title: Host cell proteins in biotechnology-derived products: A risk assessment framework.
abstract: To manufacture biotechnology products, mammalian or bacterial cells are engineered for the production of recombinant therapeutic human proteins including monoclonal antibodies. Host cells synthesize an entire repertoire of proteins which are essential for their own function and survival. Biotechnology manufacturing processes are designed to produce recombinant therapeutics with a very high degree of purity. While there is typically a low residual level of host cell protein in the final drug product, under some circumstances a host cell protein(s) may copurify with the therapeutic protein and, if it is not detected and removed, it may become an unintended component of the final product. The purpose of this article is to enumerate and discuss factors to be considered in an assessment of risk of residual host cell protein(s) detected and identified in the drug product. The consideration of these factors and their relative ranking will lead to an overall risk assessment that informs decision-making around how to control the levels of host cell proteins.
authors.affiliation: Safety Assessment, Genentech, Inc., South San Francisco, California. dezafra.christina@gene.com.
authors.forename: Christina L Zuch
authors.initials: CL
authors.lastname: de Zafra
authors.affiliation: Bioanalytical Sciences, Genentech, Inc., South San Francisco, California.
authors.forename: Valerie
authors.initials: V
authors.lastname: Quarmby
authors.affiliation: Pharma Technical Regulatory, Genentech, Inc., South San Francisco, California.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Francissen
authors.affiliation: Analytical Operations, Genentech, Inc., South San Francisco, California.
authors.forename: Martin
authors.initials: M
authors.lastname: Vanderlaan
authors.affiliation: Protein Analytical Chemistry, Genentech, Inc., South San Francisco, California.
authors.forename: Judith
authors.initials: J
authors.lastname: Zhu-Shimoni
mesh_terms: D001688:Biological Products / Q000737:chemistry* / Q000302:isolation & purification*; D001709:Biotechnology / Q000379:methods*; D004340:Drug Contamination; D006801:Humans; D011506:Proteins / Q000032:analysis*; D018570:Risk Assessment; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D001688:Biological Products; D011506:Proteins
keywords: bioprocess; host cell protein; immunogenicity; process development; safety assessment