Draft Guidance for Industry on Chemistry, Manufacturing, and Controls Postapproval Manufacturing Changes Reportable in Annual Reports; Availability, 36421-36423 [2010-15415]
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Federal Register / Vol. 75, No. 122 / Friday, June 25, 2010 / Notices
seeks a determination that DELALUTIN
(hydroxyprogesterone caproate)
injection was not withdrawn for reasons
of safety or efficacy. FDA has reviewed
the information submitted by petitioner
and has independently evaluated
relevant literature and data for adverse
event reports for DELALUTIN
(hydroxyprogesterone caproate)
injection. Based on its evaluation, FDA
does not consider this information to
indicate that DELALUTIN
(hydroxyprogesterone caproate)
injection, 125 mg/mL and 250 mg/mL,
was withdrawn for reasons of safety or
effectiveness.
For the reasons outlined in this
document, FDA determines that
DELALUTIN (hydroxyprogesterone
caproate) injection, 125 mg/mL and 250
mg/mL, was not withdrawn from sale
for reasons of safety or effectiveness.
Accordingly, the agency will continue
to list DELALUTIN
(hydroxyprogesterone caproate)
injection, 125 mg/mL and 250 mg/mL,
in the ‘‘Discontinued Drug Product List’’
section of the Orange Book. The
‘‘Discontinued Drug Product List’’
delineates, among other items, drug
products that have been discontinued
from marketing for reasons other than
safety or effectiveness. ANDAs that refer
to DELALUTIN (hydroxyprogesterone
caproate) injection, 125 mg/mL and 250
mg/mL, may be approved by the agency
as long as they meet all relevant legal
and regulatory requirements for
approval of ANDAs. If FDA determines
that labeling for these drug products
should be revised to meet current
standards, the agency will advise ANDA
applicants to submit such labeling.
In considering whether to file an
ANDA for this drug product, future
applicants should be advised that they
may not be able to obtain DELALUTIN
(hydroxyprogesterone caproate)
injection, 125 mg/mL and 250 mg/mL,
for bioequivalence testing because the
product has not been commercially
available for a number of years. An
ANDA applicant who is unable to
obtain DELALUTIN
(hydroxyprogesterone caproate)
injection, 125 mg/mL and 250 mg/mL,
for bioequivalence testing should
contact the Office of Generic Drugs for
a determination of what showing is
necessary to satisfy the requirements of
section 505(j)(2)(A)(iv) of the act. If an
ANDA is approved without a showing
of bioequivalence, the approved product
will not be considered therapeutically
equivalent (i.e., granted an AB rating) in
the Orange Book.
VerDate Mar<15>2010
16:23 Jun 24, 2010
Jkt 220001
Dated: June 21, 2010.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2010–15416 Filed 6–24–10; 8:45 am]
BILLING CODE 4160–01–S
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2010–D–0283]
Draft Guidance for Industry on
Chemistry, Manufacturing, and
Controls Postapproval Manufacturing
Changes Reportable in Annual
Reports; 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 ‘‘CMC Postapproval
Manufacturing Changes Reportable in
Annual Reports.’’ This draft guidance
provides recommendations to holders of
new drug applications (NDAs) and
abbreviated new drug applications
(ANDAs) regarding the types of changes
that may be reported in annual reports.
Specifically, the draft guidance
describes chemistry, manufacturing, and
controls (CMC) postapproval
manufacturing changes that FDA has
determined will likely present minimal
potential to have adverse effects on
product quality and, therefore, may be
reported by applicants in an annual
report. (The draft guidance excludes
positron emission tomography (PET)
drug products.)
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 23,
2010.
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://
PO 00000
Frm 00076
Fmt 4703
Sfmt 4703
36421
www.regulations.gov. Submit written
comments, including comments
regarding the proposed collection of
information, to the Division of Dockets
Management (HFA–305), Food and Drug
Administration, 5630 Fishers Lane, rm.
1061, Rockville, MD 20852.
