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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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` NDA 021928/S-033, S-034 &S-037
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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
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`December 16, 2013 (S-033 and S-034), and April 11, 2014 (S-037), submitted under section
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`505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA) for Chantix (varenicline) Tablets;
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`0.5 mg and 1 mg.
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`We acknowledge receipt of your amendments dated February 7, March 21, April 11, and 28, and
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`October 2, 2014 (S-033), January 29, February 7, April 1, 11, and 28, and October 2, and 7,
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`2014 (S-034), July 9, August 12, September 5, and October 2, 2014 (S-037).
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`These supplemental applications propose the following labeling revisions to the Package Insert:
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`S-033: the safety and efficacy of varenicline for smoking cessation in patients with
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`current or past history of major depressive disorder (MDD)
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`S-034: the safety and efficacy of varenicline for smoking cessation in patients who had
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`previously been treated with varenicline
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`S-037: proposes new 4-week trade packaging labeling
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`Supplemental application S-034 also provides for a proposed modification to the approved risk
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`evaluation and mitigation strategy (REMS).
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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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`WAIVER OF HIGHLIGHTS SECTION
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`Reference ID: 3643541
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` NDA 021928/S-033, S-034 & S-037
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` Page 2
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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 includes 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
`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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`CARTON AND IMMEDIATE CONTAINER LABELS
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`We acknowledge your September 5, 2014, submission containing final printed carton and
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`container labels.
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`REQUIRED PEDIATRIC ASSESSMENTS
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`Under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355c), all applications for new
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`active ingredients, new indications, new dosage forms, new dosing regimens, or new routes of
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`administration are required to contain an assessment of the safety and effectiveness of the
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`product for the claimed indication(s) in pediatric patients unless this requirement is waived,
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`deferred, or inapplicable.
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`Because none of these criteria apply to your application, you are exempt from this requirement.
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`Reference ID: 3643541
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` NDA 021928/S-033, S-034 & S-037
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` Page 3
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` RISK EVALUATION AND MITIGATION STRATEGY
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` The REMS for Chantix (varenicline) was originally approved on October 19, 2009, and the most
` recent modification was approved on September 19, 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 include information
`on the use of varenicline for smoking cessation in patients who had previously been treated with
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`varenicline.
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`Your proposed modified REMS, submitted on December 16, 2013, amended on April 1, 2014,
`and October 7, 2014, and appended to this letter, is approved.
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` The modified REMS consists 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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`In addition to the assessments submitted according to the timetable included in the approved
`REMS, you must submit a REMS assessment and may propose a modification to the approved
`REMS when you submit a supplemental application for a new indication for use as described in
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`section 505-1(g)(2)(A) of the FDCA.
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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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`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
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`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
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`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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`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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`Reference ID: 3643541
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` NDA 021928/S-033, S-034 & S-037
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` Page 4
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` NDA 021928 REMS ASSESSMENT
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`NEW SUPPLEMENT FOR NDA 021928
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`PROPOSED REMS MODIFICATION
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`NEW SUPPLEMENT (NEW INDICATION FOR USE)
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`FOR NDA 021928
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`REMS ASSESSMENT
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`PROPOSED REMS MODIFICATION (if included)
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`If you do not submit electronically, please send 5 copies of REMS-related submissions.
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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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`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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`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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`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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`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 or by fax to 301-847-8444.
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`Reference ID: 3643541
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` NDA 021928/S-033, S-034 & S-037
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` Page 5
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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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`Rigoberto Roca, MD
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`Deputy Director
`Division of Anesthesia, Analgesia and
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`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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`Container and Carton Labeling
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`REMS
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`Reference ID: 3643541
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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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`RIGOBERTO A ROCA
`10/15/2014
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`Reference ID: 3643541
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