Bio News & Views: Disposable Update

Single-use components proliferate in bioprocesses

By Gil Roth

When I wrote about the use of disposable components in bioprocessing last year, I was told that the industry is on the verge of an explosion. Since, I’ve received notices from more bio-CMOs about the integration of single-use systems in their new facilities and expansions. But if there’s any sign of how accepted disposable components have become, it’s the fact that most of these news items no longer highlight them as revolutionary; now they’re part of the business, and CMOs appear to be the key users.

Said Parrish Galliher, founder, president and chief technology officer of Xcellerex, Inc., “If you look at the industry, as much as 40% of it may be outsourced. Some of those companies would prefer to in-source. Meanwhile, companies that are in-sourcing want to move to lean manufacturing models. So there’s lots of pressure to increase flexibility, reduce capital costs, and lighten risk. We think use of disposable systems enables that.”

Michiel Ultee, senior director of manufacturing and technical operations at Laureate Pharma, concurred. “They’ve taken off in the last decade, and CMOs are a key economic driver of the disposables market,” he commented. “CMOs find advantage because of the need to handle multiple products in a single site. Using disposables provides a benefit to customers, but it’s also a benefit to the CMO, because it allows us to perform a rapid turnaround and keeps us from having to stock a lot of spare or replacement parts.”

Laureate Pharma recently opened an expansion to its site in Princeton, NJ, a bio-pilot plant with two production suites: one with a stainless-steel train and the other employing Wave bioreactors for cell culture. “Both suites are connected to purification rooms. We set that up intentionally so we could produce small quantities in either type of system,” he noted.

Plastic or Steel?

Single-use systems have been a boon for bio-CMO Cook Pharmica. The company’s new facility in Bloomington, IN contains only five stainless steel vessels, said Jim Fountain, manager of manufacturing sciences, upstream. “We made a conscious decision to rely fairly heavily on disposables,” Mr. Fountain remarked. “For a CMO, ease of turnaround was the major driver. When you combine that with the elimination of cleaning validation requirements, it just made sense.”

For both Messers Fountain and Ultee, use of disposables hasn’t been contingent on client requests; clients with early-stage needs haven’t come around asking whether a CMO employs single-use systems. Instead, the benefits to their respective CMOs were too obvious to be ignored, and clients have subsequently come to recognize the benefits they stand to gain. Said Mr. Fountain, “Clients may not be demanding it, but they’re becoming more aware of the need for cleaning validation and product changeover validation.”

He added, “There’s an ongoing debate about the capital savings for disposable vs. stainless steel. The initial costs are probably a little cheaper for disposables, but I think they’re relatively close to the traditional model. In my opinion, the comfort level and ease of use is what you really gain by building systems around disposable components.”

We Take Plastic

CMOs aren’t the only parties benefiting from the growth of disposable components. Suppliers and integrators are also optimistic about the market, and Sartorius S.A. has definitely put its money where it’s mouth is.

In February of this year, the company made an offer to merge with Stedim Biosystems. If the transaction closes as planned this summer, the new Sartorius Stedim Biotech S.A. will “have the realistic ambition of forming the worldwide market leader for single-use based technologies over the next five years,” according to a statement when the merger was announced. Or, as Paul Priebe, product manager, Sartorius North America, put it, “We’re in it for real.”

Citing figures from publicly held companies, Mr. Priebe described the evolution of the single-use marketplace as one that’s doubling the growth rate of the biopharma market. Still, he offered the familiar refrain that simply supplying components won’t cut it. Services — “connectology,” as it pertains to integrating disposable systems — are key.

Said Mr. Priebe, “As disposables have come into the game, a lot of the qualification was, in a sense, outsourced to the supplier. But if your integrated system is an assemblage of components from five or 10 different suppliers, it’s the end-user’s responsibility to pull all those qualification packages together and form a meaningful validation document. I could envision solutions we’d bring to market that would be covered by a single package of qualification/validation documents, simplifying the implementation process for the end-user.”

