80 FR 54295 - Nonclinical Evaluation of Endocrine-Related Drug Toxicity; Guidance for Industry; Availability

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Federal Register Volume 80, Issue 174 (September 9, 2015)

Page Range		54295-54296
FR Document		2015-22683

The Food and Drug Administration (FDA or Agency) is announcing the availability of a guidance for industry entitled ``Nonclinical Evaluation of Endocrine-Related Drug Toxicity.'' The purpose of this guidance is to clarify when additional studies are warranted after the standard toxicology tests have been conducted and there is a signal for potential adverse endocrine-related toxicity. This guidance finalizes the draft guidance entitled ``Endocrine Disruption Potential of Drugs: Nonclinical Evaluation'' issued on September 20, 2013.

Federal Register, Volume 80 Issue 174 (Wednesday, September 9, 2015)

[Federal Register Volume 80, Number 174 (Wednesday, September 9, 2015)]
[Notices]
[Pages 54295-54296]
From the Federal Register Online [www.thefederalregister.org]
[FR Doc No: 2015-22683]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2013-D-1039]

Nonclinical Evaluation of Endocrine-Related Drug Toxicity;
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 ``Nonclinical
Evaluation of Endocrine-Related Drug Toxicity.'' The purpose of this
guidance is to clarify when additional studies are warranted after the
standard toxicology tests have been conducted and there is a signal for
potential adverse endocrine-related toxicity. This guidance finalizes
the draft guidance entitled ``Endocrine Disruption Potential of Drugs:
Nonclinical Evaluation'' issued on September 20, 2013.

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: Abby Jacobs, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg., 22, Rm. 6474, Silver Spring, MD 20993-0002, 301-
796-0174.

SUPPLEMENTARY INFORMATION:

I. Background

FDA is announcing the availability of a guidance for industry
entitled ``Nonclinical Evaluation of Endocrine-Related Drug Toxicity.''
This guidance focuses on nonclinical testing designed to assess the
potential for a drug to cause endocrine effects that are

[[Page 54296]]

unintentional and adverse. The standard comprehensive test battery is
generally sufficient to identify endocrine-related toxicity. Depending
on the outcome of a standard battery of nonclinical tests, additional
nonclinical studies may be warranted to more fully characterize the
endocrine-related toxicity potential of a drug.
This guidance finalizes the draft guidance entitled ``Endocrine
Disruption Potential of Drugs: Nonclinical Evaluation'' issued on
September 20, 2013 (78 FR 57859). Revisions to the draft guidance
address public comments and try to give more clarity regarding when
additional studies could be appropriate.
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 nonclinical evaluation of endocrine-related
drug toxicity. 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 parts 312 and 314 have
been approved under OMB control numbers 0910-0014 and 0910-0001,
respectively.

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.

Dated: September 3, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-22683 Filed 9-8-15; 8:45 am]
BILLING CODE 4164-01-P

Federal Register / Vol. 80, No. 174 / Wednesday, September 9, 2015 / Notices 54295

