`
`
`
`
`DEPARTMENT OF HEALTH AND HUMAN SERVICES
`
`
`
`
`
`
`
`NDA 022272/S-042
`
`
`
`
`
`
`Food and Drug Administration
`
`
` Silver Spring, MD 20993
`
`
`SUPPLEMENT APPROVAL
`
`
` Purdue Pharma LP
`
`
` One Stamford Forum
`
` Stamford, CT 06901-3431
`
`
`Attention:
`
`
`
`
`Richard J. Fanelli, PhD
`
`
`Vice President, R&D and Regulatory Affairs
`
`
`
`
`Dear Dr. Fanelli:
`
`
`
`
`
`
`Please refer to your Supplemental New Drug Application (sNDA) dated and received January
`
`31, 2019, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA)
`
`for OXYCONTIN (oxycodone hydrochloride) Extended-Release Tablets.
`
`
`
`
`
`This “Changes Being Effected in 30 days” supplemental new drug application provides for
`
`
`
`minor modifications to the approved risk evaluation and mitigation strategy (REMS).
`
`
`RISK EVALUATION AND MITIGATION STRATEGY REQUIREMENTS
`
`The REMS for opioid analgesic products intended for use in the outpatient setting (Opioid
`
`
`Analgesic REMS), of which OXYCONTIN is a member, was originally approved on July 9,
`
`
`
`2012, and the most recent REMS modification was approved on September 18, 2018. The REMS
`
`
`consists of a Medication Guide, elements to assure safe use, and a timetable for submission of
`
`
`assessments of the REMS.
`
`
`The proposed modification to the REMS for OXYCONTIN consists of adding a Medication
`
`
`
`
`
`Guide for two authorized generics that are identical to that of the branded product, except that
`
`
`
`
`
`KVK-Tech, Inc. and Rhodes Pharmaceuticals L.P. are listed as distributors for the authorized
`
`
`
`generics.
`
`
`Your proposed modified REMS, submitted on January 31, 2019, and appended to this letter, is
`
`approved.
`
`
`This REMS uses a shared system for the elements to assure safe use and the REMS assessments.
`
`This shared system, known as the Opioid Analgesic REMS Program, currently includes the
`
`
`
`products listed on the FDA REMS website, available at http://www.fda.gov/rems.
`
`
`
`
`
`
`Other products may be added in the future if additional Opioid Analgesic NDAs or ANDAs are
`
`approved.
`
`
`Reference ID: 4519754
`
`

`

`
`
`
`
` NDA 022272/S-042
`
` Page 2
`
`
` The timetable for submission of assessments for the Opioid Analgesic REMS Program remains
`
`unchanged.
`
`
`
`
`There are no changes to the REMS assessment plan described in our September 18, 2018, letter.
`
`
`
`We remind you that in addition to the REMS assessments submitted according to the timetable in
`
`the approved REMS, you must include an adequate rationale to support a proposed REMS
`
`
`modification for the addition, modification, or removal of any of goal or element of the REMS,
`
`
`as described in section 505-1(g)(4) of the FDCA.
`
`
`
`
`We also remind you that 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.
`
`This assessment should include:
`
`
`
`
`
`a) An evaluation of how the benefit-risk profile will or will not change with the new
`
`indication;
`
`
`
`
`b) A determination of the implications of a change in the benefit-risk profile for the current
`
`REMS;
`
`
`c) If the new indication for use introduces unexpected risks: A description of those risks
`
`and an evaluation of whether those risks can be appropriately managed with the currently
`
`approved REMS.
`
`d) If a REMS assessment was submitted in the 18 months prior to submission of the
`
`
`supplemental application for a new indication for use: A statement about whether the
`
`
`
`
`REMS was meeting its goals at the time of the last assessment and if any modifications
`
`of the REMS have been proposed since that assessment.
`
`e) If a REMS assessment has not been submitted in the 18 months prior to submission of the
`
`
`
`supplemental application for a new indication for use: Provision of as many of the
`
`
`currently listed assessment plan items as is feasible.
`
`f) 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
`
`
`modification, including: Provision of the reason(s) why the proposed REMS
`
`
`modification is necessary, the potential effect on the serious risk(s) for which the REMS
`
`
`was required, on patient access to the drug, and/or on the burden on the health care
`
`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
`
`proposed modified REMS. If you are not proposing REMS modifications, provide a
`
`
`
`rationale for why the REMS does not need to be modified.
`
`
`
`
`If the assessment instruments and methodology for your REMS assessments are not included in
`
`
`the REMS supporting document, or if you propose changes to the submitted assessment
`
`instruments or methodology, you should update the REMS supporting document to include
`
`
`specific assessment instrument and methodology information at least 90 days before the
`
`assessments will be conducted. Updates to the REMS supporting document may be included in a
`new document that references previous REMS supporting document submission(s) for
`
`unchanged portions. Alternatively, updates may be made by modifying the complete previous
`
`REMS supporting document, with all changes marked and highlighted. Prominently identify the
`
`Reference ID: 4519754
`
`

