Unveiling Host Cell Protein (HCP) Coverage in Three-Dimensions (3D): Why It Matters and How to Achieve It
Host cell proteins (HCPs) are impurities derived from the host organism used in the production of genetically engineered biopharmaceuticals. Their removal is crucial for the safety and efficacy of the final product, as they can provoke unwanted immune responses and/or have undesired biological/enzymatic activities[1-4]. The sandwich enzyme-linked immunosorbent assay (ELISA) remains the most widely used method for HCP quantification throughout biopharmaceuticals product development lifecycle due to its high sensitivity, throughput, and selectivity in complex sample matrices.
Tech Briefing: Beyond the Surface: Is Going Deeper Always More Beneficial?
Host cell proteins (HCPs) are residual protein impurities expressed along with the desired biologics product. Removing HCPs in the final drug substance (DS) to an acceptable level sometimes can be challenging because of the diverse nature of the HCPs and their potential affinity for the intended product, especially for non-monoclonal antibody (non-mAb) products due to the lack of affinity purification process.
Critical HCPs: What to do with them?
Volume 1, Issue 9: Host cell proteins (HCPs) are a complex blend of various proteins that need to be depleted during the production of biotherapeutics. Any residual HCPs can pose diverse risks to quality, safety, and developability of a drug. There is manufacturing and clinical history indicating certain classes of HCPs which have been problematic, e.g. HCPs which,
FDA Federal Register: Evaluating the Immunogenicity Risk of Host Cell Proteins in Follow-On Recombinant Peptide Products
The FDA has posted a request for information and comments in the Federal Register on the subject Evaluating the Immunogenicity Risk of Host Cell Proteins in Follow-On Recombinant Peptide Products. BEBPA strongly encourages participation in this process. Comments will close on September 23, 2024.
Host Cell Proteins Remain a Hotly Debated and Emerging Topic
Volume 1, Issue 8: At the finish of the recent 12th annual Host Cell Protein Conference (May 14-16, 2024) sponsored by BEBPA in College Park, MD, Dr. Denise Krawitz gave her final summary of conference highlights. We thought it would be fun and informative for those of you who could not join us to hear a synopsis of the 3-day conference from her perspective. Below you will find excerpts from her summary:
2024 HCP Conference Survey Results (PDF)
BEBPA Blog 2024 HCP Conference Survey Results (PDF) View PDF Survey
Tech Briefing: ELISA and USP 1123.1 Interest Groups at BEBPA’s 2024 HCP Conference
The 2024 Host Cell Protein Conference will feature two Interest Groups on Day 3 which will be available only to in-person attendees. BEBPA conferences are well-known for their collegiality, opportunities for networking, and speakers/attendees who “tell it like it is,” and this is due in large part to conference Interest Groups and Workshops.
Tech Briefing: Improved Clearance of High Risk HCPs
In this year’s BEBPA Host Cell Protein Conference, we are featuring presentations covering some recent successes downstream process engineers have had in in improving the purity of biopharmaceuticals.
Tech Briefing: Pooling Industry-Wide Data for Determining Relevant HCPs
In the “early days” of BEBPA HCP Conferences, there always seemed to be at least one public request for companies to disclose information about HCPs in their products. My recollection is that these requests were always greeted with external nods of approval, but I think everyone was thinking internally, “Yeah, but what are the chances my company’s legal department is going to approve that.” In 2018 Vanderlaan et al. published a review article summarizing all clinical experiences with HCPs up to that time.[1] The case studies represented the major effects HCPs can have on product safety and efficacy: the adjuvant effect, cell line homologs of the product, immunogenic HCPs, cytokine HCPs, and HCPs that affect product stability. In recent years Regeneron published HCPs identified in 29 drug products,[2] and the BioPhorum Host Cell Protein Workstream Group published a list of common CHO HCPs reported in recombinant protein products.[3]
Tech Briefing: HCP ELISAs for Gene Therapy Products
Over the years we’ve heard more complaints about HCP ELISAs from gene and cell therapy folks than anyone else. Many of the developmental efforts have been performed in more academic or translational research environments, where the regulatory requirements of HCP analysis were not always front-and-center in the product development pathway. As a result, HCP analysis was often done late in the development process and was considered more of a check-the-box effort. Very few of these groups had the resources to develop their own HCP ELISA, so they relied on commercial kits. Many of these products are produced in HEK293 cell lines, and there are limited options for commercial HEK293 HCP ELISA kits. Thus, limited consumer choice has been another reason for the complaints. Compounding this, many in the gene therapy field are not aware of the limitations of using a commercial HCP ELISA kit. When the kit vendor changes reagent lots or does a wholesale change/upgrade of the kit, they are left wondering how to cope with HCP ELISA results that can change by as much as three-fold.