80 FR 23802 - Environmental Assessment: Questions and Answers Regarding Drugs With Estrogenic, Androgenic, or Thyroid Activity; Draft Guidance for Industry; Availability

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Federal Register Volume 80, Issue 82 (April 29, 2015)

Page Range		23802-23803
FR Document		2015-09869

The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled ``Environmental Assessment: Questions and Answers Regarding Drugs With Estrogenic, Androgenic, or Thyroid Activity.'' This guidance is intended to supplement CDER's guidance for industry on ``Environmental Assessment of Human Drug and Biologics Applications,'' issued July 1998, by addressing specific considerations for drugs that have potential estrogenic, androgenic, or thyroid pathway activity (E, A, or T activity) in environmental organisms. It is intended to help sponsors of such drugs determine whether they should submit environmental assessments (EA) for new drug applications (NDAs) and certain NDA supplements, and to clarify what information such sponsors should include if they submit a claim of categorical exclusion instead of an EA.

Federal Register, Volume 80 Issue 82 (Wednesday, April 29, 2015)

[Federal Register Volume 80, Number 82 (Wednesday, April 29, 2015)]
[Notices]
[Pages 23802-23803]
From the Federal Register Online  [www.thefederalregister.org]
[FR Doc No: 2015-09869]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2015-D-1213]


Environmental Assessment: Questions and Answers Regarding Drugs 
With Estrogenic, Androgenic, or Thyroid Activity; Draft Guidance for 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the availability of a draft guidance for industry entitled 
``Environmental Assessment: Questions and Answers Regarding Drugs With 
Estrogenic, Androgenic, or Thyroid Activity.'' This guidance is 
intended to supplement CDER's guidance for industry on ``Environmental 
Assessment of Human Drug and Biologics Applications,'' issued July 
1998, by addressing specific considerations for drugs that have 
potential estrogenic, androgenic, or thyroid pathway activity (E, A, or 
T activity) in environmental organisms. It is intended to help sponsors 
of such drugs determine whether they should submit environmental 
assessments (EA) for new drug applications (NDAs) and certain NDA 
supplements, and to clarify what information such sponsors should 
include if they submit a claim of categorical exclusion instead of an 
EA.

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 June 29, 2015.

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, 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 draft guidance document.
    Submit electronic comments on the draft 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: Raanan A. Bloom, Environmental 
Assessment Team, Center for Drug Evaluation and Research, Food and Drug 
Administration, 10903 New Hampshire Ave., Silver Spring, MD 20993-0002, 
301-796-2185, [email protected].

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a draft guidance for industry 
entitled ``Environmental Assessment: Questions and Answers Regarding 
Drugs With Estrogenic, Androgenic, or Thyroid Activity.'' The National 
Environmental Policy Act of 1969 (Pub. L. 91-190) requires all Federal 
agencies to assess the environmental impact of their actions and to 
ensure that the interested and affected public is informed of the 
environmental analyses. FDA regulations at 21 CFR part 25 specify that 
EAs must be submitted as part of certain NDAs, abbreviated new drug 
applications (ANDAs), biologic license applications (BLAs), supplements 
to such applications, and investigational new drug applications (INDs), 
and for various other actions, unless the action qualifies for a 
categorical exclusion. Failure to submit either an EA or a claim of 
categorical exclusion is sufficient grounds for FDA to refuse to file 
or approve an application (Sec.  25.15(a), 21 CFR 314.101(d)(4), and 
601.2(a) and (c)).
    Categorical exclusions for actions related to human drugs and 
biologics are listed at Sec.  25.31. This draft guidance focuses on the 
categorical exclusion for actions on NDAs and NDA supplements that 
would increase the use of an active moiety, but the estimated 
concentration of the substance at the point of entry into the aquatic 
environment would be below 1 part per billion (1 ppb) (Sec.  25.31(b)). 
Although an action that qualifies for this exclusion ordinarily does 
not require an EA, FDA will require ``at least an EA'' if 
``extraordinary circumstances'' indicate that the specific proposed 
action (e.g., the approval of the NDA) may significantly affect the 
quality of the human environment (Sec.  25.21). Research indicates that 
drugs with endocrine-related activity and, more specifically, drugs 
with E, A, or T activity have the potential to cause developmental or 
reproductive effects when present in the aquatic environment at 
concentrations below 1 ppb.\1\
---------------------------------------------------------------------------

