Liposomal drug products are playing an increasing role in the field of drug delivery. With this increased demand comes the need to increase the capabilities and capacity of manufacturing options. Continuous manufacturing techniques present a significant opportunity to address these needs for liposomal manufacturing processes. Liposomal formulations have unique considerations that impact translation from batch to continuous process designs. This article examines aspects of converting to a continuous design that were previously viewed as inconsequential in a batch process. The batch process involves the removal of ethanol through tangential flow filtration (TFF). Ethanol was found to reduce the permeability of the hollow fibers used for TFF. This effect was determined to have minimal impact on the overall batch process design but considerable influence on the design of continuous TFF such as inline diafiltration (ILDF). Using a pilot scale setup, ethanol was found to decrease permeability in an inverse manner to ethanol concentration. Further assessment found that dilution of the ethanol levels prior to diafiltration can significantly reduce the amount of ILDF stages needed and that a continuous design requires less buffer to the commensurate batch design.

Continuous improvements of cell-free synthesis (CFS) systems have generated interest in adopting the technology for the manufacture of biologics. This paper provides an evaluation of the manufacturing cost-effectiveness of CFS for a range of commercial scenarios. The evaluation was performed using an advanced techno-economic engine (TEE) built in Python. The TEE is programmed in an object-oriented environment capable of simulating a plethora of process flowsheets and predicting size and cost metrics for the process and the facility. A case study was formulated to compare the economics of whole bioprocesses based on either a CFS system or a mammalian cell system (CHO) for the manufacture of an antibody drug conjugate (ADC) at different commercial product demand levels (100 – 1000kg/year). The analysis demonstrated the potential of CFS for the commercial manufacture of biologics and identified key cost drivers related with the system. The CFS system showed approximately a two-fold increase in the cost of goods compared to CHO with a significant cost attributed to the in-house manufacture of the bacterial cell extract, necessary for the CFS reaction step in the process. A sensitivity and target analysis highlighted the impetus for further process improvements especially in the titre for the CFS process to become more competitive against well-established systems.