One of the most daunting tasks in the pharmaceutical industry is the process of scaling up bioprocesses from testing and development to commercialization. This is due to the challenges that arise when trying to maintain consistent process characteristics across differently sized reactors.
In order to maintain a consistent process through different scales of production, development must take several variables into account for bioprocesses, such as mixing time, gradients, impeller speed, reactor geometry, and more. Scale-up therefore requires solid process understanding to ensure culture homogeneity, and acquire consistent yield and quality from trials to final production.
For this reason, it can benefit companies to “standardize” their process scaling, with one option being to use reactors that offer geometrical similarities during different stages of development. To this end, Single-Use Bioreactors (SUBs) present a viable option for easing the delicate procedure of production scale-up. In general, SUBs provide substantial advantages, such as faster turnaround by avoiding in-place sterilization and cleaning, as well as reducing the risk of product cross contamination. Such benefits are especially influential for CMOs that operate with several distinct productions, or that frequently switch between productions.
Most SUB designs are based on well-known and established stirred-tank designs, meaning they combine qualities of single-use flexibility and traditional reactor components. More importantly, the geometrical and proportional similarities across SUB configurations simplifies the actual scale up (or down) process as well as potential process transfers. This results in fewer risks for companies, as the probability of changes in process variables due to reactor discrepancies is reduced.
That is not to say that SUBs are free of complications in practice. Although the structural integrity of single-use bags has improved substantially in recent years, there is the question of whether the bags can retain structural soundness when scaled to some of the highest production volumes. Also, the energy transfer from agitation is limited in SUBs compared to traditional steel reactors, due to the polymer-based structure of single-use bags. Finally, scaling SUBs to very high volumes increases the potential of leakage, particularly at the various ports in the bag - an issue that may be resolved by improved materials in the future.
One solution to these problems is to scale SUBs out rather than up, by employing several, simultaneous reactors that may be smaller, but still economically viable for commercialized production - such as 500, 1000, or 2000 L reactors. This does, however, require pushing the processes towards intensified conditions, rather than simply scaling SUBs up to the largest size available. Such an approach would offset the structural shortcoming that can occur in 4000, 5000, or 6000 L SUBs, but still remain competitive through faster turnaround, fewer carry-over risks, and lower operational costs.
By choosing to scale out into numerous tanks rather than scaling up a single reactor, manufacturers must also consider how bag sizes will impact decisions regarding requirements for electric power, storage, and handling, to determine where the optimum between size and efficiency lies. However, such considerations may be well worth the effort, in order to facilitate a straightforward and competitive development process.
For all but the largest production sizes, SUBs offer excellent scalability of production development due to their distinct advantages, whilst also incorporating more traditional benefits of steel reactors as their designs and materials continue to improve.
Taking into account these various benefits and potential pitfalls, the faster turnaround of SUBs enables organizations to rapidly test and readjust when scaling from trials to final production, and using the more standardized geometric configuration between different SUB scales reduces the risk of other variables affecting the production. This freedom to choose when and how to move between scales makes using SUBs at all scales of production a valuable approach to biopharmaceutical development.