Already standard for many biomanufacturers, disposable technology can reduce the risk of cross contamination and save on costs associated with cleaning and sterilisation, but for producing high-volume fast batches in a commercial setting the cost still outweighs the benefits, according to Gerald Kierans, Director of Technical Services at Pfizer.
Kierans, who was speaking at the 13th Annual Biological Production Forum in Dublin, Ireland yesterday, argued that whilst biomanufacturing in the future “will be substantially different to what we have today,” Pfizer is far from eager to switch to single-use systems at its high volume production biologics site in nearby Castle Grange.
The facility – which commercially produces Prevnar and Enbrel, both multi-billion dollar products, as well as growth inhibitor drug Somavert – recently saw a $100m (€73m) investment in order to double productivity, but whilst Kierans said disposable tech has occasionally been implemented to tackle bottlenecks and provide extra capacity, Grange Castle relies on automated stainless steel systems and is “not in a plastic plant mode.”
“If this technology [single-use] remains at the cost level it is at, it actually prevents us from using it and we’d want to stay with stainless steel,” he told delegates.
Whilst vendors claim the benefits of single-use include a lower capital expenditure, in truth this is only the case if the facility itself is capable of sustaining these new systems, he argued, and in fact the implementation and testing of systems can increase production time for set-up and batch production, as could the “complete fallacy” that this technology was near off-the-shelf in design.
However, “if [the technology] could produce much bigger volumes then the unit cost would come down,” he told the room.
“Single-use technology has potential if you get it right and get to a new plateau in terms of productivity. We all [both vendors and end-users] need to step up in terms of application models,” he continued. “If the industry moved to adopt more of this technology then in 8-10 years it could be substantially cheaper than it is today.”
Material Problems and Regulatory Issues
Whilst cost is the deciding factor, single-use is also being held back by a number of other issues, Kierans added.
These centered around the production and material of such systems, with Pfizer having experienced fragile polymers that can potentially lead to breaks and leaks, as well as connections that were little more than tie wraps.
He also cited the limited availability of robust gamma-irradiable sensor technologies, the need to outsource aseptic and material control to others, the low volume in mammalian production runs and the issue of extractables and leachables – an issue Sartorius is trying to combat with a QbD approach to disposable manufacturing.
However, regulatory uncertainty is also a deciding factor as single-use “is as new to them as it is to us,” he said. Under GMP requirements, any visible particles need to be investigated, even if they are polyethylene from the bag and can be filtered out at a later stage.
“Regulators say if you see a particle you need to identify it, so you are going to have to dive in there [the single-use bioreactor] and get it out.” And with both Prevnar and Enbrel clocking sales close to $4bn last year, such batch loss and hold-up is a huge financial strain, said Kierans.