(189n) Forget Throughput, It’s about the Risk- Rethinking Dead-End Membrane Filtration Scale-up

- Rethinking Dead-End Membrane Filtration Scale-Up

Kelly Wei

Purification Process Sciences

AstraZeneca

One MedImmune Way

Gaithersburg, MD 20878

USA

In the biopharmaceutical industry, purification processes utilize chromatography and filtration methods to remove process and product related impurities. Membrane filters with pore sizes of 0.2 µm or 0.45 µm are often employed between unit operations to remove small particulates and mitigate bioburden risk in accordance with current good manufacturing practice (cGMP). For chromatography, substantial effort has been devoted to understanding mechanisms and scale-up principles which enables accurate prediction of process performance and product quality. Unfortunately, the same cannot be said for filtration. The current empirical practices used for sizing inline membrane filtration are often not predictive during scale up and technology transfer. This gap in understanding can lead to costly deviations at scale. Here, we challenge the conventional filter sizing approach based on throughput and propose a new risk analysis approach based on membrane fouling mechanism. By evaluating membrane fouling behavior during scale up, we determine the mechanism and develop the appropriate filtration strategy.