A. See section
503A(b)(1)(A)(i) of the FD&C Act. Under
section 503A(c)(2), the criteria for
determining which substances should
appear on the 503A bulk drugs list
‘‘shall include historical use, reports in
peer reviewed medical literature, or
other criteria the Secretary may
identify.’’
Section 503A refers to the definition
of ‘‘bulk drug substance’’ in FDA
regulations at § 207.3(a)(4) (21 CFR
207.3(a)(4)). See section 503A(b)(1)(A)
of the FD&C Act. As defined in
E:\FR\FM\02JYN1.SGM
02JYN1
]]>Agencies
[Federal Register Volume 79, Number 127 (Wednesday, July 2, 2014)]
[Notices]
[Pages 37743-37747]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2014-15370]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2014-D-0779]
Draft Guidance for Industry on Current Good Manufacturing
Practice--Interim Guidance for Human Drug Compounding Outsourcing
Facilities Under the Federal Food, Drug and Cosmetic Act; Availability
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA) is announcing the
availability of a draft guidance for industry entitled ``Current Good
Manufacturing Practice--Interim Guidance for Human Drug Compounding
Outsourcing Facilities under Section 503B of the FD&C Act.'' This draft
guidance describes FDA's current expectations regarding compliance with
current good manufacturing practice (CGMP) requirements for facilities
that compound human drugs and register with FDA as outsourcing
facilities under the Federal Food, Drug, and Cosmetic Act (the FD&C
Act), in accordance with provisions added by the Drug Quality and
Security Act (DQSA). FDA is also soliciting public input on specific
potential alternative approaches regarding certain CGMP requirements.
These potential approaches are explained in detail in the draft
guidance.
DATES: 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 guidance before it begins work on the final version of the
guidance, submit either electronic or written comments on the draft
guidance by September 2, 2014.
ADDRESSES: Submit written requests for single copies of the draft
guidance to the Division of Drug Information, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 51, Rm. 2201, Silver Spring, MD 20993-0002. Send
one self-addressed adhesive label to assist that office in processing
your requests. See the SUPPLEMENTARY INFORMATION section for electronic
access to the draft guidance document.
Submit electronic comments on the draft guidance to https://www.regulations.gov. Submit written comments to the Division of Dockets
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane,
Rm. 1061, Rockville, MD 20852.
FOR FURTHER INFORMATION CONTACT: Brian Hasselbalch, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 51, Rm. 4364, Silver Spring, MD 20993-0002, 301-
796-3279.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of a draft guidance for industry
entitled ``Current Good Manufacturing Practice-Interim Guidance for
Human Drug Compounding Outsourcing Facilities under Section 503B of the
FD&C Act.'' On November 27, 2013, President Obama signed the DQSA
(Public Law 113-54), which added section 503B to the FD&C Act (21
U.S.C. 353b). Under section 503B(b) of the FD&C Act, a compounder can
register as an outsourcing facility with FDA. Drug products compounded
in a registered outsourcing facility can qualify for exemptions from
the FDA approval requirements in section 505 of the FD&C Act (21 U.S.C.
355) and the requirement to label products with adequate directions for
use under section 502(f)(1) of the FD&C Act (21 U.S.C. 352(f)(1)) if
the requirements in section 503B are met. Outsourcing facilities will
be inspected by FDA and must comply with other provisions of the FD&C
Act, including CGMP requirements under section 501(a)(2)(B) (21 U.S.C.
351(a)(2)(B)).
Under section 501(a)(2)(B) of the FD&C Act, a drug is deemed to be
adulterated if it is not produced in accordance with CGMP. FDA's
regulations regarding CGMP requirements for the preparation of drug
products have been established in 21 CFR parts 210 and 211. FDA intends
to issue more specific CGMP regulations for outsourcing facilities.
Until final regulations are issued, this draft guidance describes FDA's
expectations regarding outsourcing facilities and the CGMP requirements
in parts 210 and 211 during this interim period. This draft guidance
reflects FDA's intent to recognize the differences between compounding
outsourcing facilities and conventional drug manufacturers, and to
tailor CGMP requirements to the nature of the specific compounding
operations conducted by outsourcing facilities while maintaining the
minimum standards necessary to protect patients from the risks of
contaminated or otherwise substandard compounded drug products. This
draft guidance is only applicable to drugs compounded in accordance
with section 503B of the FD&C Act.
FDA intends to focus its inspectional and enforcement efforts on
those aspects of compounding operations that pose the highest risk to
patient safety. In particular, the primary focus of this draft guidance
is on those aspects of part 211 that relate to sterility assurance of
sterile drug products and the safety of compounded drug products more
generally, with respect to strength (e.g., subpotency, superpotency),
and labeling or drug product mix-ups.
