The AAV-based therapeutic market continues to evolve rapidly. The past few years have seen multiple high-profile FDA approvals for AAV-based therapeutics, with a series of regulatory decisions in the pipeline for 2025. These therapies are also expanding beyond the realm of rare genetic disease to target more common indications, including cardiovascular disease and neurological conditions such as Alzheimer’s and Parkinson’s.

Targeting larger patient populations expands the potential for AAV-therapies to transform patients' lives. But it also comes with additional complexity, due to the increased risk of variability as the process is scaled up to meet the larger patient demand. Scaling up from bench to production scale requires significant process development and optimization to achieve consistent quality and yield from batch-to-batch. These additional risk mitigation measures are both time-consuming and costly for AAV developers. In addition, developers face macroeconomic headwinds — regardless of the size of their target patient population — and must take steps to maximize cost-efficiency and strengthen the commercial viability of their AAV programs.

“AAV-based therapy development starts with a gene and a dream — and while that spark of innovation is important, it’s critical to have plans to de-risk the program by maximizing performance at the scale of production you need,” says Eva Fong, Associate Director of Process Development, Viral Vector CDMO at MilliporeSigma. Yet, many developers struggle to achieve consistent AAV production at the scale needed to reach their milestones.

Fong explains that AAV developers can benefit significantly from partnering with a CDMO, which has invested heavily in developing a demonstrated and optimized platform solution for AAV production. Utilizing a platform de-risks production and minimizes the amount of time and cost needed for process development, allowing for efficient progression to clinical trials and commercialization. Leveraging these established processes generates additional benefits including:

Increased quality and yield: Optimized upstream and downstream workflows maximize high-quality AAV production to achieve high titers and recovery, while minimizing impurities like empty and partially filled capsids. This results in more fully packaged and intact capsids, which are essential for reducing manufacturing costs per dose and enhancing the effectiveness of gene therapies.

Robust analytics: “If you have high variability in your process, it’s very difficult to consistently achieve your quality targets,” says Fong. A CDMO with strong analytical capabilities inherent to their platform can help define quality parameters for AAV production, ensuring purity and consistency of the AAV process.

Flexibility and Scalability: With the right platform and CDMO partner, developers don’t need to trade flexibility for convenience. An effective platform should offer customization options to meet the unique needs of each program while accommodating various serotypes and batch sizes. This flexibility supports cost-efficiency and reduces variability across production scales, whether you’re producing 3 liters, 1000 liters, or more.

Regulatory Support: Many of the regulatory guidelines currently applied to AAV-based therapeutics were developed with protein-based therapies in mind. “It creates a gray area around how those regulations should be interpreted for viral vector therapies, introducing risk related to the regulatory process,” Fong says. And the team must have the capability to offer regulatory support for each target market. Partnering with a CDMO who is well-versed in regulatory requirements can help navigate expectations and expedite the approval process.

Leveraging a CDMO’s established platform for AAV manufacturing can significantly streamline gene therapy development. With built-in expertise, reliable scalability, and operational efficiency, this approach helps reduce costs, mitigate risks, and accelerate the path to clinical trials— helping developers bring gene therapies to patients more quickly.

MilliporeSigma, a leader in the manufacturing of viral vectors for over 30 years, has supported four commercially available viral vector-based gene therapies. Their AAV Express platform delivers a full spectrum of support enabling streamlined and de-risked AAV production for gene therapies. As a proven, high-performing solution, the AAV Express platform provides flexibility and scalability, while reducing costs and accelerating time to clinic. By partnering with an experienced CDMO, like MilliporeSigma, developers can trust that their AAV-based gene therapies will effectively reach the patients who need them most. 

Learn more about MilliporeSigma’s viral vector CDMO services for AAV production.

MilliporeSigma is the U.S. and Canada Life Science business of Merck KGaA, Darmstadt, Germany.