`
` NDA 203214/S-026
`
`
`
`SUPPLEMENT APPROVAL
`FULFILLMENT OF POSTMARKETING
`REQUIREMENT
`
`
`PF PRISM C.V., a wholly owned subsidiary of Pfizer Inc.
`500 Arcola Road
`Collegeville, PA 19426
`
`Attention:
`
`
`
`Alicia Holsey, MS, RAC
`Senior Manager, Pfizer Global Regulatory Affairs
`
`
`Dear Ms. Holsey:
`
`Please refer to your supplemental new drug application (sNDA) dated March 26, 2020,
`received March 26, 2020, and your amendments, submitted under section 505(b) of the
`Federal Food, Drug, and Cosmetic Act (FDCA) for Xeljanz (tofacitinib) Oral Tablet.
`
`This Prior Approval supplemental new drug application provides for addition of the
`indication of treatment of active polyarticular course juvenile idiopathic arthritis (pcJIA)
`in patients 2 years of age and older.
`
`APPROVAL & LABELING
`
`We have completed our review of this application, as amended. It is approved, effective
`on the date of this letter, for use as recommended in the enclosed agreed-upon
`
`labeling.
`
`
`WAIVER OF ½ PAGE LENGTH REQUIREMENT FOR HIGHLIGHTS
`
`Please note that we have previously granted a waiver of the requirements of 21 CFR
`201.57(d)(8) regarding the length of Highlights of Prescribing Information.
`
`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
`FDA.gov.1 Content of labeling must be identical to the enclosed labeling (text for the
`Prescribing Information, Instructions for Use, and Medication 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.
`
`
` 1 http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm
`
`
`
`Reference ID: 4676373
`
`

`

`NDA 203214/S-026
`Page 2
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`
`
`Information on submitting SPL files using eList may be found in the guidance for
`industry SPL Standard for Content of Labeling Technical Qs and As.2
`
`
`The SPL will be accessible from publicly available labeling repositories.
`
`Also within 14 days, amend all pending supplemental applications that include labeling
`changes 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 Microsoft Word
`format, that includes the changes approved in this supplemental application, as well as
`annual reportable changes. To facilitate review of your submission(s), 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).
`
`CARTON AND CONTAINER LABELING
`
`
`Submit final printed carton and container labeling that are identical to the enclosed
`carton and container labeling, as soon as they are available, but no more than 30 days
`after they are printed. Please submit these labeling electronically according to the
`guidance for industry Providing Regulatory Submissions in Electronic Format — Certain
`Human Pharmaceutical Product Applications and Related Submissions Using the eCTD
`Specifications. For administrative purposes, designate this submission “Final Printed
`Carton and Container Labeling for approved NDA 203214/S-026.” Approval of this
`submission by FDA is not required before the labeling is used.
`
`REQUIRED PEDIATRIC ASSESSMENTS
`
`
`Under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355c), all applications for
`new active ingredients (which includes new salts and new fixed combinations), 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 in pediatric patients unless this requirement is waived, deferred,
`or inapplicable.
`
`This product is appropriately labeled for use in patients 2 years of age and older for this
`indication. Therefore, no additional studies are needed in this pediatric group (pcJIA).
`
`
`
`
`
`
`2 We update guidances periodically. For the most recent version of a guidance, check the FDA Guidance
`Documents Database https://www.fda.gov/RegulatoryInformation/Guidances/default.htm.
`
`U.S. Food and Drug Administration
`
`
`Silver Spring, MD 20993
`
`www.fda.gov
`
`Reference ID: 4676373
`
`

`

`NDA 203214/S-026
`Page 3
`
`
`FULFILLMENT OF POSTMARKETING REQUIREMENTS
`
`Supplemental new drug application (sNDA) 203214/S-026 provides data to address the
`following post-marketing requirement listed in the approval letter for new drug
`application 203214 dated November 6, 2012.
`
`1934-2
`
`A randomized withdrawal, double-blind, placebo-controlled trial to evaluate
`the efficacy and safety of tofacitinib in children from 2 to less than 18
`years of age with polyarticular-course juvenile idiopathic arthritis.
`
`
`
`We have reviewed your submission and conclude that the above requirements were
`fulfilled.
`
`We remind you that there are postmarketing requirements that are still open for this
`application.
`
`
`POSTMARKETING REQUIREMENTS UNDER 505(o)
`
`Section 505(o)(3) of the FDCA authorizes FDA to require holders of approved drug and
`biological product applications to conduct postmarketing studies and clinical trials for
`certain purposes, if FDA makes certain findings required by the statute.
`
`We have determined that an analysis of spontaneous postmarketing adverse events
`
`reported under subsection 505(k)(1) of the FDCA will not be sufficient to assess known
`serious risks of malignancies and serious infections (including opportunistic infections),
`assess a signal of a serious risk of thrombosis, and identify an unexpected serious risk
`of effects on growth.
`
`Furthermore, the active postmarket risk identification and analysis system as available
`
`under section 505(k)(3) of the FDCA will not be sufficient to assess these serious risks.
`
`Therefore, based on appropriate scientific data, FDA has determined that you are
`required to conduct the following:
`
`
`
`3944-1 Conduct a long-term observational safety study in pediatric patients 2-17
`years of age with polyarticular-course JIA (pcJIA) treated with tofacitinib to
`evaluate for the risk of malignancies, serious infections (including
`opportunistic infections), thrombosis, and effects on growth. The study
`should include a control group of pediatric pcJIA patients treated with
`other pcJIA medications as standard of care. Patients should be followed
`
`for 5 years.
`
`
`
`U.S. Food and Drug Administration
`
`
`Silver Spring, MD 20993
`www.fda.gov
`
`
`Reference ID: 4676373
`
`

