General Principles for Evaluating the Abuse Deterrence of Generic Solid Oral Opioid Drug Products; Guidance for Industry; Availability, 55617-55619 [2017-25248]
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Federal Register / Vol. 82, No. 224 / Wednesday, November 22, 2017 / Notices
label, labeling, and advertising
accompanying the application. The
determination of whether an order is
appropriate under section 911(g) of the
FD&C Act is based on the scientific
information submitted by the applicant
as well as the scientific evidence and
other information that is made available
to the Agency, including through public
comments.
II. Electronic Access
Persons with access to the Internet
may access the application documents
at: https://www.fda.gov/
TobaccoProducts/Labeling/
MarketingandAdvertising/
ucm546281.htm.
Dated: November 16, 2017.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2017–25224 Filed 11–21–17; 8:45 am]
BILLING CODE 4164–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2016–D–0785]
General Principles for Evaluating the
Abuse Deterrence of Generic Solid
Oral Opioid Drug Products; Guidance
for Industry; Availability
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice of availability.
The Food and Drug
Administration (FDA or Agency) is
announcing the availability of a
guidance for industry entitled ‘‘General
Principles for Evaluating the Abuse
Deterrence of Generic Solid Oral Opioid
Drug Products.’’ This guidance is
intended to assist a person who plans to
develop and submit an abbreviated new
drug application (ANDA) to seek
approval of a generic version of a solid
oral opioid drug product that references
an opioid drug product with abusedeterrent properties described in its
labeling. The guidance recommends
studies, including comparative in vitro
and pharmacokinetic (PK) studies, that
a potential ANDA applicant should
conduct and submit to FDA to
demonstrate that a generic solid oral
opioid drug product is no less abuse
deterrent than its reference listed drug
(RLD) with respect to all potential
routes of abuse.
DATES: Submit either electronic or
written comments on Agency guidances
at any time.
asabaliauskas on DSKBBXCHB2PROD with NOTICES
SUMMARY:
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ADDRESSES:
You may submit comments
as follows:
Electronic Submissions
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): Dockets
Management Staff (HFA–305), Food and
Drug Administration, 5630 Fishers
Lane, Rm. 1061, Rockville, MD 20852.
• For written/paper comments
submitted to the Dockets Management
Staff, 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–
2016–D–0785 for ‘‘General Principles
for Evaluating the Abuse Deterrence of
Generic Solid Oral Opioid 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
Dockets Management Staff 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
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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 Dockets Management
Staff. 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: https://www.gpo.gov/
fdsys/pkg/FR-2015-09-18/pdf/201523389.pdf.
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 Dockets Management
Staff, 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: Gail
Schmerfeld, Office of Generic Drugs,
Center for Drug Evaluation and
Research, Food and Drug
Administration, 10903 New Hampshire
Ave., Silver Spring, MD 20993–0002,
301–796–9291, email: gail.schmerfeld@
fda.hhs.gov.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of
a guidance for industry entitled
‘‘General Principles for Evaluating the
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Federal Register / Vol. 82, No. 224 / Wednesday, November 22, 2017 / Notices
Abuse Deterrence of Generic Solid Oral
Opioid Drug Products.’’ Prescription
opioid analgesics are an important
component of modern pain
management. However, abuse and
misuse of these drug products have
created a serious and widespread public
health problem. Addressing this public
health crisis is an FDA priority. One
potentially important step toward the
goal of creating safer opioid analgesics
has been the development of opioid
drug products that are formulated to
deter abuse. ‘‘Abuse-deterrent
properties,’’ as that term is used in the
guidance to which this notice applies
are those properties shown to
meaningfully deter abuse; abusedeterrent properties do not fully prevent
abuse or addiction. FDA considers the
development of these products a high
public health priority. It is important
that less costly generic versions of
opioids that reference listed drugs
whose labeling describes abusedeterrent properties are available to
ensure access to safe and effective
analgesics for patients who need them.
