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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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` NDA 204592/S-007, S-008
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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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`Iroko Pharmaceuticals, LLC
`One Kew Place
`150 Rouse Boulevard
`Philadelphia, PA 19112
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`Attention:
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`Paul M. Kirsch
`Vice President, Regulatory Affairs
`
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`Dear Mr. Kirsch:
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`Please refer to your Supplemental New Drug Applications (sNDAs) dated and received August
`7, 2015 (S-003) and September 4, 2015 (S-004), submitted under section 505(b of the Federal
`Food, Drug, and Cosmetic Act (FDCA) for ZORVOLEX (diclofenac) capsules.
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`We also refer to our letter dated July 9, 2015, notifying you, under Section 505(o)(4) of the
`FDCA, of new safety information that we believe should be included in the labeling for the class
`of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs). This new safety information pertains to
`the risks of Cardiovascular Thrombotic Events and Heart Failure and Edema.
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`S-007 provides for the Safety Labeling Changes required under Section 505(o)(4) of the FDCA,
`consistent with our July 9, 2015, letter.
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`S-008 provides for additional revisions to the Package Insert to incorporate the NSAIDs template
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` language, consistent with our July 9, 2015, letter.
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`APPROVAL & LABELING
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`We have completed our review of these supplemental applications. They are approved, effective
`on the date of this letter, for use as recommended in the enclosed, agreed-upon labeling text.
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`WAIVER OF HIGHLIGHTS SECTION
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`Please note that we have previously granted a waiver of the requirements of 21 CFR
`201.57(d)(8) regarding the length of Highlights of prescribing information.
`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
`automated drug registration and listing system (eLIST), as described at
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`Reference ID: 3928107
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`

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`NDA 204592/S-007, S-008
`Page 2
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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
`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
`should provide appropriate annotations, including supplement number(s) and annual report
`date(s).
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`Marketing the product(s) with FPL that is not identical to the approved labeling text may render
`the product misbranded and an unapproved new drug.
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`PROMOTIONAL MATERIALS
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`You may request advisory comments on proposed introductory advertising and promotional
`labeling. To do so, submit the following, in triplicate, (1) a cover letter requesting advisory
`comments, (2) the proposed materials in draft or mock-up form with annotated references, and
`(3) the package insert(s) to:
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`OPDP Regulatory Project Manager
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion (OPDP)
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
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`Alternatively, you may submit a request for advisory comments electronically in eCTD format.
`For more information about submitting promotional materials in eCTD format, see the draft
`Guidance for Industry (available at:
`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
`CM443702.pdf ).
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`Reference ID: 3928107
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`

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`NDA 204592/S-007, S-008
`Page 3
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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
`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
`http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf. For
`more information about submission of promotional materials to the Office of Prescription Drug
`Promotion (OPDP), see http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm.
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`All promotional materials that include representations about your drug product must be promptly
`revised to be consistent with the labeling changes approved in this supplement, including any
`new safety information [21 CFR 314.70(a)(4)]. The revisions in your promotional materials
`should include prominent disclosure of the important new safety information that appears in the
`revised package labeling. Within 7 days of receipt of this letter, submit your statement of intent
`to comply with 21 CFR 314.70(a)(4) to the address above, by fax to 301-847-8444, or
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`electronically in eCTD format. For more information about submitting promotional materials in
`eCTD format, see the draft Guidance for Industry (available at:
`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
`CM443702.pdf ).
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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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`If you have any questions, call Parinda Jani, Chief, Project Management Staff, at (301) 796-
`1232.
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`Sincerely,
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`{See appended electronic signature page}
`
`
`Sharon Hertz, MD
`Director
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`Division of Anesthesia, Analgesia, and
`Addiction Products
`Office of Drug Evaluation II
`Center for Drug Evaluation and Research
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`ENCLOSURE(S):
`Content of Labeling
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`Reference ID: 3928107
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`

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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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`SHARON H HERTZ
`05/09/2016
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`Reference ID: 3928107
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