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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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` NDA 22406/S-004
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`Food and Drug Administration
`Silver Spring MD 20993
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`SUPPLEMENT APPROVAL
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`Janssen Research & Development, LLC
`Attention: Huy Q. Truong
`Associate Director, Global Regulatory Affairs
`920 Highway 202, South
`P.O. Box 300
`Raritan, NJ 08869
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`Dear Mr. Truong:
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`Please refer to your Supplemental New Drug Application (sNDA) dated May 1, 2012, received
`May 2, 2012, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act
`(FDCA) for XARELTO® (rivaroxaban) 15 and 20 mg immediate release tablets.
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`We acknowledge receipt of your amendments dated July 26, November 13, 15, 2012,
`January 11 and February 27, 2013.
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`This “Prior Approval” supplemental new drug application provides for an assessment of the
`relative bioavailability of rivaroxaban tablets when administered under various conditions and a
`food effect study.
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`We have completed our review of this supplemental application. It is approved, effective on the
`date of this letter, for use as recommended in the enclosed, agreed-upon labeling text.
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`We note that your February 27, 2013, submission includes final printed labeling (FPL) for your
`package insert and Medication Guide. We have not reviewed this FPL. You are responsible for
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`assuring that the wording in this printed labeling is identical to that of the approved content of
`labeling in the structured product labeling (SPL) format.
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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 the FDA
`automated drug registration and listing system (eLIST), as described at
`http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. Content
`of labeling must be identical to the enclosed labeling (text for the package insert 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.
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`Reference ID: 3269742
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` NDA 22406 S-004
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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 titled
`“SPL Standard for Content of Labeling Technical Qs and As at
`http://www.fda.gov/downloads/DrugsGuidanceComplianceRegulatoryInformation/Guidances/U
`CM072392.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 includes 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 MS Word format, that includes the
`changes approved in this supplemental application, as well as annual reportable changes and
`annotate each change. To facilitate review of your submission, 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).
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`CARTON AND IMMEDIATE CONTAINER LABELS
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`Submit final printed carton and container labels that are identical to the carton and immediate
`container labels submitted on May 2, 2012, as soon as they are available, but no more than 30
`days after they are printed.
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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
`active ingredients, 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(s) in pediatric 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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`Reference ID: 3269742
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` NDA 22406 S-004
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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
`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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`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion (OPDP)
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
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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 at http://www.fda.gov/opacom/morechoices/fdaforms/cder.html;
`instructions are provided on page 2 of the form. For more information about submission of
`promotional materials to the Office of Prescription 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
`(21 CFR 314.80 and 314.81).
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`If you have any questions, call Tyree Newman, Regulatory Project Manager, at (301) 796-3907.
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`Sincerely,
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`{See appended electronic signature page}
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`
`Edvardas Kaminskas, M.D.
`Deputy Director
`Division of Hematology Products
`Office of Hematology and Oncology Products
`Center for Drug Evaluation and Research
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`ENCLOSURE(S):
`Content of Labeling
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`Reference ID: 3269742
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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/
`----------------------------------------------------
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`EDVARDAS KAMINSKAS
`03/01/2013
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`Reference ID: 3269742
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