Comment from Kline Lindsay

I strongly support this draft guidance and FDA’s efforts to reduce unnecessary animal studies through the use of Weight of Evidence approaches and other scientifically justified alternatives. I watched the 2025 FDA/NIH workshop, Reducing Animal Testing Through Innovation, Collaboration, and Open Science, Dr. Saber Hussain discussed what in my opinion is one of the most important barriers to reducing animal testing: Sponsors may have relevant evidence available but be unable to efficiently rely on it because of their uncertainty regarding what FDA will accept in a Weight of Evidence package. In a world of diminishing public trust in scientific and medical professionals, it is more important than ever that FDA professionals and their colleagues understand and trust in the members of the scientific and medical industry's abilities, knowledge, and desire to progress forward into well documented and researched evidentiary study packages that will finally remove animal models as the gold standard. Sponsors have decades of experience understanding what an acceptable animal-study package looks like. However, comparable clarity does not yet exist for many non-animal approaches. As a result, even when alternatives and relevant evidence exist, sponsors may still choose to conduct animal studies because the regulatory pathway is more familiar, predictable, and clearly defined. Even with those comforts embedded in the field, there is still an enormous cavern of error. Taking this 90+ percentage of failure once trails move from animal models to human trials and overlaying the same percentages in any other scientific field, it would be painfully obvious that such percentages are unacceptable and a hinderance to the goals needing to be met. I encourage FDA to provide additional examples, case studies, and practical guidance demonstrating what constitutes an acceptable Weight of Evidence submission and how such evidence will be evaluated. Providing a clear and concise pathway to what is required will certainly produce more confidence in moving toward non - animal models. I was particularly encouraged by discussions regarding Generally Accepted Scientific Knowledge (GASK). Expanding the practical use of GASK could help transform established evidence into usable regulatory knowledge. When knowledge is sufficiently established and broadly accepted, sponsors should have clear pathways to rely on that knowledge rather than recreating it through additional animal studies. The issue of right-to-reference also deserves continued attention. As discussed during the workshop, sponsors may identify relevant existing evidence but be unable to rely upon it because the underlying data are owned by another entity. The resulting legal negotiations, delays, and costs can unintentionally incentivize the generation of new animal data even when scientifically relevant evidence already exists. The continuous cycle of figuring out information that has already been discovered elsewhere is wasteful at best. Having a baseline of understood knowledge would push our scientific and biomedical industries to a higher baseline from which to start. This opens the door to endless opportunities to ask better questions, delve deeper into studies that had previously been slowed or on hold due to a lack of my aforementioned baseline of knowledge, and it gives the US an edge by allowing those within the field to talk amongst themselves. When we keep secrets, we only go in circles. I respectfully encourage FDA to: > Provide detailed examples of successful Weight of Evidence packages that could replace animal studies. > Clarify what types of evidence qualify as Generally Accepted Scientific Knowledge and how sponsors may rely upon such knowledge. > Develop mechanisms to reduce right-to-reference barriers that can unintentionally incentivize duplication of animal studies when relevant evidence already exists. > Promote consistency in review and implementation across divisions so sponsors have confidence that non-animal approaches will be evaluated predictably. This draft guidance represents meaningful progress. However, achieving the full potential of non-animal methods will require not only the development of alternatives, but also clear regulatory pathways that allow existing evidence and established scientific knowledge to be used effectively. Thank you for your time in reviewing my thoughts and comments.