Dr Thomas Kofoed co-founder of clinical research organisation (CRO) Alphalyse speaks to Mani Krishnan, VP/GM of Global Biopharma and Capillary Electrophoresis (CE) at SCIEX, who is working on new solutions in mass spectrometry and CE, on how new bioanalytical tools can help biologics developers better manage their risk.
Conversation
As a CRO specialising in bioanalysis for clients developing biologics, what would you say the main ‘burning issue’ is for those companies?
Biologics development is still a lot younger as an industry than traditional pharma, so there are still many challenges. One of the main issues that clients come to us about is host cell proteins (HCPs). HCPs are incredibly important because they can be biologically active and interfere with how the drug works or maybe worse, act on the patient directly. Even if the HCP isn’t bioactive, it can act as an adjuvant to raise an immune response in the patient and make them resistant to drug therapy. Given it can impact efficacy as well as safety, regulatory authorities designate HCPs as a critical quality attribute (CQA). That means any contamination by HCPs needs to be detected and monitored in the development of the bioproduction process, and carefully controlled throughout the scaled-up biomanufacturing process. This ensures any HCPs present in the final drug product are within the acceptable limits pre-specified by regulators. HCPs are a make-or-break factor for biologics.
What’s the main challenge with HCPs?
Biopharma companies struggle to find a good, reliable way of detecting and removing HCP contamination. They often ask us about how to get a good analytical method for HCPs. Especially for many new modalities, from gene therapies to next-generation antibodies, which have more complex biomanufacture considerations than normal biologics. They use various expression systems for the drug production, such as Chinese hamster ovary, E. coli, and Pichia cells. These host cells alone contain over a thousand HCPs. In addition, there are other sources of protein contamination, such as from cell culture medium supplements, for example, bovine serum albumin. So, removing all this protein contamination is a major challenge. Of course, to do that, they first need to be able to robustly detect the HCPs. That way, they can also detect when the HCPs have been successfully removed. But developing a really good single assay that can analyse the different HCP profiles hasn’t been possible using the approach favoured by traditional pharma; that is ligand binding assays, especially ELISAs.