July 16, 2020

Next Generation Process Chromatography

Chromatography is an essential part in the production of all biopharmaceuticals. Without it the industry would not be able to produce therapeutics in an economic manner. This is true for monoclonal antibodies (mAbs) that present the modern age in terms of fighting diseases such as cancer and autoimmune conditions. It is also true for gene therapies, which could be considered as the forefront of therapeutic medicine development.

So, what can we see at the frontier of process chromatography?

This week, Bioprocess Development Forum spoke with Dr. Oliver Hardick, business leader in the BioProcess group at Cytiva, about the past, present, and future of process chromatography.

Bioprocess Development Forum: What is the status today for process chromatography?

Dr. Hardick: The chromatography tools have been incrementally improving over the last 60 years. Binding capacities, range of selectivity, and the stability of affinity ligands have been vastly improved. One of the main remaining challenges is that each purification cycle today typically takes >3 hours, and when considering ancillary operations, a typical bioprocess designed today will usually run this unit operation over 2–5 days. As multiple cycles are usually run and setup, cleaning and winddown times contribute a decent proportion of this duration.

Fibro is a new chromatography technology platform that promises purification that is a true paradigm shift. The platform is also compatible with existing installed infrastructure and can fully benefit from single-use operations where this is desired.

Bioprocess Development Forum: Can you shortly describe the background of Fibro and fiber chromatography?

Dr. Hardick: The concept for using nanofibers as a chromatography support structure came from a chance meeting of Professor Dan Bracewell at UCL and Professor Bob Stevens at Rutherford Appleton Laboratory, and myself later became involved as a doctoral student. Within five years, we had developed enough data to justify the formation of Puridify, a spinout company to develop and commercialise the technology. Seven years later, Cytiva (formerly part of GE Healthcare Life Sciences) would bring Fibro to the market following the acquisition of Puridify in 2017.

Fibro is a new chromatography platform that enables the purification of therapeutic antibodies with speed and flexibility, addressing the current challenges of biopharma production, which includes the need for process intensification and manufacturing agility, especially in multiproduct facilities.

The technology is based on cellulose fibers, a material that is designed for multiple cycling and fast mass transfer. It is a connective flow adsorbent, which means purification applications can be run at very high flowrates under positive pressure while carrying out the same purification that are currently achieved with chromatography resins at slower rates. Other convective flow adsorbers have existed in bioprocessing for many years but struggle in different aspects of the separation such as capture binding capacity and dilution of the target product, which have limited their application. The surface area that Fibro exhibits provides immediate binding opportunities at high capacities of the target proteins such as mAbs. This means that a chromatographic cycle that currently takes ~3 hours can be completed in 5 minutes.

This gives the user a choice of either carrying out a very quick purification or utilizing the full lifetime (~200 cycles) of the adsorbent in a single day’s process. Furthermore, as the Fibro technology comes in prepacked formats, the setup time is just a few minutes, which removes the needs to have a preparation day ahead of running the chromatography unit operation.

Fibro uses the same buffers and volumes, as well as the same infrastructure and ligands as resin chromatography, which allow it to be adopted into existing biomanufacturing processes with no process changes or additional capital expenditures.

Bioprocess Development Forum: What are the key main benefits from your viewpoint?

Dr. Hardick: The strongest benefit of Fibro is in its flexibility, which in turn allows the user to design the rest of their process around this flexibility to ensure the greatest productivity of the overall bioprocess chain. If we consider highly efficient multi-tonne processes like the blockbusters of today, then the cost of goods of the process and facility output are already highly efficient. The cost efficiency of mAb production has been driven, thus far, by scale, which has enabled production to reach levels <$100/g. As we move towards smaller patient populations (eventually down to the smallest of one), these scale efficiencies will be eroded, which can lead the biopharma industry to a significant challenge. I believe efforts to drive down costs will need to focus on new technologies that enable new process paradigms, and I think Fibro is a good step in the right direction for this.

The way that users will benefit from Fibro will differ for different customers, or even the same customer at different sites or for different asset processes. At the heart of Fibro, we can think of designing your process without the traditional multi-day chromatography steps, and I am sure biopharmaceutical producers will find benefit in Fibro in ways that we have not even considered.

Bioprocess Development Forum: What are the next steps with the Fibro technology?

Dr. Hardick: With HiTrap™ Fibro PrismA now launched for R&D applications, the teams are working hard to ensure this is followed soon by the launch of the GMP units capable of purifying up to 15-kg mAb in a single day.

Next, we are obviously making the most of this technology being well-suited to the purification of larger entities such as viral vectors for use in gene therapy. We intend to launch both affinity and IEX Fibro Products for this space and aim to capitalize on the rapid process development opportunities that Fibro brings (hours vs. weeks), as viral vectors are much more complicated than designing a typical mAb purification process in a platform approach. There is no protein A equivalent for viral vectors; there is no magic bullet. A toolbox of affinity ligands will be required long term to support the many different viral vector serotypes. The affinity story is definitely something we are heavily developing, and teamed up with Fibro, it would be a great product. However, we also need to recognize that this nascent field can evolve in different ways, so having multiple approaches to the same challenge is important!

Beyond this, Fibro is a platform, and Cytiva has a large library of ligands that we will apply and bring to market over the coming years. The obvious step is to start with bind/elute operations where Fibro has a clear advantage over alternative convection flow adsobers.

I strongly believe that Fibro has a huge potential. We really are at the start of the development journey here and that means there is so much opportunity for future improvement—both for mAbs and other biological targets. Just like single-use bioreactors I believe that the advantages of Fibro are not immediately clear in large scale >500-kg processes but I believe that once end users have experience using this platform in a variety of applications, the adoption of the technology will be very strong.

Tags: chromatography, downstream, Mab