AAPS PharmSciTech

, 8:65 | Cite as

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

  • David Christopher
  • Wallace Adams
  • Anthony Amann
  • Craig Bertha
  • Peter R. Byron
  • William Doub
  • Craig Dunbar
  • Walter Hauck
  • Svetlana Lyapustina
  • Jolyon Mitchell
  • Beth Morgan
  • Steve Nichols
  • Ziqing Pan
  • Gur Jai Pal Singh
  • Terrence Tougas
  • Yi Tsong
  • Ron Wolff
  • Bruce Wyka
Article

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.

Keywords

Chi-square population bioequivalence particle size distribution inhaler 

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Copyright information

© American Association of Pharmaceutical Scientists 2007

Authors and Affiliations

  • David Christopher
    • 1
  • Wallace Adams
    • 2
  • Anthony Amann
    • 3
  • Craig Bertha
    • 4
  • Peter R. Byron
    • 5
  • William Doub
    • 6
  • Craig Dunbar
    • 7
  • Walter Hauck
    • 8
  • Svetlana Lyapustina
    • 9
  • Jolyon Mitchell
    • 10
  • Beth Morgan
    • 11
  • Steve Nichols
    • 12
  • Ziqing Pan
    • 1
  • Gur Jai Pal Singh
    • 2
  • Terrence Tougas
    • 13
  • Yi Tsong
    • 14
  • Ron Wolff
    • 15
  • Bruce Wyka
    • 16
  1. 1.Statistics, Schering-Plough Research InstituteKenilworth
  2. 2.Office of Generic Drugs, Center for Drug Evaluation and ResearchFood and Drug AdministrationRockville
  3. 3.ACN Pharma LLCNaperville
  4. 4.Office of New Drug Quality AssessmentCenter for Drug Evaluation and Research, Food and Drug AdministrationSilver Spring
  5. 5.Virginia Commonwealth UniversityRichmond
  6. 6.Office of Testing and ResearchCenter for Drug Evaluation and Research, Food and Drug AdministrationSt Louis
  7. 7.AlkermesCambridge
  8. 8.US PharmacopeiaRockville
  9. 9.Drinker Biddle & Reath LLPWashington DC
  10. 10.Trudell Medical InternationalLondonCanada
  11. 11.Manufacturing and Supply, GlaxoSmithKlineZebulon
  12. 12.Industrial Development, sanofi-aventisHolmes ChapelUK
  13. 13.Boehringer IngelheimRidgefield
  14. 14.Office of Biometrics, Center for Drug Evaluation and ResearchFood and Drug AdministrationRockville
  15. 15.Nektar TherapeuticsSan Carlos
  16. 16.Physical & Analytical ChemistrySchering-Plough Research InstituteUion

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