Fully continuous biosimilar manufacturing framework: A case study

Biologics manufacturing has traditionally been in fed batch mode for the last 2 decades. During the early stages of biologics manufacturing, lower cell line productivity and product instability necessitated the usage of perfusion technology. As productivity increased and mabs became more stable, perfusion was replaced by fedbatch technology, as they were simpler to scale up. However, during the past 2-3 years, the perfusion technology is making a comeback due to the novel continuous chromatography technology. Connecting the perfusion bioreactor to the continuous chromatography system creates a continuous flow of drug substance and promises the following advantages The facility footprint for a continuous manufacturing plant would be substantially lower. Our calculations show that a 10-fold reduction in bioreactor size is possible with continuous bioprocessing. So the capacity of a 2000L Fed batch Bioreactor can be achieved by a 200L continuous bioreactor. This reduces the capex by about five fold. Consumption of media per amount of DS produced is the same for fedbatch and perfusion, although the cost per liter might be lower for perfusion as it could be a more diluted version of the fedbatch media , Another major cost in bioprocessing is the Protein A resin. A significantly smaller Protein A column could be used in the continuous process and the utilization could be maximized by this strategy. As the process is more dynamic in continuous, automation and in-line analytical tools are essential for the successful implementation. Enzene Biosciences is on the forefront of the development of the continuous bioprocessing. We are in the processing of building a cGMP plant that would have a fully integrated continuous bioprocess. We have already complete a proof of concept studies in pilot scale (50L)