`

`NDA 203214/S-026
`Page 4
`
`
`The timetable you submitted on September 22, 2020 states that you will conduct this
`study according to the following schedule:
`
`
`Draft Protocol Submission:
`Final Protocol Submission:
`Trial Completion:
`
`
`Final Report Submission:
`
`
`03/2021
`
`07/2021
`
`02/2030
`
`09/2030
`
`
`
`
`3944-2 Conduct a nonclinical juvenile animal toxicity study to address the
`potential for tofacitinib to adversely affect bone development and growth.
`Effects on bone development and growth should be assessed by
`histopathological examination. Other appropriate methods might be
`included to follow up on any findings as deemed necessary. The study
`should include a recovery period to address if any observed adverse
`findings are reversible.
`
`
`The timetable you submitted on September 16, 2020 states that you will conduct this
`study according to the following schedule:
`
`
`Draft Protocol Submission:
`Final Protocol Submission:
`Trial Completion:
`
`
`Final Report Submission:
`
`
`11/2020
`
`01/2021
`
`07/2021
`
`10/2021
`
`
`
`FDA considers the term final to mean that the applicant has submitted a protocol, the
`FDA review team has sent comments to the applicant, and the protocol has been
`revised as needed to meet the goal of the study or clinical trial.3
`
`
`Submission of the protocol(s) for required postmarketing observational studies to your
`IND is for purposes of administrative tracking only. These studies do not constitute
`clinical investigations pursuant to 21 CFR 312.3(b) and therefore are not subject to the
`IND requirements under 21 CFR part 312 or FDA’s regulations under 21 CFR parts 50
`(Protection of Human Subjects) and 56 (Institutional Review Boards).
`
`
`Section 505(o)(3)(E)(ii) of the FDCA requires you to report periodically on the status of
`any study or clinical trial required under this section. This section also requires you to
`periodically report to FDA on the status of any study or clinical trial otherwise
`
`undertaken to investigate a safety issue. Section 506B of the FDCA, as well as
`
`21 CFR 314.81(b)(2)(vii) requires you to report annually on the status of any
`postmarketing commitments or required studies or clinical trials.
`
`
`
`3 See the guidance for Industry Postmarketing Studies and Clinical Trials—Implementation of Section
`505(o)(3) of the Federal Food, Drug, and Cosmetic Act (October 2019).
`https://www.fda.gov/RegulatoryInformation/Guidances/default.htm.
`U.S. Food and Drug Administration
`
`
`Silver Spring, MD 20993
`www.fda.gov
`
`
`Reference ID: 4676373
`
`

`

`NDA 203214/S-026
`Page 5
`
`
`FDA will consider the submission of your annual report under section 506B and
`21 CFR 314.81(b)(2)(vii) to satisfy the periodic reporting requirement under section
`505(o)(3)(E)(ii) provided that you include the elements listed in 505(o) and
`21 CFR 314.81(b)(2)(vii). We remind you that to comply with 505(o), your annual report
`must also include a report on the status of any study or clinical trial otherwise
`undertaken to investigate a safety issue. Failure to submit an annual report for studies
`or clinical trials required under 505(o) on the date required will be considered a violation
`of FDCA section 505(o)(3)(E)(ii) and could result in enforcement action.
`
`PROMOTIONAL MATERIALS
`
`You may request advisory comments on proposed introductory advertising and
`promotional labeling. For information about submitting promotional materials, see the
`final guidance for industry Providing Regulatory Submissions in Electronic and Non-
`Electronic Format-Promotional Labeling and Advertising Materials for Human
`
`Prescription Drugs.4
`
`You must submit final promotional materials and Prescribing Information, 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 FDA.gov.5 Information and
`
` Instructions for completing the form can be found at FDA.gov.6
`
`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 any questions, call Elaine Sit, Regulatory Project Manager, at (301) 796-
`5073.
`
`
`
`
`Sincerely,
`
` {See appended electronic signature page}
`
`Nikolay P. Nikolov, MD
`Director (Acting)
`Division of Rheumatology and Transplant Medicine
`Office of Immunology and Inflammation
`Center for Drug Evaluation and Research
`
`
`
`
`ENCLOSURE(S):
`
`
` 4 For the most recent version of a guidance, check the FDA guidance web page at
`https://www.fda.gov/media/128163/download.
`5 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf
`
`
`6 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf
`
`
`U.S. Food and Drug Administration
`
`
`Silver Spring, MD 20993
`www.fda.gov
`
`
`
`
`Reference ID: 4676373
`
`

`

`NDA 203214/S-026
`Page 6
`
`
`
`
`
`  Content of Labeling
`o Prescribing Information
`
`o Medication Guide
`
`o
`
`Instructions for Use
`
`
`
`U.S. Food and Drug Administration
`
`
`Silver Spring, MD 20993
`www.fda.gov
`
`
`Reference ID: 4676373
`
`

`

`Signature Page 1 of 1
`--------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically. Following this are manifestations of any and all
`electronic signatures for this electronic record.
`--------------------------------------------------------------------------------------------
`/s/
`------------------------------------------------------------
`
`NIKOLAY P NIKOLOV
`09/25/2020 03:38:43 PM
`
`Reference ID: 4676373
`
`(
`
`
`
`