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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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` NDA 022410/S-020
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` NDA 022410/S-022
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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, Suite 430
`Richmond, VA 23235
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` Attention:
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`Dear Mr. Paolella:
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`Please refer to your Supplemental New Drug Applications (sNDAs) dated and received April 21,
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`2014 (S-020), and January 16, 2015 (S-022), submitted under section 505(b) of the Federal Food,
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`Drug, and Cosmetic Act (FDCA) for Suboxone (buprenorphine and naloxone) sublingual film.
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`We acknowledge receipt of your amendments to S-020 dated May 23, and July 9 and 31, 2014,
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`and March 13, May 5, and August 18, 2015. We additionally acknowledge receipt of your
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`amendments to S-022 dated June 15, July 30, and August 18 and 21, 2015.
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`S-020 is a “Prior Approval” supplemental new drug application which proposes revisions to
`Section 2: DOSAGE AND ADMINISTRATION of the Package Insert to include the buccal
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`route of administration.
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`S-022 is a “Prior Approval” supplemental new drug application which proposes changes to the
`approved (REMS) as described in our December 12, 2014, letter.
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` APPROVAL & LABELING
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`We have completed our review of this supplemental application, as amended. It is approved,
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`effective on the date of this letter, for use as recommended in the enclosed, agreed-upon labeling
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`text.
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`CONTENT OF LABELING
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`As soon as possible, but no later than 14 days from the date of this letter, submit the content of
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`labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format using the FDA
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`automated drug registration and listing system (eLIST), as described at
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`http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. Content
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`of labeling must be identical to the enclosed labeling text for the package insert and Medication
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` Bruce Paolella
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` Director, Regulatory Affairs
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`Reference ID: 3821996
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` NDA 022410/S-020
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` NDA 022410/S-022
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` Page 2
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` Guide, with the addition of any labeling changes in pending “Changes Being Effected” (CBE)
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`supplements, as well as annual reportable changes not included in the enclosed labeling.
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`Information on submitting SPL files using eList may be found in the guidance for industry titled
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`“SPL Standard for Content of Labeling Technical Qs and As at http://www.fda.gov/downloads/
`DrugsGuidanceComplianceRegulatoryInformation/Guidances/UCM072392.pdf.
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` The SPL will be accessible from publicly available labeling repositories.
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`Also within 14 days, amend all pending supplemental applications that includes labeling changes
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`for this NDA, including CBE supplements for which FDA has not yet issued an action letter,
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`with the content of labeling [21 CFR 314.50(l)(1)(i)] in MS Word format, that includes the
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`changes approved in this supplemental application, as well as annual reportable changes and
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`annotate each change. To facilitate review of your submission, provide a highlighted or marked-
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`up copy that shows all changes, as well as a clean Microsoft Word version. The marked-up copy
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`should provide appropriate annotations, including supplement number(s) and annual report
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`date(s).
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`We request that the labeling approved today be available on your website within 10 days of
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`receipt of this letter.
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`CARTON AND IMMEDIATE CONTAINER LABELS
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`Submit final printed carton and immediate container labels that are identical to the enclosed
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`carton and immediate container labels submitted via email on February 6, 2015, as soon as they
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`are available, but no more than 30 days after they are printed. Please submit these labels
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`electronically according to the guidance for industry Providing Regulatory Submissions in
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`Electronic Format – Human Pharmaceutical Product Applications and Related Submissions
`Using the eCTD Specifications (June 2008). Alternatively, you may submit 12 paper copies,
`with 6 of the copies individually mounted on heavy-weight paper or similar material. For
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`administrative purposes, designate this submission “Final Printed Carton and Container
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`Labels for approved NDA 022410/S-022.” Approval of this submission by FDA is not
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`required before the labeling is used.
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`Marketing the product(s) with FPL that is not identical to the approved labeling text may render
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`the product misbranded and an unapproved new drug.
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`REQUIRED PEDIATRIC ASSESSMENTS
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`Under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355c), all applications for new
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`active ingredients, new indications, new dosage forms, new dosing regimens, or new routes of
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`administration are required to contain an assessment of the safety and effectiveness of the
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`product for the claimed indication(s) in pediatric patients unless this requirement is waived,
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`deferred, or inapplicable.
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`Reference ID: 3821996
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`•
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`Incorporate information related to
`o Buccal administration of Suboxone (buprenorphine and naloxone) sublingual film.
