BACKGROUND 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. RESULTS This paper presents 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 have 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 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. CONCLUSIONS The paper provides a comparison of the advantages and drawbacks of the various approaches that have been examined and establishes the feasibility of multiple approaches that can facilitate implementation of PAT for pooling of process chromatography columns. © 2014 Society of Chemical Industry

BACKGROUND: Membrane chromatography has been accepted as the polishing step in several commercial processes for production of monoclonal antibody therapeutics over the past decade. This study aims to compare the performance of the traditional column chromatography with membrane chromatography for the two major classes of biotherapeutics, a therapeutic protein expressed in a microbial host and a monoclonal antibody product expressed in mammalian cells. RESULTS:It is observed that membrane chromatography underperforms in applications that require high resolution separation. However, membrane chromatography offers several key advantages for applications that do not require high resolution separation, such as flow through process steps. These advantages include not only the ease of use but also a significantly lower cost (consumables and operating time). Cost advantage is also seen for cases when short manufacturing campaigns (less than 10 lots) are required and the resin will be discarded at the end of the campaign. CONCLUSIONS: This is a first-of-a-kind study with respect to examining applicability of membrane chromatography for purification of a microbial and a mammalian product and also consideration of the process economics. The study demonstrates that membrane chromatography offers significant advantages in certain applications.

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