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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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` NDA 21880/S-045
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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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` Celgene Corporation
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` Attention: Marion Ceruzzi, PhD
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` Senior Director, Regulatory Affairs
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` 400 Connell Drive, Suite 7000
` Berkeley Heights, NJ 07922
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`Dear Dr. Ceruzzi:
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`Please refer to your Supplemental New Drug Application (sNDA) dated September 1, 2015,
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`received September 1, 2015, submitted under section 505(b) of the Federal Food, Drug, and
`Cosmetic Act (FDCA) for Revlimid® (lenalidomide) Capsules, 2.5, 5, 10, 15, 20 and 25 mg.
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`This “Changes Being Effected” supplemental new drug application provides for a modification
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`to the approved Revlimid (lenalidomide) risk evaluation and mitigation strategy (REMS).
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`APPROVAL & LABELING
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` We have completed our review of this supplemental application. It is approved, effective on the
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` date of this letter.
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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
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`active ingredients, new indications, new dosage forms, new dosing regimens, or new routes of
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`administration are required to contain an assessment of the safety and effectiveness of the
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`product for the claimed indication(s) in pediatric patients unless this requirement is waived,
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`deferred, or inapplicable.
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`Because none of these criteria applies to your application, you are exempt from this requirement.
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`RISK EVALUATION AND MITIGATION STRATEGY REQUIREMENTS
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` The REMS for Revlimid® (lenalidomide) Capsules was originally approved on August 3, 2010,
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` and the most recent modification was approved on September 13, 2015. The REMS consists of
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` elements to assure safe use (ETASU), an implementation system, and a timetable for submission
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` of assessments of the REMS. Your proposed modification to the REMS consists of removal of
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` the ICD-10 code from the Patient Prescription Forms (General Patient Prescription Form and
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` Veterans Administration Patient Prescription Form).
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`Reference ID: 3838478
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` NDA 21880/S-045
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` Page 2
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` Your proposed modified REMS, submitted on September 1, 2015, and appended to this letter, is
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` approved.
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`The timetable for submission of assessments of the REMS remains the same as that approved on
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`September 13, 2015.
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`There are no changes to the REMS assessment plan described in our September 13, 2015, letter.
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` We remind you that in addition to the REMS assessments submitted according to the timetable in
` the approved REMS, you must include an adequate rationale to support a proposed REMS
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` modification for the addition, modification, or removal of any goal or element of the REMS, as
` described in section 505-1(g)(4) of the FDCA.
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` We also remind you that you must submit a REMS assessment when you submit a supplemental
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` application for a new indication for use as described in section 505-1(g)(2)(A) of the FDCA.
` This assessment should include:
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` a) An evaluation of how the benefit-risk profile will or will not change with the new
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`indication;
` b) A determination of the implications of a change in the benefit-risk profile for the current
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` REMS;
` c) If the new indication for use introduces unexpected risks: A description of those risks
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` and an evaluation of whether those risks can be appropriately managed with the currently
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` approved REMS.
` d) If a REMS assessment was submitted in the 18 months prior to submission of the
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` supplemental application for a new indication for use: A statement about whether the
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` REMS was meeting its goals at the time of that last assessment and if any modifications
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` of the REMS have been proposed since that assessment.
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` e) If a REMS assessment has not been submitted in the 18 months prior to submission of the
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` supplemental application for a new indication for use: Provision of as many of the
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` currently listed assessment plan items as is feasible.
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`f) If you propose a REMS modification based on a change in the benefit-risk profile or
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` because of the new indication of use, submit an adequate rationale to support the
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` modification, including: Provision of the reason(s) why the proposed REMS
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` modification is necessary; the potential effect on the serious risk(s) for which the REMS
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` was required, on patient access to the drug, and/or on the burden on the health care
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` delivery system; and other appropriate evidence or data to support the proposed change.
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` Additionally, include any changes to the assessment plan necessary to assess the
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` proposed modified REMS. If you are not proposing REMS modifications, provide a
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` rationale for why the REMS does not need to be modified.
