Gene therapy is on the rise. As clinical success, innovation and investment in this area strengthens, Precedence Research predicts that the cell and gene therapy market will grow at a CAGR of 22 percent by 2030. Additionally, the FDA expects it will approve 10 to 20 cell and gene therapy products a year starting in 2025, based on the current clinical pipeline. Minh Hong, Ph.D., head of commercial, viral vector CDMO services with MilliporeSigma, says that this growth is a reflection of the vast potential that gene therapy offers patients.
“As a whole, the industry is booming,” says Dr. Hong.“Unlike a traditional paradigm, where you’re trying to either manage the symptoms of a disease or trying to stop disease progression, cell and gene therapy has the potential to be curative.”
While cell and gene therapy, today, focuses primarily on rare diseases, emerging therapies are targeting larger patient populations and more chronic conditions, which means the benefits could multiply. As that happens, viral vector manufacturing — a critical component in gene therapy, which relies on modified viruses to efficiently introduce specific DNA sequences into cells — is in demand. And MilliporeSigma, which has been manufacturing viral vectors for more than 25 years, including those found in four commercially available viral vector-based gene therapies on the market, has seen an increase in inquiries from biopharma innovators interested in a CDMO partner that can support them from development through commercialization, to bring new treatments to market.
In those conversations, Dr. Hong says his team has found that therapeutic innovators face similar challenges as they navigate this relatively new space. “Even though, as an industry, we have commercial manufacturing for gene therapies, there are still a lot of process and quality unknowns due to individual genes of interest, vector types or process technology employed,” says Dr. Hong. Some common complex challenges that can disrupt, or even threaten the manufacturing and development process include:
- Process robustness. Dr. Hong says that too often, innovators are relying on processes and technologies based on early development work, which may have been designed in academic settings and weren’t built for scale. “The focus changes as a therapeutic moves through drug development into the clinic,” he says. “Implementing a robust, reproducible platform is imperative.”
- Identifying critical quality attributes. While innovators may understand a gene sequence that shows efficacy, Dr. Hong says they haven’t necessarily pinpointed the quality, quantity, potency, and other requirements of the final gene therapy product. “What is the purity you’re looking for? What is the titer you need? What is the downstream application?” he says, adding that these are all critical questions to ask early on in the development process.
- Supply chain challenges. A manufacturing process may look great on paper, but the reality will be different if critical materials are delayed or constrained, or a vendor falls short of expectations. “In this day and age, materials are at times hard to come by,” says Dr. Hong. “As an example, if you're missing one quick-connect for one tubing set and those are on back-order, you can't manufacture.”
- Unrealistic timelines. Any or all of these challenges can impact the timeline to manufacture. Dr. Hong says this is an area therapeutic innovators frequently underestimate when going from early stage to late phase.
To help gene therapy innovators identify and address these risks and accelerate the path to market, MilliporeSigma, which recently expanded its viral vector contract development manufacturing campus in Carlsbad, California, recommends their process evaluation service called the Manufacturing Gap Assessment (MGA). During the MGA, their viral vector experts identify and evaluate improvements in manufacturing, testing, process design, or sourcing to streamline therapeutic production. Depending on the gene of interest and the viral vector being used, Dr. Hong says that they will also suggest incorporating technologies that allow for scalable production; review critical process parameters and critical quality attributes for the desired product; recommend preclinical through commercial manufacturing timeline adjustments because of processes readiness and testing requirements; and address other potential risks such as backlogs or raw material availability.
Innovators who have used the service have said it was valuable to their process. "Undertaking a Manufacturing Gap Assessment with MilliporeSigma gave us a greater understanding of specific operational challenges and steps required for successful technical transfer of in-house production processes leading to implementation and execution of GMP scale production,” explained a recent MGA client in the biotech space.
Biopharma innovators of all sizes—and at all stages—have invested in this MGA, says Dr. Hong. “If you’re an early-stage innovator, we’re able to validate a strategy from a fundraising perspective,” he says. “Or if you have a very aggressive timeline, or you develop aggressive milestones, we can offer a level of assurance whether it’s going to be possible. With later-stage innovators, we can offer process optimization and scale-up recommendations to support the program as it moves from clinical to commercial manufacturing.” With almost three decades of experience in viral vector clinical and commercial manufacturing, he adds, MilliporeSigma has seen what works and what doesn’t work; and has developed long-standing relationships with key suppliers.
As new gene therapies are developed to treat a growing number of indications, patients may soon have access to novel treatment options and potential cures.These innovations take time and investment and there’s a lot at stake. Insights from a trusted CDMO partner can help the next gene therapy reach patients more quickly. “We want to try to remove the art from the science and ensure that the manufacturing is all about the science,” says Dr. Hong.
Learn more about MilliporeSigma’s viral vector CDMO services.
MilliporeSigma is the U.S. and Canada Life Science business of Merck KGaA, Darmstadt, Germany.