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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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` NDA 022406/S-019
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` NDA 022406/S-020
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`Food and Drug Administration
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` Silver Spring MD 20993
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`SUPPLEMENT APPROVAL
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` Janssen Pharmaceuticals, Inc.
` c/o Janssen Research and Development, LLC.
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` Attention: Purve Patel
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` Director, Global Regulatory Affairs
` 920 U.S. Highway 202 South
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` P.O. Box 300
` Raritan, NJ 08869
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`Dear Mr. Patel:
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`Please refer to your Supplemental New Drug Applications (sNDAs) dated February 25, 2016
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`(S-019) and February 26, 2016 (S-020), received February 25, 2016 and February 26, 2016,
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`respectively, and your amendments, submitted under section 505(b) of the Federal Food, Drug,
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`and Cosmetic Act (FDCA) for Xarelto® (rivaroxaban) tablets, 10 mg, 15 mg, and 20 mg.
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`Supplement 019 is a Prior Approval supplemental new drug application that provides for updates
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`to Section 5.3 Spinal/Epidural Anesthesia or Puncture to clarify information regarding removal
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`of epidural catheters in patients who have received rivaroxaban which takes into account the
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`clinical PK and plasma elimination.
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`Supplement 020 is a “Changes Being Effected” supplemental new drug application provides for
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`updates to the physician sample pack (for 15 mg and 20 mg): label was updated to add a color
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`band and improve readability; the count was changed from 5 tablets to 7 tablets each to better
`align with dosing for XARELTO® (rivaroxaban).
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` APPROVAL & LABELING
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`We have completed our review of these supplemental applications. It is approved, effective on
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`the date of this letter, for use as recommended in the enclosed, agreed-upon labeling text.
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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
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`at http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm.
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`Content of labeling must be identical to the enclosed labeling (text for the package insert,
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`Reference ID: 3977521
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` NDA 022406/S-019
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` NDA 022406/S-020
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` Page 2
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` Medication Guide), with the addition of any labeling changes in pending “Changes Being
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` Effected” (CBE) supplements, as well as annual reportable changes not included in the enclosed
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`labeling.
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`Information on submitting SPL files using eList may be found in the guidance for industry titled
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`“SPL Standard for Content of Labeling Technical Qs and As”
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`at http://www.fda.gov/downloads/DrugsGuidanceComplianceRegulatoryInformation/Guidances/
`UCM072392.pdf.
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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 the content of labeling [21 CFR 314.50(l)(1)(i)] in MS Word format, that includes the
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`changes approved in this supplemental application, as well as annual reportable changes and
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` annotate each change. To facilitate review of your submission, provide a highlighted or marked-
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` up copy that shows all changes, as well as a clean Microsoft Word version. The marked-up copy
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` should provide appropriate annotations, including supplement number(s) and annual report
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` date(s).
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`CARTON AND IMMEDIATE CONTAINER LABELS
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`Submit final printed carton and immediate container labels that are identical to the carton and
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`immediate-container labels submitted on February 26, 2016, as soon as they are available, but no
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`more than 30 days after they are printed. Please submit these labels electronically according to
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`the guidance for industry Providing Regulatory Submissions in Electronic Format – Human
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`Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications
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`(June 2008). Alternatively, you may submit 12 paper copies, with 6 of the copies individually
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`mounted on heavy-weight paper or similar material. For administrative purposes, designate this
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`submission “Final Printed Carton and Container Labels for approved NDA 022046/S-020.”
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`Approval of this submission by FDA is not required before the labeling is used.
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`Marketing the product(s) with FPL that is not identical to the approved labeling text may render
`the product misbranded and an unapproved new drug.
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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, 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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`Reference ID: 3977521
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` NDA 022406/S-019
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` NDA 022406/S-020
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` Page 3
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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
`comments, (2) the proposed materials in draft or mock-up form with annotated references, and
`(3) the package insert(s) 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 (available
`at: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidance
`s/UCM443702.pdf).
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`You must submit final promotional materials and package insert(s), accompanied by a Form
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`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
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`at http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf.
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`Information and Instructions for completing the form can be found
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`at http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf.
`For more information about submission of promotional materials to the Office of Prescription
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`Drug Promotion (OPDP),
`see http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm.
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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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`Reference ID: 3977521
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` NDA 022406/S-019
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` NDA 022406/S-020
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` Page 4
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` If you have any questions, call Alycia Anderson, Regulatory Project Manager, at (240) 402­
` 4270.
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` Sincerely,
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`{See appended electronic signature page}
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`Ann T. Farrell, MD
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`Director
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`Division of Hematology Products
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`Office of Hematology and Oncology Products
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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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`Carton and Container Labeling
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`Reference ID: 3977521
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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/
`----------------------------------------------------
`
`ALYCIA C ANDERSON
`08/25/2016
`Signing for Ann T. Farrell, MD
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`Reference ID: 3977521
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