The US regulatory environment is undergoing a period of rapid transformation, marked by significant changes at the FDA and evolving policies that may directly impact drug development, particularly in the fast-moving fields of cell and gene therapy.
Boyds’ Dr Katherine Bowen, Chief Regulatory Affairs Officer and Dr Eric Hardter, Director of Regulatory Affairs, explore some of the key changes and provide advice for drug developers navigating the complexities of the regulatory landscape.
The new US administration has ushered in sweeping staffing changes at the FDA, including the appointment of a new Commissioner, Marty Makary, MD and a new CBER Director, Vinay Prasad, MD. Prasad has since departed the Agency, after just a three-month stint as the Agency’s top vaccine official. The departure of influential leaders such as Peter Marks and Nicole Verdun, both of whom were instrumental in championing cell and gene therapy approvals, signals a potential shift in regulatory philosophy.
Marks and Verdun played pivotal roles in advancing approvals for cell and gene therapies (CGTs), including those for rare disease therapies, and their exit raises questions about the future of CGT regulation. Given Prasad’s previously issued statements reflective of increased scrutiny, particularly for innovative or high-risk products, drug developers could have anticipated taking a more conservative tack. This could have manifested in longer investigational development timelines and higher evidentiary standards (i.e., additional clinical trial participants), potentially resulting in increased costs.
However, as of the time of this writing it remains to be seen who will take Prasad’s place at CBER. As such it will be crucial to continue to monitor the changes at CBER, along with policy statements and guidance from the new FDA leadership to best anticipate evolving regulatory expectations.
AI in regulatory processes
The FDA announced the integration of its artificial intelligence (AI) tool, Elsa, into its internal regulatory processes. This is in line with AI adoption from other global regulators, such as the MHRA, which is piloting AI for validation and review processes.
Initial tasks to be undertaken by Elsa include clinical protocol reviews, identification of high priority inspection targets, summary of adverse events to support safety assessments, and generation of code to help develop databases for nonclinical data. FDA anticipates efficiencies should occur in shortening the time for scientific evaluations, as well as the performance of faster drug label comparisons. All inputs for Elsa will remain internal – the FDA’s cautious stance is rooted in concerns about “hallucination” – AI-generated errors or unverified outputs – and, as such, the agency is not yet accepting external AI-driven inputs for regulatory decisions.
For companies considering the use of AI in regulatory submissions or data analysis, it is essential to ensure robust validation and transparency in methodologies. Staying informed about pilot programs and guidance from both US and international regulators will help organizations anticipate future requirements and remain compliant as the regulatory landscape evolves.
Minimization of animal testing requirements to support investigational new drug (IND) applications
The FDA has developed a roadmap to reduce animal testing, aligning with the FDA Modernization Act v2.0, as well as the principles of the “3Rs” (Replacement, Reduction, Refinement). This initiative is set to begin with monoclonal antibody investigational products.
Whilst the roadmap represents a positive step forward, it’s important for IND sponsors to remember that animal testing remains the ‘gold standard,’ and the transition to alternative methods will be incremental. New approaches will require validation before they can be fully adopted, and the industry should expect a phased implementation approach.
Companies should look to engage early by participating in FDA workshops and public comment periods to help shape the implementation of new guidelines. During the transition period it will be important to remain cognizant of the roadmap status, as it may be directly influential on the types of traditional animal data and data from alternative methods to be provided as supportive safety evidence.
Read more about the FDA’s roadmap to reducing animal testing in our blog here.
New Approach Methodologies (NAMs) for preclinical validation
Also described in the FDA’s roadmap to reduce animal testing is the formalization of the use of newly termed “New Approach Methodologies (NAMs)”, including organoids and AI-based models, for preclinical safety assessment.
NAMs may hold significant promise for reducing reliance on animal studies, but their regulatory acceptance will necessitate rigorous validation. Initially, these methodologies will supplement rather than replace animal studies, particularly for biologics, as regulators assess their reliability and applicability.
To stay ahead, companies should keep apprised of the current state of NAMs research, which may include collaboration with academic and industry consortia to develop and validate new methodologies. Records of NAMs validation studies will be critical to support the nonclinical data packages for regulatory submissions and demonstrate compliance with evolving standards.
Launch of the National Priority Voucher Program
The newly introduced National Priority Voucher Program (NPVP) aims to expedite New Drug Application (NDA) and Biologics License Application (BLA) reviews for select US drug developers, potentially reducing review times from the standard 10 months to as little as one to two months after final data submission.
Eligibility for the program focuses on drugs that address manufacturing security and pandemic preparedness, though further details on application processes and qualifying “unmet needs” are still forthcoming. While the promise of accelerated timelines is undoubtedly enticing to drug developers, a phased approach to the implementation of the NPVP, including initial pilot reviews, will be enacted by the Agency.
Companies should closely monitor FDA updates regarding program criteria and application processes. Even with potentially expedited timelines, sponsors should be prepared for rigorous review standards and ensure that data packages are complete, well-organized, and able to withstand regulatory scrutiny.
Communicating with the FDA
Also noted within the NPVP press release was the importance of direct, informal communication with FDA reviewers. While a number of formal pathways exist to obtain FDA feedback, Dr Makary noted that sometimes a 15-minute phone call between FDA stakeholders and sponsors represents the most direct pathway for issue resolution.
Such communication is not guaranteed, and it must be used judiciously to be effective. Overuse or unfocused communication can dilute its impact and potentially slow down decision-making processes. To maximize effectiveness, developers should be strategic, reserving informal communications for critical, time-sensitive issues. It is also important to document all interactions thoroughly to ensure alignment between sponsor and FDA.
Tips for staying agile in a changing environment
- Stay proactive by regularly monitoring regulatory updates and adapting strategies as new policies and leadership priorities emerge
- Foster collaboration with regulators, industry groups, and academic partners to share insights and advocate for practical, patient-centered policies
- Build flexibility into development plans to accommodate shifting timelines, requirements, and funding landscapes.
Looking for regulatory affairs support?
Boyds’ award-winning team of regulatory affairs experts will closely follow developments in this area and will continue to provide updates. With long-standing relationships with the FDA, our regulatory professionals can provide clients with specialist knowledge and guidance to help support their regulatory submissions. Speak to the team today.