Upstream Flexibility Using Stirred Tank Bioreactors
November 16, 2020
When used in the context of upstream biopharmaceutical manufacturing, flexibility refers to the ease of setting up, scaling up, and switching between batches and different processes. Significantly enhanced flexibility is one of the many advantages of single-use systems (SUSs) and a key reason why the SUS adoption rate is so high.
The greater flexibility of single-use systems means that processes can be designed, developed and delivered much faster compared to stainless-steel based facilities. This aspect is especially important in the context of the global race for a vaccine against COVID-19, which requires an industry-wide effort to accelerate the development of vaccine candidates and to ultimately support the manufacture of the billions of doses needed for clinical trials and global vaccination programs. The enhanced upstream flexibility provided by SUSs has led to significant simplification of process development and scale-up. This specifically applies to decentralised manufacturing – most components of the cell culture unit operation, including the single-use bioreactor as well as auxiliary disposables such as sampling manifolds, and connectors to mixing tanks and downstream equipment, can simply be replicated at many facilities. Controlling and logging the key process variables ensures that facilities on different continents can run almost identical processes. With the degree of prior knowledge that accompanies the process blueprint, there is no need for time-consuming redesign and the building of infrastructure and hard piping like in conventional steel systems. This means existing facilities can be rapidly re-tasked and, with the necessary regulatory approval, ready to manufacture, in a matter of months rather than years. For the coronavirus vaccine, speed to manufacture is critical and upstream flexibility delivered by single-use, stirred tank has been a key enabler of the global coordination of vaccine manufacture.
Another aspect of flexibility is the ability to easily scale-up a process. SUSs can facilitate this by maintaining key cell culture parameters and fluid contact surfaces while also simplifying the integration of supporting processes such as the preparation of cell culture media using simple sterile connectors and disconnectors. This easy scale-up can allow for the potential to make clinical as well as commercial batches in the same facility, both by scaling-out and scaling-up.
SUSs also allow manufacturing facilities to simply and rapidly switch between multiple drug manufacturing processes. This is a lot more challenging with conventional steel systems. Instead of spending time cleaning and validating a steel bioreactor before a new process, one can simply install a new SUS. This SUS is effectively pre-validated as sterile and has the potential to run any process designed for that SUS and scale. This flexibility has resulted in biopharma facilities that have a higher turnaround and the potential to manufacture a range of different products as required, allowing for the business to rapidly respond to changes in drug demand. This need for flexibility is further reinforced by the fact that some new drugs (especially those with orphan drug designation) are now approved at a much quicker rate, leading to a demand for agile manufacturing facilities.
The adoption of single-use technologies, especially in upstream reduces capital investment but also allows for multiple processes to be performed using the same hardware. With little or no reusable fluid contact process elements, batch-to-batch and product-to-product contamination is eliminated. This, coupled with the much faster turnaround times compared to stainless steel based processing, makes it highly desirable to multiproduct facilities, and especially for contract development and manufacturing organisations (CDMOs).
Flexibility and speed are powerful partners and combine to support, not only the current pandemic but the changing manufacturing landscape in general. Here, some new drugs, especially those given orphan drug designation, can follow an accelerated approval process leading to an increased demand for agile manufacturing facilities.
In summary, single-use systems for the upstream phase of biopharma manufacturing have allowed the industry to enjoy easier facility start-up, quick scale-up and unprecedented agility to switch between processes. For these reasons, we expect legacy as well the factories of the future to be increasingly centered around the use of SUSs for their manufacturing needs.
Learn more about the different types of bioreactors in the blog post co-authored by Marie-Laure Collignon and Alex Williams.
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Alex Williams – Associate R&D Engineer, Research and Development
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