[Federal Register: April 20, 2005 (Volume 70, Number 75)]
[Page 20574-20575]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]



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.


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: 


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 
    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 
    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]