2010-22807. Determination That VESANOID (Tretinoin) Capsules, 10 Milligrams, Were Not Withdrawn From Sale for Reasons of Safety or Effectiveness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The Food and Drug Administration (FDA) has determined that VESANOID (tretinoin) Capsules, 10 milligrams (mg), were not withdrawn from sale for reasons of safety or effectiveness. This determination means that FDA will not begin procedures to withdraw approval of the abbreviated new drug application (ANDA) that refers to this drug product, and it will allow FDA to continue to approve ANDAs that refer to the product as long as they meet relevant legal and regulatory requirements.

FOR FURTHER INFORMATION CONTACT:

Molly Flannery, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, rm. 6237, Silver Spring, MD 20993-0002, 301-796-3543.

SUPPLEMENTARY INFORMATION:

In 1984, Congress enacted the Drug Price Competition and Patent Term Restoration Act of 1984 (Public Law 98-417) (the 1984 amendments), which authorized the approval of duplicate versions of drug products approved under an ANDA procedure. ANDA applicants 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. ANDA applicants 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 known generally 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approval of the drug's NDA or ANDA for reasons of safety or effectiveness or if FDA determines that the listed drug was withdrawn from sale for reasons of safety or effectiveness (21 CFR 314.162). Under § 314.161(a)(1) (21 CFR 314.161(a)(1)), the agency must determine whether a listed drug was withdrawn from sale for reasons of safety or effectiveness before an ANDA that refers to that listed drug may be approved.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.

VESANOID (tretinoin) Capsules, 10 mg, are the subject of NDA 20-438, held by Hoffman-La Roche Inc. (Roche), and initially approved on November 22, 1995. VESANOID is indicated for the “induction of remission in patients with acute promyelocytic leukemia (APL), French-American-British (FAB) classification M3 (including the M3 variant), characterized by the presence of the t(15;17) translocation and/or the presence of the PML/RARα [promyelocytic leukemia/retinoic acid receptor alpha] gene who are refractory to, or who have relapsed from, anthracycline chemotherapy, or for whom anthracycline-based chemotherapy is contraindicated” (VESANOID labeling).

In a letter dated December 2, 2009, Roche notified FDA that VESANOID (tretinoin) Capsules, 10 mg, were being discontinued, and FDA moved the drug product to the “Discontinued Drug Product List” section of the Orange Book. There is one approved ANDA for tretinoin capsules, 10 mg (ANDA No. 77-684); this drug product is listed in the Orange Book and, following the discontinuation of VESANOID, was designated as the reference listed drug to which new ANDAs should refer.

Rakoczy Molino Mazzochi Siwik LLP submitted a citizen petition dated March 17, 2010 (Docket No. FDA-2010-P-0157), under 21 CFR 10.30, requesting that the agency determine whether VESANOID (tretinoin) Capsules, 10 mg, were withdrawn from sale for reasons of safety or effectiveness.

After considering the citizen petition and reviewing agency records, FDA has determined under § 314.161 that VESANOID (tretinoin) Capsules, 10 mg, were not withdrawn for reasons of safety or effectiveness. The petitioner has identified no data or other information suggesting that VESANOID (tretinoin) Capsules, 10 mg, were withdrawn for reasons of safety or effectiveness. We have carefully reviewed our files for records concerning the withdrawal of VESANOID (tretinoin) Capsules, 10 mg, from sale. We have also independently evaluated relevant literature and data for possible postmarketing adverse events and have found no information that would indicate that this product was withdrawn from sale for reasons of safety or effectiveness.

Accordingly, the agency will continue to list VESANOID (tretinoin) Capsules, 10 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. FDA will not begin procedures to withdraw approval of the approved ANDA that refers to VESANOID. Additional ANDAs for tretinoin capsules, 10 mg, may also be approved by the agency as long as they meet all other legal and regulatory requirements for the approval of ANDAs. If FDA determines that labeling for this drug product should be revised to meet current standards, the agency will advise ANDA applicants to submit such labeling.

Dated: September 8, 2010.

Leslie Kux,

Acting Assistant Commissioner for Policy.