Going Viral

Like mAbs before them, gene therapies have grown in popularity for their potential to treat life-threatening and rare diseases. And with a market estimated to grow to $11.96 billion by 2025 (1), it’s clear that stakeholders believe these therapies are worth investing in.

Though the rapid growth of the sector has been positive for biotechs and patients alike, it doesn’t come without challenges. Increased demand for these products is reshaping the manufacturing landscape. From Pfizer’s recent $500 million cash injection into one of its facilities in  North Carolina (2) to Fujifilm Diosynth’s plans for the expansion of its upstream, downstream, and analytical development technologies for gene therapies (3), there is a ubiquitous awareness that manufacturing practices will have to adapt to appropriately handle the growing field. 

A major (and valid) concern for the budding sector is the dissonance between the growing need for high production capacity of viral particles and the current manufacturing capacities. The manufacturing bottlenecks are two-fold: increasing upstream productivity and overcoming downstream purification challenges in order to increase yield recovery. Increase of upstream productivity is dependent on the transfection of one or more plasmids into host mammalian cells like HEK-293 cells and derivatives, a process that puts a significant amount of strain on the manufacturing process, resulting in struggles to produce them at scale, within designated time frames and with the degree of reproducibility needed to satisfy the expectations of regulators.

An additional challenge for manufacturers is the fact that starting raw materials for the production of virus particles (plasmid DNA and transfection reagent) must be manufactured in compliance with GMP guidelines for their use as advanced therapy medicinal products (ATMP). There are few companies providing cGMP grade plasmid DNA and there were none providing cGMP grade transfection reagent until end of last year with the launch of PEIpro-GMP by Polyplus-transfection.  Moreover, switching suppliers (from non-cGMP to cGMP grade reagents) often involves changing technologies, which can be expensive and time consuming – extending development timelines by months, potentially years. 

But new technology is emerging to help the field progress. For example, from a transfection point of view, we are focusing on new transfection technology to improve product titers and drive down cost. 

Though the issues mentioned are a cause for concern, it is important to remember that the gene therapy field is young and the challenges it faces, in my opinion, aren’t insurmountable. As a more seasoned workforce develops, so too will the technology to support it. The recent wave of investment in facilities, capabilities and staff has been a positive step forward, but whether it is happening fast enough to address this widely felt problem is another question.