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` DEPARTMENT OF HEALTH & HUMAN SERVICES
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`Public Health Service
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`Food and Drug Administration
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`Rockville, MD 20857
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`SUPPLEMENT APPROVAL
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`RELEASE
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` POSTMARKETING
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`COMMITMENTS
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`NDA 021880/S-013
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`Celgene Corporation
`Attention: Michael B. Faletto
`Director, Regulatory Affairs
`86 Morris Avenue
`Summit, NJ 07901
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`Dear Mr. Faletto:
`
`Please refer to your supplemental new drug application (sNDA) dated September 19, 2008, submitted
`under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA) for Revlimid®
`(lenalidomide) 5, 10, 15 and 25 milligram Capsules.
`
`This supplemental application contains a proposed risk evaluation and mitigation strategy (REMS) for
`Revlimid® (lenalidomide) and was submitted in accordance with section 909(b)(1) of the Food and
`Drug Administration Amendments Act of 2007 (FDAAA). We note that NDA 021880 was approved
`under the provisions of 21 CFR 314.520 (Subpart H). Under section 909(b)(1) of FDAAA, we
`identified Revlimid® (lenalidomide) as a product deemed to have in effect an approved REMS
`because there were in effect on the effective date of FDAAA, March 25, 2008, elements to assure safe
`use required under 21 CFR 314.520.
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`We also refer to your submissions dated September 29, 2008, March 30, June 16, August 14, October
`9, 2009 and July 28, 2010.
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`In accordance with section 505-1 of the FDCA, we have determined that a REMS is necessary for
`Revlimid® (lenalidomide) to ensure the benefits of the drug outweigh the risk of teratogenicity. Your
`proposed REMS, submitted on September 19, 2008, as amended and appended to this letter, is
`approved. The REMS consists of a Medication Guide, elements to assure safe use, an implementation
`system, and the timetable for submission of assessments of the REMS. 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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`The REMS assessment plan should include, but is not limited to, the following information:
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`1. A report on periodic assessments of the distribution and dispensing of the Medication Guide in
`accordance with 21 CFR 208.24.
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`2. A summary of the RevAssist® program that includes the number of patients, pharmacies, and
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`prescribers registered in the program and an overall summary of the patient, pharmacy, and
`prescriber compliance with the RevAssist® program.
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`NDA 021880/S-013
`REMS
`Page 2
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`3. Patient registrations and demographics summary that includes the total number of registered
`patients, a summary of the patient demographics, and summaries of registered patients by risk
`category and diagnoses.
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`4. An assessment of healthcare provider and patient understanding regarding the safe-use of
`Revlimid® (lenalidomide) (i.e., the results of surveys administered to healthcare providers and
`patients).
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`5. Patient compliance - Information regarding the total number of completed mandatory patient
`surveys testing patient knowledge of risks and benefits as described in the product labeling or
`Medication Guide, the number of patient surveys with discrepancies, and the number of surveys
`with discrepancies by risk category. Discuss the types of discrepancies identified, conduct sub-
`analyses by high risk and low risk categories of patients, and address deviations from the
`RevAssist® program. Include information regarding the voluntary patient survey that assesses
`patients’ knowledge and compliance with risk reduction behaviors and birth control methods.
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`6. Summary of positive (and false positive) beta human chorionic gonadotrophin and/or urine
`pregnancy tests – A case summary of abnormal pregnancy test results, any reports of pregnancy,
`and the follow-up information. For each case, include the root cause analysis as to why the
`RevAssist® program was unsuccessful.
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`7. Prescriber compliance – Discuss prescriber compliance with the prescriber survey, pregnancy
`testing, and patient counseling.
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`8. Pharmacy procedures – Include an overview of pharmacy activity in terms of amount of drug
`dispensed, deviations from the RevAssist® program dispensing requirements, any pharmacy that is
`de-activated due to non-compliance, and a compliance assessment of the pharmacy component of
`the RevAssist® program.
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`9. Interventions – Provide a summary of the corrective actions developed and de-registrations, as well
`as a summary of the RevAssist® program complaints received and actions taken to address the
`complaints.
`The requirements for assessments of an approved REMS under section 505-1(g)(3) include, in section
`505-1(g)(3)(A), an assessment of the extent to which the elements to assure safe use are meeting the
`goal or goals to mitigate a specific serious risk listed in the labeling of the drug, or whether the goal or
`goals or such elements should be modified.