FOR FURTHER INFORMATION CONTACT: Jon
Clark, Center for Drug Evaluation and
Research, Food and Drug
Administration, Bldg. 51, rm. 4178,
10903 New Hampshire Ave., Silver
Spring, MD 20993–0002, 301–796–2400.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of
a draft guidance for industry entitled
‘‘CMC Postapproval Manufacturing
Changes Reportable in Annual Reports.’’
This draft guidance provides
recommendations to holders of NDAs
and ANDAs regarding the types of CMC
postapproval manufacturing changes
that FDA has determined will likely
present minimal potential to have
adverse effects on product quality, and
therefore, may be reported by applicants
in an annual report under § 314.70 (21
CFR 314.70).
In its September 2004 final report,
‘‘Pharmaceutical Current Good
Manufacturing Practices (CGMPs) for
the 21st Century—A Risk-Based
Approach’’ (Pharmaceutical Product
Quality Initiative, https://www.fda.gov/
Drugs/DevelopmentApprovalProcess/
Manufacturing/QuestionsandAnswerson
CurrentGoodManufacturing
PracticescGMPforDrugs/
ucm137175.htm), FDA stated that to
keep pace with the many advances in
quality management practices in
manufacturing and to enable the agency
to more effectively allocate its limited
regulatory resources, FDA would
implement a cooperative, risk-based
approach for regulating pharmaceutical
manufacturing. As part of this approach,
FDA determined that to provide the
most effective public health protection,
its CMC regulatory review should be
based on an understanding of product
risk and how best to manage this risk.
The number of CMC manufacturing
supplements for NDAs and ANDAs has
continued to increase over the last
several years. In connection with FDA’s
Pharmaceutical Product Quality
Initiative and its risk-based approach to
CMC review, FDA has evaluated the
types of changes that have been
submitted in CMC postapproval
manufacturing supplements and
determined that many of the changes
being reported present very low risk to
the quality of the product and do not
need to be submitted in supplements.
E:\FR\FM\25JNN1.SGM
25JNN1
36422
Federal Register / Vol. 75, No. 122 / Friday, June 25, 2010 / Notices
Based on this recent evaluation, FDA
developed a list (attached as an
appendix to the draft guidance) to
provide current recommendations to
companies regarding which
postapproval manufacturing changes for
NDAs and ANDAs may be considered to
have a minimal potential for an adverse
effect on the identity, strength, quality,
purity, or potency of the drug product
and, therefore, may be classified as a
change reportable in an annual report
(e.g., notification of a change after
implementation) rather than in a
supplement.
This draft guidance is being issued
consistent with FDA’s good guidance
practices regulation (21 CFR 10.115).
The draft guidance, when finalized, will
represent the agency’s current thinking
on CMC postapproval manufacturing
changes reportable in annual reports for
NDAs and ANDAs. 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.
II. Comments
Interested persons may submit to the
Division of Dockets Management (see
ADDRESSES) either electronic or written
comments regarding this document. It is
only necessary to send one set of
comments. It is no longer necessary to
send two copies of mailed 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.
mstockstill on DSKH9S0YB1PROD with NOTICES
III. Paperwork Reduction Act of 1995
Under the Paperwork Reduction Act
(44 U.S.C. 3501–3520) (the PRA),
Federal agencies must obtain approval
from the Office of Management and
Budget (OMB) for each collection of
information they conduct or sponsor.
‘‘Collection of information’’ is defined in
44 U.S.C. 3502(3) and 5 CFR 1320.3(c)
and includes agency requests or
requirements that members of the public
submit reports, keep records, or provide
information to a third party. Section
3506(c)(2)(A) of the PRA (44 U.S.C.
3506(c)(2)(A)) requires Federal agencies
to provide a 60-day notice in the
Federal Register concerning each
proposed collection of information
before submitting the collection to OMB
for approval. To comply with this
requirement, FDA is publishing notice
of the proposed collection of
information set forth in this document.
