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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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` NDA 021928/S-039, S-041
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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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` Pfizer, Inc.
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` 235 E. 42nd Street
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` New York, NY 10017
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`Attention:
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`Lilya I. Donohew, PhD
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`Senior Director, Worldwide Regulatory Affairs
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`Dear Dr. Donohew:
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`Please refer to your Supplemental New Drug Applications (sNDAs) dated and received October
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`13, 2015, and July 21, 2016, and your amendments, submitted under section 505(b) of the
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`Federal Food, Drug, and Cosmetic Act (FDCA) for Chantix (varenicline) Tablets; 0.5 mg and 1
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`mg.
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`We also refer to our Safety Labeling Change notification letter dated July 15, 2016, notifying
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`you, under Section 505(o)(4) of the FDCA, of new safety information that we believe should be
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`included in the labeling for Chantix (varenicline). This information pertains to the risk of
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`somnambulism.
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`These Prior Approval supplemental new drug applications propose the following revisions to the
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`package insert:
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`S-039: Changes to the DOSAGE AND ADMINISTRATION, and CLINICAL
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`STUDIES sections of the Package Insert, and modification to the approved risk
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`evaluation and mitigation strategy (REMS) for Chantix, comprising of revisions
`to the MEDICATION GUIDE, to support the reduce-to-quit paradigm.
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`S-041: Consistent with our July 15, 2016, Safety Labeling Change notification letter,
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`changes to the WARNINGS AND PRECAUTIONS, ADVERSE
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`REACTIONS, PATIENT COUNSELING INFORMATION sections of the
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`labeling. S-041 also includes additional modification to the approved REMS,
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`comprising further revisions to the MEDICATION GUIDE regarding the new
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`safety information pertaining to risk of somnambulism.
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`APPROVAL & LABELING
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`We have completed our review of these supplemental applications, as amended and 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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`Reference ID: 3971721
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` NDA 021928/S-039 & S-041
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` Page 2
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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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`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
` automated drug registration and listing system (eLIST), as described at
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` http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. Content
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`of labeling must be identical to the enclosed labeling text for the package insert, and Medication
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`Guide, with the addition of any labeling changes in pending “Changes Being Effected” (CBE)
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`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
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`“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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`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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`RISK EVALUATION AND MITIGATION STRATEGY (REMS)
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`The REMS for Chantix (varenicline) was originally approved on October 19, 2009, and the most
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`recent modification was approved on October 15, 2014. The REMS consists of a Medication
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`Guide and a timetable for submission of assessments of the REMS. Your proposed
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`modifications to the REMS consist of revisions to the Medication Guide to add new language
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`describing a reduce-to-quit regimen and to provide information about the risk of somnambulism
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`so as to furnish adequate information for the safe and effective use of the drug.
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`Reference ID: 3971721
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` NDA 021928/S-039 & S-041
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` Page 3
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` Your proposed modified REMS, submitted on October 13, 2015, and appended to this letter, is
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` approved.
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`The modified REMS consist of a Medication Guide and a timetable for submission of
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`assessments of the REMS.
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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 October 19, 2009.
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`There are no changes to the REMS assessment plan described in our October 19, 2009, letter.
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`We remind you that in addition to the REMS assessments submitted according to the timetable in
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`the approved REMS, you must include an adequate rationale to support a proposed REMS
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`modification for the addition, modification, or removal of any of goal or element of the REMS,
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`as described in section 505-1(g)(4) of the FDCA.
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`We also remind you that you must submit a REMS assessment when you submit a supplemental
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`application for a new indication for use as described in section 505-1(g)(2)(A). This assessment
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`should include:
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`a) An evaluation of how the benefit-risk profile will or will not change with the new
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`indication;
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`b) A determination of the implications of a change in the benefit-risk profile for the current
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`REMS;
`c) If the new, proposed indication for use introduces unexpected risks: A description of
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`those risks and an evaluation of whether those risks can be appropriately managed with
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`the currently approved REMS.
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`d) If a REMS assessment was submitted in the 18 months prior to submission of the
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`supplemental application for a new indication for use: A statement about whether the
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`REMS was meeting its goals at the time of the last assessment and if any modifications
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`of the REMS have been proposed since that assessment.
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`e) If a REMS assessment has not been submitted in the 18 months prior to submission of the
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`supplemental application for a new indication for use: Provision of as many of the
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`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
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`because of the new indication of use, submit an adequate rational to support the
`modification, including: Provision of the reason(s) why the proposed REMS
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`modification is necessary, the potential effect on the serious risk(s) for which the REMS
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`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 a REMS modification, provide a
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`rationale for why the REMS does not need to be modified.
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`If the assessment instruments and methodology for your REMS assessments are not included in
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`the REMS supporting document, or if you propose changes to the submitted assessment
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`Reference ID: 3971721
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` NDA 021928/S-039 & S-041
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` Page 4
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` instruments or methodology, you should update the REMS supporting document to include
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` 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
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` new document that references previous REMS supporting document submission(s) for
` unchanged portions. Alternatively, updates may be made by modifying the complete previous
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` REMS supporting document, with all changes marked and highlighted. Prominently identify the
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` submission containing the assessment instruments and methodology with the following wording
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` in bold capital letters at the top of the first page of the submission:
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`NDA 021928 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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`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 the submission containing the REMS assessments or proposed
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`modifications of the REMS with the following wording in bold capital letters at the top of the
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`first page of the submission as appropriate:
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`NDA 021928 REMS ASSESSMENT
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`NEW SUPPLEMENT FOR NDA 021928/S-000/
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`CHANGES BEING EFFECTED IN 30 DAYS
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`PROPOSED MINOR REMS MODIFICATION
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`or
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`NEW SUPPLEMENT FOR NDA 021928/S-000/
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`PRIOR APPROVAL SUPPLEMENT
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`PROPOSED MAJOR REMS MODIFICATION
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`or
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`NEW SUPPLEMENT FOR NDA 021928/S-000/
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`PRIOR APPROVAL SUPPLEMENT
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`PROPOSED REMS MODIFICATIONS DUE TO SAFETY LABEL CHANGES
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`SUBMITTED IN SUPPLEMENT XXX
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`NEW SUPPLEMENT (NEW INDICATION FOR USE)
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`FOR NDA 021928/S-000/
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`REMS ASSESSMENT
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`PROPOSED REMS MODIFICATION (if included)
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`Reference ID: 3971721
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`REMS REVISION FOR NDA 021928
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` NDA 021928/S-039 & S-041
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` Page 5
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` Should you choose to submit a REMS revision, prominently identify the submission containing
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` the REMS revisions with the following wording in bold capital letters at the top of the first page
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` of the submission:
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`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
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`as enrollment forms, are only in PDF format, they may be submitted as such, but the preference
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`is to include as many as possible in Word format.
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`If you do not submit electronically, please send 5 copies of REMS-related submissions.
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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
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`(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
`Guidance for Industry (available at:
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`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
`CM443702.pdf ).
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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
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`FDA 2253 is available at
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`http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf.
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` 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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`Reference ID: 3971721
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` NDA 021928/S-039 & S-041
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` Page 6
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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
` 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
` 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 Ayanna Augustus, PhD, RAC, Sr. Regulatory Project Manager, at
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`(301) 796-3980.
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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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`REMS
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`Reference ID: 3971721
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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
`08/12/2016
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`Reference ID: 3971721
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