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` NDA 203214/S-24
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` NDA 208246/S-10
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`SUPPLEMENT APPROVAL
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` PF PRISM C.V.
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` c/o Pfizer Inc.
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` Attention: Gary F. Perry
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` Director, Pfizer Global Regulatory Affairs
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`
` 445 Eastern Point Road
` Groton, PA 06340
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` Dear Mr. Perry:
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` Please refer to your supplemental new drug applications (sNDAs) dated June 7, 2019,
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` submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA)
` for XELJANZ (tofacitinib) and XELJANZ XR (tofacitinib) tablets.
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` We also refer to our letter dated May 9, 2019, notifying you, under Section 505(o)(4) of
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` the FDCA, of new safety information that we believe should be included in the labeling
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` for XELJANZ (tofacitinib). This information pertains to the risk of thrombosis, pulmonary
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` embolism, and all-cause mortality among rheumatoid arthritis (RA) patients taking
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` tofacitinib 10 mg twice daily (BID) relative to those taking either tofacitinib 5 mg twice
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` daily or TNF blockers in the post-marketing requirement (PMR) Study A 3921133.
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` These supplemental new drug applications provide for revisions to the labeling for
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` XELJANZ (tofacitinib) and XELJANZ XL (tofacitinib) consistent with our May 9, 2019
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` letter.
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` APPROVAL & LABELING
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` We have completed our review of this application. It is approved, effective on the date of
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` this letter, for use as recommended in the enclosed agreed-upon labeling.
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` We note that your July 23, 2019, submissions include final printed labeling (FPL) for
` your Prescribing Information, and Medication Guide. We have not reviewed this FPL.
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` You are responsible for assuring that the wording in this FPL is identical to that of the
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` approved content of labeling in the structured product labeling (SPL) format.
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`Reference ID: 4467787
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`

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` NDA 203214/S-024
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` NDA 208246/S-010
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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
` 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 Prescribing
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` Information, and Medication Guide, with the addition of any labeling changes in pending
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`“Changes Being Effected” (CBE) supplements, as well as annual reportable changes
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` 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
`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
` 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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` 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) to the
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` address above, by fax to 301-847-8444, or electronically in eCTD format. For more
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` information about submitting promotional materials in eCTD format, see the draft
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` 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.
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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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` 1 http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm
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` 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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` 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: 4467787
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`

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` NDA 203214/S-024
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` NDA 208246/S-010
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` Page 3
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` If you have any questions, call Kelly Richards, Senior Regulatory Project Manager, at
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` (240) 402-4276.
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` Sincerely,
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` {See appended electronic signature page}
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` Joyce Korvick, M.D., M.P.H.
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` Deputy Director for Safety
` Division of Gastroenterology and Inborn Errors
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` Products
` Office of Drug Evaluation III
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` Center for Drug Evaluation and Research
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` ENCLOSURE(S):
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`• Content of Labeling
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`o Prescribing Information
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`o Medication Guide
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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: 4467787
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`

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`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/
`------------------------------------------------------------
`
`JOYCE A KORVICK
`07/25/2019 05:10:03 PM
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`Reference ID: 4467787
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`(
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