VerDate Mar<15>2010
16:23 Jun 24, 2010
Jkt 220001
With respect to the following
collection of information, FDA invites
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: CMC Postapproval
Manufacturing Changes Reportable in
Annual Reports.
Description of Respondents:
Respondents to this collection of
information are applicants of approved
NDAs and ANDAs.
Burden Estimate: FDA is requesting
public comment on estimates of annual
submissions from these respondents, as
required by § 314.70 and §§ 314.71,
314.81(b)(2), and 314.97 (21 CFR 314.71,
314.81(b)(2), and 314.97) and described
in this draft guidance. Sections 314.70
and 314.71 require that supplements be
submitted to FDA for certain changes to
an approved application. Section
314.81(b)(2) requires that annual reports
be submitted to FDA (Form FDA 2252).
Section 314.97 sets forth requirements
for submitting supplements to an
approved ANDA for changes that
require FDA approval. Section 314.98(c)
requires annual reports and other
postmarketing reports for ANDAs. The
estimate for annual reports for ANDAs
is included under § 314.81(b)(2). Other
postmarketing reports under § 314.98(c)
are not implicated by this notice.
The draft guidance describes our
current thinking on the interpretation of
these requirements. Part of the intent for
this draft guidance is to reduce the
burden of reporting some manufacturing
changes. Currently, for postapproval
changes considered to be major,
applicants of NDAs and ANDAs must
submit and receive FDA approval of a
supplement before the product made
with the manufacturing change is
distributed. If a change is considered to
be moderate, an applicant must submit
a supplement at least 30 days before the
product is distributed or, in some cases,
submit a supplement at the time of
distribution. If a change is considered to
be minor, an applicant may proceed
with the change, but must notify FDA of
the change in an annual report. When a
PO 00000
Frm 00077
Fmt 4703
Sfmt 4703
change is approved via a supplemental
application, these changes currently
also must be reported in the annual
report. The draft guidance describes the
types of postapproval changes that
applicants of NDAs and ANDAs
currently submit in supplements to
NDAs or ANDAs but that, under the
draft guidance, may now be reported
only in annual reports and do not need
prior FDA approval. As a result,
applicants would no longer need to
submit supplements for such changes.
FDA currently has OMB approval for
the collection of information entitled,
‘‘Application for Food and Drug
Administration Approval to Market a
New Drug’’ (OMB Control Number
0910–0001). This collection of
information includes all information
requirements imposed by the
regulations under part 314 (21 CFR part
314) on applicants who apply for
approval of an NDA or ANDA to market
or change an approved application. In
particular, among other things, this
collection of information includes: (1)
The submission of supplements to FDA
for certain changes to an approved
application in accordance with
§§ 314.70 and 314.71; (2) the submission
of annual reports to FDA (Form FDA
2252) in accordance with § 314.81(b)(2);
(3) the submission of supplements to an
approved ANDA for changes that
require FDA approval; and (4) other
postmarketing reports for ANDAs in
accordance with § 314.98(c), of which
the estimate for annual reports is
included under § 314.81(b)(2).
Therefore, this information collection
includes the supplements to NDAs and
ANDAs and the annual reports for
NDAs and ANDAs that are described in
the draft guidance.
Under the applicable regulations and
the draft guidance, the following change
to the current approval by OMB under
the PRA is estimated: Supplements to
NDAs under §§ 314.70 and 314.71 and
supplements to ANDAs under § 314.97.
Although the submission of
supplements to NDAs and ANDAs is
approved under OMB Control Number
0910–0001, the total number of
supplements submitted per year is
estimated to be reduced based on the
recommendations in the draft guidance
because certain changes submitted as
supplements would now be submitted
in annual reports. Therefore, for such
changes, the information collection with
respect to the submission of
supplements will be reduced. Because
the number of supplements per year is
estimated to be reduced, the total
number of hours for preparing
supplements is also estimated to be
reduced.
