The landscape of cell and gene therapies is rapidly evolving, offering transformative potential for patients with previously untreatable conditions. However, the field brings with it a complex web of regulatory considerations that companies, researchers, and regulators must navigate. A recent roundtable discussion at Cell 2025 brought together experts from across the sector to share experiences, challenges, and strategies for successfully advancing these therapies through regulatory pathways.
Here, we distil the key themes and insights from that discussion, providing a broad overview of the current regulatory environment and the practical realities faced by those developing cell and gene therapies.
The Complexity of Regulatory Pathways
Cell and gene therapies are subject to rigorous regulatory scrutiny due to their novel mechanisms, manufacturing processes, and potential risks. Participants in the roundtable highlighted that regulatory requirements often extend beyond familiar territories such as the FDA, EMA or MHRA, encompassing a diverse array of agencies and frameworks. This complexity is compounded by the need to address intellectual property (IP) considerations and to tailor regulatory strategies to the specificities of each jurisdiction.
One recurring theme was the importance of understanding that regulations may "live" in different domains, requiring careful phrasing and strategic planning. The need for clear communication with regulatory bodies and the ability to adapt to evolving requirements were emphasised as critical skills for teams working in this space.
Early Engagement and Consistency in Regulatory Feedback
A key strategy discussed was the value of early and proactive engagement with regulatory authorities. Early interactions can provide valuable feedback, helping companies align their development programs with regulatory expectations and avoid costly missteps later in the process. However, participants noted that the consistency of regulatory feedback can vary, both within and across jurisdictions.
For example, while some agencies may provide consistent guidance across different applications, others may introduce additional requests for information (RFIs) or apply varying levels of scrutiny depending on the reviewers involved. This variability underscores the importance of maintaining thorough records of all regulatory interactions and being prepared to address divergent feedback as programs progress.
The Role of Regulatory Consultants and Cross-Agency Communication
Regulatory consultants play a pivotal role in guiding companies through the maze of requirements, offering expertise in strategy development, market access, and regulatory submissions. The roundtable discussion highlighted that both consultants and assessors routinely review all previous interactions with regulatory authorities, ensuring that feedback is not overlooked and that lessons learned are incorporated into future filings.
Moreover, regulatory authorities themselves often communicate across agencies and programs, sharing insights and aligning expectations where possible. This cross-agency dialogue can help harmonise standards and reduce the risk of conflicting guidance, although participants acknowledged that complete alignment remains a work in progress.
Evolving Standards and the Challenge of Impurities
The regulatory environment for cell and gene therapies is not static; it evolves in response to new scientific knowledge, emerging technologies, and real-world experience. One area of ongoing development is the management of impurities, particularly in gene therapy products. The roundtable participants noted that methods for detecting and characterising impurities are not yet fully aligned across the industry, creating uncertainty for both developers and regulators.
As new assays and analytical techniques are developed, it is crucial for companies to keep regulators informed about the status and capabilities of these methods. This transparency helps ensure that regulatory requests are grounded in current scientific reality and that expectations are managed appropriately.
Personalised and Adaptable Therapies: Regulatory Implications
A significant portion of the discussion focused on the regulatory challenges associated with personalised and adaptable therapies, such as individualized cancer vaccines. These therapies often involve complex manufacturing processes and may require frequent adjustments to composition based on patient-specific factors.
Participants debated whether each new combination of therapeutic agents should be subject to separate toxicology and biodistribution studies, given the heterogeneity of patient responses. The consensus was that regulatory strategies must balance the need for rigorous safety assessment with the practical realities of personalised medicine, and that early dialogue with regulators is essential to charting a feasible path forward.
Globalisation and Regional Differences
The globalisation of clinical development adds another layer of complexity to regulatory considerations. The roundtable highlighted differences in regulatory approaches between regions such as the UK, China, and Australia. For example, some countries have recently opened up to allow rare disease therapies developed abroad to be tested and approved for local use, while others maintain more restrictive policies.
These regional differences necessitate tailored regulatory strategies and may influence decisions about where to conduct clinical trials, manufacture products, and seek initial approvals. Companies must remain agile and informed about the evolving global landscape to maximise the chances of successful product development and commercialisation.
The Importance of Data, Analytics, and AI
As cell and gene therapies become more sophisticated, so too do the data and analytics required to support regulatory submissions. The use of advanced bioinformatics platforms, single-cell RNA sequencing, and artificial intelligence (AI) is increasingly common in both product development and regulatory interactions.
Participants discussed the challenges of ensuring data integrity and consistency across different laboratories and jurisdictions, particularly when transferring complex analytical methods. Regulators are taking a keen interest in the robustness of these platforms, and companies must be prepared to demonstrate the reliability and reproducibility of their data.
Safety, Labelling, and Special Populations
Safety remains paramount in the regulatory evaluation of cell and gene therapies. The roundtable addressed specific concerns such as the potential impact of therapies on fertility and pregnancy, as well as the need for clear labelling and risk communication. Participants agreed that ongoing studies and post-marketing surveillance will be critical to fully understanding and managing these risks.
Conclusion: Toward Greater Alignment and Innovation
The regulatory landscape for cell and gene therapies is characterised by complexity, variability, and rapid evolution. Success in this environment requires early and ongoing engagement with regulators, a willingness to adapt strategies as new information emerges, and a commitment to transparency and collaboration across the sector.
While challenges remain – particularly in areas such as impurity testing, personalised medicine, and global harmonisation – the roundtable discussion underscored the sector’s resilience and capacity for innovation. By working together to align standards, share knowledge, and advocate for practical regulatory approaches, stakeholders can help ensure that the promise of cell and gene therapies is realised for patients worldwide.
