`NDA 021880/S-054
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`
`
`
` SUPPLEMENT APPROVAL
`
` REMS MODIFICATION
`
`
`
`Celgene Corporation
`
`Attention: Lisa Suttner, MS, RAC
`
`Director, Regulatory Affairs
`
`556 Morris Avenue
`
`
`Summit, NJ 07901
`
`
`
`Dear Ms. Suttner:
`
`
`
`
`Please refer to your supplemental new drug application dated and received
`
`
`December 8, 2017, and your amendments, submitted under section 505(b) of the
`
`
`Federal Food, Drug, and Cosmetic Act (FDCA) for Revlimid (lenalidomide) capsules.
`
`
`
`
`We acknowledge receipt of your amendment dated February 15, 2019, which
`
`
`
`
`constituted a complete response to our June 6, 2018, action letter. We also refer to
`
`
`your REMS amendments received August 16, 2019, February 7, 2020, and
`
`April 1, 2020.
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`
`
`
`
`This Prior Approval supplemental new drug application provides for modifications to the
`
`
`approved Revlimid (lenalidomide) risk evaluation and mitigation strategy (REMS).
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`
`
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`We have completed our review of this supplemental application, as amended. It is
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`approved effective on the date of this letter.
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`RISK EVALUATION AND MITIGATION STRATEGY (REMS) REQUIREMENTS
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`The REMS for Revlimid (lenalidomide) was originally approved on August 3, 2010, and
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`the most recent REMS modification was approved on May 28, 2019. The REMS
`
`consists of elements to assure safe use, an implementation system, and a timetable for
`
`submission of assessments of the REMS.
`
`
`
`Your proposed modification to the REMS establishes a shared system (SS) REMS for
`
`
`
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`the elements to assure safe use and the implementation system required for the
`
`
`
`reference listed drug (RLD) Revlimid (lenalidomide) and ANDAs referencing Revlimid
`
`(lenalidomide) called the lenalidomide REMS Program, which will become applicable on
`
`
`
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`the date of full approval of the first ANDA joining a shared system with Revlimid. The
`
`modification being approved results in a two-part REMS consisting of: (1) the
`
`
`requirements of the previously approved Revlimid REMS, and (2) the new shared
`
`
`system REMS for lenalidomide products. The requirements of the previously approved
`
`
`
`
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`Revlimid REMS will remain applicable until full approval of the first ANDA joining a
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`Reference ID: 4675177
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`

`

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` NDA 021880/S-054
` Page 2
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`shared system with Revlimid, at which time, they will automatically be replaced by the
`requirements of the shared system.
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`
`
` Your proposed modified REMS, submitted on April 1, 2020, amended and appended to
`
` this letter, is approved.
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`
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`The timetable for submission of assessments of the modified REMS remains the same
`
`as that approved on September 13, 2015.
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`
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`The REMS assessment plan applicable to the previously approved Revlimid REMS
`
`
`
`
`
`must include, but is not limited to, the following:
`
`
`Health Outcomes and/or Surrogates of Health Outcomes
`
`
`1. Pregnancies: (per reporting period and cumulatively)
`
`
`a. Number of pregnancies reported
`
`
`
`b. Outcome of each pregnancy
`
`
`
`c. Follow-up of outstanding pregnancy reports
`
`
`
`d. Root cause analysis of each reported pregnancy
`
`
`e. Link to most recent Periodic Safety Update Report (PSUR) or Periodic
`
`
`
`Benefit-Risk Evaluation Report (PBRER) that provides information on
`
`worldwide pregnancies. Discussion of any new information provided in the
`
`PSUR or PBRER regarding pregnancy
`
`
`
`Program Implementation and Operations
`
`
`
`2. Reporting on the restricted distribution program: (per current and previous two
`
`
`reporting periods and cumulatively; where applicable)
`
`
`a. The number of pharmacies and physicians certified, and patients enrolled
`
`
`
`b. Patient demographics for the current REMS assessment reporting period to
`
`
`
`include gender, age, diagnosis, females of reproductive potential (FRP)
`
`
`
`c. Number of female patients for whom pregnancy testing can be discontinued
`
`
`
`
`because menopause has been documented by follicle-stimulating
`
`hormone/luteinizing hormone (FSH/LH) levels
`
`
`3. Data on the use of the mobile device application to conduct REMS functions (per
`
`
`
`
`current and previous two reporting periods and cumulatively)
`
`a. Number of downloads of the mobile application
`
`
`
`
`
`b. Uses of the mobile application, and the functions conducted via the mobile
`
`
`
`
`application
`
`c. Number of prescribers using the mobile application for REMS functions, the
`
`
`
`
`
`number of instances of using the mobile application, and the functions
`
`
`conducted via the mobile application
`
`
`
`
`
`U.S. Food and Drug Administration
`
`Silver Spring, MD 20993
`
`www.fda.gov
`
`
`
`Reference ID: 4675177
`
`

