How to Accelerate Process Characterization

The Problem

APC’s partner company had a pipeline molecule which had recently received “fast track” status. The fast track designation required rapid process characterization of six crystallization-isolation operations within their 10-step product synthesis.

The Breakthrough

A unique workflow was employed to accelerate process characterisation of 6 process steps in just 10 weeks.

The Impact

The record speed at which the data was collected not only accelerated the drug to market, but it also allowed for enough drug substance to be released for compassionate use. 

The client was operating under a very aggressive timeline in line with the new “fast track” designation of the product. A full process characterisation was scheduled to be completed in only 2.5 months. Therefore, it was crucial that the characterization through DoE of each of the six steps was undertaken simultaneously. This required a high level of quality oversight, whilst simultaneously generating, interrogating, and understanding large volumes of process data.

Along with the timeline, several challenges presented themselves within the process. As the DoE set points are chosen to allow for statistical interpretation it is important to execute the experiments in a highly accurate manner. However, operations such as evaporative crystallisations and bi-phasic reverse additions pose risks to experimental accuracy due to the inherent variability in operation. APC scientists identified mitigation strategies to ensure representative and repeatable data collection.  

The completion of rapid process characterisation led to an operational design space identified for five steps along with point of failure analysis and recommendations for large scale manufacturing. 130 experiments and 1000s of HPLC samples along with countless observations and PAT trends were delivered to the client at APC’s highest internal quality level to ensure data provided was suitable for FDA filings. This breakthrough allowed for enough drug substance to be released for compassionate use, and impact someone’s life who has tried many other lines of treatment.