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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`NDA 022334/S-021, S-023, S-024
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`NDA 203985/S-002, S-004, S-005
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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 Corp.
`Attention: Lincy Thomas, Pharm.D., MBA
`Director, Drug Regulatory Affairs
`One Health Plaza
`East Hanover, NJ 07936
`
`Dear Dr. Thomas:
`
`Please refer to your supplemental new drug applications identified below, 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, and Afinitor Disperz (everolimus) Tablets for Oral Suspension,
`2 mg, 3 mg, and 5 mg.
`
`
`RECEIPT
`LETTER
`
`
` DATE
` DATE
`May 10, 2013 May 10, 2013
`
`
`
`June 18, 2013
`
`
`June 18, 2013
`
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`May 31, 2013 May 31, 2013
`
`
`
`
`
`
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`June 19, 2013
`
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`June 19, 2013
`
`
`PROPOSES:
`
`
`These “Prior Approval”
`supplemental new drug
`applications propose to add
`
`impaired wound healing to the
`
`WARNINGS AND
`PRECAUTIONS section of the
`Package Insert and to the Patient
`Package Insert.
`
`
`These “Prior Approval”
`supplemental new drug
`applications propose to add a
`Postmarketing Experience
`subsection to the ADVERSE
`REACTIONS section of the
`Package Insert and to add acute
`pancreatitis to this subsection.
`
`
`
` SUPPLEMENT PRODUCT
`
`022334/S-021
`
`203985/S-002
`
`022334/S-023
`
`203985/S-004
`
`Afinitor
`(everolimus)
`Tablets, 2.5 mg,
`5 mg, 7.5 mg, and
`10 mg
`
`Afinitor Disperz
`(everolimus)
`Tablets for Oral
`Suspension, 2 mg,
`3 mg, and 5 mg
`
`Afinitor
`(everolimus)
`Tablets, 2.5 mg,
`5 mg, 7.5 mg, and
`10 mg
`
`Afinitor Disperz
`(everolimus)
`Tablets for Oral
`Suspension, 2 mg,
`3 mg, and 5 mg
`
`
`Reference ID: 3458822
`
`

`

`NDA 022334/S-021, S-023, S-024
`NDA 203985/S-002, S-004, S-005
`Page 2
`
`
`022334/S-024
`
`203985/S-005
`
`May 31, 2013 May 31, 2013
`
`June 20, 2013
`
`
`June 21, 2013
`
`
`Afinitor
`(everolimus)
`Tablets, 2.5 mg,
`5 mg, 7.5 mg,
`and 10 mg
`
`Afinitor Disperz
`(everolimus)
`Tablets for Oral
`Suspension, 2 mg,
`3 mg, and 5 mg
`
`
`These “Prior Approval”
`supplemental new drug
`applications propose to revise
`the DOSAGE AND
`ADMINISTRATION,
`WARNINGS AND
`PRECAUTIONS, ADVERSE
`REACTIONS, DRUG
`INTERACTIONS, USE IN
`SPECIFIC POPULATIONS,
`CLINICAL
`PHARMACOLOGY,
`NONCLINICAL
`TOXICOLOGY, CLINICAL
`STUDIES, HOW SUPPLIED
`and STORAGE AND
`HANDLING sections of the
`Package Insert.
`
`
`We also refer to our approval letter dated February 20, 2013, which contained the following errors:
`
`The Approval letter references an incorrect NDA number for Afinitor. On page 1 of the
`Approval letter and in the Header on pages 2, 3, and 4:
`
`
`NDA 022234/S-021, S-023, S-024
`
`NDA 203985/S-002, S-004, S-005
`
`
`should be:
`
`
`
`
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`NDA 022334/S-021, S-023, S-024
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`NDA 203985/S-002, S-004, S-005
`
`
`
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`In addition, Table 9 of Section 6.4 of the Package Insert incorrectly duplicates the 'Hematology'
`
`
`section header.
`
`
`This replacement approval letter incorporates the correction of the errors. The effective approval
`
`date will remain February 20, 2013, the date of the original approval letter.
`
`
`
`We acknowledge receipt of your amendments to NDA 022334/S-021 dated August 23, 2013;
`
`
`November 1, 2013; November 13, 2013; November 25, 2013; and January 10, 2014, and your
`
`amendments to NDA 203985/S-002 dated August 23, 2013; November 1, 2013;
`
`November 13, 2013; November 25, 2013; and January 10, 2014.
`
`
`In addition, we acknowledge receipt of your amendments to NDA 022334/S-023 dated
`
`August 23, 2013; August 27, 2013; November 1, 2013; November 13, 2013;
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`November 25, 2013; and January 10, 2014, and your amendments to NDA 203985/S-004 dated
`
`
`Reference ID: 3458822
`
`

`

`NDA 022334/S-021, S-023, S-024
`NDA 203985/S-002, S-004, S-005
`Page 3
`
`August 23, 2013; August 28, 2013; November 1, 2013; November 13, 2013;
`
`November 25, 2013; and January 10, 2014.
`
`
`Also, we acknowledge receipt of your amendments to NDA 022334/S-024 dated
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`August 23, 2013; October 8, 2013; November 1, 2013; November 13, 2013; November 25, 2013;
`
`and January 10, 2014, and your amendments to NDA 203985/S-005 dated August 23, 2013;
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`October 8, 2013; October 18, 2013; November 1, 2013; November 13, 2013; November 25,
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`2013; and January 10, 2014.
`
`
`APPROVAL & LABELING
`
`We have completed our review of these supplemental applications, as amended. They are
`approved, effective on the date of this letter, for use as recommended in the enclosed, agreed-
`upon labeling text.
`
`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 the enclosed labeling (text for the package insert, text for the
`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.
`
`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
`
`
`
`The SPL will be accessible from publicly available labeling repositories.
`
`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).
`
`
`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
`
`Reference ID: 3458822
`
`

`

`NDA 022334/S-021, S-023, S-024
`NDA 203985/S-002, S-004, S-005
`Page 4
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`comments, (2) the proposed materials in draft or mock-up form with annotated references, and
`(3) the package insert(s) to:
`
`
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion (OPDP)
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
`
`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 or by fax to 301-847-8444.
`
`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 Frank Cross, Jr., Senior Regulatory Health Project Manager, at
`(301) 796-0876.
`
`Sincerely,
`
`
`{See appended electronic signature page}
`
`
`
`
`Amna Ibrahim, M.D.
`
`
`
`Deputy Division Director
`
`
`Division of Oncology Products 1
`
`Office of Hematology and Oncology Products
`
`Center for Drug Evaluation and Research
`
`
`ENCLOSURE:
`
`Content of Labeling
`
`Patricia Keegan, M.D.
`
`Director
`Division of Oncology Products 2
`Office of Hematology and Oncology Products
`Center for Drug Evaluation and Research
`
`Reference ID: 3458822
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`AMNA IBRAHIM
`02/20/2014
`
`PATRICIA KEEGAN
`02/20/2014
`
`Reference ID: 3458822
`
`