`

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` NDA 021880/S-054
` Page 3
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` 4. REMS Pharmacy Compliance (per current reporting period and previous two
`
`
` reporting periods and for 5c. and 5d. cumulatively beginning June 4, 2018)
` a. Provide a copy of the Non-Compliance plan to include the following:
`
`
`
`
` i. Criteria for non-compliance
`
`
`
` ii. Actions taken to address non-compliance for each event identified
`
` iii. Criteria for de-certification
`
` b. Provide a copy of the audit plan
`
`
`
` c. Report of audit findings
`
`
`
` i. The number of audits expected, and the number of audits conducted
`
`
` ii. The number and type of deficiencies noted
`
`
`
` 1. Number that successfully completed a corrective and preventative
`
`
` (CAPA) plan within 30 days of receipt of CAPA
` 2. Describe actions taken for any that did not complete the CAPA
`
` within 30 days of receipt of CAPA
`
`
` 3. Include a unique ID for each pharmacy that had deviations to track
`
`
` deviations over time
`
`
`
` i. Documentation of completion of training for relevant staff
`
`
` ii. The existence of documented processes and procedure for
`
` complying with the REMS
`
`
` d. Non-compliance events: for each event provide the following
`
` i. Source of the report
`
`
`
` ii. Description of the event
`
` iii. Cause of the event
`
`
`
` iv. Corrective actions taken
`
` v. Events:
`
` 1. Number of Revlimid prescriptions dispensed that were written by
`
`
` non-certified prescribers
` 2. Number of Revlimid prescriptions dispensed by non-certified
`
`
` pharmacies
` 3. Number of Revlimid prescriptions dispensed to de-enrolled or non-
`
`
` enrolled patients
` 4. Number of times a Revlimid prescription was dispensed because a
`
`
`
` certified pharmacy bypassed REMS authorization processes
` 5. Number of shipments sent to non-certified pharmacies, sources of
`
`
`
`
`
` the reports, and actions taken to prevent future occurrences
` 6. Number of pharmacies who were de-certified for non-compliance
`
`
`
` and reasons for de-certification
`
`
`
`Safe Use Behaviors
`
`
`
`
`5. Documentation of safe use conditions (per current and previous two reporting
`
`
`periods and cumulatively, where applicable)
`
`
`
`
`
`
`
`U.S. Food and Drug Administration
`
`Silver Spring, MD 20993
`
`www.fda.gov
`
`
`
`Reference ID: 4675177
`
`

`

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` NDA 021880/S-054
` Page 4
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` Based on information collected from the mandatory surveys (used to document
`
`
`
`
` safe use conditions) provide information that could represent potential fetal
` exposure or that might result in a delay or interruption in treatment.
`
`
`
`
`
`Provide the following in a tabular format:
`
`
`
`
`a. The total number of authorization numbers issued and the number of
`
`authorization numbers flagged.
`
`
`b. The number and proportion of flagged authorization numbers intended for an
`
`FRP due to questions in the mandatory surveys related to pregnancy testing
`
`
`
`c. The number and proportion of flags that caused a delay in treatment initiation
`
`
`
`
`or a gap in therapy for patients due to REMS processes as the proportion of
`
`flagged authorization numbers compared to total authorization numbers.
`
`
`
`
`Include the time to resolution of flags in days (mean, minimum, maximum) for
`
`the reporting period and for each previous reporting period. Include the
`
`
`
`number of patients with a delay in treatment or a gap in therapy due to REMS
`
`processes.
`
`
`
`
`Knowledge, Attitude, Behavior
`
`
`6. Inform prescribers, patients, and pharmacists on the serious risks and safe-use
`
`
`
`
`conditions for Revlimid/lenalidomide (per current reporting period and previous
`
`
`two reporting periods beginning June 4, 2018)
`
`
`
`a. Ensure that Revlimid will only be dispensed to patients enrolled in the
`
`
`Revlimid REMS Program with evidence or other documentation of safe-use
`conditions
`
`i. Number and proportion of total number of unflagged patient survey
`
`
`
`questions answered relating to knowledge compared to the total number
`
`
`of patient survey questions relating to knowledge reported per patient
`
`risk category
`
`b. Ensure healthcare providers counsel patients on the benefits and risks of
`
`
`
`Revlimid therapy, including risks described in the boxed warnings
`
`i. Number and proportion of total number of unflagged prescriber surveys
`
`
`compared to the total number of prescriber surveys reported per risk
`
`category
`
`
`
`c. Educate pharmacies on the risks and safe-use conditions of Revlimid
`
`
`
`i. Total number of pharmacy quizzes administered
`
`
`ii. Number of pharmacists with a passing rate/Total number of certified
`
`
`
`pharmacists on the last day of the reporting period
`
`
`
`7. The requirements for assessments of an approved REMS under section 505­
`
`
`
`1(g)(3) include, with respect to each goal included in the strategy, an assessment
`
`of the extent to which the approved strategy, including each element of the
`strategy, is meeting the goal or whether one or more such goals or such
`
`elements should be modified.
`
`
`
`
`U.S. Food and Drug Administration
`
`Silver Spring, MD 20993
`
`www.fda.gov
`
`
`
`Reference ID: 4675177
`
`

