The Potential Impact of Continuous Processing on the Practice and Economics of Biopharmaceutical Manufacturing

Progression of continuous downstream processing of monoclonal antibodies: Current trends and challenges

“…As several batch processes are carried out simultaneously, the time required to convert a batch process to continuous mode is minimal and the industry can define and identify a unique batch more readily for regulatory purposes. Regardless of the economic benefits of operation in a continuous mode, some limitations such as complexity in valve arrangements, packing variability with multicolumn systems, operating robustness, challenges in process characterization, validation and regulatory concerns hold their implementation at larger manufacturing scales (Mothes et al, ; Stock, Bisschops, & Ransohoff, ).…”

“…Equipment manufacturers have incorporated additional valves, pH and conductivity probes, UV monitors, pressure gauges and control hardware in a continuous chromatography system to ensure consistent product quality. In a GMP environment, these additional components translate to increased complexity in regular operation and process automation compared to a batch process (Jagschies, ; Stock et al, ). This complexity increases with the increase in number of columns.…”

“…Regardless of the economic benefits of operation in a continuous mode, some limitations such as complexity in valve arrangements, packing variability with multicolumn systems, operating robustness, challenges in process characterization, validation and regulatory concerns hold their implementation at larger manufacturing scales (Mothes et al, 2016;Stock, Bisschops, & Ransohoff, 2014).…”

“…The regulatory agencies strongly support continuous manufacturing, provided the manufactures develop a well understood robust process that can meet the product quality attributes under controlled manufacturing steps (Nasr et al, ). However, the lack of experience in getting regulatory approval for continuous bioprocessing creates an uncertainty in the industry (Stock et al, ). To meet the regulatory levels of product quality assurance, the continuous manufacturing process needs to be developed and optimized under a set of critical process parameters (CPPs) enabling a rich knowledge‐based filing.…”

A simplified techno‐economic model for the molecular pharming of antibodies

“…Traditionally, mAbs have been produced using a batch manufacturing strategy, but following the lead from other manufacturing industries, the benefits of continuous production have been considered, particularly with the adoption of continuous fermentation, continuous centrifuges for clarification, and various forms of continuous chromatography (such as simulated moving bed chromatography) for downstream processing (Bisschops, ; Patil & Walther, ). The economic ramifications of continuous manufacturing in the field of biopharmaceuticals have therefore been evaluated in detail (Pollock, Ho, & Farid, ; Stock, Bisschops, & Ransohoff, ) and robust TEA models have been developed, which allow the assessment of process changes for biopharmaceuticals as well as conventional small‐molecule drugs (Hassan, ; Jolliffe & Gerogiorgis, ).…”