DEPARTMENT OF HEALTH & HUMAN SERVICES
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`Public Health Service
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` Food and Drug Administration
`Rockville, MD 20857
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`NDA 21-436 / S-028
`NDA 21-713 / S-020
`NDA 21-729 / S-013
`NDA 21-866 / S-014
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`Otsuka Pharmaceutical Development & Commercialization, Inc.
`Attention: Kusuma Mallikaarjun, Ph.D.
`Senior Director, Regulatory Affairs
`2440 Research Boulevard
`Rockville, MD 20850
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`Dear Dr. Mallikaarjun:
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`Please refer to your supplemental new drug applications dated and received on May 5, 2009,
`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, and 30 mg [NDA 21-436], ABILIFY
`(aripiprazole) Oral Solution 1 mg / mL [NDA 21-713], ABILIFY DISCMELT (aripiprazole) Orally
`Disintegrating Tablets 10 mg and 15 mg [NDA 21-729], and ABILIFY (aripiprazole) Injection
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`9.75 mg / 1.3 mL (7.5 mg / mL) [NDA 21-866].
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`We acknowledge receipt of your submissions dated June 17, 2009, to each of the supplements
`referenced above.
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`Reference is made to our letter dated April 5, 2009, notifying you, under Section 505(o)(4) of the
`FDCA, of new safety information that we believe should be included in the labeling for the entire
`class of antipsychotic drugs. This information pertains to the risk of leukopenia, neutropenia, and
`agranulocytosis.
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`We also refer you to the letter we sent on June 2, 2009, informing you that we determined that a 30-
`day extension of the discussion period was warranted to allow us to complete our review and reach
`agreement on the content of the labeling. We also refer to modified labeling language that we sent
`to you via email on June 9, 2009.
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`The supplemental new drug applications, as amended, provide for the addition of the subsection
`PRECAUTIONS/ Leukopenia, Neutropenia and Agranulocytosis to the labeling for ABILIFY
`(aripiprazole).
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`We have completed our review of these supplemental applications, as amended. These applications
`are approved, effective on the date of this letter, for use as recommended in the enclosed agreed-
`upon labeling text (text for the package insert).
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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 as described at
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`page 2
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`NDA 21-436 / S-028
`NDA 21-713 / S-020
`NDA 21-729 / S-013
`NDA 21-866 / S-014
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`http://www.fda.gov/oc/datacouncil/spl.html that is identical to the enclosed labeling (text for the
`package insert). Upon receipt, we will transmit that version to the National Library of Medicine for
`public dissemination. For administrative purposes, please designate this submission, “SPL for
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`approved supplements NDA 21-436 / S-028, NDA 21-713 / S-020, NDA 21-729 / S-013, and
`NDA 21-866 / S-014.”
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`In addition, within 21 days of the date of this letter, amend any pending applications for these
`NDAs with content of labeling in structured product labeling (SPL) format to include the changes
`approved in these applications.
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`Failure to make these changes within the specified period of time could make your product
`misbranded under 21 USC 321(n) and 352(a).
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`We request that the revised labeling approved today be available on your website within 10 days of
`receipt of this letter.
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`LETTERS TO HEALTH CARE PROFESSIONALS
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`If you issue a letter communicating important information about this drug product (i.e., a “Dear
`Health Care Professional” letter), we request that you submit a copy of the letter to these NDAs and
`a copy to the following address:
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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, please contact Doris J. Bates, Ph.D., Safety Regulatory Project Manager,
`at (301)796-2260.
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`Sincerely,
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` {See appended electronic signature page}
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`Thomas P. Laughren, M.D.
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` Director
`Division of Psychiatry Products
`Office of Drug Evaluation I
`Center for Drug Evaluation and Research
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`Enclosure: Package Insert labeling
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`MEDWATCH
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`Food and Drug Administration
`5515 Security Lane
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`HFD-001, Suite 5100
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`Rockville, MD 20852
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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.
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`/s/
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`Mitchell Mathis
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`7/19/2009 07:53:08 AM
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`For Dr. Laughren
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