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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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` NDA 201655/S-020
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`Food and Drug Administration
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` Silver Spring MD 20993
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`SUPPLEMENT APPROVAL
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` Endo Pharmaceuticals, Inc.
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` 1400 Atwater Drive
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` Malvern, PA 19355
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`Attention:
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`Dear Dr. Chapman:
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`Please refer to your Supplemental New Drug Application (sNDA) dated October 23, 2015,
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`submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA) for
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`OPANA ER (oxymorphone HCl) extended-release tablets.
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`We acknowledge receipt of your amendment dated April 4, 2016.
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`This supplemental new drug application provides for proposed modifications to the approved
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`risk evaluation and mitigation strategy (REMS) for OPANA ER. This supplement is in response
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`to our August 27, 2015, REMS Modification Notification letter, and our February 23, 2016,
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`email to the REMS Program Companies (RPC) advising you that your proposed REMS
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`modification should also include changes to the ER/LA Opioid Analgesics REMS Blueprint for
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`Prescriber Education to incorporate product-specifc language for recently approved NDAs.
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`We have completed our review of this supplemental application, as amended. It is approved,
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`effective on the date of this letter.
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`RISK EVALUATION AND MITIGATION STRATEGY REQUIREMENTS
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` The REMS for extended release and long-acting (ER/LA) opioid analgesics products, of which
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` OPANA ER is a member, was originally approved on July 9, 2012, and the most recent REMS
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` modification was approved on June 26, 2015. The REMS consists of a Medication Guide,
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` elements to assure safe use, and a timetable for submission of assessments of the REMS.
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`In order to ensure the benefits of OPANA ER outweigh its risks, we determined that you were
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`required to make the following REMS modifications:
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`Tara Chapman, PharmD
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`Senior Director, Regulatory Affairs
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`Changes to the ER/LA Opioid Analgesics REMS Blueprint for Prescriber
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`Education to include the following information:
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`1. Incorporation of information regarding the use of OxyContin in
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`the pediatric population
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`Reference ID: 3919789
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` NDA 201655/S-020
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` Page 2
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` 2. Addition of information to the titration recommendations of
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` OxyContin for adult patients
` 3. Product-specific information for a recently approved ER/LA
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` opioid analgesic, MorphaBond (morphine sulfate extended-
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` release) tablets
` 4. Product-specific information for a recently approved ER/LA
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` opioid analgesic, Belbuca (buprenorphine) buccal film
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`Your proposed modified REMS, submitted on April 4, 2016, and appended to this
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`letter, is approved.
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`This REMS uses a single, shared system for the elements to assure safe use and the REMS
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`assessments. This single shared system, known as the ER/LA Opioid Analgesics REMS
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`Program, currently includes the products listed on the FDA REMS website, available at
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`http://www.fda.gov/rems.
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`Other products may be added in the future if additional NDAs or ANDAs are approved.
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`The timetable for submission of assessments of the ER/LA Opioid Analgesic REMS Program
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`remains unchanged.
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`There are no changes to the REMS assessment plan described in our June 26, 2015, letter.
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`We remind you that in addition to the REMS assessments submitted according to the timetable in
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`the approved REMS, you must include an adequate rationale to support a proposed REMS
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`modification for the addition, modification, or removal of any goal or element of the REMS, as
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`described in section 505-1(g)(4) of the FDCA.
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`We also remind you that you must submit a REMS assessment when you submit a supplemental
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`application for a new indication for use as described in section 505-1(g)(2)(A) of the FDCA.
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`This assessment should include:
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`a) An evaluation of how the benefit-risk profile will or will not change with the new
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`indication;
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`b) A determination of the implications of a change in the benefit-risk profile for the current
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`REMS;
`c) If the new indication for use introduces unexpected risks: A description of those risks
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`and an evaluation of whether those risks can be appropriately managed with the currently
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`approved REMS.
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`d) If a REMS assessment was submitted in the 18 months prior to submission of the
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`supplemental application for a new indication for use: A statement about whether the
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`REMS was meeting its goals at the time of that last assessment and if any modifications
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`of the REMS have been proposed since that assessment.