The 1984 amendments include what that GLUCAGON (glucagon DEPARTMENT OF HEALTH AND
is now section 505(j)(7) of the Federal hydrochloride) for injection, EQ 1 mg HUMAN SERVICES
Food, Drug, and Cosmetic Act (21 U.S.C. base/vial and EQ 10 mg base/vial, was
355(j)(7)), which requires FDA to not withdrawn for reasons of safety or Food and Drug Administration
publish a list of all approved drugs. effectiveness. The petitioner has [Docket No. FDA–2013–D–1039]
FDA publishes this list as part of the identified no data or other information
‘‘Approved Drug Products With suggesting that GLUCAGON (glucagon Nonclinical Evaluation of Endocrine-
Therapeutic Equivalence Evaluations,’’ hydrochloride) for injection, EQ 1 mg Related Drug Toxicity; Guidance for
which is known generally as the base/vial and EQ 10 mg base/vial, was Industry; Availability
‘‘Orange Book.’’ Under FDA regulations,
withdrawn for reasons of safety or AGENCY: Food and Drug Administration,
drugs are removed from the list if the
effectiveness. We have carefully HHS.
Agency withdraws or suspends
approval of the drug’s NDA or ANDA reviewed our files for records
ACTION: Notice.
for reasons of safety or effectiveness or concerning the withdrawal from sale of
if FDA determines that the listed drug GLUCAGON (glucagon hydrochloride) SUMMARY: The Food and Drug
was withdrawn from sale for reasons of for injection, EQ 1 mg base/vial and EQ Administration (FDA or Agency) is
safety or effectiveness (21 CFR 314.162). 10 mg base/vial. We have also announcing the availability of a
A person may petition the Agency to independently evaluated relevant guidance for industry entitled
determine, or the Agency may literature and data for possible ‘‘Nonclinical Evaluation of Endocrine-
determine on its own initiative, whether postmarketing adverse events. We have Related Drug Toxicity.’’ The purpose of
a listed drug was withdrawn from sale reviewed the available evidence and this guidance is to clarify when
for reasons of safety or effectiveness. determined that the product was not additional studies are warranted after
This determination may be made at any withdrawn from sale for reasons of the standard toxicology tests have been
time after the drug has been withdrawn safety or effectiveness. conducted and there is a signal for
from sale, but must be made prior to potential adverse endocrine-related
Accordingly, the Agency will toxicity. This guidance finalizes the
approving an ANDA that refers to the
listed drug (§ 314.161 (21 CFR 314.161)). continue to list GLUCAGON (glucagon draft guidance entitled ‘‘Endocrine
FDA may not approve an ANDA that hydrochloride) for injection, EQ 1 mg Disruption Potential of Drugs:
does not refer to a listed drug. base/vial and EQ 10 mg base/vial, in the Nonclinical Evaluation’’ issued on
GLUCAGON (glucagon ‘‘Discontinued Drug Product List’’ September 20, 2013.
hydrochloride) for injection, EQ 1 mg section of the Orange Book. The DATES: Submit either electronic or
base/vial and EQ 10 mg base/vial, is the ‘‘Discontinued Drug Product List’’ written comments on Agency guidances
subject of NDA 12–122 held by Eli Lilly, delineates, among other items, drug at any time.
and initially approved onNovember 14, products that have been discontinued ADDRESSES: Submit written requests for
1960. GLUCAGON is indicated for from marketing for reasons other than single copies of this guidance to the
treatment of severe hypoglycemia and as safety or effectiveness. ANDAs that refer Division of Drug Information, Center for
a diagnostic aid in the radiologic to GLUCAGON (glucagon Drug Evaluation and Research, Food
examination of the stomach, duodenum, hydrochloride) for injection, EQ 1 mg and Drug Administration, 10001 New
small bowel, and colon. base/vial and EQ 10 mg base/vial, may
Under NDA 12–122, GLUCAGON Hampshire Ave., Hillandale Building,
be approved by the Agency as long as 4th Floor, Silver Spring, MD 20993–
(glucagon hydrochloride) for injection, they meet all other legal and regulatory
EQ 1 mg base/vial and EQ 10 mg base/ 0002. Send one self-addressed adhesive
requirements for the approval of label to assist that office in processing
vial, was produced from animal sources.
ANDAs. However, it is the Agency’s your requests. See the SUPPLEMENTARY
On September 11, 1998, FDA approved
Eli Lilly’s NDA 20–928 for GLUCAGON view that it would be challenging for a INFORMATION section for electronic
(glucagon rDNA origin), 1mg/vial. prospective applicant to provide access to the guidance document.
Subsequently, Eli Lilly discontinued adequate data to meet the statutory Submit electronic comments on the
sales of animal-sourced GLUCAGON in requirements for an ANDA that relies on guidance to http://www.regulations.gov.
2002. In 2005, FDA moved animal- NDA 12–122 for GLUCAGON (glucagon Submit written comments to the
sourced GLUCAGON (glucagon hydrochloride) for injection in the Division of Dockets Management (HFA–
hydrochloride) for injection, EQ 1 mg absence of comparative data with the 305), Food and Drug Administration,
base/vial and EQ 10 mg base/vial, to the animal-sourced glucagon approved in 5630 Fishers Lane, Rm. 1061, Rockville,
‘‘Discontinued Drug Product List’’ NDA 12–122. MD 20852.
section of the Orange Book. FOR FURTHER INFORMATION CONTACT:
Dated: September 2, 2015.
Walter G. Jump, on behalf of Abby Jacobs, Center for Drug Evaluation
Leslie Kux, and Research, Food and Drug
Cornerstone Regulatory, submitted a
citizen petition dated August 7, 2007 Associate Commissioner for Policy. Administration, 10903 New Hampshire
(Docket No. FDA–2007–P–0248), under [FR Doc. 2015–22673 Filed 9–8–15; 8:45 am] Ave., Bldg., 22, Rm. 6474, Silver Spring,
21 CFR 10.30, requesting that the BILLING CODE 4164–01–P MD 20993–0002, 301–796–0174.
Agency determine whether animal- SUPPLEMENTARY INFORMATION:
sourced GLUCAGON (glucagon
I. Background
hydrochloride) for injection, EQ 1 mg
Lhorne on DSK5TPTVN1PROD with NOTICES

