FDA endorses prior knowledge use in gene therapy development

Background

The new draft guidance was developed as part of FDA’s PDUFA VII commitment to create clearer pathways for using existing knowledge in cell and gene therapy development. Although the guidance focuses on genome editing products, FDA notes that many of its recommendations may also apply to other gene therapies, including AAV-based products, nanoparticle delivery systems, and certain cell therapies. However, FDA emphasizes that additional product-specific considerations will still apply and may limit the extent of leverage depending on how the therapy is designed and manufactured.

The guidance provides additional details regarding data FDA considers “generally accepted scientific knowledge,” a term introduced and discussed in FDA’s 2023 draft guidance titled, “Generally Accepted Scientific Knowledge in Applications for Drug and Biological Products: Nonclinical Information,” by establishing the circumstances in which a sponsor may rely on prior knowledge to support development programs. The draft guidance also reflects FDA’s broader effort to make development of advanced therapies more efficient. It complements earlier draft guidance on “Platform Technology Designation Program for Drug Development,” “Considerations for the use of the Plausible Mechanism Framework to Develop Individualized Therapies that Target Specific Genetic Conditions with Known Biological Cause Plausible Mechanism Framework,” and “Safety Assessment of Genome Editing in Human Gene Therapy Products Using Next-Generation Sequencing.” Together, these draft guidance documents are designed to streamline gene therapy submissions, balancing the need for more efficient development with FDA’s expectations for robust scientific justification.

What is “prior knowledge”?

In the new draft guidance, FDA defines “prior knowledge” as information that can reasonably support development of a new product based on what is already known. This includes:

• Public knowledge, such as well-established scientific findings and peer-reviewed literature; and
• Platform knowledge, meaning experience gained from developing or manufacturing similar products or using similar technologies.

This knowledge can come from a company’s own prior work, third-party data (such as master files), published research, or collaborative industry efforts.

Importantly, FDA makes clear that “platform knowledge” in this guidance is different from the formal “platform technology” designation program established by statute. Sponsors do not need a formal designation to rely on prior knowledge. Instead, they must show that the existing information is relevant to their specific product.

How sponsors may leverage prior knowledge, and where FDA draws the line

When leveraging prior knowledge to support product approval, sponsors must evaluate how similar their product is to the product associated with the prior data, providing justification for any differences. Prior knowledge can only be leveraged where there is a clear scientific rationale showing that the data is applicable. Sponsors intending to leverage prior knowledge for product approval should provide a detailed comparison of relevant similarities and differences and engage FDA early (e.g., pre IND)

A.     CMC and manufacturing (highest impact area)

The appropriateness of leveraging prior knowledge in CMC and manufacturing depends on similarity in structure, formulation, manufacturing process, facility, intended mechanism and other factors.

• Analytical methods and validation. Platform analytical methods and validation data may be reused across similar products to reduce qualification and validation burden, provided differences (e.g., guide RNA sequences or sample matrices) do not materially affect performance. Targeted, product-specific verification may be sufficient where differences exist.
• Specifications and lot release. Prior knowledge may support selection of quality attributes and acceptance criteria across similar products (e.g., guide RNAs with similar structure and manufacturing), but identity and potency remain product-specific and generally require additional justification.
• Stability and shelf life. Stability data from similar products may support early-phase development and, in some cases, inform commercial shelf life, but cannot replace long-term real-time stability data at the BLA stage.
• Comparability, process characterization, and validation. Platform data may inform comparability strategies and process parameter criticality, and in some cases may support reduced PPQ batch expectations, where supported by sufficiently similar processes.

B.     Nonclinical development (risk-based leveraging)

The ability to leverage prior nonclinical knowledge depends on the similarity and differences between products. Sponsors may rely on prior in vitro, in silico, in vivo, and analogous product data to support early development using a stepwise, risk-based approach. Certain biological activity data may be leveraged across products with the same on-target edits, although editor- and guide RNA-specific effects must still be evaluated. Leveraging depends on similarity across vectors, formulations, delivery, dose, and regimen, and may extend in limited circumstances to biodistribution, toxicology, DART, and genotoxicity data where product attributes are sufficiently similar.

