Optimizing Vectors to Standardize Success

An important aspect of regenerative medicines is optimizing the supply and manufacturing of important components, such as viral vectors, which are crucial for the delivery of cell and gene therapies.

Improving yield of viral vectors will primarily be achieved via scale-up, process improvements, and cell line development, says Emily Moran, senior vice-president of Vector Manufacturing and Supply Chain, Center for Breakthrough Medicines. Scale-up will go from the standard 200-L volume to 2000-L volume. Process improvements include alternating tangential flow filtration (ATF) on the production bioreactor, novel DNA for transfection, improved primary and polishing chromatography columns, and improved drug product formulation, Moran emphasizes.

In terms of producer or packaging cell line development, a combination of integrated adenoviral helper (i.e., Ad helper) genes, replication/capsid genes (i.e., rep and cap) and/or gene-of-interest to reduce/eliminate plasmid need will be needed to improve yields, Moran adds.

The scale-up and process improvements are expected to result in significantly increased batch yields and significant reduction in cost of goods (COGS), Moran says. These improvements would enable cost reduction for developing a single product and enable the ability to treat higher and/or repeat dose targets, she explains. In the end, patient access to these therapies will likely improve as the COGS goes down and overall throughput is improved across manufacturing facilities.

Another goal in the quest for improving viral vector yields is the standardization of manufacturing, Moran points out. Standardization includes implementing a similar order of unit operations, process technologies, and control strategies across manufacturing processes. Such standardization would enable improved consistency of the quality profile of viral vectors (e.g., adeno-associated virus-based vectors) going into humans as well as the ability to connect product attributes to clinical outcomes, Moran explains.

Other benefits of standardization include the improved ability to compare clinical outcomes across products from different companies; reduced investment in process/analytical/preclinical development, allowing for investment of more products; and the streamlining of the supply chain from a materials perspective for both development and manufacturing activities, which would increase speed to market and decrease cost, Moran states.

Currently, near patient manufacturing is an increasingly urgent goal. Proximity to patients reduces vein-to-vein time, which, in return, should improve patient access and outcomes, Moran emphasizes. Furthermore, having decentralized networks can improve product access and availability. The latter may come at a higher cost and increased variability in quality, however, due to distributed manufacturing, Moran concludes.

About the author

Feliza Mirasol is the science editor for BioPharm International.

Article details

BioPharm International
Vol. 36, No. 2
February 2023
Page: 11

Citation

When referring to this article, please cite it as Mirasol, F. Optimizing Vectors to Standardize Success. BioPharm International 2023, 36 (2), 11.