Implementation of New Process Technologies and Professional Project Management
At Richter-Helm the investment in new technology is not focusing only on adding new manufacturing scales: A good alternative 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 the Pichia pastoris technology is an additional option.
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.
The technical capabilities of a CMO alone will not be sufficient to serve the future needs of the customers; professional project execution is also a major success factor.
It is extremely important for a CMO to be prepared for the different requirements of different customers from small startups to big pharma. The project approach, e.g., regarding the regulatory consultancy required, will be extremely dependent on this. Project management that ensures close collaboration and communication between all parties is becoming more and more important, also driven by the trend toward long-lasting partnerships and strategic alliances between developers and manufacturers.