The FDA has published a draft guidance that would permit makers of gene therapy (GT) products to leverage prior knowledge in their product development programs. The draft indicated that the agency is open to the use of prior knowledge for other types of products as well, part of the FDA's attempts to promote therapies for rare diseases.
The FDA's Center for Biologics Evaluation and Research (CBER) committed to developing the guidance as part of the Prescription Drug User Fee Agreement VII (PDUFA VII), a five-year agreement that expires Sept. 30, 2027. The draft encompasses both in-vivo and ex-vivo gene editing, but the agency said manufacturers may apply the terms of the final guidance to cell therapy products as well.
Both CBER and the FDA Center for Drug Evaluation and Research have emphasized the need for treatments for rare diseases in the first part of 2026. CBER held a May 18 webinar on the use of surrogate endpoints for rare diseases drug development and has developed a pilot program for advancing the science of endpoints for these rare diseases. CBER is collaborating with CDER and the Center for Devices and Radiological Health in these programs.
The draft guidance also states that gene therapy products that do not entail gene editing may also be able to leverage the features of the guidance when finalized. The same applies to nanoparticle-based gene therapies and adeno-associated viral vectors, the inclusion of which may drive the need for collaboration between CBER and the two other product centers.
The draft guidance includes two categories of prior knowledge that manufacturers can deploy across a therapy's product life cycle, starting with public knowledge. Public knowledge, or generally accepted scientific knowledge, may be limited to scientific principles of long standing, and may be found in peer-reviewed literature or compendia.
The second type of prior knowledge described in the draft guidance is platform knowledge, or experience with the development and manufacture of specific products and processes. A platform can be a mechanism of action, a delivery method, or a combination of these. However, some of these may be proprietary to a single manufacturer and hence unavailable to other manufacturers in the absence of the assent of the originator.
Prior knowledge of an existing gene therapy can be leveraged at several points in the product development cycle, such as the selection of analytical methods, benchmarks for stability and process validation data. This and other types of information would appear in the chemistry, manufacturing and controls (CMC) documentation for the product.
However, the credibility of these prior methods hinges on several factors, starting with the molecular similarities between the candidate product and the comparator product or gene editing mechanism. Similarities between the two manufacturing processes may also play a role in affirming the credibility of the prior knowledge, as may the presumed therapeutic mechanism.
For non-clinical/pre-clinical product assessment, the manufacturer can make use of prior knowledge with an appropriate consideration of the type of product and the proposed indication for use. For instance, a manufacturer can cite other products that make use of a similar or the same gene editing technology to evaluate the gain or loss of gene function as a consequence of gene knockout or knock-in. In the case of in-vivo gene editing products, prior knowledge can be obtained by a comparison of manufacturing processes and whether both products make use of a viral capsid that may or may not carry and deliver therapeutic DNA.
With regard to the use of prior clinical trial data as part of the clinical trial design process, the draft guidance recommends the sponsor contact the FDA for discussions of considerations such as dose-limiting toxicity thresholds. The draft also describes the opportunities for use of prior knowledge for considerations such as the conduct of a clinical trial and the duration of longer-term follow-up studies. The FDA is accepting comments from stakeholders through Sept. 1, 2026.