Earlier this week, GE Healthcare debuted a "factory-in-a-box" designed for the speedy and adaptable production of viral vectors, the delivery vehicle that underpins many of the cell and gene therapies in development today.
Dubbed KUBio, GE's modular manufacturing facility is a redesigned model of a unit GE currently sells by the same name to manufacturers of monoclonal antibodies.The new viral vector unit is part of the corporate giant's bet that providing production tools to makers of cell and gene therapies will be a lucrative business.
A KUBio unit is a standalone building containing what GE calls a FlexFactory — its take on a single-use biomanufacturing platform.
In most of the other FlexFactories GE has sold around the world, by comparison, companies build their own buildings, or retrofit an old facility. At present, GE has more than 40 FlexFactories, with 15 of them in the U.S., said Parrish Galliher, chief technology officer of upstream bioprocess at GE Healthcare's Life Sciences division, in an interview Tuesday during Interphex 2018.
So far, only three KUBios for the production of monoclonal antibodies have been sold — one to Pfizer Inc. in China, another to JHL Biotech Inc. in China, and a third to an undisclosed client.
While GE has not yet sold one of its newer-model KUBios, the new units are designed to be biosafety level 2-compliant, which allows for the production of viral vectors from human cell lines. By virtue of this designation, the units can also be used to produce vaccines, cell therapies and — according to Galliher — some gene therapies.
This type of modularity isn't new. But it's making a comeback, boosted by a growing emphasis on single-use technology, says Galliher. Single-use has eliminated 90% of the piping inside legacy facilities, among other benefits, so newer modules are much cheaper to build, ship and install.
BioPharma Dive sat down with Galliher to discuss how the new units affect production costs and where GE's future focus in the bioprocessing realm will lie.
The following interview has been condensed and edited for clarity.
What is GE's future focus and how do the new viral vector suites fit into that?
Parrish Galliher: Our strategy is to leverage our current technology offering into this space, and we're doing that very aggressively. So instead of investing an enormous amount of money in R&D to create new products that are just targeted at vector production or cell therapies, we see immediately how to apply what we're already building and selling to customers around the world for making antibodies to the cell and gene therapy folks. We sold a FlexFactory for cell therapies to a company in China.
What types of modular units does GE plan to release in the future?
Galliher: We've done a lot of work in the microbial space. The industry is moving to smaller molecules that can be produced in non-mammalian expression systems such as yeast, insect cells, bacteria, etc. Those types of cell lines require a different type of bioreactor called a fermenter. We began developing a fermenter in 2005 and launched a 50 L around 2010, and last year we launched a 500 L. We have been preparing for the future of alternative expression systems and cell lines to produce biologics and vaccines.
For instance, a number of subunit vaccines are produced in bacteria. We've laid the groundwork to be able to support that new field as it grows through the industry.
Why do you think that is?
Galliher: Because it takes two weeks to grow a mammalian cell line, [they are] very susceptible to contamination, media is very expensive, equipment is complicated. Escherichia coli grows in two days. Now the trick, of course, is purifying the drug out of the E. coli — and that is probably less efficient than purifying antibodies from CHO cells — but we'll figure that out. And if you can get it down in yeast, they secrete [your product] — now you have a simpler purification scheme.
But it's not all slam dunk. Glycosylation has to be figured out, purification techniques, efficiencies, cost of goods… the challenges are more downstream for purification. But in the cell line, if you have a CHO making an antibody, and now you are going to make that antibody in yeast, the yeasts are going to put different sugars on that antibody, so that's a problem. It's not just downstream that's a challenge; it's also potentially the upstream.
But there is so much pressure on the industry to increase efficiency and throughput and do it in smaller and more productive systems — this is why microbial systems are getting a lot more attention now.
Have there been head-to-head studies on products made with GE's FlexFactories versus those made in traditional manufacturing settings?
Galliher: The pharma companies runs head-to-head studies. Shire purchased a single-use production line for a drug that was already on the market — Vpriv [velaglucerase alfa for injection] — and they had to demonstrate it was equivalent or biocomparable to the drug that was on the market. They were successful at doing that. They are now licensed by FDA and EMA for that single-use production plant.
In that case they had all this historical data of making the drug in stainless steel and wanted to expand capacity. They were at 500 L stainless steel, and we scaled them up to 2000 L tank — scaled the process up fourfold.
Another company just completed their single-use facility in Singapore. That drug was being produced in a stainless-steel plant ... they brought that drug to the Singapore plant and demonstrated they could produce it to be comparable.
How much does cost of goods play into cost of cell or gene therapies?
Galliher: Vector production is pretty much independent of the patient [in large-scale, off-the-shelf production]. It's not patient-driven, so you can scale up to get economies of scale. We are applying our knowledge and experience of making antibodies and other drugs for the last 40 years to the whole business of making vectors.
Increasing cell densities, yields, improving media formulation, improving purification yields — all the things you want to do to maximize the productivity of your process — those all apply to making vectors. That's why my advice to the company is not to solely bet the farm on autologous cell therapies — while autologous is growing fast with a lot of potential, there are also many other growing areas within the space. There are already two companies that have published that they are going to allogeneic.
Can FlexFactories help to bring the cost down of some of these cell and gene therapies — and will the cost savings be passed onto patients?
Galliher: If you look historically at biologics, prices have gone up two- or threefold over the last 10 years, and the cost of goods has been coming down because of all the efficiencies that people are applying. There is no connection between the cost of goods and sales price.
Is the vector business a long-term opportunity, then?
Galliher: We see that long term. Full-length antibodies, antibody fragments are next — there are more of those in the clinic now. Fusion proteins, antibody conjugates, and bispecific antibodies as well. They are smaller molecules in general, which is why I think people are thinking about alternative expression systems.