    \1\ For example, see Section II.C (pp. 7-13) of USFDA, 2013, 
``Response to Citizen Petition to the FDA Commissioner under the 
National Environmental Policy Act and Administrative Procedure Act 
Requesting an Amendment to an FDA Rule Regarding Human Drugs and 
Biologics,'' Docket No. FDA-2010-P-0377; U.S. Environmental 
Protection Agency (USEPA), Endocrine Disruptor Screening Program 
(EDSP), last accessed February 17, 2015, at http://www.epa.gov/endo; 
and Organisation for Economic Co-operation and Development (OECD), 
OECD Work Related to Endocrine Disrupters, last accessed February 
17, 2015, at http://www.oecd.org/env/ehs/testing/oecdworkrelatedtoendocrinedisrupters.htm.
---------------------------------------------------------------------------

    FDA has, on a case-by-case basis, requested additional information 
from sponsors of NDAs and NDA supplements for drugs with E, A, or T 
activity to help it determine whether extraordinary circumstances 
exist. However, late cycle requests for additional environmental 
information have the potential to delay approval of applications. 
Accordingly, this guidance is intended to clarify that sponsors of 
drugs with potential E, A, or T activity should consult with the Agency 
early in product development concerning the information FDA may need to 
determine whether an EA will be required or whether a claim of 
categorical exclusion will be acceptable, and what information should 
be included in the EA or claim of categorical exclusion.
    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 this topic. 
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.

[[Page 23803]]

II. 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.

III. The Paperwork Reduction Act of 1995

    This draft guidance refers to previously approved 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 collections of information in part 25 have been approved 
under OMB control number 0910-0322 and the collections of information 
in part 314 have been approved under OMB control number 0910-0001.

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.

    Dated: April 23, 2015.
Peter Lurie,
Associate Commissioner for Public Health Strategy and Analysis.
[FR Doc. 2015-09869 Filed 4-28-15; 8:45 am]
 BILLING CODE 4164-01-P

