You Can’t Call It Cheatin’: FDA Draft Guidance Provides a Framework for Leveraging Prior Knowledge in Genome Editing Product Development

Key Takeaways

• The Food and Drug Administration (“FDA”) issued recent draft guidance describing how sponsors of human gene therapy products incorporating genome editing may leverage prior knowledge, including public and platform knowledge, to streamline development across chemistry, manufacturing, and controls (“CMC”), nonclinical, and clinical programs.
• The guidance provides a structured framework and practical table mapping leveraging proposals to submission types, offering sponsors a roadmap for more efficient regulatory engagement.
• The guidance may be particularly useful for rare disease programs, where small patient populations and tight development timelines make redundant data generation particularly costly.

“You can’t call it cheatin’, she reminds me of you,” the Gin Blossoms sang on their 1996 album Congratulations I’m Sorry. For sponsors developing genome editing therapies, FDA’s new draft guidance offers a similar reassurance: relying on what is already known is not cutting corners. It is sound regulatory science.

On June 2, 2026, FDA issued “Leveraging Prior Knowledge in the Development of Human Gene Therapy Products Incorporating Genome Editing,” a draft guidance on how sponsors may use prior knowledge, to be defined shortly in this Bulletin, to streamline development and accelerate regulatory review.¹ Issued by the Center for Biologics Evaluation and Research (“CBER”) under a Prescription Drug User Fee Act (“PDUFA”) VII commitment, the guidance addresses how existing CMC, nonclinical, and clinical knowledge may support the development of genome editing products involving ex vivo and in vivo modification of human somatic cells.

As background, in January 2024, FDA issued guidance on “Human Gene Therapy Products Incorporating Human Genome Editing,” covering product design, manufacturing, nonclinical evaluations, and early-phase clinical trial design.² That guidance did not address how sponsors might rely on existing data to avoid repeating studies already conducted for similar products. The new draft guidance fills that gap by establishing a framework for leveraging publicly available science and proprietary platform data across CMC, nonclinical, and clinical programs.

In this Bulletin, we highlight key points of the guidance and offer our own observations.³

Highlights

• The draft guidance encourages sponsors to build on existing knowledge, rather than generating new data from scratch. FDA explains that both publicly available science and proprietary platform data may support regulatory submissions for genome editing products, reducing duplicative effort.
• The guidance is directed at human gene therapy products that use ex vivo or in vivo genome editing of human somatic cells. FDA notes that certain recommendations could also apply to other cell and gene therapy products, including adeno-associated viral (“AAV”) vectors, nanoparticle-based therapies, and ex vivo-modified cell-based products.
• The guidance establishes three categories of knowledge, drawn from FDA’s definitions:
  • “Public knowledge” is defined by FDA as “generally accepted scientific knowledge” that is “based on widely accepted scientific principles that are typically long-standing,” such as peer-reviewed publications, regulatory guidance documents, and pharmacopeial standards.
  • “Platform knowledge” is defined by FDA as “knowledge gained from developing and manufacturing a specific type of product across multiple programs.” This category may include proprietary data held in Investigational New Drug (“IND”) applications or master files.⁴
  • “Prior knowledge,” as used in the guidance, is an umbrella term encompassing both public and platform knowledge.
• Whether leveraging is scientifically sound depends on a multi-factor analysis. FDA identifies relevant variables including molecular structure, cell source, manufacturing process, formulation, on-target genomic edits, and therapeutic mechanism. For in vivo products, route of administration, dosing regimen, and dose levels also matter.
• On the CMC front, FDA identifies several categories of prior knowledge that may be leveraged:
  • Analytical Methods: According to FDA, platform analytical procedures may be carried over to products with similar structural profiles, though sponsors should confirm that each method performs adequately for the specific product.
  • Lot Release Specifications: Prior knowledge may support justification of which quality attributes to include and what acceptance criteria to set.
  • Stability Data: Leveraging may be appropriate when products share similar composition, formulation, and container closure systems.
  • Comparability Data: Prior knowledge may inform comparability study design when manufacturing changes are introduced.
  • Process Characterization and Process Validation: Platform process knowledge may support risk assessments and reduce the scope of product-specific process validation studies.
• For nonclinical development, the guidance takes a product-type-specific approach to leveraging:
  • For ex vivo products, FDA indicates that biological activity data tied to specific genomic edits may be shared between products making the same edits. Nonclinical safety data from cell manufacturing steps (e.g., expansion, selection, activation) may also apply across products using comparable processes.
  • For in vivo products, leveraging depends on how closely products share a delivery system, formulation, biodistribution profile, and target tissue. FDA notes that toxicology data may be shared when products use the same delivery platform and route of administration.
  • Instead of nonclinical studies on animals, leveraging clinical data from adult patients may be applicable for determining pediatric starting dose levels, with appropriate justification.
• The guidance treats bioinformatics data differently depending on its type. Off-target editing data may be shared between products only when they use the same guide RNAs, genome editors, and cell type; FDA cautions that such data is “generally not scientifically appropriate for leveraging if drug products edit different genomic locations.” By contrast, next-generation sequencing methods, analysis pipelines, and study designs may be more broadly leveraged across multiple product types.
• For clinical development, the guidance distinguishes between leveraging prior data to inform trial design (e.g., dose selection, dose-limiting toxicity (“DLT”) definitions, monitoring intervals) and leveraging prior data to inform trial conduct or analysis (e.g., abbreviating safety, efficacy, or pharmacokinetic (“PK”) databases based on prior clinical experience with similar products).
• For public knowledge, the guidance states that referenced material should be included in the submission with sufficient detail. For platform knowledge, sponsors may submit data directly or cross-reference prior INDs or master files using a Letter of Authorization under 21 C.F.R. 312.23(b). At the Biologics License Application (“BLA”) stage, however, FDA expects applicants to submit drug substance and drug product information directly, reflecting the expectation that sponsors will have “knowledge of and direct control over the manufacturing process” at licensure.
• FDA encourages sponsors to discuss leveraging proposals with the agency through pre-IND meetings or other formal FDA meetings early in development.
• The guidance includes a table that maps types of prior knowledge to the appropriate submission vehicles, providing a practical reference for sponsors.

