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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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` NDA 201655/S-016
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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 Pharmacuticals, Inc.
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` 1400 Atwater Drive
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` Malvern, PA 19355
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`Attention: Tara Chapman, PharmD
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`Sr. Director, Regulatory Affairs
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`Dear Dr. Chapman:
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`Please refer to your Supplemental New Drug Application (sNDA) dated and received June 26,
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`2014, 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 amendments dated August 7, 2014, and January 12, 2015.
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`This Prior Approval supplemental new drug application proposes the addition of a REMS for the
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`authorized generic for OPANA ER (oxymorphone HCl) extended-release tablets.
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`APPROVAL & LABELING
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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, for use as recommended in the enclosed, agreed-upon labeling
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`text.
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`CONTENT OF LABELING
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`As soon as possible, but no later than 14 days from the date of this letter, submit the content of
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`labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format using the FDA
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`automated drug registration and listing system (eLIST), as described at
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`http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. Content
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`of labeling must be identical to the enclosed labeling text for the Medication Guide, with the
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`addition of any labeling changes in pending “Changes Being Effected” (CBE) supplements, as
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`well as annual reportable changes not included in the enclosed labeling.
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`Information on submitting SPL files using eList may be found in the guidance for industry titled
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`“SPL Standard for Content of Labeling Technical Qs and As at
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`http://www.fda.gov/downloads/DrugsGuidanceComplianceRegulatoryInformation/Guidances/U
`CM072392.pdf
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`Reference ID: 3693219
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` NDA 201655/S-016
` Page 2
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` The SPL will be accessible from publicly available labeling repositories.
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`Also within 14 days, amend all pending supplemental applications that includes labeling changes
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`for this NDA, including CBE supplements for which FDA has not yet issued an action letter,
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`with the content of labeling [21 CFR 314.50(l)(1)(i)] in MS Word format, that includes the
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`changes approved in this supplemental application, as well as annual reportable changes and
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`annotate each change. To facilitate review of your submission, provide a highlighted or marked-
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`up copy that shows all changes, as well as a clean Microsoft Word version. The marked-up copy
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`should provide appropriate annotations, including supplement number(s) and annual report
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`date(s).
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`We request that the labeling approved today be available on your website within 10 days of
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`receipt of this letter.
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`CARTON AND IMMEDIATE CONTAINER LABELS
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`We acknowledge your June 26, 2014, submission containing final printed carton and container
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`labels.
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`RISK EVALUATION AND MITIGATION STRATEGY REQUIREMENTS
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`Section 505-1 of the FDCA authorizes FDA to require the submission of a risk evaluation and
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`mitigation strategy (REMS), if FDA makes a determination that such a strategy is necessary to
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`ensure that the benefits of the drug outweigh the risks [section 505-1(a)].
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`In accordance with section 505-1 of the FDCA, we have determined that a REMS is necessary
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`for the authorized generic for OPANA ER, oxymorphone HCl extended-release tablets, to ensure
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`the benefits of the drug continue to outweigh the risks of adverse outcomes (addiction,
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`unintentional overdose, and death) resulting from inappropriate prescribing, abuse, and misuse.
`The REMS for OPANA ER (oxymorphone HCl) was originally approved on December 9, 2011,
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`and REMS modifications were approved on July 9, 2012, April 15, 2013, and August 19, 2014.
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`The proposed REMS for oxymorphone HCl extended-release tablets is identical to the modified
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`OPANA ER REMS which was approved on August 19, 2014, with the exception of the
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`Medication Guide, which is revised to substitute the authorized generic name oxymorphone HCl
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`extended-release tablets for the trade name OPANA ER.
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`Your proposed REMS for the authorized generic, oxymorphone HCl extended-release tablets,
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`submitted on August 7, 2014, and appended to this letter, is approved.
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`The REMS consists of a Medication Guide, elements to assure safe use, and a timetable for
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`submission of assessments of the REMS.
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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 extended-release/long-acting (ER/LA)
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`Reference ID: 3693219
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` NDA 201655/S-016
` Page 3
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` Opioid Analgesics REMS Program, currently includes the products listed on the FDA REMS
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` website, available at
` http://www.fda.gov/downloads/Drugs/DrugSafety/InformationbyDrugClass/UCM348818.pdf
`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 REMS and the assessment plan for the
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` authorized generic of OPANA ER tablets remains the same as that described in our REMS
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` modification approval letter dated July 9, 2012, for OPANA ER, a member of the ER/LA Opioid
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` Analgesic REMS Program.
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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 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
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` result in enforcement action.
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` Under section 505-1(g)(2)(C), FDA may require the submission of a REMS assessment if FDA
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` determines that that an assessment is needed to evaluate whether the approved strategy should be
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` modified to ensure the benefits of the drug outweigh the risks of the drug or minimize the burden
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` on the health care delivery system of complying with the strategy.
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` We remind you that in addition to the assessments submitted according to the timetable included
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` in the approved REMS, you must submit a REMS assessment to the approved REMS when you
`submit a supplemental application for a new indication for use as described in section 505­
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` 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
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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
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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
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` 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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`Prominently identify the 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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`Reference ID: 3693219
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` NDA 201655/S-016
` Page 4
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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
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`REMS ASSESSMENT
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`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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`PROMOTIONAL MATERIALS
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`You may request advisory comments on proposed introductory advertising and promotional
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`labeling. To do so, submit the following, in triplicate, (1) a cover letter requesting advisory
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`comments, (2) the proposed materials in draft or mock-up form with annotated references, and
`(3) the package insert(s) to:
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`Food and Drug Administration
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`Center for Drug Evaluation and Research
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`Office of Prescription Drug Promotion (OPDP)
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`5901-B Ammendale Road
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`Beltsville, MD 20705-1266
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`You must submit final promotional materials and package insert(s), accompanied by a Form
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`FDA 2253, at the time of initial dissemination or publication [21 CFR 314.81(b)(3)(i)]. Form
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`FDA 2253 is available at
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`http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf.
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`Information and Instructions for completing the form can be found at
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`http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf. For
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`more information about submission of promotional materials to the Office of Prescription Drug
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`Promotion (OPDP), see http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm.
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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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`Reference ID: 3693219
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` NDA 201655/S-016
` Page 5
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` If you have any questions, call Lisa Basham, Senior Regulatory Health Project Manager, at (301)
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` 796-1175.
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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
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`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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`ENCLOSURES:
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`Content of Labeling
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`Carton and Container Labeling
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`REMS
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`Reference ID: 3693219
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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
`01/28/2015
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`Reference ID: 3693219
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