base/vial and EQ 10 mg base/vial, was FDA is announcing the availability of
withdrawn from sale for reasons of a guidance for industry entitled
safety or effectiveness. ‘‘Nonclinical Evaluation of Endocrine-
After considering the citizen petition, Related Drug Toxicity.’’ This guidance
reviewing Agency records, and based on focuses on nonclinical testing designed
the information we have at this time, to assess the potential for a drug to
FDA has determined under § 314.161 cause endocrine effects that are

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54296 Federal Register / Vol. 80, No. 174 / Wednesday, September 9, 2015 / Notices

unintentional and adverse. The standard Dated: September 3, 2015. to assist that office in processing your
comprehensive test battery is generally Leslie Kux, requests. See the SUPPLEMENTARY
sufficient to identify endocrine-related Associate Commissioner for Policy. INFORMATION section for electronic
toxicity. Depending on the outcome of [FR Doc. 2015–22683 Filed 9–8–15; 8:45 am] access to the draft guidance document.
a standard battery of nonclinical tests, BILLING CODE 4164–01–P
Submit electronic comments on the
additional nonclinical studies may be revised draft guidance to http://
warranted to more fully characterize the www.regulations.gov. Submit written
endocrine-related toxicity potential of a DEPARTMENT OF HEALTH AND comments to the Division of Dockets
drug. HUMAN SERVICES Management (HFA–305), Food and Drug
This guidance finalizes the draft Administration, 5630 Fishers Lane, Rm.
guidance entitled ‘‘Endocrine Food and Drug Administration 1061, Rockville, MD 20852.
Disruption Potential of Drugs: [Docket No. FDA–2013–D–0221] FOR FURTHER INFORMATION CONTACT:
Nonclinical Evaluation’’ issued on Khushboo Sharma, Center for Drug
September 20, 2013 (78 FR 57859). Formal Dispute Resolution: Appeals Evaluation and Research, Food and
Revisions to the draft guidance address Above the Division Level; Revised Drug Administration, 10903 New
public comments and try to give more Draft Guidance for Industry and Hampshire Ave., Bldg. 22, Rm. 6468,
clarity regarding when additional Review Staff; Availability Silver Spring, MD 20993–0002, 301–
studies could be appropriate. 796–0700; or Stephen Ripley, Center for
AGENCY: Food and Drug Administration, Biologics Evaluation and Research,
This guidance is being issued HHS.
consistent with FDA’s good guidance Food and Drug Administration, 10903
ACTION: Notice. New Hampshire Ave., Bldg. 71, Rm.
practices regulation (21 CFR 10.115).
The guidance represents the current SUMMARY: The Food and Drug 7301, Silver Spring, MD 20993–0002,
thinking of FDA on nonclinical Administration (FDA or Agency) is 240–402–7911.
evaluation of endocrine-related drug announcing the availability of a revised SUPPLEMENTARY INFORMATION:
toxicity. It does not establish any rights draft guidance for industry and review I. Background
for any person and is not binding on staff entitled ‘‘Formal Dispute
FDA or the public. You can use an Resolution: Appeals Above the Division FDA is announcing the availability of
alternative approach if it satisfies the Level.’’ This guidance is intended to a revised draft guidance for industry
requirements of the applicable statutes provide recommendations for industry and review staff entitled ‘‘Formal
and regulations. and review staff on the procedures in Dispute Resolution: Appeals Above the
the Center for Drug Evaluation and Division Level.’’ In the course of the
II. The Paperwork Reduction Act of Research (CDER) and Center for review of applications for user fee
1995 Biologics Evaluation and Research products, a wide variety of scientific
(CBER) for resolving scientific and/or and/or medical issues are discussed that
This guidance refers to previously are critical to a sponsor’s drug product
approved collections of information that medical disputes that cannot be
resolved at the division level. This development program. Sometimes, a
