The EveryLife Foundation submitted comments in response to the FDA’s draft guidance on the Plausible Mechanism Framework for the development of individualized therapies targeting specific genetic conditions with known biological causes. Comments reflected input from the Foundation’s Community Congress coalition partners.
The Plausible Mechanism Framework is a set of recommendations to help those developing individualized therapies generate sufficient evidence that the therapies are safe and effective and can be manufactured appropriately. The Framework is not a new regulatory pathway, but it IS an updated approach to how individualized therapies could be approved through the existing pathways. To learn more about the framework, visit our website: FDA Takes Important Step Toward Individualized Therapies – EveryLife Foundation for Rare Diseases
Our comments included requests for the FDA to clarify how the Framework will be applied to broader populations and technologies, and suggestions for how to maximize the impact of the Framework, including:
- Ensure a flexible and feasibility-driven approach to allow the opportunity for individualized therapies to go through a commercial approval model that could benefit a broader patient population over time.
- Use the Rare Disease Innovation Hub to convene conversations about operationalizing the framework.
- Develop scenario-based case studies outlining appropriate and inappropriate use of the framework.
- Ensure provision of adequate FDA resources, specifically noting the impact of appropriate staffing and scientific expertise. Additional resources should be used to develop natural histories and biomarkers for rare diseases.
- Encourage the use of large data platforms to leverage parallel preclinical, toxicology, and manufacturing knowledge.
- Clarify how patient preference data and patient experience data will be formally incorporated into Framework reviews and product labeling.
- Identify how to engage patient organizations and other stakeholders to characterize populations and create drug development tools in a timely manner.
- Develop dedicated guidance addressing evidence standards for the use of surrogate markers as drug development tools eligible for use under the Framework.
- Consider establishing a streamlined qualification pathway for novel surrogate markers proposed for use under the Framework.
Click here to view our full comments. We look forward to continuing to work with the FDA and the rare disease community to further operationalize the Plausible Mechanism Framework. We will keep you posted as soon as there are updates.
