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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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` NDA 201655/S-021
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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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`Endo Pharmaceuticals, Inc.
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`1400 Atwater Drive
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`Malvern, PA 19355
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`Attention:
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`Tara Chapman. PharmD
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`Senior Director, Regulatory Affairs
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`Dear Dr. Chapman:
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`Please refer to your Supplemental New Drug Application (sNDA) dated and received April 20,
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`2016, and your amendments, submitted under section 505(b) of the Federal Food, Drug, and
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`Cosmetic Act (FDCA) for OPANA ER (oxymorphone hydrochloride) Extended-Release Tablets.
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`We also refer to our letter dated March 22, 2016, notifying you, under Section 505(o)(4) of the
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`FDCA, of new safety information that we believe should be included in the labeling for OPANA
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`ER. This information pertains to the risks of serotonin syndrome with concomitant use of
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`serotonergic drugs; adrenal insufficiency; androgen deficiency; and anaphylaxis, angioedema,
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`and other hypersensitivity reactions.
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`Additionally, we refer to our letter dated August 31, 2016, notifying you, under Section
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`505(o)(4) of the FDCA, of new safety information that we believe should be included in the
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`labeling for OPANA ER. This information pertains to the risks of concomitant use of opioid
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`analgesics with benzodiazepines or other central nervous system depressants.
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`Supplement S-021 provides for the Safety Labeling Changes required under Section 505(o)(4) of
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`the FDCA, consistent with our March 22 and August 31, 2016, letters, and additional revisions to
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`the Package Insert.
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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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`WAIVER OF HIGHLIGHTS SECTION
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`Please note that we have previously granted a waiver of the requirements of 21 CFR
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`201.57(d)(8) regarding the length of Highlights of prescribing information.
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`Reference ID: 4028719
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`NDA 201655/S-021
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`Page 2
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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
`of labeling must be identical to the enclosed labeling text, with the addition of any labeling
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`changes in pending “Changes Being Effected” (CBE) supplements, as well as annual reportable
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`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
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`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 include 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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`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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`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
`(3) the package insert(s) to:
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`OPDP Regulatory Project Manager
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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
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`Beltsville, MD 20705-1266
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`Alternatively, you may submit a request for advisory comments electronically in eCTD format.
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`For more information about submitting promotional materials in eCTD format, see the draft
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`Reference ID: 4028719
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`NDA 201655/S-021
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`Page 3
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` Guidance for Industry (available at:
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`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
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` CM443702.pdf ).
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` You must submit final promotional materials and package insert(s), accompanied by a Form
` 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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`All promotional materials that include representations about your drug product must be promptly
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`revised to be consistent with the labeling changes approved in this supplement, including any
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`new safety information [21 CFR 314.70(a)(4)]. The revisions in your promotional materials
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`should include prominent disclosure of the important new safety information that appears in the
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`revised package labeling. Within 7 days of receipt of this letter, submit your statement of intent
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`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
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`eCTD format, see the draft Guidance for Industry (available at:
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`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
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`(21 CFR 314.80 and 314.81).
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`If you have any questions, call Mark Liberatore, PharmD; Safety Regulatory Project Manager, at
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`(301) 796-2221.
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`Sincerely,
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`{See appended electronic signature page}
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`Sharon Hertz, MD
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`Director
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`Division of Anesthesia, Analgesia,
`and 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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`ENCLOSURE(S):
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`Content of Labeling
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`Reference ID: 4028719
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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
`12/16/2016
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`Reference ID: 4028719
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