Federal Register / Vol. 70, No. 171 / Tuesday, September 6, 2005 / Notices 53019 

ways to minimize the burden of the 

collection of information on 

respondents, including the use of 

automated collection techniques or 

other forms of information technology. 

Comments submitted in response to 

this notice will be summarized and 

included in the request for OMB 

approval of the proposed information 

collection. All comments will become a 

matter of public record. 

Dated: August 12, 2005. 

Carolyn M. Clancy, 

Director. 

[FR Doc. 05–17617 Filed 9–2–05; 8:45 am] 

BILLING CODE 4160–90–M 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. 2004P–0379] 

Determination That Penthrane 

(Methoxyflurane) Inhalation Liquid, 

99.9 Percent, Was Withdrawn From 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 Penthrane (methoxyflurane) 

Inhalation Liquid, 99.9 percent, was 

withdrawn from sale for reasons of 

safety or effectiveness. The agency will 

not accept or approve abbreviated new 

drug applications (ANDAs) for 

methoxyflurane inhalation liquid, 99.9 

percent. 

FOR FURTHER INFORMATION CONTACT: 

Mary Catchings, 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 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 (§ 314.162 (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. 

Penthrane (methoxyflurane) 

Inhalation Liquid, 99.9 percent, was the 

subject of NDA 13–056, held by Abbott 

Laboratories (Abbott). Penthrane is a 

potent inhalation anesthetic indicated to 

provide anesthesia for surgical 

procedures in which total duration of 

administration is anticipated to be 4 

hours or less (not to be used at 

concentrations that provide skeletal 

muscle relaxation). Penthrane was also 

indicated to provide analgesia in 

obstetrics and in minor surgical 

procedures and for use by selfadministration using hand held 

inhalers. In the Federal Register of 

August 16, 2001 (66 FR 43017), FDA 

withdrew approval of NDA 13–056 for 

Penthrane after Abbott notified the 

agency that Penthrane was no longer 

being marketed under NDA 13–056 and 

requested withdrawal of that 

application. Penthrane was then moved 

to the ‘‘Discontinued Drug Product List’’

section of the Orange Book. 

In a citizen petition dated August 25, 

2004 (Docket No. 2004P–0379/CP1), 

submitted under § 10.30 (21 CFR 10.30), 

and in accordance with § 314.161, AAC 

Consulting Group requested that the 

agency determine whether Penthrane 

(methoxyflurane) Inhalation Liquid, 

99.9 percent, was withdrawn from sale 

for reasons of safety or effectiveness. 

We have carefully reviewed our files 

for records concerning the withdrawal 

of Penthrane (methoxyflurane) 

Inhalation Liquid, 99.9 percent, 

including the NDA file for this drug 

product. We have also independently 

evaluated relevant literature and data 

for possible postmarketing adverse 

event reports. FDA has determined 

under §§ 314.161 and 314.162(a)(2) that 

Penthrane (methoxyflurane) Inhalation 

Liquid, 99.9 percent, was withdrawn 

from sale for reasons of safety. FDA’s 

review shows that methoxyflurane, a 

volatile anesthetic agent, is associated 

with serious, irreversible, and even fatal 

nephrotoxicity and hepatotoxicity in 

humans. FDA has also reviewed the 

latest approved labeling for Penthrane 

and has determined that this labeling is 

inadequate. FDA believes that the risks 

of toxicity outweigh any potential 

benefits if methoxyflurane is used 

according to the latest approved 

labeling. Since the initial approval of 

Penthrane in 1962, with a subsequent 

finding of efficacy in the Federal 

Register of December 11, 1981 (46 FR 

60652), alternative safe and effective 

anesthetics have been approved by FDA 

and entered the market. FDA has 

determined that new clinical studies are 

necessary before methoxyflurane could 

be considered for reintroduction to the 

market. The agency has determined, 

under § 314.161, that Penthrane 

(methoxyflurane) Inhalation Liquid, 

99.9 percent was withdrawn from sale 

for reasons of safety. Therefore, 

Penthrane (methoxyflurane) Inhalation 

Liquid, 99.9 percent, will be removed 

from the list of drug products published 

in the Orange Book. FDA will not accept 

or approve ANDAs that refer to this 

drug product. 

Dated: August 29, 2005. 

Jeffrey Shuren, 

Assistant Commissioner for Policy. 

[FR Doc. 05–17559 Filed 9–2–05; 8:45 am] 

BILLING CODE 4160–01–S 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket Nos. 2005M–0158, 2005M–0159, 

2005M–0129, 2005M–0160, 2005M–0130, 

2005M–0151, 2005M–0117, 2005M–0118, 

2005M–0241, 2005M–0191, 2005M–0192, 

2005M–0193, 2005M–0270] 

Medical Devices; Availability of Safety 

and Effectiveness Summaries for 

Premarket Approval Applications 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) is publishing a