BEBPA Blog
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]
In this year’s BEBPA HCP Conference, Dr. Victor Chrone of Alphalyse will present what should be another step in deepening our collective understanding of HCPs in biologics. Dr. Chrone will discuss the HCP database Alphalyse has generated from their projects over the years. This database includes HCPs from 45 different cell lines as well as AAV and Lentivirus vectors:
The extensive database provides information about commonly found HCPs in similar drug types and insights into the process clearance of problematic HCPs. This information enhances our understanding of HCP profiles in biologics manufacturing and empowers informed decision-making for HCP clearance and monitoring. For example, we have evaluated hundreds of mAb in-process samples and purified DS for the levels of lipases that may degrade polysorbate in the DP. The information has enabled us to develop a high sensitivity LC-MS assay specifically for lipases in mAbs… The presentation will include insights about problematic HCPs across drug types and essential method parameters for assay quality control.
HCP identity is not everything though; identification of HCPs needs to be paired with risk-assessment. De Zafra et al. published the foundational HCP risk assessment framework in 2015.[4] In this conference, two representatives from the BioPhorum HCP Workstream Group will take a look at the de Zafra’s framework and the Group’s expansion of it:
The BioPhorum development group HCP workstream brought together a team of industry experts to develop a comprehensive guidance to assess clinical safety risks upon identification of individual HCPs, incorporating regulatory considerations and industry experience. The guidance includes an expansion of the existing clinical risk assessment framework developed by de Zafra et al. and recommendations on the information and product specific data that can be leveraged at each stage in development. The review also includes guidance on how to proceed if a risk is identified, as well as real-world case studies using the recommended framework.
New data, and new ways to analyze data – the BEBPA HCP Conference’s goal is to stay abreast of these exciting developments and provide a forum for presentation and open discussion. These are just some of the topics and talks happening at this HCP meeting. Additional topics include:
- Regulatory Evaluation and Perspective of HCP Assays
- Developing ELISA Assays
- HCPs Impact Product Stability
- BioProcessing and Removal of HCPs
- USP HCP Projects: Updates
- Mass Spectrometry Analysis
- And many Case Studies
Click HERE to see all the topics being discussed.
This is the premier HCP meeting to attend where scientist gather to discuss best practices, happenings in the field and share war stories. Sign up today, before prices increase and space fills up. The conference is happening May 14-16, 2024 in College Park, Maryland. We look forward to seeing you there!
Recent References:
[1] Martin Vanderlaan, Judith Zhu-Shimoni, Sansan Lin, Feny Gunawan, Thomas Waerner, Kevin E Van Cott, Experience with host cell protein impurities in biopharmaceuticals. Biotechnol Prog. 2018 Jul;34(4):828-837. doi: 10.1002/btpr.2640.
[2] Rosalynn Molden, Mengqi Hu, Sook Yen E, Diana Saggese, James Reilly, John Mattila, Haibo Qiu, Gang Chen, Hanne Bak, Ning Li. Host cell protein profiling of commercial therapeutic protein drugs as a benchmark for monoclonal antibody-based therapeutic protein development. MAbs. 2021 Jan-Dec;13(1):1955811. doi: 10.1080/19420862.2021.1955811.
[3] Marisa Jones et al., “High-risk” host cell proteins (HCPs): A multi-company collaborative view. Biotechnol Bioeng. 2021 Aug;118(8):2870-2885. doi: 10.1002/bit.27808..
[4] Christina L Zuch de Zafra, Valerie Quarmby, Kathleen Francissen, Martin Vanderlaan, Judith Zhu-Shimoni. Host cell proteins in biotechnology-derived products: A risk assessment framework. Biotechnol Bioeng. 2015 Nov;112(11):2284-91. doi: 10.1002/bit.25647.