Process analytical technology (PAT) is gradually being implemented in the biopharmaceutical industry due to the potential for continuous real-time quality assurance resulting in improved operational control and compliance. Process chromatography remains the primary unit operation for purification of biotech therapeutics for separation of the various host cell related, process related, and product related impurities and variants. The latter often have very similar physicochemical properties to that of the product and hence in the absence of baseline separation, a robust pooling strategy is required to ensure consistent product quality. This talk will present an evaluation of a variety of PAT based and pseudo-PAT based approaches for pooling a real commercial process chromatography column. The pseudo-PAT approaches that have been evaluated include ultraviolet (UV) absorbance, % peak height, retention time, and relative retention time. These approaches do not involve direct measurement of product quality attributes, but are operationally simpler to implement. Two other PAT based approaches will  also been considered.The first involves use of a feed forward control based model that uses as an input the retention time of a characteristic<br/>peak that elutes prior to the main peak. The second PAT based approach involves use of a rapid HPLC method that can facilitate near-real-time decision making on pooling. The talk will provide a comparison of the advantages and drawbacks of the various approaches that have been examined and establish the feasibility of multiple approaches that can facilitate implementation of PAT for pooling of process chromatography columns.

Comparison of PAT based approaches for making real-time pooling decisions for process chromatography – use of feed forward control

249th National Meeting (2015)

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