Determination That TRANDATE (Labetalol Hydrochloride) Tablets, 300 Milligrams and 400 Milligrams, Were Not Withdrawn From Sale for Reasons of Safety or Effectiveness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(FDA) has determined that TRANDATE (labetalol hydrochloride) tablets, 300 milligrams (mg) and 400 mg, were not withdrawn from sale for reasons of safety or effectiveness.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 abbreviated new drug applications (ANDAs) that refer to these drug products, and it will allow FDA to continue to approve ANDAs that refer to the products as long as the ANDAs meet relevant legal and regulatory requirements.

FOR FURTHER INFORMATION CONTACT:

Deborah Livornese, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, rm. 6306, Silver Spring, MD 20993-0002, 301-796-0719.

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 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approval of the drug's NDA or ANDA for reasons of safety or effectiveness or if FDA determines that the listed drug was withdrawn from sale for reasons of safety or effectiveness (§ 314.162 (21 CFR 314.162)).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. Under § 314.161(a)(2), FDA must determine whether a listed drug was withdrawn from sale for reasons of safety or effectiveness whenever a listed drug is voluntarily withdrawn from sale and ANDAs that refer to the listed drug have been approved. Section 314.161(d) provides that if FDA determines that a listed drug was withdrawn from sale for reasons of safety or effectiveness, the Agency will initiate proceedings that could result in the withdrawal of approval of the ANDAs that refer to the listed drug.

TRANDATE (labetalol hydrochloride) tablets, 300 mg and 400 mg, are the subject of NDA 18-716, held by Prometheus Laboratories, Inc., and initially approved on August 1, 1984. TRANDATE is indicated for the management of hypertension. TRANDATE (labetalol hydrochloride) tablets, 300 mg and 400 mg, are currently listed in the “Discontinued Drug Product List” section of the Orange Book. TRANDATE (labetalol hydrochloride) tablets, 400 mg, have never been marketed. 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.

JRRapoza Associates, Inc., submitted a citizen petition dated June 16, 2010 (Docket No. FDA-2010-P-0326), under 21 CFR 10.30, requesting that the Agency determine whether TRANDATE (labetalol hydrochloride) tablets, 300 mg, were withdrawn from sale for reasons of safety or effectiveness. Although the citizen petition did not address the 400 mg strength, on our own initiative, we have also determined whether that strength was withdrawn for safety or effectiveness reasons.

After considering the citizen petition and reviewing Agency records, FDA has determined under § 314.161 that TRANDATE (labetalol hydrochloride) tablets, 300 mg and 400 mg, were not withdrawn for reasons of safety or effectiveness. The petitioner has identified no data or other information suggesting that TRANDATE (labetalol hydrochloride) tablets, 300 mg and 400 mg, were withdrawn for reasons of safety or effectiveness. We have carefully reviewed our files for records concerning the withdrawal of TRANDATE (labetalol hydrochloride) tablets, 300 mg and 400 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 TRANDATE (labetalol hydrochloride) tablets, 300 mg and 400 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 approved ANDAs that refer to the TRANDATE products listed in this document. Additional ANDAs that refer to these products 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.