title: Establishing a control system using QbD principles.
abstract: Quality by design (QbD) is a global regulatory initiative with the goal of enhancing pharmaceutical development through the proactive design of pharmaceutical manufacturing process and controls to consistently deliver the intended performance of the product. The principles of pharmaceutical development relevant to QbD are described in the ICH guidance documents (ICHQ8-11). An integrated set of risk assessments and their related elements developed at Roche/Genentech were designed to provide an overview of product and process knowledge for the production of a recombinant monoclonal antibody. This chapter describes the elements and tools used to establish acceptance criteria and an attribute testing strategy (ATS) for product variants and process related impurities. The acceptable ranges for CQAs are set based on their potential impact on efficacy and safety/immunogenicity. This approach is focused on the management of patient impacts, rather than simply maintaining a consistent analytical profile. The ATS tools were designed to identify quality attributes that required process and/or testing controls, or that could be captured in a monitoring system to enable lifecycle management of the control strategy.
authors.affiliation: Pharma Technical Development, Roche Diagnostics GmbH, Nonnenwald 2, 82377 Penzberg, Germany. Electronic address: jochen_felix.kepert@roche.com.
authors.forename: J Felix
authors.initials: JF
authors.lastname: Kepert
authors.affiliation: Pharma Technical Development, Genentech, South San Francisco, CA 94080, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Cromwell
authors.affiliation: Pharma Technical Development Biotech Europe, F. Hoffmann-La Roche Ltd, 4070 Basel, Switzerland.
authors.forename: Niklas
authors.initials: N
authors.lastname: Engler
authors.affiliation: Pharma Technical Development Biotech Europe, F. Hoffmann-La Roche Ltd, 4070 Basel, Switzerland.
authors.forename: Christof
authors.initials: C
authors.lastname: Finkler
authors.affiliation: Analytical Development, Novartis Pharma AG, Werk Klybeck, Basel, Switzerland.
authors.forename: Gerald
authors.initials: G
authors.lastname: Gellermann
authors.affiliation: Pharma Technical Development, Genentech, South San Francisco, CA 94080, USA.
authors.forename: Lynn
authors.initials: L
authors.lastname: Gennaro
authors.affiliation: Pharma Technical Development, Genentech, South San Francisco, CA 94080, USA.
authors.forename: Reed
authors.initials: R
authors.lastname: Harris
authors.affiliation: Pharma Technical Development, Genentech, South San Francisco, CA 94080, USA.
authors.forename: Raquel
authors.initials: R
authors.lastname: Iverson
authors.affiliation: Pharma Technical Development, Genentech, South San Francisco, CA 94080, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Kelley
authors.affiliation: Pharma Technical Development, Genentech, South San Francisco, CA 94080, USA.
authors.forename: Lynne
authors.initials: L
authors.lastname: Krummen
authors.affiliation: Pharma Technical Development, Genentech, South San Francisco, CA 94080, USA.
authors.forename: Nathan
authors.initials: N
authors.lastname: McKnight
authors.affiliation: Biologics Quality Control, Genentech, South San Francisco, CA 94080, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Motchnik
authors.affiliation: Pharma Technical Development Biotech Europe, F. Hoffmann-La Roche Ltd, 4070 Basel, Switzerland.
authors.forename: Volker
authors.initials: V
authors.lastname: Schnaible
authors.affiliation: Pharma Technical Development, Genentech, South San Francisco, CA 94080, USA.
authors.forename: Ron
authors.initials: R
authors.lastname: Taticek
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000235:genetics* / Q000302:isolation & purification* / Q000627:therapeutic use; D006801:Humans; D011786:Quality Control; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D011994:Recombinant Proteins
keywords: Control strategy; Critical quality attributes; Quality by design