If the summary in section 9.2 of the
approved labeling for the RLD indicates
that FDA has concluded that the RLD
has properties that are expected to (or
have been shown through postmarketing
studies to) deter abuse, the potential
ANDA applicant should evaluate its
proposed generic drug to show that it is
no less abuse deterrent than the RLD
with respect to all of the potential routes
of abuse. This will ensure the generic
drug is no less abuse-deterrent than the
RLD with respect to all potential routes
of abuse and minimize the risk of
shifting abuse to other, potentially more
dangerous routes. This guidance
describes FDA’s current thinking on the
studies that should be conducted by a
potential ANDA applicant and
submitted to FDA in an ANDA to
demonstrate that a generic solid oral
opioid drug product is no less abuse
deterrent than its RLD with respect to
all potential routes of abuse. These
studies are in addition to other studies
that may be needed to support ANDA
approval (e.g., as described in productspecific guidances).
The final guidance, like the draft
guidance, focuses on the general
principles for developing and evaluating
the abuse deterrence of generic solid
oral opioid drug products formulated to
incorporate physical or chemical
barriers, agonist/antagonist
combinations, aversive agents, or a
combination of two or more of these
technologies. FDA will continue to
assess the state of science and, as novel
technologies develop, will address them
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by issuing additional guidance, as
appropriate.
In the Federal Register of March 25,
2016, FDA announced the availability of
the draft guidance for industry ‘‘General
Principles for Evaluating the Abuse
Deterrence of Generic Solid Oral Opioid
Drug Products’’ (81 FR 16186). FDA
subsequently announced in the Federal
Register of October 6, 2016, and held on
October 31–November 1, 2016, a public
meeting to discuss scientific and
technical issues relating to formulation
development and premarket evaluation
of opioid drug products with abusedeterrent properties (81 FR 69532). This
final guidance reflects our consideration
of comments made in the dockets for the
draft guidance (Docket No. FDA–2016–
D–0785) and for the public meeting
(Docket No. FDA–2016–N–2896) and
comments made during the public
meeting, and provides the Agency’s
current thinking with respect to the
general principles for evaluating the
abuse deterrence of generic solid oral
opioid drug products.
Among other changes, the final
guidance eliminates the
recommendation to use a control to
identify discriminatory study conditions
for comparing the proposed generic
opioid drug product (the test (T)
product) and the RLD (reference (R)
product). Instead, FDA recommends
that a potential ANDA applicant
conduct extraction studies to assess the
particular vulnerabilities of T and R
products to inform the comparison of
their abuse deterrence. The final
guidance also provides more detailed
recommendations regarding the conduct
of in vivo studies, specifically
comparative PK studies of manipulated
T and R products to evaluate the
potential for abuse by the oral and nasal
routes of administration.
Appendix 1 of the final guidance
continues to describe some of the ways
in which the T and R products can be
physically manipulated and provides
recommendations for conducting
extraction studies to assess the
particular vulnerabilities of the T and R
products to inform the comparison of
their abuse deterrence. FDA continues
to recommend potential ANDA
applicants follow a tier-based approach
to extractability testing to efficiently
compare a T product to its R product
and limit the number of tests required
for evaluating the abuse deterrence of
the T product, but has modified some of
the initial recommendations regarding
solvents.
Appendix 2 provides
recommendations for evaluating abuse
by ingestion. In the final guidance, FDA
clarifies the circumstances under which
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a potential applicant should conduct a
comparative oral PK study. Appendices
3, 4, and 5 provide modified
recommendations for evaluating abuse
by injection, insufflation, and smoking,
respectively.
The guidance addresses the general
principles for evaluating abuse
deterrence in generic solid oral opioid
drug products. FDA may provide
additional testing recommendations in
future product-specific guidances. For
example, FDA may recommend in a
product-specific guidance that a
potential ANDA applicant evaluate
human abuse potential (for example,
evaluate a study subject’s willingness to
take drug again) if R product contains a
known aversive agent. Further, FDA
will continue to assess the state of the
science and, as novel technologies
develop, will address them by issuing
revised or additional guidance, as
appropriate.
