E9-19641. Determination That DEMADEX (Torsemide) Injection, 20 Milligrams/2 Milliliter (10 Milligrams/Milliliter) and 50 Milligrams/5 Milliliter (10 Milligrams/Milliliter), Was Not Withdrawn From Sale for Reasons of Safety or Effectiveness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) is announcing its determination that DEMADEX (torsemide) injection, 20 milligrams (mg)/2 milliliter (mL) (10 mg/mL) and 50 mg/5 mL (10 mg/mL), was not withdrawn from sale for reasons of safety or effectiveness. This determination will allow FDA to approve abbreviated new drug applications (ANDAs) for torsemide injection, 20 mg/2mL (10 mg/mL) and 50 mg/5 mL (10 mg/mL), if all other legal and regulatory requirements are met.

FOR FURTHER INFORMATION CONTACT:

Nikki Mueller, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, rm. 6312, 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 (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of the drug's NDA or ANDA for reasons of safety or effectiveness, or if FDA determines that the listed drug was withdrawn from sale for reasons of safety or effectiveness (21 CFR 314.162).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.

PharmaForce, Inc., submitted a citizen petition dated August 5, 2008 (Docket No. FDA-2008-P-0443), under 21 CFR 10.30 requesting that the agency determine whether DEMADEX (torsemide) injection, 20 mg/2 mL (10 mg/mL) and 50 mg/5 mL (10 mg/mL), was withdrawn from sale for reasons of safety or effectiveness. DEMADEX (torsemide) injection is the subject of NDA 20-137, held by Roche Pharmaceuticals (Roche) and was initially approved on August 23, 1993. DEMADEX is indicated for the treatment of edema associated with congestive heart failure, renal disease, or hepatic disease. Roche notified FDA on June 16, 2008, that it was no longer marketing DEMADEX (torsemide) injection, 20 mg/2 mL (10 mg/mL) and 50 mg/5 mL (10 mg/mL), and the drug product was moved to the “Discontinued Drug Product List” section of the Orange Book.

FDA has reviewed its records and, under § 314.161, has determined that DEMADEX (torsemide) injection, 20 mg/2 mL (10 mg/mL) and 50 mg/5 mL (10 mg/mL), was not withdrawn from sale for reasons of safety or effectiveness. The petitioner identified no data or other information suggesting that DEMADEX (torsemide) injection, 20 mg/2 mL (10 mg/mL) and 50 mg/5 mL (10 mg/mL), was withdrawn for reasons of safety or effectiveness. FDA has independently evaluated relevant literature and data for possible postmarketing adverse events and has 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 DEMADEX (torsemide) injection, 20 mg/2 mL (10 mg/mL) and 50 mg/5 mL (10 mg/mL), 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 DEMADEX (torsemide) injection, 20 mg/2 mL (10 mg/mL) and 50 mg/5 mL (10 mg/mL), may be approved by the agency if all other legal and regulatory requirements for the approval of ANDAs are met. 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: August 7, 2009.

Jeffrey Shuren,

Associate Commissioner for Policy and Planning.