We began the interview with a discussion about deciding when single-use bioreactors are a good fit for a fermentation process. Mr. Clapp listed several questions that can help with the decision. Questions like how big is the product market and how much production capacity is needed are important considerations for ensuring appropriate scale. Companies must decide how important the benefits that single-use technologies bring are to their business model. Benefits to consider include: lower capital expenditures, reduced contamination risk, more efficient equipment utilization and higher throughput. Ken said if one or more of these considerations are important then single-use is worth exploring.
Once a company has decided that single-use is worth researching further, Ken shared that it is important to look at the technology to see if it matches the process, this initially happens as a paper exercise. After screening on paper, if it looks promising, then companies should perform demonstration runs to ensure capacity and quality can be maintained for that product.
Next we talked about the types of processes that are a good fit for single-use. Ken explained that companies that are producing high value, biologically relevant therapeutics like antibody fragments and recombinant proteins make the best fit. The system isn’t a good fit for industrial manufacturing, for example, ethanol production. Bioreactors are available up to 500 L, so a company must also evaluate their capacity needs and whether they want to use a scale up (larger vessels) or a scale out (multiple smaller vessels) approach.
I then said that the benefits of single-use have been widely recognized, but what about people who are asking whether plastic bags are strong enough to withstand the rigorous demands of fermentation. Ken said it is a question he gets frequently. He explains that to meet these rigorous demands, first you have to understand what contributes to the stress on bags and identify these as engineering challenges. Once identified, these challenges can be addressed with good engineering, bag fabrication design and via the bag manufacturing process. He also said that another important part of ensuring bag integrity is making certain that the staff is trained on proper handling of bags. Good training goes a long way to maintain bag integrity and this is a fact that has been proven in cell culture applications as well. Ken points out that working with single-use systems is a different way of working compared to stainless steel and there has to be an understanding of what a bag is and what it isn’t.
I then asked about recommendations for transitioning from stainless steel to single-use and what it looks like from process development through scale up. He said the organizations’ experience level with single-use systems shapes the transition. It is important to stage a fermentation run and make sure all the supporting elements are in place. Process development efforts smooth transition to larger scale up, and just like in cell culture manufacturing, the effort put in during process development really pays off with easier scale up.
I then asked what considerations companies should keep in mind when transitioning to single-use. He mentioned that being open to change is important. The key to utilizing the opportunities associated with single-use is to rethink your operation and various parts of the business. It is a chance to abandon legacy operations and adopt more flexible manufacturing.
We then discussed the biggest reasons a company decides to switch to single-use. Ken shared that companies switch mainly for business reasons including greater flexibility, more productivity in less time, faster throughput and less operation complexity. With two of the biggest reasons being reduced contamination risk and reduced capital expenditures.
We ended the interview with Ken sharing closing thoughts with listeners. He said that he believes single-use is here to stay and that adoption has continued to increase in cell culture based manufacturing. Single-use systems have even moved into more demanding culture situations like high density culture and longer processing times. The same gains can be achieved by using single-use systems for fermentation and the hurdles to adoption have been lowered by the experience in cell culture.
For more information on microbial fermentation, please see part 1 of this podcast:
Single-use bioreactors for fermentation – It’s now a reality that deserves consideration