Host cell proteins (HCPs) are a complex and diverse group of proteins produced by the cells used in biopharmaceutical manufacturing processes. We’d like to think that analytical methods used for release of a biopharmaceutical product are unambiguous – i.e., methods having well-defined target analyte(s), complete analyte coverage, high specificity, and a high degree of confidence in the results. The HCP ELISA, which is often used as a release assay, barely has any of those desirable traits. So, what other methods can we use to assess the purity of products? Outside of other immunoassays, mass spectrometry (LC-MS/MS) is most used. However, despite all the high-tech features of this method, it also is imperfect, especially when it comes to being a release assay.

Compounding the analytical ambiguity are the regulatory guidelines regarding HCPs. There is no specific limit on total HCP level, nor are there guidelines on the allowable number or identity of individual HCPs within a product. The regulatory agencies put the burden on the sponsor, requiring that they show HCPs are minimized to an extent that does not compromise safety or efficacy of the final product. That is perfectly reasonable, but how does one know in advance what will happen? In the HCP field, there are so many questions one can ask:

• Can a commercial HCP ELISA kit be used, and if so, for how long?
• Should a platform or process-specific HCP ELISA be used?
• What animals should be used to generate HCP ELISA antibodies?
• How are HCP ELISA reagents’ life-cycles managed?
• What if new ELISA reagents give different results?
• When (if ever) should mass spectrometry be used?
• How much more effort is needed to improve the product purity?
• Will the risk assessment methods used provide reliable results?

People who work in this field get acclimated to dealing with open-ended questions. This is what makes a conference like the BEBPA HCP Conference so valuable. In a field where there are (1) unknown target analytes, (2) imperfect analytical methods, and (3) case-by-case regulatory guidelines, there is no substitute for leaning on the wisdom of those who have gone before. The 2024 BEBPA HCP Conference will bring together top-ranked scientists and engineers to share insights into purification and HCP analysis.

This conference will also feature presentations and extended discussions on regulatory expectations and guidelines related to HCPs. This year we are pleased to announce that Dr. Nadine Ritter, Dr. Emily Schacter, Dr. Erika Friedl, and Dr. Roman Drews will be in attendance and sharing their industrial and regulatory experience in dealing with HCPs among a variety of modalities.

HCPs Then and Now: What Has Changed, What Remains the Same
Nadine Ritter, President and Sr Analytics Advisor, Global Biotech Experts

Regulatory Expectations for Evaluation of Host Cell Proteins: Principles and Practices
Emily Schacter, Independent Consultant, ThinkFDA, LLC

HCP Control Strategies and Regulatory Requirements
Erika Friedl, Senior Quality Expert, Paul-Ehrlich-Institute

Control Strategy for Lentivirus Vector-derived HCPs Impuriy in CAR-T Final Drug Product
Roman Drews, Head of Regulatory Affairs CMC, Arcellx, Inc.

These are just a few of the great topics and talks planned for the upcoming BEBPA Host Cell Protein Conference happening May 14-16 in College Park, Maryland. These conferences do sell out, so please sign up today and join us. If traveling is not in your budget, the main podium talks will be available to attendees joining us virtually.