title: A new roadmap for biopharmaceutical drug product development: Integrating development, validation, and quality by design.
abstract: Quality by design (QbD) is a science- and risk-based approach to drug product development. Although pharmaceutical companies have historically used many of the same principles during development, this knowledge was not always formally captured or proactively submitted to regulators. In recent years, the US Food and Drug Administration has also recognized the need for more controls in the drug manufacturing processes, especially for biological therapeutics, and it has recently launched an initiative for Pharmaceutical Quality for the 21st Century to modernize pharmaceutical manufacturing and improve product quality. In the biopharmaceutical world, the QbD efforts have been mainly focused on active pharmaceutical ingredient processes with little emphasis on drug product development. We present a systematic approach to biopharmaceutical drug product development using a monoclonal antibody as an example. The approach presented herein leverages scientific understanding of products and processes, risk assessments, and rational experimental design to deliver processes that are consistent with QbD philosophy without excessive incremental effort. Data generated using these approaches will not only strengthen data packages to support specifications and manufacturing ranges but hopefully simplify implementation of postapproval changes. We anticipate that this approach will positively impact cost for companies, regulatory agencies, and patients, alike.
authors.affiliation: Late Stage Pharmaceutical and Processing Development, Genentech Inc., South San Francisco, California 94080; Biologics Pharmaceutical Development, Novartis Pharma AG, CH-4002 Basel, Switzerland. Electronic address: sheryl.martin-moe@novartis.com.
authors.forename: Sheryl
authors.initials: S
authors.lastname: Martin-Moe
authors.affiliation: Late Stage Pharmaceutical and Processing Development, Genentech Inc., South San Francisco, California 94080.
authors.forename: Fredric J
authors.initials: FJ
authors.lastname: Lim
authors.affiliation: Late Stage Pharmaceutical and Processing Development, Genentech Inc., South San Francisco, California 94080.
authors.forename: Rita L
authors.initials: RL
authors.lastname: Wong
authors.affiliation: Late Stage Pharmaceutical and Processing Development, Genentech Inc., South San Francisco, California 94080.
authors.forename: Alavattam
authors.initials: A
authors.lastname: Sreedhara
authors.affiliation: Biologics MSAT, Genentech Inc., South San Francisco, California 94080.
authors.forename: Jagannathan
authors.initials: J
authors.lastname: Sundaram
authors.affiliation: Biologics MSAT, Genentech Inc., South San Francisco, California 94080.
authors.forename: Samir U
authors.initials: SU
authors.lastname: Sane
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry; D001702:Biopharmaceutics / Q000295:instrumentation / Q000379:methods / Q000592:standards*; D002626:Chemistry, Pharmaceutical / Q000295:instrumentation / Q000379:methods / Q000592:standards; D003257:Consumer Product Safety; D004339:Drug Compounding / Q000295:instrumentation / Q000379:methods / Q000592:standards; D055808:Drug Discovery / Q000295:instrumentation / Q000379:methods / Q000592:standards*; D017408:Guidelines as Topic; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000592:standards*; D011786:Quality Control; D018570:Risk Assessment; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods / Q000592:standards*
chemical_list: D000911:Antibodies, Monoclonal; D004364:Pharmaceutical Preparations