ASGCT Supports Further Alignment of Regulations with Scientific Advancement in CGT

Advancing Real-World Data Integration for CGT Development

ASGCT recently submitted comments to FDA's docket on Exploration of Health Level Seven Fast Healthcare Interoperability Resources (HL7 FHIR) for Study Data Created From Real-World Data Sources. Real-world data - health information captured outside traditional clinical trials through electronic health records, patient registries, and claims databases - presents significant opportunities for CGT development, particularly for rare disease therapies where traditional trial designs may be unethical or unfeasible. 

Currently, over 4,000 gene, cell, and RNA therapies are in development globally, with more than 2,000 gene therapies in the pipeline. For many of these innovative treatments, RWD can fill critical evidence gaps, support external control arms when randomized controlled trials are impractical, and enhance post-approval safety monitoring. However, the current regulatory landscape presents challenges: variability in data quality, unstandardized submission processes, and a case-by-case evaluation approach that creates uncertainty for sponsors. 

ASGCT's key recommendations include:

• Developing CGT-specific data element standards that reflect the durable treatment effects and long-term follow-up requirements characteristic of these therapies  

• Coordinating cross-center collaboration within FDA to harmonize standards for externally controlled trials using real-world evidence 

• Increasing transparency of FDA-collected data through standardized FHIR APIs to reduce duplicative data capture efforts 

The Society emphasized that standardized, interoperable RWD systems would provide sponsors with clearer pathways for evidence generation while enabling regulators to consistently evaluate this evidence across different therapeutic areas and modalities.

Balancing Deregulation with Scientific Rigor 

ASGCT also responded to the Department of Health and Human Services' Request for Information on Ensuring Lawful Regulation and Unleashing Innovation to Make America Healthy Again, which implements the administration's previous executive order directing agencies to eliminate 10 regulations for each new regulation issued. 

While the Society supports the retirement of regulations that no longer serve meaningful public health purposes, ASGCT emphasized the critical importance of maintaining the release of timely, science-based FDA guidance for the rapidly evolving CGT field. The Society noted that CGT science is advancing at an unprecedented pace, with 79 new gene therapy clinical trials initiated in Q1 2025 alone. 

ASGCT specifically advocated for: 

• Publication of CBER's scheduled 2025 guidance documents, including final guidance on potency assurance for cellular and gene therapy products, safety testing of human allogeneic cells, and long-awaited draft guidance on accelerated approval pathways for rare diseases 

• Better alignment of congressionally established policy tools, such as the Advanced Manufacturing Technologies Designation Program and Platform Technology Designation Program, with current regulatory frameworks 

• Converting high-traffic CGT guidance documents to "living resources" that can be updated periodically without reopening entire guidance processes 

The Society maintains that clear regulatory guidance reduces scientific uncertainty, enables more strategic resource allocation by sponsors, and ultimately accelerates the delivery of transformative therapies to patients.

Supporting Regulatory Innovation for Transformative Therapies 

Both comment letters reflect ASGCT’s commitment to supporting regulatory innovation that matches the pace of scientific advancement, while maintaining robust safety oversight. The Society recognizes that CGTs often present unique regulatory challenges due to their complexity, durability of effect, and the frequent involvement of rare disease populations where traditional development paradigms may not apply. 

These recommendations aim to create a regulatory environment that reduces unnecessary burdens while preserving the scientific rigor essential for patient safety and therapeutic progress. By advocating for standardized approaches to real-world evidence, streamlined guidance processes, and better integration of existing policy tools, ASGCT seeks to ensure regulatory frameworks evolve alongside the science they govern.

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