23802 Federal Register / Vol. 80, No. 82 / Wednesday, April 29, 2015 / Notices

Interested persons may submit to the DATES: Although you can comment on focuses on the categorical exclusion for
Division of Dockets Management (see any guidance at any time (see 21 CFR actions on NDAs and NDA supplements
ADDRESSES) electronic or written 10.115(g)(5)), to ensure that the Agency that would increase the use of an active
comments and written or electronic considers your comment on this draft moiety, but the estimated concentration
petitions. It is only necessary to send guidance before it begins work on the of the substance at the point of entry
one set of comments. Identify comments final version of the guidance, submit into the aquatic environment would be
with the docket number found in either electronic or written comments below 1 part per billion (1 ppb)
brackets in the heading of this on the draft guidance by June 29, 2015. (§ 25.31(b)). Although an action that
document. If you submit a written ADDRESSES: Submit written requests for qualifies for this exclusion ordinarily
petition, two copies are required. A single copies of the draft guidance to the does not require an EA, FDA will
petition submitted electronically must Division of Drug Information, Center for require ‘‘at least an EA’’ if
be submitted to http:// Drug Evaluation and Research, Food ‘‘extraordinary circumstances’’ indicate
www.regulations.gov, Docket No. FDA– and Drug Administration, 10001 New that the specific proposed action (e.g.,
2013–S–0610. Comments and petitions Hampshire Ave., Hillandale Building, the approval of the NDA) may
that have not been made publicly 4th Floor, Silver Spring, MD 20993– significantly affect the quality of the
available on http://www.regulations.gov 0002. Send one self-addressed adhesive human environment (§ 25.21). Research
may be viewed in the Division of label to assist that office in processing indicates that drugs with endocrine-
Dockets Management between 9 a.m. your requests. See the SUPPLEMENTARY related activity and, more specifically,
and 4 p.m., Monday through Friday. INFORMATION section for electronic drugs with E, A, or T activity have the
Dated: April 23, 2015. access to the draft guidance document. potential to cause developmental or
Peter Lurie, Submit electronic comments on the reproductive effects when present in the
draft guidance to http:// aquatic environment at concentrations
Associate Commissioner for Public Health
Strategy and Analysis. www.regulations.gov. Submit written below 1 ppb.1
comments to the Division of Dockets FDA has, on a case-by-case basis,
[FR Doc. 2015–09902 Filed 4–28–15; 8:45 am]
Management (HFA–305), Food and Drug requested additional information from
BILLING CODE 4164–01–P
Administration, 5630 Fishers Lane, Rm. sponsors of NDAs and NDA
1061, Rockville, MD 20852. supplements for drugs with E, A, or T
DEPARTMENT OF HEALTH AND FOR FURTHER INFORMATION CONTACT: activity to help it determine whether
HUMAN SERVICES Raanan A. Bloom, Environmental extraordinary circumstances exist.
Assessment Team, Center for Drug However, late cycle requests for
Food and Drug Administration Evaluation and Research, Food and additional environmental information
Drug Administration, 10903 New have the potential to delay approval of
[Docket No. FDA–2015–D–1213] Hampshire Ave., Silver Spring, MD applications. Accordingly, this guidance
20993–0002, 301–796–2185, is intended to clarify that sponsors of
Environmental Assessment: Questions drugs with potential E, A, or T activity
and Answers Regarding Drugs With CDER.EA.Team@fda.hhs.gov.
SUPPLEMENTARY INFORMATION:
should consult with the Agency early in
Estrogenic, Androgenic, or Thyroid product development concerning the
Activity; Draft Guidance for Industry; I. Background information FDA may need to determine
Availability whether an EA will be required or
FDA is announcing the availability of
AGENCY: Food and Drug Administration, a draft guidance for industry entitled whether a claim of categorical exclusion
HHS. ‘‘Environmental Assessment: Questions will be acceptable, and what
and Answers Regarding Drugs With information should be included in the
ACTION: Notice.
Estrogenic, Androgenic, or Thyroid EA or claim of categorical exclusion.
SUMMARY: The Food and Drug Activity.’’ The National Environmental This draft guidance is being issued
Administration (FDA or Agency) is Policy Act of 1969 (Pub. L. 91–190) consistent with FDA’s good guidance
announcing the availability of a draft requires all Federal agencies to assess practices regulation (21 CFR 10.115).
guidance for industry entitled the environmental impact of their The draft guidance, when finalized, will
‘‘Environmental Assessment: Questions actions and to ensure that the interested represent the Agency’s current thinking
and Answers Regarding Drugs With and affected public is informed of the on this topic. It does not create or confer
Estrogenic, Androgenic, or Thyroid environmental analyses. FDA any rights for or on any person and does
Activity.’’ This guidance is intended to regulations at 21 CFR part 25 specify not operate to bind FDA or the public.
supplement CDER’s guidance for that EAs must be submitted as part of An alternative approach may be used if
industry on ‘‘Environmental Assessment certain NDAs, abbreviated new drug such approach satisfies the
of Human Drug and Biologics applications (ANDAs), biologic license requirements of the applicable statutes
Applications,’’ issued July 1998, by applications (BLAs), supplements to and regulations.
addressing specific considerations for such applications, and investigational
1 For example, see Section II.C (pp. 7–13) of
drugs that have potential estrogenic, new drug applications (INDs), and for
USFDA, 2013, ‘‘Response to Citizen Petition to the
androgenic, or thyroid pathway activity various other actions, unless the action FDA Commissioner under the National
(E, A, or T activity) in environmental qualifies for a categorical exclusion. Environmental Policy Act and Administrative
organisms. It is intended to help Failure to submit either an EA or a Procedure Act Requesting an Amendment to an
FDA Rule Regarding Human Drugs and Biologics,’’
mstockstill on DSK4VPTVN1PROD with NOTICES

