(367e) Modulating Antibody Glycosylation Using Traditional and PAT Methods

Control of critical quality attributes (CQAs) is essential for the manufacture of high-quality biologics. Control over glycosylation of antibodies within specified ranges can be challenging but is crucial for product efficacy, immunogenicity and pharmacokinetics. Particularly for biosimilar products, the glycosylation ranges for demonstrating similarity to the innovator product can be very small. Changes in bioreactor process parameters at the manufacturing scale could impact glycosylation outside the specified ranges.

Several bench-scale experiments were conducted to understand the relationship between TAF and early culture pH. It was demonstrated that the TAF of the product harvested was affected by pH early in the culture. Given this information, pH control was improved using traditional univariate setpoint control in the early phase of bioreactor culture. This resulted in lots with acceptable TAF.

More sophisticated bench-scale studies were carried out to understand the effect of initial pH in combination with other levers with the aim of constructing a predictive model. The pH was intentionally manipulated in early culture to create a defined disturbance in TAF. A Process Analytical Technology (PAT) strategy was used to monitor and control TAF at large-scale.