Batch to the future: Amid single-use and 100 g/L, stainless steel will continue to shine

Titers are up and single-use is widespread, but commercial drugmakers will continue to use stainless steel bioreactors for unmet medical needs, GE’s Parrish Galliher told BPI West delegates.

Industry convened in Santa Clara, California, for BPI West this week to hear the latest bioprocessing developments and share manufacturing strategies.

While much of the attention focused on productivity improvement and disruptive technologies, Parrish Galliher, CTO of Upstream at GE Healthcare Life Sciences and founder of Xcellerex, told delegates not to lose sight of the role traditional large stainless steel bioreactor tanks will play in supporting future drug production needs.

Image: iStock/Traimak_Ivan

“We grew up with very successful stainless steel facilities for multi-ton capacity. These have produced, as we know, all the blockbusters that we have today,” he told delegates.

Single-use and high titers

The advent of single-use systems and the well-documented benefits it brings has taken some of the shine off stainless steel over the past decade. But when it comes to commercial production, single-use bioreactors have always suffered from size limitations due to pressure challenges from the increased weight of the liquid. (ABEC does offer 4,000 L disposable systems, but 2,000 L is generally viewed as the upper limit among vendors and users).

The commercial issue with single-use is being resolved, Galliher said, through increased titers. “In the last 10 or 20 years, a major advance that’s affected all of us is the improvement of titers in cell culture practices, mainly for antibodies, and it just continues to ramp up.”

Parrish Galliher spoke at BPI West in Santa Clara, CA

He noted the recent announcement from WuXi Biologics that it has achieved cell culture productivity for an Fc-fusion protein of 51 g/L potentially and is confident it can be scaled up using its 4,000 L single-use process.

“We project that based on these rates of titer increases I would expect to see 100 g/L by 2020,” said Galliher.

Steel crazy after all these years

But despite the technology and titer advances, Galliher told delegates stainless steel tanks continue to be used to make the top-selling biologics, as well as produce “very efficiently” the biosimilar products which have entered the market over the past decade.

This will continue in the short and long-term, he continued, especially as new biologics to treat high patient population diseases such as Alzheimers, dementia, cancer and diabetes move through the clinic.

“We’re going to need them [stainless steel systems] for unmet medical needs, which have potentially very large capacity requirements for these diseases. So we see stainless steel being a major player going forward and helping us to address the mega-ton capacities that are going to be required.”

His views are backed up by recent investments, in particular from contract development and manufacturing organizations (CDMOs), in stainless steel tanks. While the likes of WuXi, AGC Bio, Patheon and Catalent continue to expand their single-use capacity, some of the largest investments have been in fixed stainless steel systems by Celltrion, Samsung BioLogics, and – announced this week – Fujifilm Diosynth Biotechnologies.

Speaking to BioProcess Insider in August last year, Samsung BioLogics that biosimilar contracts “will be helpful to utilize our facility” last August. And earlier in 2018, CEO TH Kim told this journalist the risk of under-capacity in his CDMO’s 360,000 L of stainless steel tanks will be low due to the new therapies for high patient population diseases referred to by Galliher.