The viral vector technology behind COVID-19 vaccines developed by Johnson & Johnson and AstraZeneca PLC is challenging to manufacture at scale, and the pandemic has strained supply chains that also serve the growing field of gene and cell therapy.

A viral vector is a modified virus used to deliver genetic material into cells. In the case of vaccines from J&J, AstraZeneca and China's CanSino Biologics Inc., as well as Russia's Sputnik V vaccine, the viral vector delivers genetic information that kickstarts an immune response to prevent COVID-19 infection.

These four vaccines, which emerged in late 2020 and early 2021, joined a list of gene and cell therapies that also make use of viral vectors, and data analytics and consulting company GlobalData forecasts 100 more of these therapies will be approved in the next six years, according to a May 24 report.

That number of approvals is likely to overload the relatively new and complicated manufacturing process that requires specialist facilities to supply the needed viral vectors.

Viral vector gene and cell therapies approved in the U.S. include Novartis AG's Zolgensma for spinal muscular atrophy and Kymriah for leukemia; lymphoma drug Yescarta from Gilead Sciences Inc.'s Kite arm; and vision loss therapy Luxturna from Roche Holding AG's Spark Therapeutics, among others. Additionally, two Ebola vaccines from J&J have been approved in Europe.

But the biopharma industry is developing a vast number of viral vector-based therapies and vaccines with more than 3,000 in the pipeline, according to GlobalData. A large majority of these are still in the preclinical stages and many years from reaching market, but the need for viral vector manufacturing is poised to grow exponentially, GlobalData PharmSource Associate Editor Fiona Barry told S&P Global Market Intelligence.

"This bottleneck has been brewing for a while, long before the pandemic," Barry said. "But any investments now are only going to be good, because aside from the current pandemic, we're always going to need vaccines for other infections."

Pharmaceutical companies that depend on viral vectors for existing or upcoming therapies and vaccines are scaling up facilities and developing more efficient processes, while contract manufacturers are building new sites, Barry said.

Some of the leading life sciences companies have invested in viral vector technology with acquisitions in the space, such as Thermo Fisher Scientific Inc.'s January purchase of Henogen SA, the viral vector manufacturing business of France's Groupe Novasep SAS, for about $880 million.

And in May, Charles River Laboratories International Inc. picked up viral vector specialist Vigene Biosciences Inc. for $350 million.

Other large-scale manufacturers of viral vectors include Catalent Inc. and Emergent BioSolutions Inc., although Emergent has faced challenges due to contamination concerns at a plant in Baltimore that produces the J&J COVID-19 vaccine.

Slow start for new tech

The viral vector bottleneck is not the result of a lack of investment on the part of manufacturers but rather the novelty of the technology, Barry said.

"It's just a new technology, relatively speaking," Barry said. "It's really comparable to biologics manufacturing of monoclonal antibodies, which are maybe a generation or two ahead — when they first came out, it was a slow process to make them."

A revolution in manufacturing monoclonal antibodies in a much faster way has led to drugs like AbbVie Inc.'s Humira becoming the best-selling treatment in the world, despite a challenging biological process at its core.

This could end up being the case for viral vectors, but the revolution will require standardization of processes along the way as well as viability from a cost perspective, Barry said.

Peter Marks, director of the U.S. Food and Drug Administration's Center for Biologics Evaluation and Research, addressed the challenges of gene therapy manufacturing in a March 2020 discussion.

"Manufacturing in this area is really a challenge," Marks said. "We're still making vectors much the same way that we made them at the turn of the millennium, and we really need to figure out how to move that forward."