[Federal Register Volume 80, Number 82 (Wednesday, April 29, 2015)]
[Notices]
[Pages 23802-23803]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-09869]


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

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With Estrogenic, Androgenic, or Thyroid Activity; Draft Guidance for 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the availability of a draft guidance for industry entitled 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draft guidance before it begins work on the final version of the 
guidance, submit either electronic or written comments on the draft 
guidance by June 29, 2015.

ADDRESSES: Submit written requests for single copies of the draft 
guidance to the Division of Drug Information, Center for Drug 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section for electronic access to the draft guidance document.
    Submit electronic comments on the draft guidance to http://www.regulations.gov.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