80 FR 58491 - Controlled Correspondence Related to Generic Drug Development; Guidance for Industry; Availability

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Federal Register Volume 80, Issue 188 (September 29, 2015)

Page Range		58491-58492
FR Document		2015-24621

The Food and Drug Administration (FDA or Agency) is announcing the availability of a guidance for industry entitled ``Controlled Correspondence Related to Generic Drug Development''. The guidance document provides information regarding the process by which human generic drug manufacturers and related industry can submit correspondence to FDA requesting information on generic drug development. This guidance also describes FDA's process for providing communications related to such correspondence.

Federal Register, Volume 80 Issue 188 (Tuesday, September 29, 2015)

[Federal Register Volume 80, Number 188 (Tuesday, September 29, 2015)]
[Notices]
[Pages 58491-58492]
From the Federal Register Online [www.thefederalregister.org]
[FR Doc No: 2015-24621]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2014-D-1167]

Controlled Correspondence Related to Generic Drug Development;
Guidance for Industry; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing
the availability of a guidance for industry entitled ``Controlled
Correspondence Related to Generic Drug Development''. The guidance
document provides information regarding the process by which human
generic drug manufacturers and related industry can submit
correspondence to FDA requesting information on generic drug
development. This guidance also describes FDA's process for providing
communications related to such correspondence.

DATES: Submit either electronic or written comments on Agency guidances
at any time.

ADDRESSES: Submit written requests for single copies of this guidance
to the Division of Drug Information, Center for Drug Evaluation and
Research, Food and Drug Administration, 10001 New Hampshire Ave.,
Hillandale Building, 4th Floor, 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 guidance document.
Submit electronic comments on the guidance to http://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: Maryll Toufanian, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave, Bldg. 75, Rm. 1684, Silver Spring, MD 20993-0002, 240-
402-7944, Maryll.Toufanian@fda.hhs.gov.

SUPPLEMENTARY INFORMATION:

I. Background

FDA is announcing the availability of a guidance for industry
entitled ``Controlled Correspondence Related to Generic Drug
Development''. The guidance document provides information regarding the
process by which human generic drug manufacturers and related industry
can submit correspondence to FDA requesting information on generic drug
development. This guidance also describes FDA's process for providing
communications related to such correspondence.
Under the provisions of the Generic Drug User Fee Amendments of
2012 (GDUFA), FDA agreed to certain obligations as laid out in the
Generic Drug User Fee Act Program Performance Goals and Procedures for
fiscal years 2013 through 2017 (the GDUFA Commitment Letter) that
accompanies the legislation (Ref. 1). Among those obligations is FDA's
commitment to performance metrics for its responses to controlled
correspondence for fiscal years 2015 through 2017.
This guidance finalizes the draft guidance announced in the Federal
Register on August 27, 2014 (79 FR 51180). The Agency considered
comments on the draft guidance while finalizing this guidance.
Generally, we revised the draft guidance to provide clarifying and
explanatory information that will assist human generic drug
manufacturers and related industry as they submit controlled
correspondence to FDA. Changes from the draft guidance include a
description of a process to submit information to update the Agency's
Inactive Ingredient Database and a description of enhanced
communication to requestors regarding the status of their controlled
correspondence.
Two comment threads on the draft guidance benefit from additional

[[Page 58492]]