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` If the assessment instruments and methodology for your REMS assessments are not included in
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` the REMS supporting document, or if you propose changes to the submitted assessment
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` instruments or methodology, you should update the REMS supporting document to include
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` specific assessment instrument and methodology information at least 90 days before the
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` assessments will be conducted. Updates to the REMS supporting document may be included in a
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`Reference ID: 3838478
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` NDA 21880/S-045
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` Page 3
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` new document that references previous REMS supporting document submission(s) for
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` unchanged portions. Alternatively, updates may be made by modifying the complete previous
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` REMS supporting document, with all changes marked and highlighted. Prominently identify the
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` submission containing the assessment instruments and methodology with the following wording
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` in bold capital letters at the top of the first page of the submission:
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`NDA 21880 REMS CORRESPONDENCE
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`(insert concise description of content in bold capital letters, e.g.,
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`UPDATE TO REMS SUPPORTING DOCUMENT - ASSESSMENT
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`METHODOLOGY)
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`An authorized generic drug under this NDA must have an approved REMS prior to marketing.
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`Should you decide to market, sell, or distribute an authorized generic drug under this NDA,
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`contact us to discuss what will be required in the authorized generic drug REMS submission.
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`We remind you that section 505-1(f)(8) of FDCA prohibits holders of an approved covered
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`application with elements to assure safe use from using any element to block or delay approval
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`of an application under section 505(b)(2) or (j). A violation of this provision in 505-1(f) could
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`result in enforcement action.
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`Prominently identify any submission containing the REMS assessments or proposed
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`modifications of the REMS with the following wording in bold capital letters at the top of the
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`first page of the submission as appropriate:
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`NDA 21880 REMS ASSESSMENT
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`NEW SUPPLEMENT FOR NDA 21880/S-000
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`CHANGES BEING EFFECTED IN 30 DAYS
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`PROPOSED MINOR REMS MODIFICATION
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`or
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`or
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`NEW SUPPLEMENT FOR NDA 21880/S-000
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`PRIOR APPROVAL SUPPLEMENT
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`PROPOSED MAJOR REMS MODIFICATION
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`or
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`NEW SUPPLEMENT FOR NDA 21880/S-000
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`PRIOR APPROVAL SUPPLEMENT
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`PROPOSED REMS MODIFICATIONS DUE TO SAFETY LABEL CHANGES
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`SUBMITTED IN SUPPLEMENT XXX
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`NEW SUPPLEMENT (NEW INDICATION FOR USE)
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`Reference ID: 3838478
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` NDA 21880/S-045
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` Page 4
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` FOR NDA 21880/S-000
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` REMS ASSESSMENT
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` PROPOSED REMS MODIFICATION (if included)
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` Should you choose to submit a REMS revision, prominently identify the submission containing
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` the REMS revisions with the following wording in bold capital letters at the top of the first page
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` of the submission:
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`To facilitate review of your submission, we request that you submit your proposed modified
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`REMS and other REMS-related materials in Microsoft Word format. If certain documents, such
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`as enrollment forms, are only in PDF format, they may be submitted as such, but the preference
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`is to include as many as possible in Word format.
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`If you do not submit electronically, please send 5 copies of REMS-related submissions.
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`REPORTING REQUIREMENTS
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`We remind you that you must comply with reporting requirements for an approved NDA
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`(21 CFR 314.80 and 314.81).
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`If you have any questions, call Ms. Diane Leaman, Safety Regulatory Project Manager, at
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`(301) 796-1424.
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`REMS REVISIONS FOR NDA 21880
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`Sincerely,
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`{See appended electronic signature page}
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`Ann Farrell, MD
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`Director
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`Division of Hematology Products
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`Office Hematology Oncology Products
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`Center for Drug Evaluation and Research
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`ENCLOSURE:
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`REMS
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`Reference ID: 3838478
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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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`DIANE V LEAMAN
`10/27/2015
`for Ann Farrell, MD
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`Reference ID: 3838478
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