Implementation of New Process Technologies
At Richter-Helm the investment in new technology is not focusing only on adding new (higher) manufacturing scales; though this generally would be a first reaction after thinking of COG, considering decreasing costs with larger manufacturing scale.
A good alternative to simple scale-up is the implementation of new process technologies that can achieve higher yields, and, at the same time, increased quality or better process robustness at least for certain process steps. During the past years the biomanufacturing industry has made substantial improvements in expression and fermentation technologies. In terms of microbial production, innovative E. coli expression systems combined with high density fermentation regimes can lead to yields up to 20 g of the target protein per liter fermentation broth as was recently shown by Richter-Helm for a fusion protein process.
In addition to high product yields in many cases it is important to find the appropriate expression system for high-quality products that show no or only low expression rates in E. coli. In these cases the use of other bacterial expression hosts, e.g., Bacillus or Pseudomonas strains can help. To deal with even more complex proteins like enzymes or antibody fragments Pichia pastoris technology is another option to use. Thus a multipurpose facility for manufacturing biopharmaceuticals needs to be equipped for the use of all expression systems to be able to reduce up-front investment costs from the very beginning.
New expression systems lead to high primary product yields, which need to be dealt with in purification processes. Thus optimization of the downstream processes is necessary. It was reported recently that the implementation of EBA technology can reduce the total process cost by up to 56%. Other new purification technologies that can be implemented include multicolumn counter current solvent gradient purification (MCSGP), which reduces the loss of product in chromatography steps.
An ongoing trend in biopharmaceutical product development is the covalent modification of proteins by chemical or enzymatic cross linking (e.g., PEGylation, HESylation, Polyasialation) to increase the half life of the products in humans. All these technologies need to be usable in a real multipurpose facility as well.
It goes without saying that all the technologies mentioned in this article are scalable. As a CMO, to offer your customer the possibility to go from bench to market with one manufacturer, it is important to offer more than one scale. At Richter-Helm three different manufacturing scales are available (lab, pilot, large) to implement each project at the best matching scale without high costs for large equipment or the number of batches.