Dr. Denise Krawitz provided an excellent wrap up on the last day of BEBPA’s 11^th Annual HCP Conference held in May 2023 in Dubrovnik, Croatia. Her quick 10-minute summary captured the essence of the conference and highlighted topics covered during the conference, as well as providing a sneak peek into future topics.

Highlighted Conference Topics Included:

• Low Abundance HCPs
• Regulatory Guidance
• HCP Critical Reagent Characterization Methods
• Advanced MS Topics – critical look at MS
• Critical Reagent Generation and Qualification
• Phase-Specific HCP Strategies
• Intro to Mass Spectrometry
• Risk Assessment

She also provided a look forward to the 2024 conference topics, which is happening in College Park, Maryland, May 14-16, 2024. Based upon the discussions and questions asked at the conference, she predicted that the following elements will be in the conference:

• In vitro immunogenicity assays, activity (e.g. histamine release)
• Risk assessment case-studies
• Cell line engineering for reduction of HCPs
• Gene and cell therapy, vaccines
• Improvements in MS data analysis – case studies
• Activity assays (e.g. lipase or protease activity)

If you are interested in seeing the summary slides they are available here.

One of the popular onsite workshops covered risk assessment of HCPs. Attendees worked on a simulated test case provided by Christina de Zafra, Director, Nonclinical Sciences Department, Seagen, Denise Krawitz, Principal Consultant, CMC Paradigms LLC and Fengqiang Wang, Principal Scientist, Merck.

At the heart of the problem for establishing the risk of the HCPs in different products is the complex nature of HCPs. Because of this complexity, regulatory agencies are reluctant to stipulate a generic acceptable HCP range. Historically, it’s generally believed that, in many cases, HCPs can constitute 1–100 ng/mg (1–100 ppm) of a biological product, based on results from an HCP enzyme-linked immunosorbent assay (ELISA) (Ref. 4). However, unlike single protein impurities (such as Protein A), the varying mixture and types of HCPs in different products can drive differing clinical concerns. In addition, the indication of the proposed drug and how it is administered to the patient play important roles.

Dr. de Zafra, one of the workshop moderators, has published an HCP Risk Assessment Guideline (Ref. 2) that asks the following questions:

• What is the HCP in question?
• What did we know about its function?
• Where is it located in the host cell?
• How different are the hamster and human variants? (Assuming a CHO expression system)
• Do we have experience with that protein from material administered either to animals in a nonclinical setting or to human clinical-trial subjects.
• What development stage is the drug program?
• What is the product’s proposed indication: Is it designed to treat cancer in adults, or is it in the realm of pediatrics? Obviously, those indications raise different risk factors.
• How is the drug administered – by intravenous, subcutaneous, or intravitreal injection?
• Are we giving the drug as a single dose, or would it be administered every week for a prescribed period to treat a chronic condition?

With these questions in mind, the attendees broke into small groups and discussed their proposed approach. Interestingly, most groups arrived at similar conclusions, despite using a variety of assessment tools.