He also noted that one of hot terms in the industry is Hybrid Systems. “These are setups employing ‘reusable systems’ for things that don’t have viable disposable solutions, like A-chromatography, or large-scale bioreactors. There will be plenty of hybrid processes out there in the mid-term,” he commented.

Vax Number$

But the biggest influence on disposable biomanufacturing may be the vaccine market. Last issue, I wrote about the ways in which the fill/finish marketplace is being roiled by the boom in vaccine development. As it turns out, disposable components could benefit from (and help allay) our pandemic fears.

“I think the biggest drivers in our business are vaccines,” said Dr. Helene Pora, who holds global responsibility for single-use technologies at Pall Life Sciences. “Until very recently the manufacturing processes for vaccines were based on outdated technologies. Now they’re moving to cell-based systems, and the scale at which they’re operating is matching perfectly with the scale of single-use systems: that is, rarely over 2000 liters.”

The “rapid rollout” factor is also important, said Dr. Pora: “The response to a potential emergency situation also plays a role. In the case of a pandemic, you may need to be able to ramp up vaccine manufacturing, perhaps in places you didn’t manufacture it before. With disposable systems, it can be almost a portable manufacturing setup.”

Pall recently expanded its Kleenpak line of aseptic connectors with 1/4″ and 3/8″ sizes. According to a company statement, “The new sizes enable vaccine manufacturers to apply the safety and efficiency benefits of instant aseptic connections throughout more of their disposable operations to help speed time to market and comply with GMPs.”

Susan Dexter, chief business officer at Xcellerex, agreed with the prominent role of vaccines in the disposable bioprocessing field. “The technology as we employ it is definitely in the ‘sweet spot’ for vaccines: between 1,000 and 2,000 liters,” she said. In addition, she pointed out that her company’s system, the FlexFactory, keeps the human operator outside of the cleanroom space. “No offense to people,” said Ms. Dexter, “but they’re the #1 source of contamination of bio-products.” She added that the system can increases efficiency of manufacturing team by keeping it in a single room. “It makes knowledge transfer much easier when the operators don’t have to be isolated from each other.”

Bigger is Blah?

While I assumed that there’s a degree of “reactor envy” in the single-use field, most people I spoke to contend that disposable systems may never need to scale up to sizes that rival the largest stainless steel tanks. I asked several CMOs and component suppliers if they foresaw the day of 20,000-liter disposable bioreactors — if the scale of such a thing is even possible — and most agreed that there may never be a demand for such things.

Said one marketer, “There are definitely logistical issues as you scale up. That is, the bags start getting heavy! So I think there’ll be a breakeven point where improved processes trump the need for scale.”

Another remarked, “The drugs that needed those massive tanks are old, and they were developed with older technologies, and older cell lines that were less expressive. Productivity levels have increased today, so smaller production sizes are sufficient for yield.”

A third commented, “Some say the last 20,000 liter bioreactor has been built.”

So factors such as increased expression and increased potency — leading to smaller and/or less frequent doses — may mitigate against the development of giant-scale disposable bioreactors. Said Ms. Dexter, “If a new product did need to go to such large scale, future facilities could be built using disposable systems so that the only tank that’s stainless steel is the reactor tank. After all, water disposal and availability are crucial, so if you can reduce the production train, then you reduce the need for water systems.”

Mr. Ultee at Laureate added, “I still think you’re not going to replace large-scale steel tanks. But most WFI is used for cleaning; if you can avoid that by using tank liners, etc., you can save a lot of capital costs. So that’s the greater driver, not the need to compete with major-scale biomanufacturers, but to develop enough to get into multi-thousand liter production.”

As these systems continue to gain acceptance in the marketplace, we’ll see suppliers continue to innovate to meet the needs of CMOs and biopharma companies. And if biogenerics and/or biosimilars gain true marketing approval, we could see a huge new market for single-use systems. . . .

Gil Roth has been the editor of Contract Pharma since its inception in 1999. He can be reached at [email protected].