Downstream unit process operations used in biological drug manufacturing have changed significantly in recent years. Biopharmaceutical companies must support a large, diverse portfolio, across different manufacturing sites, with many programs requiring high concentration to meet clinical dosing for subcutaneous injection. In particular, the ultrafiltration and diafiltration (UF/DF) process operation, the final step in biologics processing, has presented significant challenges. To ensure process consistency and provide process validation, Process Analytical Technology (PAT) can be a valuable addition to the manufacturing process. Size exclusion chromatography (SEC) based PAT methods were developed for a liquid chromatography system with built-in autosampler. These methods measure the concentrations of the excipients arginine, histidine and high molecular weight species, and were found to be comparable to orthogonal offline methods. An in-line A280 monitoring instrument with variable pathlength extension technology was tested with several portfolio assets, and found to be comparable to offline A280 method up to 260 g/L. These PAT applications are setup as a platform system for monitoring of multiple attributes over a wide dynamic range. In summary, these PAT tools are suitable at present for in process monitoring during GMP and commercial manufacturing, with future potential for real-time feedback control of the process.

Development of In-line and on-line process analytical technology tools for high concentration biologics processes

ACS Fall 2021

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