title: Adapting viral safety assurance strategies to continuous processing of biological products.
abstract: There has been a recent drive in commercial large-scale production of biotechnology products to convert current batch mode processing to continuous processing manufacturing. There have been reports of model systems capable of adapting and linking upstream and downstream technologies into a continuous manufacturing pipeline. However, in many of these proposed continuous processing model systems, viral safety has not been comprehensively addressed. Viral safety and detection is a highly important and often expensive regulatory requirement for any new biological product. To ensure success in the adaption of continuous processing to large-scale production, there is a need to consider the development of approaches that allow for seamless incorporation of viral testing and clearance/inactivation methods. In this review, we outline potential strategies to apply current viral testing and clearance/inactivation technologies to continuous processing, as well as modifications of existing unit operations to ensure the successful integration of viral clearance into the continuous processing of biological products. Biotechnol. Bioeng. 2017;114: 21-32. © 2016 Wiley Periodicals, Inc.
authors.affiliation: DBRRII, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, 20993.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Johnson
authors.affiliation: DBRRII, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, 20993.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Brown
authors.affiliation: DBRRII, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, 20993.
authors.forename: Scott C
authors.initials: SC
authors.lastname: Lute
authors.affiliation: DBRRII, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, 20993.
authors.forename: Kurt A
authors.initials: KA
authors.lastname: Brorson
mesh_terms: D000818:Animals; D001688:Biological Products / Q000592:standards*; D019149:Bioreactors / Q000592:standards*; D002460:Cell Line; D012449:Safety; D013678:Technology, Pharmaceutical / Q000592:standards*; D014765:Viral Vaccines; D014771:Virion; D014776:Virus Cultivation / Q000592:standards*; D014780:Viruses
chemical_list: D001688:Biological Products; D014765:Viral Vaccines
keywords: continuous processing; viral clearance; viral safety