Show Notes:

Our interview began with a discussion about the evolution of continuous bioprocessing. Dr. Levison explained how many industries have adopted continuous manufacturing and have been operating this way for some time. The real pioneering of continuous manufacturing came from the automotive industry and later was adopted in other areas.

I asked about ways continuous bioprocessing could be used to solve challenges and address certain pain points in biomanufacturing. Dr. Levison discussed how today the industry uses discontinuous batch processes, which have been largely successful, but there is always room for improvement. For instance, in batch processing one has to wait for cell culture to complete, around 10 days, then there is downstream that adds another 5-10 days, this necessitates several hold steps. These hold steps are inconvenient, take up facility space, and require large volumes of buffer, raw materials and fluid disposal.  These are examples of the pain points that could be addressed with continuous processing.

We then talked about how people interested in the technology could decide whether it is a good fit for their process. Dr. Levison reminded me that continuous is an evolution of an existing process that still utilizes many of the same process steps. So it isn’t as big of a change as some may think. He recommended that people talk with experts in the field of continuous or go to suppliers in the field for more information. For instance, Pall utilizes their Westborough continuous facility to educate interested parties on continuous manufacturing. They also offer process development services to assist customers in evaluating their processes and helping with the transition from batch to continuous.

Next, I asked if there were specific situations where continuous biomanufacturing was not a good fit? Dr. Levison said most would be, but possibly a process done very infrequently, once or twice a year, would not be a good fit or with certain chromatographic steps that need unusually long residence times.

I was curious if Dr. Levison could tell us when he thought the majority of biomanufacturing would be done with end to end continuous manufacturing. He provided a great analogy. He said that 10-15 years ago single use technologies were dismissed, but if you look today, the technology is very well established. We can apply this same kind of approach to continuous biomanufacturing. Considering that new molecules currently in pre-clinical could be manufactured using continuous processes, these new products would be on the market within the next 5-10 years depending on indications, complexity of clinical trials and speed to market. The significant drivers to reduce cost of goods in the industry may also influence speed of adoption. Based on these factors, Dr. Levison thinks that continuous manufacturing will be used and widely talked about over the next 5-10 years.

Then we talked about what still needs to be addressed in order to fully realize end to end continuous biomanufacturing. Dr. Levison said that while we still have a way to go, the technologies exist, scalabilty has been proven, and it has been demonstrated that continuous processing works in biomanufacturing. The challenges lie with automation and control of the entire system. We still need to introduce rapid analytics, at-line or on-line monitoring and the big goal of real-time release.

I asked why Pall decided to champion this technology and he said that Pall has a lot of experience in process development and manufacturing, that they had moved into single-use technologies early on, and felt they could leverage their experience and systems to become the leader in continuous bioprocessing.

Last, I asked Dr. Levison if he had anything else to add for listeners. He said scalability is very important for new technologies. If you are going to try and change the direction of processes from batch to continuous, you must be able to show not just lab scale, but that it is scalable up to the levels used in commercial manufacturing today. It is important to work closely with end users to demonstrate that their projects can be scaled to appropriate levels.

Dr. Levison provided an example of one end user collaboration on a scale up project done with Merck. The project required scale up of multi-column chromatography from Pall’s Cadence TM BioSMB PD system up to the Cadence BioSMB process 350 system, which is capable of handling the contents of a 2,000 liter bioreactor. The full study can be found here – Continuous Chromatography – Scalability from Process Development to CGMP Manufacturing.