Food and Drug Administration, HHS.
The Food and Drug Administration (FDA) is withdrawing approval of the new drug applications (NDAs) for ROWASA (mesalamine) Rectal Suppositories, 500 milligrams (mg), and LUVOX (fluvoxamine maleate) 25-mg, 50-mg, 100-mg, and 150-mg tablets, held by Solvay Pharmaceuticals, Inc., 901 Sawyer Rd., Marietta, GA 30062. Solvay has voluntarily withdrawn these NDAs in response to audit findings indicating possible inaccuracies noted in the chemistry, manufacturing, and controls (CMC) section of the applications. Solvay has agreed to permit FDA to withdraw approval of the applications, thereby waiving its opportunity for a hearing. In addition, FDA has determined that LUVOX (fluvoxamine maleate) 25-mg, 50-mg, 100-mg, and 150-mg tablets was not withdrawn from sale for reasons of safety or effectiveness. This determination will allow FDA to continue to approve abbreviated new drug applications (ANDAs) for fluvoxamine maleate 25-mg, 50-mg, 100-mg, and 150-mg tablets.
Effective September 3, 2003.Start Further Info
FOR FURTHER INFORMATION CONTACT:
Florine P. Purdie, Center for Drug Evaluation and Research (HFD-7), Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857, 301-594-2041.End Further Info End Preamble Start Supplemental Information
FDA recently became aware of possible inaccuracies in the CMC section of two of Solvay's applications approved by the agency. The two Solvay NDAs involved were: (1) NDA 19-919 for ROWASA (mesalamine) Rectal Suppositories, 500 mg, and (2) NDA 20-243 for LUVOX (fluvoxamine maleate) 25-mg, 50-mg, 100-mg, and 150-mg tablets. These findings, along with other information submitted to the agency by Solvay, provided sufficient justification to initiate proceedings to withdraw approval of these two products. The agency notified Solvay in writing of these eterminations and, in accordance with § 314.150(d) (21 CFR 314.150(d)), offered Solvay the opportunity to permit FDA to withdraw approval of the applications.
Subsequently, in letters dated March 28, 2002, and May 14, 2002, respectively, Solvay requested withdrawal of the NDAs under § 314.150(d), thereby waiving its opportunity for a hearing. Solvay also withdrew these drug products from the market. Under § 314.150(d), approval of these two NDAs is being withdrawn.
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 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 under an NDA. Sponsors of ANDAs do not have to repeat the extensive clinical testing otherwise necessary to gain approval of an 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 (the 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 withdrawn 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), the agency must determine whether a listed drug was withdrawn from sale for reasons of safety or effectiveness: (1) Before an ANDA that refers to that listed drug may be approved or, (2) whenever a listed drug is voluntarily withdrawn from sale, and ANDAs that referred to the listed drug have been approved. FDA may not approve an ANDA that does not refer to a listed drug.
The agency has already determined that ROWASA (mesalamine) Rectal Suppositories, 500 mg, was not withdrawn from sale for reasons of safety and effectiveness. On May 24, 2001, FDA published its determination in the Federal Register (66 FR 28753). Since that time, ANDAs that refer to ROWASA (mesalamine) Rectal Suppositories, 500 mg, may be approved by the agency.
Because numerous approved ANDAs for fluvoxamine maleate relied on LUVOX as the reference listed drug in their applications, FDA must also make a determination of reasons for voluntary withdrawal of LUVOX under § 314.161(a)(2). The agency has determined that Solvay Pharmaceuticals, Inc.'s, LUVOX (fluvoxamine maleate) 25-mg, 50-mg, 100-mg, and 150-mg tablets was not withdrawn from sale for reasons of safety or effectiveness.
LUVOX is indicated for the treatment of obsessions and compulsions in patients with obsessive compulsive disorder. In the course of an audit, FDA discovered inaccuracies in the CMC section of the LUVOX (fluvoxamine maleate) application. Although these findings raised concerns about the drug product as manufactured by Solvay, they do not affect the safety or efficacy of fluvoxamine maleate in treating obsessive compulsive disorder. LUVOX was withdrawn from sale following Start Printed Page 52404FDA's written request under § 314.150(d). The agency's independent evaluation of relevant information has not found any data that would indicate LUVOX (fluvoxamine maleate) was withdrawn for reasons of safety or effectiveness.
After reviewing its records, FDA determines that, for the reasons outlined in the previous paragraph, LUVOX (fluvoxamine maleate) 25-mg, 50-mg, 100-mg, and 150-mg tablets was not withdrawn from sale for reasons of safety or effectiveness. Accordingly, the agency will list Solvay's LUVOX (fluvoxamine maleate) 25-mg, 50-mg, 100-mg, and 150-mg tablets in the “Discontinued Drug Product List” section of the “Orange Book.” The “Discontinued Drug Product List” identifies, among other items, drug products that have been discontinued from marketing for reasons other than safety or effectiveness. ANDAs for fluvoxamine maleate 25-mg, 50-mg, 100-mg, and 150-mg tablets may continue to be approved by the agency.
Therefore, under section 505(e) of the act approval of the NDAs listed above, and all amendments and supplements thereto, is withdrawn, effective September 3, 2003.Start Signature
Dated: August 21, 2003.
Assistant Commissioner for Policy.
[FR Doc. 03-22359 Filed 9-2-03; 8:45 am]
BILLING CODE 4160-01-S