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Bristol Myers Squibb’s cancer cell therapy Breyanzi. Johnson & Johnson and AstraZeneca’s recombinant COVID-19 vaccines. Novartis’ gene therapy Zolgensma. All of these, plus many others, are united by a common element of production—viral vectors. That’s creating big problems for the industry.

Viral vectors are engineered viruses used to deliver gene therapies, gene-modified cell therapies—such as Novartis’ CAR-T Kymriah—and certain vaccines. And their shortage is already upon us, thanks to manufacturing approaches that simply haven’t kept pace with the advance of cell and gene therapies.

Add to that the role of viral vectors in AstraZeneca and Johnson & Johnson’s COVID-19 vaccines, plus a looming wave of new drug approvals, and the bottleneck is due to tighten even more. That’s unless regulators, biopharmas and contract manufacturers step up in a big way, GlobalData said in a recent report.

Many CDMOs in the vector field have been sounding the alarm. When VIVEbiotech sketched out a 400% increase in vector production in Spain, CEO Gurutz Linazasoro cited a “significant increase” in demand.

And Byung Se So, CEO of fledgling CDMO Matica, put it even more bluntly in a recent statement: “The global demand for virus products continues to outpace the capacity for production.”

Vector capacity vexed
Even as cell and gene therapies advance rapidly through the clinic and reach the market, viral vector manufacturing is “maybe a generation or two behind something like monoclonal antibody manufacturing,” Fiona Barry, associate editor at GlobalData’s PharmSource, told Fierce Pharma. The industry’s monoclonal antibody production quickly became “more standardized” and “partially automated,” she said.

“That’s the kind of revolution that we need for viral vectors,” she added.

As it stands, strained capacity, inefficient manufacturing and the need for complex, specialized facilities have all played a role in the shortage of viral vectors, GlobalData said.

All told, 14 gene therapies, gene-modified cell therapies and recombinant vector vaccines are already approved and sold in Europe, Japan, the United Kingdom and the United States, according to the report.

Over the next six years or so, 100 or more vector-hungry cell and gene therapies are expected to cross the regulatory finish line. Once those therapies launch at commercial scale, the viral vector bottleneck will really close in, Barry said.

Meanwhile, the “more immediate stress” on the viral vector supply chain is the demand stemming from COVID-19 vaccines—including Russia’s Sputnik V and Cansino’s Ad5-nCoV—GlobalData points out. While mRNA shots from Pfizer and Moderna were the first to reach the public in the U.S., many other countries are depending on vector-based shots, which are cheaper to make, easier to produce and simpler to transport than mRNA vaccines.

While initially turbulent vaccine rollouts have smoothed in places like the U.S. and the U.K., that certainly isn’t true for much of the world, Barry noted. The world still has “billions of doses to go,” she said.

Delivering a solution
To crank out enough viral vectors to meet “near-future need,” the industry would need 3 to 6 billion liters of bioreactor capacity a year, GlobalData figures. It currently has less than 1% of that.

Addressing the shortage will take a two-pronged approach, Barry estimates. The first, and perhaps the most straightforward solution, is for companies simply invest and scale up, she said.

Major CDMOs—such as Catalent, Thermo Fisher and Lonza—as well as Big Pharmas Johnson & Johnson, AstraZeneca, Bristol Myers Squibb, Gilead Sciences and Novartis have all been making moves in this arena, whether through facility and equipment investments or M&A.

Take Thermo Fisher, for instance. The CDMO made its first gene therapy foray—but certainly not its last—back in 2019, when it snapped up viral vector producer Brammer Bio for $1.7 billion. Then in January, Thermo Fisher laid out $878.2 million in cash for Novasep’s viral vector manufacturing division, Henogen.

Novasep, for its part, inked a multiyear pact with AstraZeneca in November to chip in on large-scale production of adenovirus vector for its COVID-19 vaccine.

Major drugmakers such as Gilead and Sanofi have gotten in on the action, too. In July 2019, Gilead’s Kite Pharma blueprinted a 67,000-square-foot facility in California to churn out viral vectors for use in CAR-T therapies like its own Yescarta. Until then, the company had relied on contractors.

Later that same year, Sanofi, lagging its peers in the gene therapy arena, said it would retrofit a vaccine plant in France to work on vector-based gene therapies.

Still, it’s not “enough to just build out, build out, build out,” Barry explained. The industry also needs to introduce serious improvements to manufacturing efficiency and getting there will take expertise and innovation. Regulators getting behind standardized viral platforms could be another boon, she added.

Biopharmas and contract manufacturers are already hard at work on upgrades to the viral vector manufacturing process, GlobalData noted. Change is needed both upstream and downstream, Barry said, with the upstream phase—the stage at which cells are grown—particularly lacking. Changes there could come in the form of better cell lines, suspension cultures and upsized scale.

Meanwhile, the FDA’s Peter Marks, who directs its Center for Biologics Evaluation and Research, has previously voiced support for standardized viral vector platforms, Barry pointed out. What many experts want to see is the introduction of standardized platforms that biopharma developers and CMOs could deploy. That could in turn shorten R&D time and make it easier for contractors to switch between products, she said.

by Fraiser Kansteiner

Source: fiercepharma.com