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

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.

Raman spectroscopy as a process analytical technology for pharmaceutical manufacturing and bioprocessing

“…Regulatory support, combined with recognized scientific and financial benefits, are major factors in the widespread adoption of QbD and PAT [42–44]. The philosophical shift to QbD has encouraged new risk-based approaches in real-time release testing, continuous manufacturing, and statistical process control.…”

An Integrated Lab‐on‐a‐chip Approach to Study Heterogeneous Enantioselective Catalysts at the Microscale

“…Not only can the development of the respective materials be regarded as an art of its own, but the testing of the suitability and performance of the precious materials is often just as, or even more, time intensive. In flow chemistry, this elaborate process includes testing of various substrates, solvents, and additives with subsequent analysis of the reaction mixtures via complex analytical techniques …”

Biocatalytic Process Design and Reaction Engineering

“…This can be achieved by taking discrete samples during the manufacturing process, which are transported to the analytical instruments and analysed off-line or by designing on-line analytical instrumentation which are integrated into the manufacturing process as analytical in-process controls. PAT is of much interest for a better understanding of the process in development 36 or for controlling critical unit operations like reactions, workup, crystallization and drying 37 . In the innovative transaminase-catalysed process for manufacturing the sitagliptin API 38 , the particle size distribution of the API is an important quality specification.…”