82 FR 5581 - Assessment of Abuse Potential of Drugs; Guidance for Industry; Availability

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Federal Register Volume 82, Issue 11 (January 18, 2017)

Page Range		5581-5583
FR Document		2017-01024

The Food and Drug Administration (FDA or Agency) is announcing the availability of a guidance for industry entitled ``Assessment of Abuse Potential of Drugs.'' This guidance is intended to assist sponsors of investigational new drugs and applicants for approval of a new drug in evaluating whether their new drug product has abuse potential. Specifically, this guidance provides recommendations for assessing the abuse potential of central nervous system (CNS)-active new drugs. Drug products with abuse potential generally contain drug substances that are active within the CNS and produce psychoactive effects such as euphoria and hallucinations. Thus, if a drug substance is CNS-active, the new drug product containing that drug substance will likely need to undergo a thorough assessment of its abuse potential and may be subject to control under the Controlled Substances Act (CSA). This guidance finalizes the draft guidance of the same name issued on January 27, 2010.

Federal Register, Volume 82 Issue 11 (Wednesday, January 18, 2017)

[Federal Register Volume 82, Number 11 (Wednesday, January 18, 2017)]
[Notices]
[Pages 5581-5583]
From the Federal Register Online [www.thefederalregister.org]
[FR Doc No: 2017-01024]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2010-D-0026]

Assessment of Abuse Potential of Drugs; 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 ``Assessment of
Abuse Potential of Drugs.'' This guidance is intended to assist
sponsors of investigational new drugs and applicants for approval of a
new drug in evaluating whether their new drug product has abuse
potential. Specifically, this guidance provides recommendations for
assessing the abuse potential of central nervous system (CNS)-active
new drugs. Drug products with abuse potential generally contain drug
substances that are active within the CNS and produce psychoactive
effects such as euphoria and hallucinations. Thus, if a drug substance
is CNS-active, the new drug product containing that drug substance will
likely need to undergo a thorough assessment of its abuse potential and
may be subject to control under the Controlled Substances Act (CSA).
This guidance finalizes the draft guidance of the same name issued on
January 27, 2010.

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

ADDRESSES: You may submit comments as follows:

Electronic Submissions

[[Page 5582]]

Submit electronic comments in the following way:
Federal eRulemaking Portal: https://www.regulations.gov.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to https://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 https://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-2010-D-0026 for ``Assessment of Abuse Potential of Drugs; Guidance
for Industry; Availability.'' Received comments will be placed in the
docket and, except for those submitted as ``Confidential Submissions,''
publicly viewable at https://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 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 https://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 https://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: Dominic Chiapperino, Controlled
Substance Staff, Center for Drug Evaluation and Research, Bldg. 51, Rm.
5148, Food and Drug Administration, 10903 New Hampshire Ave., Silver
Spring, MD 20993, 301-796-1183.

SUPPLEMENTARY INFORMATION:

I. Background

FDA is announcing the availability of a guidance for industry
entitled ``Assessment of Abuse Potential of Drugs.'' Under the Federal
Food, Drug, and Cosmetic Act, an abuse potential assessment is part of
the general evaluation of the safety and efficacy of a new drug to be
used under medical supervision. Additionally, if a new drug has abuse
potential, the Secretary of Health and Human Services (HHS) is required
under the CSA (21 U.S.C. 801 et seq.) to make a recommendation for
scheduling to the Drug Enforcement Administration (DEA). The regulatory
responsibilities for this process are described in Title 21, United
States Code (U.S.C.) 811. FDA, in consultation with the National
Institute on Drug Abuse (NIDA) conducts the medical and scientific
analysis on behalf of HHS. Specifically, the Controlled Substance Staff
of FDA performs this scientific evaluation of the abuse potential of a
drug for FDA, in consultation with NIDA, as described in a Memorandum
of Understanding (MOU) of March 8, 1985 (50 FR 9518) (available at;
http://www.fda.gov/AboutFDA/PartnershipsCollaborations/MemorandaofUnderstandingMOUs/DomesticMOUs/ucm116365.htm). When an
applicant submits a New Drug Application (NDA) for a drug with abuse
potential to FDA for review, the applicant is required to propose a CSA
schedule for the new drug (21 CFR 314.50(d)(5)(vii)). The applicant's
proposal is considered by the Agency during its evaluation of the
drug's abuse potential. FDA prepares a scientific analysis with a
recommendation for scheduling the drug under the CSA, as warranted,
based on consideration of all relevant and available data. This
recommendation is forwarded by the HHS Assistant Secretary for Health
to DEA for their consideration in the decision on final scheduling of
the drug.
Under new legislation enacted in 2015, the Improving Regulatory
Transparency for New Medical Therapies Act (Pub. L. 114-89), upon
receipt of both: (1) Notification from FDA that a marketing application
has been approved by FDA and (2) the scheduling recommendation of HHS
with respect to the subject drug in the marketing application, DEA
shall within 90 days schedule the drug by rulemaking, thus establishing
the effective date of approval for the drug product. See 21 U.S.C.
355(x); see also Public Law 114-89 (November 25, 2015). Control under
Schedules II, III, IV, or V results in schedule-specific regulatory
requirements relating to the drug's labeling, prescribing, dispensing,
advertising, manufacturing, distribution, importation/exportation,
promotion, marketing, and legitimate use in medical treatment. See
generally 21 U.S.C. 821-831 and 21 CFR 1300-1321. Scheduling of a
substance in the CSA is for the purpose of reducing abuse and
diversion.