Potential ANDA applicants may pose
questions regarding evaluation of abuse
deterrence for a generic solid oral opioid
drug product through FDA’s pre-ANDA
program. The goals of the pre-ANDA
program are to clarify regulatory
expectations for prospective applicants
early in the development process, assist
applicants in developing more complete
submissions, promote a more efficient
and effective ANDA review process, and
reduce the number of review cycles
required to obtain ANDA approval,
particularly for complex products. FDA
considers abuse-deterrent opioids to be
products that fall within the definition
of complex product as that term has
been defined in the GDUFA
Reauthorization Performance Goals and
Program Enhancements Fiscal Years
2018–2022, which can be found at
https://www.fda.gov/downloads/
ForIndustry/UserFees/GenericDrugUser
Fees/UCM525234.pdf. The pre-ANDA
program provides for, among other
things, submission of controlled
correspondence and requests for formal
meetings between FDA and applicants
on complex generic drug development
issues.
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 ‘‘General Principles
for Evaluating the Abuse Deterrence of
Generic Solid Oral Opioid Drug
Products.’’ 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. This guidance is not
subject to Executive Order 12866.
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Federal Register / Vol. 82, No. 224 / Wednesday, November 22, 2017 / Notices
WhiteOakCampusInformation/
ucm241740.htm.
II. Electronic Access
Persons with access to the internet
may obtain the guidance at either
https://www.fda.gov/Drugs/Guidance
ComplianceRegulatoryInformation/
Guidances/default.htm or https://
www.regulations.gov.
FOR FURTHER INFORMATION CONTACT:
Lieutenant Commander Jamila Mwidau,
Food and Drug Administration, Center
for Drug Evaluation and Research,
10903 New Hampshire Ave., Bldg. 22,
Rm. 4481, Silver Spring, MD 20993;
301–796–4989, Jamila.Mwidau@
fda.hhs.gov.
SUPPLEMENTARY INFORMATION:
Dated: November 16, 2017.
Anna K. Abram,
Deputy Commissioner for Policy, Planning,
Legislation, and Analysis.
[FR Doc. 2017–25248 Filed 11–21–17; 8:45 am]
BILLING CODE 4164–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2017–N–6230]
Tenth Annual Sentinel Initiative; Public
Workshop
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice of public workshop.
The Food and Drug
Administration (FDA) is announcing a
public workshop entitled ‘‘Tenth
Annual Sentinel Initiative Public
Workshop.’’ The purpose of this 2-day
public workshop is to bring the
stakeholder community together to
discuss a variety of topics on active
medical product surveillance. Attendees
will leave with a deeper understanding
of how to use the Sentinel System tools
to address safety questions.
DATES: The public workshop will be
held on February 7 and 8, 2018. Day 1
of the public workshop will be held on
February 7, 2018, from 9 a.m. to 4:30
p.m. Day 2 of the public workshop will
be held on February 8, 2018, from 9 a.m.
to 2 p.m. See the SUPPLEMENTARY
INFORMATION section for registration date
and information.
ADDRESSES: The public workshop will
be held at two separate locations. On
Day 1 the public workshop will be held
at the Hyatt Regency Bethesda, 1
Bethesda Metro Center, Bethesda, MD
20814. On Day 2 the public workshop
will be held at the FDA White Oak
Campus, 10903 New Hampshire Ave.,
Bldg. 31, Rm. 1503 (the Great Room),
Silver Spring, MD 20993–0002.
Entrance for the public workshop
participants (non-FDA employees) is
through Building 1 where routine
security check procedures will be
performed. For parking and security
information, please refer to https://
www.fda.gov/AboutFDA/
WorkingatFDA/BuildingsandFacilities/
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SUMMARY:
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I. Background
The purpose of this 2-day public
workshop is to bring the stakeholder
community together to discuss a variety
of topics on active medical product
surveillance. Day 1 will be convened by
the Duke-Margolis Center for Health
Policy at Duke University with support
by a cooperative agreement with FDA.