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`o Newly approved transmucosal buprenorphine containing product, Bunavail
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`(buprenorphine and naloxone film), into the REMS materials.
`o Three newly approved strengths of a transmucosal buprenorphine-containing
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`product, Zubsolv (buprenorphine and naloxone tablets), into the REMS materials.
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` NDA 022410/S-020
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` NDA 022410/S-022
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` Page 3
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` Because this drug product for this indication has an orphan drug designation, you are exempt
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`RISK EVALUATION AND MITIGATION STRATEGY REQUIREMENTS
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`The REMS for Suboxone sublingual film was originally approved on August 30, 2010, and most
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`recently modified on April 28, 2014. The REMS consists of a Medication Guide, elements to
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`assure safe use, an implementation system, and a timetable for submission of assessments of the
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`REMS. In order to ensure the benefits of Suboxone sublingual film outweigh its risks, we
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`determined that you were required to make the following REMS modifications:
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`In our December 12, 2014, letter, we also encouraged you to:
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`• Consolidate the three product-specific REMS into a single REMS encompassing Subutex
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`sublingual tablets, Suboxone sublingual tablets, and Suboxone sublingual film.
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`• Develop a REMS website that includes information on the consolidated REMS for
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`Subutex sublingual tablets, Suboxone sublingual tablets, and Suboxone sublingual film.
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`Your proposed modified REMS, submitted on August 18, 2015, and appended to this letter, is
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`approved.
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`Your modified REMS must be fully operational no later than 30 calendar days from the date of
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`this letter.
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`The timetable for submission of assessments of the REMS will remain the same as that approved
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`on August 30, 2010. There are no changes to the REMS assessment plan described in our
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`August 30, 2010, letter.
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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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`modification for the addition, modification, or removal of any of goal or element of the REMS,
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`as 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). This assessment
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`Reference ID: 3821996
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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;
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` REMS;
` 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
`approved REMS.
`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 that the last assessment and if any
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`modifications of the REMS have been proposed since that assessment.
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`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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`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
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`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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`was required, on patient access to the drug, and/or on the burden on the health care
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`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
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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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` NDA 022410/S-020
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` NDA 022410/S-022
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` Page 4
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`c)
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`d)
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`e)
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`f)
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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
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`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 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 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,
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`contact us to discuss what will be required in the authorized generic drug REMS submission.
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`Reference ID: 3821996
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` NDA 022410/S-020
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` NDA 022410/S-022
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` Page 5
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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
`result in enforcement action.
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`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
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`first page of the submission as appropriate:
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` NDA 022410 REMS ASSESSMENT
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`NEW SUPPLEMENT FOR 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 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 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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`NEW SUPPLEMENT (NEW INDICATION FOR USE)
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`FOR 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 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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`If you do not submit electronically, please send 5 copies of REMS-related submissions.
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`Reference ID: 3821996
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` NDA 022410/S-020
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` NDA 022410/S-022
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` Page 6
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` PROMOTIONAL MATERIALS
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`You may request advisory comments on proposed introductory advertising and promotional
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`labeling. To do so, submit the following, in triplicate, (1) a cover letter requesting advisory
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`comments, (2) the proposed materials in draft or mock-up form with annotated references, and
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`(3) the package insert(s) to:
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`Food and Drug Administration
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`Center for Drug Evaluation and Research
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`Office of Prescription Drug Promotion (OPDP)
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`5901-B Ammendale Road
`Beltsville, MD 20705-1266
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`You must submit final promotional materials and package insert(s), accompanied by a Form
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`FDA 2253, at the time of initial dissemination or publication [21 CFR 314.81(b)(3)(i)]. Form
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`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
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`http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf. For
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`more information about submission of promotional materials to the Office of Prescription Drug
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`Promotion (OPDP), see http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm.
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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 Matthew Sullivan, Supervisory Regulatory Health Project
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`Manager, at (301) 796-1245.
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`Sincerely,
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`{See appended electronic signature page}
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`Rigoberto Roca, MD
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`Deputy Director
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`Division of Anesthesia, Analgesia, and
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`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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`ENCLOSURES:
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`Content of Labeling
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`Carton and Container Labeling
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`REMS
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`Reference ID: 3821996
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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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`RIGOBERTO A ROCA
`09/22/2015
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`Reference ID: 3821996
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