[Federal Register Volume 66, Number 135 (Friday, July 13, 2001)]
[Notices]
[Pages 36794-36795]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-17538]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 97N-0314]


Guidance for Industry on Levothyroxine Sodium Products--
Enforcement of August 14, 2001, Compliance Date and Submission of New 
Applications; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of a guidance for industry entitled ``Levothyroxine Sodium 
Products--Enforcement of August 14, 2001, Compliance Date and 
Submission of New Applications.'' This guidance discusses how FDA plans 
to exercise its enforcement discretion after August 14, 2001, with 
regard to levothyroxine sodium products that are marketed without 
approved applications. This guidance also answers certain frequently 
asked questions concerning the submission of applications for 
levothyroxine sodium products. It replaces the previously issued 
guidance entitled ``Levothyroxine Sodium, Questions and Answers'' 
(February 2001).

DATES: Submit written or electronic comments on agency guidances at any 
time.

ADDRESSES: Submit written requests for single copies of this guidance 
to the Division of Drug Information (HFD-240), Center for Drug 
Evaluation and Research, Food and Drug Administration, 5600 Fishers 
Lane, Rockville, MD 20857. Send one self-addressed adhesive label to 
assist that office in processing your requests. Submit written comments 
on the guidance to the Dockets Management Branch (HFA-305), Food and 
Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. 
Submit electronic comments to http://www.fda.gov/dockets/ecomments. See 
the SUPPLEMENTARY INFORMATION section for electronic access to the 
guidance document.

FOR FURTHER INFORMATION CONTACT: David T. Read, Center for Drug 
Evaluation and Research (HFD-7), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, 301-594-2041.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a guidance for industry 
entitled ``Levothyroxine Sodium Products--Enforcement of August 14, 
2001 Compliance Date and Submission of New Applications.'' This 
guidance discusses how FDA plans to exercise its enforcement discretion 
after August 14, 2001, with regard to levothyroxine sodium products 
that are marketed without approved applications. This guidance also 
answers certain frequently asked questions concerning the submission of 
applications for levothyroxine sodium products and replaces the 
previously issued guidance entitled ``Levothyroxine Sodium, Questions 
and Answers'' (February 2001) (see 66 FR 13935, March 8, 2001).
    In the Federal Register of August 14, 1997 (62 FR 43535), FDA 
announced that orally administered levothyroxine sodium drug products 
are new drugs. The notice stated that by August 14, 2000, manufacturers 
who wish to continue to market these products must obtain approved 
applications as required by section 505 of the Federal Food, Drug, and 
Cosmetic Act (the act) (21 U.S.C. 355) and 21 CFR part 314. The notice 
stated that after August 14, 2000, any orally administered drug product 
containing levothyroxine sodium that is introduced or delivered for 
introduction into interstate commerce without an approved application 
will be subject to regulatory action, unless found by FDA to be not 
subject to the new drug requirements of the act under a citizen 
petition submitted for that product. FDA issued a second Federal 
Register notice on April 26, 2000 (65 FR 24488), extending the deadline 
for obtaining approved applications until August 14, 2001.
    The agency permitted orally administered levothyroxine sodium 
products to remain on the market during this period of time without 
approved new drug applications to give manufacturers time to conduct 
the required studies, prepare applications, and have them approved. FDA 
stated in the 1997 Federal Register notice that levothyroxine sodium 
products are used to treat hypothyroidism, and no alternative drug is 
relied on by the medical community as an adequate substitute.
    As of June 2001, two orally administered levothyroxine sodium 
products have been approved by FDA. These approved products have been 
evaluated by FDA and found to be safe and effective for their intended 
uses. FDA has not evaluated the safety and effectiveness of unapproved 
marketed products, but it has determined that no currently marketed 
unapproved orally-administered levothyroxine sodium product is 
generally recognized as safe and effective (see 62 FR 43535 at 43538, 
August 14, 1997).
    Notwithstanding the fact that there are now two approved 
applications for orally administered levothyroxine sodium, FDA has 
determined that it will take time for the millions of patients taking 
unapproved products to switch to approved products, and for 
manufacturers of approved products to scale up their production and to 
introduce this increased production into the distribution chain. To 
provide time for manufacturers of approved products to scale up their 
production and for patients and health care providers to make a 
reasonable transition from unapproved to approved products, FDA has 
decided to continue to exercise its enforcement discretion by 
establishing a gradual phase-out of unapproved products. The phase-out 
plan and a number of frequently asked questions are addressed in this 
guidance.
    This guidance is being issued consistent with FDA's good guidance 
practices regulation (21 CFR 10.115; 65 FR 56468, September 19, 2000). 
The guidance is being implemented immediately without prior public 
comment because there are public health reasons for the immediate 
implementation of the guidance document. The guidance pertains to the 
agency's exercise of enforcement discretion and it is being issued to 
facilitate planning by patients, health care providers, manufacturers, 
and distributors who need information about the agency's plans to 
transition patients from unapproved to approved levothyroxine sodium 
products after August 14, 2001. The guidance represents the agency's 
current thinking on this topic. It does not create or confer any rights 
for or on any person and does not operate to bind FDA or the public. An 
alternative approach may be used if such approach satisfies the 
requirements of the applicable statutes and regulations.

II. Comments

    Interested persons may, at any time, submit written or electronic 
comments

[[Page 36795]]

on the guidance to the Dockets Management Branch (address above). Two 
copies of any comments are to be submitted, except that individuals may 
submit one copy. Comments are to be identified with the docket number 
found in brackets in the heading of this document. The guidance and 
received comments are available for public examination in the Dockets 
Management Branch between 9 a.m. and 4 p.m., Monday through Friday.

III. Electronic Access

    Persons with access to the Internet may obtain the document at 
either
http://www.fda.gov/cder/guidance/index.htm or http://www.fda.gov/ohrms/dockets/default.htm.

    Dated: July 9, 2001.
Margaret M. Dotzel,
Associate Commissioner for Policy.
[FR Doc. 01-17538 Filed 7-12-01; 8:45 am]
BILLING CODE 4160-01-S