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` NDA 021436/S-044/S-045
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` NDA 202971/S-013
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` NDA 207202/S-002/S-004
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` NDA 021713/S-035/S-036
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` NDA 021729/S-027/S-028
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` NDA 021866/S-029/S-030
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`SUPPLEMENT APPROVAL
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`Otsuka Pharmaceutical Company, Ltd.
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`Attention: Dana Cahill, PhD
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`Director, Global Regulatory Affairs
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`2440 Research Blvd.
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`Rockville, MD 20850
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`Dear Dr. Cahill:
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`Please refer to your Supplemental New Drug Applications (sNDA) dated and received
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`April 2, 2019 (NDA 207202/S-002), January 16, 2020 (NDAs 021436/S-044, 021713/S
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`035, 021729/S-027, 021866/S-029), January 28, 2020 (NDAs 021436/S-045, 021713/S
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`036, NDA 021729/S-028, 021866/S-030), and January 29, 2020 (NDAs 202971/S-013,
`207202/S-004), submitted under section 505(b) of the Federal Food, Drug, and
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`Cosmetic Act (FDCA) for Abilify (aripiprazole) tablets (NDA 021436), Abilify Maintena
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`(aripiprazole) for extended-release injectable suspension (NDA 202971), Abilify MyCite
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`(aripiprazole tablets with sensor) (NDA 207202), Abilify (aripiprazole) oral solution (NDA
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`021713), Abilify Discmelt (aripiprazole) orally disintegrating tablets (NDA 021729), and
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`Abilify (aripiprazole) injection for intramuscular use (NDA 021866).
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`We acknowledge receipt of your amendment, submitted to NDA 021436/S-044, dated
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`January 16, 2020, which constituted a complete response to our November 13, 2019,
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`action letter.
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`NDAs 021436/S-045; 207202/S-004; 021713/S-036; 021729/S-087; 021866/S-030;
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`202971/S-013
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`We also refer to our letter dated December 5, 2019, notifying you, under Section
`505(o)(4) of the FDCA, of new safety information that we believe should be included in
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`the labeling for aripiprazole. This information pertains to the risk of drug reaction with
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`eosinophilia and systemic symptoms (DRESS).
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`These supplemental new drug applications provide for revisions to the labeling for
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`aripiprazole consistent with our December 5, 2019, letter.
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`Reference ID: 4556968
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` NDAs 021436/S-044/S-045, 202971/S-013, 207202/S-002/S-004, 021713/S-035/S-036,
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`021729/S-027/S-028, 021866/S-029/S-030
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` Page 2
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`NDAs 021436/S-044; 207202/S-002; 021713/S-035; 021729/S-027; 021866/S-029
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` These supplemental new drug applications provide for the addition of the term
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` “oculogyric crisis” in the Postmarketing Experience section of the Prescribing
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` Information.
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`APPROVAL & LABELING
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`We have completed our review of these applications, as amended. They are approved,
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`effective on the date of this letter, for use as recommended in the enclosed agreed-
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`upon labeling.
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` WAIVER OF ½ PAGE LENGTH REQUIREMENT FOR HIGHLIGHTS
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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
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`content of labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format using
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`the FDA automated drug registration and listing system (eLIST), as described at
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`FDA.gov.1 Content of labeling must be identical to the enclosed labeling (text for the
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`Prescribing Information and Medication Guide), with the addition of any labeling
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`changes in pending “Changes Being Effected” (CBE) supplements, as well as annual
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`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
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`industry SPL Standard for Content of Labeling Technical Qs and As.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 that include labeling
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`changes for this NDA, including CBE supplements for which FDA has not yet issued an
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`action letter, with the content of labeling [21 CFR 314.50(l)(1)(i)] in Microsoft Word
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`format, that includes the changes approved in this supplemental application, as well as
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`annual reportable changes. To facilitate review of your submission(s), provide a
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`highlighted or marked-up copy that shows all changes, as well as a clean Microsoft
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`Word version. The marked-up copy should provide appropriate annotations, including
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`supplement number(s) and annual report date(s).
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` 1 http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm
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` 2 We update guidances periodically. For the most recent version of a guidance, check the FDA Guidance
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` Documents Database https://www.fda.gov/RegulatoryInformation/Guidances/default.htm.
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`U.S. Food and Drug Administration
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`Silver Spring, MD 20993
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`www.fda.gov
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`Reference ID: 4556968
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` NDAs 021436/S-044/S-045, 202971/S-013, 207202/S-002/S-004, 021713/S-035/S-036,
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`021729/S-027/S-028, 021866/S-029/S-030
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` Page 3
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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
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` new active ingredients (which includes new salts and new fixed combinations), new
` indications, new dosage forms, new dosing regimens, or new routes of administration
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` are required to contain an assessment of the safety and effectiveness of the product for
` the claimed indication in pediatric patients unless this requirement is waived, deferred,
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` or inapplicable.
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`Because none of these criteria apply to your application, you are exempt from this
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`requirement.
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`PROMOTIONAL MATERIALS
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`All promotional materials that include representations about your drug product must be
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`promptly revised to be consistent with the labeling changes approved in this
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`supplement, including any new safety information [21 CFR 314.70(a)(4)]. The revisions
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`in your promotional materials should include prominent disclosure of the important new
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`safety information that appears in the revised labeling. Within 7 days of receipt of this
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`letter, submit your statement of intent to comply with 21 CFR 314.70(a)(4) to the
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`address above, by fax to 301-847-8444, or electronically in eCTD format. For more
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`information about submitting promotional materials in eCTD format, see the draft
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`guidance for industry Providing Regulatory Submissions in Electronic and Non-
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`Electronic Format-Promotional Labeling and Advertising Materials for Human
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`Prescription Drugs.
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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 Ermias Zerislassie, Safety Regulatory Project Manager,
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`at (301) 796-2770.
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`Sincerely,
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`{See appended electronic signature page}
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`Tiffany R. Farchione, MD
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`
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`Director (Acting)
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`Division of Psychiatry
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`Office of Neuroscience
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`Center for Drug Evaluation and Research
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`U.S. Food and Drug Administration
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`
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`Silver Spring, MD 20993
`www.fda.gov
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`Reference ID: 4556968
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`NDAs 021436/S-044/S-045, 202971/S-013, 207202/S-002/S-004, 021713/S-035/S-036,
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`021729/S-027/S-028, 021866/S-029/S-030
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`Page 4
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`ENCLOSURES:
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`• Content of Labeling
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`o Prescribing Information
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`o Medication Guide
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`U.S. Food and Drug Administration
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`
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`Silver Spring, MD 20993
`www.fda.gov
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`Reference ID: 4556968
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`
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`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/
`------------------------------------------------------------
`
`TIFFANY R FARCHIONE
`02/05/2020 12:21:33 PM
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`Reference ID: 4556968
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`