title: On developing a process for conducting extractable-leachable assessment of components used for storage of biopharmaceuticals.
abstract: Extractables and leachables are product-related impurities that result from product contact with components such as gaskets, stoppers, storage bags, cartridges, and prefilled syringes that are used for processing, storage, and/or delivery of biopharmaceuticals. These impurities are a concern for patients due to potential effects on product quality and safety. It is possible that such an impurity could directly impact the patient or indirectly impact the patient by interacting with the protein therapeutics and forming protein adducts. Adducts and leachables may or may not be detected as product-related impurities in routine stability indicating assays depending on the rigor of the analytical program. The need for the development of a thorough and holistic extractable and leachable program based on risk assessment, review of existing literature, and consolidation of industry best practices is discussed. Standardizing component use within an organization enables streamlining of the extractable-leachable program. Our strategy for an extractable-leachable program is divided into different stages, each stage detailing the activities and the department within the organization that is responsible for execution of these activities. The roles and responsibilities of the key stakeholders are identified. The integration of analytical activities with health-based risk-assessment information into the design of an extractable-leachable program is highlighted.
authors.affiliation: Department of Late Stage Pharmaceutical and Processing Development, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA. wakankar.aditya@gene.com
authors.forename: Aditya A
authors.initials: AA
authors.lastname: Wakankar
authors.forename: Y John
authors.initials: YJ
authors.lastname: Wang
authors.forename: Eleanor
authors.initials: E
authors.lastname: Canova-Davis
authors.forename: Stacey
authors.initials: S
authors.lastname: Ma
authors.forename: Dieter
authors.initials: D
authors.lastname: Schmalzing
authors.forename: Josh
authors.initials: J
authors.lastname: Grieco
authors.forename: Terry
authors.initials: T
authors.lastname: Milby
authors.forename: Theresa
authors.initials: T
authors.lastname: Reynolds
authors.forename: Kellen
authors.initials: K
authors.lastname: Mazzarella
authors.forename: Ed
authors.initials: E
authors.lastname: Hoff
authors.forename: Stephen
authors.initials: S
authors.lastname: Gomez
authors.forename: Sherry
authors.initials: S
authors.lastname: Martin-Moe
mesh_terms: D001688:Biological Products / Q000032:analysis / Q000592:standards; D003257:Consumer Product Safety; D004340:Drug Contamination / Q000517:prevention & control*; D004349:Drug Packaging / Q000592:standards*; D004355:Drug Stability; D004356:Drug Storage; D004364:Pharmaceutical Preparations / Q000032:analysis / Q000592:standards; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods*
chemical_list: D001688:Biological Products; D004364:Pharmaceutical Preparations