Written by expert: Evert, Associate Director DSP
With the first gene therapies now being on the market, the production quantities for gene therapy vectors are increasing to satisfy the demand. A steady increase of product titers and the corresponding change in impurity composition represent a challenge for development and optimization of viral vector production processes. The availability of purification processes, or downstream processes (DSP), capable of handling these increasing quantities and concentrations are becoming a bottleneck for many manufacturing processes. The DSP should deliver viral vectors with levels of purity and biological activity at par with regulatory standards. It should be irrespective of the permeations inherent in any USP process.
Advancements in downstream processing of viral vectors
Viruses far exceed the dimension of proteins used in pharmaceutical applications with respect to weight and size. Therefore, purification of viruses is more complex than simply ‘plugging’ viruses into existing protein purification schemes. This will not yield adequate results. For example, in chromatography the traditional bead chromatography methods are not ideally suited for most viruses; due to the size of viruses, which diffuse much more slowly compared to proteins. Additionally, viruses may be excluded or be entrapped in the chromatographic bead pores. These pores normally contain the majority of binding sites. Also, viruses, being complex macromolecular assemblies, have significantly lower titers compared to proteins. Therefore, the ability to handle large volumes is also beneficial and is limited in traditional beads.
More recent innovations, such as membranes and monoliths are much more suitable for viral applications. This is, for example, due to their accessible binding sites and large pore sizes. Moreover, they do not rely on diffusive transport. Membranes and monoliths also have benefits in containment, because they can be single-use and pre-packed, while traditional columns are often packed by the operator. Other benefits of the non-traditional methods over the use of beads are lower buffer consumption, due to the relatively small bed volume and lower process times, owing to the high flow rates that can be employed. The only downside of membranes is a lower resolution, but for many virus-based products a high resolution is not required.
Future needs in DSP
These non-traditional chromatography methods are already able to tackle part of the DSP capacity bottleneck, but at Batavia my team and I are working on new innovations to meet future requirements and cope with the increases in USP productivity and market requirements.
We are dedicated to help bring biopharmaceuticals to the market at higher speed, with reduced costs, and with a higher success rate. Batavia Biosciences has vast experience in producing and purifying viral vectors. Our experienced DSP-experts are well equipped to take on any challenge associated with purification of biopharmaceuticals.