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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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` NDA 020732/S-013
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` NDA 020733/S-017
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` NDA 022410/S-025
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` Food and Drug Administration
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` Silver Spring MD 20993
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`SUPPLEMENT APPROVAL
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`Indivior Inc.
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`10710 Midlothian Turnpike
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`Suite 430
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`Richmond, VA 23235
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`Attention:
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`Bruce Paolella
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`Director of Regulatory Affairs North America
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`Dear Mr. Paolella:
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`Please refer to your Supplemental New Drug Applications (sNDAs) received January 13, 2016,
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`and your amendments, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic
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`Act (FDCA) for SUBUTEX (buprenorphine HCl) sublingual tablets, SUBOXONE
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`(buprenorphine and naloxone) sublingual tablets, and SUBOXONE (buprenorphine and
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`naloxone) sublingual film.
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`These Prior Approval supplemental new drug applications propose modifications to the approved
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`risk evaluation and mitigation strategy (REMS) for SUBUTEX (buprenorphine HCl) sublingual
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`tablets, SUBOXONE (buprenorphine and naloxone) sublingual tablets, and SUBOXONE
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`(buprenorphine and naloxone) sublingual film. These supplements are in response to our
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`November 12, 2015, REMS Modification Notification letter.
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`APPROVAL
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`We have completed our review of these supplemental applications, as amended. They are
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`approved, effective on the date of this letter.
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`RISK EVALUATION AND MITIGATION STRATEGY (REMS) REQUIREMENT
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`The REMS for SUBUTEX (buprenorphine HCl) sublingual tablets and the REMS for
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`SUBOXONE (buprenorphine and naloxone) sublingual tablets were originally approved on
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`December 22, 2011. The REMS for SUBOXONE (buprenorphine and naloxone) sublingual film
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`was originally approved on August 30, 2010. Each REMS was most recently modified on
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`September 22, 2015 to consolidate the three product-specific REMS into a single REMS. The
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`REMS consists of a Medication Guide, elements to assure safe use, an implementation system,
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`and a timetable for submission of assessments of the REMS.
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`Reference ID: 3956127
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` NDA 020732/S-013
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` NDA 020733/S-017
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` NDA 022410/S-025
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` Page 2
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` In order to minimize the burden on the healthcare delivery system of complying with the REMS,
` we determined that you were required to make REMS modifications to the following REMS
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` materials to provide more succinct and clear risk information for prescribers and pharmacists:
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`•
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`•
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`•
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`•
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` the Office-Based Buprenorphine Therapy for Opioid Dependence: Important
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` Information for Pharmacists Brochure
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` the Office-Based Buprenorphine Therapy for Opioid Dependence: Important
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` Information for Prescribers Brochure
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` the Appropriate Use Checklist
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` the Dear Prescriber Letter
` the Dear Pharmacist Letter
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` Your proposed modified REMS, submitted on July 1, 2016, and appended to this letter is
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` approved.
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` The timetables for submission of assessments of the REMS remain the same as that approved on
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` December 22, 2011.
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` There are no changes to the REMS assessment plan described in our December 22, 2011, letters.
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` We remind you that in addition to the REMS assessments submitted according to the timetable in
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` the approved REMS, you must include an adequate rationale to support a proposed REMS
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`described in section 505-1(g)(4) of the FDCA.
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` We also remind you that you must submit a REMS assessment when you submit a supplemental
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` application for a new indication for use as described in section 505-1(g)(2)(A) of the FDCA.
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` This assessment should include:
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` a) An evaluation of how the benefit-risk profile will or will not change with the new
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` indication;
` b) A determination of the implications of a change in the benefit-risk profile for the current
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` REMS;
` c) If the new indication for use introduces unexpected risks: A description of those risks
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` and an evaluation of whether those risks can be appropriately managed with the currently
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`approved REMS.
` d) If a REMS assessment was submitted in the 18 months prior to submission of the
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` supplemental application for a new indication for use: A statement about whether the
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` REMS was meeting its goals at the time of the last assessment and if any modifications
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` of the REMS have been proposed since that assessment.
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` e) If a REMS assessment has not been submitted in the 18 months prior to submission of the
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` supplemental application for a new indication for use: Provision of as many of the
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` currently listed assessment plan items as is feasible.
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`Reference ID: 3956127
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` NDA 020732/S-013
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` NDA 020733/S-017
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` NDA 022410/S-025
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` Page 3
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` f) If you propose a REMS modification based on a change in the benefit-risk profile or
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` 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
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` modification is necessary, the potential effect on the serious risk(s) for which the REMS
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` delivery system; and other appropriate evidence or data to support the proposed change.
