Federal Register / Vol. 69, No. 206 / Tuesday, October 26, 2004 / Notices 62447

companies listed below, that engages 

either directly or through a subsidiary or 

other company, in a nonbanking activity 

that is listed in § 225.28 of Regulation Y 

(12 CFR 225.28) or that the Board has 

determined by Order to be closely 

related to banking and permissible for 

bank holding companies. Unless 

otherwise noted, these activities will be 

conducted throughout the United States.

Each notice is available for inspection 

at the Federal Reserve Bank indicated. 

The notice also will be available for 

inspection at the offices of the Board of 

Governors. Interested persons may 

express their views in writing on the 

question whether the proposal complies 

with the standards of section 4 of the 

BHC Act. Additional information on all 

bank holding companies may be 

obtained from the National Information 

Center website at www.ffiec.gov/nic/.

Unless otherwise noted, comments 

regarding the applications must be 

received at the Reserve Bank indicated 

or the offices of the Board of Governors 

not later than November 9, 2004.

A. Federal Reserve Bank of Cleveland

(Cindy C. West, Banking Supervisor) 

1455 East Sixth Street, Cleveland, Ohio 

44101–2566:

1. Tri–State 1st Banc, Inc., East 

Liverpool, Ohio; to acquire MDH 

Investment Management, Inc., East 

Liverpool, Ohio, and thereby engage in 

permissible investment advisory 

activities, pusuant to section 

225.28(b)(6)(i) of Regulation Y.

Board of Governors of the Federal Reserve 

System, October 20, 2004.

Robert deV. Frierson,

Deputy Secretary of the Board.

[FR Doc. 04–23891 Filed 10–25–04; 8:45 am]

BILLING CODE 6210–01–S

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES

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Withdrawn From Sale for Reasons of 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withdrawn from sale for reasons of 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 § 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 § 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 § 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]

BILLING CODE 4160–01–S