title: Statistical approaches to determine analytical variability and specifications: application of experimental design and variance component analysis.
abstract: Assessment of analytical variability is recognized as an important factor for the establishment of specifications. Estimation of the variance for an analytical procedure can be accomplished using a variety of approaches. The approach of variance component analysis was applied retrospectively, as well as prospectively, to estimate analytical variance. The prospective approach also included the use of experimental design. Recent new drug substance examples illustrating these approaches are presented. In these examples, the analytical property of potency was evaluated. Factors examined in the experimental design include laboratory, day, analyst, instrument and column. Process variability can also be determined by variance component analysis. For a stable drug substance, combining the analytical and process variances provides an estimate on the total variance for the analytical property of potency. With the total variability statistically derived, an appropriate specification that is consistent with process and analytical capability can be established.
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Lafayette, IN 47902, USA tsang_paul_k@lilly.com
authors.forename: P K
authors.initials: PK
authors.lastname: Tsang
authors.forename: J S
authors.initials: JS
authors.lastname: Larew
authors.forename: L A
authors.initials: LA
authors.lastname: Larew
authors.forename: T W
authors.initials: TW
authors.lastname: Miyakawa
authors.forename: J D
authors.initials: JD
authors.lastname: Hofer
mesh_terms: D000704:Analysis of Variance; D002626:Chemistry, Pharmaceutical; D015507:Drugs, Investigational; D011446:Prospective Studies; D012107:Research Design; D012189:Retrospective Studies
chemical_list: D015507:Drugs, Investigational