(131g) Challenges in Membrane Separations during Production of Viral Vectors for Gene Therapy

The development of reliable, scalable production processes for viral vectors is a key challenge in the rapidly emerging field of gene therapy. The aggressive timelines often planned for the development of these treatments lead to a limited fundamental understanding of the key separation operations. Consequently, these processes can be costly, inconsistent, and inefficient, with recovery in downstream purification trains as low as 20 percent or less.

In this presentation, an overview is presented of the role of membrane separations in the purification of viral vectors such as lentivirus and adeno-associated virus for gene therapy, including ultrafiltration/diafiltration, chromatography, viral safety, and sterile filtration steps. Particular emphasis will be given to the key technical challenges common across the industry, with perspectives of how in some cases membrane processes provide unique opportunities to solve these problems while in other cases there are significant barriers to their successful implementation. For several unit operations, specific case studies and supporting data of ongoing research will illustrate low recovery and other performance limitations often observed during process development as well as some of the potential underlying causes. This overview and case study are intended to highlight the specific needs for increased research in this emerging field as well as to challenge some of the preconceptions surrounding the limitations of membrane processes with viral vectors.