September 10, 2024

LC-MS for improving decision making and mitigating risk in process development

CASSS MS 2024 -- Host-cell proteins (HCPs) pose a risk both to patient safety by means of immunogenic response, and to drug substance integrity by enzymatic digestion and degradation. Effective removal of the impurities while minimizing loss of the drug substance is a major challenge and milestone in the drug development life-cycle. ELISA offers excellent sensitivity for HCP content but is only able to provide total HCP abundance and is reliant on expensive polyclonal reagents. LC-MS is able to identify and quantify individual HCPs, allowing a purification strategy to be developed around known impurities using a quality-by-design approach in-line with ICH Q14. A phase-appropriate approach to HCP characterisation should be carefully considered in-line with the phase of product development for efficient process development and risk mitigation.
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September 10, 2024

Formulation development to limit protein glycation

CASSS MS 2024 -- Formulation development is a crucial element of biopharmaceutical development, to maintain structural integrity whilst minimising the level of post-translational modifications (PTMs). Labcorp has developed a standardised workflow for formulation development. Following a design of experiments (DoE) study on thermally stressed pembrolizumab, a potential stability issue with glycation was identified. In this study, the effect of formulation on glycation and the effect of glycation on antigen binding were assessed in the forced degradation of lead formulations phase. The study also gave the opportunity to test the feasibility of an LC-MS multi‑attribute monitoring (MAM) method for monitoring glycation.
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September 7, 2024

Evaluation of immunosuppression in a murine model of respiratory syncytial virus (RSV) infection

ERS Congress 2024 -- Respiratory syncytial virus (RSV) is a major global pathogen, predominantly affecting infants, often leading to bronchiolitis and lower respiratory tract disease (LRTD). RSV is mainly replicated in respiratory ciliated epithelium and analysis of patient samples with severe RSV has shown significantly elevated neutrophil and macrophage content, enriched with pro-inflammatory cytokines such as TNFα, IL-6, IL-1a, IL-8, IL-9, IL-10 and IL-17, which impact the pathogenesis of RSV infection. Currently there are no licensed vaccines for this pathogen, and therefore the implementation of functional animal models for studying this virus is of high importance. This study aimed to establish a murine model of RSV infection, which induced clinical signs and inflammatory responses representative of human RSV infection.
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