[[Page 5583]]

This guidance provides important recommendations to sponsors,
applicants, and potential applicants in the approaches to collecting
data that should comprise the abuse potential assessment submitted in
the marketing application to FDA if one is required pursuant to Sec.
314.50(d)(5)(vii).
In the Federal Register of January 27, 2010 (75 FR 4400), FDA
issued the draft guidance for industry ``Assessment of Abuse Potential
of Drugs.'' Based on the 2010 draft guidance, and consideration of
comments received from the public, this guidance provides the Agency's
current thinking with respect to the scientific methods recommended to
assess abuse potential. The guidance also adds more detailed discussion
about key questions and decision points to consider during drug
development that will likely determine the appropriate studies for
sponsors and applicants to conduct to address the abuse potential of
their new drug, inform appropriate labeling of the product upon its
approval, and allow a thorough scientific and medical evaluation to
support scheduling decisions in accordance with the CSA. In addition,
this guidance takes into consideration other guidance issued and
legislation enacted since 2010.
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 assessment of abuse potential of drugs. 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 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 collection of information in part 314, including Sec.
314.50(d)(5)(vii), has been approved under OMB control number 0910-
0001. The collection of information in 21 CFR part 312 for
investigational drugs has been approved under OMB control number 0910-
0014. The collection of information in the guidance ``Formal Meetings
Between the FDA and Sponsors or Applicants of PDUFA Products'' has been
approved under OMB control number 0910-0429. The collection of
information in 21 CFR 201.56 and 201.57, prescription drug labeling,
has been approved under OMB control number 0910-0572. The collection of
information in 21 CFR part 58, Good Laboratory Practice for Nonclinical
Studies, has been approved under OMB control number 0910-0119.

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
https://www.regulations.gov.

Dated: January 12, 2017.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2017-01024 Filed 1-17-17; 8:45 am]
BILLING CODE 4164-01-P

Federal Register / Vol. 82, No. 11 / Wednesday, January 18, 2017 / Notices 5581

FOR FURTHER INFORMATION CONTACT: In a letter dated March 19, 2009, Endo to SYMMETREL. Additional ANDAs
Stefanie S. Kraus, Center for Drug Pharmaceuticals notified FDA that that refer to SYMMETREL (amantadine
Evaluation and Research, Food and SYMMETREL (amantadine hydrochloride), Syrup, 50 mg/5 mL,
Drug Administration, 10903 New hydrochloride), Syrup, 50 mg/5 mL, was may be approved by the Agency as long
Hampshire Ave., Bldg. 51, Rm. 6215, being discontinued and requested as they meet all other legal and
Silver Spring, MD 20993–0002, 301– withdrawal of NDA016023 for that regulatory requirements for the approval
796–9585. product. FDA moved the drug product of ANDAs. If FDA determines that
SUPPLEMENTARY INFORMATION: In 1984, to the ‘‘Discontinued Drug Product List’’ labeling for this drug product should be
Congress enacted the Drug Price section of the Orange Book and revised to meet current standards, the
Competition and Patent Term announced in the Federal Register of Agency will advise ANDA applicants to
Restoration Act of 1984 (Pub. L. 98–417) July 21, 2010 (75 FR 42455), that FDA submit such labeling.
(the 1984 amendments), which was withdrawing approval of NDA Dated: January 12, 2017.
authorized the approval of duplicate 016023, effective August 20, 2010.
Leslie Kux,
versions of drug products under an Hyman, Phelps & McNamara
submitted a citizen petition dated Associate Commissioner for Policy.
ANDA procedure. ANDA applicants [FR Doc. 2017–01064 Filed 1–17–17; 8:45 am]
must, with certain exceptions, show that August 3, 2016 (Docket No. FDA–2016–
the drug for which they are seeking P–2469), under 21 CFR 10.30, BILLING CODE 4164–01–P

