Document ID: FDA-2015-D-1213-0004
Agency: fda
Document Type: Notice
Title: Environmental Assessment: Questions and Answers Regarding Drugs With Estrogenic, Androgenic, or Thyroid Activity; Guidance for Industry;
Availability
Posted Date: 2016-03-07T05:00Z

[Federal Register Volume 81, Number 44 (Monday, March 7, 2016)]
[Notices]
[Pages 11811-11812]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-04964]

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

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; Guidance for 
Industry; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability.

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

SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing 
the availability of a guidance for industry entitled ``Environmental 
Assessment: Questions and Answers Regarding Drugs With Estrogenic, 
Androgenic, or Thyroid Activity.'' It is intended to help sponsors of 
such drugs determine whether they should submit environmental 
assessments (EA) for drug applications and certain supplements, and to 
clarify what information such sponsors should include if they submit a 
claim of categorical exclusion instead of an EA.

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

ADDRESSES: You may submit comments as follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to http://www.regulations.gov 
will be posted to the docket unchanged. Because your comment will be 
made public, you are solely responsible for ensuring that your comment 
does not include any confidential information that you or a third party 
may not wish to be posted, such as medical information, your or anyone 
else's Social Security number, or confidential business information, 
such as a manufacturing process. Please note that if you include your 
name, contact information, or other information that identifies you in 
the body of your comments, that information will be posted on http://www.regulations.gov.
     If you want to submit a comment with confidential 
information that you do not wish to be made available to the public, 
submit the comment as a written/paper submission and in the manner 
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand delivery/Courier (for written/paper 
submissions): Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Division of 
Dockets Management, FDA will post your comment, as well as any 
attachments, except for information submitted, marked and identified, 
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No. 
FDA-2015-D-1213 for Environmental Assessment: Questions and Answers 
Regarding Drugs with Estrogenic, Androgenic, or Thyroid Activity. 
Received comments will be placed in the docket and, except for those 
submitted as ``Confidential Submissions,'' publicly viewable at http://www.regulations.gov or at the Division of Dockets Management between 9 
a.m. and 4 p.m., Monday through Friday.
     Confidential Submissions--To submit a comment with 
confidential information that you do not wish to be made publicly 
available, submit your

[[Page 11812]]

comments only as a written/paper submission. You should submit two 
copies total. One copy will include the information you claim to be 
confidential with a heading or cover note that states ``THIS DOCUMENT 
CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will review this copy, 
including the claimed confidential information, in its consideration of 
comments. The second copy, which will have the claimed confidential 
information redacted/blacked out, will be available for public viewing 
and posted on http://www.regulations.gov. Submit both copies to the 
Division of Dockets Management. If you do not wish your name and 
contact information to be made publicly available, you can provide this 
information on the cover sheet and not in the body of your comments and 
you must identify this information as ``confidential.'' Any information 
marked as ``confidential'' will not be disclosed except in accordance 
with 21 CFR 10.20 and other applicable disclosure law. For more 
information about FDA's posting of comments to public dockets, see 80 
FR 56469, September 18, 2015, or access the information at: http://www.fda.gov/regulatoryinformation/dockets/default.htm.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to http://www.regulations.gov and insert the docket number, found in brackets in 
the heading of this document, into the ``Search'' box and follow the 
prompts and/or go to the Division of Dockets Management, 5630 Fishers 
Lane, Rm. 1061, Rockville, MD 20852.
    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.

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, CDER.EA.Team@fda.hhs.gov.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a guidance for industry 
entitled ``Environmental Assessment: Questions and Answers Regarding 
Drugs with Estrogenic, Androgenic, or Thyroid Activity.'' This guidance 
finalizes the draft of the same name that published on April 29, 2015. 
The National Environmental Policy Act of 1969 (NEPA) 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 new drug applications 
(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 
(21 CFR 25.15(a), 314.101(d)(4) and 601.2(a) and (c)).
    Categorical exclusions for actions related to human drugs and 
biologics are listed at 21 CFR 25.31. This 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) (21 CFR 
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 (21 CFR 25.21). Research indicates 
that drugs with endocrine-related activity and, more specifically, 
drugs with Estrogenic, Androgenic, or Thyroid Activity (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 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 Environmental Assessment: Questions and 
Answers Regarding Drugs With Estrogenic, Androgenic, or Thyroid 
Activity. 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. The Paperwork Reduction Act of 1995

    This 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 21 CFR part 25 have been 
approved under OMB control number 0910-0322 and the collections of 
information in 21 CFR part 314 have been approved under OMB control 
number 0910-0001.

III. Electronic Access

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

    Dated: March 1, 2016.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2016-04964 Filed 3-4-16; 8:45 am]
BILLING CODE 4164-01-P