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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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` NDA 200533/S-011
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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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` Janssen Research and Development, LLC
` on behalf of Janssen Pharmaceuticals Inc.
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` 920 Route 202 South, P.O. Box 300
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` Raritan, NJ 08869-0602
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`Attention: Tania Hillmer, MS, RAC
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`Associate Director, Regulatory Affairs
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`Dear Ms. Hillmer:
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`Please refer to your Supplemental New Drug Application (sNDA) dated and received June 11,
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`2014, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA) for
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`NUCYNTA ER (tapentadol) extended-release tablets.
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`We acknowledge receipt of your amendments dated July 31 and August 6, 2014.
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`This supplemental new drug application provides for modifications to the approved risk
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`evaluation and mitigation strategy (REMS) for NUCYNTA ER.
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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
`The REMS for the ER/LA Opioid Analgesics REMS, of which NUCYNTA ER is a member,
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`was originally approved on July 9, 2012, and the most recent REMS modification was approved
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`on April 15, 2013. The REMS consists of a Medication Guide, elements to assure safe use, and a
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`timetable for submission of assessments of the REMS. Your proposed modifications to the
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`REMS consist of:
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`Revisions to the ER/LA Opioid Analgesics REMS Blueprint, ER/LA opioid analgesic
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`REMS Website, and the Dear Prescriber Letter (DHCP) letter to incorporate the
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`following safety labeling changes:
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`i. New indication for ER/LA opioid analgesics.
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`ii. New warning for Neonatal Opioid Withdraw Syndrome (NOWS).
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`iii. Updated language for the following Warnings and Precautions:
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`1. Addiction, Abuse, and Misuse
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`2. Life-Threatening Respiratory Depression
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`3. Accidental Ingestion
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`Reference ID: 3612200
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` NDA 200533/S-011
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` Page 2
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` 4. Cytochrome P450 3A4 Interaction (for applicable products)
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` iv. Revisions to the Blueprint to incorporate updated product-specific titration
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` language.
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`Changes to the ER/LA Opioid Analgesics REMS Blueprint to include product-specific
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`information for ER/LA opioids approved after the last ER/LA REMS modification on
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`April 15, 2013.
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`Your proposed modified REMS, received on August 6, 2014, 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 are jointly completed by the ER/LA opioid analgesic application holders. This
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`single shared system, known as the ER/LA Opioid Analgesics REMS Program, currently
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`includes the products listed on the FDA REMS website, available at
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`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 ER/LA Opioid Analgesic REMS Program
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`REMS is due annually on July 9. There are no changes to the REMS assessment plan.
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`The requirements for assessments of an approved REMS under section 505-1(g)(3) include with
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`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
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`goals or such elements should be modified.
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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 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).
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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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`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 200533 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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`Reference ID: 3612200
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` NDA 200533/S-011
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` Page 3
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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
`result in enforcement action.
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`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,
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`contact us to discuss what will be required in the authorized generic drug REMS submission.
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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 200533 REMS ASSESSMENT
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`NEW SUPPLEMENT FOR NDA 200533
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`PROPOSED REMS MODIFICATION
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`NEW SUPPLEMENT (NEW INDICATION FOR USE)
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`FOR NDA 200533
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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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`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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`If you have questions, call Dominic Chiapperino, PhD, Senior Regulatory Health Project
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`Manager, at 301-796-1138.
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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 Drugs
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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: 3612200
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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
`08/19/2014
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`Reference ID: 3612200
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