title: Parametric two-tier sequential quality assurance test of delivery dose uniformity of multiple-dose inhaler and dry powder inhaler drug products.
abstract: The delivery dose uniformity is one of the most critical requirements of dry powder inhaler and metered dose inhaler products. In 1998, the U.S. Food and Drug Administration recommended a two-tier acceptance sampling plan in the Draft Guidance of Metered Dose Inhaler and Dry Powder Inhaler Drug Products Chemistry, Manufacturing and Controls. The two-tier procedure is a modification of the United States Pharmacopeia (USP) sampling plan of dose content uniformity. It employed a zero tolerance criterion. In addition, it has a near-zero probability acceptance at the second tier. In this article, a two-tier sequential tolerance interval approach is proposed that is equivalent to a two-tier two one-sided testing procedure. It controls the probability of the product delivering below a prespecified effective dose and the probability of the product delivering over a prespecified safety dose.
authors.affiliation: Office of Biostatistics/Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland 20993, USA. yi.tsong@fda.hhs.gov
authors.forename: Yi
authors.initials: Y
authors.lastname: Tsong
authors.forename: Meiyu
authors.initials: M
authors.lastname: Shen
authors.forename: Richard T
authors.initials: RT
authors.lastname: Lostritto
authors.forename: Guiragos K
authors.initials: GK
authors.lastname: Poochikian
mesh_terms: D036501:Metered Dose Inhalers / Q000592:standards*; D009330:Nebulizers and Vaporizers / Q000592:standards*; D010602:Pharmacopoeias as Topic; D011208:Powders; D011336:Probability; D011786:Quality Control; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D011208:Powders