E9-28871. Determination That ABILIFY DISCMELT (Aripiprazole) Orally Disintegrating Tablets, 20 Milligrams and 30 Milligrams, Were Not Withdrawn From Sale for Reasons of Safety or Effectiveness

AGENCY:

Food and Drug Administration, HHS.

ACTION:

Notice.

SUMMARY:

The Food and Drug Administration (FDA) has determined that ABILIFY DISCMELT (aripiprazole) orally disintegrating tablets, 20 milligrams (mg) and 30 mg, were not withdrawn from sale for reasons of safety or effectiveness. This determination will allow FDA to approve abbreviated new drug applications (ANDAs) for aripiprazole orally disintegrating tablets, 20 mg and 30 mg, if all other legal and regulatory requirements are met.

FOR FURTHER INFORMATION CONTACT:

Nam Kim, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, rm. 6320, Silver Spring, MD 20993-0002, 301-796-3601.

SUPPLEMENTARY INFORMATION:

In 1984, Congress enacted the Drug Price Competition and Patent Term Restoration Act of 1984 (Pub. L. 98-417) (the 1984 amendments), which authorized the approval of duplicate versions of drug products approved under an ANDA procedure. ANDA sponsors must, with certain exceptions, show that the drug for which they are seeking approval contains the same active ingredient in the same strength and dosage form as the “listed drug,” which is a version of the drug that was previously approved. Sponsors of ANDAs do not have to repeat the extensive clinical testing otherwise necessary to gain approval of a new drug application (NDA). The only clinical data required in an ANDA are data to show that the drug that is the subject of the ANDA is bioequivalent to the listed drug.

The 1984 amendments include what is now section 505(j)(7) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355(j)(7)), which requires FDA to publish a list of all approved drugs. FDA publishes this list as part of the “Approved Drug Products With Therapeutic Equivalence Evaluations,” which is generally known as the “Orange Book.” Under FDA regulations, drugs are removed from the list if the agency withdraws or suspends approval of the drug's NDA or ANDA for reasons of safety or effectiveness or if FDA determines that the listed drug was withdrawn from sale for reasons of safety or effectiveness (§ 314.162 (21 CFR 314.162)).

Under § 314.161(a)(1) (21 CFR 314.161(a)(1)), the agency must determine whether a listed drug was withdrawn from sale for reasons of safety or effectiveness before an ANDA that refers to that listed drug may be approved. FDA may not approve an ANDA that does not refer to a listed drug.

ABILIFY DISCMELT (aripiprazole) orally disintegrating tablets, 20 mg and 30 mg, are the subject of approved NDA 21-729 held by Otsuka Pharmaceutical Company, Limited (Otsuka). ABILIFY (aripiprazole) is indicated for the treatment of schizophrenia, for the acute and maintenance treatment of manic and mixed episodes associated with bipolar I disorder, as an adjunctive therapy to either lithium or valproate for the acute treatment of manic and mixed episodes associated with bipolar I disorder, for use as an adjunctive therapy to antidepressants for the treatment of major depressive disorder, for the treatment of irritability associated with autistic disorder, and for the acute treatment of agitation associated with schizophrenia or bipolar I disorder, manic or mixed.

FDA approved the NDA for ABILIFY DISCMELT (aripiprazole) orally disintegrating tablets, including the 20-mg and 30-mg strengths, on June 7, 2006. Otsuka has never marketed the 20-mg and 30-mg strengths of ABILIFY DISCMELT (aripiprazole) orally disintegrating tablets, and the 20-mg and 30-mg strength orally disintegrating tablets are listed in the “Discontinued Drug Product List” of the Orange Book.

Rakoczy Molino Mazzochi Siwik LLP submitted a citizen petition dated May 29, 2008 (Docket No. FDA-2008-P-0330), under 21 CFR 10.30, requesting that the agency (1) determine that ABILIFY DISCMELT (aripiprazole) orally disintegrating tablets, 20 mg and 30 mg, were discontinued from sale for reasons unrelated to safety and efficacy and (2) accept ANDAs for aripiprazole orally disintegrating tablets, 20 mg and 30 mg, and determine that such ANDAs are eligible for approval if all other legal and regulatory requirements are met. After considering the citizen petition and reviewing agency records, FDA has determined that ABILIFY DISCMELT (aripiprazole) orally disintegrating tablets, 20 mg and 30 mg, were not withdrawn from sale for reasons of safety or effectiveness. To date, Otsuka has not marketed ABILIFY DISCMELT (aripiprazole) orally disintegrating tablets, 20 mg and 30 mg. In previous instances (see, e.g., 72 FR 9763, March 5, 2007; 61 FR 25497, May 21, 1996), the agency has determined that, for purposes of §§ 314.161 and 314.162, never marketing an approved drug product is equivalent to withdrawing the drug from sale.

The petitioner identified no data or other information suggesting that ABILIFY DISCMELT (aripiprazole) orally disintegrating tablets, 20 mg and 30 mg, were withdrawn from sale as a result of safety or effectiveness concerns. FDA has reviewed its files for records concerning the withdrawal of ABILIFY DISCMELT (aripiprazole) orally disintegrating tablets, 20 mg and 30 mg. There is no indication that Otsuka's decision not to market ABILIFY DISCMELT (aripiprazole) orally disintegrating tablets, 20 mg and 30 mg, commercially is a function of safety or effectiveness concerns, and no information has been submitted to the docket concerning the reason for which ABILIFY DISCMELT (aripiprazole) orally disintegrating tablets, 20 mg and 30 mg, were withdrawn from sale. FDA's independent evaluation of relevant information has uncovered nothing that would indicate that ABILIFY DISCMELT (aripiprazole) orally disintegrating tablets, 20 mg and 30 mg, were withdrawn from sale for reasons of safety or effectiveness.

For the reasons outlined in this document, FDA has determined that ABILIFY DISCMELT (aripiprazole) orally disintegrating tablets, 20 mg and 30 mg, were not withdrawn from sale for reasons of safety or effectiveness. Accordingly, the agency will continue to list ABILIFY DISCMELT (aripiprazole) orally disintegrating tablets, 20 mg and 30 mg, in the “Discontinued Drug Product List” section of the Orange Book. The “Discontinued Drug Product List” delineates, among other items, drug products that have been discontinued from marketing for reasons other than safety or effectiveness. ANDAs that refer to ABILIFY DISCMELT (aripiprazole) orally disintegrating tablets, 20 mg and 30 mg, may be approved by the agency as long as they meet all relevant legal and regulatory requirements for approval of ANDAs. If FDA determines that labeling for these drug products should be revised to meet current standards, the agency will advise ANDA applicants to submit such labeling.

Dated: November 30, 2009.

David Horowitz,

Assistant Commissioner for Policy.