Viral clearance (VC) studies have been a crucial safety measure in the development of biologic drugs since the 1990s. These studies are designed to assess the manufacturing processes of biologic drugs to ensure the effective removal or inactivation of viruses. While regulatory guidelines for VC studies have been partially updated over time, the complexity of designing these studies persists due to the continuous evolution of biologics, various production methods, and the ongoing need to interpret guidelines in light of new information and technologies.
One of the primary challenges in viral clearance studies lies in determining the appropriate scope of the study. Although guidelines exist, they often allow for interpretation, requiring companies to adapt the study scope to their specific product while minimizing costs and remaining compliant with regulatory standards. The 2025 Viral Safety and Viral Clearance (VSVC) Summit by Charles River gathered experts to address these challenges and discuss strategies for effective VC, including reducing test scopes outlined in ICH Q5A (R2) guidelines and exploring innovative methodologies like the use of virus-like particles.
In the realm of cell and gene therapy development, where viral vectors play a significant role, tailored viral safety strategies are essential. While cell therapies focus on sourcing controls and extensive testing due to limitations in viral clearance, products based on viral vectors require rigorous VC. Despite the lack of detailed regulatory guidance for early-phase VC studies involving viral vectors, health authorities increasingly expect companies to have VC data in place by the time of IND/CTA submission.
An important aspect of improving VC efficiency lies in the utilization of innovative approaches like co-spiking with viruses such as murine leukaemia virus (MuLV) and Minute virus of mice (MVM) in Good Laboratory Practice (GLP) studies. This approach not only optimizes material usage but also demonstrates benefits in terms of cost-effectiveness and overall study design. Moreover, the introduction of virus-like particles (VLPs) as alternatives in VC studies presents both advantages and limitations, with regulatory restrictions on their use based on their ability to mimic specific viral particles.
The shift from batch to continuous manufacturing (CM) in production processes has posed challenges in defining validated downscale processes for VC studies. While inactivation steps like low pH treatment can be easily adapted, processes involving multicolumn chromatography, such as Protein A chromatography, present complexities in defining critical parameters for VC studies. Regulatory agencies are increasingly providing flexibility in VC strategies, emphasizing the need for scientific rigor and justified approaches in alignment with evolving guidelines.
Overall, the landscape of viral clearance studies continues to evolve, with a focus on adapting strategies to individual products, exploring innovative methodologies, and fostering cross-industry collaboration to establish best practices. By staying abreast of regulatory expectations, leveraging novel approaches, and enhancing scientific understanding, companies can navigate the complexities of viral clearance efficiently while ensuring the safety and efficacy of biologic drugs.
Key Takeaways:
– Tailored viral clearance strategies are essential in cell and gene therapy development, emphasizing the need for product-specific approaches.
– Innovative methodologies such as co-spiking with viruses and the use of virus-like particles offer potential benefits in optimizing viral clearance studies.
– Challenges in transitioning from batch to continuous manufacturing processes underscore the importance of defining critical parameters for effective viral clearance studies.
– Regulatory flexibility in viral clearance strategies necessitates a deep scientific understanding and collaborative efforts to establish safe and efficient practices.
Tags: viral clearance, chromatography, viral vectors, clinical trials, affinity chromatography, regulatory, cell therapies, upstream, gene therapy
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