DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration
Silver Spring MD 20993

NDA 207932/S-001
SUPPLEMENT APPROVAL
Endo Pharmaceuticals, Inc.
1400 Atwater Drive
Malvern, PA 19355
Attention:  

Paula Clark
Senior Director, Regulatory Affairs

Dear Ms. Clark:
Please refer to your Supplemental New Drug Application (sNDA) dated April 4, 2016, submitted
under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA) for BELBUCA
(buprenorphine HCl) buccal film.
This supplemental new drug application provides for proposed modifications to the approved
risk evaluation and mitigation strategy (REMS) for BELBUCA. This supplement is in response
to our February 23, 2016, email to the REMS Program Companies (RPC) advising you that your
proposed REMS modification should also include changes to the ER/LA Opioid Analgesics
REMS Blueprint for Prescriber Education to incorporate product-specifc language for recently
approved NDAs.
We have completed our review of this supplemental application, as amended. It is approved,
effective on the date of this letter.
RISK EVALUATION AND MITIGATION STRATEGY REQUIREMENTS
The REMS for extended release and long-acting (ER/LA) opioid analgesics products, of which
BELBUCA is a member, was originally approved on July 9, 2012, and the most recent REMS
modification was approved on June 27, 2015. BELBUCA was approved and became part of the
ER/LA Opioid Analgesic REMS on October 23, 2015. The REMS consists of a Medication
Guide, elements to assure safe use, and a timetable for submission of assessments of the REMS.
In order to ensure the benefits of BELBUCA outweigh its risks, we determined that updates to
your REMS approved on October 23, 2015, were necessary.
Your proposed modified REMS, submitted on April 4, 2016, and appended to this letter, is
approved.

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This REMS uses a single, shared system for the elements to assure safe use and the REMS
assessments. This single shared system, known as the ER/LA Opioid Analgesics REMS
Program, currently includes the products listed on the FDA REMS website, available at
http://www.fda.gov/rems.
Other products may be added in the future if additional NDAs or ANDAs are approved.
The timetable for submission of assessments of the ER/LA Opioid Analgesic REMS Program
remains unchanged.
There are no changes to the REMS assessment plan described in our October 23, 2015, NDA
Approval letter.
We remind you that in addition to the REMS assessments submitted according to the timetable in
the approved REMS, you must include an adequate rationale to support a proposed REMS
modification for the addition, modification, or removal of any goal or element of the REMS, as
described in section 505-1(g)(4) of the FDCA.
We also remind you that you must submit a REMS assessment when you submit a supplemental
application for a new indication for use as described in section 505-1(g)(2)(A) of the FDCA.
This assessment should include:
a) An evaluation of how the benefit-risk profile will or will not change with the new
indication;
b) A determination of the implications of a change in the benefit-risk profile for the current
REMS;
c)  If the new indication for use introduces unexpected risks: A description of those risks
and an evaluation of whether those risks can be appropriately managed with the currently
approved REMS.
d)  If a REMS assessment was submitted in the 18 months prior to submission of the
supplemental application for a new indication for use: A statement about whether the
REMS was meeting its goals at the time of that last assessment and if any modifications
of the REMS have been proposed since that assessment.
e)  If a REMS assessment has not been submitted in the 18 months prior to submission of the
supplemental application for a new indication for use: Provision of as many of the
currently listed assessment plan items as is feasible.
f)  If you propose a REMS modification based on a change in the benefit-risk profile or
because of the new indication of use, submit an adequate rationale to support the
modification, including: Provision of the reason(s) why the proposed REMS
modification is necessary, the potential effect on the serious risk(s) for which the REMS
was required, on patient access to the drug, and/or on the burden on the health care
delivery system; and other appropriate evidence or data to support the proposed change.
Additionally, include any changes to the assessment plan necessary to assess the
proposed modified REMS. If you are not proposing REMS modifications, provide a
rationale for why the REMS does not need to be modified.

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If the assessment instruments and methodology for your REMS assessments are not included in
the REMS supporting document, or if you propose changes to the submitted assessment
instruments or methodology, you should update the REMS supporting document to include
specific assessment instrument and methodology information at least 90 days before the
assessments will be conducted. Updates to the REMS supporting document may be included in a
new document that references previous REMS supporting document submission(s) for
unchanged portions. Alternatively, updates may be made by modifying the complete previous
REMS supporting document, with all changes marked and highlighted. Prominently identify the
submission containing the assessment instruments and methodology with the following wording
in bold capital letters at the top of the first page of the submission:
NDA 207932 REMS CORRESPONDENCE

(insert concise description of content in bold capital letters) e.g., 

UPDATE TO REMS SUPPORTING DOCUMENT - ASSESSMENT 

METHODOLOGY

An authorized generic drug under this NDA must have an approved REMS prior to marketing.
Should you decide to market, sell, or distribute an authorized generic drug under this NDA,
contact us to discuss what will be required in the authorized generic drug REMS submission.
We remind you that section 505-1(f)(8) of FDCA prohibits holders of an approved covered
application from using any element to assure safe use to block or delay approval of an
application under section 505(b)(2) or (j) or to prevent application of such element under 505­
1(i)(1)(B) to a drug that is subject of an ANDA. A violation of this provision in 505-1(f) could
result in enforcement action.
Prominently identify any submission containing the REMS assessments or proposed
modifications of the REMS with the following wording in bold capital letters at the top of the
first page of the submission as appropriate:
NDA 207932 REMS ASSESSMENT
NEW SUPPLEMENT FOR NDA 207932/S-000/
CHANGES BEING EFFECTED IN 30 DAYS
PROPOSED MINOR REMS MODIFICATION
or
NEW SUPPLEMENT FOR NDA 207932/S-000
PRIOR APPROVAL SUPPLEMENT
PROPOSED MAJOR REMS MODIFICATION
or
NEW SUPPLEMENT FOR NDA 207932/S-000 

PRIOR APPROVAL SUPPLEMENT


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PROPOSED REMS MODIFICATIONS DUE TO SAFETY LABEL CHANGES
SUBMITTED IN SUPPLEMENT XXX
NEW SUPPLEMENT (NEW INDICATION FOR USE)
FOR NDA 207932/S-000
REMS ASSESSMENT
PROPOSED REMS MODIFICATION (if included)
Should you choose to submit a REMS revision, prominently identify the submission containing
the REMS revisions with the following wording in bold capital letters at the top of the first page
of the submission:
REMS REVISIONS FOR NDA 207932
To facilitate review of your submission, we request that you submit your proposed modified
REMS and other REMS-related materials in Microsoft Word format. If certain documents, such
as enrollment forms, are only in PDF format, they may be submitted as such, but the preference
is to include as many as possible in Word format.
If you do not submit electronically, please send 5 copies of REMS-related submissions.
REPORTING REQUIREMENTS
We remind you that you must comply with reporting requirements for an approved NDA
(21 CFR 314.80 and 314.81).

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If you have any questions, call Mark Liberatore, PharmD; Safety Regulatory Project Manager, at
(301) 796-2221.
Sincerely,
{See appended electronic signature page}
Judith A. Racoosin, MD, MPH
Deputy Director of Safety
Division of Anesthesia, Analgesia,
and Addiction Products
Office of Drug Evaluation II
Center for Drug Evaluation and Research
ENCLOSURE(S):
REMS

Reference ID: 3919815

 --------------------------------------------------------------------------------------------------------This is a representation of an electronic record that was signed
electronically and this page is the manifestation of the electronic
signature.
--------------------------------------------------------------------------------------------------------/s/
---------------------------------------------------JUDITH A RACOOSIN
04/20/2016

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