Industry Perspectives on Process Analytical Technology: Tools and Applications in API Development

TLDR

PAT can improve R&D efficiency, reduce sampling hazards, enable rapid analysis of hazardous or heterogeneous processes, and as understanding grows, it helps shrink critical parameters and simplify monitoring toward commercial manufacturing. The IQ Consortium reports on the current state of PAT for API development in branded pharmaceutical companies. The article illustrates the use of an API process workflow to show why and how the industry applies PAT tools during development. PAT measurements provide data that reveal unknown intermediates, mechanisms, and process relationships, and often lead to simplified controls that are either off‑line or correlated with basic manufacturing measurements such as temperature and pressure.

Abstract

The IQ Consortium reports on the current state of process analytical technology (PAT) for active pharmaceutical ingredient (API) development in branded pharmaceutical companies. The article uses an API process workflow (process steps from raw material identification through to finished API) to provide representative examples, including why and how the pharmaceutical industry uses PAT tools in API development. The use of PAT can improve R&D efficiency and minimize personnel hazards associated with sampling hazardous materials for in-process testing. Although not all steps or chemical processes are readily amenable to the use of the PAT toolbox, when appropriate, PAT enables reliable and rapid (real or near time) analyses of processes that may contain materials that are highly hazardous, transient, or heterogeneous. These measurements can provide significant data for developing process chemistry understanding, and they may include the detection of previously unknown reaction intermediates, mechanisms, or relationships between process variables. As the process becomes defined and understanding is gained through these measurements, the number of parameters suspected to be critical is reduced. As the process approaches the commercial manufacturing stage and the process design space is established, a simplification of the monitoring and control technology, as much as is practical, is desired. In many cases, this results in controls being either off-line, or if in situ control is required, the results from PAT are correlated with simple manufacturing measurements such as temperature and pressure.