Use of PAT principles for the open‐loop control of laboratory and pilot‐scale chromatography columns

Abstract

BACKGROUND: Recently, there has been increased interest in employing process analytical technologies (PAT) that combine an understanding of how operating parameters affect product quality together with real-time analysis to achieve efficient process manipulation during operation and thereby ensure that product outputs meet specifications. Primarily intended as the basis of control strategies for full-scale manufacturing systems, such techniques can bring significant benefits for steps such as chromatographic separations. Rapid at-line monitoring of a target product can also enable the design of more sophisticated development trials than are generally used at present, whereby data gathered during development can be used to initiate the use of control techniques that drive a process to achieve target values for outputs such as yield or purity. Furthermore, the acquisition of rapid at-line data also frees the operator from having to perform potentially laborious off-line assays.

Application of process analytical technology for downstream purification of biotherapeutics

“…4,5 A stopped-flow analyzer has been used for at-line real-time measurement of product during HIC chromatography. 11 The at-line data such as the breakthrough curves shown in this paper gave the operator real-time confirmation that the process was proceeding according to plan. The at-line data also allowed for high resolution data to be collected, enhancing the characterization and development of the process.…”

“…A stopped‐flow analyzer has been used for at‐line real‐time measurement of product during HIC chromatography . The at‐line data such as the breakthrough curves shown in this paper gave the operator real‐time confirmation that the process was proceeding according to plan.…”

Mini‐review: soft sensors as means for PAT in the manufacture of bio‐therapeutics

“…From a quality control perspective monitoring of critical quality attributes in the downstream stages are as important. Soft sensors could there play a profound role for improving process performance …”

“…Soft sensors could there play a profound role for improving process performance. 121 Consequently, further development of bioanalytical methods for on-line use would enhance the prospect for soft sensors in bio-therapeutic processes. A very interesting prospect for this is the miniaturisation and microfluidic approaches which have great potential for this.…”