Skip to main content

Advertisement

SpringerLink
Log in

Maximal Usage Trial: An Overview of the Design of Systemic Bioavailability Trial for Topical Dermatological Products

  • Clinical Trials
  • Published:
Therapeutic Innovation & Regulatory Science Aims and scope Submit manuscript

Abstract

Dermatologic diseases can present in varying forms and severity, ranging from the individual lesion and up to almost total skin involvement. Pharmacokinetic assessment of topical drug products has previously been plagued by bioanalytical assay limitations and the lack of a standardized study design. Since the mid-1990’s the US Food and Drug Administration has developed and implemented a pharmacokinetic maximal usage trial (MUsT) design to help address these issues. The MUsT design takes into account the following elements: the enrollment of patients rather than normal volunteers, the frequency of dosing, duration of dosing, use of highest proposed strength, total involved surface area to be treated at one time, amount applied per square centimeter, application method and site preparation, product formulation, and use of a sensitive bioanalytical method that has been properly validated. This paper provides a perspective of pre-MUsT study designs and a discussion of the individual elements that make up a MUsT.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Campbell LS, Chevalier M, Levy RA, Rhodes A. Hypothalamic-pituitary-adrenal axis suppression related to topical glucocorticoid therapy in a child with psoriatic exfoliative erythroderma. Pediatr Dermatol. 2012;29:101–104.

    Article  Google Scholar 

  2. Gilbertson EO, Spellman MC, Piacquadio DJ, Mulford MI. Super potent topical corticosteroid use associated with adrenal suppression: clinical considerations. J Am Acad Dermatol. 1998;38:318–321.

    Article  CAS  Google Scholar 

  3. Tempark T, Phatarakijnirund V, Chatproedprai S, Watcharasindhu S, Supornsilchai V, Wananukul S. Exogenous Cushing’s syndrome due to topical corticosteroid application: case report and review literature. Endocrine. 2010;38:328–34.

    Article  CAS  Google Scholar 

  4. Federal Register. 42 FR 1648; January 7, 1977 (US).

  5. Code of Federal Regulations. Title 21, part 320.21; 2012 (US).

  6. Bickers DR, Lim HW, Margolis D, et al. The burden of skin diseases: 2004 a joint project of the American Academy of Dermatology Association and the Society for Investigative Dermatology. J Am Acad Dermatol. 2006;55:490–500.

    Article  Google Scholar 

  7. Code of Federal Regulations. Title 21, part 320.24; 2012 (US).

  8. Bashaw ED. Bioequivalence of Topical Drugs: Alternative Approaches. London, UK: Bio International; 2008.

    Google Scholar 

  9. Bashaw ED. Microdialysis role in the development and optimization of topical drug delivery: the regulatory viewpoint. http://mediaserver.aaps.org/meetings/09AM/Slides/11.11.09_Wed/concourse%20hall%20152/1400/E%20Dennis%20Bashaw.pdf. Published 2009. Accessed January 9, 2014.

  10. Bashaw ED. Establishing therapeutic equivalence: an overview. http://www.nxtbook.com/nxtbooks/aaps/pswc2010_preliminary/index.php?startid=160. Published 2010. Accessed January 9, 2014.

  11. FDA. Draft guidance for industry: acne vulgaris—developing drugs for treatment. http://www.fda.gov/downloads/Drugs/…/Guidances/UCM071292.pdf. Published 2005. Accessed January 9, 2014.

  12. Tang-Liu DD, Matsumoto RM, Usansky JI. Clinical pharmacokinetics and drug metabolism of tazarotene: a novel topical treatment for acne and psoriasis. Clin Pharmacokinet. 1999;37:273–287.

    Article  CAS  Google Scholar 

  13. FDA. [Tazorac gel label; approved on February 25, 2011]. http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020600s008lbl.pdf. Published 2011. Accessed January 9, 2014.

  14. FDA. NDA 204153: clinical pharmacology and biopharmaceutics reviews. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204153Orig1s000ClinPharmR.pdf. Published 2012. Accessed January 7, 2014.

