title: Product Quality Research Institute evaluation of cascade impactor profiles of pharmaceutical aerosols. Part 3. Final report on a statistical procedure for determining equivalence.
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.
authors.affiliation: Statistics, Schering-Plough Research Institute, Kenilworth, NJ, USA.
authors.forename: David
authors.initials: D
authors.lastname: Christopher
authors.forename: Wallace
authors.initials: W
authors.lastname: Adams
authors.forename: Anthony
authors.initials: A
authors.lastname: Amann
authors.forename: Craig
authors.initials: C
authors.lastname: Bertha
authors.forename: Peter R
authors.initials: PR
authors.lastname: Byron
authors.forename: William
authors.initials: W
authors.lastname: Doub
authors.forename: Craig
authors.initials: C
authors.lastname: Dunbar
authors.forename: Walter
authors.initials: W
authors.lastname: Hauck
authors.forename: Svetlana
authors.initials: S
authors.lastname: Lyapustina
authors.forename: Jolyon
authors.initials: J
authors.lastname: Mitchell
authors.forename: Beth
authors.initials: B
authors.lastname: Morgan
authors.forename: Steve
authors.initials: S
authors.lastname: Nichols
authors.forename: Ziqing
authors.initials: Z
authors.lastname: Pan
authors.forename: Gur Jai Pal
authors.initials: GJ
authors.lastname: Singh
authors.forename: Terrence
authors.initials: T
authors.lastname: Tougas
authors.forename: Yi
authors.initials: Y
authors.lastname: Tsong
authors.forename: Ron
authors.initials: R
authors.lastname: Wolff
authors.forename: Bruce
authors.initials: B
authors.lastname: Wyka
mesh_terms: D000047:Academies and Institutes; D000280:Administration, Inhalation; D000281:Administration, Intranasal; D000336:Aerosols; D016009:Chi-Square Distribution; D003627:Data Interpretation, Statistical; D004867:Equipment Design; D017408:Guidelines as Topic; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000737:chemistry*; D011786:Quality Control; D015203:Reproducibility of Results; D013678:Technology, Pharmaceutical / Q000295:instrumentation* / Q000379:methods / Q000592:standards; D013810:Therapeutic Equivalency; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000336:Aerosols; D004364:Pharmaceutical Preparations