Key discussion topics will include an
update on the state of FDA’s Sentinel
Initiative, key safety surveillance
activities, and emerging uses of the
Sentinel System. In addition, panelists,
representing diverse stakeholder
perspectives, will provide comments on
Sentinel and opportunities to expand its
analytic capabilities. This workshop
will also provide an opportunity for
stakeholder engagement and input on
Sentinel’s continued modernization.
Day 2 will be a public workshop
sponsored by FDA targeting researchers
who are experienced in using claims
data and will build upon prior public
training conducted by FDA on July 10,
2017 (82 FR 19063, April 25, 2017). This
second day of the workshop will
address more advanced training topics,
including Sentinel’s inferential analytic
capabilities and methods of identifying
unexpected safety concerns. Attendees
will leave with a deeper understanding
of how to use the Sentinel System tools
to address safety questions. Attendees
are encouraged to review the material
FDA presented on July 10, 2017, by
visiting the Web site: https://
www.sentinelinitiative.org/
communications/sentinel-initiativeevents/public-sentinel-training-fda.
II. Participating in the Public Workshop
Registration: To attend the public
workshop, you may register for one or
both days, but you must register for each
day of the workshop separately. The
Duke-Margolis Center for Health Policy
at Duke University will manage
registration for Day 1 and FDA will
manage registration for Day 2.
Day 1: To attend the public workshop
on Day 1, you must register before
February 6, 2018, by visiting https://
healthpolicy.duke.edu/events/10thannual-sentinel-public-workshop. You
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may also register for the live webcast by
visiting this Web page. There will be no
onsite registration.
When registering, please provide the
following information: Your name, title,
company or organization (if applicable),
postal address, telephone number, and
email address. There is no registration
fee. However, registration will be on a
first-come, first-served basis because
seating is limited. A 1-hour lunch break
is scheduled, but food will not be
provided. There are multiple restaurants
within walking distance of Hyatt
Regency Bethesda. If you need special
accommodations due to a disability,
please contact Elizabeth Murphy at the
Duke-Margolis Center for Health Policy
(202–621–2801, email:
elizabeth.g.murphy@duke.edu) no later
than February 6, 2018.
Streaming Webcast for Day 1: The
workshop will be webcast (archived
video footage will be available following
the workshop at https://
healthpolicy.duke.edu/events/10thannual-sentinel-public-workshop).
Persons interested in viewing the live
webcast must register online before
February 6, 2018. Early registration is
recommended because webcast
connections are limited. Webcast
participants will be sent technical
system requirements in advance of the
event. Prior to joining the streaming
webcast of the public workshop, it is
recommended that you review these
technical system requirements.
All Day 1 event materials will be
available to registered attendees via
email before the workshop at the DukeMargolis Web site at https://
healthpolicy.duke.edu/events/10thannual-sentinel-public-workshop.
Day 2: To register to attend Day 2 of
the workshop in person or virtually via
webcast, you must register before
February 6, 2018, by visiting: https://
www.eventbrite.com/e/february-8-2018training-at-fda-tickets-37914164286.
Please provide complete contact
information for each attendee, including
name, title, affiliation, telephone
number, and email address. Registration
is free and based on space availability,
with priority given to early registrants.
Early registration is recommended
because seating is limited; therefore,
FDA may limit the number of
participants from each organization. If
time and space permit, onsite
registration will be provided beginning
at 8 a.m.
If you need special accommodations
due to a disability, please contact
Lieutenant Commander Jamila Mwidau
no later than January 24, 2018.