`

`
`
` NDA 022272/S-042
`
` Page 3
`
`
` submission containing the assessment instruments and methodology with the following wording
`
` in bold capital letters at the top of the first page of the submission:
`
`
`
`
`
`
`
`
`NDA 022272 REMS CORRESPONDENCE
`
`
`(insert concise description of content in bold capital letters, e.g.,
`
`
`UPDATE TO REMS SUPPORTING DOCUMENT - ASSESSMENT
`
`
`METHODOLOGY
`
`
`
`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,
`
`
`contact us to discuss what will be required in the authorized generic drug REMS submission.
`
`
`
`We remind you that section 505-1(f)(8) of FDCA prohibits holders of an approved covered
`
`
`
`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
`
`result in enforcement action.
`
`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
`
`first page of the submission as appropriate:
`
`
`
`
`
`NDA 022272 REMS ASSESSMENT
`
`
`
`NEW SUPPLEMENT FOR NDA 022272/S-0xx
`
`
`CHANGES BEING EFFECTED IN 30 DAYS
`
`
`PROPOSED MINOR REMS MODIFICATION
`
`
`
`
`or
`
`
`
`
`
`NEW SUPPLEMENT FOR NDA 022272/S-0xx
`
`
`PRIOR APPROVAL SUPPLEMENT
`
`
`PROPOSED MAJOR REMS MODIFICATION
`
`
`
`or
`
`
`
`
`
`NEW SUPPLEMENT FOR NDA 022272/S-0xx
`
`PRIOR APPROVAL SUPPLEMENT
`
`
`PROPOSED REMS MODIFICATIONS DUE TO SAFETY LABELING
`
`
`CHANGES SUBMITTED IN SUPPLEMENT XXX
`
`
`
`
`or
`
`
`
`NEW SUPPLEMENT (NEW INDICATION FOR USE)
`
`
`
`
`FOR NDA 022272/S-0xx
`
`
`REMS ASSESSMENT
`
`
`PROPOSED REMS MODIFICATION (if included)
`
`
`Reference ID: 4519754
`
`

`

`
`
` NDA 022272/S-042
`
` Page 4
`
`
`
` Should you choose to submit a REMS revision, prominently identify the submission containing
`
` the REMS revisions with the following wording in bold capital letters at the top of the first page
`
`
` of the submission:
`
`
`
`REMS REVISIONS FOR NDA 022272
`
`
`
`
`To facilitate review of your submission, we request that you submit your proposed modified
`
`REMS and other REMS-related materials in Microsoft Word format. If certain documents, such
`
`
`as enrollment forms, are only in PDF format, they may be submitted as such, but the preference
`
`
`
`is to include as many as possible in Word format.
`
`
`PROMOTIONAL MATERIALS
`
`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:
`
`
`
`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
`
`
`
`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 ).
`
` 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
`
` 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.
`
`
`
`
`
`
`
`Reference ID: 4519754
`
`

`

`
`
`
`
` NDA 022272/S-042
`
` Page 5
`
`
` REPORTING REQUIREMENTS
`
`
`
`
`We remind you that you must comply with reporting requirements for an approved NDA
`
`
`(21 CFR 314.80 and 314.81).
`
`
`
`
`
`
`If you have any questions, call Selma Kraft; Regulatory Project Manager, at (240) 402-9700.
`
`
`
`Sincerely,
`
`
`{See appended electronic signature page}
`
`
`Sharon Hertz, MD
`
`Director
`
`Division of Anesthesiology, Addiction Medicine,
`
`
`and Pain Medicine
`
`Office of Neuroscience
`
`Center for Drug Evaluation and Research
`
`
`
`ENCLOSURES:
`
`Medication Guides
`
`REMS
`
`Reference ID: 4519754
`
`

`

`Signature Page 1 of 1
`--------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically. Following this are manifestations of any and all
`electronic signatures for this electronic record.
`--------------------------------------------------------------------------------------------
`/s/
`------------------------------------------------------------
`
`SHARON H HERTZ
`11/14/2019 10:05:18 AM
`
`Reference ID: 4519754
`
`