`

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` NDA 021880/S-054
` Page 5
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` The REMS Assessment Plan applicable to the Lenalidomide shared system REMS
`
`
`
`
`
` must include, but is not limited to, the following items:
`
` Health Outcomes and/or Surrogates of Health Outcomes
`
`
`
`
`
` 1. Pregnancies: (per reporting period and cumulatively)
`
`
`
` a. Number of pregnancies reported
`
` b. Outcome of each pregnancy
`
`
`
`
` c. Follow-up of outstanding pregnancy reports
`
`
`
` d. Root cause analysis of each reported pregnancy
`
`
` e. Link to most recent Periodic Safety Update Report (PSUR) or Periodic
`
`Benefit-Risk Evaluation Report (PBRER) that provides information on
`worldwide pregnancies. Discussion of any new information provided in the
`
`PSUR or PBRER regarding pregnancy.
`
`
`
`
`
`Program Implementation and Operations
`
`
`
`
`
`
`
`2. Reporting on the restricted distribution program: (per current and previous two
`
`
`reporting periods and cumulatively; where applicable)
`
`
`a. The number of pharmacies and physicians certified, and patients enrolled
`
`
`
`b. Patient demographics for the current REMS assessment reporting period to
`
`
`
`include gender, age, diagnosis, females of reproductive potential (FRP)
`
`
`
`c. Number of female patients for whom pregnancy testing can be discontinued
`
`
`
`because menopause has been documented by follicle-stimulating
`
`hormone/luteinizing hormone (FSH/LH) levels
`
`
`3. Data on the use of the mobile device application to conduct REMS functions (per
`
`
`
`current and previous two reporting periods and cumulatively)
`
`a. Number of downloads of the mobile application
`
`
`
`
`
`b. Uses of the mobile application, and the functions conducted via the mobile
`
`
`
`
`application
`
`c. Number of prescribers using the mobile application for REMS functions, the
`
`
`
`
`
`number of instances of using the mobile application, and the functions
`
`
`
`conducted via the mobile application
`
`
`4. REMS Pharmacy Compliance (per current and previous two reporting periods
`
`
`and cumulatively; where applicable)
`
`
`a. Provide a copy of the Non-Compliance plan to include the following:
`
`
`
`
`i. Criteria for non-compliance
`
`
`ii. Actions taken to address non-compliance for each event identified
`
`
`
`iii. Criteria for de-certification
`
`
`b. Provide a copy of the audit plan
`
`
`
`c. Report of audit findings
`
`
`
`i. The number of audits expected, and the number of audits conducted
`
`
`
`
`
`
`
`
`U.S. Food and Drug Administration
`
`Silver Spring, MD 20993
`
`www.fda.gov
`
`
`
`Reference ID: 4675177
`
`

