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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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` NDA 203214/S-005
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` Food and Drug Administration
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` Silver Spring MD 20993
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`SUPPLEMENT APPROVAL
`REMS MODIFICATION APPROVAL
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`PF PRISM C.V.
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`c/o Pfizer, Inc.
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`445 Eastern Point Road
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`Groton, CT 06340
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` Attention: Nickie V. Kilgore, D.V.M.
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` Director, Worldwide Regulatory Strategy
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`Dear Dr. Kilgore:
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`Please refer to your Supplemental New Drug Application (sNDA) dated September 25, 2013,
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`submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA) for
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`Xeljanz (tofacitinib) Tablets, 5 mg, and your risk evaluation and mitigation strategy (REMS)
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`assessment dated March 25, 2014.
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`We acknowledge receipt of your amendments dated November 22, 2013 (2), and March 6, 10,
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`and 25, 2014.
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`This Prior Approval supplemental new drug application provides for revisions to the
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`WARNINGS and PRECAUTIONS, ADVERSE REACTIONS, and Medication Guide to update
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`the product label regarding viral hepatitis and non-melanoma skin cancers.
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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 package insert, Medication
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`Guide), with the addition of any labeling changes in pending “Changes Being Effected” (CBE)
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`supplements, as well as annual reportable changes not included in the enclosed labeling.
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`Reference ID: 3478164
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` NDA 203214/S-005
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` Page 2
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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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`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,
` 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-
` 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
` 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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` REQUIRED PEDIATRIC ASSESSMENTS
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`Under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355c), all applications for new
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`active ingredients, new indications, new dosage forms, new dosing regimens, or new routes of
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`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,
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`deferred, or inapplicable.
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`Because none of these criteria apply to your application, you are exempt from this requirement.
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`RISK EVALUATION AND MITIGATION STRATEGY REQUIREMENTS
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`The REMS for Xeljanz (tofacitinib) was originally approved on November 6, 2012, and a REMS
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`modification was approved on November 8, 2013. The REMS consists of a Medication Guide,
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`communication plan, and a timetable for submission of assessments of the REMS. Your
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`proposed modifications to the REMS consist of revisions to the Medication Guide, Dear
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`Healthcare Provider Letter, Dear Pharmacist Letter, and Journal Information Pieces to
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`incorporate information regarding viral hepatitis and the risk of non-melanoma skin cancer
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`associated with Xeljanz.
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`Your proposed modified REMS, submitted on March 10, 2014, and appended to this letter, is
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`approved.
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`The timetable for submission of assessments of the REMS will remain the same as that approved
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`on November 6, 2012.
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`Reference ID: 3478164
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`NDA 203214/S-005
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`Page 3
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`There are no changes to the REMS assessment plan described in our November 6, 2012, letter.
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`In addition to the assessments submitted according to the timetable included in the approved
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`REMS, you must submit a REMS assessment and may propose a modification to the approved
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`REMS when you submit a supplemental application for a new indication for use as described in
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`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
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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
`in bold capital letters at the top of the first page of the submission:
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`NDA 203214 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,
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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 with the following wording in bold capital letters at the top of the first page of the
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`submission:
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`NDA 203214 REMS ASSESSMENT
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`NEW SUPPLEMENT FOR NDA 203214
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`PROPOSED REMS MODIFICATION
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`NEW SUPPLEMENT (NEW INDICATION FOR USE)
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`FOR NDA 203214
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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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`Reference ID: 3478164
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` NDA 203214/S-005
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` Page 4
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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
` comments, (2) the proposed materials in draft or mock-up form with annotated references, and
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` (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
`http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf.
`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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`All promotional materials that include representations about your drug product must be promptly
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`revised to be consistent with the labeling changes approved in this supplement, including any
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`new safety information [21 CFR 314.70(a)(4)]. The revisions in your promotional materials
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`should include prominent disclosure of the important new safety information that appears in the
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`revised package labeling. Within 7 days of receipt of this letter, submit your statement of intent
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`to comply with 21 CFR 314.70(a)(4) to the address above or by fax to 301-847-8444.
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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: 3478164
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`NDA 203214/S-005
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`Page 5
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`If you have any questions, call Philantha Bowen, Senior Regulatory Project Management
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`Officer, at (301) 796-2466.
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`Sincerely,
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`{See appended electronic signature page}
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`Sally Seymour, M.D.
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`Deputy Director for Safety
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`Division of Pulmonary, Allergy, and Rheumatology
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`Products
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`Office of Drug Evaluation II
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`ENCLOSURE(S):
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`Content of Labeling
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`REMS
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`Reference ID: 3478164
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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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`SALLY M SEYMOUR
`03/26/2014
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`Reference ID: 3478164
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