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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`NDA 020732/S-017
`NDA 020733/S-021
`NDA 022410/S-030
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`Food and Drug Administration
`Silver Spring MD 20993
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`SUPPLEMENT APPROVAL
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`Indivior Inc.
`10710 Midlothian Turnpike
`Suite 430
`Richmond, VA 23235
`
`Attention: Vanita Dimri, MS, RAC
`Senior Manager, Regulatory Affairs
`
`
`Dear Ms. Dimri:
`
`Please refer to your Supplemental New Drug Applications (sNDAs) dated and received July 21,
`2017, and your amendments, submitted under section 505(b) of the Federal Food, Drug, and
`Cosmetic Act (FDCA) for SUBUTEX (buprenorphine) sublingual tablets (NDA 020732/S-017),
`SUBOXONE (buprenorphine and naloxone) sublingual tablets (NDA 020733/S-021), and
`SUBOXONE (buprenorphine and naloxone) sublingual film (NDA 022410/S-030).
`
`These Prior Approval supplemental new drug applications propose modifications to the approved
`risk evaluation and mitigation strategy (REMS) for SUBUTEX sublingual tablets, SUBOXONE
`sublingual tablets, and SUBOXONE sublingual film. The REMS was modified to align the
`REMS document and materials with the safety labeling changes for medication assisted
`treatment (MAT) products approved on December 16, 2016, that addresses the addition of
`language related to neonatal opioid withdrawal syndrome (NOWS) to the Warnings and
`Precautions Section of the Prescribing Information.
`
`These supplements are in response to our July 6, 2017, REMS Modification Notification
`communication.
`
`We have completed our review of these supplemental applications, as amended. They are
`approved, effective on the date of this letter.
`
`RISK EVALUATION AND MITIGATION STRATEGY REQUIREMENTS
`
`The REMS for SUBOXONE (buprenorphine and naloxone) sublingual film was originally
`approved on August 30, 2010. The REMS for SUBUTEX (buprenorphine) sublingual tablets
`and the REMS for SUBOXONE (buprenorphine and naloxone) sublingual tablets were originally
`approved on December 22, 2011. Each REMS was most recently modified on July 7, 2016, to
`consolidate the three product-specific REMS into a single REMS. The REMS consists of a
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`Reference ID: 4155069
`
`

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`NDA 020732/S-017
`NDA 020733/S-021
`NDA 022410/S-030
`Page 2
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`Medication Guide, elements to assure safe use, an implementation system, and a timetable for
`submission of assessments of the REMS.
`
`In order to ensure the benefits of SUBUTEX sublingual tablets, SUBOXONE sublingual tablets,
`and SUBOXONE sublingual film outweigh the risks of accidental overdose, misuse, and abuse,
`we determined that you were required to make modifications consistent with the safety labeling
`changes approved on December 16, 2016, to the following REMS materials,:
`
`
`•
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`•
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`•
`•
`•
`•
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`the Office-Based Buprenorphine Therapy for Opioid Dependence: Important
`Information for Prescribers Brochure
`the Office-Based Buprenorphine Therapy for Opioid Dependence: Important
`Information for Pharmacists Brochure
`the Dear Prescriber Letter
`the Dear Pharmacist Letter
`the Appropriate Use Checklist
`the REMS website
`
`
`Your proposed modified REMS, submitted on July 21, 2017, and appended to this letter, is
`approved.
`
`The timetables for submission of assessments of the REMS remain the same as that approved on
`December 22, 2011.
`
`There are no changes to the REMS assessment plan described in our July 13, 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 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;
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`Reference ID: 4155069
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`

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`NDA 020732/S-017
`NDA 020733/S-021
`NDA 022410/S-030
`Page 3
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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.
`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.
`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
`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 020732
`NDA 020733
`NDA 022410 REMS CORRESPONDENCE
`(insert concise description of content in bold capital letters, e.g., )
`UPDATE TO REMS SUPPORTING DOCUMENT - ASSESSMENT
`METHODOLOGY
`
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`An authorized generic drug under these NDAs must have an approved REMS prior to marketing.
`Should you decide to market, sell, or distribute an authorized generic drug under one or more of
`these NDAs, contact us to discuss what will be required in the authorized generic drug REMS
`submission.
`
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`Reference ID: 4155069
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`

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`NDA 020732/S-017
`NDA 020733/S-021
`NDA 022410/S-030
`Page 4
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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.
`
`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 020732
`NDA 020733
`NDA 022410 REMS ASSESSMENT
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`NEW SUPPLEMENT FOR
`NDA 020732/S-000, NDA 020733/S-000, and NDA 022410/S-000
`CHANGES BEING EFFECTED IN 30 DAYS
`PROPOSED MINOR REMS MODIFICATION
`
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`or
`
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`NEW SUPPLEMENT FOR
`NDA 020732/S-000, NDA 020733/S-000, and NDA 022410/S-000
`PRIOR APPROVAL SUPPLEMENT
`PROPOSED MAJOR REMS MODIFICATION
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`or
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`NEW SUPPLEMENT FOR
`NDA 020732/S-000, NDA 020733/S-000, and NDA 022410/S-000
`PRIOR APPROVAL SUPPLEMENT
`PROPOSED REMS MODIFICATIONS DUE TO SAFETY LABEL CHANGES
`SUBMITTED IN SUPPLEMENT XXX
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`
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`or
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`NEW SUPPLEMENT (NEW INDICATION FOR USE) FOR
`NDA 020732/S-000, NDA 020733/S-000, and NDA 022410/S-000
`REMS ASSESSMENT
`PROPOSED REMS MODIFICATION (if included)
`
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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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`Reference ID: 4155069
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`

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`NDA 020732/S-017
`NDA 020733/S-021
`NDA 022410/S-030
`Page 5
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`REMS REVISIONS FOR NDA 020732, NDA 020733, and NDA 022410
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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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`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 Mark Liberatore, PharmD, Safety Regulatory Project Manager, at
`(301) 796-2221.
`
`
`Sincerely,
`
`{See appended electronic signature page}
`
`Judith A. Racoosin, MD, MPH
`Deputy Director for Safety
`Division of Anesthesia, Analgesia,
` and Addiction Products
`Office of Drug Evaluation II
`Center for Drug Evaluation and Research
`
`
`ENCLOSURE:
`REMS
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`Reference ID: 4155069
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`

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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/
`----------------------------------------------------
`
`JUDITH A RACOOSIN
`09/19/2017
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`Reference ID: 4155069
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