[Federal Register Volume 70, Number 171 (Tuesday, September 6, 2005)]
[Notices]
[Page 53019]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 05-17559]
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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99.9 Percent, Was Withdrawn From Sale for Reasons of Safety or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.
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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withdrawn from sale for reasons of safety or effectiveness.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listed drug was withdrawn from sale for reasons of safety or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 (Sec. 314.162 (21 CFR 314.162)).
Under Sec. 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 self-administration 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 Sec. 10.30 (21 CFR 10.30), and in accordance
with Sec. 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
Sec. Sec. 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 Sec. 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