In an industry as dependent on cutting-edge technology as bioprocessing, there will inevitably be a huge range of ever-changing challenges facing manufacturers. However, for Parrish M. Galliher, CTO Upstream at Xcellerex at GE Healthcare Life Sciences, one issue currently stands above all others: “The biggest challenge right now is the rate of change of drug design.”
Galliher describes how as drug diversity increases, “so the timescale to respond from a manufacturer’s perspective must by definition shrink…The manufacturer’s tool chest is beginning to be pressed for technologies that afford speed of change and many facilities being built are increasingly at risk of becoming obsolete.”
And it’s not just the speed of change that is causing challenges for manufacturers:
“There’s increasing diversity in the process architecture entering the scene as pipelines evolve past traditional full size mAbs. Even within large drug companies that have legacy blockbuster mAb stainless steel facilities, there are now cell therapy companies making drugs at the bench scale.”
All this is exacerbated by the fact that the regulations mean the industry is a “fairly conservative space” so it’s “not an environment where you can turn on a dime and modify your plant. It takes a year or two to modify traditional facilities, and two to three years to build them from the ground up.”
Furthermore, in Galliher’s mind, this isn’t a challenge that is going to change any time soon; quite the opposite in fact:
“It’s a realistic outlook to accept that diversity is going to continue and the rate of change will increase. Genomics and personalized/precision medicines are really starting to get going and if you play that out, it means we’ve got nearly seven billion genomes to treat since we’re all different. As medical science goes in that direction, we’ve got to expect diversity in drug design and host/vector expression systems to increase.”
Manufacturers therefore now find themselves in an environment where the product is changing faster than the technology can be built, regulations make it difficult to change strategy quickly, and the challenge is only going to increase in coming years. So, what exactly can manufacturers do to combat this?
“Reducing the possibility of obsolescence of our facilities and technologies”
When approaching the issue, Galliher believes that unfortunately there is no single solution for manufacturers “in terms of what process architecture would you bet on, what type of facility would you build, how big it would be and where you would build it”. He adds that: “The likelihood of finding a panacea process technology or approach that sets you up for anything is very low based on the history of manufacturing technology within this industry. For example, there’s still the potential for anything from a super-potent autologous cell therapy, to that product becoming a blockbuster, going allogeneic and requiring enormous facilities.”
However, that’s not to say there are not smart moves manufacturers can make when planning facilities. Galliher recommends that the first vital step should be defining your focus: “You should firstly try and narrow the class of molecules, the host/vector expression systems that you want to work in and the disease indications that you want to focus on, and secondly think about the scale your chosen therapy could require down the road.”
Whilst this essential first step can improve the effectiveness of the initial designs, the unpredictable future of the industry shouldn’t be forgotten. Galliher highlights how manufacturers should expect and be ready to repeatedly adapt and change any facilities, and should therefore remain as agile as possible. He explains:
“Manufacture light. Don’t build facilities that need a 10-15 year life to pay for themselves – that time-constant is totally inconsistent with the time-constant of change in the industry in regards to what can happen to drugs in the clinic and the speed of which drug design is advancing. You should approach it like camping: you should pack light. Building stainless steel technologies is much more risky than building with a technology that is easy to change, easy to rip out and throw away in the event that your drug fails in the clinic or some other curve ball hits you whilst you’re in clinical development. Keep it simple, design it to be rapidly re-configurable in a ‘plug-and-play’ manner so you can respond quickly to rate of change.”
With drug diversity at an all-time high Galliher also emphasises that the perfect facility that can meet the demands of every drug type and scale is not possible:
“There should be a certain palette of technologies in your toolbox that will follow the 80:20 rule. 80% of drugs have very similar unit operations for the manufacturer and they just differ in scale. As scale continues to collapse, that 80% will become the focal point of many process designs.”
Ultimately, the speed at which the bioprocessing industry is changing is both hugely exciting and hugely challenging for manufacturers. Drug diversity is only going to continue to increase and the future will remain near impossible to predict. However, by following a few simple rules the risk can be minimised, and having the advice of experienced professionals like Parrish Galliher certainly helps too.