Parametric Two-Tier Sequential Quality Assurance Test of Delivery Dose Uniformity of Multiple-Dose Inhaler and Dry Powder Inhaler Drug Products |
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| Authors: | Yi Tsong Meiyu Shen Richard T. Lostritto Guiragos K. Poochikian |
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| Affiliation: | 1. Office of Biostatistics/Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration , Silver Spring, Maryland, USA yi.tsong@fda.hhs.gov;3. Office of Biostatistics/Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration , Silver Spring, Maryland, USA;4. Office of New Drug Quality Assurance/Office of Pharmaceutical Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration , Silver Spring, Maryland, USA |
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| 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 In 1998, the U.S. Food and Drug Administration recommended a two-tier acceptance sampling plan in the Draft Guidance of Metered Dose Inhaler and Dry Powder Inhaler Drug Products Chemistry, Manufacturing and Controls.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. |
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| Keywords: | Delivered dose uniformity Double one-sided test FDA draft guidance method Tolerance interval Two-tier group sequential |
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