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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`NDA 022334/S-025
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`NDA 203985/S-007
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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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`Novartis Pharmaceuticals Corporation
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`Attention: Lincy Thomas, Pharm.D.
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`Senior Associate Director, Drug Regulatory Affairs
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`One Health Plaza
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`East Hanover, NJ 07936-1080
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`Dear Dr. Thomas:
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`Please refer to your supplemental new drug applications dated October 18, 2013,
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`received October 18, 2013, submitted under section 505(b) of the Federal Food, Drug, and
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`Cosmetic Act for Afinitor® (everolimus) Tablets, 2.5 mg, 5 mg, 7.5 mg, and 10 mg, and
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`Afinitor® Disperz (everolimus) Tablets for Oral Suspension, 2 mg, 3 mg, and 5 mg.
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`We acknowledge receipt of your amendments dated February 13, 2014; March 4, 2014;
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`April 15, 2014; April 23, 2014; May 9, 2014; and June 9, 2014.
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`These “Prior Approval” supplemental new drug applications provide for the following:
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`1. Revision to Section 5.1, 5.2, to include information on opportunistic infection such as
`pneumocystis jiroveci pneumonia (PJP) as requested on April 9 and 15, 2014.
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`2. Revision to Section 6.6 Adverse Reactions, Postmarketing Experience, to add the
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`following events: cholecystitis, cholelithiasis, arterial thrombotic events and reflex
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`sympathetic dystrophy as requested in our Supplement Request letter dated
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`September 30, 2013.
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`3. Corresponding revisions have been made to HIGHLIGHTS OF PRESCRIBING
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`INFORMATION. Minor formatting revisions have also been made throughout the
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`labeling.
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`APPROVAL & LABELING
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`We have completed our review of these supplemental applications, as amended. They are
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`approved, effective on the date of this letter, for use as recommended in the enclosed,
`agreed-upon labeling text.
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`Reference ID: 3534929
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`NDA 022334/S-025
`NDA 203985/S-007
`Page 2
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`WAIVER OF HIGHLIGHTS SECTION
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`Please note that we have previously granted a waiver of the requirements of 21 CFR
`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
`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
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`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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`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
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` date(s).
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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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`Reference ID: 3534929
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`NDA 022334/S-025
`NDA 203985/S-007
`Page 3
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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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`All promotional materials that include representations about your drug product must be promptly
`revised to be consistent with the labeling changes approved in this supplement, including any
`new safety information [21 CFR 314.70(a)(4)]. The revisions in your promotional materials
`should include prominent disclosure of the important new safety information that appears in the
`revised package labeling. Within 7 days of receipt of this letter, submit your statement of intent
`to comply with 21 CFR 314.70(a)(4) to the address above or by fax to 301-847-8444.
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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}
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`Amna Ibrahim, M.D.
`Acting Director
`Division of Oncology Products 1
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`Office of Hematology and Oncology Products
`Center for Drug Evaluation and Research
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`ENCLOSURE:
`Content of Labeling
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`Patricia Keegan, M.D.
`Director
`Division of Oncology Products 2
`Office of Hematology and Oncology Products
`Center for Drug Evaluation and Research
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`Reference ID: 3534929
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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
`07/01/2014
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`JOSEPH E GOOTENBERG on behalf of PATRICIA KEEGAN
`07/01/2014
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`Reference ID: 3534929
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