John Sterling Editor in Chief Genetic Engineering & Biotechnology News
Interview with Nigel Darby, Advisor, GE Healthcare Life Sciences
Nigel Darby, Ph.D., joined GE Healthcare Life Sciences in 2003 and served until 2016 as vice president of the bioprocess business, which develops manufacturing technology that is used in the production of biopharmaceuticals. He is currently an advisor to the GE Healthcare CEO and a board member of Vineti and Asymptote.
GEN recently paid a visit to GE Healthcare at the company’s largest life sciences site globally in Uppsala, Sweden, and took the opportunity to interview Dr. Darby.
GEN: What do you view as the key trends in the biopharma market?
Darby: It’s rapid growth. The industry is enjoying significant increases in biopharmaceutical revenues and lots of new drug approvals. It is also addressing unmet medical needs for some quite challenging diseases.
The competitiveness of the market also stands out. If you look at cancer immunotherapy, for example, there are many players involved. Each indication is extremely dynamic in terms of the number of companies and molecules competing.
The interest we see from customers in emerging markets continues to astound me in light of the availability of funds to build manufacturing capacity. But often that capacity is quite speculative regarding for what it will be used.
The other major biotrend is biosimilars. New biosimilars are being approved in Europe and North America on a regular basis. What we must wait to see is will the impact of biosimilars on the market be as significant as the introduction of generics in other areas?
GEN: You mentioned earlier that the industry is “meeting unmet medical needs for some quite challenging diseases.” What is the main unmet medical need that is now being addressed?
Darby: If you look at where the biggest growth in the biopharmaceutical market is taking place, it has been in cancer. With the introduction of immunotherapy antibodies such as Opdivo (nivolumab) and Keytruda (pembrolizumab), and CAR-T cell therapies, there have been remarkable therapeutic results that would be extremely difficult to emulate with conventional therapies.
GEN: What else besides the uncertainty about biosimilars represents important challenges facing the bioindustry on a global basis?
Darby: Given the industry’s rapid growth, the capacity to service that growth in relation to the entire supply chain will be critical, especially if you are thinking about the base capacity for manufacturing biopharmaceuticals. But then there is also the whole supply chain behind it. For companies like ours a key issue we always need to keep in mind is have we dimensioned our capacity correctly to meet the supply demands of a rapidly growing biopharmaceutical market?
In the emerging markets, we have the challenge of what type of capacity is it that those markets need? Often these can be markets where it may be more difficult to set up manufacturing capability. On the other hand, because those markets are more or less a clean sheet, there is perhaps more of an opportunity to adopt the most optimal manufacturing solutions.
In the well-developed markets where we already have a lot of existing infrastructure we cannot necessarily write-off that infrastructure to put in place the best and most modern technology. You could argue that there is more of an opportunity in emerging markets to implement the very latest of manufacturing technologies on offer.
GEN: Picking up on your point regarding the uncertainty around capacity planning, what’s being done to address this uncertainty?
Darby: When you are thinking about capacity, you need to build the capacity early enough so that if your drug is approved you have sufficient capacity ready at launch. But that brings up the point that when determining how much capacity you will build you are managing a significant financial risk. If you build capacity and do not utilize it, that has a significant negative impact on manufacturing costs. On the other hand, building too little capacity may not allow you to meet market demand for a successful drug.
With the modern technologies we have in place, we can build manufacturing capacity more quickly, which potentially allows you to build it at a later stage in the clinical cycle where you have more certainty that a drug will reach the market. Since you now can build capacity quickly you are able to start with a relatively small infrastructure and low capital investment and build out as demand increases.
All the technologies we focus on are concentrated around process intensification, which is trying to make sure that you have methods that allow you to maximize the output from the smallest possible facility. Today we are talking about building small economical facilities that perhaps have four 2,000-liter bioreactors. If you go back 20 years, you would have been building facilities that contained four 20,000-liter bioreactors to achieve the same output.
GEN: In addition to smaller bioreactors, what are some other technologies that companies like GE Healthcare are working on to reduce the capital risk?
Darby: Every successive generation of chromatography resin we bring to market, most recently MabSelect PrismA, allows you to work at a higher productivity. The product impacts the purification process such that the chromatography column size can be reduced, along with the buffer, water, and time requirements, thus enabling smaller and less expensive facility designs.
A massive amount of the running cost in a biomanufacturing facility is simply the management of water. Building the tank space needed to store all the buffers before you use them is also a significant capital cost.
GE has technologies that simplify the manufacture of buffers and reduce the number of batches and volumes of buffers that you may need to prepare. That can translate into reduction of the cost in what is really a non-value-added activity. For example, in-line conditioning is a technology that is versatile in reducing buffer consumption or the need to make buffers in bulk and can significantly reduce storage costs.
We are also thinking about continuous biomanufacturing, whether upstream or downstream. It’s probably a much longer- term opportunity because although well-accepted in upstream manufacturing, I do not know of any approved continuous downstream chromatography processes. There is some uncertainty about the application of this technology from a regulatory perspective, but the technique will offer some specific advantages in particular cases for improving the overall cost economics of manufacturing.
GEN: How do you think cell therapy will change the biomanufacturing process?
Darby: I think it best to answer this question from the perspective of what we have tried to do at GE. It has been a question of how we have built on the experience in the bioprocess space. Given the requirements of cell therapy manufacturing and its personalized nature, there is a lot of focus on single-use technology.
Many of the products and technologies that we first brought to market in mainstream bioprocessing are finding a strong level of adoption in the cell therapy manufacturing workflow. If you look at that workflow, what we have tried to do is create an end-to-end solution, which solves key manufacturing challenges. For example, taking cells that are growing in several liters of media in a single-use bioreactor, and concentrating them so you get a volume which can be dosed to the patient.
Keep in mind that many of these treatments are manufactured well away from the patient. You then have the challenge of a supply chain that moves between the patient, a centralized manufacturing facility, and then back to the patient. So, freezing and thawing technologies are critical for that and we have invested quite significantly in technologies that refine these processes for cell therapies.
One of the biggest challenges that you have in the cell therapy area is perhaps something that is not particularly what you would see as a high-tech barrier—how you control the process so that you are sure that the right cells go into the right patient. This is a key regulatory concern. We decided a few years ago to establish a startup, Vineti, and spin it out of GE to offer a software solution that will allow companies to manage the patient care workflow in a reliable and compliant way.
GEN: What are GE’s strengths as a supplier to the biomanufacturing segment of the industry?
Darby: I’ve already mentioned our broad portfolio, exemplified by single-use technologies, cell culture media, smart hardware solutions, and the MabSelect family of chromatography resins. These combine to create a cost-effective manufacturing solution.
We do a good deal of investing in facilities and supply chains and in the support of products. Many of our products are now being purchased by people who perhaps have less experience in biomanufacturing. There is considerable demand to help these individuals negotiate the biomanufacturing process and to make sure that they can optimally utilize our products.
Automation is a vast area for investment as our factories increasingly rely on automated technologies to help them work efficiently. This is the case not only in our own factories, but we have also taken stakes in businesses such Ireland-based Zenith, which helps our customers integrate automation into their manufacturing facilities.
As automation gives us more ability to control and monitor our processes, we are giving increasing attention to the use of data management and digitalization, particularly in biomanufacturing, to help understand how variability, especially in raw materials, is impacting the manufacturing output, and using that data to help us learn how to optimize future processes.