FDA Draft Guidance on Gene Editing: More Light at the Regulatory Sky

Karoline Hahn, KCR Senior Consultant for Advanced Therapies

Gene editing as a tool for new therapeutics is entering the drug development space at a fast pace. The US Food and Drug Administration (FDA) had acknowledged this technological progress by releasing the draft guidance document, “Human Gene Therapy Products Incorporating Human Genome Editing”1 to the industry. For the first time, the FDA addresses quality, non-clinical and clinical aspects of gene editing medicinal products in one document.

While quality requirements are basically the same for gene editing and viral vector-based gene therapy products, safety requirements are more specific to gene editing.

Not surprisingly, off-target gene editing and genomic integrity are the primary safety concern of the FDA´s considerations. Preclinical safety studies should be designed to identify potential risks associated with administration of the gene editing product, including the characterization of on- and off-target activity, chromosomal structural changes, and their biological consequences. A surrogate gene editing product may be acceptable for safety evaluation as genomic sequences between animals and humans differ. However, when using in vivo gene editing, assessment of off-target editing effects may be challenging.

The FDA´s focus is on the unintended consequences of on- and off-target editing that could perpetuate from these products. Again, off-target gene editing effects and genome integrity must be addressed thoroughly in the clinical study, aside from the general risks coming along with gene therapy, such as immunogenicity or hepatotoxicity. Consequently, the required long-term follow-up must have a duration of 15 years.

Currently, all therapeutic products using gene editing target rare, debilitating conditions. In general, testing starts in patients with severe or advanced disease. However, due to their condition, interpretation of safety and efficacy data may be challenging. With this guidance, the FDA finally considers the inclusion of subjects with moderate or less advanced disease in first-in-human clinical trials, which is an important step towards meaningful drug development

This draft guidance joins a series of previous FDA guidance documents on the topics, all calling for a tailored, product-specific solution. It is obvious that the one-size-fits-all approach is not for gene therapy products.


1: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/human-gene-therapy-products-incorporating-human-genome-editing

About KCR:

KCR is a clinical development solutions provider creating value for biotechnology and pharmaceutical organizations. Founded in 1997, our expert teams support clients with full-service clinical development capabilities across three main areas: Trial Execution, Consulting and Placement. KCR operates across North America, Europe, and Australia, with main office locations in Boston, US, Berlin, Germany, and Warsaw, Poland. Our geographical coverage across 25+ countries, cutting-edge technical capabilities and tailored offerings allow for the optimized delivery of solutions to develop life-changing therapies. KCR offers access to an estimated population of 1.1 billion people. For more information visit www.kcrcro.com.

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KCR is an international clinical development solutions provider for the bio-pharmaceutical & medical device industries.