E:\FR\FM\25JNN1.SGM
25JNN1
Federal Register / Vol. 75, No. 122 / Friday, June 25, 2010 / Notices
Based on FDA’s knowledge of
supplements and annual reports to
NDAs and ANDAs, as well as the
agency’s familiarity with the time
needed to prepare supplements and
annual reports, our estimates for this
information collection are as follows:
The total number of supplements
submitted per year is estimated to be
reduced based on the recommendations
in the draft guidance. Based on the
number of CMC manufacturing
supplements received for NDAs and
ANDAs during 2008, FDA estimates that
it will receive annually approximately
800 responses under §§ 314.70 and
314.71 for NDAs and approximately
2,075 responses under § 314.97 for
ANDAs. The number of annual
frequencies per response will decrease
36423
accordingly. FDA estimates that
approximately the same number of
respondents will submit responses
under §§ 314.70, 314.71, and 314.97 and
each response will take approximately
the same amount of time to prepare as
in the information collection currently
approved under OMB Control Number
0910–0001.
TABLE 1.—ESTIMATED ANNUAL REPORTING BURDEN1
21 CFR Section
No. of Respondents
Annual Frequency
per Response
Total Annual
Responses
Hours Per
Response
Total Hours
314.70 and 314.71
281 (same as
currently approved)
2.85
800
150 (same as
currently approved)
120,000
314.97
215 (same as
currently approved)
9.65
2,075
80 (same as
currently approved)
166,000
Total Hours
1 There
286,000
are no capital costs or operating and maintenance costs associated with this collection of information.
listed below may be obtained by writing
to the indicated licensing contact at the
Office of Technology Transfer, National
Institutes of Health, 6011 Executive
Boulevard, Suite 325, Rockville,
Maryland 20852–3804; telephone: 301/
496–7057; fax: 301/402–0220. A signed
Confidential Disclosure Agreement will
be required to receive copies of the
patent applications.
Therefore, the estimated annual
reporting burden for this information
collection is 286,000 hours.
IV. 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 21, 2010.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2010–15415 Filed 6–24–10; 8:45 am]
BILLING CODE 4160–01–S
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
Government-Owned Inventions;
Availability for Licensing
mstockstill on DSKH9S0YB1PROD with NOTICES
AGENCY: National Institutes of Health,
Public Health Service, HHS.
ACTION: Notice.
SUMMARY: The inventions listed below
are owned by an agency of the U.S.
Government and are available for
licensing in the U.S. in accordance with
35 U.S.C. 207 to achieve expeditious
commercialization of results of
federally-funded research and
development. Foreign patent
applications are filed on selected
inventions to extend market coverage
for companies and may also be available
for licensing.
ADDRESSES: Licensing information and
copies of the U.S. patent applications
VerDate Mar<15>2010
16:23 Jun 24, 2010
Jkt 220001
A New Class of Antibiotics: Natural
Inhibitors of Bacterial Cytoskeletal
Protein FtsZ To Fight Drug-Susceptible
and Multi-Drug Resistant Bacteria
Description of Invention: The risk of
infectious diseases epidemic has been
alarming in recent decades. This is not
only because of the increase incident of
so-called ‘‘super bugs,’’ but also because
of the scarce number of potential
antibiotics in the pipeline. Currently,
the need for new antibiotics is greater
than ever! The present invention by the
National Institute of Diabetes and
Digestive and Kidney Disease (NIDDK),
part of the National Institute of Health
(NIH), address this urgent need. The
invention is a new class of
chrysophaentin antibiotics that inhibit
the growth of broad-spectrum, drugsusceptible, and drug-resistant bacteria.
Derived from the yellow algae
Chrysophaeum taylori, the inventor has
extracted 8 small molecules of natural
products and tested for antimicrobial
activity against drug resistant bacteria,
methicillin-resistant Staphylococcus
aureus (MRSA) and vancomycinresistant Enterococcus faecalis (VRE), as
well as other drug susceptible strains.
