` NDA 202439/S-031
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`NDA 022406/S-035
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` SUPPLEMENT APPROVAL
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`Janssen Pharmaceuticals Inc.
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`Attention: Purve Patel
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`Director, Global Regulatory Affairs
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`920 US Highway 202, PO Box 300
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`Raritan, NJ 08869-0602
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`Dear Ms. Patel:
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`Please refer to your supplemental new drug application (sNDA) for NDA 202439 dated 12 June
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`2019, received 12 June 2019, and your amendments, submitted under section 505(b) of the
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`Federal Food, Drug, and Cosmetic Act (FDCA) for Xarelto (rivaroxaban) tablets.
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`We also refer to your supplemental new drug application (sNDA) for NDA 022406 dated 21
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`February 2020, received 21 February 2020, submitted under Section 505(b) for Xarelto
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`(rivaroxaban) tablets.
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`These Prior Approval supplemental new drug applications provide for changes to the WARNING
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`& PRECAUTIONS section of the package insert, Section 5.8 ‘Patients with Prosthetic Heart
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`Valves’ based on the GALILEO trial as well as minor modifications.
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`APPROVAL & LABELING
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`We have completed our review of these applications, as amended. They are approved, effective
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`on the date of this letter, for use as recommended in the enclosed agreed-upon labeling.
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`WAIVER OF ½ PAGE LENGTH REQUIREMENT FOR HIGHLIGHTS
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`Please note that we have previously granted a waiver of the requirements of 21 CFR
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`201.57(d)(8) regarding the length of Highlights of Prescribing Information.
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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 FDA.gov.1 Content of
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`labeling must be identical to the enclosed labeling (text for the Prescribing Information and
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`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
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`enclosed labeling.
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` 1 http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm
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`Reference ID: 4572803
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` NDA 202439/S-031
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` NDA 022406/S-035
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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 SPL
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`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 changes
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`for this NDA, including CBE supplements for which FDA has not yet issued an action letter, with
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`the content of labeling [21 CFR 314.50(l)(1)(i)] in Microsoft Word format, that includes the
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`changes approved in this supplemental application, as well as annual reportable changes. To
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`facilitate review of your submission(s), provide a highlighted or marked-up copy that shows all
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`changes, as well as a clean Microsoft Word version. The marked-up copy should provide
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`appropriate annotations, including supplement number(s) and annual report date(s).
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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 (which includes new salts and new fixed combinations), new indications, new
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`dosage forms, new dosing regimens, or new routes of administration are required to contain an
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`assessment of the safety and effectiveness of the product for the claimed indication in pediatric
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`patients unless this requirement is waived, 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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`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
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`comments, (2) the proposed materials in draft or mock-up form with annotated references, and
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`(3) the Prescribing Information to:
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`OPDP Regulatory Project Manager
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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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`Alternatively, you may submit a request for advisory comments electronically in eCTD format.
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`For more 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-Electronic
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`Format-Promotional Labeling and Advertising Materials for Human Prescription Drugs.3
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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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` 3 When final, this guidance will represent the FDA’s current thinking on this topic. For the most recent version of
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` a guidance, check the FDA guidance web page at
` 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: 4572803
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` NDA 202439/S-031
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` NDA 022406/S-035
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` Page 3
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`You must submit final promotional materials and Prescribing Information, accompanied by a
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`Form 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 FDA.gov.4 Information and Instructions for completing the form can be
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`found at FDA.gov.5 For more information about submission of promotional materials to the
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`Office of Prescription Drug Promotion (OPDP), see FDA.gov.6
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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 Bridget Kane, Regulatory Project Manager, at (240) 402-2170.
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`Sincerely,
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`{See appended electronic signature page}
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`Norman Stockbridge, MD, PhD
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`Director
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`Division of Cardiovascular and Renal Products
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`Office of Drug Evaluation I
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`Center for Drug Evaluation and Research
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`ENCLOSURE:
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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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`Cc:
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`Janssen Pharmaceuticals, Inc.
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`Attention: Huy Truong
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`Associate Director, Global Regulatory Affairs
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`920 U.S. Highway 202, PO Box 300
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`Raritan, NJ 08869-0602
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` 4 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf
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` 5 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf
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` 6 http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.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: 4572803
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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/
`------------------------------------------------------------
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`NORMAN L STOCKBRIDGE
`03/10/2020 09:45:29 AM
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`Reference ID: 4572803
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`(
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