Regulatory Lessons Learned From COVID-19: Anomaly to Precedent

The COVID-19 pandemic was disruptive in many ways, including to cell and gene therapy development. But some of those disruptions may bring positive change that is here to stay, including to the regulatory environment for cell and gene therapy, as we heard during the Annual Meeting session sponsored by the Regulatory Affairs Committee. During this session, which you can watch here, key regulators from the EMA and FDA shared lessons learned from COVID-19. 

The new head of the EMA Emer Cooke kicked off the session, sharing that cell and gene therapy work continues to grow at EMA even amidst the pandemic, and it represents a significant portion of PRIME designations. While the biggest pandemic-related changes at the EMA may have been the increased visibility and public attention to the Agency, the pandemic also brought increased regulatory and procedural agility, including more use of fast track procedures and conditional marketing authorization for COVID-19 vaccines and therapeutics, with learnings that could benefit the cell and gene therapy space into the future. The pandemic also saw EMA increasing the use of expertise pooling and work sharing, collaborating with other regulators, and relying on technology to enable virtual interactions and remote inspections. Ms. Cooke believes that while some of these elements might evolve into more hybrid approaches in the future, such as a mix of in-person and virtual meetings, there is no going back on others, including the level of international collaboration.  

Wilson Bryan, M.D., from the U.S. FDA continued the session by sharing the state of the workload at the Office of Tissues and Advanced Therapies (OTAT), which he heads. OTAT workload overall continued to grow despite the pandemic, but this was driven more by cell therapy than gene therapy, with the latter seeing a plateau in INDs vs 2019 likely due to the pandemic-driven challenges in development. FDA engaged substantially with cell and gene therapy sponsors during the pandemic, particularly related to management of ongoing clinical trials, and key learnings from those interactions should last into the future.  Among them, the increased use of telemedicine and wearable devices is expected to continue, as is the increased communication and rapid issuance of more streamlined guidance documents from FDA. Additionally, the increased collaboration between government bodies and sponsors, as well as among sponsors on platform trials, is another benefit. In what may have been the most important topic for many cell and gene therapy sponsors with trials disrupted by the pandemic, Bryan also commented on FDA’s willingness to work with sponsors around missing data, indicating they would look at the totality of the dataset, but acknowledging that beyond a certain point this could impact interpretation and reliability of results.

Two additional talks elaborated on the challenges and opportunities of remote clinical trials. Genevieve Laforet, M.D., Ph.D., from Aspa Therapeutics described how the pandemic triggered them to convert an ongoing natural history study, critical to the development of a gene therapy for Canavan disease, to a fully remote trial. This pivot was enabled by close collaboration with stakeholders, including on what could be done remotely and what would need to be modified, such as the study documentation and rater training, and how to test the validity of the approach with a pilot study. Their experience provided insight into some of the pros and cons of remote assessments, an area that is in focus for Science37, which Jonathan Cotliar, M.D., described in the final talk of the session. Efforts to advance decentralized clinical trials had begun years ago but were certainly accelerated along with the evolving regulatory framework driven by the pandemic. These remote approaches could be particularly valuable for cell and gene therapy products where access to geographically dispersed rare disease patients and long-term follow up can be key challenges.     

The Q&A session further cemented the panelists’ views that the most valuable lessons learned from the pandemic are increased collaboration between regulators, sponsors, and other key stakeholders, as well as advances in the employment of technology to enable remote clinical trials, virtual inspections, and virtual regulatory interactions – things that all of us hope are at least partially here to stay. 

Dr. Zoschg Canniere is head of regulatory affairs at Spark Therapeutics and a member of ASGCT's Regulatory Affairs Committee.

Related Articles