COVID-19 Impacts on Agency Interaction on Cell and Gene Therapy Products

COVID-19 Impacts on Agency Interaction on Cell and Gene Therapy Products

By Niki Gallo, Associate Principal Consultant, Regulatory Affairs

The effect of COVID-19 on therapy development has been a double-edged sword. While our industry has experienced unparalleled opportunities for innovation to develop therapies for diagnoses and treatment of COVID-19, the development of non-COVID therapies has been faced with uncertainty and hindrance. For cell and gene therapy products, the pandemic’s impact means a shift in communication and timelines, but the obstacles are not insurmountable.

In general terms, COVID-19 did not impact the life science industry with the same immediate financial impact that travel, tourism, local small businesses, education, and food service industries suffered. Instead, I witnessed a collective effort from health authorities and device and drug sponsors to fight COVID-19 together, from the expeditious development of diagnostic agents and kits to the re-purposing of commercially available therapies that may treat COVID-19, to the development of new complex vaccines and therapeutics to eliminate COVID-19. Amid these efforts, most of our industry has been able to maintain their clinical development programs with some minor delays. Although, those companies with more limited resources and funding have seen more significant delays and even discontinuation of their programs.

Non-COVID therapies have been impacted but continue to receive critical support. Dr. Peter Marks, Director of the Center for Biologics Evaluation and Research (CBER), US FDA, stated in a fireside chat with Janet Lambert, CEO of Alliance for Regenerative Medicine (ARM) during the ARM 2020 Meeting on the Mesa that the FDA is very committed to moving gene therapies, cell therapies, and other novel cell-based therapies ahead. Dr. Marks has in multiple speaking engagements messaged his excitement and enthusiasm for the continued development of cell and gene therapies, and his mission has trickled down to the offices and divisions within CBER’s Office of Tissue and Advanced Therapies (OTAT), the FDA office responsible for the review of cell and gene therapies.

In response to the pandemic, the FDA has created new taskforces and workstreams to collaborate with the industry on the development of COVID-19 related products while maintaining the existing tremendous workload from the cell and gene therapy sector. Before COVID-19, CBER was recruiting scientists and medical professionals intending to double in size for a more efficient and diligent review of the numerous anticipated cell and gene therapy IND applications. Unfortunately, this goal was not reached before COVID-19 hit, and to maintain the pace of submitting well over 200 cell and gene therapy IND applications in 2020 in addition to the COVID-19 applications, CBER has had to pull in staff from other jurisdictions, offices, and divisions to support the tremendous workload. This may account for the new regulatory project managers, or multiple regulatory project managers one sponsor may interact with on one application.

The Agency is by no means lowering their bar, and they remain dedicated to its mission to bring safe and effective therapies to patients in need. However, the stress of new workstreams on top of existing work will mean delays in promised communication and feedback for formal sponsor meetings and procedures that fall out of the PDUFA timeline window. COVID-19 related products remain the priority, and CBER is aware that delayed communication can slow development and innovation as sponsors wait. They want to do right by sponsors, but currently there just aren’t enough hours in the day nor bodies at CBER to maintain the pre-COVID-19 pace and momentum in the gene and cell therapy space. The tremendous stress and workload have not caused the Agency to modify their data standards or assessment of risk versus benefit of proposed therapies, in my opinion. Human health and safety remain the top priority.

The US FDA, like many of us, is working remotely and this transition has had an impact on communication. Currently, the Agency does not allow the in-person, face-face meetings that many of us feel are critical to establishing a collaborative relationship. Interacting with the FDA, especially face-to-face, is an integral part of developing innovative cell and gene therapies because in early development the FDA is likely to have more of a collaborative approach to working with Sponsors, whereas in late phase development the FDA communication will be more formal. Additionally, the in-person format may allow for the opportunity to have some informal hallway conversations with members of the FDA team following the meeting to further discuss or clarify any topics that may have been cut short during the allotted meeting timeframe. Remote communication limits the opportunities for the in-formal “hallway conversations” that at times can be informative to development plans.

Despite the challenges COVID-19 presents to the Agency, the data quality and expectations required to permit the initiation or continuance of clinical trials to support marketing applications have not changed during the pandemic. The evidence of this is widespread with for example the receipt of detailed written feedback (either preliminary feedback or Written Response Only) that spans multiple pages before a sponsor meeting, clinical holds placed on original IND applications not permitting clinical studies to proceed, clinical holds on ongoing studies placed due to safety concerns, and refusal to file letters issued for BLAs. The staff at FDA are overburdened by working on many product applications simultaneously, however, they are still providing meaningful feedback and scrutinizing each submission that comes across their desks.

In summary, the impact of COVID-19 on the development of cell and gene therapy products has been mainly on how Sponsors interact with the Agency. The level or type of data needed to support a product’s use in humans remains the same. Knowing that Agency correspondence may be delayed, or procedures may extend beyond their PDUFA timeline in some select instances, a Sponsor should be proactive with “at-risk” activities to stay ahead of the delays and should always seek to maintain a good relationship with the assigned regulatory project manager through transparent and thoughtful communication. COVID-19 may impact the timing of interactions with the Agency, but it is not affecting the integrity or quality of the feedback and communication the Agency provides. Cell and gene therapy products can, and should, continue to advance in their development, even with the focus on COVID-19 research, diagnoses, and treatment.