`
`
`
`DEPARTMENT OF HEALTH AND HUMAN SERVICES
`
`
`
`
`
`
` NDA 022334/S-038
`
`
`
`
`
`
`
`
`Food and Drug Administration
`
`
` Silver Spring MD 20993
`
`
`
`SUPPLEMENT APPROVAL
`
`
`
`
` Novartis Pharmaceuticals Corporation
` Attention: Katie Chon, Pharm.D.
`
` Director, Drug Regulatory Affairs, Oncology Global Development
`
`
` One Health Plaza
` East Hanover, NJ 07936
`
`
`
`
`
`Dear Dr. Chon:
`
`
`
`
`
`Please refer to your Supplemental New Drug Application (sNDA) dated February 1, 2016,
`
`
`
`
`
`received February 1, 2016, and your amendments, 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.
`
`
`
`
`
`
`This “Prior Approval” supplemental new drug application provides for the addition of pulmonary
`
`
`
`hypertension to WARNINGS AND PRECAUTIONS (Section 5.1) and heart failure to
`
`
`
`
`ADVERSE REACTIONS, Postmarketing Experience (Section 6.6) as requested in our
`
`Supplement Request letter dated October 14, 2015.
`
`
`APPROVAL & LABELING
`
`
`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
`
`
`text and with the minor editorial revision indicated below.
`
`
`1. The list of RECENT MAJOR CHANGES under the HIGHLIGHTS OF PRESCRIBING
`
`
`
`
`
`
`
`INFORMATION was reordered to match the section order as they appear in the FULL
`
`PRESCRIBING INFORMATION.
`
`
`
`CONTENT OF LABELING
`
`
`
`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, except with the revisions indicated, the enclosed labeling (text
`
`
`
`
`for the 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.
`
`Reference ID: 3944879
`
`
`
`
`
`
`
`
`
`
`
`
`
` NDA 022334/S-038
`
` Page 2
`
`
`
`
`
` Information on submitting SPL files using eLIST may be found in the guidance for industry title
`
` “SPL Standard for Content of Labeling Technical Qs and As” at
`
`
`http://www.fda.gov/downloads/DrugsGuidanceComplianceRegulatoryInformation/Guidances/U
`CM072392.pdf.
`
`
`The SPL will be accessible via publicly available labeling repositories.
`
`
`
`
`
` Also within 14 days, amend all pending supplemental applications 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 with the revisions
`
`
`
`
`
` indicated above 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).
`
`REQUIRED PEDIATRIC ASSESSMENTS
`
`
`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.
`
`
`Because none of these criteria apply to your application, you are exempt from this requirement.
`
`
`PROMOTIONAL MATERIALS
`
`
`
`
`
`
`
`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:
`
`
`
`OPDP Regulatory Project Manager
`
`Food and Drug Administration
`
`Center for Drug Evaluation and Research
`
`Office of Prescription Drug Promotion (OPDP)
`
`5901-B Ammendale Road
`
`Beltsville, MD 20705-1266
`
`
`
`
`
`Alternatively, you may submit a request for advisory comments electronically in eCTD format.
`For more information about submitting promotional materials in eCTD format, see the draft
`
`
`Guidance for Industry (available at:
`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
`CM443702.pdf ).
`
`
`
`
`Reference ID: 3944879
`
`
`
`
`
`
`
` NDA 022334/S-038
`
` Page 3
`
`
` You must submit final promotional materials and package insert(s), accompanied by a Form
`
`
`
` FDA 2253, at the time of initial dissemination or publication [21 CFR 314.81(b)(3)(i)]. Form
`
` 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.
`
`
`
`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, by fax to 301-847-8444, or
`
`
`
`
`electronically in eCTD format. For more information about submitting promotional materials in
`
`
`
`eCTD format, see the draft Guidance for Industry (available at:
`
`
`
`
`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
`CM443702.pdf ).
`
`
`
`REPORTING REQUIREMENTS
`
`
`We remind you that you must comply with reporting requirements for an approved NDA
`
`
`
`
`(21 CFR 314.80 and 314.81).
`
`
`
`
`If you have any questions, call Susan Jenney, Regulatory Project Manager, at (301) 796-0062.
`
`
`
`
`
`Sincerely,
`
`
`{See appended electronic signature page}
`
`
`Geoffrey Kim, M.D.
`
`Director
`
`Division of Oncology Products 1
`
`Office of Hematology and Oncology Products
`
`Center for Drug Evaluation and Research
`
`
`
`
`
`
`
`ENCLOSURE:
`
`Content of Labeling
`
`
`
`
`
`Reference ID: 3944879
`
`
`
`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`GEOFFREY S KIM
`06/14/2016
`
`Reference ID: 3944879
`
`