Interview with Professor Charles Cooney on Bioprocessing

We had the opportunity to sit down with Charles L. Cooney (Robert T. Haslam Professor of Chemical Engineering, MIT) to discuss what he sees as being on the horizon for biopharmaceuticals and single-use; how the field has advanced since the publication of his white paper on continuous bioprocessing; and some of the advantages and challenges in single-use technology. An excerpt from our interview is published below. 

What are some of the general trends you see in the biopharmaceutical market?

 Cooney: There is a major trend within the industry of intensification, integration, and interrogation. That trend is in response to the need to manufacture high quality at smaller scales (given the changes in the market dynamics); the need to be paying increasing attention to cost (both operating and capital) and the need to flexibly meet market demands that carry with it substantial uncertainty. There’s also an increasing interest in distributed manufacturing, where you would not have a centralized drug substance facility, but rather, use a smaller scale distributed system in order to access specific markets. This interest is driven by the business case, which is different for new products vs. existing products, and then it’s enabled by advances in equipment.

Your white paper on continuous bioprocessing came out five years ago – how has the field advanced since then, and what are the concerns of biopharmaceuticals investing in single-use technology?

 Cooney: The fundamental process flow diagram looks like it did 30 years ago, but single-use technology, integration between unit processes (upstream/downstream are examples) has enabled you to do intensification and integration in a very flexible way. When you now look at the single-use systems, these integrated systems, you realize you are dependent on the interface between your culture, your product, and these flexible surfaces that represent single-use technologies. Moreover, since you’re going from a stainless system to a single-use system, you also need to think about how you use not just traditional sensors or analytics, but how you can develop single-use sensors and make them compatible with this very flexible technology (single-use). One of the advantages of single-use systems is that they are pre-sterilized.  What this does is to add to your execution strategy greater importance on the supply chain of not just the raw materials that lead to your product, but the raw materials that touch your product.  

Also, you’re not only concerned with the single-use piece that is in contact with your process, but you are concerned with the transport and integrity of the components themselves, and hence it’s not just the single-use bag, it’s the bag around the bag.

Speaking of equipment, are so many options necessary due to the fluidity of the field and if so, you think the industry will coalesce once the pace of technology starts to slow? Do you think one system will win out over the rest when it comes to standardization, or will there always be the need for customization?

Cooney: When I talk to the drug manufacturers, they complain about the absence of standards, particularly for connectivity. One of the reasons they complain is that they want the flexibility of being able to order different pieces of kit from different vendors. When I talk to the vendors, and I would say Pall is one strong example, they would like to standardize all of their equipment so that it is easily integrate-able, but their marketing push is to sell the whole line, end-to-end to the customer. The customer pushes back and says, “we don’t want to buy the whole line from you – we want the flexibility of choosing bags from one company, separator systems from another, chromatographic columns from yet another." So not surprisingly, there’s a tension between standardization and customization.

I often think of it as being reminiscent of videotapes between Beta Max and VHS – you know, one survived, and one didn’t. I don’t have an inside perspective, necessarily, I assume that the dominant player is going to set the dominant standard, and I think Sartorius is as close to being the dominant player as anybody. Having said that, I’m struck by the recent purchase by Danaher, who bought Pall a number of years ago and have now bought GE Healthcare. GE is one of the elephants in the room and perhaps this will be a step towards standardization.

It has been said that the era of "Blockbuster" drugs is over – how do you think that will affect the market?

Cooney: I still think we’ll have the occasional blockbuster – I mentioned DUPIXENT® (dupilumab), the Sanofi Regeneron drug that I think will fall under that category – but by far, the evolution of new FDA approvals and processes is going to the specialty markets, and the specialty markets have a number of interesting characteristics. First of all, oncology is increasingly becoming a specialty market as we are continuing to learn how to differentiate one cancer from another. I think that pattern is going to continue; I think we’re still at the early stages of cancer diagnostics and being able to select the right therapy.

Then there are a wide variety of other biologics for dealing with unmet medical needs and rare diseases – they’re all going to be small processes. The evolution of single-use technology is one of the major advances in bioprocessing that enables one to create flexibility in your process design. It allows one to operate smaller plants economically and because the regulatory environment has changed with breakthrough designation or accelerated approval designation, you need to get from your clinical trial to the market faster. It used to be it took 4-5 years to get a big stainless-steel plant online, and now you can do it in 2 years with single-use tech. One option is in a ballroom facility as opposed to a highly segmented manufacturing plant, and this gives you even more flexibility. Then with intensification and integration, you can put multiple products into the ballroom because you don’t need much space; it’s an integrated system, so it’s closed; you’re not worried about cross product contamination, and because everything’s single-use, it comes in pre-sterilized.

One of the biggest concerns with single-use technologies are extractables and leachables and how they affect the final product – how do you see the regulations addressing this?

Cooney: I would like to believe that a scientific understanding of what extractables and leachables might be would facilitate more comfort with the issue. There have been some bad experiences with extractables and leachables, probably one of the most dramatic is with EPO with a rubber stopper a number of years ago. And people want the data, and it’s very expensive to get as you know. So, I think this is going to continue to be an issue for some time. And I don’t see a way around having to do the extractables and leachables studies in order to get the data to support your filing and to support your business. The good news is once you have acceptable products, acceptable materials, so long as the manufacturer doesn’t change their process, you can rely on that. It may be with time we’ll accumulate enough data to build up a level of confidence.