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`Assessments of an approved REMS must also include, under section 505-1(g)(3)(B) and (C),
`information on the status of any postapproval study or clinical trial required under section 505(o) or
`otherwise undertaken to investigate a safety issue. You can satisfy these requirements in your REMS
`assessments by referring to relevant information included in the most recent annual report required
`under section 506B and 21 CFR 314.81(b)(2)(vii) and including any updates to the status information
`since the annual report was prepared. Failure to comply with the REMS assessments provisions in
`505-1(g) could result in enforcement action.
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`We remind you that in addition to the assessments submitted according to the timetable included in the
`approved REMS, you must submit a REMS assessment and may propose a modification to the
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`NDA 021880/S-013
`REMS
`Page 3
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`approved REMS when you submit a supplemental application for a new indication for use as described
`in Section 505-1(g)(2)(A) of FDCA.
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`Prominently identify the amendment containing the REMS assessments or proposed modifications
`with the following wording in bold capital letters at the top of the first page of the submission:
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`NDA 021880 REMS ASSESSMENT
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`NEW SUPPLEMENT FOR NDA 021880
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`PROPOSED REMS MODIFICATION
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`REMS ASSESSMENT
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`NEW SUPPLEMENT (NEW INDICATION FOR USE)
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`FOR NDA 021880
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`REMS ASSESSMENT
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`PROPOSED REMS MODIFICATION (if included)
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`If you do not submit electronically, please send 5 copies of REMS-related submissions.
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`POSTMARKETING COMMITMENTS
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`The approval letter dated December 27, 2005, listed the following postmarketing commitments:
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`#4
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`You have agreed to submit a Pregnancy Exposure follow-up plan which will document your
`plan to follow-up pregnancy exposures to their outcome. This plan may be submitted as a post-
`marketing commitment.
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`You have agreed to submit an Evaluation Plan of RevAssist to FDA within 3 to 6 months of
`approval. Please include, at a minimum, plans to study the Pharmacy Audit Plan, Outcomes of
`Pregnancy Exposures, and the Knowledge Surveys of physicians, nurses, and patients.
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`#5
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`Because the requirement to develop a pregnancy exposure follow-up plan has been incorporated into
`the REMS, and you are now required to report all exposed pregnancies under section 505(k)(1) as
`described above, you are hereby released from PMC numbers 4 and 5.
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`DEAR HEALTHCARE PROFESSIONAL LETTER
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`If you decide to issue a letter communicating important safety-related information about this drug
`product (i.e., a “Dear Health Care Professional” letter), we request that you submit, at least 24 hours
`prior to issuing the letter, an electronic copy of the letter to this <NDA, BLA, or ANDA>, to
`CDERMedWatchSafetyAlerts@fda.hhs.gov, and to the following address:
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`MedWatch
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`Food and Drug Administration
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`Suite 12B-05
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`5600 Fishers Lane
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`Rockville, MD 20857
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`NDA 021880/S-013
`REMS
`Page 4
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`LABELING
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`As soon as possible, but no later than 14 days from the date of this letter, submit, using the FDA
`automated drug registration and listing system (eLIST), the content of labeling [21 CFR 314.50(l)] in
`structured product labeling (SPL) format, as described at
`http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm, that is
`identical to the enclosed labeling (text for the package insert and text for the Medication Guide)
`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/UCM07
`2392.pdf.
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`The SPL will be accessible from publicly available labeling repositories.
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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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`As part of the approval under Subpart H, as required by 21 CFR 314.550, you must submit all
`promotional labeling as well as advertisements at least 30 days before the intended time of initial
`distribution of the labeling or initial publication of the advertisement. Send one copy to the Division of
`Drug Oncology Products and two copies of the promotional materials and the package insert directly
`to:
`
`
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Division of Drug Marketing, Advertising, and Communications
`Food and Drug Administration
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
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`If you have any questions, please call Amy Baird, Regulatory Project Manager, at (301)796-2313.
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`Sincerely,
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`{See appended electronic signature page}
`
`
`Robert Justice, M.D., M.S.
`Director
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`Division of Drug Oncology Products
`Office of Oncology Drug Products
`Center for Drug Evaluation and Research
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`NDA 021880/S-013
`REMS
`Page 5
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`Enclosures:
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`Approved REMS
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`Medication Guide
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`Educational materials
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`RevAssist Enrollment forms
`Final product labeling
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`Application
`Type/Number
`--------------------
`NDA-21880
`NDA-21880
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`Submission
`Type/Number
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`SUPPL-13
`PMR/PMC-1
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`Submitter Name
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`Product Name
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`------------------------------------------
`--------------------
`CELGENE CORP REVLIMID(LENALIDOMIDE)
`CELGENE CORP REVLIMID(LENALIDOMIDE)
`
`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`ROBERT L JUSTICE
`08/03/2010
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