( .I# I U.S. FOOD & DRUG
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`ADMINISTRATION
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` NDA 203214/S-031
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`SUPPLEMENT APPROVAL
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` PF Prism C.V.
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` 500 Arcola Road
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` Collegeville, PA 19426
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`Attention: Alicia Holsey, MS
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`Director, Global Regulatory Affairs
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`Dear Ms. Holsey:
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`Please refer to your supplemental new drug application (sNDA) dated and received
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`September 10, 2021, and your amendments, submitted under section 505(b) of the
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`Federal Food, Drug, and Cosmetic Act (FDCA) for Xeljanz (tofacitinib).
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`We also refer to our letter dated August 23, 2021, notifying you, under Section 505(o)(4)
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`of the FDCA, of new safety information that we believe should be included in the
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`labeling for Janus kinase inhibitor (JAKi) products approved for inflammatory conditions.
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`This information pertains to the increased risks of major adverse cardiovascular events,
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`malignancy, thrombosis, and mortality upon the assessment of a postmarketing safety
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`study.
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`This supplemental new drug application provides for revisions to the labeling for Xeljanz
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`(tofacitinib), consistent with our August 23, 2021 safety labeling change notification
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`letter.
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`APPROVAL & LABELING
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`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
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`labeling.
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`Reference ID: 4898129
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` NDA 203214/S-031
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` Page 2
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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
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`content of labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format using
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`the FDA automated drug registration and listing system (eLIST), as described at
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`FDA.gov.1 Content of labeling must be identical to the enclosed labeling (text for the
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`Prescribing Information, Instructions for Use, and Medication Guide), with the addition of
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`any labeling changes in pending “Changes Being Effected” (CBE) supplements, as well
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`as annual reportable changes not included in the enclosed labeling.
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`Information on submitting SPL files using eList may be found in the guidance for
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`industry SPL Standard for Content of Labeling Technical Qs and As.2
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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 include labeling
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`changes for this NDA, including CBE supplements for which FDA has not yet issued an
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`action letter, with the content of labeling [21 CFR 314.50(l)(1)(i)] in Microsoft Word
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`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
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`highlighted or marked-up copy that shows all changes, as well as a clean Microsoft
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`Word version. The marked-up copy should provide appropriate annotations, including
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`supplement number(s) and annual report date(s).
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`PROMOTIONAL MATERIALS
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`You may request advisory comments on proposed introductory advertising and
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`promotional labeling. For information about submitting promotional materials, see the
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`final guidance for industry Providing Regulatory Submissions in Electronic and Non-
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`Electronic Format-Promotional Labeling and Advertising Materials for Human
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`Prescription Drugs.3
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` 1 http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm
`2 We update guidances periodically. For the most recent version of a guidance, check the FDA Guidance
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`Documents Database https://www.fda.gov/RegulatoryInformation/Guidances/default.htm.
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` 3 For the most recent version of a guidance, check the FDA guidance web page at
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` https://www.fda.gov/media/128163/download.
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`U.S. Food and Drug Administration
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`Silver Spring, MD 20993
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`www.fda.gov
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`Reference ID: 4898129
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` NDA 203214/S-031
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` Page 3
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` You must submit final promotional materials and Prescribing Information, accompanied
` by a Form FDA 2253, at the time of initial dissemination or publication
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` [21 CFR 314.81(b)(3)(i)]. Form FDA 2253 is available at FDA.gov.4 Information and
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`Instructions for completing the form can be found at FDA.gov.5
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`All promotional materials that include representations about your drug product must be
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`promptly revised to be consistent with the labeling changes approved in this
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`supplement, including any new safety information [21 CFR 314.70(a)(4)]. The revisions
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`in your promotional materials should include prominent disclosure of the important new
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`safety information that appears in the revised labeling. Within 7 days of receipt of this
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`letter, submit your statement of intent to comply with 21 CFR 314.70(a)(4).
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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 any questions, call Ms. June Germain, Safety Regulatory Project Manager,
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`at 301-796-4024.
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`Sincerely,
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`{See appended electronic signature page}
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`Ozlem Belen, MD, MPH
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`Deputy Director
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`Division of Rheumatology and Transplant
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`Medicine
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`Office of Immunology and Inflammation
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`Center for Drug Evaluation and Research
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`ENCLOSURE: Content of Labeling
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` 4 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf
`5 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf
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`U.S. Food and Drug Administration
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`Silver Spring, MD 20993
`www.fda.gov
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`Reference ID: 4898129
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`Signature Page 1 of 1
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`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.
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`/s/
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`OZLEM A BELEN
`12/02/2021 05:15:48 PM
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`Reference ID: 4898129
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