(523g) Early Formulation Screening to Predict Long-Term Stability in Novel Antibody Products

Antibody-based biologics such as monoclonal antibodies (mAbs) are a fast-growing segment of the pharmaceuticals market due to their distinctive therapeutic potential. The increase in number of approvals and blockbuster successes over the recent years have generated immense interest in the field. However, formulation development remains a challenge as there is not a one size fits all formulation formula or stability characterisation tool. Early stability data is not only important for designing the final drug formulation and storage conditions, it can also help assess manufacturability of the molecule during to find potential manufacturing problems at an earlier stage to save time and cost further along the process.

During early drug discovery, there are limited amounts of protein available and time pressure to screen as many candidates and conditions as possible. However, traditional stability studies are time consuming and expensive. Consequently, there is a high demand for accurate stability prediction tools, which provides surrogate endpoints measurements indicative of long-term storage stability. In this study we utilise differential scanning fluorimetry (DSF) and dynamic light scattering (DLS) to measure colloidal and conformational stability of proteins in a variety of formulation conditions and correlate the effects to aggregation propensity. Polyclonal IgG were used to optimise experimental procedures: requiring only 20 µg of protein per replicate for DSF and 50 µg of protein per replicate for DLS. Results showed characteristic shifts in the thermal stability with changing formulation conditions with polyclonal IgG and infliximab. Negative shifts in apparent melting temperature (T_ma) recorded with infliximab also resulted in the highest monomer loss after storage at 40°C for 4-weeks.