title: Determination of critical quality attributes for monoclonal antibodies using quality by design 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 identification of critical quality attributes (CQAs) as an important first step for QbD development of biopharmaceuticals. A systematic scientific based risk ranking and filtering approach allows a thorough understanding of quality attributes and an assignment of criticality for their impact on drug safety and efficacy. To illustrate the application of the approach and tools, a few examples from monoclonal antibodies are shown. The identification of CQAs is a continuous process and will further drive the structure and function characterization of therapeutic proteins.
authors.affiliation: Pharma Technical Development, Roche Diagnostics GmbH, Nonnenwald 2, 82377 Penzberg, Germany. Electronic address: nadja.alt@roche.com.
authors.forename: Nadja
authors.initials: N
authors.lastname: Alt
authors.affiliation: Pharma Technical Development, Genentech, South San Francisco, CA 94080, USA.
authors.forename: Taylor Y
authors.initials: TY
authors.lastname: Zhang
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, Genentech, South San Francisco, CA 94080, USA.
authors.forename: Ron
authors.initials: R
authors.lastname: Taticek
authors.affiliation: Research and Early Development, Genentech, South San Francisco, CA 94080 USA.
authors.forename: Valerie
authors.initials: V
authors.lastname: Quarmby
authors.affiliation: Pharma Research and Early Development, Roche Innovation Center Munich, Roche Diagnostics GmbH, Nonnenwald 2, 82377 Penzberg, Germany.
authors.forename: Tilman
authors.initials: T
authors.lastname: Schlothauer
authors.affiliation: Pharma Technical Development Biotech Europe, F. Hoffmann-La Roche Ltd, 4070 Basel, Switzerland.
authors.forename: Hermann
authors.initials: H
authors.lastname: Beck
authors.affiliation: Pharma Research and Early Development, Roche Innovation Center Munich, Roche Diagnostics GmbH, Nonnenwald 2, 82377 Penzberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Emrich
authors.affiliation: Pharma Technical Development, Genentech, South San Francisco, CA 94080, USA.
authors.forename: Reed J
authors.initials: RJ
authors.lastname: Harris
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D011786:Quality Control; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D011994:Recombinant Proteins
keywords: Critical quality attribute; Quality by design; Risk ranking and filtering