title: Assessment Methodology for Process Validation Lifecycle Stage 3A.
abstract: The paper introduces evaluation methodologies and associated statistical approaches for process validation lifecycle Stage 3A. The assessment tools proposed can be applied to newly developed and launched small molecule as well as bio-pharma products, where substantial process and product knowledge has been gathered. The following elements may be included in Stage 3A: number of 3A batch determination; evaluation of critical material attributes, critical process parameters, critical quality attributes; in vivo in vitro correlation; estimation of inherent process variability (IPV) and PaCS index; process capability and quality dashboard (PCQd); and enhanced control strategy. US FDA guidance on Process Validation: General Principles and Practices, January 2011 encourages applying previous credible experience with suitably similar products and processes. A complete Stage 3A evaluation is a valuable resource for product development and future risk mitigation of similar products and processes. Elements of 3A assessment were developed to address industry and regulatory guidance requirements. The conclusions made provide sufficient information to make a scientific and risk-based decision on product robustness.
authors.affiliation: Apotex Inc., 150 Signet Drive, Toronto, Ontario, M9L 1T9, Canada.
authors.forename: Naheed
authors.initials: N
authors.lastname: Sayeed-Desta
authors.affiliation: Apotex Inc., 150 Signet Drive, Toronto, Ontario, M9L 1T9, Canada. apazhaya@apotex.com.
authors.forename: Ajay Babu
authors.initials: AB
authors.lastname: Pazhayattil
authors.affiliation: Apotex Inc., 150 Signet Drive, Toronto, Ontario, M9L 1T9, Canada.
authors.forename: Jordan
authors.initials: J
authors.lastname: Collins
authors.affiliation: Apotex Inc., 150 Signet Drive, Toronto, Ontario, M9L 1T9, Canada.
authors.forename: Shu
authors.initials: S
authors.lastname: Chen
authors.affiliation: Apotex Inc., 150 Signet Drive, Toronto, Ontario, M9L 1T9, Canada.
authors.forename: Marzena
authors.initials: M
authors.lastname: Ingram
authors.affiliation: Apotex Inc., 150 Signet Drive, Toronto, Ontario, M9L 1T9, Canada.
authors.forename: Jana
authors.initials: J
authors.lastname: Spes
mesh_terms: D000818:Animals; D001702:Biopharmaceutics / Q000592:standards; D002626:Chemistry, Pharmaceutical / Q000379:methods / Q000592:standards*; D006801:Humans; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000737:chemistry / Q000592:standards*; D015203:Reproducibility of Results
chemical_list: D004364:Pharmaceutical Preparations
keywords: FDA PV guidance; Stage 3A; continued process verification; ongoing process verification; process validation lifecycle stages