PAT tools for fermentation processes
The publication of the Process Analytical Technology (PAT) guidance has been one of the most important milestones for pharmaceutical production during the past ten years. The ideas outlined in the PAT guidance are also applied in other industries, for example the fermentation industry. Process knowledge is central in PAT projects. This manuscript therefore gives a brief overview of a number of PAT tools for collecting process knowledge on fermentation processes: on-line sensors, mechanistic models and small-scale equipment for high-throughput experimentation. The manuscript ends with a short perspective on future developments.
The publication of the Process Analytical Technology (PAT) guidance (1) has been an important milestone for the pharmaceutical industry, since this document finally made it clear that regulators were in favour of establishment of more efficient production processes. A central statement in the PAT guidance is “quality should not be tested in to products, it should be built in by design”. Focus in the PAT guidance is thus on acquiring process knowledge – including identification of the effect of critical process parameters (CPPs) on critical quality attributes (CQAs) of the final product – which is subsequently used to improve the process design and operation such that product quality can be increasingly guaranteed on the basis of on-line measurements combined with suitable process control strategies (“real time release”), as illustrated in Figure 1.
Originally intended for the pharmaceutical industry, the ideas outlined in the PAT guidance have also spread towards other industries, for example the food and the fermentation industry. The aim of many early PAT projects has been on introduction of advanced on-line analysis eq ...