title: Parametric two-stage sequential quality assurance test of dose content uniformity.
abstract: The United States Pharmacopeia (USP) content uniformity sampling acceptance plan consisting of a two-stage sampling plan with criteria on sample mean and number of out-of-range tablets is the standard for compendium. It is, however, often used mistakenly for lot quality assurance. In comparison to the Japan Phamacopeia (JP) procedure, USP procedure is less discriminative between lots with on-target mean and small variance and lots with off-target mean and large variance. The new European Pharmacopeia (EP) and USP harmonized test adopted a tolerance interval approach. But the "no-difference zone" criteria modification for off-target products make the approaches biased in favor of off-target products. We propose a parametric tolerance interval procedure to test a two-sided specification that is equivalent to the test of two one-sided hypotheses. Testing against a lower specification is to assure that the drug product is not under-dosed for the sake of efficacy. On the other hand, testing against an upper specification is to assure that the drug product is not over-dosed for the sake of safety. The operating curves of the proposed procedure are compared with those of the USP test to illustrate the difference in acceptance probability against the mean and variance of the lot.
authors.affiliation: Division of Biometrics VI, Office of Biostatistics, CDER, U.S. FDA, Silver Spring, Maryland, USA. tsong@cder.fda.gov
authors.forename: Yi
authors.initials: Y
authors.lastname: Tsong
authors.forename: Meiyu
authors.initials: M
authors.lastname: Shen
mesh_terms: D000465:Algorithms; D002626:Chemistry, Pharmaceutical / Q000379:methods* / Q000592:standards; D005060:Europe; D007564:Japan; D015233:Models, Statistical; D010602:Pharmacopoeias as Topic / Q000592:standards*; D011336:Probability; D011786:Quality Control; D013607:Tablets / Q000737:chemistry*; D014481:United States
chemical_list: D013607:Tablets