Industry stakeholders are urging the U.S. Food and Drug Administration (FDA) to broaden its recent draft guidance regarding prior knowledge in gene therapy development. This request aims to encompass a wider range of cell and gene therapies (CGT), not limited to genome editing techniques.
Context of the Draft Guidance
In June, the FDA released draft guidance that outlines how sponsors can utilize prior knowledge, particularly in chemistry, manufacturing, and controls (CMC), as well as nonclinical and clinical knowledge, in the context of gene therapies involving ex vivo and in vivo genome editing of human somatic cells. The FDA indicated that this information is particularly relevant for the development of gene therapies targeting rare diseases.
Despite the guidance’s focus on genome editing products, industry representatives seek clarification on its applicability to other CGT products, such as adeno-associated viral (AAV) vectors and nanoparticle-based gene therapy products.
Industry Concerns
The Pharmaceutical Research and Manufacturers of America (PhRMA) and the Biotechnology Innovation Organization (BIO) have voiced concerns that the title of the draft guidance could mislead stakeholders into believing that leveraging prior knowledge is primarily relevant to genome editing technologies. They proposed changing the title to “Leveraging Prior Knowledge in the Development of Human Cell and Gene Therapy Products” to reflect its broader applicability.
BIO emphasized that the principles outlined in the guidance are widely applicable across various CGT products. They encouraged the FDA to clearly delineate which recommendations pertain to non-genome-editing modalities and to provide concrete examples of their implementation.
Request for a Structured Framework
Both PhRMA and BIO have recommended that the FDA adopt a structured, risk-based framework to guide how prior knowledge can be leveraged. They noted that the ability to utilize prior knowledge hinges on the similarities between products, manufacturing processes, and other attributes. Clarifying how sponsors should assess and document these similarities could enhance predictability and consistency in regulatory interactions.
PhRMA expressed that the current draft guidance lacks a clear framework to evaluate the extent to which prior knowledge can be relied upon. This ambiguity could result in uncertainty for sponsors regarding when they can fully depend on prior knowledge, when bridging data is necessary, and when new data must be generated.
Clarification on Proprietary Information
PhRMA has also urged the FDA to clarify its stance on the use of proprietary information within the guidance. They highlighted that while the draft acknowledges the varied ways in which prior knowledge can be generated, it simultaneously maintains restrictive views on using master files and referenced information in biologics license applications (BLAs).
The group has requested that the guidance affirm the protection of proprietary information while allowing the use of prior knowledge, provided that sponsors have the necessary legal permissions. This distinction is crucial to ensure that the guidance does not unintentionally undermine existing protections for confidential data.
Lifecycle and Long-Term Follow-Up Considerations
PhRMA has called for clarity on how prior knowledge can be applied throughout the product lifecycle, as well as a more explicit process for reconsidering long-term follow-up (LTFU) requirements. Although the FDA has suggested flexibility in LTFU expectations, the draft guidance lacks specifics on how this flexibility will be operationalized.
The group advocates for a risk-based framework that could adapt LTFU requirements based on the accumulation of safety data from similar products or platforms. This would allow for a more tailored approach to monitoring therapies over time.
Early Engagement and Transparency
Both PhRMA and BIO encourage the FDA to engage with sponsors at any stage of the drug development process regarding the use of prior knowledge. They also suggest that the agency provide more transparency about its expectations, which would empower sponsors to develop informed regulatory strategies without needing to rely solely on preliminary meetings for guidance.
Additional Considerations
Friends of Cancer Research has also weighed in, advocating for a structured framework for leveraging prior knowledge that would include scientific justifications. They stressed that similarity assessments should be contextual, considering specific inferences rather than broad comparisons between products.
Furthermore, there is a call for greater clarity on how prior knowledge can streamline clinical development, particularly for individualized therapies. Friends have suggested the FDA clarify how information can be cross-referenced across various submissions, enhancing the efficiency of the regulatory process.
Conclusion
As the landscape of gene therapies evolves, the FDA’s guidance plays a critical role in shaping the regulatory environment. Expanding the scope of this guidance to reflect a broader application of prior knowledge could foster innovation and efficiency in the development of diverse CGT products. By addressing industry concerns and enhancing clarity, the FDA can enhance the regulatory framework, ultimately benefiting patients in need of cutting-edge therapies.
- Key Takeaways:
- Industry stakeholders advocate for an expanded FDA draft guidance on prior knowledge in CGT development.
- A structured, risk-based framework is suggested for leveraging prior knowledge effectively.
- Clarification on proprietary information and its use in regulatory submissions is essential.
- There is a need for transparency and early engagement from the FDA throughout the drug development process.
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