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Product quality research institute evaluation of cascade impactor profiles of pharmaceutical aerosols, part 3: Final report on a statistical procedure for determining equivalence

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Abstract

The purpose of this article is to report final results of the evaluation of a chi-square ratio test proposed by the US Food and Drug Administration (FDA) for demonstrating equivalence of aerodynamic particle size distribution (APSD) profiles of nasal and orally inhaled drug products. A working group of the Product Quality Research Institute previously published results demonstrating some limitations of the proposed test. In an effort to overcome the test’s limited discrimination, the group proposed a supplemental test, a population bioequivalence (PBE) test for impactor-sized mass (ISM). In this final report the group compares the chi-square ratio test to the ISM-PBE test and to the combination of both tests. The basis for comparison is a set of 55 realistic scenarios of cascade impactor data, which were evaluated for equivalence by the statistical tests and independently by the group members. In many instances, the combined application of these 2 tests appeared to increase the discriminating ability of the statistical procedure compared with the chi-square ratio test alone. In certain situations the chi-square ratio test alone was sufficient to determine equivalence of APSD profiles, while in other situations neither of the tests alone nor their combination was adequate. This report describes all of these scenarios and results. In the end, the group did not recommend a statistical test for APSD profile equivalence. The group did not investigate other in vitro tests, in vivo issues, or other statistical tests for APSD profile comparisons. The studied tests are not intended for routine quality control of APSD.

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Author information

Author notes

  1. Gur Jai Pal Singh

    Present address: Watson Laboratories, Inc., Corona, CA

Authors and Affiliations

  1. Statistics, Schering-Plough Research Institute, Kenilworth, NJ

    David Christopher & Ziqing Pan

  2. Office of Generic Drugs, Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, MD

    Wallace Adams & Gur Jai Pal Singh

  3. ACN Pharma LLC, Naperville, IL

    Anthony Amann

  4. Office of New Drug Quality Assessment, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD

    Craig Bertha

  5. Virginia Commonwealth University, Richmond, VA

    Peter R. Byron

  6. Office of Testing and Research, Center for Drug Evaluation and Research, Food and Drug Administration, St Louis, MO

    William Doub

  7. Alkermes, Cambridge, MA

    Craig Dunbar

  8. US Pharmacopeia, Rockville, MD

    Walter Hauck

  9. Drinker Biddle & Reath LLP, 1500 K St. N.W., Ste 1100, 20005-1209, Washington DC

    Svetlana Lyapustina

  10. Trudell Medical International, London, Ontario, Canada

    Jolyon Mitchell

  11. Manufacturing and Supply, GlaxoSmithKline, Zebulon, NC

    Beth Morgan

  12. Industrial Development, sanofi-aventis, Holmes Chapel, Cheshire, UK

    Steve Nichols

  13. Boehringer Ingelheim, Ridgefield, CT

    Terrence Tougas

  14. Office of Biometrics, Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, MD

    Yi Tsong

  15. Nektar Therapeutics, San Carlos, CA

    Ron Wolff

  16. Physical & Analytical Chemistry, Schering-Plough Research Institute, Uion, NJ

    Bruce Wyka

Authors
  1. David Christopher
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  2. Wallace Adams
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  3. Anthony Amann
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  4. Craig Bertha
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  5. Peter R. Byron
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  6. William Doub
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  7. Craig Dunbar
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  8. Walter Hauck
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  9. Svetlana Lyapustina
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  10. Jolyon Mitchell
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  11. Beth Morgan
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  12. Steve Nichols
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  13. Ziqing Pan
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  14. Gur Jai Pal Singh
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  15. Terrence Tougas
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  16. Yi Tsong
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  17. Ron Wolff
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  18. Bruce Wyka
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Corresponding author

Correspondence to Svetlana Lyapustina.

Additional information

Published: November 2, 2007

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Christopher, D., Adams, W., Amann, A. et al. Product quality research institute evaluation of cascade impactor profiles of pharmaceutical aerosols, part 3: Final report on a statistical procedure for determining equivalence. AAPS PharmSciTech 8, 90 (2007). https://doi.org/10.1208/pt0804090

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  • DOI: https://doi.org/10.1208/pt0804090

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