sponsors of such drugs determine claim of categorical exclusion is
Docket No. FDA–2010–P–0377; U.S. Environmental
whether they should submit sufficient grounds for FDA to refuse to Protection Agency (USEPA), Endocrine Disruptor
environmental assessments (EA) for new file or approve an application Screening Program (EDSP), last accessed February
drug applications (NDAs) and certain (§ 25.15(a), 21 CFR 314.101(d)(4), and 17, 2015, at http://www.epa.gov/endo; and
NDA supplements, and to clarify what 601.2(a) and (c)). Organisation for Economic Co-operation and
Development (OECD), OECD Work Related to
information such sponsors should Categorical exclusions for actions Endocrine Disrupters, last accessed February 17,
include if they submit a claim of related to human drugs and biologics 2015, at http://www.oecd.org/env/ehs/testing/
categorical exclusion instead of an EA. are listed at § 25.31. This draft guidance oecdworkrelatedtoendocrinedisrupters.htm.

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Federal Register / Vol. 80, No. 82 / Wednesday, April 29, 2015 / Notices 23803

II. Comments Workshop’’ that appeared in the Federal notice. This notice solicits comments on
Interested persons may submit either Register of April 17, 2015 (80 FR information collection on financial
electronic comments regarding this 21248). The document announced a disclosure by clinical investigators.
document to http://www.regulations.gov public workshop. The document was DATES: Submit either electronic or
or written comments to the Division of published with the incorrect title. This written comments on the collection of
Dockets Management (see ADDRESSES). It document corrects that error. information by June 29, 2015.
is only necessary to send one set of FOR FURTHER INFORMATION CONTACT: ADDRESSES: Submit electronic
comments. Identify comments with the Leslie Wheelock, Office of the comments on the collection of
docket number found in brackets in the Commissioner, Food and Drug information to http://
heading of this document. Received Administration, 10903 New Hampshire www.regulations.gov. Submit written
comments may be seen in the Division Ave., Bldg. 1, Rm. 4345, Silver Spring, comments on the collection of
of Dockets Management between 9 a.m. MD, 301–796–8450, FAX: 301–847– information to the Division of Dockets
and 4 p.m., Monday through Friday, and 8106, leslie.wheelock@fda.hhs.gov. Management (HFA–305), Food and Drug
will be posted to the docket at http:// SUPPLEMENTARY INFORMATION: In the Administration, 5630 Fishers Lane, rm.
www.regulations.gov. Federal Register of April 17, 2015, in 1061, Rockville, MD 20852. All
FR Doc. 2015–08846, on page 21248 the comments should be identified with the
III. The Paperwork Reduction Act of following correction(s) is/are made: docket number found in brackets in the
1995 1. On page 21248, in the second heading of this document.
This draft guidance refers to column, starting at the sixth sentence of FOR FURTHER INFORMATION CONTACT: FDA
previously approved collections of the first paragraph, the title PRA Staff, Office of Operations, Food
information that are subject to review by ‘‘Methodological Considerations to and Drug Administration, 8455
the Office of Management and Budget Address Unmeasured Information Colesville Rd., COLE–14526, Silver
(OMB) under the Paperwork Reduction About Important Health Factors in Spring, MD 20993–0002, PRAStaff@
Act of 1995 (44 U.S.C. 3501–3520). The Pharmacoepidemiology Studies that fda.hhs.gov.
collections of information in part 25 Rely on Electronic Healthcare Databases SUPPLEMENTARY INFORMATION: Under the
have been approved under OMB control to Evaluate the Safety of Regulated PRA (44 U.S.C. 3501–3520), Federal
number 0910–0322 and the collections Pharmaceutical Products in the Agencies must obtain approval from the
of information in part 314 have been Postapproval Setting’’ is corrected to Office of Management and Budget
approved under OMB control number read ‘‘Inadequate Information on (OMB) for each collection of
0910–0001. Important Health Factors in information they conduct or sponsor.
Pharmacoepidemiology Studies Relying ‘‘Collection of information’’ is defined
IV. Electronic Access
on Healthcare Databases.’’ in 44 U.S.C. 3502(3) and 5 CFR
Persons with access to the Internet Dated: April 23, 2015. 1320.3(c) and includes Agency requests
may obtain the document at either or requirements that members of the
Peter Lurie,
http://www.fda.gov/Drugs/Guidance public submit reports, keep records, or
Associate Commissioner for Public Health
ComplianceRegulatoryInformation/ provide information to a third party.
Strategy and Analysis.
Guidances/default.htm or http:// Section 3506(c)(2)(A) of the PRA (44
[FR Doc. 2015–09966 Filed 4–28–15; 8:45 am]
www.regulations.gov. U.S.C. 3506(c)(2)(A)) requires Federal
BILLING CODE 4164–01–P
Dated: April 23, 2015. Agencies to provide a 60-day notice in
Peter Lurie, the Federal Register concerning each
Associate Commissioner for Public Health DEPARTMENT OF HEALTH AND proposed collection of information,
Strategy and Analysis. HUMAN SERVICES including each proposed extension of an
[FR Doc. 2015–09869 Filed 4–28–15; 8:45 am]
existing collection of information,
Food and Drug Administration before submitting the collection to OMB
BILLING CODE 4164–01–P
for approval. To comply with this
[Docket No. FDA–2012–N–0280] requirement, FDA is publishing notice
DEPARTMENT OF HEALTH AND of the proposed collection of
Agency Information Collection
HUMAN SERVICES information set forth in this document.
Activities; Proposed Collection; With respect to the following
Comment Request; Financial collection of information, FDA invites
Food and Drug Administration Disclosure by Clinical Investigators comments on these topics: (1) Whether
[Docket No. FDA–2015–N–0001] the proposed collection of information
AGENCY: Food and Drug Administration,
HHS. is necessary for the proper performance
Addressing Inadequate Information on
ACTION: Notice. of FDA’s functions, including whether
Important Health Factors in
the information will have practical
Pharmacoepidemiology Studies
SUMMARY: The Food and Drug utility; (2) the accuracy of FDA’s
Relying on Healthcare Databases;
Administration (FDA) is announcing an estimate of the burden of the proposed
Public Workshop; Correction
opportunity for public comment on the collection of information, including the
AGENCY: Food and Drug Administration, proposed collection of certain validity of the methodology and
HHS. information by the Agency. Under the assumptions used; (3) ways to enhance
mstockstill on DSK4VPTVN1PROD with NOTICES

