When Marc Gaal meets people whose lives have been changed by gene therapy, he gets emotional. As the director of program management for viral vectors, Gaal has worked in MilliporeSigma’s viral vector manufacturing business since 1995, so the industry’s progress feels personal.
“Gene therapy is now seeing the curative efficacy that it once envisioned 30 years ago,” he says. “These therapies are in real people, and there are dozens of case studies out there and patient profiles that we share to motivate our team. We’ve had patients who have received the therapy we supported come and visit. It puts a tear in our eyes, and inspires us to do our best.”
Gaal was originally hired as the businesses’ second employee. Back then, he mentions, researchers were making advances using viral vectors in gene therapy, but they needed help in manufacturing the viruses. “A group of seven of us built a clean room right on the University of California, San Diego campus with the intent to produce clinical-grade vectors for the researchers on campus,” he recalls.
Leap ahead to today, and there are 23 commercially approved gene therapies on the market, four of which are supported by MilliporeSigma. In addition, the team has made more than 1,000 viral vector batches for more than 200 clients, and it’s passed nine inspections by six global agencies.
As the gene therapy industry evolves and demand grows, biopharma innovators are learning, first-hand, the complexities of manufacturing. Gaal says the expert guidance of a contract testing, development, and manufacturing organization (CTDMO) such as MilliporeSigma provides support from early development through commercialization, to bring new treatments to market.
“Our sole purpose is to manufacture these products under the highest quality standards so that the patient can receive that curative efficacy,” says Gaal. He shared five ways that an experienced CTDMO can guide biopharma innovators in their gene therapy journeys.
- Providing access to a de-risked manufacturing facility. In manufacturing, you must have a solid foundation and manage the five sources of variability, says Gaal: materials, methods, people, equipment, and facility. A commercial CTDMO knows the importance of providing a consistent and robust manufacturing operation, which is fundamental to regulatory approval. “While manufacturing for a new modality, like viral vectors, shares similarities with other biologic manufacturing, there are some important differences that an experienced team has already incorporated into their facility design and processes,” says Gaal.
- Offering guidance for a streamlined path to GMP manufacturing. Gaal says that there are still manufacturing processes and quality unknowns with viral vectors, which can threaten development and manufacturing protocols. That’s why his team offers manufacturability assessments, that identify and evaluate improvements in manufacturing, testing, process design, or sourcing to streamline therapeutic production. “We also use platform approaches for viral vector manufacturing with optimized and defined upstream and downstream processes to deliver de-risked, reproducible workflows and accelerate the development timelines, while providing industry-leading titers and robust recovery yields,” says Gaal.
- Assisting in selecting the appropriate viral vector. There’s a common misconception that all viral vectors are the same. Gaal helps clients understand that this is simply not true. “Different viruses have different charges, different sizes, different stability profiles, and different safety testing methods,” he says. “Each virus has a unique production process, and every subclass of virus has modifications within that process. That needs to be understood so that you’re not trying to apply a one-size-fits-all manufacturing process and thus obtaining poor yields or poor purity.” Every variation of a virus is nuanced, and an experienced viral vector CTDMO understands that and knows how to work with each one.
- Connecting to a global network. Supply chain constraints can throw off production and disrupt timelines. When working with an experienced CTDMO customers can benefit from robust supply networks around the world. “During the COVID pandemic, everyone had real challenges getting needed materials,” says Gaal. “But through our network, we were able to maintain consistent production for our clinical and commercial viral vector clients.”
- Demystifying the regulatory process. Gaal has been working with regulatory agencies since viral vector manufacturing was in its infancy. He and his team consider every encounter with the agencies a valuable exchange. They have guided clients on manufacturing process decisions to be in line with regulatory expectations. Additionally, they have implemented suggestions gained from agencies to help clients avoid regulatory setbacks, and provide dedicated and customized support for regulatory filings, inspections, and responses throughout a product’s lifecycle. “You want to go into each inspection with a lot of confidence, knowing you did everything right,” says Gaal. “Working with a CTDMO that has a strong regulatory track record and strong quality management system goes a long way in giving you that level of assurance.”
Gene therapy is still in the early days, says Gaal, and the possibilities are unlimited. “Gene therapy is not disease-target limited. It is repairing a damaged gene, and there are 7,000 disease targets that gene therapy can work on and fix in a curative mode, not just a treatment,” he says. “We're only at the tip of the iceberg.”
When manufacturing and developing therapies, experience matters. By partnering with an accomplished CTDMO, like MilliporeSigma, gene therapy innovators can benefit from guidance and support, which in turn gives them confidence and peace of mind so they can focus on reaching the patients who need these therapies the most. Learn more about MilliporeSigma’s viral vector CTDMO services.
MilliporeSigma is the U.S. and Canada Life Science business of Merck KGaA, Darmstadt, Germany.