On the way to submitting a biologics license application (BLA), there are thousands of lab hours required. The largest and most critical work package in late stage downstream process (DSP) development are process characterization studies (PCS). With the PCS results, one should be able to identify the critical process parameters (CPPs) and to define the proven acceptable ranges of the input parameters (PARs), with the final goal of designing a robust manufacturing process that is able to deliver a drug with constant quality. Currently, the industrial standard is to carry out lab scale experiments with multivariate process parameter adjustments and to use response surface models to approximate the univariate influences of process parameters on the critical quality attributes (CQAs).<br/>This practice still requires a large number of wet lab experiments. Furthermore, a gap between different scales and low resolution of statistical models used due to multivariate experimental design would deliver unreliable results.<br/>In the presented work, we investigated the feasibility of using mechanistic modeling to identify CPPs and PARs of the polishing chromatography step of an on-going late stage project in DSP. A calibrated and validated mechanistic model was used to predict PCS experiments carried out in the wet-lab. With this knowledge, dependencies between potential CPPs and CQAs were determined and the PARs could be defined using this mechanistic model.

Replacing process characterization studies by applying mechanistic model simulations: Smart way to accelerating BLA submission?

ACS Fall 2020 Virtual Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.