Structurally, the molecules represent a
new class of antibiotic that also likely
work through a distinct mechanism of
PO 00000
Frm 00078
Fmt 4703
Sfmt 4703
action from that of current antibiotics,
which is key for the further
development of antibiotics that inhibit
drug-resistant strains.
The bacterial cytoskeletal protein FtsZ
is a GTPase and has structural homology
to the eukaryotic cytoskeletal protein
tubulin, but lacks significant sequence
similarity. FtsZ is essential for bacterial
cell division. It is responsible for Z-ring
assembly in bacteria, which leads to
bacterial cell division. Experiments
show that the disclosed compounds are
competitive inhibitors of GTP binding to
FtsZ, and must bind in the GTP-binding
site of FtsZ. Inhibition of FtsZ stops
bacterial cell division and is a validated
target for new antimicrobials. FtsZ is
highly conserved among all bacteria,
making it a very attractive antimicrobial
target.
Applications:
• Therapeutic potential for curing
bacterial infections in vivo, including
for clinical and veterinary applications.
• Antiseptics in hospital sittings.
• Since FtsZ is structurally similar,
but do not share sequence homology to
eukaryotic cytoskeletal protein tubulin,
these compounds may have antitumor
properties against some cancer types or
cell lines.
Advantages:
• Structurally distinct antimicrobial
compounds.
• Attack newly validated antibacterial
targeted protein FtsZ.
• These compounds have a unique
mechanism of action which inhibit FtsZ
by inhibiting FtsZ GTPase activity.
• Inhibit drug-susceptible and drugresistant bacteria.
Development Status:
E:\FR\FM\25JNN1.SGM
25JNN1
]]>Agencies
[Federal Register Volume 75, Number 122 (Friday, June 25, 2010)]
[Notices]
[Pages 36421-36423]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2010-15415]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2010-D-0283]
Draft Guidance for Industry on Chemistry, Manufacturing, and
Controls Postapproval Manufacturing Changes Reportable in Annual
Reports; 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 ``CMC
Postapproval Manufacturing Changes Reportable in Annual Reports.'' This
draft guidance provides recommendations to holders of new drug
applications (NDAs) and abbreviated new drug applications (ANDAs)
regarding the types of changes that may be reported in annual reports.
Specifically, the draft guidance describes chemistry, manufacturing,
and controls (CMC) postapproval manufacturing changes that FDA has
determined will likely present minimal potential to have adverse
effects on product quality and, therefore, may be reported by
applicants in an annual report. (The draft guidance excludes positron
emission tomography (PET) drug products.)
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 23, 2010.
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, including comments
regarding the proposed collection of information, to the Division of
Dockets Management (HFA-305), Food and Drug Administration, 5630
Fishers Lane, rm. 1061, Rockville, MD 20852.
FOR FURTHER INFORMATION CONTACT: Jon Clark, Center for Drug Evaluation
and Research, Food and Drug Administration, Bldg. 51, rm. 4178, 10903
New Hampshire Ave., Silver Spring, MD 20993-0002, 301-796-2400.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of a draft guidance for industry
entitled ``CMC Postapproval Manufacturing Changes Reportable in Annual
Reports.'' This draft guidance provides recommendations to holders of
NDAs and ANDAs regarding the types of CMC postapproval manufacturing
changes that FDA has determined will likely present minimal potential
to have adverse effects on product quality, and therefore, may be
reported by applicants in an annual report under Sec. 314.70 (21 CFR
314.70).
In its September 2004 final report, ``Pharmaceutical Current Good
Manufacturing Practices (CGMPs) for the 21st Century--A Risk-Based
Approach'' (Pharmaceutical Product Quality Initiative, https://www.fda.gov/Drugs/DevelopmentApprovalProcess/Manufacturing/QuestionsandAnswersonCurrentGoodManufacturingPracticescGMPforDrugs/ucm137175.htm), FDA stated that to keep pace with the many advances in
quality management practices in manufacturing and to enable the agency
to more effectively allocate its limited regulatory resources, FDA
would implement a cooperative, risk-based approach for regulating
pharmaceutical manufacturing. As part of this approach, FDA determined
that to provide the most effective public health protection, its CMC
regulatory review should be based on an understanding of product risk
and how best to manage this risk.
