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Press Release
PRIM&R Submits Comment to FDA on Draft Guidance for ‘Plausible Mechanism Framework’
FOR IMMEDIATE RELEASE
May 15, 2026 BOSTON— Public Responsibility in Medicine and Research (PRIM&R), a nonprofit organization with more than 3,500 members across the research enterprise, submitted a formal comment to the U.S. Food and Drug Administration (FDA) in response to its Draft Guidance on the Plausible Mechanism Framework for individualized therapies targeting specific genetic conditions.
The FDA has previously described plausible mechanism as “a novel framework through which cutting-edge treatments tailor-made for patients with ultra-rare diseases can be used as a basis for FDA approval.”
As stated in the federal agency’s request for comment, “FDA is announcing the availability of a draft document entitled ‘Considerations for the use of the Plausible Mechanism Framework to Develop Individualized Therapies that Target Specific Genetic Conditions with Known Biological Cause.’ The draft guidance describes considerations for generating substantial evidence of effectiveness and evidence of safety of individualized therapies based on a plausible mechanism framework. The guidance specifically discusses genome editing and RNA-based therapies; however, the general concepts may apply to other types of individualized therapies.”
PRIM&R’s recommendations, submitted April 27, identify several areas where the FDA’s draft guidance could be strengthened, including the need for clear eligibility thresholds for when the framework applies. “PRIM&R's members, many of whom serve on IRBs throughout the United States, need clear standards to fulfill their oversight responsibilities. This guidance presents an opportunity for the FDA to clarify whether all criteria must be met and what is required before proceeding with the plausible mechanism framework,” PRIM&R Executive Director Ivy R. Tillman, EdD, CIP wrote in the submission to the FDA.
Institutional Review Boards, or IRBs, review and monitor biomedical research involving people. IRBs have the authority to approve, require modifications, or disapprove research, according to the Code of Federal Regulations.
Additionally, PRIM&R’s comment submission to the FDA notes, “PRIM&R appreciates that the guidance encourages the following to address key risks of gene-editing (GE) therapies: long-term follow-up studies to collect data on delayed adverse reactions; and the use of subject-level stopping rules that allow for clinical judgement.”
“These provisions reflect the type of careful, participant-centered thinking that should guide the framework as it continues to develop,” Tillman wrote.
To read the full text of PRIM&R’s submission to the FDA, click here.
May 15, 2026 BOSTON— Public Responsibility in Medicine and Research (PRIM&R), a nonprofit organization with more than 3,500 members across the research enterprise, submitted a formal comment to the U.S. Food and Drug Administration (FDA) in response to its Draft Guidance on the Plausible Mechanism Framework for individualized therapies targeting specific genetic conditions.
The FDA has previously described plausible mechanism as “a novel framework through which cutting-edge treatments tailor-made for patients with ultra-rare diseases can be used as a basis for FDA approval.”
As stated in the federal agency’s request for comment, “FDA is announcing the availability of a draft document entitled ‘Considerations for the use of the Plausible Mechanism Framework to Develop Individualized Therapies that Target Specific Genetic Conditions with Known Biological Cause.’ The draft guidance describes considerations for generating substantial evidence of effectiveness and evidence of safety of individualized therapies based on a plausible mechanism framework. The guidance specifically discusses genome editing and RNA-based therapies; however, the general concepts may apply to other types of individualized therapies.”
PRIM&R’s recommendations, submitted April 27, identify several areas where the FDA’s draft guidance could be strengthened, including the need for clear eligibility thresholds for when the framework applies. “PRIM&R's members, many of whom serve on IRBs throughout the United States, need clear standards to fulfill their oversight responsibilities. This guidance presents an opportunity for the FDA to clarify whether all criteria must be met and what is required before proceeding with the plausible mechanism framework,” PRIM&R Executive Director Ivy R. Tillman, EdD, CIP wrote in the submission to the FDA.
Institutional Review Boards, or IRBs, review and monitor biomedical research involving people. IRBs have the authority to approve, require modifications, or disapprove research, according to the Code of Federal Regulations.
Additionally, PRIM&R’s comment submission to the FDA notes, “PRIM&R appreciates that the guidance encourages the following to address key risks of gene-editing (GE) therapies: long-term follow-up studies to collect data on delayed adverse reactions; and the use of subject-level stopping rules that allow for clinical judgement.”
“These provisions reflect the type of careful, participant-centered thinking that should guide the framework as it continues to develop,” Tillman wrote.
To read the full text of PRIM&R’s submission to the FDA, click here.
About PRIM&R
Since 1974, PRIM&R has advanced the highest ethical standards in the conduct of research. We accomplish this mission through education, membership services, professional certification, public policy initiatives, and community building. PRIM&R is a 501(c)3 nonprofit. Find out more at www.primr.org
Media Contact:
Daniel McLean
Public Engagement Manager
Public Responsibility in Medicine and Research (PRIM&R)
Direct: 617-303-1877
dmclean@primr.org
www.primr.org