title: Interdependence of drug substance physical properties and corresponding quality control strategy.
abstract: In quality by design (QbD) paradigm, specifications on active pharmaceutical ingredients (APIs) are a critical component of the overall control strategy to ensure drug product quality. In establishing appropriate specifications for highly correlated API properties, multivariate specifications were advocated recently (Duchesne C, MacGregor JF. 2004. J Qual Technol 36:78-94). In this text, we reviewed several scenarios where API properties are of varying degrees of intercorrelation, and discussed the corresponding control strategies. One scenario was further analyzed, in which high degree of property intercorrelation could afford a single univariate specification and, thereby, simplify the control strategy. In the case study provided, we first mapped the potential design space of the API physical properties, and subsequently compared the effectiveness of univariate and multivariate control strategies. On the basis of the comparison, a single univariate control scheme was proposed and boundary was defined. Finally, width of the design space for API physical properties was assessed, and the effectiveness of the API manufacturing process control was preliminarily evaluated.
authors.affiliation: Small Molecule Pharmaceutical Development, Genentech, Inc, South San Francisco, California 94080, USA. ycui@gene.com
authors.forename: Yong
authors.initials: Y
authors.lastname: Cui
authors.forename: Xiling
authors.initials: X
authors.lastname: Song
authors.forename: Mark
authors.initials: M
authors.lastname: Reynolds
authors.forename: King
authors.initials: K
authors.lastname: Chuang
authors.forename: Minli
authors.initials: M
authors.lastname: Xie
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011786:Quality Control
chemical_list: D004364:Pharmaceutical Preparations