title: Process characterization and Design Space definition.
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 (MAb). This chapter describes the tools used for the characterization and validation of MAb manufacturing process under the QbD paradigm. This comprises risk assessments for the identification of potential Critical Process Parameters (pCPPs), statistically designed experimental studies as well as studies assessing the linkage of the unit operations. Outcome of the studies is the classification of process parameters according to their criticality and the definition of appropriate acceptable ranges of operation. The process and product knowledge gained in these studies can lead to the approval of a Design Space. Additionally, the information gained in these studies are used to define the 'impact' which the manufacturing process can have on the variability of the CQAs, which is used to define the testing and monitoring strategy.
authors.affiliation: Pharma Technical Development, Roche Diagnostics GmbH, Sandhofer Str. 116, 68305 Mannheim, Germany. Electronic address: christian.hakemeyer@roche.com.
authors.forename: Christian
authors.initials: C
authors.lastname: Hakemeyer
authors.affiliation: Pharma Technical Development, Genentech, South San Francisco, CA 94080, USA.
authors.forename: Nathan
authors.initials: N
authors.lastname: McKnight
authors.affiliation: Pharma Technical Development, Genentech, South San Francisco, CA 94080, USA.
authors.forename: Rick
authors.initials: R
authors.lastname: St John
authors.affiliation: Pharma Technical Development, Genentech, South San Francisco, CA 94080, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Meier
authors.affiliation: Pharma Technical Development, Genentech, South San Francisco, CA 94080, USA.
authors.forename: Melody
authors.initials: M
authors.lastname: Trexler-Schmidt
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, Roche Diagnostics GmbH, Nonnenwald 2, 82377 Penzberg, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Zettl
authors.affiliation: Pharma Technical Development Biotech Europe, F. Hoffmann-La Roche Ltd, 4070 Basel, Switzerland.
authors.forename: Robert
authors.initials: R
authors.lastname: Puskeiler
authors.affiliation: Pharma Technical Development, Roche Diagnostics GmbH, Nonnenwald 2, 82377 Penzberg, Germany.
authors.forename: Annika
authors.initials: A
authors.lastname: Kleinjans
authors.affiliation: Pharma Technical Development, Genentech, South San Francisco, CA 94080, USA.
authors.forename: Fred
authors.initials: F
authors.lastname: Lim
authors.affiliation: Pharma Technical Development Biotech Europe, F. Hoffmann-La Roche Ltd, 4070 Basel, Switzerland.
authors.forename: Christine
authors.initials: C
authors.lastname: Wurth
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: Design space; Monoclonal antibody; Process characterization; Process validation; Quality by design (QbD)