Challenges And Innovation In Gene Therapy Manufacturing

By Austin Dower, Manager, and Christian Hermanas, Sr. Manager, Project Farma

Formulating and executing a biotherapeutic development and manufacturing strategy requires a comprehensive evaluation of existing state-of-the-art technology for a given therapeutic modality, as well as the emerging trends that may impact a long-range scale-up plan. Most organizations are limited to technologies that limit them to “scale-out” for expansions rather than scale up. Scale-out is the expansion process of adding trains in parallel, compared to the traditional scale-up process for biologics where sites expand their process with larger and larger bioreactors.

These limitations are largely the result of the novelty of the processes, as much of what has been pioneered at the laboratory scale is still being optimized for larger-scale processes. Additionally, any processes utilizing non-suspension cell lines requires the use of novel bioreactor designs. As the technology and processes continue to develop, the manufacturing models lean towards building parallel laboratory-style production scale-outs.  The labor costs and quality risks that accompany this strategy necessitate additional investigation and investment into the cutting-edge technologies being pioneered for larger-scale cell and gene therapy production. Several trends in the industry have emerged in recent years to meet these demands: single-use technologies, modular cleanrooms, improved bioprocessing to allow scale up and increase yields, and automated processes.