[Federal Register: October 26, 2004 (Volume 69, Number 206)]
[Page 62447]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]



Food and Drug Administration

[Docket No. 2003P-0090]

Determination That SERZONE (Nefazodone Hydrochloride) 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Withdrawn From Sale for Reasons of Safety or Effectiveness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) has determined that 
SERZONE (nefazodone hydrochloride (HCl)) was not withdrawn from sale 
for reasons of safety or effectiveness. This determination means that 
FDA will not begin procedures to suspend approval of abbreviated new 
drug applications (ANDAs) for nefazodone HCl, and FDA may continue to 
approve ANDAs for nefazodone HCl.

FOR FURTHER INFORMATION CONTACT: Nicole Mueller, Center for Drug 
Evaluation and Research (HFD-7), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, 301-594-2041.

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 
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. Sponsors of ANDAs 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 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 Under FDA regulations, drugs are withdrawn from the list if the 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drug was withdrawn from sale for reasons of safety or effectiveness (21 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)(1) and (a)(2) (21 CFR 314.161(a)(1) and 
(a)(2)), the agency must determine whether a listed drug was withdrawn 
from sale for reasons of safety or effectiveness both before an ANDA 
that refers to that listed drug may be approved and if an ANDA 
referring to that listed drug has already been approved. FDA may not 
approve an ANDA that does not refer to a listed drug, and, under Sec.  
314.161(d), FDA must pursue suspension of approval for an ANDA if the 
agency determines the listed drug to which the ANDA refers was 
withdrawn for reasons of safety or effectiveness.
    SERZONE (nefazodone HCl) is the subject of approved NDA 20-152 held 
by the Bristol-Meyers Squibb Co. (BMS). SERZONE is indicated for the 
treatment of depression. The Public Citizen Health Research Group 
(PCHRG) submitted a citizen petition to the agency, dated March 6, 
2003, requesting that we immediately remove SERZONE from the market 
because of adverse events associated with the drug (cases of serious 
liver toxicity). On May 19, 2004, BMS announced that for commercial 
business reasons, particularly declining sales and increased generic 
competition, BMS would be discontinuing all sales and manufacture of 
SERZONE in the U.S. market effective June 14, 2004. Because of the 
potential for continued marketing of generic versions of nefazodone 
after BMS's withdrawal of SERZONE from sale, the issues raised in 
PCHRG's petition still warranted agency response. FDA responded to the 
petition in a letter dated June 14, 2004, denying the petition and 
explaining our reasons for concluding that the available data did not 
justify the agency's removal of nefazodone from the market. The agency 
also concluded, however, that the safe use of the drug could be 
improved through additional risk management measures, and BMS made 
changes to the product labeling to discourage the drug's use as a 
first-line drug (i.e., to encourage physicians to consider using other 
treatments first). The labeling for generic versions of nefazadone now 
must include these changes.
    Having independently evaluated relevant literature and data, 
including from FDA's Adverse Event Reporting System, for possible 
postmarketing adverse event reports, FDA has now also determined, under 
Sec.  314.161, that BMS's voluntary withdrawal from sale of SERZONE was 
not for reasons of safety or effectiveness. Accordingly, the agency 
will list SERZONE (nefazodone HCl) 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. Approved ANDAs that refer to the SERZONE (nefazodone 
HCl) are unaffected by the withdrawal of SERZONE from the market. 
Additional ANDAs for nefazodone HCl may also be approved by the agency.

    Dated: October 15, 2004.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 04-23857 Filed 10-25-04; 8:45 am]