`
`
`
`DEPARTMENT OF HEALTH AND HUMAN SERVICES
`
`
`
`
`
`
`NDA 021880/S-050
`
`
`
`
`
`
`Food and Drug Administration
`Silver Spring MD 20993
`
`SUPPLEMENT APPROVAL
`REMS MODIFICATION
`
`
`
`Celgene Corporation
`Attention: Lisa Suttner, MS, RAC
`Director, Regulatory Affairs
`86 Morris Ave
`Summit, NJ 07901
`
`
`Dear Ms. Suttner:
`
`Please refer to your Supplemental New Drug Application (sNDA) dated December 13, 2016,
`received December 13, 2016, and your amendments submitted under section 505(b) of the
`Federal Food, Drug, and Cosmetic Act (FDCA) for Revlimid® (lenalidomide) 2.5, 5, 10, 15, 20
`and 25 mg.
`
`This supplemental new drug application constitutes a major modification to the approved risk
`evaluation and mitigation strategy (REMS).
`
`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.
`
`RISK EVALUATION AND MITIGATION STRATEGY REQUIREMENTS
`
`The REMS for Revlimid® (lenalidomide) was originally approved on August 3, 2010, and the
`most recent modification was approved on February 22, 2017. 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 the following:
`1. Removal of reference to the previous REMS program names.
`2. Removal of the CD-ROM/desktop software as a method to enroll patients into the REMS.
`3. Addition of clarifying language regarding contraception use by patients enrolled in the
`REMS.
`
`Reference ID: 4116893
`
`
`
`NDA 021880/S-050
`Page 2
`
`
`
`4. Update the name of the Veterans Health Administration in the REMS document and
`materials.
`5. Addition of a tear-off quick reference guide for prescribers in the REMS at a Glance
`appended materials.
`6. Addition of REMS contraception information for patients to be used by non-prescribing
`healthcare providers.
`7. Addition of an updated brochure regarding emergency contraception.
`
`
`
`Your proposed modified REMS, submitted on December 13, 2016; amended April 6, 2016 and
`May 31, 2017, and appended to this letter, is approved.
`
`The timetable for submission of assessments of the REMS remains the same as that approved on
`September 13, 2015.
`
`There are no changes to the REMS assessment plan described in our January 25, 2017 letter.
`
`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
`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.
`
`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:
`
`
`a) An evaluation of how the benefit-risk profile will or will not change with the new
`indication;
`b) A determination of the implications of a change in the benefit-risk profile for the current
`REMS;
`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.
`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 the last assessment and if any modifications
`of the REMS have been proposed since that assessment.
`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.
`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
`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.
`
`Reference ID: 4116893
`
`
`
`NDA 021880/S-050
`Page 3
`
`
`
`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.
`
`
`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
`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:
`
`
`NDA 021880 REMS CORRESPONDENCE
`(insert concise description of content in bold capital letters, e.g.,
`UPDATE TO REMS SUPPORTING DOCUMENT - ASSESSMENT
`METHODOLOGY
`
`
`An authorized generic drug under this NDA must have an approved REMS prior to marketing.
`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.
`
`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.
`
`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:
`
`
`NDA 021880 REMS ASSESSMENT
`
`NEW SUPPLEMENT FOR NDA 021880/ S-000
`CHANGES BEING EFFECTED IN 30 DAYS
`PROPOSED MINOR REMS MODIFICATION
`
`
`
`NEW SUPPLEMENT FOR NDA 021880/ S-000
`PRIOR APPROVAL SUPPLEMENT
`PROPOSED MAJOR REMS MODIFICATION
`
`
`or
`
`or
`
`Reference ID: 4116893
`
`
`
`NDA 021880/S-050
`Page 4
`
`
`
`
`
`
`NEW SUPPLEMENT FOR NDA 021880/ S-000
`PRIOR APPROVAL SUPPLEMENT
`PROPOSED REMS MODIFICATIONS DUE TO SAFETY LABEL
`CHANGES SUBMITTED IN SUPPLEMENT XXX
`
`or
`
`
`NEW SUPPLEMENT (NEW INDICATION FOR USE)
`FOR NDA 021880/ S-000
`REMS ASSESSMENT
`PROPOSED REMS MODIFICATION (if included)
`
`
`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:
`
`
`
`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.
`
`If you do not submit electronically, please send 5 copies of REMS-related submissions.
`
`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 Laura Wall, Regulatory Project Manager, at (301) 796-2237.
`
`
`REMS REVISIONS FOR NDA 021880
`
`Sincerely,
`
`{See appended electronic signature page}
`
`Barry W. Miller, MS, CRNP
`Acting Deputy Director for Safety
`Division of Hematology Products
`Office of Hematology and Oncology Products
`Center for Drug Evaluation and Research
`
`
`ENCLOSURE:
`REMS
`
`
`
`Reference ID: 4116893
`
`
`
`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`BARRY W MILLER
`06/27/2017
`
`Reference ID: 4116893
`
`