Disruptive single-use technologies (SUTs) continue to emerge into the bioprocess equipment market, meeting processing demands while providing improved performance. SUTs come with inherent benefits of accelerating drug development whilst driving down costs and reducing facility footprint. Yet the efficiency, scale and performance capabilities of stainless steel products are undeniable. This means that even as industrial firms seek continuous solutions, a hybrid of the technologies will be needed.
Concerns with continuous
The issues of continuous have been well documented for years, and are related to specific processing requirements and chemical characteristics. Debate over whether or not these issues can be overcome continues. Generally, the concerns are:
- Lack of homogeneity in the continuous vessel, including nutrient shortages or regions of cell accumulations
- Long-term operability and maintenance of sterility
- Poor short-term flexibility to handle multiple products, due to long run times
- High cost and long times required for process development using complex continuous culture systems in the lab
Genetic instability of cells
Despite these challenges, the benefits of continuous are too great to ignore, from more consistent quality attribute profiles of drug products, to the large volume of product produced for a given volume of media.
This makes continuous processing the ideal choice for large-scale processes with downstream purification that can accommodate this type of production. For example, where the product consists of optimal cell strains, such as Dunaliella salina (used widely in cosmetic and dietary supplement products), which are highly evolved to grow even under extreme conditions, the concerns over contaminating organism and genetic instability over long-term culture are few.
While the greatest focus is on efficiency and reliability, continuous processes also need to be considered on a capacity basis. After all, bioprocessing does not lend itself to scaling as easily as it does in other industries. There is an argument for the industry adopting continuous processes in a similar way to the oil industry. There is, however, a significant difference between an oil refinery producing 8 million L of crude oil a day, and a large pharmaceutical plant producing less than 40,000 L per day.
Achieving scalability will take a combination of regulatory changes and technological improvements in SUT and stainless steel systems, particularly downstream. The user will also need to determine the most beneficial path for their process through the use of SUT, stainless steel or hybrid processing.
In the rare occasions where biopharmaceutical shortages have occurred due to problems with continuous perfusion systems, batch methods continue to fall short when it comes to overall facility flexibility, product quality and cost.
The role of stainless steel
Despite higher titers, the size limitations and durability of many single-use bioreactor systems will continue to be a concern. The integrity of a bag cannot be ensured under high pressures and the heavy weight of a liquid, and 2000L is generally considered the upper limit for disposable systems.
While these systems excel in small scale batch processes, the manufacture of some of the world’s top-selling biologics rely on stainless steel systems. In the event of a significant breakthrough in new biologics with large patient populations such as Alzheimer’s, diabetes, cancer and dementia, stainless steel systems are essential, not simply for their capacity but their ability to efficiently produce products and will need to be employed in continuous processes.
The success of any biopharmaceutical company depends on their ability to be flexible and adjust their production capacity in response to rapidly changing demand forecasts and unexpected results in clinical trials (late stage failure or an unexpected acceleration). With that in mind, and with the understanding that adopting hybrid systems is an essential part of meeting the future, the development of new platforms that allow for the evolution and integration of continuous bioprocessing systems should be given consideration.