Parametric two-tier sequential quality assurance test of delivery dose uniformity of multiple-dose inhaler and dry powder inhaler drug products

J Biopharm Stat. 2008;18(5):976-84. doi: 10.1080/10543400802287222.

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 In 1998, the U.S. Food and Drug Administration recommended a two-tier acceptance sampling plan in the Draft Guidance of Metered Dose Inhaler and Dry Powder Inhaler Drug Products Chemistry, Manufacturing and Controls.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.

MeSH terms

  • Metered Dose Inhalers / standards*
  • Nebulizers and Vaporizers / standards*
  • Pharmacopoeias as Topic
  • Powders
  • Probability
  • Quality Control
  • United States
  • United States Food and Drug Administration

Substances

  • Powders