approval contains the same active requesting that the Agency determine
ingredient in the same strength and whether SYMMETREL (amantadine
hydrochloride), Syrup, 50 mg/5 mL, was DEPARTMENT OF HEALTH AND
dosage form as the ‘‘listed drug,’’ which HUMAN SERVICES
is a version of the drug that was withdrawn from sale for reasons of
previously approved. ANDA applicants safety or effectiveness.
After considering the citizen petition Food and Drug Administration
do not have to repeat the extensive
and reviewing Agency records and [Docket No. FDA–2010–D–0026]
clinical testing otherwise necessary to
based on the information we have at this
gain approval of a new drug application Assessment of Abuse Potential of
time, FDA has determined under
(NDA). Drugs; Guidance for Industry;
§ 314.161 that SYMMETREL
The 1984 amendments include what Availability
(amantadine hydrochloride), Syrup, 50
is now section 505(j)(7) of the Federal
mg/5 mL, was not withdrawn for AGENCY: Food and Drug Administration,
Food, Drug, and Cosmetic Act (21 U.S.C.
reasons of safety or effectiveness. The HHS.
355(j)(7)), which requires FDA to
petitioner has identified no data or other
publish a list of all approved drugs. ACTION: Notice of availability.
information suggesting that this drug
FDA publishes this list as part of the
product was withdrawn for reasons of SUMMARY: The Food and Drug
‘‘Approved Drug Products With
safety or effectiveness. We have Administration (FDA or Agency) is
Therapeutic Equivalence Evaluations,’’
carefully reviewed our files for records announcing the availability of a
which is known generally as the
concerning the withdrawal of guidance for industry entitled
‘‘Orange Book.’’ Under FDA regulations,
SYMMETREL (amantadine ‘‘Assessment of Abuse Potential of
drugs are removed from the list if the
hydrochloride), Syrup, 50 mg/5 mL, Drugs.’’ This guidance is intended to
Agency withdraws or suspends
from sale. We have also independently assist sponsors of investigational new
approval of the drug’s NDA or ANDA
evaluated relevant literature and data drugs and applicants for approval of a
for reasons of safety or effectiveness or
for possible postmarketing adverse new drug in evaluating whether their
if FDA determines that the listed drug
events. We have reviewed the available new drug product has abuse potential.
was withdrawn from sale for reasons of
evidence and determined that this drug Specifically, this guidance provides
safety or effectiveness (21 CFR 314.162).
product was not withdrawn from sale recommendations for assessing the
A person may petition the Agency to
for reasons of safety or effectiveness.1 abuse potential of central nervous
determine, or the Agency may
Accordingly, the Agency will system (CNS)-active new drugs. Drug
determine on its own initiative, whether
continue to list SYMMETREL products with abuse potential generally
a listed drug was withdrawn from sale
(amantadine hydrochloride), Syrup, 50 contain drug substances that are active
for reasons of safety or effectiveness.
mg/5 mL, in the ‘‘Discontinued Drug within the CNS and produce
This determination may be made at any
Product List’’ section of the Orange psychoactive effects such as euphoria
time after the drug has been withdrawn
Book. The ‘‘Discontinued Drug Product and hallucinations. Thus, if a drug
from sale, but must be made prior to
List’’ delineates, among other items, substance is CNS-active, the new drug
approving an ANDA that refers to the
drug products that have been product containing that drug substance
listed drug (§ 314.161 (21 CFR 314.161)).
discontinued from marketing for reasons will likely need to undergo a thorough
FDA may not approve an ANDA that
other than safety or effectiveness. FDA assessment of its abuse potential and
does not refer to a listed drug.
will not begin procedures to withdraw may be subject to control under the
SYMMETREL (amantadine
approval of approved ANDAs that refer Controlled Substances Act (CSA). This
hydrochloride), Syrup, 50 mg/5 mL, is
the subject of NDAs 016023 and 017118, guidance finalizes the draft guidance of
1 Due to high levels of resistance to currently
held by Endo Pharmaceuticals, and the same name issued on January 27,
circulating Influenza A viruses, the Centers for
initially approved on February 14, 1968, Disease Control and Prevention currently 2010.
and July 20, 1976, respectively. recommends against using amantadine to treat DATES: Submit either electronic or
mstockstill on DSK3G9T082PROD with NOTICES

Influenza A. Given the potential for viral
SYMMETREL is indicated for the reassortment, however, amantadine may be
written comments on Agency guidances
prophylaxis and treatment of signs and effective against future Influenza A viruses. at any time.
symptoms of infection caused by Consistent with this, the current label for ADDRESSES: You may submit comments
various strains of influenza A virus. SYMMETREL (amantadine hydrochloride), Syrup,
50 mg/5 mL, was revised to caution prescribers to
as follows:
SYMMETREL is also indicated for the consider susceptibility and clinical benefit when
treatment of parkinsonism and drug- Electronic Submissions
deciding whether to use amantadine to treat
induced extrapyramidal reactions. Influenza A.

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Document Created: 2018-02-01 15:19:23
Document Modified: 2018-02-01 15:19:23

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 of availability.
Dates		Submit either electronic or written comments on Agency guidances at any time.
Contact		Dominic Chiapperino, Controlled Substance Staff, Center for Drug Evaluation and Research, Bldg. 51, Rm. 5148, Food and Drug Administration, 10903 New Hampshire Ave., Silver Spring, MD 20993, 301-796-1183.
FR Citation		82 FR 5581

82 FR 5581 - Assessment of Abuse Potential of Drugs; Guidance for Industry; Availability

DEPARTMENT OF HEALTH AND HUMAN SERVICESFood and Drug Administration

Federal Register Volume 82, Issue 11 (January 18, 2017)

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration