The merits of continuous processing over batch processing are well known in the manufacturing industry. Continuous operation results in shorter process times due to omission of hold steps, higher productivity due to reduced shutdown costs, and lowers labor requirement. Over the past decade, there has been an increasing interest in continuous processing within the bioprocessing community, specifically those involved in production of biotherapeutics. Continuous operations in upstream processing (perfusion) have been performed for decades. However, recent development of continuous downstream operations has led the industry to envisage an integrated bioprocessing platform for efficient production. The regulators, key players in the biotherapeutic industry, have also expressed their interest and willingness in this migration from the traditional batch processing. This paper aims to review major developments in continuous bioprocessing in the past decade. A discussion of pros and cons of the different proposed approaches has also been presented.

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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