PAT for Scale-up from Lab to Manufacturing
Pilot Plant Fault Detection and Optimization
As a process is scaled up from the lab to pilot plant, PAT can ensure that each step is proceeding as intended. Researchers apply PAT to develop a “signature” or "fingerprint" to monitor process reproducibility during technology transfer. During scale-up, engineers often rely on PAT to verify consistent endpoint in batch processes or steady state operation in continuous processing. Inline monitoring provides continuous streams of data which does not require samples to be collected, prepared, and analyzed. This enables researchers to make decisions quickly without waiting for offline data. Thus, the knowledge-rich process information obtained with PAT allows for rapid troubleshooting, optimization, and fault detection. When an unexpected process deviation occurs, PAT can often be used to identify the root cause such as a variation in upstream process conditions, impurities, or raw materials. PAT improves safety by providing insight into progress of exothermic reactions, and where sampling may pose operator hazards.
Improving Scale-up with PAT - Roche Ireland
Troubleshooting and Control in Production
Ideally, a process is robust enough that it does not require monitoring when it reaches the manufacturing scale. However, many processes require close monitoring ensure consistency or improve downstream operations, especially when they first reach the manufacturing scale. PAT applications in manufacturing are often classified in two areas: a) Knowledge collection to improve the overall robustness of a process, including troubleshooting to identify the root cause of a process deviation; b) Process control for a batch or continuous process, especially where offline measurements are unstable, infrequent, time consuming, or hazardous.
Often, the return on investment for PAT is clear on the manufacturing scale since elimination of failures, increase in yield, and increase in cycle time can offer significant savings. Considerations of implementing PAT in manufacturing include: safety in a classified explosive environment, chemical compatibility, cGMP requirements, communication with a manufacturing control system, and mounting in with process equipment.
In Situ Process Analysis for Process Control - Lubrizol