discussion here. Specifically, FDA received numerous comments regarding
two categories of requests that FDA proposed in the draft guidance to
exclude from the controlled correspondence process. First, FDA received
comments requesting that the Agency refrain from excluding requests for
product-specific guidance on demonstrating bioequivalence. FDA declines
to revise the guidance in this fashion. As set out in the draft
guidance, the short timeframe contemplated for the controlled
correspondence responses is inconsistent with the well-established
process for issuing product-specific recommendations described in the
guidance for industry on ``Bioequivalence Recommendations for Specific
Products (June 2010)'', as well as with the principles in the GDUFA
Commitment Letter regarding the Regulatory Science Initiative. Rather
than incorporating such guidance development into the controlled
correspondence process, FDA's Office of Generic Drugs (OGD) is
developing a separate process for product-specific guidance
development.
This approach is being managed by the Division of Therapeutic
Performance (DTP) within OGD's Office of Research and Standards,
involves representatives from numerous divisions and offices within
OGD, and provides for timely posting of product-specific
recommendations to facilitate generic drug development. Requests for
product-specific guidance development received through the general
GenericDrugs@fda.hhs.gov email account are forwarded directly to DTP
for consideration and tracking. Prioritization of guidance development
is based on a variety of factors, including public health needs,
industry demand for generic development, anticipated expiration of
reference listed drug exclusivity, formulation features and
predictability of in vivo performance, OGD experience with similar
formulations or product types, and the feasibility of different
approaches to demonstrate bioequivalence (e.g., pharmacokinetic/
pharmacodynamics studies, comparative clinical endpoint studies, and in
vitro approaches). FDA anticipates that this targeted development
approach will expedite the availability of product-specific guidances
while supporting the important policies of transparency and maximizing
benefit to the public health.
Second, FDA received comments regarding its proposed method of
responding to requests related to issues for which the Agency has not
yet determined a policy. Upon review of the comments, FDA is revising
its recommendations related to such inquiries. As described in the
guidance, if there is a better mechanism for a requestor to obtain
comment from FDA on the subject of the request than through a
controlled correspondence, the Agency will direct the requestor to such
a mechanism, e.g., a pre-abbreviated new drug application meeting
request or the Regulatory Science Initiative. For requests for which
the controlled correspondence pathway is the best mechanism, but that
raise issues for which FDA has not determined appropriate policy, such
requests will remain open until such policy decision is made.
This guidance is being issued consistent with FDA's good guidance
practices regulation (21 CFR 10.115). The guidance represents the
current thinking of FDA on controlled correspondence related to generic
drug development. It does not establish any rights for any person and
is not binding on FDA or the public. You can use an alternative
approach if it satisfies the requirements of the applicable statutes
and regulations.

II. Paperwork Reduction Act of 1995

This guidance refers to collections of information that are subject
to review by the Office of Management and Budget (OMB) under the
Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520). The collection
of information has been approved under OMB control number 0910-0797.

III. Comments

Interested persons may submit either electronic comments regarding
this document to http://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 http://www.regulations.gov.

IV. Electronic Access

Persons with access to the Internet may obtain the document at
either http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm or http://www.regulations.gov.

V. Reference

The following reference has been placed on display in the Division
of Dockets Management (see ADDRESSES) and may be seen by interested
persons between 9 a.m. and 4 p.m., Monday through Friday, and is
available electronically at http://www.regulations.gov.
(FDA has verified the Web site address in this reference section,
but we are not responsible for any subsequent changes to the Web
site after this document publishes in the Federal Register.)
1. Generic Drug User Fee Act Program Performance Goals and
Procedures (GDUFA Commitment Letter) for fiscal years 2013 through
2017, available at http://www.fda.gov/downloads/ForIndustry/UserFees/GenericDrugUserFees/UCM282505.pdf.

Dated: September 22, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-24621 Filed 9-28-15; 8:45 am]
BILLING CODE 4164-01-P

Federal Register / Vol. 80, No. 188 / Tuesday, September 29, 2015 / Notices 58491