are subject to review by the Office of sponsor may disagree with the Agency
Management and Budget (OMB) under guidance describes procedures for
formally appealing such disputes to the on a matter, and a dispute arises.
the Paperwork Reduction Act of 1995 Because these disputes often involve
(44 U.S.C. 3501–3520). The collections office or center level and providing
information to assist FDA officials in complex scientific and/or medical
of information in 21 CFR parts 312 and matters, it is critical that there be
314 have been approved under OMB resolving the issue(s) presented. This
draft guidance revises the draft guidance procedures in place to help ensure
control numbers 0910–0014 and 0910– open, prompt discussion of such
0001, respectively. of the same name issued March 13,
2013. disputes. The procedures and policies
III. Comments described in this guidance are intended
DATES: Although you can comment on to promote rapid resolution of scientific
Interested persons may submit either any guidance at any time (see 21 CFR and/or medical disputes between
electronic comments regarding this 10.115(g)(5)), to ensure that the Agency sponsors and CDER or CBER.
document to http://www.regulations.gov considers your comment on this revised This draft guidance revises the draft
or written comments to the Division of draft guidance before it begins work on guidance of the same name issued
Dockets Management (see ADDRESSES). It the final version of the guidance, submit March 13, 2013 (78 FR 15955). Based on
is only necessary to send one set of either electronic or written comments the docket comments for the draft
comments. Identify comments with the on the draft guidance by December 8, guidance as well as on its own
docket number found in brackets in the 2015. initiative, FDA made the following
heading of this document. Received ADDRESSES: Submit written requests for changes. The scope of the guidance was
comments may be seen in the Division single copies of the draft guidance to the expanded to include formal dispute
of Dockets Management between 9 a.m. Division of Drug Information, Center for resolution requests for human drug
and 4 p.m., Monday through Friday, and Drug Evaluation and Research, Food applications covered under the
will be posted to the docket at http:// and Drug Administration, 10001 New Biosimilar User Fee Act of 2012.
www.regulations.gov. Hampshire Ave., Hillandale Building, Additionally, certain areas were revised
IV. Electronic Access 4th Floor, Silver Spring, MD 20993– to provide more clarity, such as when a
Lhorne on DSK5TPTVN1PROD with NOTICES

0002, or Office of Communication, matter is and is not appropriate for a
Persons with access to the Internet Outreach, and Development, Center for formal dispute resolution request, and
may obtain the document at either Biologics Evaluation and Research, information to include in the supporting
http://www.fda.gov/Drugs/Guidance Food and Drug Administration, 10903 background information. Also, this
ComplianceRegulatoryInformation/ New Hampshire Ave., Bldg. 71, Rm. guidance clarifies that CDER and CBER
Guidances/default.htm or http:// 3128, Silver Spring, MD 20993–0002. intend to manage formal requests for
www.regulations.gov. Send one self-addressed adhesive label appeals of scientific and/or medical

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Document Created: 2015-12-15 09:53:05
Document Modified: 2015-12-15 09:53:05

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		Abby Jacobs, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg., 22, Rm. 6474, Silver Spring, MD 20993-0002, 301- 796-0174.
FR Citation		80 FR 54295

80 FR 54295 - Nonclinical Evaluation of Endocrine-Related Drug Toxicity; Guidance for Industry; Availability

DEPARTMENT OF HEALTH AND HUMAN SERVICESFood and Drug Administration

Federal Register Volume 80, Issue 174 (September 9, 2015)

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration