The Biotechnology Innovation Organization (BIO) submitted comments supporting the FDA’s proposed Plausible Mechanism Framework, which is intended to help evaluate safety and efficacy for individualized and disease-targeted therapies when large randomized trials are impractical. BIO urged the agency to broaden applicability, add definitions and operational detail, and expand flexibility for CMC expectations for individualized therapies. The group also recommended clearer guidance on using prior knowledge and platform technologies across the product lifecycle.