Streaming Webcast of the Public
Workshop Day 2: The FDA training
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]]>Agencies
[Federal Register Volume 82, Number 224 (Wednesday, November 22, 2017)]
[Notices]
[Pages 55617-55619]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2017-25248]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2016-D-0785]
General Principles for Evaluating the Abuse Deterrence of Generic
Solid Oral Opioid Drug Products; 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 ``General
Principles for Evaluating the Abuse Deterrence of Generic Solid Oral
Opioid Drug Products.'' This guidance is intended to assist a person
who plans to develop and submit an abbreviated new drug application
(ANDA) to seek approval of a generic version of a solid oral opioid
drug product that references an opioid drug product with abuse-
deterrent properties described in its labeling. The guidance recommends
studies, including comparative in vitro and pharmacokinetic (PK)
studies, that a potential ANDA applicant should conduct and submit to
FDA to demonstrate that a generic solid oral opioid drug product is no
less abuse deterrent than its reference listed drug (RLD) with respect
to all potential routes of abuse.
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: 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): Dockets Management Staff (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
For written/paper comments submitted to the Dockets
Management Staff, 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-2016-D-0785 for ``General Principles for Evaluating the Abuse
Deterrence of Generic Solid Oral Opioid 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 Dockets Management
Staff 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 Dockets Management Staff. 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: https://www.gpo.gov/fdsys/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
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 Dockets Management Staff, 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: Gail Schmerfeld, Office of Generic
Drugs, Center for Drug Evaluation and Research, Food and Drug
Administration, 10903 New Hampshire Ave., Silver Spring, MD 20993-0002,
301-796-9291, email: gail.schmerfeld@fda.hhs.gov.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of a guidance for industry
entitled ``General Principles for Evaluating the
[[Page 55618]]
Abuse Deterrence of Generic Solid Oral Opioid Drug Products.''
Prescription opioid analgesics are an important component of modern
pain management. However, abuse and misuse of these drug products have
created a serious and widespread public health problem. Addressing this
public health crisis is an FDA priority. One potentially important step
toward the goal of creating safer opioid analgesics has been the
development of opioid drug products that are formulated to deter abuse.
``Abuse-deterrent properties,'' as that term is used in the guidance to
which this notice applies are those properties shown to meaningfully
deter abuse; abuse-deterrent properties do not fully prevent abuse or
addiction. FDA considers the development of these products a high
public health priority. It is important that less costly generic
versions of opioids that reference listed drugs whose labeling
describes abuse-deterrent properties are available to ensure access to
safe and effective analgesics for patients who need them.
If the summary in section 9.2 of the approved labeling for the RLD
indicates that FDA has concluded that the RLD has properties that are
expected to (or have been shown through postmarketing studies to) deter
abuse, the potential ANDA applicant should evaluate its proposed
generic drug to show that it is no less abuse deterrent than the RLD
with respect to all of the potential routes of abuse. This will ensure
the generic drug is no less abuse-deterrent than the RLD with respect
to all potential routes of abuse and minimize the risk of shifting
abuse to other, potentially more dangerous routes. This guidance
describes FDA's current thinking on the studies that should be
conducted by a potential ANDA applicant and submitted to FDA in an ANDA
to demonstrate that a generic solid oral opioid drug product is no less
abuse deterrent than its RLD with respect to all potential routes of
abuse. These studies are in addition to other studies that may be
needed to support ANDA approval (e.g., as described in product-specific
guidances).
The final guidance, like the draft guidance, focuses on the general
principles for developing and evaluating the abuse deterrence of
generic solid oral opioid drug products formulated to incorporate
physical or chemical barriers, agonist/antagonist combinations,
aversive agents, or a combination of two or more of these technologies.
FDA will continue to assess the state of science and, as novel
technologies develop, will address them by issuing additional guidance,
as appropriate.
