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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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` NDA 201655/S-022
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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 August 24, 2016,
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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 hydrochloride) Extended-Release Tablets.
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`This supplemental new drug application provides for proposed modifications to the approved
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`Extended Release and Long-Acting Opioid Analgesic risk evaluation and mitigation strategy
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`(REMS) to relocate the product-specific information section of the Blueprint for Prescriber
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`Education.
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`We have completed our review of this supplemental application. It is approved, effective on the
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`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 analgesic products, of which
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`OPANA ER (oxymorphone hydrochloride) is a member, was originally approved on July 9,
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`2012, and the most recent REMS modification was approved on April 20, 2016. The REMS
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`consists of a Medication Guide, elements to assure safe use, and a timetable for submissions of
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`assessments of the REMS.
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`Your proposed modifications to the REMS consist of the relocation of the product-specific
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`information section from the Blueprint for Prescriber Education to the FDA website located at
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`http://www.fda.gov/downloads/Drugs/DrugSafety/InformationbyDrugClass/UCM515636.pdf.
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` Your proposed modified REMS, submitted on August 24, 2016, and appended to this letter, is
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`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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`Tara Chapman, PharmD
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`Senior Director, Regulatory Affairs
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`Reference ID: 3992822
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` NDA 201655/S-022
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` Page 2
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`http://www.accessdata.fda.gov/scripts/cder/rems/index.cfm?event=RemsDetails.page&REMS=1
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` 7.
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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 for 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 the last assessment and if any modifications
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`of the REMS have been proposed since that assessment.
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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.
`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
`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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`the REMS supporting document, or if you propose changes to the submitted assessment
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`instruments or methodology, you should update the REMS supporting document to include
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`Reference ID: 3992822
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` NDA 201655/S-022
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` Page 3
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` specific assessment instrument and methodology information at least 90 days before the
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` 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
`1(i)(1)(B) to a drug that is subject of an ANDA. A violation of this provision in 505-1(f) could
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`result in enforcement action.
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`Prominently identify any submission containing the REMS assessments or proposed
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`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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`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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`Reference ID: 3992822
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` NDA 201655/S-022
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` Page 4
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` or
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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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`If you have any questions, call Mark Liberatore, PharmD; Safety Regulatory Project Manager, at
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`(301) 796-2221.
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`REMS REVISIONS FOR NDA 201655
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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 for 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:
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`REMS
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`Reference ID: 3992822
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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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`SHARON H HERTZ on behalf of JUDITH A RACOOSIN
`09/30/2016
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`Reference ID: 3992822
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`(
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