  15. FDA. [Natroba suspension label; approved January 18, 2011]. http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022408lbl.pdf. Published 2011. Accessed January 9 2014.

  16. FDA. [Ulesfia lotion label; approved July 12, 2012]. http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022129s005lbl.pdf. Published 2011. Accessed January 9, 2014.

  17. FDA. [Avage cream label; approved September 30, 2002]. http://www.accessdata.fda.gov/drugsatfda_docs/label/2002/21184s2lbl.pdf. Published 2002. Accessed January 9, 2014.

  18. Yentzer BA. Improving adherence to medical treatments. http://www.aad.org/ScientificSessions/Am2012/handouts.aspx. Published 2012. Accessed February 24, 2014.

  19. Franz TJ, Lehman PA, McGuire EL. In vivo methods for the assessment of percutaneous absorption in man. In: Zatz JL, ed. Skin Permeation: Fundamentals and Application. Wheaton, IL: Allured Publishing Co; 1993:73–92.

    Google Scholar 

  20. FDA. Notification to pharmaceutical companies: acceptance of third-party data integrity audit for Cetero studies conducted from March 1, 2008 to August 31, 2009. http://www.fda.gov/Drugs/DrugSafety/ucm265559.htm. Published 2012. Accessed January 9, 2014.

  21. Reuters. FDA finds U.S. drug research firm faked documents. http://www.reuters.com/article/2011/07/26/us-fda-cetero-violation-idUSTRE76P7E320110726. Published 2011. Accessed February 20, 2014.

  22. Newswire PR. Cetero reaches final resolution with the Food and Drug Administration. http://www.prnewswire.com/news-releases/cetero-reaches-final-resolution-with-the-food-and-drug-administration-148658885.html. Published 2012. Accessed February 20, 2014.

  23. FierceBiotech. Report: CRO with a scandal-plagued past shuts down, leaving patients stranded. http://www.fiercebiotech.com/story/cro-scandal-plagued-past-shuts-down-leaving-patients-stranded/2013-03-21. Published 2013. Accessed February 20, 2014.

  24. FDA. Guidance for industry: nonsterile semisolid dosage forms. Scale-up and postapproval changes: chemistry, manufacturing, and controls; in vitro release testing and in vivo bioequivalence documentation. http://www.fda.gov/downloads/Drugs/…/Guidances/UCM070930.pdf. Published 1997. Accessed January 9, 2014.

  25. Benfeldt E, Serup J, Menne T. Microdialysis vs suction blister technique for in vivo sampling of pharmacokinetics in the human dermis. Acta Derm Venereol. 1999;79:338–342.

    Article  CAS  Google Scholar 

  26. Saar BG, Contreras-Rojas LR, Xie XS, Guy RH. Imaging drug delivery to skin with stimulated Raman scattering microscopy. Mol Pharm 2011;8:969–975.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. US Food and Drug Administration, 10903 New Hampshire Avenue, Building 51, Room 3134, Silver Spring, MD, 20993, USA

    Edward Dennis Bashaw PharmD, Doanh C. Tran PhD, Chinmay G. Shukla PhD & Xiaomei Liu PharmD

Authors
  1. Edward Dennis Bashaw PharmD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Doanh C. Tran PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chinmay G. Shukla PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiaomei Liu PharmD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Edward Dennis Bashaw PharmD.

Additional information

Authors’ Note

While the authors are employees of the US Food and Drug Administration, the opinions and views expressed in this paper are their own and do not reflect US Food and Drug Administration policy or official guidance.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bashaw, E.D., Tran, D.C., Shukla, C.G. et al. Maximal Usage Trial: An Overview of the Design of Systemic Bioavailability Trial for Topical Dermatological Products. Ther Innov Regul Sci 49, 108–115 (2015). https://doi.org/10.1177/2168479014539157

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1177/2168479014539157

Keywords

Search

Navigation