Advertisement

The AAPS Journal

, Volume 7, Issue 1, pp E47–E53 | Cite as

Bioequivalence studies for levothyroxine

  • Sanford BoltonEmail author
Article

Abstract

The Food and Drug Administration (FDA) Guidance for Bioavailability and Bioequivalence Studies for Levothyroxine has been challenged by companies that manufacture brand-name products. Their contention is that the current guidance does not adequately address the endogenous background levels of the drug, and that the ratios of the PK parameters, a basis for approval of equivalence, are not assessed correctly. In particular, they conclude that products that have a potency differing by 12.5% cannot be differentiated using the present guideline and criteria for acceptance of bioequivalence. They claim that such a difference can be a public health hazard because of the perception among practitioners that levothyroxine is a narrow therapeutic index drug. This article describes the procedure recommended in the current Guidance for Levothyroxine and demonstrates that the methods recommended are adequate and will accept products that are therapeutically equivalent. To date, no generic product accepted as equivalent using FDA Guidances has been shown to result in a safety and efficacy profile different from its brand counterpart.

Keywords

Levothyroxine Bioequivalence Study AAPS Journal Narrow Therapeutic Index Drug Blood Level Data 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Food and Drug Administration, Center for Drug Evaluation and Research. Guidance for Industry Levothyroxine Sodium Tablets—In Vivo Pharmacokinetic and Bioavailability Studies and In Vitro Dissolution Testing. Rockville, MD: February 2001.Google Scholar
  2. 2.
    Citizen's Petition. Jones Pharma, Inc. March 28, 2003.Google Scholar
  3. 3.
    Citizen's Petition. Abbott Laboratories. August 25, 2003.Google Scholar
  4. 4.
    Blakesley V, Awni W, Locke C, Ludden T, Granneman GR, Braverman LE. Are bioequivalence studies of levothyroxine sodium formulations in euthyroid volunteers reliable?Thyroid. 2004;14:191–200.PubMedCrossRefGoogle Scholar
  5. 5.
    Food and Drug Administration. FDA Advisory Committee for Pharmaceutical Science.Briefing Document From Abbott Laboratories. Rockville, MD; May 12–13, 2003. Available at: http://www.fda.gov/ ohrms/dockets/ac/03/briefing/3926B1_02_A-Abbott%20.htm. Accessed March 23, 2005.Google Scholar
  6. 6.
    Mylan Laboratories, Inc.Levothyroxine Sodium Tablets. Canonsburg, PA: Mylan Laboratories, Inc; 2000:76–187.Google Scholar
  7. 7.
    Food and Drug Administration. FDA Advisory Committee for Pharmaceutical Science. Record of Proceedings. March 13, 2003. Available at: http://www.fda.gov/ohrms/dockets/ac/cder03.html# Pharmaceutical Science. Accessed March 23, 2005.Google Scholar
  8. 8.
    Citizen's Petition. Abbott Laboratories. August 25, 2003.Google Scholar
  9. 9.
    Food and Drug Administration. FDA Response to Abbott Petition, Citizen's Petition #2003P-0126/CP1, Document PDN 1. June 29, 2004.Google Scholar
  10. 10.
    Carr D, McLeod DT, Parry G, Thornes HM. Fine adjustment of thyroxine replacement dosage: comparison of the thyrotrophin releasing hormone test using a sensitive thyrotrophin assay with measurement of free thyroid hormones and clinical assessment.J Clin Endocrinol. 1988;28:325–333.CrossRefGoogle Scholar
  11. 11.
    Food and Drug Administration. Code of Federal Regulations. Title 21, Volume 5: CFR 320.33. Available at: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfefr/CFRSearch.cfm?fr=320.24. Accessed: March 23, 2005.Google Scholar
  12. 12.
    Bolton S, Bon C.Pharmaceutical Statistics, Practical and Clinical Applications. 4th ed. New York, NY: Marcel Dekker; 2003.Google Scholar
  13. 13.
    Health Canada. Expert Advisory Committee on Bioavailability. Record of Proceedings. April 16, 2003. Available at http://www.hc-sc.gc.ca/hpfbdgpsa/tpd-dpt/2003-04-16_e.html. Accessed March 23, 2005.Google Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2005

Authors and Affiliations

  1. 1.Sanford BoltonUniversity of ArizonaTucson

Personalised recommendations