The number of CMC manufacturing supplements for NDAs and ANDAs has
continued to increase over the last several years. In connection with
FDA's Pharmaceutical Product Quality Initiative and its risk-based
approach to CMC review, FDA has evaluated the types of changes that
have been submitted in CMC postapproval manufacturing supplements and
determined that many of the changes being reported present very low
risk to the quality of the product and do not need to be submitted in
supplements.
[[Page 36422]]
Based on this recent evaluation, FDA developed a list (attached as
an appendix to the draft guidance) to provide current recommendations
to companies regarding which postapproval manufacturing changes for
NDAs and ANDAs may be considered to have a minimal potential for an
adverse effect on the identity, strength, quality, purity, or potency
of the drug product and, therefore, may be classified as a change
reportable in an annual report (e.g., notification of a change after
implementation) rather than in a supplement.
This draft guidance is being issued consistent with FDA's good
guidance practices regulation (21 CFR 10.115). The draft guidance, when
finalized, will represent the agency's current thinking on CMC
postapproval manufacturing changes reportable in annual reports for
NDAs and ANDAs. 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.
II. Comments
Interested persons may submit to the Division of Dockets Management
(see ADDRESSES) either electronic or written comments regarding this
document. It is only necessary to send one set of comments. It is no
longer necessary to send two copies of mailed 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.
III. Paperwork Reduction Act of 1995
Under the Paperwork Reduction Act (44 U.S.C. 3501-3520) (the PRA),
Federal agencies must obtain approval from the Office of Management and
Budget (OMB) for each collection of information they conduct or
sponsor. ``Collection of information'' is defined in 44 U.S.C. 3502(3)
and 5 CFR 1320.3(c) and includes agency requests or requirements that
members of the public submit reports, keep records, or provide
information to a third party. Section 3506(c)(2)(A) of the PRA (44
U.S.C. 3506(c)(2)(A)) requires Federal agencies to provide a 60-day
notice in the Federal Register concerning each proposed collection of
information before submitting the collection to OMB for approval. To
comply with this requirement, FDA is publishing notice of the proposed
collection of information set forth in this document.
With respect to the following collection of information, FDA
invites 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: CMC Postapproval Manufacturing Changes Reportable in Annual
Reports.
Description of Respondents: Respondents to this collection of
information are applicants of approved NDAs and ANDAs.
Burden Estimate: FDA is requesting public comment on estimates of
annual submissions from these respondents, as required by Sec. 314.70
and Sec. Sec. 314.71, 314.81(b)(2), and 314.97 (21 CFR 314.71,
314.81(b)(2), and 314.97) and described in this draft guidance.
Sections 314.70 and 314.71 require that supplements be submitted to FDA
for certain changes to an approved application. Section 314.81(b)(2)
requires that annual reports be submitted to FDA (Form FDA 2252).
Section 314.97 sets forth requirements for submitting supplements to an
approved ANDA for changes that require FDA approval. Section 314.98(c)
requires annual reports and other postmarketing reports for ANDAs. The
estimate for annual reports for ANDAs is included under Sec.
314.81(b)(2). Other postmarketing reports under Sec. 314.98(c) are not
implicated by this notice.
