A wide range of new technologies offers the next generation of oligonucleotide manufacturers a choice in how they will commercially manufacture their products. That’s the view of a technical expert with experience working with small biotechs and large pharmaceutical companies.

According to Barrie Cassey, PhD, a former technical director at GSK, the tide of oligonucleotide therapies now reaching the clinical stage is driving companies to commit to cheaper high-production techniques, such as enzymatic ligation.

“What’s driving this technology is the ability to make [oligonucleotide therapies] at scale,” he says.

According to Cassey, most oligonucleotide drugs are currently produced by solid-phase techniques, but the capacity for commercial manufacturing is limited globally, with most therapies being for rare disease patients. However, looking at products in Phase III, 40% target large patient populations, Cassey says, and this rises to around 50% for products in Phase II.

“If you extrapolate, assuming 70% of these Phase III assets become commercial (which is pretty conservative), your total demand could rise to six to seven tons globally, which is more than all global capacity today,” he explains.

Overall, within eight years, global manufacturing demand could reach as high as 30 tons—far outstripping current manufacturing capabilities, Cassey says. Moreover, drugs targeting large patient populations (e.g., statins) have traditionally needed to be cheap to manufacture, he says.

To get around this, large pharmaceutical companies are increasingly looking at new techniques for oligonucleotide manufacture, such as experimenting with fragmentation versus whole molecule approaches. One company has invested $250 million in a manufacturing plant using enzymatic ligation, Cassey adds.

Overall, Cassey says, the take-home message is that new techniques are closer than many people think, with some companies already offering them for preclinical manufacture.

“These technologies are almost ready to go and, if someone wanted to use them in twelve months, it might be possible,” he says. “It’s just about getting the right conditions for everything to coalesce together.”