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`Reference ID: 3919789
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` NDA 201655/S-020
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` Page 3
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` e) If a REMS assessment has not been submitted in the 18 months prior to submission of the
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` supplemental application for a new indication for use: Provision of as many of the
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` currently listed assessment plan items as is feasible.
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`f) If you propose a REMS modification based on a change in the benefit-risk profile or
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` because of the new indication of use, submit an adequate rationale to support the
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` modification, including: Provision of the reason(s) why the proposed REMS
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` modification is necessary, the potential effect on the serious risk(s) for which the REMS
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` 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
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`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
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` instruments or methodology, you should update the REMS supporting document to include
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` 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
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` new document that references previous REMS supporting document submission(s) for
` unchanged portions. Alternatively, updates may be made by modifying the complete previous
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` REMS supporting document, with all changes marked and highlighted. Prominently identify the
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` submission containing the assessment instruments and methodology with the following wording
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` in bold capital letters at the top of the first page of the submission:
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`NDA 201655 REMS CORRESPONDENCE
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`(insert concise description of content in bold capital letters) e.g.,
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`UPDATE TO REMS SUPPORTING DOCUMENT - ASSESSMENT
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`METHODOLOGY
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`An authorized generic drug under this NDA must have an approved REMS prior to marketing.
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`Should you decide to market, sell, or distribute an authorized generic drug under this NDA,
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`contact us to discuss what will be required in the authorized generic drug REMS submission.
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`We remind you that section 505-1(f)(8) of FDCA prohibits holders of an approved covered
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`application from using any element to assure safe use to block or delay approval of an
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`application under section 505(b)(2) or (j) or to prevent application of such element under 505­
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`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.
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`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
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`first page of the submission as appropriate:
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`NDA 201655 REMS ASSESSMENT
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`Reference ID: 3919789
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` NDA 201655/S-020
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` Page 4
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` NEW SUPPLEMENT FOR NDA 201655/S-000/
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` CHANGES BEING EFFECTED IN 30 DAYS
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` PROPOSED MINOR REMS MODIFICATION
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`or
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`NEW SUPPLEMENT FOR NDA 201655/S-000
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`PRIOR APPROVAL SUPPLEMENT
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`PROPOSED MAJOR REMS MODIFICATION
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`or
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`NEW SUPPLEMENT FOR NDA 201655/S-000
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`PRIOR APPROVAL SUPPLEMENT
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`PROPOSED REMS MODIFICATIONS DUE TO SAFETY LABEL CHANGES
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`SUBMITTED IN SUPPLEMENT XXX
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`NEW SUPPLEMENT (NEW INDICATION FOR USE)
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`FOR NDA 201655/S-000
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`REMS ASSESSMENT
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`PROPOSED REMS MODIFICATION (if included)
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`Should you choose to submit a REMS revision, prominently identify the submission containing
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`the REMS revisions with the following wording in bold capital letters at the top of the first page
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`of the submission:
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`To facilitate review of your submission, we request that you submit your proposed modified
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`REMS and other REMS-related materials in Microsoft Word format. If certain documents, such
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`as enrollment forms, are only in PDF format, they may be submitted as such, but the preference
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`is to include as many as possible in Word format.
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`If you do not submit electronically, please send 5 copies of REMS-related submissions.
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`REPORTING REQUIREMENTS
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` We remind you that you must comply with reporting requirements for an approved NDA
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` (21 CFR 314.80 and 314.81).
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`REMS REVISIONS FOR NDA 201655
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`Reference ID: 3919789
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` NDA 201655/S-020
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` Page 5
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` If you have any questions, call Mark Liberatore, PharmD; Safety Regulatory Project Manager, at
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`Sincerely,
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`{See appended electronic signature page}
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`Judith A. Racoosin, MD, MPH
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`Deputy Director of Safety
`Division of Anesthesia, Analgesia,
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`and Addiction Products
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`Office of Drug Evaluation II
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`Center for Drug Evaluation and Research
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`ENCLOSURE(S):
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`REMS
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`Reference ID: 3919789
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`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
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`JUDITH A RACOOSIN
`04/20/2016
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`Reference ID: 3919789
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`(
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