[Federal Register: September 3, 2003 (Volume 68, Number 170)]
[Notices]               
[Page 52403-52404]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr03se03-53]                         

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 2003N-0369]

 
Solvay Pharmaceuticals, Inc.; Withdrawal of Approval of Two New 
Drug Applications; Determination That LUVOX (Fluvoxamine Maleate) 25-
Milligram, 50-mg, 100-mg, and 150-mg Tablets Was Not Withdrawn for 
Reasons of Safety or Effectiveness

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: 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withdrawn these NDAs in response to audit findings indicating possible 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maleate) 25-mg, 50-mg, 100-mg, and 150-mg tablets was not withdrawn 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.

DATES: Effective September 3, 2003.

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.

SUPPLEMENTARY 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 Sec.  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 Sec.  
314.150(d), thereby waiving its opportunity for a hearing. Solvay also 
withdrew these drug products from the market. Under Sec.  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 Sec.  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 
Sec.  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

[[Page 52404]]

FDA's written request under Sec.  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.

    Dated: August 21, 2003.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 03-22359 Filed 9-2-03; 8:45 am]

BILLING CODE 4160-01-S