Analytical Technology and PAT

O ur ability to develop advanced bioprocess control and optimization strategies is directly linked to the availability of relevant in situ sensors or real-time analytical instrumentation and, as such, was identified as a research funding priority by the National Science and Technology Council in 1995 (131). Demand for rapid monitoring techniques is being driven by • a need to build better process models • a general desire for improved control of feeding and other process parameters • a requirement to develop robust, standardized, transferable, and operator-independent processes • the necessity of complying with the FDA’s process analytical technology (PAT) guidance. Bioprocess monitoring techniques and their associated sensors and analytics can be classified with respect to their level of invasiveness, ranging from off-line and at-line employment of analytical instrumentation to on-line integration of analyzers. Various on-line configurations are available, including direct in situ sensor insertion as well as in situ and ex situ sampling loops with in-line analyzers (Figure 11).