Food and Drug Administration
`Silver Spring, MD 20993
`
`SUPPLEMENT APPROVAL
`
`DEPARTMENT OF HEALTH AND HUMAN SERVICES
`
`NDA 200533/S-001
`
`Janssen Research & Development, LLC
` on behalf of Janssen Pharmaceuticals, Inc.
`920 Route 202
`Raritan, NJ 08869
`
`Attention: Tania Hillmer, MS, RAC
`Associate Director, Regulatory Affairs
`
`
`Dear Ms. Hillmer:
`
`Please refer to your Supplemental New Drug Application (sNDA) dated and received October
`28, 2012, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA)
`for Nucynta ER (tapentadol) extended-release oral tablets, 50 mg, 100 mg, 150 mg, 200, mg, and
`250 mg.
`
`We acknowledge receipt of your amendment(s) dated January 6 (2), 17, and 20, February 17,
`March 13, April 20, June 21, July 16 and 25, and August 24 and 27, 2012, and your risk
`evaluation and mitigation strategy (REMS) assessment dated July 16, 2012.
`
`This “Prior Approval” supplemental new drug application provides for the use of Nucynta ER
`(tapentadol) for the management of neuropathic pain associated with diabetic peripheral
`neuropathy (DPN) in adults when a continuous, around-the-clock opioid analgesic is needed for
`an extended period of time and also provides for proposed modifications to the approved risk
`evaluation and mitigation strategy (REMS), which is part of the single, shared system REMS for
`Extended Release and Long-Acting Opioid Analgesics.
`
`We have completed our review of this supplemental application, as amended. It is approved,
`effective on the date of this letter, for use as recommended in the enclosed, agreed-upon labeling
`text.
`
`CONTENT OF LABELING
`
`As soon as possible, but no later than 14 days from the date of this letter, submit the content of
`labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format using the FDA
`automated drug registration and listing system (eLIST), as described at
`http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. Content
`of labeling must be identical to the enclosed labeling (text for the package insert and Medication
`
`Reference ID: 3181514
`
`

`

`
`
` NDA 200533/S-001
`Page 2
`
`Guide), with the addition of any labeling changes in pending “Changes Being Effected” (CBE)
`supplements, as well as annual reportable changes not included in the enclosed labeling.
`
`Information on submitting SPL files using eLIST may be found in the guidance for industry
`titled “SPL Standard for Content of Labeling Technical Qs and As” at
`http://www.fda.gov/downloads/DrugsGuidanceComplianceRegulatoryInformation/Guidances/U
`CM072392.pdf.
`
`The SPL will be accessible from publicly available labeling repositories.
`
`Also within 14 days, amend all pending supplemental applications for this NDA, including CBE
`supplements for which FDA has not yet issued an action letter, with the content of labeling
`[21 CFR 314.50(l)(1)(i)] in MS Word format, that includes the changes approved in this
`supplemental application, as well as annual reportable changes and annotate each change. To
`facilitate review of your submission, provide a highlighted or marked-up copy that shows all
`changes, as well as a clean Microsoft Word version. The marked-up copy should provide
`appropriate annotations, including supplement number(s) and annual report date(s).
`
`We request that the labeling approved today be available on your website within 10 days of
`receipt of this letter.
`
`REQUIRED PEDIATRIC ASSESSMENTS
`
`Under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355c), all applications for new
`active ingredients, new indications, new dosage forms, new dosing regimens, or new routes of
`administration are required to contain an assessment of the safety and effectiveness of the
`product for the claimed indication(s) in pediatric patients unless this requirement is waived,
`deferred, or inapplicable.
`
`We are waiving the pediatric study requirement for this application because necessary studies are
`impossible or highly impracticable. The number of pediatric patients with neuropathic pain
`associated with DPN is too small to study.
`
`RISK EVALUATION AND MITIGATION STRATEGY REQUIREMENTS
`
`The REMS for Nucynta ER (tapentadol) was originally approved on August 25, 2011, and a
`REMS modification was approved 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. This
`REMS uses a single, shared system for the elements to assure safe use and the REMS
`assessments. Your proposed modifications to the REMS consist of a revised Medication Guide to
`include information about the new approved use of Nucynta ER and a revised Blueprint for
`Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics (FDA Blueprint)
`to make technical corrections.
`
`Reference ID: 3181514
`
`

`

`
`
` NDA 200533/S-001
`Page 3
`
`Your proposed modified REMS is approved and appended to this letter.
`
`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.
`
`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 1 or more such
`goals or such elements should be modified.
`
`In addition to the assessments submitted according to the timetable included 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) of FDCA.
`
`We remind you that section 505-1(f)(8) of the 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.
`
`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 200533 REMS CORRESPONDENCE
`
`(insert concise description of content in bold capital letters, e.g.,
`
`UPDATE TO REMS SUPPORTING DOCUMENT - ASSESSMENT
`
`METHODOLOGY)
`
`
`If you currently distribute or plan to distribute an authorized generic product under this NDA,
`you must submit a complete proposed REMS that relates only to the authorized generic product.
`Submit a proposed REMS, REMS supporting document, and any required appended documents
`as a prior approval supplement. Approval of the proposed REMS is required before you may
`market your authorized generic product.
`
`Reference ID: 3181514
`
`

`

`
`
` NDA 200533/S-001
`Page 4
`
`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 200533 REMS ASSESSMENT
`
`NEW SUPPLEMENT FOR NDA 200533
`
`PROPOSED REMS MODIFICATION
`
`
`NEW SUPPLEMENT (NEW INDICATION FOR USE)
`
`FOR NDA 200533
`REMS ASSESSMENT
`PROPOSED REMS MODIFICATION (if included)
`
`If you do not submit electronically, please send 5 copies of REMS-related submissions.
`
`PROMOTIONAL MATERIALS
`
`You may request advisory comments on proposed introductory advertising and promotional
`labeling. To do so, submit the following, in triplicate, (1) a cover letter requesting advisory
`comments, (2) the proposed materials in draft or mock-up form with annotated references, and
`(3) the package insert(s) to:
`
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion (OPDP)
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
`
`You must submit final promotional materials and package insert(s), accompanied by a Form
`
`FDA 2253, at the time of initial dissemination or publication [21 CFR 314.81(b)(3)(i)]. Form
`
`FDA 2253 is available at http://www.fda.gov/opacom/morechoices/fdaforms/cder.html;
`instructions are provided on page 2 of the form. For more information about submission of
`promotional materials to the Office of Prescription Drug Promotion (OPDP), see
`http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm.
`
`REPORTING REQUIREMENTS
`
`We remind you that you must comply with reporting requirements for an approved NDA
`(21 CFR 314.80 and 314.81).
`
`Reference ID: 3181514
`
`

`

`
`
` NDA 200533/S-001
`Page 5
`
`If you have any questions, call Dominic Chiapperino, Ph.D., Senior Regulatory Health Project
`Manager, at (301) 796-1183.
`
`Sincerely,
`
`{See appended electronic signature page}
`
`Bob A. Rappaport, M.D.
`
`Director
`Division of Anesthesia, Analgesia, and
`Addiction Products
`Office of Drug Evaluation II
`Center for Drug Evaluation and Research
`
`ENCLOSURE(S):
`Content of Labeling
`REMS
`
`Reference ID: 3181514
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`BOB A RAPPAPORT
`08/28/2012
`
`Reference ID: 3181514
`
`