`
`
`
`DEPARTMENT OF HEALTH AND HUMAN SERVICES
`
`
`
`
`
`
` NDA 201655/S015
`
`
`
`
`
`
`
`
`
`Food and Drug Administration
`
`Silver Spring MD 20993
`
`SUPPLEMENT APPROVAL
`
`
`Endo Pharmaceuticals, Inc.
`1400 Atwater Drive
`Malvern, PA 19355
`
`Attention:
`
`Tara Chapman, PharmD
`
`Director, Regulatory Affairs
`
`
`
`Dear Dr. Chapman:
`
`
`Please refer to your Supplemental New Drug Application (sNDA) dated and received June 13,
`2014, 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 amendment dated August 7, 2014.
`
`This supplemental new drug application provides for modifications to the approved risk
`evaluation and mitigation strategy (REMS) for OPANA ER.
`
`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 the ER/LA Opioid Analgesics REMS, of which OPANA ER is a member, was
`originally approved on July 9, 2012, and the most recent REMS modification was approved on
`April 15, 2013. 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:
`
`
`
`
`Revisions to the ER/LA Opioid Analgesics REMS Blueprint, ER/LA opioid analgesic
`REMS Website, and the Dear Prescriber Letter (DHCP) letter to incorporate the
`following safety labeling changes:
`
`i. New indication for ER/LA opioid analgesics.
`
`ii. New warning for Neonatal Opioid Withdraw Syndrome (NOWS).
`
`iii. Updated language for the following Warnings and Precautions:
`
`1. Addiction, Abuse, and Misuse
`
`2. Life-Threatening Respiratory Depression
`
`3. Accidental Ingestion
`
`4. Cytochrome P450 3A4 Interaction (for applicable products)
`
`Reference ID: 3612219
`
`

`

`NDA 201655/S-015
`Page 2
`
`
`
`
`iv. Revisions to the Blueprint to incorporate updated product-specific titration
`language.
`
`
`
`
`Changes to the ER/LA Opioid Analgesics REMS Blueprint to include product-specific
`information for ER/LA opioids approved after the last ER/LA REMS modification on
`April 15, 2013.
`
`Your proposed modified REMS, received on August 7, 2014, and appended to this letter, is
`approved.
`
`This REMS uses a single, shared system for the elements to assure safe use, and the REMS
`assessments are jointly completed by the ER/LA opioid analgesic application holders. 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/downloads/Drugs/DrugSafety/InformationbyDrugClass/UCM348818.pdf
`
`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
`
`REMS is due annually on July 9. There are no changes to the REMS assessment plan.
`
`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.
`
`We remind you that in addition to the REMS assessments submitted according to the timetable in
`
`the approved REMS, 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).
`
`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 201655 REMS CORRESPONDENCE
`
`(insert concise description of content in bold capital letters, e.g.,
`
`UPDATE TO REMS SUPPORTING DOCUMENT - ASSESSMENT
`
`METHODOLOGY)
`
`
`
`
`
`Reference ID: 3612219
`
`

`

`NDA 201655/S-015
`Page 3
`
`
`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.
`
`
`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.
`
`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:
`
`
`NDA 201655 REMS ASSESSMENT
`
`NEW SUPPLEMENT FOR NDA 201655
`
`PROPOSED REMS MODIFICATION
`
`
`NEW SUPPLEMENT (NEW INDICATION FOR USE)
`
`FOR NDA 201655
`REMS ASSESSMENT
`PROPOSED REMS MODIFICATION (if included)
`
`
`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).
`
`If you have questions, call Lisa Basham, Senior Regulatory Health Project Manager, at (301)
`796-1175.
`
`
`Sincerely,
`
`{See appended electronic signature page}
`
`
`Judith A. Racoosin, MD, MPH
`Deputy Director for Safety
`Division of Anesthesia, Analgesia,
`and Addiction Drugs
`Office of Drug Evaluation II
`Center for Drug Evaluation and Research
`
`
`ENCLOSURE:
`REMS
`
`
`Reference ID: 3612219
`
`

`

`---------------------------------------------------------------------------------------------------------
`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
`08/19/2014
`
`Reference ID: 3612219
`
`