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` Additionally, include any changes to the assessment plan necessary to assess the
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` proposed modified REMS. If you are not proposing REMS modifications, provide a
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` 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
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`the REMS supporting document, or if you propose changes to the submitted assessment
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`instruments or methodology, you should update the REMS supporting document to include
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`specific assessment instrument and methodology information at least 90 days before the
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`assessments will be conducted. Updates to the REMS supporting document may be included in a
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`new document that references previous REMS supporting document submission(s) for
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`unchanged portions. Alternatively, updates may be made by modifying the complete previous
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`REMS supporting document, with all changes marked and highlighted. Prominently identify the
`submission containing the assessment instruments and methodology with the following wording
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`in bold capital letters at the top of the first page of the submission:
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`NDA 020732
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`NDA 020733
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`NDA 022410 REMS CORRESPONDENCE
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`(insert concise description of content in bold capital letters, e.g.,)
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`UPDATE TO REMS SUPPORTING DOCUMENT - ASSESSMENT
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`METHODOLOGY
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`An authorized generic drug under these NDAs must have an approved REMS prior to marketing.
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`Should you decide to market, sell, or distribute an authorized generic drug under these NDAs,
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`contact us to discuss what will be required in the authorized generic drug REMS submission.
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`We remind you that section 505-1(f)(8) of FDCA prohibits holders of an approved covered
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`application with elements to assure safe use from using any element to block or delay approval
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`of an application under section 505(b)(2) or (j). A violation of this provision in 505-1(f) could
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`result in enforcement action.
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`Prominently identify any submission containing the REMS assessments or proposed
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`modifications of the REMS with the following wording in bold capital letters at the top of the
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`first page of the submission as appropriate:
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`Reference ID: 3956127
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` NDA 020732/S-013
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` NDA 020733/S-017
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` NDA 022410/S-025
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` Page 4
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` NDA 020732
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` NDA 020733
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` NDA 022410 REMS ASSESSMENT
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`NEW SUPPLEMENT FOR
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`NDA 020732/S-000/; NDA 020733/S-000/; NDA 022410/S-000/
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`CHANGES BEING EFFECTED IN 30 DAYS
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`PROPOSED MINOR REMS MODIFICATION
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`or
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`NEW SUPPLEMENT FOR
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`NDA 020732/S-000/; NDA 020733/S-000/; NDA 022410/S-000/
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`PRIOR APPROVAL SUPPLEMENT
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`PROPOSED MAJOR REMS MODIFICATION
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`or
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`NEW SUPPLEMENT FOR
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`NDA 020732/S-000/; NDA 020733/S-000/; NDA 022410/S-000/
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`PRIOR APPROVAL SUPPLEMENT
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`PROPOSED REMS MODIFICATIONS DUE TO SAFETY LABEL CHANGES
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`SUBMITTED IN SUPPLEMENT XXX
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`or
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`NEW SUPPLEMENT (NEW INDICATION FOR USE) FOR
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`NDA 020732/S-000/; NDA 020733/S-000/; NDA 022410/S-000/
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`REMS ASSESSMENT
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`PROPOSED REMS MODIFICATION (if included)
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`Should you choose to submit a REMS revision, prominently identify the submission containing
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`the REMS revisions with the following wording in bold capital letters at the top of the first page
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`of the submission:
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`REMS REVISIONS FOR NDA 020732/S-000/; NDA 020733/S-000/; NDA 022410/S-000/
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`To facilitate review of your submission, we request that you submit your proposed modified
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`REMS and other REMS-related materials in Microsoft Word format. If certain documents, such
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`as enrollment forms, are only in PDF format, they may be submitted as such, but the preference
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`is to include as many as possible in Word format.
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`Reference ID: 3956127
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` NDA 020732/S-013
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` NDA 020733/S-017
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` NDA 022410/S-025
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` Page 5
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` If you do not submit electronically, please send 5 copies of REMS-related submissions.
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`REPORTING REQUIREMENTS
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`We remind you that you must comply with reporting requirements for an approved NDA
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`(21 CFR 314.80 and 314.81).
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`If you have any questions, call Mark Liberatore, PharmD, Safety Regulatory Project Manager, at
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`(301) 796-2221.
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`Sincerely,
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`{See appended electronic signature page}
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`Judith A. Racoosin, M.D., M.P.H.
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`Deputy Director of Safety
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`Division of Anesthesia, Analgesia,
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`and Addiction Products
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`Office of Drug Evaluation II
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`Center for Drug Evaluation and Research
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`ENCLOSURE:
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`REMS
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`Reference ID: 3956127
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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/
`----------------------------------------------------
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`JUDITH A RACOOSIN
`07/07/2016
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`Reference ID: 3956127
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