II. Specific Request for Comments and Information
In addition to comments on the draft guidance generally, FDA is
requesting comments and related supporting information on the following
specific issues: (1) alternative approaches that would enable an
outsourcing facility to have confidence in the quality of incoming
components from sources used by multiple outsourcing facilities without
each individual outsourcing facility having to conduct periodic
laboratory testing to confirm the information in the third-party
supplier's certificate of analysis and (2) alternative approaches that
would minimize the need for outsourcing facilities to establish an in-
house laboratory while providing confidence about the accuracy of
testing performed by a third party used by more than one outsourcing
facility. FDA has described these potential alternative approaches in
the draft guidance and is seeking public comment on these and any other
alternative approaches.
This draft guidance is being issued consistent with FDA's good
guidance practices regulation (21 CFR 10.115). The draft guidance, when
finalized, will
[[Page 37744]]
represent the Agency's current thinking on ``Current Good Manufacturing
Practice-Interim Guidance for Human Drug Compounding Outsourcing
Facilities under Section 503B of the FD&C Act.'' It does not create or
confer any rights for or on any person and does not operate to bind FDA
or the public. An alternative approach may be used if such approach
satisfies the requirements of the applicable statutes and regulations.
III. Comments
Interested persons may submit electronic comments regarding this
document to https://www.regulations.gov, or written comments to the
Division of Dockets Management (see ADDRESSES). It is only necessary to
send one set of comments. Identify comments with the docket number
found in brackets in the heading of this document. Received comments
may be seen in the Division of Dockets Management between 9 a.m. and 4
p.m., Monday through Friday, and will be posted to the docket at https://www.regulations.gov.
IV. Paperwork Reduction Act of 1995
This draft guidance contains information collection provisions that
are subject to review by the Office of Management and Budget (OMB)
under the Paperwork Reduction Act of 1995 (the PRA) (44 U.S.C. 3501-
3520). The title, description, and respondent description of the
information collection are given under this section with an estimate of
the annual recordkeeping, third-party disclosure, and reporting
burdens. Included in the estimate is the time for reviewing
instructions, searching existing data sources, gathering and
maintaining the data needed, and completing and reviewing the
collection of information.
We invite comments on these topics: (1) Whether the proposed
collection of information is necessary for the proper performance of
FDA's functions, including whether the information will have practical
utility; (2) the accuracy of FDA's estimate of the burden of the
proposed collection of information, including the validity of the
methodology and assumptions used; (3) ways to enhance the quality,
utility, and clarity of the information to be collected; and (4) ways
to minimize the burden of the collection of information on respondents,
including through the use of automated collection techniques, when
appropriate, and other forms of information technology.
Title: Guidance for Industry, Current Good Manufacturing Practice--
Interim Guidance for Human Drug Compounding Outsourcing Facilities
under Section 503B of the FD&C Act.
Description: The draft guidance describes FDA's expectations
regarding compliance with CGMP requirements for facilities that
register with FDA as outsourcing facilities under section 503B of the
FD&C Act. The primary focus of the draft guidance is on sterility
assurance of sterile products and the safety of compounded drug
products with respect to strength (e.g., subpotency, superpotency), and
labeling or drug product mix-ups. OMB has already approved the
information collection (recordkeeping) contained in FDA's CGMP
regulations in part 211 (OMB control number 0910-0139). FDA believes
that much of the recordkeeping burden that would result from the draft
guidance is already incurred by outsourcing facilities in the normal
course of their business activities. Thus, the burden estimates for
these ``usual and customary'' business practices are not included in
the calculation of burden that follows (see 5 CFR 1320.3(b)(2).
The draft guidance contains the following collections of
information under the PRA:
1. Facility Design
The draft guidance describes those elements of facility design of
outsourcing facilities that are considered critical to assuring the
quality of compounded sterile drug products at those facilities. For
example, the draft guidance states that sterile drugs should be
produced only in ISO 5 or better air quality, and that the ISO 5 zone
or critical area must be qualified (i.e., shown to meet the
specifications). In section III.A, the draft guidance lists certain
studies and tests which should be successfully performed for
outsourcing facilities, and states that the results of these studies
and tests should be documented.