PONDIMIN (fenfluramine HCl) and PONDEREX (fenfluramine HCl) INFORMATION section for electronic
tablets, 20 mg, and PONDEREX capsules were withdrawn from sale for access to the guidance document.
(fenfluramine HCl) capsules, 20 mg, reasons of safety or effectiveness. This Submit electronic comments on the
were the subject of NDA 16–618, held determination is consistent with FDA’s guidance to http://www.regulations.gov.
by Wyeth Pharmaceuticals, and were prior request and Wyeth Submit written comments to the
initially approved on June 14, 1973. Pharmaceutical’s withdrawal of Division of Dockets Management (HFA–
PONDIMIN (fenfluramine HCl) PONDIMIN (fenfluramine HCl) tablets 305), Food and Drug Administration,
sustained release tablets, 60 mg, was the and PONDEREX (fenfluramine HCl) 5630 Fishers Lane, Rm. 1061, Rockville,
subject of NDA 16–618, held by Wyeth capsules from the market for reasons of MD 20852.
Pharmaceuticals, and was initially safety or effectiveness. The Agency FOR FURTHER INFORMATION CONTACT:
approved in 1982. PONDIMIN and previously removed PONDIMIN Maryll Toufanian, Center for Drug
PONDEREX were indicated for (fenfluramine HCl) tablets and Evaluation and Research, Food and
treatment of obesity. PONDEREX (fenfluramine HCl) capsules Drug Administration, 10903 New
In 1997, FDA asked that PONDIMIN from the list of drug products published Hampshire Ave, Bldg. 75, Rm. 1684,
(fenfluramine HCl) tablets and in the Orange Book. FDA will not accept Silver Spring, MD 20993–0002, 240–
PONDEREX (fenfluramine HCl) capsules or approve any ANDAs that refer to 402–7944, Maryll.Toufanian@fda.
be withdrawn from the market after these drug products. hhs.gov.
receiving new evidence that the
Dated: September 23, 2015. SUPPLEMENTARY INFORMATION:
products were associated with valvular
heart disease (September 15, 1997, FDA Leslie Kux,
I. Background
Announces Withdrawal Fenfluramine Associate Commissioner for Policy.
and Dexfenfluramine (Fen-Phen), [FR Doc. 2015–24619 Filed 9–28–15; 8:45 am] FDA is announcing the availability of
available on the Internet at http:// BILLING CODE 4164–01–P
a guidance for industry entitled
www.fda.gov/Drugs/DrugSafety/Post ‘‘Controlled Correspondence Related to
marketDrugSafetyInformationfor Generic Drug Development’’. The
PatientsandProviders/ucm179871.htm; DEPARTMENT OF HEALTH AND guidance document provides
see FDA November 1997 Fen-Phen HUMAN SERVICES information regarding the process by
Safety Update Information, available on which human generic drug
the Internet at http://www.fda.gov/ Food and Drug Administration manufacturers and related industry can
Drugs/DrugSafety/PostmarketDrug submit correspondence to FDA
SafetyInformationforPatientsand [Docket No. FDA–2014–D–1167] requesting information on generic drug
Providers/ucm072820.htm). Wyeth development. This guidance also
Controlled Correspondence Related to describes FDA’s process for providing
Pharmaceuticals subsequently
Generic Drug Development; Guidance communications related to such
discontinued marketing these products.
for Industry; Availability correspondence.
On October 8, 1998, FDA issued a
Notice of Proposed Rulemaking AGENCY: Food and Drug Administration, Under the provisions of the Generic
proposing to include certain drug HHS. Drug User Fee Amendments of 2012
products on a list of drug products that (GDUFA), FDA agreed to certain
ACTION: Notice. obligations as laid out in the Generic
had been withdrawn or removed from
the market because such drugs products SUMMARY: The Food and Drug Drug User Fee Act Program Performance
or components of such drug products Administration (FDA or Agency) is Goals and Procedures for fiscal years
had been found to be unsafe or not announcing the availability of a 2013 through 2017 (the GDUFA
effective, and which could not be guidance for industry entitled Commitment Letter) that accompanies
compounded under section 503A of the ‘‘Controlled Correspondence Related to the legislation (Ref. 1). Among those
FD&C Act (63 FR 54082). FDA identified Generic Drug Development’’. The obligations is FDA’s commitment to
in that notice ‘‘all drug products guidance document provides performance metrics for its responses to
containing fenfluramine information regarding the process by controlled correspondence for fiscal
hydrochloride.’’ The notice also noted which human generic drug years 2015 through 2017.
that fenfluramine HCl tablets, formerly manufacturers and related industry can This guidance finalizes the draft
marketed as PONDIMIN tablets, were submit correspondence to FDA guidance announced in the Federal
associated with valvular heart disease, requesting information on generic drug Register on August 27, 2014 (79 FR
and the manufacturer voluntarily development. This guidance also 51180). The Agency considered
withdrew the drug from the market. describes FDA’s process for providing comments on the draft guidance while
This proposed rule was finalized in 64 communications related to such finalizing this guidance. Generally, we
FR 10944 (March 8, 1999), 21 CFR correspondence. revised the draft guidance to provide
216.24. clarifying and explanatory information
In the Federal Register of May 5, 2004 DATES: Submit either electronic or that will assist human generic drug
(69 FR 25124), FDA issued a notice that written comments on Agency guidances manufacturers and related industry as
it was withdrawing approval of 92 new at any time. they submit controlled correspondence
drug applications and 49 abbreviated ADDRESSES: Submit written requests for to FDA. Changes from the draft
new drug applications, including single copies of this guidance to the guidance include a description of a
asabaliauskas on DSK5VPTVN1PROD with NOTICES