AGG Observations

• Although the guidance targets genome editing products, sponsors of other cell and gene therapy products, including AAV vectors and nanoparticle-based therapies, should assess whether the leveraging framework may apply to their programs as well.
• FDA draws a distinction between “public knowledge” and “platform knowledge” that has practical implications for how sponsors package their submissions. Public knowledge can be referenced by citing published literature or pharmacopeial standards directly in the submission. Platform knowledge, by contrast, may involve proprietary data that requires cross-referencing INDs or master files with a Letter of Authorization from the data owner. Sponsors should classify whether their prior knowledge as “public” or “platform” to determine which submission pathway applies.
• The guidance does not offer a bright-line test for when leveraging is permissible. Instead, it calls for a factor analysis across variables such as molecular structure, manufacturing process, and therapeutic mechanism. Sponsors should develop a scientific rationale for each dataset they intend to leverage, anticipating FDA scrutiny of how closely the data fits the specific product.
• FDA notes that the guidance’s recommendations are not exhaustive and invites sponsors to propose additional leveraging approaches. Knowledge may also be leveraged progressively as experience accumulates. This indicates openness, but sponsors should recognize that a justification for applicability is required in every case.
• Section III of the guidance provides a roadmap organized around CMC, nonclinical, and clinical development, with specific examples of leverageable data. The table in Section IV maps leveraging proposals to submission types. Sponsors should use these as a starting point for FDA engagement.
• Sponsors should use pre-IND or other formal FDA meetings to discuss leveraging proposals early but should frame discussions at a conceptual level to preserve flexibility. Rare disease programs evolve as platform knowledge accumulates, and locking in specific datasets prematurely may constrain future options.
• The IND-to-BLA transition poses a practical challenge for sponsors relying on third-party data. Cross-referencing through Letters of Authorization works during the investigational phase, but FDA expects direct submission of drug substance and drug product data at the BLA stage. Sponsors building strategies around third-party master files should plan early for internalizing that knowledge or establishing independent manufacturing control.
• Off-target editing data is a notable exception to the leveraging framework. Unlike manufacturing or analytical method data, off-target profiles are tied to the specific genomic location being edited. Each new target will likely require its own off-target and genomic integrity assessment, which sponsors should factor into timelines and budgets for multi-target portfolios.
• This guidance is part of a broader set of FDA actions, including the Plausible Mechanism Framework, CMC Flexibilities guidance, and the next-generation sequencing safety assessment draft guidance, that together form an interlocking regulatory ecosystem designed to lower development barriers for genome editing products. While the rare disease space stands to benefit most, several of these initiatives apply to cell and gene therapy products more broadly.
• The guidance remains in draft form. Comments may be submitted by September 1, 2026, through Regulations.gov under Docket No. FDA-2026-D-1257. Stakeholders should consider submitting comments during the open period, particularly when the guidance is vague or unclear. Engaging now can help shape the final version.

In sum, sponsors developing genome editing therapies can’t call it cheatin’ when they leverage prior knowledge, so long as they can justify why the science applies. Companies that engage early with FDA and build leveraging strategies into their development plans may find the path to patients move considerably faster.

For questions on the guidance, please contact a member of AGG’s Food & Drug team.

[1] The draft guidance is available here. The authors note that the Bulletin does not exhaustively summarize the guidance. We provide a summary of some key points and examples described in the draft guidance.

[2] FDA Guidance for Industry, “Human Gene Therapy Products Incorporating Human Genome Editing” (January 2024), available here.

[3]

[4] The agency notes that some terminology used in this draft guidance may conflict with uses elsewhere in the Federal Food, Drug, & Cosmetic Act, such as the use of the term “platform” which differs from that in Section 506K of the FD&C Act, as modified by the PREVENT Pandemics Act.