How to create a toolbox to assess your high-risk HCPs
Host cell proteins (HCPs) are process-related impurities derived from host cells that may co-purify with a biopharmaceutical drug product.
The detection, quantitation, and removal of HCPs from the final biotherapeutic process can be complex and some HCPs can be considered high-risk. They include those that are immunogenic, biologically active, or enzymatically active with the potential to degrade either product molecules or excipients used in the product formulation. They may also be difficult to purify.
Although there are only a few known cases where HCPs directly impact patient safety, there is no standard approach to understand the origin of their co-purification and how to address the related issues.
This is why BioPhorum has published High-risk host cell proteins (HCPS): A multi-company collaborative view
This provides a list of frequently seen HCPs that co-purify during downstream processing, a list of high-risk HCPs, and recommendations for developing a comprehensive analytical toolbox to assess the impact of individual HCPs.
Written by BioPhorum Development Group’s Host Cell Proteins Workstream, the paper suggests that tiered immunogenicity risk assessments could help establish the possible link between high-risk HCPs and patient safety.
The work was informed by a survey of Workstream members that gauged how companies responded when HCPs were detected. The list of frequently seen and high-risk HCPs is classified into different risk categories based on reported biologic functions, the potential for immunogenicity, and the impact on therapeutic drug or formulation.
A subteam of members performed extensive literature searches to understand the impact of high-risk HCPs and discussed members’ collective experiences. These discussions focused on biopharmaceuticals produced in Chinese Hamster Ovary (CHO) cells and purified by a Protein A affinity column and additional polishing steps.
Published in the peer-reviewed Biotechnology & Bioengineering journal, the paper includes recommendations for establishing a comprehensive analytical strategy to accurately measure known HCP impurities. If a high-risk HCP has been identified, the paper also discusses how to develop a control strategy to monitor or eliminate it.
One of the independent peer reviewers said the paper was an “excellent review of current best practices for host cell protein impurities. Likely to become the most cited reference on this topic.”
Regulators are becoming increasingly focused on HCPs to ensure that companies are monitoring and controlling them correctly. Using the BioPhorum approach will help companies develop a robust control strategy that will smooth the submission process and reduce the risk of regulator challenges.
HCP searchable database
The toolbox includes a database that will save industry a significant amount of time when searching for information on these impurities. It will initially contain details of HCPs specifically focusing on biotherapeutics produced in CHO cells, but it is hoped the scope of the list can be broadened to other host cell lines. Frequently seen HCPs found throughout different processing steps are identified within the database.
“The ability to collaborate with 26 different companies through BioPhorum was very powerful and resulted in a meaningful publication,” said Marisa Jones, Scientific Leader, Biological Process Residuals, Structure & Function Characterization, CMC Analytical at GSK. “This provides a list of frequently seen HCPs all in one place, including specific information about each protein such as the molecular weight, isoelectric point, and a link to UniProt. The specific list of high-risk HCPs that companies should be aware of is a very helpful resource, and we hope the online database on BioPhorum’s website will be a useful resource for years to come.”
The common HCPs that are considered problematic and therefore ‘high-risk’ are also identified. The database further classifies these into four major categories based on their impact on product quality, formulation, direct biological function in humans, and immunogenicity.
Also included is the function of the protein, the associated references for each protein, and the specific type of impact (on drug or patient) such as aggregation, fragmentation, modification, or immunogenicity. The dynamic database will continue to be updated when new CHO proteins are identified and/or reported in the literature.
Although companies deal with unique circumstances during their product development and perform the HCP-risk assessment on a case-by-case basis, this paper will guide industry on targeting high-risk HCP characterization and proactively mitigate against the risks posed by them in biological products.
Cell and gene therapies (CGTs) have enormous potential to create personalized therapeutics for patients with diseases...