Comment submitted by Angela Meccariello

I am an Assistant Professor in the Department of Life Sciences at Imperial College London, where I lead a research programme developing next-generation genetic technologies for the sustainable control of agricultural insect pests. My research spans evolutionary genetics, insect sex determination, and genome engineering, combining fundamental biological discoveries with translational technologies for agriculture. During my PhD, I led the discovery of Maleness-on-the-Y (MoY), the master male-determining gene in the Mediterranean fruit fly (Ceratitis capitata), a landmark discovery that transformed our understanding of insect sex determination and enabled new strategies for precision genetic pest control. My laboratory now develops CRISPR-based technologies, genetic sexing systems, Y chromosome engineering, and improved Sterile Insect Technique (SIT) approaches. I submit these comments as an independent academic scientist with expertise in the development and biosafety of genetic technologies for agricultural pest management. I support EPA's rigorous, transparent, and evidence-based evaluation of KNOCKOUT SWD under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). Technologies of this kind should be evaluated according to the best available scientific evidence, their biological properties, and their environmental safety profile rather than on the novelty of the underlying biotechnology. Modern agriculture faces increasing pressure from invasive insect pests while conventional insecticide-based control is challenged by resistance, regulatory constraints, and concerns regarding impacts on biodiversity and beneficial insects. These challenges require innovative, environmentally responsible solutions that complement existing integrated pest management programmes. KNOCKOUT SWD represents an important scientific advancement because it builds directly upon the well-established principles of the Sterile Insect Technique rather than replacing them. SIT has been implemented safely worldwide for more than seventy years and has demonstrated that releasing sterile males can suppress pest populations without establishing self-sustaining populations or causing long-term environmental persistence. KNOCKOUT SWD preserves these proven biological principles while improving efficiency by replacing irradiation with precise genetic engineering and eliminating the need for conventional sex-sorting systems. From my scientific perspective, the most important feature of KNOCKOUT SWD is that biological containment is engineered directly into the technology itself. Sterility, self-limitation, and the absence of persistence are intrinsic biological characteristics rather than operational assumptions. Released insects are sterile males that produce no viable offspring; consequently, the engineered traits cannot establish, persist, or spread through wild populations. Once releases cease, the introduced genetic material disappears naturally. This clearly distinguishes the technology from self-sustaining genetic systems designed to spread over multiple generations. Equally important is its species specificity. Population suppression depends entirely upon successful mating with the target species, substantially reducing the potential for direct effects on pollinators, natural enemies, and other non-target insects. Compared with broad-spectrum insecticides, this represents a far more precise and environmentally responsible approach to pest management. The technology also provides an important degree of operational control. Continued suppression depends entirely on continued releases of sterile males. If releases stop, the suppressive effect also stops, providing a predictable and reversible system that can be adjusted or discontinued whenever necessary. As scientists developing advanced genetic technologies, we recognise that innovation must always be accompanied by rigorous regulatory oversight. In my opinion, KNOCKOUT SWD incorporates multiple independent biological safeguards, including sterility, self-limitation, species specificity, non-persistence, and reversibility, that together provide a strong environmental safety profile directly relevant to EPA's assessment under FIFRA. Regulatory decisions on technologies such as KNOCKOUT SWD extend beyond a single product. They help define how scientifically robust, biologically contained, self-limiting genetic technologies will be evaluated in the future. Maintaining a rigorous, evidence-based regulatory framework is therefore essential not only for environmental protection but also for enabling responsible innovation that can address major challenges in sustainable agriculture and global food security. Thank you for the opportunity to provide these comments and for your careful consideration of this application.