TestAVec comment on FDA Draft Guidance on Gene Editing for Industry

Is gene therapy safety regulation keeping pace with the science?

The FDA's recent draft guidance on the safety assessment of genome editing products is an important milestone. Its emphasis on next-generation sequencing, long-read sequencing and robust genomic analysis reflects the remarkable advances that have transformed our ability to detect unintended genomic alterations.

But the science has already moved further.

In a comment submitted by us at TestAVec and Brunel University of London, we argue that evaluating genome editing outcomes alone is no longer sufficient. 

Patient safety depends on three interconnected questions:

Vector Integrity – What is actually being delivered to the patient? Long-read sequencing has revealed that viral vectors often contain heterogeneous and unexpected nucleic acid species, including rearranged genomes and host-derived sequences.

Genome Integrity – What genomic changes occur after delivery? This remains a critical component of safety assessment, and we strongly support the FDA's recommendations for comprehensive genomic characterisation.

Biological Consequence – What do those genomic changes actually do inside human cells? Recent human cell-based multi-omics studies show that similar integration events can produce very different biological outcomes, meaning DNA sequence alone cannot always predict clinical risk.

Our proposal is straightforward: future regulatory frameworks should integrate these three complementary pillars into a single evidence-based approach that follows the complete pathway from manufacturing through vector composition, genome modification, cellular response and ultimately patient outcome.

As gene therapies become increasingly sophisticated, regulation must evolve alongside them. By combining comprehensive vector characterisation, genomic analysis and human functional biology, we believe regulators can achieve a more complete and clinically relevant assessment of safety, ultimately helping to bring safer gene therapies to patients with greater confidence.