A boom in the expansion of contract manufacturing organizations (CMOs) is underway, as these companies brace for the development of viral vectors to satisfy the spike in drug treatments that demand them. But at the moment, there is a worrisome shortage of viral vectors that, by some estimates, means waiting more than a year. Consequently, drug companies are balancing the cost of production delays against the challenges of bringing viral vector production in-house, versus trusting the CMO pipeline.
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Earlier this year, a report by Root Analysis indicated that “since 2000, more than 115 new CMOs have been established in order to cater to the growing demand for novel biologics that have specific manufacturing requirements.” In fact, the biopharma contract manufacturing market overall is expected to grow at an annualized rate of 8.1 percent.
Among the drivers of this growth include the viral vectors required for the development of new drug therapies. From my own observation, it seems that nearly every CMO with viral vectors in their available pipeline is expanding as quickly as they can afford to do, with the anticipated growth curve of viral vector manufacturing over the next five years expected to be as much as 20 percent a year.
This explosive growth in the marketplace is actually driven by a staggering current shortage of viral vector raw materials. As far back as 2017, The New York Times cited Dr. Jim Wilson, director of the gene therapy program at UPenn’s Perelman School of Medicine, as saying that firms exploring new gene therapies may wait for years in line for bespoke viruses.
Anecdotally, we have not heard that 2017 estimate change by much. Our own discussions with industry insiders indicate that pharma companies using a CMO to produce viral vectors may face a wait list of as much as 16-18 months. If you’re a drug company trying to be the first to market, that can be devastating news.
How is the industry reacting to this market phenomenon? What we’re seeing at the moment are larger, more established companies looking to expand their infrastructure with viral vector manufacturing capability. With the assistance of engineering consulting firms, these companies are developing and designing in-house capabilities so that they can to do viral vector manufacturing and R&D on their own. (Will this end up contributing to a reversal of fortunes down the road for the CMO industry, which is staking a large part of its growth on this aspect? The jury is still out.)
Large pharma companies already familiar with monoclonal antibody production may not be too thrown off by the technology required to bring viral vector manufacturing in-house. While the process is different, the manufacturing of viral vectors uses many of the same technologies as mAbs, and the resident knowledge can be leveraged accordingly. For others, however, viral vector manufacturing is uncharted territory.
As the Alliance of Advanced BioMedical Engineering points out, the process of producing vector stocks “must be carried out in a Good Manufacturing Practice (GMP) facility in cleanroom conditions with minimal open processing.” Unfortunately, gene therapy developers usually don’t have GMP facilities to make their own vectors for clinical trials. They see outsourcing as more cost effective than building a new facility.
Smaller companies will need to understand the very basics — from how viral vector manufacturing works to the kind of design considerations that need to be taken into account for the spaces in the rooms.
Entire volumes can be written about initiating the production of viral vectors. At the very highest level, some of the phases of production are the same as for mAbs — cell culture, harvest, purification, and bulk fill. But there are key differences.
Take airflow control as one example. It’s critical to understand and design to optimize pressurization for containment. How do you zone rooms together? How do you maintain boundaries for where the viruses are manufactured and contained? For companies unfamiliar with the particular demands of viral vector manufacturing, it can be daunting to know where to begin.
To manage through the viral vector shortage while CMOs ramp up in capacity, drug companies need to educate themselves on what’s required to produce these critical materials. Until the growth of CMOs allows for production of viral vectors to catch up with industry demand, the drug industry must balance the risk of delay with a thoughtful consideration to initiate in-house production.