Product Quality Research Institute evaluation of cascade impactor profiles of pharmaceutical aerosols. Part 3. Final report on a statistical procedure for determining equivalence.
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.
Christopher
David
D
Statistics, Schering-Plough Research Institute, Kenilworth, NJ, USA.
Adams
Wallace
W
Amann
Anthony
A
Bertha
Craig
C
Byron
Peter R
PR
Doub
William
W
Dunbar
Craig
C
Hauck
Walter
W
Lyapustina
Svetlana
S
Mitchell
Jolyon
J
Morgan
Beth
B
Nichols
Steve
S
Pan
Ziqing
Z
Singh
Gur Jai Pal
GJ
Tougas
Terrence
T
Tsong
Yi
Y
Wolff
Ron
R
Wyka
Bruce
B
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
D000336:Aerosols; D004364:Pharmaceutical Preparations