“High‐risk” host cell proteins (HCPs): A multi‐company collaborative view

Abstract

Host cell proteins (HCPs) are process-related impurities that may copurify with biopharmaceutical drug products. Within this class of impurities there are some that are more problematic. These problematic HCPs can be considered high-risk and can include those that are immunogenic, biologically active, or enzymatically active with the potential to degrade either product molecules or excipients used in formulation. Some have been shown to be difficult to remove by purification. Why should the biopharmaceutical industry worry about these high-risk HCPs? What approach could be taken to understand the origin of its copurification and address these *Marisa Jones and Nisha Palackal should be considered joint first authors About Biophorum Development Group (BPDG): Since its inception in 2004, BioPhorum has become a trusted environment in which senior leaders of the biopharmaceutical industry come together to share and discuss openly the emerging trends and challenges facing their industry.BioPhorum currently comprises more than 3800 active participants in seven "phorums" covering cell and gene therapy, drug substance, development, fill-finish, a technology roadmap, information technology, and supply partners. The Host Cell Protein (HCP) Workstream is part of the Development Group (BPDG). This article is a composite view of opinions shared by the whole of the BPDG-HCP Workstream and should not be attributed to the individual positions of the participating companies.

Host cell protein detection gap risk mitigation: quantitative IAC-MS for ELISA antibody reagent coverage determination

“…[13][14][15] Monitoring of residual HCPs by ELISA is indispensable for quality control and risk assessment. 1,2,25 Therefore, it is highly relevant that the ELISA antibody reagent provides sufficient coverage of the HCPs throughout the whole DSP, as different sample conditions can influence detection. For this reason, the ELISA antibody reagent was investigated further to assess how well it recognizes the HCPs in different steps of the DSP.…”

“…For example, comparing direct HCPs and IAC HCP detection from samples with high HCP levels (CCF) can be used as the basis for identification of possible HCP detection gaps of the ELISA antibody with a particular focus on already described highrisk HCPs. 25 The relevance of these gaps can be further assessed for correlation in samples like UFDF or DS for different bioproducts.…”

“…24 Thus, MS is a valuable method for monitoring HCP clearance during process development, and its use significantly improves risk assessment in HCP control. 25 Affinity purification by immunoaffinity chromatography (IAC) coupled to MS is a selective and sensitive approach for isolation and identification of binding partners to a specific target protein and is widely used for the discovery of proteinprotein interactions. 26,27 This approach, however, also can be used for evaluating more complex mixtures, as done herein for the determination of ELISA antibody coverage.…”

Host cell protein profiling of commercial therapeutic protein drugs as a benchmark for monoclonal antibody-based therapeutic protein development

“…Benchmarking HCP in commercial biotherapeutic products provides valuable information for the biotechnology industry, which aims to develop pure and safe biotherapeutic products through process optimization. 13 Knowledge of HCP levels across approved protein therapeutics would help to determine the current industry standard for HCP clearance during production. However, the enzyme-linked immunosorbent assay (ELISA) methods that are commonly used for HCP analysis cannot be readily compared across companies and drugs due to differences in HCP populations from different host cell lines and differences in the immunoreactivity against HCP for different ELISA kits.…”

Holistic Analytical Characterization and Risk Assessment of Residual Host Cell Protein Impurities in an Active Pharmaceutical Ingredient (API) Synthesized by Biocatalysts

“…Residual HCP impurity in biological drug substance or drug product are generally considered as a critical quality attribute (CQA) due to its potential impact on product quality, safety, and efficacy (FDA, 1997;Guideline, 1999). The impacts can be classified into four main categories: 1) immunogenicity; 2) adjuvant effects; 3) biological activities; and 4) enzymatic activities (Jones et al, 2021;Vanderlaan et al, 2018;X. Wang et al, 2009).…”