C.     Clinical development (design and evidence strategy)

Sponsors may leverage prior clinical experience to inform dose selection, safety monitoring, re-dosing strategies, and endpoint selection, and may in some cases rely on prior clinical data to support abbreviated safety or efficacy datasets where no clinically meaningful differences are expected based on product or population characteristics. FDA also encourages appropriate use of natural history studies and real-world evidence, subject to early engagement to ensure the data are fit for purpose.

D.     Clear boundaries where prior knowledge cannot be leveraged

The guidance makes clear that certain categories of prior knowledge remain inherently product-specific and are generally not appropriate for leveraging across programs. For example, FDA indicates that off-target assessment data cannot be leveraged as prior knowledge across products using different guide RNAs or sequence-recognition components, are specific to each genomic locus and therefore not transferable across products targeting different sites, and that genomic integrity data cannot be readily leveraged where products have different genomic targets.

The guidance allows for different but similar biological products to be developed based on what is already known. It therefore advances some way towards a pathway outside of the biosimilars context for sponsors to leverage their own pioneering work, or the pioneering work of other sponsors, without costly reinvention or duplication of existing data. The absence of anything like a 505(b)(2) pathway for biological products was a notable issue in the discussion leading up to the Biological Product Competition and Innovation Act. But moving forward, sponsors will now be able to leverage preexisting data (with suitable justification and authorization) in development. This is not a new abbreviated on “middle” pathway between 351(a) and 351(k). There remain only two pathways for the licensure of biological products. The guidance is intended to facilitate efficiencies in the development phase that may lead to the submission of a 351(a) BLA. While the guidance does not directly address the issue of data protection when one sponsor relies on another sponsors proprietary data, it can be inferred that this is only permitted where there is appropriate authorization (right of reference). The guidance references 21 CFR 600.2(g), which allows sponsors of investigational biologics to incorporate information by reference to a master file. This requires a right of reference. Any relied upon data must then generally be submitted directly to the BLA and to do so would require authorization, access, and control.

FDA’s guidance responds to practical challenges for gene therapies

The draft guidance makes clear that sponsors may leverage both public and platform knowledge, but must do so in a way that enables FDA to evaluate the scientific applicability of the referenced data. Where sponsors rely on publicly available information, submissions should include sufficiently detailed underlying materials, along with a clear explanation of relevance and any necessary bridging or confirmatory data. Where platform knowledge is used, sponsors may provide the data directly or reference prior INDs or master files (with appropriate authorization), including in certain cases cross-referencing a primary IND when studying multiple product versions in an early-phase trial. In all cases, however, the submission must clearly explain why the leveraged knowledge applies to the specific product under review.

Importantly, FDA draws a distinction at the BLA stage: while certain information (such as excipient data) may be cross-referenced with authorization, applicants are generally expected to include full information for drug substance and drug product components, reflecting FDA’s expectation that sponsors have direct control over the manufacturing process at the time of licensure. Accordingly, FDA recommends early engagement through meetings such as FDA’s INTERACT or pre‑IND meetings to align on proposed leveraging strategies and avoid issues later in development.

Conclusion

The guidance signals a meaningful shift toward greater acceptance of well-justified efficiencies in genome editing development programs. For sponsors operating in an environment where rare disease constraints, cost pressures, and manufacturing complexity can make development particularly burdensome, the ability to rely on prior knowledge—whether internal, third-party, or publicly available—offers a clearer path to reduce duplication and more efficiently deliver important therapies to patients. At the same time, FDA reiterates that sponsors cannot automatically leverage prior knowledge: success will depend on a sponsor’s ability to demonstrate true scientific comparability and provide a disciplined, product-specific rationale. Accordingly, sponsors should proactively assess where prior knowledge can be leveraged across their portfolios and engage FDA early in development, because the most effective use of this flexibility will depend on aligning scientific and regulatory strategy from the outset.

FDA invites comments on the draft guidance through September 1, 2026. If you may be interested in submitting a comment or have questions about gene therapy development regulations, feel free to reach out to any of the authors of this alert or the Hogan Lovells attorney with whom you regularly work.

Authored by Elizabeth Jungman, Jason Conaty, Bryan Walsh, and Ashley Grey