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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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` NDA 202788/S-010
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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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`Insys Therapeutics, Inc.
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`444 South Ellis St
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`Chandler, AZ 85224
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` Attention: Willene Brondum
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` Senior Manager, Regulatory Affairs
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`Dear Ms. Brondum:
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`Please refer to your Supplemental New Drug Application (sNDA) dated September 25, 2012,
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`received September 25, 2012, submitted under section 505(b) of the Federal Food, Drug, and
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`Cosmetic Act (FDCA) for Subsys (fentanyl sublingual spray), 100, 200, 400, 600, and
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`800 mcg.
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`We acknowledge receipt of your amendment dated October 17, 2013, and your risk evaluation and
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`mitigation strategy (REMS) assessment dated December 21, 2012.
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`This supplemental new drug application provides for modifications to the approved REMS for
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`Subsys (fentanyl sublingual spray), which is part of the single shared system REMS, the
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`Transmucosal Immediate-Release Fentanyl (TIRF) REMS Access Program.
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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.
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`RISK EVALUATION AND MITIGATION STRATEGY REQUIREMENTS
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`The REMS for Subsys (fentanyl sublingual spray was originally approved on January 4, 2012. The
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`REMS was last modified on June 5, 2012. 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.
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`Your proposed modification to the TIRF REMS, including appended REMS materials as applicable,
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`consists of the following:
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`• Revised terminology, processes, and definitions for outpatient pharmacies
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`• Revised attestations for physicians and patients to address concerns regarding patient access
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`• Revised Program Overview and Frequently Asked Questions to improve clarity and content
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`• Updated REMS materials to reflect the completion of the transition phase for the TIRF
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`REMS Access Program
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`Reference ID: 3403281
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` NDA 202788/S-010
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` Page 2
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` Your proposed modified REMS, submitted on September 26, 2012, jointly amended on September
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` 24, 2013, by the TIRF REMS Industry Group (TRIG), and appended to this letter, is approved.
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`The TIRF REMS Access Program includes the following products:
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`NDA 020747 Actiq (fentanyl citrate) oral transmucosal lozenge and its authorized generic
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`NDA 021947 Fentora (fentanyl buccal tablets)
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`NDA 022266 Onsolis (fentanyl buccal soluble film)
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`NDA 022510 Abstral (fentanyl) sublingual tablets
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`NDA 022569 Lazanda (fentanyl) nasal spray
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`NDA 202788 Subsys (fentanyl) sublingual spray
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`ANDA 077312 Fentanyl Citrate Oral Transmucosal Lozenge
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`ANDA 078907 Fentanyl Citrate Oral Transmucosal Lozenge
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`Other products may be added in the future if additional TIRF NDAs or ANDAs are approved.
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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 of an
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`application under section 505(b)(2) or (j). A violation of this provision in 505-1(f) could result in
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`enforcement action.
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`The timetable for submission of assessments of the REMS will remain the same as that approved on
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`June 5, 2012.
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`There are no changes to the REMS assessment plan described in our January 4, 2012, letter.
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`In addition to the assessments submitted according to the timetable included in this approved
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`REMS, you must submit a REMS assessment when you submit a supplemental application for a new
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`indication for use as described in section 505-1(g)(2)(A) of the FDCA.
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`If the assessment instruments and methodology for your REMS assessments are not included in the
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`REMS supporting document, or if you propose changes to the submitted assessment instruments or
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`methodology, you should update the REMS supporting document to include specific assessment
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`instrument and methodology information at least 90 days before the assessments will be conducted.
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`Updates to the REMS supporting document may be included in a new document that references
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`previous REMS supporting document submission(s) for unchanged portions. Alternatively, updates
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`may be made by modifying the complete previous REMS supporting document, with all changes
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`marked and highlighted. Prominently identify the submission containing the assessment instruments
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`and methodology with the following wording in bold capital letters at the top of the first page of the
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`submission:
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`NDA 202788 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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`Reference ID: 3403281
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` NDA 202788/S-010
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` Page 3
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` An authorized generic drug under this NDA 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 this NDA, contact
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`Prominently identify any submission containing the REMS assessments or proposed modifications
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`with the following wording in bold capital letters at the top of the first page of the
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`submission:
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`NDA 202788
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`REMS ASSESSMENT
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`NEW SUPPLEMENT FOR NDA 202788: NEW INDICATION OF USE
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`PROPOSED REMS MODIFICATION
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`REMS ASSESSMENT
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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 (21 CFR
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`314.80 and 314.81).
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`If you have any questions, call Matthew Sullivan, Senior Regulatory Project Manager, at
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`301-796-1245.
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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 for Safety
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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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`REMS
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`Reference ID: 3403281
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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
`11/07/2013
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`Reference ID: 3403281
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