`

`
`
`
` NDA 021880/S-054
` Page 6
`
`
`
`
`
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` ii. The number and type of deficiencies noted
`
`
`
`
` 1. Number that successfully completed a corrective and preventative
`
` (CAPA) plan within 30 days of receipt of CAPA
` 2. Describe actions taken for any that did not complete the CAPA
`
` within 30 days of receipt of CAPA
`
`
` 3. Include a unique ID for each pharmacy that had deviations to track
`
`
` deviations over time
`
` iii. Documentation of completion of training for relevant staff
`
`
`
`
` iv.
`
` The existence of documented processes and procedure for complying
`
` with the REMS
`
` d. Non-compliance events: for each event provide the following
`
` i. Source of the report
`
`
`
` ii. Description of the event
`
` iii. Cause of the event
`
`
`
` iv. Corrective actions taken
`
` v. Events:
`
` 1. Number of lenalidomide prescriptions dispensed that were written
`
`
` by non-certified prescribers
` 2. Number of lenalidomide prescriptions dispensed by non-certified
`
`
`
` pharmacies
` 3. Number of lenalidomide prescriptions dispensed to de-enrolled or
`
`
` non-enrolled patients
` 4. Number of times a lenalidomide prescription was dispensed
`
`
`
`because a certified pharmacy bypassed REMS authorization
`
` processes
` 5. Number of shipments sent to non-certified pharmacies, sources of
`
`
`
`
`
` the reports, and actions taken to prevent future occurrences
` 6. Number of pharmacies who were de-certified for non-compliance
`
`
`
` and reasons for de-certification
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Safe Use Behaviors
`
`
`
`5. Documentation of safe use conditions (per current and previous two reporting
`
`
`periods and cumulatively; where applicable)
`
`
`
`
`Based on information collected from the mandatory surveys (used to document
`
`
`safe use conditions) provide information that could represent potential fetal
`
`
`
`exposure or that might result in a delay or interruption in treatment.
`
`
`
`Provide the following in a tabular format:
`
`
`a. The total number of authorization numbers issued, and the number of
`
`
`
`
`authorization numbers flagged.
`
`b. The number and proportion of flagged authorization numbers intended for an
`
`
`FRP due to questions in the mandatory surveys related to pregnancy testing
`
`
`
`
`
`
`U.S. Food and Drug Administration
`
`Silver Spring, MD 20993
`
`www.fda.gov
`
`
`
`Reference ID: 4675177
`
`

`

`
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` NDA 021880/S-054
` Page 7
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`
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` c. The number and proportion of flags that caused a delay in treatment initiation
`
`
`
`
`
` or a gap in therapy for patients due to REMS processes as the proportion of
` flagged authorization numbers compared to total authorization numbers.
`
`
`
`
` Include the time to resolution of flags in days (mean, minimum, maximum) for
` the reporting period and for each previous reporting period. Include the
`
`
`
` number of patients with a delay in treatment or a gap in therapy due to REMS
` processes.
`
`
`
`
`
`Knowledge, Attitude, Behavior
`
`
`6. Inform prescribers, patients, and pharmacists on the serious risks and safe-use
`
`
`
`conditions for lenalidomide (per current and previous two reporting periods and
`
`
`
`cumulatively, where applicable)
`
`
`a. Ensure that lenalidomide will only be dispensed to patients enrolled in the
`
`
`lenalidomide REMS Program with evidence or other documentation of safe-
`
`use conditions
`
`i. Number and proportion of total number of unflagged patient survey
`
`
`
`questions answered relating to knowledge compared to the total number
`
`
`of patient survey questions relating to knowledge reported per patient
`
`risk category
`
`b. Ensure healthcare providers counsel patients on the benefits and risks of
`
`
`
`lenalidomide therapy, including risks described in the boxed warnings
`
`i. Number and proportion of total number of unflagged prescriber surveys
`
`
`
`
`compared to the total number of prescriber surveys reported per risk
`
`category
`
`c. Educate pharmacies on the risks and safe-use conditions of lenalidomide
`
`
`
`i. Total number of pharmacy quizzes administered
`
`
`ii. Number of pharmacists with a passing rate/Total number of certified
`
`
`
`pharmacists on the last day of the reporting period
`
`
`
`
`7. The requirements for assessments of an approved REMS under section
`
`
`
`
`505-1(g)(3) include, with respect to each goal included in the strategy, an
`
`assessment of the extent to which the approved strategy, including each element
`
`
`of the strategy, is meeting the goal or whether one or more such goals or such
`
`elements should be modified.
`
`
`
`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 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:
`
`
`
`
`
`
`U.S. Food and Drug Administration
`
`Silver Spring, MD 20993
`
`www.fda.gov
`
`
`
`Reference ID: 4675177
`
`

