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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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` NDA 21880/S-047
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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: Lisa Suttner, MS, RAC
`Director, Regulatory Affairs
`400 Connell Drive, Suite 7000
`Berkeley Heights, NJ 07922
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`Dear Ms. Suttner:
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`Please refer to your Supplemental New Drug Application (sNDA) dated February 25, 2016,
`received February 25, 2016, 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 minor
`modifications to the risk evaluation and mitigation strategy (REMS).
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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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`RISK EVALUATION AND MITIGATION STRATEGY REQUIREMENTS
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`The REMS for REVLIMID® (lenalidomide) was originally approved on August 3, 2010, and the
`most recent modification was approved on December 1, 2015. The REMS consists of elements
`to assure safe use, an implementation system, and a timetable for submission of assessments of
`the REMS. Your proposed modifications to the REMS consist of a change in contact
`information for emergency contraception information, addition of flow charts to the Prescriber
`Guide and the Patient Guide for clarity, adding clarifying language to the prescriber enrollment
`forms about the authorization number, add unacceptable forms of birth control to the Education
`and Counseling Checklist and Patient Prescriber Agreement Forms (PPAFs), replacement of
`“doctor” with “healthcare provider” throughout the PPAF, changing the trademark symbols to
`registered trademark symbols, and inserting a “Forgot Password” screenshot in the Celgene Risk
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`Management Website User Guide.
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`Reference ID: 3921494
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`NDA 21880/S-047
`Page 2
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`Your proposed modified REMS, submitted on February 25, 2016, and appended to this letter, is
`approved.
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`The timetable for submission of assessments of the REMS remains the same as that approved on
`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
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`the approved REMS, you must include an adequate rationale to support a proposed REMS
`modification for the addition, modification, or removal of any of 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
`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
`indication;
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`b) A determination of the implications of a change in the benefit-risk profile for the current
`REMS;
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`c) If the new indication for use introduces unexpected risks: A description of those risks
`and an evaluation of whether those risks can be appropriately managed with the currently
`approved REMS.
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`d) If a REMS assessment was submitted in the 18 months prior to submission of the
`supplemental application for a new indication for use: A statement about whether the
`REMS was meeting its goals at the time of that the last assessment and if any
`modifications 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
`supplemental application for a new indication for use: Provision of as many of the
`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
`because of the new indication of use, submit an adequate rationale to support the
`modification, including: Provision of the reason(s) why the proposed REMS
`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
`delivery system; and other appropriate evidence or data to support the proposed change.
`Additionally, include any changes to the assessment plan necessary to assess the
`proposed modified REMS. If you are not proposing REMS modifications, provide a
`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
`the REMS supporting document, or if you propose changes to the submitted assessment
`instruments or methodology, you should update the REMS supporting document to include
`specific assessment instrument and methodology information at least 90 days before the
`assessments will be conducted. Updates to the REMS supporting document may be included in a
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`Reference ID: 3921494
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`NDA 21880/S-047
`Page 3
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`new document that references previous REMS supporting document submission(s) for
`unchanged portions. Alternatively, updates may be made by modifying the complete previous
`REMS supporting document, with all changes marked and highlighted. Prominently identify the
`submission containing the assessment instruments and methodology with the following wording
`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,
`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
`application with elements to assure safe use from using any element to block or delay approval
`of an application under section 505(b)(2) or (j). A violation of this provision in 505-1(f) could
`result in enforcement action.
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`Prominently identify any submission containing the REMS assessments or proposed
`modifications of the REMS with the following wording in bold capital letters at the top of the
`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
`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: 3921494
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`NDA 21880/S-047
`Page 4
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`FOR NDA 21880/S-000
` REMS ASSESSMENT
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`PROPOSED REMS MODIFICATION (if included)
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`REMS REVISIONS FOR NDA 21880
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`Should you choose to submit a REMS revision, prominently identify the submission containing
`the REMS revisions with the following wording in bold capital letters at the top of the first page
`of the submission:
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`To facilitate review of your submission, we request that you submit your proposed modified
`REMS and other REMS-related materials in Microsoft Word format. If certain documents, such
`as enrollment forms, are only in PDF format, they may be submitted as such, but the preference
`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
`(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
`(301) 796-1424.
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`Sincerely,
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`{See appended electronic signature page}
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`Barry W. Miller
`Acting Deputy Director for Safety
`Division of Hematology Products
`Office of Hematology Products
`Center for Drug Evaluation and Research
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`ENCLOSURE:
`REMS
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`Reference ID: 3921494
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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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`BARRY W MILLER
`04/22/2016
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`Reference ID: 3921494
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