We estimate that annually a total of approximately 50 outsourcing
facilities \1\ (``No. of Recordkeepers'' in table 1, row 1) will
individually document approximately 20 studies and tests (``Total
Annual Records'' in table 1, row 1) that are critical to assuring the
quality of compounded sterile drug products. We also estimate that
preparing and maintaining each record as described in the draft
guidance will take on average approximately 1.5 hours for each record
(``Average Burden per Recordkeeping'' in table 1, row 1).
---------------------------------------------------------------------------
\1\ This is an estimate of the number of facilities that will
register as outsourcing facilities in fiscal year 2014 (which runs
from October 1, 2013 to September 30, 2014). As of April 30, 2014,
40 facilities had registered as outsourcing facilities, and on
average, 2 facilities have registered each month for the past 3
months, but these estimates are highly uncertain. Annual
establishment fees will be assessed for each outsourcing facility
registered on or after October 1, 2014. It is unknown how many
facilities will remain as registered outsourcing facilities once
these fees take effect.
---------------------------------------------------------------------------
2. Control Systems and Procedures for Maintaining Suitable Facilities
The draft guidance describes certain controls, procedures, and
documentation that should be established and followed for maintaining
suitable facilities and to prevent contamination and mix-ups during the
course of aseptic operations at outsourcing facilities. Procedures must
be established that assign responsibility for and describe cleaning
schedules, methods, equipment, and materials. In addition, the guidance
describes that procedures should ensure recording of instances when
there is a loss of positive pressure in the clean room during
production.
We estimate that annually a total of approximately 50 outsourcing
facilities (``No. of Recordkeepers'' in table 1, row 2) will
individually establish and maintain approximately 3 records (procedures
and documentation) for maintaining suitable outsourcing facilities
(``Total Annual Records'' in table 1, row 2). We also estimate that
preparing and maintaining each record as described in section III.B of
the draft guidance will take on average approximately 5 hours for each
record (``Average Burden per Recordkeeping'' in table 1, row 2).
3. Environmental and Personnel Monitoring
Under the draft guidance, procedures for environmental and
personnel monitoring in the aseptic processing area for viable,
nonviable, and total particulate matter should be established and
followed in outsourcing facilities. The procedures should include
establishing the validity of the microbiological media, including the
preparation, sterilization, and growth potential of the media used in
performing tests.
We estimate that annually a total of approximately 50 outsourcing
facilities (``No. of Recordkeepers'' in table 1, row 3) will
individually establish approximately 1,200 environmental and personnel
monitoring procedures and records to document test results (``Total
Annual Records'' in table 1, row 3) for the aseptic processing areas.
We also estimate that preparing and maintaining the environmental and
personnel monitoring procedures as described in section III.C of the
draft guidance will take on average approximately 0.25
[[Page 37745]]
hours for each record (``Average Burden per Recordkeeping'' in table 1,
row 3).
4. Equipment, Containers, and Closures
Procedures and documentation should be established and maintained
for testing compounding equipment and containers and closures to ensure
the quality of compounded drug products at outsourcing facilities.
We estimate that annually a total of approximately 50 outsourcing
facilities (``No. of Recordkeepers'' in table 1, row 4) will
individually establish and maintain approximately 1,000 procedures and
documentation for testing equipment, containers, and closures (``Total
Annual Records'' in table 1, row 4) in the aseptic processing areas. We
also estimate that preparing and maintaining these procedures and
documentation as described in section III.D of the draft guidance will
take on average approximately 0.25 hours for each record (``Average
Burden per Recordkeeping'' in table 1, row 4).
5. Components
Procedures should be established and records maintained concerning
the source and quality of components such as raw materials or
ingredients used in producing compounded sterile drug products at
outsourcing facilities.
We estimate that annually a total of approximately 50 outsourcing
facilities (``No. of Recordkeepers'' in table 1, row 5) will
individually establish and maintain approximately 240 records of
testing to ensure the quality of components used in producing
compounded drugs, as recommended in section III.E of the draft guidance
(``Total Annual Records'' in table 1, row 5). We also estimate that
preparing and maintaining these records will take on average
approximately 4 hours for each record (``Average Burden per
Recordkeeping'' in table 1, row 5).
6. Production and Process Controls
Production and process documentation and procedures, such as batch
records, must be established to assure the quality of compounded
sterile drug products at outsourcing facilities. Training on aseptic
technique, cleanroom behavior, gowning, and procedures covering aseptic
manufacturing area operations must be established. Sterilization
validation of operations (e.g., holding vessels, filling equipment,
lyophilizer) and periodic verification activities and results must be
documented.
