June 15, 2014 (Vol. 34, No. 12)

An Interview with Nigel Darby, Ph.D., VP, Bioprocess, GE Healthcare Life Sciences

Beset by multiple challenges—declining R&D efficiency, rising healthcare costs, and unmet medical needs—the biopharmaceutical industry is keen to better its bioprocessing practices. The success and safety of biopharmaceuticals suggest that the tools for making safe, effective biological therapeutics already exist. These strengths, bioprocessors believe, will continue to be used to good advantage. Indeed, it is through innovative combinations of existing technologies that bioprocessors plan to deliver long-term sustainability.

GEN: What are some of the future directions for bioprocessing?

Dr. Darby They mostly involve creating greater flexibility. Bioprocess infrastructure has traditionally been large, very expensive, and dedicated to the production of one molecule. Greater flexibility implies the ability to push more batches of product through the facility and/or make it multiproduct, the implementations of which will be game changing.

For one, it allows manufacturing to move from the exclusive domain of huge corporations toward much smaller players. Think of this “democratization” of bioprocessing as part of globalization. Another aspect will be the ability to handle broadly changing biopharmaceutical portfolios, particularly with respect to niche medicines manufactured in what are, by today’s standards, small quantities.

Nigel Darby, Ph.D., VP

GEN: By “niche medicines” are you referring to personalized medicine?

Dr. Darby Not necessarily, but personalized medicine is one piece of it. In today’s marketplace, perhaps six or seven antibody drugs are produced at ton scale. We will increasingly see a richer portfolio in terms of numbers of molecules, but with many of those products serving smaller patient populations identified by diagnostics.

GEN: But these products will cost the same to investigate and test. Doesn’t this scenario mean lower sales for the same amount of effort?

Dr. Darby We’re seeing over and over that as long as a new therapeutic successfully addresses a critical medical need, and patients are appropriately stratified to receive that treatment, the market can withstand some pretty high medicine costs. For example, very rare diseases, such as Pompe disease, are now treatable with enzyme replacement therapies, but at costs that may be hundreds of thousands of dollars per year. They have to be priced that high to ensure a reasonable profit for the developers.

But once the therapies are approved, patients, at least in many wealthier countries, have access to the drugs. One issue that is easily overlooked in the price-benefit equation is the cost of otherwise hospitalizing patients versus treating them with a drug. It’s an interesting dilemma that thus far is only being addressed in countries with advanced economies.

GEN: We’ve heard that innovation—new drugs for unmet needs—was the primary shortcoming in our industry. True or false, and why?

Dr. Darby Much more serious than innovation is the problem that blockbuster drugs are going off patent more quickly than our ability to replace them. From my perspective, the early-stage pipelines are full of innovative drugs that aim to tackle unmet medical needs. But launches are simply not keeping pace. Not only is development-stage innovation not dead, but the perseverance companies are showing, to get their products through trials for the right patient populations, is astounding.

I think the problem may be more true for small molecule new chemical entities, where all the easy targets have been played out. By contrast, biopharmaceutical development has so many more ways to intervene biologically. Many antibodies today are hitting targets that small molecules can’t touch.

GEN: Describe some smart combinations of existing tools and their potential impact on the future of bioprocessing.

Dr. Darby If you were building a facility from scratch today, you wouldn’t do it the way it was done five or ten years ago. For example, today you would design with single- use technology in mind to provide maximum flexibility. That becomes critical to reduce the amount of time spent on non-value-adding processes in manufacturing. So the question becomes how to retrofit legacy facilities, many of which are running on technologies from 20 years ago, to be more productive? There are many ways, actually.

Today’s chromatography media drive two to three times more productivity than those from the 1990s, which translates into processing a batch much more quickly. If you can speed up or intensify your process effectively, you can drive more batches through a facility and lower the cost of each individual batch. For an antibody process, that might be worth $25 million or more in sales—provided you can sell the product.

Still, other technologies deliver lower setup and take-down times, faster column packing, less maintenance, and of course all the well-documented benefits of single use. It all comes down to replacing low-value activity with high-value operations. It doesn’t sound very glamorous, but it is quite effective.

GEN: What constitutes sustainability in the context of bioprocessing?

Dr. Darby It’s about making these medicines more affordable and accessible, and getting away from situations where biopharmaceuticals are medicines only for the wealthy. This is becoming increasingly important as the industry globalizes from the perspectives of manufacturing and markets.

Considerations regarding reimbursement are not the same in China as in North America. What is ultimately desirable is to construct the smallest possible facility and drive productivity through it as much as possible. Doing so will ensure that the investment and running cost of the facility will not weigh down the cost of a biopharmaceutical. Think about it: 70% of the cost of goods in antibody manufacturing consists of fixed costs, for example, depreciation on capital and the millions required just to keep the facility running.

Unless you’re driving productivity and batches through your facility, and implementing process intensification where appropriate, it’s pretty hard to get the economics to work. Part of the exercise is converting what was previously a single-product facility into a multiproduct facility to ensure capacity is maximally utilized. Think of this adaptation as facility intensification.

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