Jeanne Linke Northrop: When it comes to developing a cell culture scaling strategy who takes on that challenge within an organization?
Andreas Castan: I believe it depends on the size of the company and the stage the project is currently on. In smaller companies with fewer projects the PD team takes a large responsibility and follows the process for clinical manufacturing. On the other hand, in larger organizations with broad portfolio of projects it is managed by the MSAT team—which is the link between PD and the manufacturer. The CMC journey is complex with many stages such as functional groups.
Jeanne Linke Northrop: Are there special skills required by that person to define that scaling strategy?
Andreas Castan: Yes, there are two important skill sets required. Knowing the process of the development history and critical parameters is important. For instance, all the ranges for the operating parameters such as the ranges for pH and feed rates. On the other hand, it is also important to know the equipment with the mass transfer characteristics. The tech transfer and bioreactor scaling are tasks that require versatile skill set in the team.
Jeanne Linke Northrop: How are they developing that tech transfer and scaling process today? What tools are they using?
Andreas Castan: The organizations which includes CMOs have acquired elaborated template available that captures the critical information, and operating parameters for the transfer process related information. FMEA are the central documents for transferring information between the two teams. On the other hand, there are no universal tools available when it comes to scaling the oxygen transfers, CO2 stripping, and flow regime in the bioreactor. Excel sheets are and personal experience are used to make calculations. However, these excel sheets are not maintained well and not traceable. There is a difference between a common language especially when the process transfer is performed to another department in the organization.
Jeanne Linke Northrop: In your opinion, what is the major challenge PD or MSAT scientists face with scaling today?
Andreas Castan: It is a need for a common language and common tools when scaling between bioreactors—it begins with aligning on the scaling relevant equations. It is important to have well characterized bioreactors by physical measurement and experiments. It is also amended by CFD calculations which could describe things which cannot be measured. You need calculation power to calculate multiple scaling relevant power meters. Thereafter, the operating power meters for gassing regime is predicted. For example, scaling is centered around a few highly skilled and experienced individuals. The availability of common tools will result in the democratization of scaling.
Jeanne Linke Northrop: What are some of the consequences of continuing to do it that way?
Andreas Castan: The consequences of not having tools available that create a common language and facilitate a structured scaling exercise result in taking chances in bioreactor scaling and taking unnecessary risks. I have often experienced the mentality like, " We have scaled a similar process before. Therefore, it will work this time as well. However, different cell lines may differ significantly in their oxygen requirement and behavior in the bioreactor. By doing the math upfront and taking all available data into consideration it will significantly increase the success of the tech transfer.
Jeanne Linke Northrop: How do you see these challenges changing over the next few years?
Andreas Castan: I foresee that the pressure on the industry will accelerate development timelines—it will also include bioreactor scaling and tech transfer. In order to accomplish these goals, there is a need for a universal language and to use easy tools that PD scientists and MSAT engineers may use to secure successful scaling. These tools require high quality characterization data of the use bioreactors. Stainless steel bioreactors merge with the described tools which may be a challenge for the upcoming years. However, when we have the universal language, easy to use tools, and characterization data in place, I believe we have removed the major challenges and bottlenecks in successful bioreactor scaling.