Impact on Facilities
Several speakers focused on the impact of single-use processing on facilities. Robert Steininger, senior vp for manufacturing at Acceleron Pharma, addressed this from the perspective of small or emerging biotechnology firms. His presentation was based on a recent project in which Acceleron assembled a new biomanufacturing plant within a building constructed for metal-working early in the 20th century. The production suites occupy what had previously been the plant’s office space.
While acknowledging the need for “a lot of capital” to produce “boatloads” of a protein, Steininger identified preclinical and early clinical batches as the sweet spots for single use, particularly for designing a facility around disposability and delivered media and buffers. Disposables-only facilities are particularly attractive to contract manufacturers, whose businesses thrive or fail based on responsiveness and controlling production timelines.
Another group that should consider the disposables-only approach is firms that deal with highly potent or toxic drugs, which require very high standards for cleaning and control. “Single use can mitigate most of the cleaning and containment validation associated with these products,” Steininger said.
In specifying single-use-only, the predominant time and cost savings for new facilities involves utilities—particularly water and steam—and associated capital costs. Deployment of single-use equipment exploits the utilities at the supplier’s end, for example water and steam used during media/buffer preparation and storage, and cleaning/sanitizing operations in the manufacture of bags, tubing, and connectors.
“You’re benefiting from the economies of scale at suppliers who can make water and steam in much higher quantity,” Steininger noted. “Of course, since you’re tied into their quality and regulatory systems, you have to buy into the fact that they are reliable vendors.”
The adoption of platform technologies, particularly for monoclonal antibodies, has aided the cause of single-use processing, and with it the emergence of facilities designed specifically for that purpose. Platform technologies consisting of one major upstream operation and two or three predictable separation steps minimize uncertainty with regard to equipment, supply, and facility.
Companies with substantial investment in stainless steel piping can also benefit when expanding or augmenting pipelines with several early-stage clinical or preclinical products. But here the economic arguments become murky if, for example, piping can be introduced easily from an adjoining suite. “It’s tough to ignore your original investment,” Steininger notes.
Scaleup and technology transfer are additional considerations. When large-scale production inevitably occurs in stainless steel regardless of the early-stage production equipment, many established firms prefer to run processes as similarly as possible at large and small scales.
Platform Technology Enablers
Benefits of the platform approach were amply illustrated by a talk presented by Jonathan Royce, bioprocess category leader, bioprocess at GE Life Sciences. Royce walked listeners through an antibody manufacturing project in case-study style, which included a comparison between GE’s single-use ReadyToProcess™ (RTP) manufacturing platform and conventional processing steps. The bottom line: RTP can reduce processing times by half, he said.
Dr. Royce began with the question of what is realistic in terms of directing investment toward disposable processing, particularly for clinical materials. “If you really wanted to do everything in disposable format, you probably could, given the varying degrees of maturity within existing technology,” he explained.
For example, bioreactors range widely in size, formats, stirring, aeration, and other capabilities. Options are also available in the automation of filtration and chromatography operations, but not as many as for fermentation and cell culture. “They still have room to grow, in terms of variety and options, to reach the capabilities of stainless steel. But there is no question that if you were determined, you can do everything in disposable format. The question then becomes, is it worth it, and how do you make that decision?”
A naïve view would conclude that the decision reduces to “mere” accounting, of which examples abound. But this tack is self-limiting, Royce explained, because until recently accounting focused primarily on cost, or more narrowly cost of goods and capital preservation.
“My thesis is that there is a lot more opportunity gain that can be made available through smart investments that either speed the flow of products through the pipeline, or that improve process reliability, than there is money to take out in the form of cost of goods,” he said. “We need to start thinking more of investment to unlock revenue potential—to get more products through the clinic and into the marketplace faster—rather than preserving capital.”
One consideration for optimizing opportunity costs—and for utilizing disposables generally—is how to treat high-ticket equipment such as ultrafiltration membranes and chromatography resins. Here Royce suggested the hybrid approach, whereby equipment is used for a campaign and then discarded, rather than using every last cycle promised by vendor specifications. Ancillary equipment like bags and tubing would be used once and discarded as usual. One area where GE and some of its competitors are already pushing this philosophy is for prepacked chromatography columns.
The hybrid approach can be viewed as a balance between strict single-use, which is often too expensive for high-value equipment, and the difficulties in transitioning high product-contact materials from one molecule to another. Ultrafiltration membranes require time, materials, and personnel to recondition; chromatography columns even more so.
Associated costs may be justified given the high investment in these products. However, the validation burden is significantly higher when switching molecules. These costs, added to safety and quality concerns, may tip the economics in favor of “discarding” the last 20% to 30% of a resin’s or membrane’s usability.
At the same time, Royce cautioned that saving time does not always translate to financial savings. “It works if you can operate with fewer people, or move more product through the plant with the same number of workers. If trading labor costs for increased consumables cost is the only trade-off, it generally makes sense to go through single use.” But saving time at the expense of idle capacity brings no benefit.