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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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` NDA 022334/S-027
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`Food and Drug Administration
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`Silver Spring MD 20993
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`SUPPLEMENT APPROVAL
`FULFILLMENT OF POSTMARKETING
`COMMITMENT
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`Novartis Pharmaceuticals Corporation
`Attention: Lincy Thomas, Pharm.D., MBA
`Director, Drug Regulatory Affairs
`One Health Plaza
`East Hanover, NJ 07936-1080
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`Dear Dr. Thomas:
`
`Please refer to your Supplemental New Drug Application (sNDA) dated March 18, 2014,
`received April 11, 2014, submitted under section 505(b) of the Federal Food, Drug, and
`Cosmetic Act (FDCA) for Afinitor® (everolimus) Tablets, 2.5 mg, 5 mg, 7.5 mg, and 10 mg.
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`We acknowledge receipt of your amendments dated April 24, 2014, July 24, 2014,
`September 19, 2014, October 10, 2014, October 15, 2014, and October 27, 2014.
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`This “Prior Approval” supplemental new drug application provides the final overall survival
`(OS) results for study CRAD001Y2301 (BOLERO-2) and updates Section 14.1 Advanced
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`Hormone Receptor-Positive, HER2-Negative Breast Cancer of the Package Insert.
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`APPROVAL & LABELING
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`We have completed our review of this supplemental application, as amended. It is approved,
`effective on the date of this letter, for use as recommended in the enclosed, agreed-upon labeling
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`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
`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, text for the
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`patient package insert), 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: 3675090
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`NDA 022334/S-027
`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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`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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`FULFILLMENT OF POSTMARKETING COMMITMENT
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`We have received your submission dated March 17, 2014, containing the final report for the
`following postmarketing commitment listed in the July 20, 2012, approval letter.
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`1899-1:
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`Submit a final report, including datasets, for the final overall survival results from
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`trial CRAD001Y2301 (BOLERO-2).
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`We have reviewed your submission and conclude that the above commitment was fulfilled.
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`We remind you that there is a postmarketing commitment listed in the July 20, 2012, approval
`letter that is still open.
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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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`Reference ID: 3675090
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`NDA 022334/S-027
`Page 3
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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/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf.
`Information and Instructions for completing the form can be found at
`http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf. 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 Frank Cross, Jr, Senior Regulatory Health Project Manager, at
`(301) 796-0876.
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`Sincerely,
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`{See appended electronic signature page}
`
`Amna Ibrahim, M.D.
`Acting Director
`Division of Oncology Products 1
`Office of Hematology and Oncology Products
`Center for Drug Evaluation and Research
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`ENCLOSURE:
`Content of Labeling
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`Reference ID: 3675090
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`
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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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`AMNA IBRAHIM
`12/18/2014
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`Reference ID: 3675090
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