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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`NDA 202788/S-005
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`NDA 202788/S-006
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`Food and Drug Administration
`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
`Senior Manager, Refdgulatory Affairs
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`Dear Ms. Brondum:
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`Please refer to your Supplemental New Drug Applications (sNDAs) dated and received June 27,
`2012, (S005) and September 7, 2012, (S006) submitted pursuant to section 505(b)(2) of the
`Federal Food, Drug, and Cosmetic Act (FDCA) for Subsys (fentanyl sublingual spray), 100, 200,
`400, 600, and 800 mcg.
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`We acknowledge receipt of your amendments to S005 dated January 17, and June 11, 21, and 27,
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`2013, and your risk evaluation and mitigation strategy (REMS) assessment dated December 21,
`2012.
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`Supplement 005 is a “Prior Approval” supplemental new drug application which proposes initial
`dosing recommendations to assist prescribers in converting patients from Actiq (fentanyl citrate)
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`lozenges to Subsys (fentanyl sublingual spray), as well as a modification to the approved REMS
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`for 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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`Supplement 006 is a “Changes Being Effected in 30 days” supplemental new drug application,
`which provides for new 10 count carton configurations of the previously approved devices.
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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, for use as recommended in the enclosed, agreed-
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`upon labeling 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
`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
` of labeling must be identical to the enclosed labeling (text for the package insert and Medication
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`Reference ID: 3350257
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` NDA 202788/S-005 and S-006
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`Page 2
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`Guide), with the addition of any labeling changes in pending “Changes Being Effected” (CBE)
`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
`“SPL Standard for Content of Labeling Technical Qs and As at
`http://www.fda.gov/downloads/DrugsGuidanceComplianceRegulatoryInformation/Guidances/U
`CM072392.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
`for this NDA, including CBE supplements for which FDA has not yet issued an action letter,
`with the content of labeling [21 CFR 314.50(l)(1)(i)] in MS Word format, that includes the
`changes approved in this supplemental application, as well as annual reportable changes and
`annotate each change. To facilitate review of your submission, provide a highlighted or marked-
`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
`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 container labels that are identical to the enclosed carton labels as
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`soon as they are available, but no more than 30 days after they are printed.
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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
`and at that time became part of the single shared system REMS, the Transmucosal Immediate-
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`Release Fentanyl (TIRF) REMS Access Program. The REMS was last modified on June 5,
`2012. 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.
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`Your proposed modification to the REMS, including appended REMS materials as applicable,
`consists of a revised TIRF REMS Knowledge Assessment and TIRF REMS Education Program
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`to include initial dosing recommendations to assist prescribers in converting patients from Actiq
`(fentanyl citrate) lozenges to Subsys (fentanyl sublingual spray).
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`Your proposed modified REMS, submitted on January 17, 2013, amended June 11, 21, and 27,
`2013, and appended to this letter, is approved.
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`The TIRF REMS Access Program includes the following products:
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`Reference ID: 3350257
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` NDA 202788/S-005 and S-006
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`Page 3
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` NDA 020747
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`Actiq (fentanyl citrate) oral transmucosal lozenge and its authorized
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`generic
`NDA 021947
`Fentora (fentanyl buccal tablets)
`NDA 022266 Onsolis (fentanyl buccal soluble film)
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`Abstral (fentanyl) sublingual tablets
`NDA 022510
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`NDA 022569 Lazanda (fentanyl) nasal spray
`NDA 202788
`Subsys (fentanyl) sublingual spray
`ANDA 077312 Fentanyl Citrate Oral Transmucosal Lozenge
`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 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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`The timetable for submission of assessments of the REMS will remain the same as that approved
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`on 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
`REMS, 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.
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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,
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`contact us to discuss what will be required in the authorized generic drug REMS submission.
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`Prominently identify any submission containing the REMS assessments or proposed
`modifications with the following wording in bold capital letters at the top of the first page of the
`submission:
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`NDA 202788
`REMS ASSESSMENT
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`NEW SUPPLEMENT FOR NDA 202788
`PROPOSED REMS MODIFICATION
`REMS ASSESSMENT
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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 314.80 and 314.81).
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`Reference ID: 3350257
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` NDA 202788/S-005 and S-006
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`Page 4
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` If you have any questions, call Matt Sullivan, Senior Regulatory Project Manager, at
`(301) 796-1245.
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`Sincerely,
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`{See appended electronic signature page}
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`Bob A. Rappaport, M.D.
`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
`Center for Drug Evaluation and Research
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`ENCLOSURE(S):
`Content of Labeling
`Carton Labeling
`REMS
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`Reference ID: 3350257
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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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`BOB A RAPPAPORT
`07/31/2013
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`Reference ID: 3350257
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