PONDIMIN (fenfluramine HCl) tablets Division of Drug Information, Center for process to submit information to update
and PONDEREX (fenfluramine HCl) Drug Evaluation and Research, Food the Agency’s Inactive Ingredient
capsules, under section 505(e) of the and Drug Administration, 10001 New Database and a description of enhanced
FD&C Act. Consistent with § 314.161 Hampshire Ave., Hillandale Building, communication to requestors regarding
and its prior rulemaking on 4th Floor, Silver Spring, MD 20993– the status of their controlled
compounded drug products under 21 0002. Send one self-addressed adhesive correspondence.
CFR 216.24, FDA has determined that label to assist that office in processing Two comment threads on the draft
PONDIMIN (fenfluramine HCl) tablets your requests. See the SUPPLEMENTARY guidance benefit from additional

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58492 Federal Register / Vol. 80, No. 188 / Tuesday, September 29, 2015 / Notices

discussion here. Specifically, FDA comments, FDA is revising its and may be seen by interested persons
received numerous comments regarding recommendations related to such between 9 a.m. and 4 p.m., Monday
two categories of requests that FDA inquiries. As described in the guidance, through Friday, and is available
proposed in the draft guidance to if there is a better mechanism for a electronically at http://
exclude from the controlled requestor to obtain comment from FDA www.regulations.gov.
correspondence process. First, FDA on the subject of the request than (FDA has verified the Web site address in
received comments requesting that the through a controlled correspondence, this reference section, but we are not
Agency refrain from excluding requests the Agency will direct the requestor to responsible for any subsequent changes to
for product-specific guidance on such a mechanism, e.g., a pre- the Web site after this document publishes in
the Federal Register.)
demonstrating bioequivalence. FDA abbreviated new drug application 1. Generic Drug User Fee Act Program
declines to revise the guidance in this meeting request or the Regulatory Performance Goals and Procedures (GDUFA
fashion. As set out in the draft guidance, Science Initiative. For requests for Commitment Letter) for fiscal years 2013
the short timeframe contemplated for which the controlled correspondence through 2017, available at http://www.fda.
the controlled correspondence pathway is the best mechanism, but that gov/downloads/ForIndustry/UserFees/
responses is inconsistent with the well- raise issues for which FDA has not GenericDrugUserFees/UCM282505.pdf.
established process for issuing product- determined appropriate policy, such Dated: September 22, 2015.
specific recommendations described in requests will remain open until such Leslie Kux,
the guidance for industry on policy decision is made. Associate Commissioner for Policy.
‘‘Bioequivalence Recommendations for This guidance is being issued
Specific Products (June 2010)’’, as well [FR Doc. 2015–24621 Filed 9–28–15; 8:45 am]
consistent with FDA’s good guidance
as with the principles in the GDUFA practices regulation (21 CFR 10.115). BILLING CODE 4164–01–P
Commitment Letter regarding the The guidance represents the current
Regulatory Science Initiative. Rather thinking of FDA on controlled
than incorporating such guidance DEPARTMENT OF HEALTH AND
correspondence related to generic drug
development into the controlled HUMAN SERVICES
development. It does not establish any
correspondence process, FDA’s Office of rights for any person and is not binding Food and Drug Administration
Generic Drugs (OGD) is developing a on FDA or the public. You can use an
separate process for product-specific alternative approach if it satisfies the [Docket No. FDA–2015–D–3327]
guidance development. requirements of the applicable statutes
This approach is being managed by and regulations. E6(R2) Good Clinical Practice;
the Division of Therapeutic Performance International Conference on
(DTP) within OGD’s Office of Research II. Paperwork Reduction Act of 1995 Harmonisation; Draft Guidance for
and Standards, involves representatives This guidance refers to collections of Industry; Availability
from numerous divisions and offices information that are subject to review by AGENCY: Food and Drug Administration,
within OGD, and provides for timely the Office of Management and Budget HHS.
posting of product-specific (OMB) under the Paperwork Reduction
recommendations to facilitate generic ACTION: Notice.
Act of 1995 (44 U.S.C. 3501–3520). The
drug development. Requests for collection of information has been SUMMARY: The Food and Drug
product-specific guidance development approved under OMB control number Administration (FDA or Agency) is
received through the general Generic 0910–0797. announcing the availability of a draft
Drugs@fda.hhs.gov email account are
III. Comments guidance entitled ‘‘E6(R2) Good Clinical
forwarded directly to DTP for
Practice.’’ The draft guidance was
consideration and tracking. Interested persons may submit either prepared under the auspices of the
Prioritization of guidance development electronic comments regarding this International Conference on
is based on a variety of factors, document to http://www.regulations.gov Harmonisation of Technical
including public health needs, industry or written comments to the Division of Requirements for Registration of
demand for generic development, Dockets Management (see ADDRESSES). It Pharmaceuticals for Human Use (ICH).
anticipated expiration of reference listed is only necessary to send one set of The draft guidance amends the guidance
drug exclusivity, formulation features comments. Identify comments with the
and predictability of in vivo entitled ‘‘E6 Good Clinical Practice:
docket number found in brackets in the Consolidated Guidance’’ (E6(R1)) to
performance, OGD experience with heading of this document. Received
similar formulations or product types, encourage implementation of improved
comments may be seen in the Division and more efficient approaches to
and the feasibility of different of Dockets Management between 9 a.m.
approaches to demonstrate clinical trial design, conduct, oversight,
and 4 p.m., Monday through Friday, and recording, and reporting, and also
bioequivalence (e.g., pharmacokinetic/ will be posted to the docket at http://
pharmacodynamics studies, updates standards regarding electronic
www.regulations.gov. records and essential documents. The
comparative clinical endpoint studies,
and in vitro approaches). FDA IV. Electronic Access draft guidance is intended to improve
anticipates that this targeted Persons with access to the Internet clinical trial quality and efficiency
development approach will expedite the may obtain the document at either while maintaining human subject
protection. FDA is making this draft
asabaliauskas on DSK5VPTVN1PROD with NOTICES

