Comment from Anonymous

April 24, 2026 Division of Dockets Management (HFA-305), Food and Drug Administration Re: Docket No. FDA-2026-D-1256: Considerations for the use of the Plausible Mechanism Framework to Develop Individualized Therapies that Target Specific Genetic Conditions with Known Biological Cause; Draft Guidance for Industry. Dear Food and Drug Administration Representatives, As students and future engineering professionals in bioengineering and biotechnology, we appreciate the opportunity to comment on the draft guidance issued by the U.S Food and Drug Administration regarding the Plausible Mechanism Framework for individualized gene therapies. While we recognize the potential for these therapies to be transformative in the treatment of life-threatening genetic diseases, we believe that the regulatory framework must be more robust in addressing the unique ethical challenges posed by individualized treatments. We respectfully urge the FDA to strengthen this guidance to more fully address the ethical, safety, and equity challenges these treatments introduce; challenges that are especially acute given how rapidly gene editing technologies such as CRISPR are advancing beyond the pace of existing legislative frameworks. Our first ethical issue revolves around the reliance on a “plausible mechanism” of action rather than having extensive clinical evidence typically required for drug approval. Authorizing treatment on the basis of theoretical benefit, rather than demonstrated clinical outcomes, raises a fundamental engineering ethics question: at what evidentiary threshold does human application become acceptable? This concern is compounded when patients are in life-threatening situations and may feel they have no alternative. We recommend that the FDA implement mandatory, structured long-term monitoring requirements for all therapies approved under this framework, including minimum follow-up periods and standardized reporting. The requirements would bridge the evidentiary gap that the plausible mechanism standard creates while still enabling access to potentially life saving treatments. Our second concern is informed consent and patient vulnerability. Patients eligible for these therapies often face life-threatening conditions, making them highly vulnerable due to the severity of their condition. The experimental and personalized nature of these treatments may increase the risk of creating therapeutic misconception, where hope and bias compromise a patient's ability to provide truly informed consent. We recommend that the FDA require consent protocols specifically designed for this framework, ones that clearly and explicitly distinguish between a theoretical mechanism of action and proven clinical results. Consent materials should be reviewed by an independent bioethics board and written in plain language accessible to patients without a scientific background. A third ethical risk is that individualized therapies will highly favor those with significant social capital and wealth, creating a utilitarian tension between allocating vast resources to treat a single individual versus investing in therapies that benefit larger populations. We advocate for the development of clear selection frameworks to ensure that access is based on medical necessity rather than socioeconomic status. From an engineering ethics perspective, ensuring rapid technological advancement does not outpace our responsibility to protect public welfare. Engineers and institutions developing these technologies bear a duty, independent of what regulation requires, to consider the full societal consequences of their work. We urge the FDA to use this guidance as an opportunity to set a strong precedent: one that affirms patient safety, equitable access, and ethical oversight as non-negotiable foundations for any individualized therapy approved under the Plausible Mechanism Framework. We thank the FDA for the opportunity to participate in this process and for its continued commitment to science-based ethically grounded policymaking. Respectfully submitted, Undergraduate Students, College of Engineering University of California, Berkeley