[Federal Register Volume 64, Number 111 (Thursday, June 10, 1999)]
[Notices]
[Page 31280]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-14751]



DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration
[Docket No. 99D-1149]


Draft Guidance for Industry on in Vivo Pharmacokinetics and 
Bioavailability Studies and in Vitro Dissolution Testing for 
Levothyroxine Sodium Tablets; 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availability of a draft guidance for industry entitled ``In Vivo 
Pharmacokinetics and Bioavailability Studies and in Vitro Dissolution 
Testing for Levothyroxine Sodium Tablets.'' The draft guidance contains 
agency recommendations on how to design in vivo pharmacokinetics and 
bioavailability studies and perform in vitro dissolution testing for 
levothyroxine sodium tablets.
DATES: Written comments on the draft guidance may be submitted by 
August 9, 1999. General comments on documents are welcome at any time.

ADDRESSES: Copies of this draft guidance for industry can be obtained 
on the Internet at ``http://www.fda.gov/cder/guidance/index.htm''. 
Submit written requests for single copies of the draft guidance to the 
Drug Information Branch (HFD-210), 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 Submit written comments on the draft 
guidance to the Dockets Management Branch (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. 
Comments and requests are to be identified with the docket number found 
in brackets in the heading of this document.

FOR FURTHER INFORMATION CONTACT: Michael J. Fossler, Center for Drug 
Evaluation and Research (HFD-870), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, 301-827-6417.

SUPPLEMENTARY INFORMATION: FDA is announcing the availability of a 
draft guidance for industry entitled ``In Vivo Pharmacokinetics and 
Bioavailability Studies and in Vitro Dissolution Testing for 
Levothyroxine Sodium Tablets.'' This draft guidance contains agency 
recommendations on how to design in vivo pharmacokinetics and 
bioavailability studies and perform in vitro dissolution testing for 
levothyroxine sodium tablets, which were identified as new drugs in a 
notice published in the Federal Register of August 14, 1997 (62 FR 
43536).
    Levothyroxine sodium was introduced into interstate commerce during 
the 1950's without approval of new drug applications (NDA's) for the 
drug products. As a result of concerns about the stability and 
consistent potency of the products, the agency announced that orally 
administered drug products containing levothyroxine sodium were new 
drugs (62 FR 43536). The notice stated that a manufacturer who wished 
to continue to market orally administered levothyroxine sodium products 
had to submit an NDA. The agency allowed current manufacturers 3 years 
to obtain approved NDA's, until August 14, 2000.
     A number of firms have contacted FDA for advice regarding how to 
conduct bioavailability studies and in vitro dissolution testing for 
levothyroxine sodium tablets. Because of this interest, and the need to 
provide consistent advice to all firms who intend to submit NDA's for 
this product, FDA has developed this draft guidance on designing in 
vivo pharmacokinetics and bioavailability studies and performing in 
vitro dissolution testing for levothyroxine sodium tablets. The 
guidance documents FDA's current thinking on this subject. Although the 
guidance is being submitted in draft for comment, FDA recognizes that 
sponsors of already marketed levothyroxine sodium products that are 
required to obtain approved NDA's by August 14, 2000, may already have 
begun to conduct bioavailability and dissolution studies. The study 
design described in this guidance may be used for these studies or an 
alternative approach may be used. In either case, the study designs 
will be acceptable if scientifically justified. FDA will revise the 
study designs described in the guidance in accordance with any comments 
received, if appropriate.
     This level 1 draft guidance is being issued consistent with FDA's 
good guidance practices (62 FR 8961, February 27, 1997). The draft 
guidance represents the agency's current thinking on in vivo 
pharmacokinetics and bioavailability studies and in vitro dissolution 
testing for levothyroxine sodium tablets. 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, regulations, or both.
     Interested persons may, on or before August 9, 1999, submit to the 
Dockets Management Branch (address above) written comments on the draft 
guidance. 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 
draft guidance and received comments may be seen in the office above 
between 9 a.m. and 4 p.m., Monday through Friday.

    Dated: June 3, 1999.
Peggy Dotzel,
Acting Associate Commissioner for Policy Coordination.
[FR Doc. 99-14751 Filed 6-9-99; 8:45 am]
BILLING CODE 4160-01-F