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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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` NDA 203752/S-004
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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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` Noven Pharmaceuticals, Inc.
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` Attention: Audrey B. Alivio
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` Senior Manager, Regulatory Affairs
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` Empire State Building
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`350 Fifth Avenue, 37th Floor
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`New York, NY 10118
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`Dear Ms. Alivio:
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`Please refer to your Supplemental New Drug Application (sNDA) dated and received November
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`26, 2013, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA)
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`for Minivelle (estradiol transdermal system) 0.025 mg/day, 0.0375 mg/day, 0.05 mg/day, 0.075
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`mg/day, and 0.1 mg/day.
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`We acknowledge receipt of your amendments dated February 25, March 21, July 22, and (2)
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`September 19, 2014.
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`This supplemental new drug application provides for a new indication for the prevention of
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`postmenopausal osteoporosis, the addition of a 0.025 mg/day dose, updated language for Section
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`5.15 Severe Anaphylactic/Anaphylactoid Reactions and Angioedema, and the addition of Section
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`6.2 Postmarketing Experience.
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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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`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
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`of labeling must be identical to the enclosed labeling (text for the package insert, text for the
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`patient package insert, Medication Guide), with the addition of any labeling changes in pending
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`“Changes Being Effected” (CBE) supplements, as well as annual reportable changes not
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`included in the enclosed labeling.
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`Reference ID: 3632965
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` NDA 203752/S-004
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` Page 2
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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
`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
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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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`CARTON AND IMMEDIATE CONTAINER LABELS
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`Submit final printed carton and immediate container labels that are identical to the enclosed
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`carton and immediate container labels and carton and immediate container labels submitted on
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`July 22, 2014, as soon as they are available, but no more than 30 days after they are printed.
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`Please submit these labels electronically according to the guidance for industry Providing
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`Regulatory Submissions in Electronic Format – Human Pharmaceutical Product Applications
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`and Related Submissions Using the eCTD Specifications (June 2008). Alternatively, you may
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`submit 12 paper copies, with 6 of the copies individually mounted on heavy-weight paper or
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`similar material. For administrative purposes, designate this submission “Final Printed Carton
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`and Container Labels for approved NDA 203752/S-004.” Approval of this submission by
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`FDA is not required before the labeling is used.
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`Marketing the product(s) with final printed labeling that is not identical to the approved labeling
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`text may render the product misbranded and an unapproved new drug.
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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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`We are waiving the pediatric study requirement for this application because necessary studies are
`impossible or highly impractical, because post-menopausal osteoporosis does not occur in the
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`pediatric population.
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`Reference ID: 3632965
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` NDA 203752/S-004
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` Page 3
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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
`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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`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
`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 or by fax to 301-847-8444.
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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 George A. Lyght, Pharm.D., Sr. Regulatory Health Project
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`Manager, at (301) 796-0948.
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`Sincerely,
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`{See appended electronic signature page}
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`Hylton V. Joffe, M.D., M.M.Sc
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`Director
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`Division of Bone, Reproductive, and Urologic Products
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`Office of Drug Evaluation III
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`Center for Drug Evaluation and Research
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`Reference ID: 3632965
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` NDA 203752/S-004
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` Page 4
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` ENCLOSURES:
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` Content of Labeling
` Carton and Container Labeling
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`Reference ID: 3632965
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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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`HYLTON V JOFFE
`09/23/2014
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`Reference ID: 3632965
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