`

`
`
`
` NDA 021880/S-054
` Page 8
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` 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 that 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. 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 21880 REMS ASSESSMENT METHODOLOGY
`
`
`
`(insert concise description of content in bold capital letters, e.g.,
`
`
`ASSESSMENT METHODOLOGY, PROTOCOL, SURVEY METHODOLOGIES,
`
`
`AUDIT PLAN, DRUG USE STUDY)
`
`
`
`
`U.S. Food and Drug Administration
`
`
`Silver Spring, MD 20993
`
`www.fda.gov
`
`Reference ID: 4675177
`
`

`

`NDA 021880/S-054
`
`
`Page 9
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`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 21880 REMS ASSESSMENT
`
`
`
`or
`
`
`
`
`
`NEW SUPPLEMENT FOR NDA 21880/S-000
`
`
`
`CHANGES BEING EFFECTED IN 30 DAYS
`
`
`PROPOSED MINOR REMS MODIFICATION
`
`
`
`
`
`or
`
`
`
`NEW SUPPLEMENT FOR NDA 21880/S-000
`
`
`
`PRIOR APPROVAL SUPPLEMENT
`
`
`
`PROPOSED MAJOR REMS MODIFICATION
`
`
`
`
`or
`
`
`
`
`
`NEW SUPPLEMENT FOR NDA 21880/S-000
`
`
`PRIOR APPROVAL SUPPLEMENT
`
`
`PROPOSED REMS MODIFICATIONS DUE TO SAFETY LABELING
`CHANGES SUBMITTED IN SUPPLEMENT XXX
`
`
`
`
`
`
`
`or
`
`
`
`NEW SUPPLEMENT (NEW INDICATION FOR USE)
`
`FOR NDA 21880/S-000
`
`
`
`REMS ASSESSMENT
`
`
`PROPOSED REMS MODIFICATION (if included)
`
`
`
`
`
`
`
`U.S. Food and Drug Administration
`
`Silver Spring, MD 20993
`
`www.fda.gov
`
`
`
`Reference ID: 4675177
`
`

`

`
`
`
`
` REMS REVISIONS FOR NDA 21880
`
`
`
`
` NDA 021880/S-054
` Page 10
`
`
`
`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, or website screenshots are only in PDF format,
`
`
`they may be submitted as such, but Word format is preferred.
`
`
`SUBMISSION OF REMS DOCUMENT IN SPL FORMAT
`
`FDA can accept the REMS document in Structured Product Labeling (SPL) format. If
`
`you intend to submit the REMS document in SPL format, as soon as possible, but no
`
`later than 14 days from the date of this letter, submit the REMS document in SPL format
`
`
`
`
`
`
`using the FDA automated drug registration and listing system (eLIST).
`
`
`For more information on submitting REMS in SPL format, please email
`
`
`
`FDAREMSwebsite@fda.hhs.gov.
`
`
`REQUIRED PEDIATRIC ASSESSMENTS
`
`
`Under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355c), all applications for
`
`
`
`new active ingredients (which includes new salts and new fixed combinations), 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 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.
`
`
`REPORTING REQUIREMENTS
`
`
`
` We remind you that you must comply with reporting requirements for an approved NDA
`
` (21 CFR 314.80 and 314.81).
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`U.S. Food and Drug Administration
`
`Silver Spring, MD 20993
`
`www.fda.gov
`
`
`
`Reference ID: 4675177
`
`

`

`
` NDA 021880/S-054
` Page 11
`
`
`
`
`
`
` If you have any questions you may contact Felicia Diggs, Safety Regulatory Project
` Manager, at 240-402-4932 or via email at Felicia.diggs@fda.hhs.gov.
`
`
`
`
`
`
`
`
`
`
`
`
`
` Sincerely,
`
`
`
`{See appended electronic signature page}
`
`
`Shaily Arora, PharmD
`
`
`
`
`Associate Director for Safety (Acting)
`
`Office of Oncologic Diseases
`
`
`Center for Drug Evaluation and Research
`
`
`
`
`
`ENCLOSURE:
`
`
`• REMS
`
`
`
`
`
`
`U.S. Food and Drug Administration
`
`Silver Spring, MD 20993
`
`www.fda.gov
`
`
`
`Reference ID: 4675177
`
`

`

`Signature Page 1 of 1
`--------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically. Following this are manifestations of any and all
`electronic signatures for this electronic record.
`--------------------------------------------------------------------------------------------
`/s/
`------------------------------------------------------------
`
`SHAILY ARORA
`09/24/2020 09:26:27 AM
`
`Reference ID: 4675177
`
`(
`
`
`
`