In the Federal Register of March 25, 2016, FDA announced the
availability of the draft guidance for industry ``General Principles
for Evaluating the Abuse Deterrence of Generic Solid Oral Opioid Drug
Products'' (81 FR 16186). FDA subsequently announced in the Federal
Register of October 6, 2016, and held on October 31-November 1, 2016, a
public meeting to discuss scientific and technical issues relating to
formulation development and premarket evaluation of opioid drug
products with abuse-deterrent properties (81 FR 69532). This final
guidance reflects our consideration of comments made in the dockets for
the draft guidance (Docket No. FDA-2016-D-0785) and for the public
meeting (Docket No. FDA-2016-N-2896) and comments made during the
public meeting, and provides the Agency's current thinking with respect
to the general principles for evaluating the abuse deterrence of
generic solid oral opioid drug products.
Among other changes, the final guidance eliminates the
recommendation to use a control to identify discriminatory study
conditions for comparing the proposed generic opioid drug product (the
test (T) product) and the RLD (reference (R) product). Instead, FDA
recommends that a potential ANDA applicant conduct extraction studies
to assess the particular vulnerabilities of T and R products to inform
the comparison of their abuse deterrence. The final guidance also
provides more detailed recommendations regarding the conduct of in vivo
studies, specifically comparative PK studies of manipulated T and R
products to evaluate the potential for abuse by the oral and nasal
routes of administration.
Appendix 1 of the final guidance continues to describe some of the
ways in which the T and R products can be physically manipulated and
provides recommendations for conducting extraction studies to assess
the particular vulnerabilities of the T and R products to inform the
comparison of their abuse deterrence. FDA continues to recommend
potential ANDA applicants follow a tier-based approach to
extractability testing to efficiently compare a T product to its R
product and limit the number of tests required for evaluating the abuse
deterrence of the T product, but has modified some of the initial
recommendations regarding solvents.
Appendix 2 provides recommendations for evaluating abuse by
ingestion. In the final guidance, FDA clarifies the circumstances under
which a potential applicant should conduct a comparative oral PK study.
Appendices 3, 4, and 5 provide modified recommendations for evaluating
abuse by injection, insufflation, and smoking, respectively.
The guidance addresses the general principles for evaluating abuse
deterrence in generic solid oral opioid drug products. FDA may provide
additional testing recommendations in future product-specific
guidances. For example, FDA may recommend in a product-specific
guidance that a potential ANDA applicant evaluate human abuse potential
(for example, evaluate a study subject's willingness to take drug
again) if R product contains a known aversive agent. Further, FDA will
continue to assess the state of the science and, as novel technologies
develop, will address them by issuing revised or additional guidance,
as appropriate.
Potential ANDA applicants may pose questions regarding evaluation
of abuse deterrence for a generic solid oral opioid drug product
through FDA's pre-ANDA program. The goals of the pre-ANDA program are
to clarify regulatory expectations for prospective applicants early in
the development process, assist applicants in developing more complete
submissions, promote a more efficient and effective ANDA review
process, and reduce the number of review cycles required to obtain ANDA
approval, particularly for complex products. FDA considers abuse-
deterrent opioids to be products that fall within the definition of
complex product as that term has been defined in the GDUFA
Reauthorization Performance Goals and Program Enhancements Fiscal Years
2018-2022, which can be found at https://www.fda.gov/downloads/ForIndustry/UserFees/GenericDrugUserFees/UCM525234.pdf. The pre-ANDA
program provides for, among other things, submission of controlled
correspondence and requests for formal meetings between FDA and
applicants on complex generic drug development issues.
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 ``General Principles for Evaluating the
Abuse Deterrence of Generic Solid Oral Opioid Drug Products.'' 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. This guidance
is not subject to Executive Order 12866.
[[Page 55619]]
II. Electronic Access
Persons with access to the internet may obtain the guidance at
either https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm or
https://www.regulations.gov.
Dated: November 16, 2017.
Anna K. Abram,
Deputy Commissioner for Policy, Planning, Legislation, and Analysis.
[FR Doc. 2017-25248 Filed 11-21-17; 8:45 am]
BILLING CODE 4164-01-P