We estimate that annually a total of approximately 50 outsourcing
facilities (``No. of Recordkeepers'' in table 1, row 6) will
individually establish and maintain approximately 5,000 records
pertaining to production and process controls, such as validation
procedures and training, to assure the quality of compounded sterile
drug products (``Total Annual Records'' in table 1, row 6). We also
estimate that preparing and maintaining these records, as described in
section III.F of the draft guidance, will take on average approximately
0.25 hours for each record (``Average Burden per Recordkeeping'' in
table 1, row 6).
7. Release Testing
Compounded drug products produced at outsourcing facilities must be
tested to determine whether they meet final product specifications
prior to release for distribution, and procedures for final release
testing must be established and followed.
We estimate that annually a total of approximately 50 outsourcing
facilities (``No. of Recordkeepers'' in table 1, row 7) will
individually establish and maintain approximately 240 records
pertaining to final release testing of compounded drug products,
including release testing procedures and documentation (``Total Annual
Records'' in table 1, row 7). We also estimate that preparing and
maintaining these records, as described in section III.G of the draft
guidance, will take on average approximately 4 hours for each record
(``Average Burden per Recordkeeping'' in table 1, row 7).
If sterility testing is not completed prior to release under
certain conditions described in section III.G of the draft guidance,
procedures must be established that specify that if the product fails
to meet a criterion for sterility, all healthcare and other facilities
that received the product must be immediately notified of the test
results and provided with any appropriate information and
recommendations to aid in the treatment of patients; the notification
must be documented; and FDA must be notified in writing.
We estimate that annually a total of approximately 10 outsourcing
facilities (``No. of Respondents'' in table 2, row 1) will individually
send approximately 1 notification of test results to all healthcare and
other facilities that received the compounded drug product and provide
them with any appropriate information and recommendations to aid in the
treatment of patients (``Total Annual Disclosures'' in table 2, row 1).
We also estimate that preparing and sending each notification will take
approximately 5 hours (``Average Burden per Disclosure'' in table 2,
row 1).
We also estimate that annually, a total of approximately 10
outsourcing facilities (``No. of Respondents'' in table 3) will
individually submit to FDA 1 notification of the test results for any
compounded drug product that fails to meet a sterility criterion
(``Total Annual Responses'' in table 3). Preparing and submitting this
information will take approximately 5 hours per notification (``Average
Burden per Response'' in table 3).
8. Laboratory Controls
Each laboratory used to conduct testing of components, in-process
materials, and finished drug products for outsourcing facilities must
follow written procedures for the conduct of each test and document the
results, establish sampling and testing procedures to ensure that
components, in-process materials, and drug products conform to the
product specifications, and keep complete records of all tests
performed to ensure compliance with established specifications and
standards, including examinations and assays.
We estimate that annually a total of approximately 50 outsourcing
facilities (``No. of Recordkeepers'' in table 1, row 8) will
individually establish and maintain approximately 1,000 laboratory
records as described in section III.H of the draft guidance (``Total
Annual Records'' in table 1, row 8). We also estimate that preparing
and maintaining these records will take on average approximately 0.5
hours for each record (``Average Burden per Recordkeeping'' in table 1,
row 8).
9. Stability/Expiration Dating
Stability testing is used to ensure that a drug product will retain
its quality (in particular, strength) and remain sterile through the
labeled expiration date. The draft guidance recommends that procedures
established by outsourcing facilities for assessing the stability of
drug products should include: (1) using stability-indicating test
methods that are reliable, meaningful and specific; (2) evaluating
samples of the drug product in the same container closure system in
which the drug product will be marketed; (3) evaluating samples for
stability that are representative of the lot or batch from which they
were obtained and are stored under suitable conditions; and (4) testing
to evaluate antimicrobial effectiveness (resistance to antimicrobial
contamination) for drug products labeled or intended to be multiple
dose.
We estimate that annually a total of approximately 50 outsourcing
facilities (``No. of Recordkeepers'' in table 1, row
[[Page 37746]]
9) will individually establish and maintain approximately 90 procedures
for stability studies to determine an expiration date (``Total Annual
Records'' in table 1, row 9) for compounded drug products. We also
estimate that preparing and maintaining these procedures as described
in section III.I of the draft guidance will take approximately 5 hours
for each record (``Average Burden per Recordkeeping'' in table 1, row
9).
