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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`NDA 020732/S-019
`NDA 020733/S-023
`NDA 022410/S-033
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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
`November 20, 2017, and your amendments, submitted under section 505(b) of the Federal Food,
`Drug, and Cosmetic Act (FDCA) for SUBUTEX (buprenorphine) sublingual tablets (S-019),
`SUBOXONE (buprenorphine and naloxone) sublingual tablets (S-023), and SUBOXONE
`(buprenorphine and naloxone) sublingual film (S-033).
`
`These supplemental applications, submitted as “Changes Being Effected in 30 days”
`supplements, proposed modification to the approved risk evaluation and mitigation strategy
`(REMS) for SUBUTEX sublingual tablets, SUBOXONE sublingual tablets, and SUBOXONE
`sublingual film to include the authorized generic of SUBOXONE sublingual film.
`
`We have completed our review of these supplemental applications, as amended, and they are
`approved, effective on the date of this letter.
`
`RISK EVALUATION AND MITIGATION STRATEGY (REMS) REQUIREMENTS
`
`The REMS for SUBUTEX sublingual tablets and SUBOXONE sublingual tablets were
`originally approved on December 22, 2011. The REMS for SUBOXONE sublingual film was
`originally approved on August 30, 2010. Each REMS was most recently modified on September
`22, 2015, to consolidate the three product-specific REMS into a single REMS. 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 adding the authorized generic for SUBOXONE sublingual film.
`
`In accordance with section 505-1 of the FDCA, we have determined that the proposed REMS
`modification is necessary to ensure the benefits of the drug outweigh the risks.
`
`Reference ID: 4276171
`
`

`

`NDA 020732/S-019
`NDA 020733/S-023
`NDA 022410/S-033
`Page 2
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`Your proposed modified REMS, submitted on November 20, 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 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.
`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.
`
`Reference ID: 4276171
`
`

`

`NDA 020732/S-019
`NDA 020733/S-023
`NDA 022410/S-033
`Page 3
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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 ASSESSMENT METHODOLOGY
`
`
`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
`
`NEW SUPPLEMENT FOR
`NDA 020732/S-000/; NDA 020733/S-000/; NDA 022410/S-000/
`CHANGES BEING EFFECTED IN 30 DAYS
`PROPOSED MINOR REMS MODIFICATION
`
`
`
`NEW SUPPLEMENT FOR
`NDA 020732/S-000/; NDA 020733/S-000/; NDA 022410/S-000/
`PRIOR APPROVAL SUPPLEMENT
`PROPOSED MAJOR REMS MODIFICATION
`
`or
`
`or
`
`
`NEW SUPPLEMENT FOR
`
`Reference ID: 4276171
`
`

`

`NDA 020732/S-019
`NDA 020733/S-023
`NDA 022410/S-033
`Page 4
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`NDA 020732/S-000/; NDA 020733/S-000/; NDA 022410/S-000/
`PRIOR APPROVAL SUPPLEMENT
`PROPOSED REMS MODIFICATIONS DUE TO SAFETY LABEL CHANGES
`SUBMITTED IN SUPPLEMENT XXX
`
`
`
`or
`
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`NEW SUPPLEMENT (NEW INDICATION FOR USE)
`FOR NDA 020732/S-000/; NDA 020733/S-000/; NDA 022410/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:
`
`REMS REVISIONS FOR NDA 020732/S-000/; NDA 020733/S-000/; NDA 022410/S-000/
`
`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 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
`REMS_Website@fda.hhs.gov.
`
`PROMOTIONAL MATERIALS
`
`You may request advisory comments on proposed introductory advertising and promotional
`labeling. To do so, submit the following, in triplicate, (1) a cover letter requesting advisory
`comments, (2) the proposed materials in draft or mock-up form with annotated references, and
`(3) the package insert(s) to:
`
`
`OPDP Regulatory Project Manager
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion (OPDP)
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`Reference ID: 4276171
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`

`

`NDA 020732/S-019
`NDA 020733/S-023
`NDA 022410/S-033
`Page 5
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`5901-B Ammendale Road
`Beltsville, MD 20705-1266
`
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`Alternatively, you may submit a request for advisory comments electronically in eCTD format.
`For more information about submitting promotional materials in eCTD format, see the draft
`Guidance for Industry (available at:
`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
`CM443702.pdf ).
`
`You must submit final promotional materials and package insert(s), accompanied by a Form
`FDA 2253, at the time of initial dissemination or publication [21 CFR 314.81(b)(3)(i)]. Form
`FDA 2253 is available at
`http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf.
`Information and Instructions for completing the form can be found at
`http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf. For
`more information about submission of promotional materials to the Office of Prescription Drug
`Promotion (OPDP), see http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm.
`
`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 Swati Patwardhan, Regulatory Project Manager, at
`(301) 796-4085.
`
`
`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
`
`
`ENCLOSURES:
`Content of Labeling
`Carton and Container Labeling
`REMS
`
`
`
`Reference ID: 4276171
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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
`06/11/2018
`
`Reference ID: 4276171
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`