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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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` NDA 201655/S-005
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`Food and Drug Administration
`Silver Spring MD 20993
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`SUPPLEMENT APPROVAL
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`Endo Pharmaceuticals Inc.
`1400 Atwater Drive
`Malvern, PA 19355
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`Attention: Tara Chapman, Pharm.D.
`Director, Regulatory Affairs
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`
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`Dear Dr. Chapman:
`
`Please refer to your Supplemental New Drug Application (sNDA) dated and received October
`19, 2012, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA)
`for OPANA ER (oxymorphone hydrochloride extended-release) Tablets.
`
`We acknowledge receipt of your amendments dated November 26, 2012, and January 7 and
`March 27, 2013.
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`This supplemental new drug application proposes modifications to the approved risk evaluation
`and mitigation strategy (REMS) for OPANA ER.
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`We have completed our review of this supplemental application, as amended. It is approved,
`effective on the date of this letter.
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` RISK EVALUATION AND MITIGATION STRATEGY REQUIREMENTS
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`The REMS for OPANA ER was originally approved on December 9, 2011, and modified on July
`9, 2012. The REMS consists of a Medication Guide, elements to assure safe use, and a timetable
`for submission of assessments of the REMS. Your proposed modifications to the REMS consist
`of:
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` Revisions to Section VI. Specific Drug information for ER/LA Opioid Analgesic
`Products of the FDA Blueprint
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` Revisions to the REMS Website, including the landing page and the webpage listing
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`covered products under the REMS program
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` Revisions to individual product Medication Guides for relevant drugs
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` Revision to the REMS document to remove ANDA holders from the Timetable for
`Submission of Assessments
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`Reference ID: 3292639
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`

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` NDA 201655/S-005
`Page 2
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`Your proposed modified REMS, submitted on March 27, 2013, and appended to this letter, is
`approved.
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`The timetable for submission of assessments of the REMS will remain the same as that approved
`on July 9, 2012. There are no changes to the REMS assessment plan described in our July 9,
`2012 letter.
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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 Analgesic REMS
`Program, currently includes the products listed in Appendix 1. Other products may be added in
`the future if additional NDAs or ANDAs are approved.
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`We remind you that section 505-1(f)(8) of FDCA prohibits holders of an approved covered
`application with elements to assure safe use from using any element to block or delay approval
`of an application under section 505(b)(2) or (j). A violation of this provision in 505-1(f) could
`result in enforcement action.
`
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`The requirements for assessments of an approved REMS under section 505-1(g)(3) include with
`respect to each goal included in the strategy, an assessment of the extent to which the approved
`strategy, including each element of the strategy, is meeting the goal or whether one or more such
`goals or such elements should be modified.
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`In addition to the assessments submitted according to the timetable included in the approved
`REMS, you may propose a modification to the approved REMS when you submit a
`supplemental application for a new indication for use as described in section 505-1(g)(2)(A) of
`the FDCA.
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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:
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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,
`contact us to discuss what will be required in the authorized generic drug REMS submission.
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`Reference ID: 3292639
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`

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` NDA 201655/S-005
`Page 3
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`Prominently identify the 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:
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`NDA 201655 REMS ASSESSMENT
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`NEW SUPPLEMENT FOR NDA 201655
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`PROPOSED REMS MODIFICATION
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`NEW SUPPLEMENT (NEW INDICATION FOR USE)
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`FOR NDA 201655
`REMS ASSESSMENT
`PROPOSED REMS MODIFICATION (if included)
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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
`(21 CFR 314.80 and 314.81).
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`If you have any questions, call Lisa E. Basham, Senior Regulatory Health Project Manager, at
`(301) 796-1175.
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`Sincerely,
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`{See appended electronic signature page}
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`Judith A. Racoosin, M.D., M.P.H.
`Deputy Director for Safety
`Division of Anesthesia, Analgesia,
`and Addiction Products
`Office of Drug Evaluation II
`Center for Drug Evaluation and Research
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`ENCLOSURE:
`REMS
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`Reference ID: 3292639
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`NDA 019813
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`NDA 022321
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` NDA 201655/S-005
`Page 4
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` Appendix 1 List of applications
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`NDA 021260
`AVINZA (morphine sulfate) extended-release capsules and its generic
`equivalent
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`NDA 021306
`BUTRANS (buprenorphine) Transdermal System for transdermal
`administration
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`NDA 006134
`DOLOPHINE (methadone hydrochloride) tablets and its generic equivalents
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`ANDA 087997
`Methadone Oral Solution and its generic equivalents ANDA 087393
`Methadone Oral Solution and its generic equivalents ANDA 089897
`Methadone Oral Concentrate
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` DURAGESIC (Fentanyl Transdermal System) for transdermal administration
`and its generic equivalents
`EMBEDA (morphine sulfate and naltrexone hydrochloride) extended- release
`capsules
`EXALGO (hydromorphone HCl) Extended-Release Tablets
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`NDA 021217
`KADIAN (morphine sulfate) extended-release capsules and its generic
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`NDA 020616
`equivalent
`MS CONTIN (morphine sulfate) controlled-release tablets and its generic
`equivalents
`NUCYNTA ER (tapentadol) extended-release oral tablets
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`NDA 200533
`OPANA ER (oxymorphone hydrochloride) Extended-Release tablets
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`NDA 201655
`OPANA ER (oxymorphone hydrochloride) Extended-Release tablets and its
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`NDA 021610
`generic equivalents
`OXYCONTIN (oxycodone hydrochloride controlled-release) Tablets
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`
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`NDA 019516
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`NDA 022272
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`Reference ID: 3292639
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`

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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
`04/15/2013
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`Reference ID: 3292639
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