Can Single-Use Technology Be Used In Protein Purification?
By Trisha Gladd, Editor, Life Science Connect
One major advantage of single-use technology are the lower costs associated with the implementation of disposables, such as the smaller footprint and the reduction in operating costs. However, not all areas of the drug development process have been able to be transferred to a single-use platform. One of these areas is protein purification. I recently spoke with Iwan Roberts, chief operating officer and co-founder of Puridify, a company developing bioprocessing technologies for biomolecule manufacturing, about this challenge in the industry and what can be done to overcome it.
Gladd: Why is it a challenge to successfully use single-use technology in protein purification?
Dr. Roberts: The packed columns used today in the primary/product capture stage of the drug manufacturing process are large and very expensive. You have to amortize the initial investment of those packed columns over multiple batches in order to pay it off. You see some people using pre-packed columns and plastic housings, which yield certain benefits in terms of validation effort and flexibility. But the productivity of these packed columns fundamentally limits them from being cost-effective in a single-use fashion.
Gladd: What can be done to overcome these challenges?
Dr. Roberts: New product capture approaches are required that give the same separation performance but that don’t fundamentally change operations in our highly-regulated industry. Multicolumn chromatography systems and convective flow adsorbents are ways to increase productivity per unit volume, moving us towards a scenario where single use operation is economically feasible.
Gladd: Why would an end-to-end single use process be so impactful?
Dr. Roberts: It’s an increasing trend for drug manufacturers to explore running multiple products in a facility to adapt to inherent uncertainties in drug development and improve asset utilization once commercialized. Key to this shift are single-use systems, which increase facility productivity, because they’re able to offer fast turnarounds by reducing validation and increasing flexibility as there is minimal fixed infrastructure.
However, in downstream processing, to handle titers that have raised hundreds to thousands fold in the last few decades, larger and larger chromatography systems have been used as an attempt to keep up (some reaching up to two meters at production scale). Incremental technology improvements with respect to binding capacity and flowrate have avoided chromatography becoming a killer bottleneck, but this has stifled innovation. So, industry has been left with this huge column that’s incredibly expensive and practically cumbersome. By having a single-use product capture stage, you no longer have a large column that requires moving in and out of your processing suite between campaigns or between products. This can increase plant productivity and, ultimately, improve how plants are operated and designed, such as multi-product, geographically local or rapid response manufacturing.
Gladd: What technologies are you exploring at your company to overcome this challenge?
Dr. Roberts: We have developed a single-use nanofiber chromatography technology that utilizes ligands like Protein A more effectively. A combination of high flowrates and high capacities allows productivity in terms of grams of product purified per liter of adsorbent, per hour to be maximized. In practice, this means for an equivalent bioreactor harvest, a smaller unit like ours can be used to purify the same load through rapidly recycling. As a smaller unit is used, the economics are such that the unit can be disposed of afterwards. The units are pre-loaded with adsorbent and are compatible with existing equipment, so suited to end-to-end disposable operations. The solid nature of the material simplifies scaling, and with each purification run taking only a few minutes, process development is faster.
Gladd: Are there any trends you think will be problematic for the growth of single-use technology in 2016? Are there any that you think will accelerate its adoption?
Dr. Roberts: The regulatory bodies are being supportive and encouraging early interaction to avoid later stage show stoppers. In addition to this, the drug manufacturers and suppliers are making efforts to standardize the performance and compliance criteria of single-use products. Although there is some way to go, this is certainly going to help further the growth of single-use technologies. Fully-integrated, continuous manufacturing is another area that has strong growth potential, and I believe that single-use technologies have their part to play in supporting those processes. Single-use is never going to be the right choice for every drug manufacturer or product, so it’s not the be-all and end-all of bioprocessing development. However, it does fit with many of the evolving needs of the industry, so we think it’s here to stay.