If you’re navigating a viral vector regulatory journey feeling uncertain about where to go next, you’re not alone.
Gene therapies are bringing exciting and new clinical possibilities to complex diseases, and it’s this newness that also makes the path to patients especially challenging. As regulators seek to understand novel mechanisms of action, manufacturing workflows, safety profiles, and clinical effects of breakthrough formulations, innovation continues to drive change.
“While a regulatory pathway does exist, it isn’t specifically tailored to gene therapies, so our viral vector customers are looking for advice on how to approach the approval process,” says Sandra Racordon-Pape, Director, Regulatory Science and Strategy at Cytiva. “You need to evolve because the space is evolving every day.”
Here, Racordon-Pape outlines three ways developers of viral vector-based gene therapies can find a smooth road through uncertainties in gene therapy regulations to successfully reach approval.
1. Tap regulatory resources early
While the regulatory approval process is often intimidating, Racordon-Pape says drug developers and manufacturers shouldn’t procrastinate. “Something that we really emphasize with our customers is how they should quickly engage with regulators because it helps to de-risk their application,” she explains. “Before filing an IND, you have the opportunity to ask questions, gain scientific insight, and test the waters to get good feedback and understand key milestones from the very beginning. This type of meeting isn’t used often enough.”
With viral vector manufacturing still in its infancy, Racordon-Pape strongly recommends learning from those who came before you as you enter your regulatory journey. “Leverage the experience of others to understand what to do and what not to do,” she advises, highlighting that the FDA has recently leaned into transparency and made complete response letters (CRLs) public to help this cause. She also highlights that agencies, in general, are striving for efficient approvals with programs such as orphan and platform designation, along with published guidance, to help viral vector developers successfully meet their milestones.
Racordon-Pape further explains that it’s not only important to use the available resources when entering the viral vector production space ― since the landscape is still being developed, you can also help shape it. She adds, “I think it’s important to engage with committees and review draft regulation and guidelines to really understand what they mean, add input, and propose amendments to help build a better future.”
2. Drive consistency and control in viral vector manufacturing
“When developing a therapy, it’s essential to be fully confident and assured in the strength and quality of your data,” says Racordon-Pape. “If you don’t feel comfortable standing behind your results, you shouldn’t submit your application to regulators.”
From a regulatory perspective, manufacturing safe gene therapies comes down to process consistency and control ― and demonstrating both is especially important in viral vector production where workflows are still being refined. “You can’t submit for approval if you have inconsistencies in your process, as that means there are inconsistencies in your product and its therapeutic effects,” Racordon-Pape explains.
What can help drive consistency and control? Automation. “Even at an early stage, automating workflows shows regulators that you are disciplined in minimizing risk,” she says. “You need to be able to demonstrate data integrity, align GMP and QMS [quality management systems], and ensure a robust change control in your process.”
To drive safety, regulators will also focus on the presence of impurities. “We see our customers having challenges with the characterization of impurities,” says Racordon-Pape. “Regulators will need to see that you have a comprehensive strategy around impurities, including the control of raw and starting materials, how you’ve tested your method, why you've chosen it ― all this justification should make the regulator confident in your therapy.”
3. Collaborate for regulatory efficiency
Racordon-Pape recommends working with suppliers that offer regulatory services and support to streamline the journey to approval. “Treat your supplier like part of your team to make the most of the collaboration,” she advises. “This can really help you achieve success more quickly.”
Collaboration can be especially helpful if your company lacks its own internal regulatory support. Cytiva works to fill that gap by providing regulatory services through a dedicated team of over 100 specialists across various fields. "We can assist with drafting CMC [chemistry, manufacturing, and control] sections of your application, or even comprehensive support tailored to your specific needs,” says Racordon-Pape “Our customers benefit from direct access to those who are familiar with both the equipment used in their processes and the teams responsible for preparing CMC content, ensuring a smooth and informed regulatory journey.”
The regulatory team at Cytiva helps customers in the very early stages plan their gene therapy regulation roadmap to get to each critical milestone, outlining how long the journey will take. Services and support are also available all the way to commercialization and GMP ― where the regulatory process can become even more tricky.
GMP is key to producing viral vector-based gene therapies that are safe for patients and of necessary quality, and a robust QMS is critical for achieving GMP compliance. Racordon-Pape adds, “We’ve seen instances where therapeutics fail because of the GMP, which delays application and the release on the market. We have a lot of good resources to demonstrate how to meet GMP compliance.”
The regulatory services offered by Cytiva include helping customers overcome challenges associated with implementing GMP and a robust QMS for gene therapies, especially during the transition from clinical to commercial manufacturing. “We can provide guidance on regulatory requirements, facilitate alignment of CMC with GMP standards, and assist in interpreting and applying complex, evolving regulations specific to advanced therapies,” explains Racordon-Pape. Additionally, these services can help organizations prepare and review necessary documentation, and conduct gap analyses to identify compliance risks.
The regulatory team at Cytiva also assists regulatory agency interactions, ensuring timely submissions and addressing agency feedback efficiently. “We visit customers to really discuss their problems face-to-face and gain the understanding we need to best work with them. Then, we can help them engage in meetings,” explains Racordon-Pape. “It's like, give me your hand and I'll guide you through.”
In summary, it takes quick action to build bridges between regulators, manufacturers, and suppliers to pave the fastest route to viral vector approval ― something Racordon-Pape and the regulatory team at Cytiva are helping to facilitate through trainings, customer outreach, and agency engagement.
“I think the challenge with regulatory is to make it accessible to people, and we need to adapt because we’ve been on somewhat of an island,” she explains. “Regulatory is nothing if you don't consider the manufacturing activities, control activities, and development. All these elements are important to your filing.”
And in this fast-changing gene therapy regulation landscape, silos only serve as roadblocks on the path to patients.