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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`Food and Drug Administration
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` Silver Spring MD 20993
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` NDA 203214/S-008
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`SUPPLEMENT APPROVAL
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` REMOVE REMS ELEMENT
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` REMS ASSESSMENT PLAN REVISION
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`PF PRISM C.V.
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`c/o Pfizer, Inc.
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`445 Eastern Road
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`Groton, CT 06340
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`Attention: James T. Mayne, PhD, DABT
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`Senior Director, Worldwide Safety and Regulatory
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`Dear Dr. Mayne:
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`Please refer to your Supplemental New Drug Application (sNDA) dated and received November
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`7, 2014, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA)
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`for Xeljanz (tofacitinib) 5 mg tablets.
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`We also refer to our REMS Modification Notification letter, dated September 9, 2014, in which
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`we notified you that the Medication Guide should be removed as an element of the REMS to
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`decrease the burden on the healthcare delivery system of complying with the REMS. We also
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`notified you that the REMS assessment plan should be revised.
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`This Prior Approval Supplemental New Drug Application proposes to eliminate the requirement
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`for the approved Medication Guide as an element of the approved Xeljanz REMS.
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`We have completed our review of this supplemental application. It is approved, effective on the
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`date of this letter.
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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 REMS
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`modifications were approved on November 8, 2013 and March 26, 2014. The REMS consists of
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`a Medication Guide, communication plan, and timetable for submission of assessment of the
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`REMS.
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`Your proposed modification to the REMS consists of eliminating the requirement for the
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`Medication Guide as an element of the REMS.
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`We have determined that maintaining the Medication Guide as part of the approved labeling is
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`adequate to address the serious and significant public health concern and meets the standard in
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`Reference ID: 3700802
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` NDA 203214/S-008
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` Page 2
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` 21 CFR 208.1. Therefore, it is no longer necessary to include the Medication Guide as an
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` element of the approved REMS to ensure that the benefits of Xeljanz (tofacitinib) outweigh the
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` risks.
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`Therefore, we agree with your proposal, and a Medication Guide is no longer required as part of
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`the REMS for Xeljanz (tofacitinib).
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`Your proposed modified REMS submitted on November 7, 2014 and appended to this letter is
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`approved.
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`The modified REMS consists of a communication plan and a timetable for submission of
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`assessments for the REMS.
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`We remind you that the Medication Guide will continue to be part of the approved labeling for
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`Xeljanz (tofacitinib) in accordance with 21 CFR 208.
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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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`REMS ASSESSMENT PLAN
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`Our March 26, 2014, Supplement Approval/REMS Modification Approval, letter described the
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`REMS assessment plan. As described in our September 9, 2014, letter, the REMS assessment
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`plan should be revised to remove the Survey of Patient Knowledge and Understanding since the
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`REMS goals will be revised to only include healthcare providers.
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`The revised REMS assessment plan should include, but is not limited to the following:
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`i. A survey of physicians’ knowledge and understanding of the serious risks of tofacitinib
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`will be made.
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`ii. A survey of pharmacists’ knowledge and understanding of the serious risks of
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`tofacitinib will be made.
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`iii. An assessment and conclusions regarding the success of the REMS in meeting the
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`stated goals will be made.
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`iv. An assessment of the communication plan including:
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`o The source(s) of the list of healthcare professionals to whom the Dear Healthcare Provider
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` Letter, Dear Pharmacist Letter are distributed
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` Journal information pieces published, including date and journal name, volume, and issue
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`o The date of launch of the communication plan (Dear Healthcare Provider Letter, Dear
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`Pharmacist Letter, website, and journal information pieces)
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`Reference ID: 3700802
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` NDA 203214/S-008
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` Page 3
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`o The number of recipients of the Dear Healthcare Provider and Dear Pharmacist Letters
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`o Date(s) of distribution of the Dear Healthcare Provider and Dear Pharmacist Letters
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`o The number of returned and refused letters
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` 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
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`goals or such elements should be modified.
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`In addition to the assessments submitted according to the timetable included in the approved
`REMS, you must submit a REMS assessment and may propose a modification to the approved
`REMS when you submit a supplemental application for a new indication for use as described in
`section 505-1(g)(2)(A) of 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
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`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.
`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 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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`Reference ID: 3700802
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` NDA 203214/S-008
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` Page 4
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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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`REQUIRED PEDIATRIC ASSESSMENTS
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` 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
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` administration are required to contain an assessment of the safety and effectiveness of the
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` 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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` REPORTING REQUIREMETNS
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`We remind you that you must comply with reporting requirements for an approved NDA (21
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`CFR 314.80 and 314.81).
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`If you have any questions, call Carol F. Hill, Safety Regulatory Health Project Manager, at (301)
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`796-1226.
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`Sincerely,
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`{See appended electronic signature page}
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`Sally Seymour, MD
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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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`Center for Drug Evaluation and Research
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`ENCLOSURES:
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`REMS
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`Reference ID: 3700802
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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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`CAROL F HILL
`02/11/2015
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`SALLY M SEYMOUR
`02/11/2015
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`Reference ID: 3700802
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