ACTION: Notice; correction. Paperwork Reduction Act of 1995 (the the quality, utility, and clarity of the
PRA), Federal Agencies are required to information to be collected; and (4)
SUMMARY: The Food and Drug publish notice in the Federal Register ways to minimize the burden of the
Administration is correcting a notice concerning each proposed collection of collection of information on
entitled ‘‘Addressing Inadequate information, including each proposed respondents, including through the use
Information on Important Health Factors extension of an existing collection of of automated collection techniques,
in Pharmacoepidemiology Studies information, and to allow 60 days for when appropriate, and other forms of
Relying on Healthcare Databases; Public public comment in response to the information technology.

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Document Created: 2015-12-16 08:26:04
Document Modified: 2015-12-16 08:26:04

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		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 June 29, 2015.
Contact		Raanan A. Bloom, Environmental Assessment Team, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Silver Spring, MD 20993-0002, 301-796-2185, [email protected]
FR Citation		80 FR 23802

80 FR 23802 - Environmental Assessment: Questions and Answers Regarding Drugs With Estrogenic, Androgenic, or Thyroid Activity; Draft Guidance for Industry; Availability

DEPARTMENT OF HEALTH AND HUMAN SERVICESFood and Drug Administration

Federal Register Volume 80, Issue 82 (April 29, 2015)

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration