DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Silver Spring MD 20993 NDA 205637/S-009 SUPPLEMENT APPROVAL Biodelivery Sciences International, Inc. 4131 Parklake Ave, Suite 225 Raleigh, NC 27612 Attention: Chris Prue, RPh, MBA Vice President, Regulatory Affairs and Quality Assurance Dear Mr. Prue: Please refer to your Supplemental New Drug Application (sNDA) dated and received January 8, 2016, and your amendments, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA) for BUNAVAIL (buprenorphine and naloxone) buccal film. This Prior Approval supplemental new drug application proposes modifications to the approved risk evaluation and mitigation strategy (REMS) for BUNAVAIL, which is part of the waivergranted shared system REMS, the Buprenorphine-containing Transmucosal products for Opioid Dependence (BTOD) REMS Program. This supplement is in response to our November 12, 2015, REMS Modification Notification letter. APPROVAL We have completed our review of this supplemental application, as amended. It is approved, effective on the date of this letter. RISK EVALUATION AND MITIGATION STRATEGY (REMS) REQUIREMENT The REMS for BUNAVAIL was originally approved on June 6, 2014, as part of the waivergranted shared system BTOD REMS. Your REMS was most recently modified on February 12, 2015. 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. 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 materials to provide more succinct and clearer risk information for prescribers and pharmacists: • the Office-Based Buprenorphine Therapy for Opioid Dependence: Important Information for Pharmacists Brochure • the Office-Based Buprenorphine Therapy for Opioid Dependence: Important Information for Prescribers Brochure Reference ID: 3956122 NDA 205637/S-009 Page 2 • the Appropriate Use Checklist • the Dear Prescriber Letter • the Dear Pharmacist Letter Your proposed modified REMS, submitted on July 6, 2016, and appended to this letter, is approved. The BTOD REMS currently includes the products listed on the FDA REMS website, available at http://www.accessdata.fda.gov/scripts/cder/rems/index.cfm Other products may be added to the BTOD REMS in the future if additional BTOD NDAs or ANDAs are approved. We remind you that section 505-1(f)(8) of FDCA prohibits holders of an approved covered application from using any element to assure safe use 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. The timetable for submission of assessments of the REMS remains the same as that approved on June 6, 2014. 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 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. Reference ID: 3956122 NDA 205637/S-009 Page 3 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 205637 REMS CORRESPONDENCE (insert concise description of content in bold capital letters, e.g.,) UPDATE TO REMS SUPPORTING DOCUMENT - ASSESSMENT METHODOLOGY 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. 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 205637 REMS ASSESSMENT NEW SUPPLEMENT FOR NDA 205637/S-000/ CHANGES BEING EFFECTED IN 30 DAYS PROPOSED MINOR REMS MODIFICATION or NEW SUPPLEMENT FOR NDA 205637/S-000/ PRIOR APPROVAL SUPPLEMENT PROPOSED MAJOR REMS MODIFICATION Reference ID: 3956122 NDA 205637/S-009 Page 4 or NEW SUPPLEMENT FOR NDA 205637/S-000/ PRIOR APPROVAL SUPPLEMENT PROPOSED REMS MODIFICATIONS DUE TO SAFETY LABEL CHANGES SUBMITTED IN SUPPLEMENT XXX or NEW SUPPLEMENT (NEW INDICATION FOR USE) FOR NDA 205637/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 205637 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. If you do not submit electronically, please send 5 copies of REMS-related submissions. 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, M.D., M.P.H. Deputy Director of Safety Division of Anesthesia, Analgesia, and Addiction Products Office of Drug Evaluation II Center for Drug Evaluation and Research Reference ID: 3956122 NDA Page 5 ENCLOSURE: REMS Reference ID: 3956122 --------------------------------------------------------------------------------------------------------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 07/07/2016 Reference ID: 3956122