When we began writing about single-use components and systems for biopharma processes early last decade, a wait-and-see attitude prevailed. In the years that followed, the disposables question became the disposables answer, and their use has proliferated across the marketplace, both for in-house and contract manufacturing operations. We spoke to several single-use technology providers to get a sense of where the strongest areas of growth lie.
“The market for single-use systems is clearly accelerating,” said Dr. Christel Fenge, vice president, Marketing and Product Management, Fermentation Technologies at Sartorius Stedim Biotech. Sartorius’ 2005 acquisition of Stedim made it a player in the field, especially when coupled with the bioreactor control competencies the company gained from an early acquisition. Dr. Fenge remarked that classical, multi-use bioreactors still count for the lion’s share of the business, but she predicted that single-use technology (SUT) will reach a 50/50 split within the next five years. “SUT comprises more than bioreactors, of course: there’s filtration, purification systems, etc. They’re all part of the pie.” And, she added, “Asia has become as large as the North American market for us,” while noting Europe remains SSB’s top market.
All the providers we spoke to agreed that Asia has become a huge market for SUT.
The key, it appears, is the lack of legacy infrastructure. Western companies with installed bases of large reusable systems wrestled over questions of sunk costs, while startups in emerging markets have been able to leapfrog them by opting for disposable biosystems. These startups may not be pursuing innovative biologics, but they can certainly pursue biosimilars and biobetters with less capital outlay for manufacturing facilities.
One provider noted, “In the west (and Singapore), there’s an overcapacity in stainless steel tanks. There’s been a shift from blockbuster drugs produced in massive quantities to niche-busters, so we’re moving toward smaller volumes at the same time that titers in bioreactors are getting higher. The puts a dent in Big Stainless. But those old systems don’t exist in the rest of the far east, so they’re free to invest in proven single-use systems. They can say, ‘We want biomanufacturing capacity. How do we get there?’”
“We’re seeing a lot of activity in Asia,” said Paul Chapman, head of biopharm process solutions at EMD Millipore. “China is booming, as is South Korea. They see the benefits of SUT, in terms of cost, speed, prevalidation of systems.” In May 2011, Millipore opened a 2,500-sq.-m. Biopharmaceutical Technical and Training Center in Shanghai, to provide support, training and validation services for customers’ operations in China.
Jeff Craig, ATMI LifeSciences’ global director, Business Development and Marketing, remarked, “India is another market that’s blowing through the roof. Indian companies are looking for proven manufacturing technology and have been very quick to adopt it rather than spending time evaluating it. They see the proven benefits and want to roll this out on a commercial scale for cell therapy, stem cells and recombinant technology.”
“We’ve seen a disproportionate amount of interest from emerging markets. SUT lowers the barriers of entry for new players,” said Kenneth P. Clapp, senior director, Global Market-ing and Product Management, Xcellerex. “These players can be in emerging regions, with a desire to compete in a unique way against more established companies from other markets.”
So who are the end-users? Besides covering a wide geographic footprint, the customer base for SUT is very much a mix of big and small, and in-house and CMO. Said Mr. Craig, “We're seeing very large organizations with specific mid-phase projects that look promising. Incremental implementations are happening. Big pharma are the clients; there are initiatives at every major player out there.”
At the same time, said Mr. Chapman, small and emerging biotechs can benefit from the rapid development speed that SUT unlocks. “For customers, having ‘fail fast’ ability is important. If you're in preclinical, you want tox material very fast. Phase I is the same thing; you’re not working in big quantities. Disposable systems like our Mobius FlexReady Solutions lend themselves to that speed and lower cost. So, they get smaller volumes, faster and cheaper, with less worry about revalidation of process. At each step, this can save two months to either kill a project or move it to the next phase. Every size of client can find benefits in different stages of the process.”
Said Mr. Clapp, “We see interest from all types of companies, from mid-size biotechs to large biopharma, even some divisions of chemical/specialty chemical conglomerates that are looking for cost-effective, risk-reduced biomanufacturing capacity.”
On the CMO side, customers have similar needs to innovator biopharmas, but weigh them differently. “Flexibility and cost of goods are key for them,” Mr. Craig remarked. “CMOs have been some of the earliest adopters and biggest customers in the industry.
In my previous life with a CMO, my experience was that you sometimes had to ask the client to buy equipment, and then it would end up in storage area. With SUT, the capital outlay is much smaller, and speed is much quicker.”
Dr. Fenge agreed, commenting, “CMOs are very important accounts. Some serve as a kind of multiplier of early projects, so they have a great perspective on the needs for innovation of SUT.” Her company recently launched a 2L single-use bioreactor called the UniVessel, intended for small-scale protein expression to media or process optimization studies.
Mr. Clapp commented, “CMOs are in a tough market; many companies are trying to be competitive, while managing their capacity and equipment mix. SUT is one of the best tools a CMO can employ to manage its business. Some of the real value of a system like ours comes from reducing facility infrastructure needs. There’s the reduction in cleaning and the associated validation in a multi-product/client operation.” He knows whence he speaks: Xcellerex also functions as a CMO, focusing on preclinical through Phase II.
Xcellerex recently made news by selling several of its single-use bioproduction systems, including the FlexFactory platform, to Gallus, a new bio-CMO based in St. Louis, MO. Mr. Clapp commented, “For Gallus’ situation, SUT makes the most sense; it provides rapid deployment at a much lower risk.”
As single-use technology has proliferated, providers now look at methods of differentiation. Seeing to avoid commoditization, ATMI Life Sciences has stressed both its technology offerings — it acquired LevTech (where Mr. Craig was co-founder), developers of the maglev disposable mixer that we wrote about many years ago, in 2008, and Atrelis, a provider of cell culture research and manufacturing scale-up technologies, in 2010 — and a value proposition for the films used in its bags. Said Mr. Craig, “ATMI manufactures its own disposable vessels. We offer supply chain security, cleanliness, integrity testing (to avoid leaks), visibility (have it be crystal clear), and a delivery program for on-time delivery.” The company recently introduced Helium Integrity Testing on its bags, sensitive to holes 10 microns in size.
Dr. Fenge commented, “I don’t think we’re headed for commoditization yet. This field is very driven by the expertise, and it’s not so easy to standardize. Security of supply is very important for the bags: traceability of raw materials, extractables and leachables profiles, and the like. Customers are aware of these issues and you can’t make a splash with a cheap offering.”
One provider noted that the industry call for standardization in bags — and the lower costs that represents — often gets muted by demands for customization: “You strive for standards to reduce costs and enhance economies of scale, and then the end-user instantly wants to customize.”
So where is SUT headed in the future? Our providers’ consensus was that bioprocessing systems will get smarter and that we’ll see hybridization of SUT and stainless steel for some applications where pure SUT is unfeasible. In the realm of failed predictions, our earlier articles that mentioned 5,000L disposable bioreactors seems to have gone by the wayside; most of our providers said that 2,000L and under is the sweet spot, thanks to the aforementioned increases in titers.
Said Dr. Fenge, “There are a multitude of single-use bioreactors these days.
Companies have proposed either rocking motion designs and stirred tank designs. Numerous proposals are out there, and I expect we’ll see some consolidation in the next five years. Companies with broader offerings will be more successful.”
Gil Y. Roth has been editor of Contract Pharma since it debuted in 1999. He can be reached at firstname.lastname@example.org.