The draft guidance describes our current thinking on the
interpretation of these requirements. Part of the intent for this draft
guidance is to reduce the burden of reporting some manufacturing
changes. Currently, for postapproval changes considered to be major,
applicants of NDAs and ANDAs must submit and receive FDA approval of a
supplement before the product made with the manufacturing change is
distributed. If a change is considered to be moderate, an applicant
must submit a supplement at least 30 days before the product is
distributed or, in some cases, submit a supplement at the time of
distribution. If a change is considered to be minor, an applicant may
proceed with the change, but must notify FDA of the change in an annual
report. When a change is approved via a supplemental application, these
changes currently also must be reported in the annual report. The draft
guidance describes the types of postapproval changes that applicants of
NDAs and ANDAs currently submit in supplements to NDAs or ANDAs but
that, under the draft guidance, may now be reported only in annual
reports and do not need prior FDA approval. As a result, applicants
would no longer need to submit supplements for such changes.
FDA currently has OMB approval for the collection of information
entitled, ``Application for Food and Drug Administration Approval to
Market a New Drug'' (OMB Control Number 0910-0001). This collection of
information includes all information requirements imposed by the
regulations under part 314 (21 CFR part 314) on applicants who apply
for approval of an NDA or ANDA to market or change an approved
application. In particular, among other things, this collection of
information includes: (1) The submission of supplements to FDA for
certain changes to an approved application in accordance with
Sec. Sec. 314.70 and 314.71; (2) the submission of annual reports to
FDA (Form FDA 2252) in accordance with Sec. 314.81(b)(2); (3) the
submission of supplements to an approved ANDA for changes that require
FDA approval; and (4) other postmarketing reports for ANDAs in
accordance with Sec. 314.98(c), of which the estimate for annual
reports is included under Sec. 314.81(b)(2). Therefore, this
information collection includes the supplements to NDAs and ANDAs and
the annual reports for NDAs and ANDAs that are described in the draft
guidance.
Under the applicable regulations and the draft guidance, the
following change to the current approval by OMB under the PRA is
estimated: Supplements to NDAs under Sec. Sec. 314.70 and 314.71 and
supplements to ANDAs under Sec. 314.97. Although the submission of
supplements to NDAs and ANDAs is approved under OMB Control Number
0910-0001, the total number of supplements submitted per year is
estimated to be reduced based on the recommendations in the draft
guidance because certain changes submitted as supplements would now be
submitted in annual reports. Therefore, for such changes, the
information collection with respect to the submission of supplements
will be reduced. Because the number of supplements per year is
estimated to be reduced, the total number of hours for preparing
supplements is also estimated to be reduced.
[[Page 36423]]
Based on FDA's knowledge of supplements and annual reports to NDAs
and ANDAs, as well as the agency's familiarity with the time needed to
prepare supplements and annual reports, our estimates for this
information collection are as follows: The total number of supplements
submitted per year is estimated to be reduced based on the
recommendations in the draft guidance. Based on the number of CMC
manufacturing supplements received for NDAs and ANDAs during 2008, FDA
estimates that it will receive annually approximately 800 responses
under Sec. Sec. 314.70 and 314.71 for NDAs and approximately 2,075
responses under Sec. 314.97 for ANDAs. The number of annual
frequencies per response will decrease accordingly. FDA estimates that
approximately the same number of respondents will submit responses
under Sec. Sec. 314.70, 314.71, and 314.97 and each response will take
approximately the same amount of time to prepare as in the information
collection currently approved under OMB Control Number 0910-0001.
Table 1.--Estimated Annual Reporting Burden\1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
Annual Frequency Total Annual Hours Per
21 CFR Section No. of Respondents per Response Responses Response Total Hours
--------------------------------------------------------------------------------------------------------------------------------------------------------
314.70 and 314.71 281 (same as 2.85 800 150 (same as 120,000
currently currently
approved) approved)
--------------------------------------------------------------------------------------------------------------------------------------------------------
314.97 215 (same as 9.65 2,075 80 (same as 166,000
currently currently
approved) approved)
--------------------------------------------------------------------------------------------------------------------------------------------------------
Total Hours 286,000
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.
Therefore, the estimated annual reporting burden for this
information collection is 286,000 hours.
IV. 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 21, 2010.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2010-15415 Filed 6-24-10; 8:45 am]
BILLING CODE 4160-01-S
