One could summarize all objections to disposables with one question: Is product produced in a plastic container of the same quality as that manufactured in more traditional stainless steel and glass bioreactors? Biotechs and contract manufacturers, whose very existence depends on consistency, have embraced disposables but temper their enthusiasm with due diligence.
Mid-sized CMO Avid Bioservices has “always” used disposables for storage and buffer prep, says Rich Richieri, senior vice president of manufacturing, but the company is taking its time in validating disposable bioreactors. Avid has been particularly focused on maintaining traditional bioreactor geometry and making sure that the cells were mixed and sparged in an equivalent manner. So far everything checks out.
Last November, Avid began comparing batches run in 1,000 L single-use bioreactors with product produced in its three stainless steel tanks. “We haven’t noticed any differences so far through typical lot-release testing,” Richieri notes, “but our next campaign will look much more deeply into extractables.” Leachables and extractables from bags have been on the worry lists of every biomanufacturer, bag vendor, and all major regulatory agencies.
As a mid-sized manufacturer, Avid is perhaps emblematic of that middle ground in process volume, where battles between steel and plastic are ongoing. Jeff Jackson, sales director at Bosch Packaging, recognizes this fuzzy divide.
According to Jackson, Bosch has introduced the industry’s first filling line with fully disposable product contact surfaces. The company also sells traditional steel reusable systems, though. “There comes a point—and I can’t say specifically where that is—where costs associated with acquiring and setting up a dedicated filling machine become burdensome.”
The amortization of those costs, he says, works better for a run of one million vials vs. a 20,000-vial run. “If you’re producing a large number of doses of a single product, there is no chance of cross-contamination and you only need one dedicated set of hardware, or perhaps one backup as well. You wouldn’t have a huge investment in dedicated contact parts.”
It has been argued that the purchase of used equipment could make steel bioreactors even more cost-effective, over lifetime use, than disposable bags, while amortizing the environmental impact of producing the steel and fabricating it into a GMP-worthy vessel even more favorably. Generally, the arguments for used equipment can be quite compelling: used equipment is widely available, is significantly less expensive than brand-new, and the environmental hit for its manufacture has already been taken.
Moyer believes this is a gross oversimplification. While quality used products can be had for a song in non-GMP industries, biomanufacturers are extremely wary of purchasing used equipment with a high product contact profile for making drugs. On the most basic level, a bioreactor must fit a manufacturing suite and have specific utilities serving it. Knocking down walls, raising ceilings, and rearranging the plumbing are themselves capital expenditures.
Reliability is an even more serious issue. “By the time a company goes under or otherwise disposes of capital equipment, there is usually no one around who can find the documentation,” Moyer says. Under pressure to close the facility and get everything valuable out the door, large steel tanks would likely be dismantled by low-level technicians or simply get torn out. Parts get left behind or mishandled, creating a nightmare for reassembly. “The longer it sits, the more likely it will be sold by the pound,” he adds. “It’s difficult to resell this type of equipment to a GMP industry.”
End-users are loath to spend precious resources reconstructing and recommissioning a complex piece of equipment. Moyer notes the psychological factors that come into play: Even if a bioreactor is returned to apparent working order, the manager who decided to purchase it would be on the hot seat for many months for any problem that arises.
In short, it is hard to find a discouraging word regarding disposables that actually sticks. The marketplace is vibrant and expanding through start-ups, partnerships, and, paradoxically, the acquisition of single-use technologies and entire companies by vendors whose reputations were built in glass and stainless steel bioreactors.
Despite raising numerous problems, Moyer is an unabashed convert to disposables. “I’ve worked with stainless steel tanks for a long time, but now my eyes have been opened to disposables. It’s a significant change, but even large, risk-averse companies have jumped on the bandwagon. There’s no doubt that any biomanufacturer operating below a couple of thousand liters should consider disposables.”