[Federal Register: April 20, 2005 (Volume 70, Number 75)]
[Notices]
[Page 20574-20575]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr20ap05-70]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. 2005N-0137]
Levothyroxine Sodium Therapeutic Equivalence; Public Meeting
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice of public meeting; request for comments.
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SUMMARY: The Food and Drug Administration (FDA) is announcing a public
meeting on the therapeutic equivalence of levothyroxine sodium drug
products. This will be a workshop involving FDA staff and
representatives of three medical societies: The American Thyroid
Association (ATA), the Endocrine Society, and the American Association
of Clinical Endocrinologists (AACE). The purpose of the public meeting
is to discuss FDA's regulatory standards and methodological approaches
for determining therapeutic equivalence between levothyroxine sodium
drug products. The agency is seeking comments and input from interested
constituencies, including patient advocacy and education groups, and
pharmaceutical sponsors.
DATES: The public meeting will be held on May 23, 2005, from 8:30 a.m.
to 5 p.m. Submit written or electronic comments by July 23, 2005.
ADDRESSES: The public meeting will be held at the National
Transportation Safety Board Boardroom and Conference Center, 429
L'Enfant Plaza, SW., Washington, DC 20594, 202-314-6421. The center can
be reached by Metro using the L'Enfant Plaza station on the green,
yellow, blue, and orange lines. For directions, see http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://ntsb.gov/events/newlocation.htm.
(FDA has verified the Web site address, but FDA
is not responsible for any changes to the Web site after this document
publishes in the Federal Register.)
Submit written comments to the Division of Dockets Management (HFA-
305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061,
Rockville, MD 20852. Submit electronic comments to http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/dockets/ecomments
.
FOR FURTHER INFORMATION CONTACT: Rose Cunningham, Center for Drug
Evaluation and Research (HFD-006), Food and Drug Administration, 5600
Fishers Lane, Rockville, MD 20852, 301-443-5595, e-mail:
cunninghamr@cder.fda.gov.
SUPPLEMENTARY INFORMATION:
I. Background
In the Federal Register of August 14, 1997 (62 FR 43535), FDA
declared that oral drug products containing levothyroxine sodium were
considered new drugs and subject to regulation as such. The document
called for new drug applications (NDAs) for levothyroxine sodium
products from sponsors wishing to market such products in the United
States after August 14, 2000. This deadline was eventually extended to
August 14, 2001.
The NDAs submitted for levothyroxine sodium products included
literature references supporting the safety and effectiveness of
levothyroxine sodium for the proposed indications and full
manufacturing information supporting the purity, potency, and stability
of the products. Manufacturers were required to target 100 percent of
the labeled levothyroxine sodium content at release. (Some
manufacturers had historically added a ``stability overage'' to give
their products a longer shelf-life.) In addition, bioavailability and
in vitro dissolution studies were required to establish that the
products were readily and consistently absorbed across the range of
dosage strengths proposed to be marketed. To assist manufacturers, in
December 2000, FDA published a guidance on the conduct of in vivo
pharmacokinetic and bioavailability studies and in vitro dissolution
tests on these products.
FDA has approved seven NDAs for levothyroxine sodium products. None
were originally rated as interchangeable with any other. Since their
approval, FDA has approved supplemental NDAs from some sponsors
demonstrating the therapeutic equivalence (interchangeability) of their
products to other approved levothyroxine sodium products. The agency
has also approved one levothyroxine sodium product under an abbreviated
new drug application (ANDA).
ATA, the Endocrine Society, and AACE have questioned FDA's
regulatory and scientific standards for determination of therapeutic
equivalence of levothyroxine sodium products, particularly FDA's
bioequivalence methodology.
[[Page 20575]]
II. Scope of the Public Meeting
The public meeting is intended to review FDA's regulatory and
scientific approach to levothyroxine sodium products, including
manufacturing standards, in vitro dissolution studies, and
bioavailability/bioequivalence methods.
The public meeting will also review clinical, scientific, and
methodological issues relevant to the possible use of serum thyrotropin
concentration as a pharmacodynamic measure of levothyroxine sodium
bioequivalence.
The public meeting will include representatives from FDA and from
the three medical societies. A series of brief presentations will frame
the issues under consideration, followed by panel discussions involving
speakers and moderators, with questions and comments from the audience.
Other interested constituencies (e.g., patient advocacy and education
groups, pharmaceutical sponsors, general public) will have an
opportunity to provide input during the question and comment periods.
III. Registration, Agenda, and Presentations
No registration is required to attend the meeting. Seating will be
on a first-come, first-served basis. If you need special accommodations
due to a disability, please contact (see FOR FURTHER INFORMATION
CONTACT).
The agenda for public meeting will be available on FDA's Center for
Drug Evaluation and Research Web site at http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/cder/meeting/levothyroxine.htm
and at the meeting. After the meeting, the
agenda, presentations, and transcript will be placed on file in the
Division of Dockets Management under the docket number found in the
heading of this document and on CDER's Web site identified previously.
IV. Comments
Interested persons may submit to the Division of Dockets Management
(see ADDRESSES) written or electronic comments on the topics discussed
in this document. Submit two copies of mailed comments, except that
individuals may submit one paper copy. Comments are to be identified
with the docket number found in brackets in the heading of this
document. Received comments are available for public examination in the
Division of Dockets Management between 9 a.m. and 4 p.m., Monday
through Friday.
V. Transcripts
Copies of the transcript may be requested in writing from the
Freedom of Information Office (HFI-35), Food and Drug Administration,
5600 Fishers Lane, rm. 12A-16, Rockville, MD 20857, approximately 20
working days after the meeting at a cost of 10 cents per page or on
compact disc at a cost of $14.25 each. You may also examine the
transcript at the Division of Dockets Management between 9 a.m. and 4
p.m., Monday through Friday.
Dated: April 14, 2005.
Jeffery Shuren,
Assistant Commissioner for Policy.
[FR Doc. 05-7883 Filed 4-19-05; 8:45 am]
BILLING CODE 4160-01-S