10. Packaging and Labels
Packaging of sterile drugs must ensure the sterility and integrity
of the product until it is administered to a patient, and product
labels must contain required information and labeling operations must
include controls to prevent mix-ups. Procedures should be established
by outsourcing facilities for packaging and labeling operations for
compounded sterile drug products, including the following: (1) The
container, closure, and packaging systems should provide adequate
protection against foreseeable external factors in storage, shipment,
and use that can cause contamination or deterioration; (2) packaging
records should include specimens of all labels used; procedures should
be established for issuance of labels, examination of issued labels,
reconciliation of used labels to prevent mix-ups; (3) there should be
physical/spatial separation between different labeling and packaging
operations to prevent mix-ups; and (4) controls should be established
that assure proper identification of any filled containers of sterile
products that are stored unlabeled for any period of time.
We estimate that annually a total of approximately 50 outsourcing
facilities (``No. of Recordkeepers'' in table 1, row 10) will
individually establish and maintain approximately 20 procedures and
records for packaging operations and labels (``Total Annual Records''
in table 1, row 10) for compounded drug products. We also estimate that
preparing and maintaining these procedures and records as described in
section III.J of the draft guidance will take approximately 5.5 hours
for each record (``Average Burden per Recordkeeping'' in table 1, row
10).
11. Quality Assurance Activities
A quality control unit must be established by outsourcing
facilities to oversee various aspects of compounded sterile drug
production and to monitor quality assurance. The responsibilities of
the quality control unit must be established in procedures and should
include investigations and development and oversight of appropriate
corrective actions and preventive actions regarding: Rejected lots of
finished product, unexpected results or trends, validation and
stability failures, and process deviations or equipment malfunctions
that involve critical equipment. The quality control unit also is
responsible for ensuring that sampling and testing are conducted to
ensure that appropriate specifications are met, and for product
complaint handling.
We estimate that annually a total of approximately 50 outsourcing
facilities (``No. of Recordkeepers'' in table 1, row 11) will
individually establish approximately 8 procedures on the
responsibilities of the quality control unit (``Total Annual Records''
in table 1, row 10) as described in section III.K of the draft
guidance. We also estimate that preparing and maintaining these
procedures will take approximately 3 hours for each record (``Average
Burden per Recordkeeping'' in table 1, row 11).
The total estimated recordkeeping, third party disclosure, and
reporting burdens for the draft guidance are as follows:
Table 1--Estimated Annual Recordkeeping Burden \1\
----------------------------------------------------------------------------------------------------------------
Number of Average burden
Type of recordkeeping Number of records per Total annual per Total hours
recordkeepers recordkeeper records recordkeeping
----------------------------------------------------------------------------------------------------------------
Facility Design............... 50 20 1,000 1.5............. 1,500
Control Systems and Procedures 50 3 150 5............... 750
For Maintaining Suitable
Facilities.
Environmental and Personnel 50 1,200 60,000 0.25 (15 15,000
Monitoring. minutes).
Equipment, Containers, and 50 1,000 50,000 0.25 (15 12,500
Closures. minutes).
Components.................... 50 240 12,000 4............... 48,000
Production and Process 50 5,000 250,000 0.25 (15 62,500
Controls. minutes).
Release Testing............... 50 240 12,000 4............... 48,000
Laboratory Controls........... 50 1,000 50,000 0.5 (30 minutes) 25,000
Stability/Expiration Dating... 50 90 4,500 5............... 22,500
Packaging and Labels.......... 50 20 1,000 5.5............. 5,500
Quality Assurance Activities.. 50 8 400 3............... 1,200
---------------------------------------------------------------------------------
Total..................... 50 8,821 441,050 ................ 242,450
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
Table 2--Estimated Annual Third-Party Disclosure Burden \1\
----------------------------------------------------------------------------------------------------------------
Type of disclosure & proposed Number of Frequency per Total annual Average burden
21 CFR section respondents disclosure disclosures per disclosure Total hours
----------------------------------------------------------------------------------------------------------------
Notification that a compounded 10 1 10 5............... 50
drug product fails to meet a
sterility criterion.
An expiration date is added to 50 540 27,000 0.25 (15 6,750
the compounded drug product's minutes).
label.
---------------------------------------------------------------------------------
Total..................... 6,800
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
[[Page 37747]]
Table 3--Estimated Annual Reporting Burden \1\
----------------------------------------------------------------------------------------------------------------
Number of Average
Type of reporting & proposed 21 Number of responses per Total annual burden per Total hours
CFR section respondents respondent responses response
----------------------------------------------------------------------------------------------------------------
Notification to FDA that a 10 1 10 5 50
compounded drug product fails
to meet a sterility criterion..
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
V. Electronic Access
Persons with access to the Internet may obtain the document at
either https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm or https://www.regulations.gov.
Dated: June 25, 2014.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2014-15370 Filed 7-1-14; 8:45 am]
BILLING CODE 4164-01-P