availability of product-specific http://www.fda.gov/Drugs/Guidance
guidances while supporting the ComplianceRegulatoryInformation/ guidance available for comment on the
important policies of transparency and Guidances/default.htm or http:// sections that are additions to ICH E6(R1)
maximizing benefit to the public health. www.regulations.gov. and marked as ‘‘ADDENDUM.’’
Second, FDA received comments DATES: Although you can comment on
regarding its proposed method of V. Reference any guidance at any time (see 21 CFR
responding to requests related to issues The following reference has been 10.115(g)(5)), to ensure that the Agency
for which the Agency has not yet placed on display in the Division of considers your comment on the sections
determined a policy. Upon review of the Dockets Management (see ADDRESSES) of this draft guidance marked as

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Document Created: 2015-12-15 09:47:12
Document Modified: 2015-12-15 09:47:12

Category		Regulatory Information
Collection		Federal Register
sudoc Class		AE 2.7: GS 4.107: AE 2.106:
Publisher		Office of the Federal Register, National Archives and Records Administration
Section		Notices
Action		Notice.
Dates		Submit either electronic or written comments on Agency guidances at any time.
Contact		Maryll Toufanian, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave, Bldg. 75, Rm. 1684, Silver Spring, MD 20993-0002, 240- 402-7944, [email protected]
FR Citation		80 FR 58491

80 FR 58491 - Controlled Correspondence Related to Generic Drug Development; Guidance for Industry; Availability

DEPARTMENT OF HEALTH AND HUMAN SERVICESFood and Drug Administration

Federal Register Volume 80, Issue 188 (September 29, 2015)

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration