We began the podcast with a brief introduction from Fabien Moncaubeig on vaccine and viral vector manufacturing. In this introduction he discussed that the protocols for vaccine and viral vector manufacturing are similar although vaccine manufacturing has a longer history. Both have used adherent cell lines in cell factories or roller bottles. The challenge with these systems is that in order to increase volume you have to scale out rather than scale up. In scaling out you increase the number of pieces of equipment, the overall manufacturing footprint, and the number of employees needed for operation, thus the cost doesn’t decrease significantly. Another option for manufacturing is suspension culture using microcarriers for the cells to attach to. The advantage here is that you can achieve large volumes, however it does take a good deal of process development time for optimization. iCELLis provides a fixed-bed scale up solution, but it is different from traditional fixed bed technology in a couple key ways. First it is scalable and has a scale down model with the iCELLis Nano. Second, in traditional fixed bed bioreactors, there is no sampling possible, so analyzing the metabolites is the only way to examine cell health. In the iCELLis, live monitoring of cell density is possible using the Aber Capacitance probe. We then talked with the inventor of the iCELLis, Jose Castillo about what led him to develop the iCELLis and he spoke about being frustrated with the vaccine manufacturing process and how he was looking to change vaccine scale up. He wanted to focus on process intensification and increased cell density. This is how he began his work on iCELLis. Now as CTO of Univercells, he is focused on ready to use processes for virus manufacturing and the iCELLis is a big part of that work. He spoke of the acquisition of the iCELLis technology by Pall and said it was a great decision. He felt that in order for the iCELLis technology to reach full adoption that it needed the support of a large company who could guarantee the supply chain and provide broad customer support for implementation. As a follow up, I asked Mario Phillips, Vice President and General Manager, Single-Use Technologies, Pall Life Sciences, how he saw the iCELLis fitting into Pall’s overall product portfolio. He explained that the industry, including Pall, was moving toward a solutions based approach to supply. Instead of just supplying equipment, Pall is focusing on providing solutions via a platform approach with upstream and downstream support for the entire workflow. We then discussed implementation of the iCELLis technology with Fabien Moncaubeig, Head of Cell Culture Technologies at Pall. This was a particularly interesting discussion, as we talked about making the decision to move into suspension culture vs. staying in adherent. Fabien explained that this decision depends on how key questions are answered. He often guides customers through this decision making process by finding out how much they need to produce, by when, and what is their current process. By discussing these topics, they can then come up with a short term and a long term plan. For example, the short term plan might be to stay in adherent cells using iCELLis for Phase II, because companies need to produce material quickly for clinical study and because they may not want to invest time and resources into process development of a suspension process at this point. Long term, the plan may be to move into suspension culture because companies can achieve a higher capacity and will need to meet a growing demand for their product. Single use, stirred tank bioreactors can reach 2,000 liters, however the iCELLis only reaches 500 square meters, which is roughly the equivalent of 1,000 liter stirred tank. By moving into suspension, companies may find that they can produce more product at lower cost with high volumes, but this is a long term focus. I then asked about how one could increase production in iCELLis. He explained that in increasing production you have a couple options, the first is to increase the size -either of the bioreactor or the number of bioreactors. The second, and the one Fabien recommends, is to optimize the productivity of the process. This can mean optimizing media or optimizing the cell line through cell line engineering. He said he felt there was a need for cell line engineering of adherent cells, which is an area the industry has excelled at with suspension CHO, but not much time has been spent on adherent cells. He felt this could provide quite an advantage, particularly in Gene Therapy applications. I then asked what were some of the biggest application areas for the iCELLis and he said Gene Therapy applications has had the highest demand and that customers’ requests are usually that they want manufacturing “quick and easy.” They need a high number of viral vectors very quickly and the iCELLis enables this time frame and keeps the costs down. They also have interest from vaccine manufacturers. As a follow up to the discussion on Gene Therapy, I asked Hanna Lesch, Research and Development Director at Finvector Vision Therapies about her experiences using the iCELLis for viral vector production. Hanna described how Finvector is working on viral vector based gene therapies and that they were an early adopter of the iCELLis platform. She said they conducted early feasibility studies in the iCELLis Nano and the results were promising. For their feasibility studies, they compared productivity in the iCELLis Nano to shake flask results. With support from Pall, they then worked on process development and scale up, things like cell seeding, media optimization, feeding strategy, etc. She said that the scaling up was pretty straight forward from the Nano to the iCELLis 500 and that they got consistent production, which was really helpful in process validation. Since the material they are producing is going to be used in clinical trials, I asked about the regulatory response. Hanna said that so far the FDA has been satisfied with the process and has no issues. We then discussed with Mario recommendations for those who are thinking that they may want to implement iCELLis in their manufacturing process. He recommended spending time in process development with the iCELLis Nano to develop a robust process, which would make the move into the larger scale production more efficient. He also said it was important to really understand the value proposition in terms of the cost savings for capital and operational costs. He said scientists are often convinced about the technology in terms of performance, but also need to also show the other benefits. He said because it is a different approach to growing adherent cells, there is a longer adoption time. With over 100 customers actively in process development with the iCELLis, it seems that they are well on their way toward adoption. Some of the ways in which Pall has sought to reduce the adoption barriers is by providing a great deal of process development data in the iCELLis to customers and to provide process development services. In addition, Mario felt that the iCELLis provides solutions to key industry issues. For instance the iCELLis can reduce manufacturing costs, provide the safety of an automated, closed system and can also reduce time to market by eliminating the process development work of adapting adherent cells to suspension. Mario estimated that by using the iCELLis, one could cut time to market by up to ½. Thank you to our panel for this podcast, it was a very informative discussion on vaccine and viral vector manufacturing and the iCELLis as an innovative, enabling technology.

Show Notes

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