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`DEPARTMENT OF HEALTH & HUMAN
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` SERVICES
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`NDAs 21436/S029, 21729/S014, 21713/S021, 21866/S016
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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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`Otsuka Pharmaceutical Development & Commercialization, Inc.
`Attention: David Goldberger
`Senior Director, Regulatory Affairs
`100 Overlook Center, 1st Floor
`Princeton, NJ 08540
`
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`Dear Mr. Goldberger:
`
`Please refer to your Supplemental New Drug Applications (sNDA) dated and received April 16,
`2010, submitted under section 505(b) of the Federal Food Drug, and Cosmetic Act (FDCA) for
`Abilify (aripiprazole) tablets 2 mg, 5 mg, 10 mg, 15 mg, 20 mg, 30 mg (NDA 21436), oral
`solution 1mg/ml (NDA 21713), orally disintegrating tablet 10 mg, 15 mg (NDA 21729), and
`injectable formulation 9.75 mg/1.3 mL single-dose vial (NDA 21866).
`
`We acknowledge receipt of your submissions dated June 21, 2010, June 25, 2010, November 30,
`2010, and January 26, 2011.
`
`These Prior Approval supplemental new drug applications provide for the use of Abilify
`(aripiprazole) tablet, oral solution, orally disintegrating tablet, and injectable formulation for the
`maintenance treatment of bipolar I disorder as an adjunct to lithium or valproate.
`
`We have completed our review of these supplemental applications. They are approved, effective
`on the date of this letter, for use as recommended in the enclosed, agreed-upon labeling 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, please submit the
`content of 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
`http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. Content
`of labeling must be identical to the enclosed labeling (text for the package insert and Medication
`Guide). For administrative purposes, please designate this submission, “SPL for approved
`sNDAs 21-436/S029, 21-729/S014, 21-713/S021, 21-866/S016.”
`
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`Information on submitting SPL files using eLIST may be found in the guidance for industry
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`titled “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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`Reference ID: 2906732
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` NDAs 21436/S029, 21729/S014, 21713/S021, 2-866/S016
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`Page 2
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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 for this NDA, including CBE
`supplements for which FDA has not yet issued an action letter, with the content of labeling
`[21 CFR 314.50(l)(1)(i)] in MS Word format, that includes the 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-up copy that shows all
`changes, as well as a clean Microsoft Word version. The marked-up copy should provide
`appropriate annotations, including supplement number(s) and annual report date(s).
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`REQUIRED PEDIATRIC ASSESSMENTS
`
`
`Under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355c), all applications for new
`active ingredients, new indications, new dosage forms, new dosing regimens, or new routes of
`administration are required to contain an assessment of the safety and effectiveness of the
`product for the claimed indication(s) in pediatric patients unless this requirement is waived,
`deferred, or inapplicable.
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`We are waiving the pediatric study requirement for ages 0 to 9 years because necessary studies
`are impossible or highly impracticable. This is because bipolar disorder cannot be reliably
`diagnosed in this age group, and therefore appropriate studies cannot be developed or carried out.
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`In addition, studies are completed in the 10-17 age group, given that we have adult data for
`adjunctive maintenance. Given that efficacy has been established for acute monotherapy
`treatment of manic and mixed episodes associated with bipolar I disorder in a population aged
`10-17, in our judgment, adjunctive maintenance efficacy can be extrapolated to the 10-17 age
`group from the adult adjunctive maintenance study. Therefore, no additional pediatric studies
`are needed at this time.
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`PROMOTIONAL MATERIAL
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`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:
`
`
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Division of Drug Marketing, Advertising, and Communications
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
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`
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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
`FDA 2253 is available at http://www.fda.gov/opacom/morechoices/fdaforms/cder.html;
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`Reference ID: 2906732
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` NDAs 21436/S029, 21729/S014, 21713/S021, 2-866/S016
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`Page 3
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`instructions are provided on page 2 of the form. For more information about submission of
`promotional materials to the Division of Drug Marketing, Advertising, and Communications
`(DDMAC), see http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm.
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`LETTERS TO HEALTH CARE PROFESSIONALS
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`If you decide to issue a letter communicating important safety-related information about this
`drug product (i.e., a “Dear Health Care Professional” letter), we request that you submit, at least
`24 hours prior to issuing the letter, an electronic copy of the letter to this NDA to the following
`address:
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`MedWatch Program
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`Office of Special Health Issues
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`Food and Drug Administration
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`10903 New Hampshire Ave
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`Building 32, Mail Stop 5353
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`Silver Spring, MD 20993
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`REPORTING REQUIREMENTS
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`We remind you that you must comply with reporting requirements for an approved NDA
`(21 CFR 314.80 and 314.81).
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`If you have any questions, call Sonny Saini, Pharm.D., MBA, Regulatory Project Manager, at
`(301) 796-0532.
`
`
`Sincerely,
`
`{See appended electronic signature page}
`
`
`Thomas Laughren, M.D.
`Director
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`Division of Psychiatry Products
`Office of Drug Evaluation I
`Center for Drug Evaluation and Research
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`Enclosure
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`Content of Labeling
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`Reference ID: 2906732
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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/
`----------------------------------------------------
`
`THOMAS P LAUGHREN
`02/16/2011
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`Reference ID: 2906732
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`