(~Ji Ii U.S. FOOD & DRUG
`
`AD M IN I STRATIO N
`
`• ,~~\.-
`
`
`NDA 202788/S-028
`
`
`
`SUPPLEMENT APPROVAL
`
`
`BTcP Pharma LLC
`c/o West Therapeutics Development, LLC
`1033 Skokie Boulevard
`Suite 620
`Northbrook, IL 60062
`
`Attention: Mahlaqa Patel
`Vice President, Regulatory Affairs and Quality Assurance
`
`
`Dear Ms. Patel:
`
`Please refer to your supplemental new drug application (sNDA) dated and received
`October 7, 2021, submitted under section 505(b) of the Federal Food, Drug, and
`Cosmetic Act (FDCA) for Subsys (fentanyl sublingual spray).
`
`This “Changes Being Effected” sNDA provides for proposed modification to the
`approved Transmucosal Immediate-Release Fentanyl (TIRF) Risk Evaluation and
`Mitigation Strategy (REMS).
`
`We have completed our review of this supplemental application. It is approved, effective
`on the date of this letter.
`
`RISK EVALUATION AND MITIGATION STRATEGY (REMS) REQUIREMENTS
`
`
`The REMS for TIRF products, of which Subsys is a member, was originally approved on
`
`December 28, 2011, and the most recent REMS modification was approved on
`December 23, 2020. Subsys was approved and incorporated into the shared system
`REMS as result of approval on January 4, 2012. The REMS consists of a Medication
`Guide, elements to assure safe use, an implementation system, and a timetable for
`submission of assessments of the REMS.
`
`Your proposed modification to the REMS consists of changes in order to narrow the
`number of annual outpatient pharmacy audits required, not to exceed 400 pharmacies.
`The REMS Document was updated to reflect that TIRF application holders must
`annually audit all certified outpatient pharmacies, or a maximum of 400, that have
`received at least one shipment of a TIRF medicine in the past 12 months.
`
`Your proposed modified REMS, submitted to Drug Master File (DMF)
`6, 2021, amended and appended to this letter, is approved.
`
`
`on October
`
`-
`
`
`
`Reference ID: 4898464
`
`(b) (4)
`
`

`

`NDA 202788/S-028
`Page 2
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`
`The timetable for submission of assessments of the REMS remains the same as that
`approved on December 23, 2020.
`
`There are no changes to the REMS assessment plan described in our December 23,
`2020, 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 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 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.
`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
`
`U.S. Food and Drug Administration
`
`
`Silver Spring, MD 20993
`www.fda.gov
`
`f)
`
`
`Reference ID: 4898464
`
`

`

`NDA 202788/S-028
`Page 3
`
`
`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 202788 REMS ASSESSMENT METHODOLOGY
`
`
`(insert concise description of content in bold capital letters, e.g.,
`
`ASSESSMENT METHODOLOGY, PROTOCOL, SURVEY METHODOLOGIES,
`
`AUDIT PLAN, DRUG USE STUDY)
`
`
`
`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 202788 REMS ASSESSMENT
`
`
`
`or
`
`
`NEW SUPPLEMENT FOR NDA 202788/S-000
`CHANGES BEING EFFECTED IN 30 DAYS
`PROPOSED MINOR REMS MODIFICATION
`
`
`or
`
`
`NEW SUPPLEMENT FOR NDA 202788/S-000
`PRIOR APPROVAL SUPPLEMENT
`
`PROPOSED MAJOR REMS MODIFICATION
`
`or
`
`
`
`
`
`
`
`U.S. Food and Drug Administration
`
`
`Silver Spring, MD 20993
`www.fda.gov
`
`Reference ID: 4898464
`
`

`

`NDA 202788/S-028
`Page 4
`
`
`
`
`
`NEW SUPPLEMENT FOR NDA 202788/S-000
`PRIOR APPROVAL SUPPLEMENT
`
`PROPOSED REMS MODIFICATIONS DUE TO SAFETY LABELING
`CHANGES SUBMITTED IN SUPPLEMENT 028
`
`
`
`or
`
`
`NEW SUPPLEMENT (NEW INDICATION FOR USE)
`FOR NDA 202788/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, 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.
`
`REPORTING REQUIREMENTS
`
`
`We remind you that you must comply with reporting requirements for an approved NDA
`(21 CFR 314.80 and 314.81).
`
`
`
`REMS REVISIONS FOR NDA 202788
`
`
`
`
`U.S. Food and Drug Administration
`
`
`Silver Spring, MD 20993
`www.fda.gov
`
`Reference ID: 4898464
`
`

`

`NDA 202788/S-028
`Page 5
`
`
`If you have any questions, call LCDR Jessica Voqui, PharmD, MS, Associate Director
`
`for Postmarket Regulatory Science, at 301-796-2915.
`
`
`
`
`Sincerely,
`
`{See appended electronic signature page}
`
`
`CDR Mark A. Liberatore, PharmD, RAC
`Deputy Director for Safety
`Division of Anesthesiology, Addiction Medicine,
`and Pain Medicine
`Office of Neuroscience
`Center for Drug Evaluation and Research
`
`
`ENCLOSURE:
` REMS
`
`
`
`
`
`U.S. Food and Drug Administration
`
`
`Silver Spring, MD 20993
`www.fda.gov
`
`Reference ID: 4898464
`
`

`

`Signature Page 1 of 1
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`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/
`------------------------------------------------------------
`
`MARK A LIBERATORE
`12/03/2021 10:41:52 AM
`
`Reference ID: 4898464
`
`