Artificial intelligence and real-world data for drug and food safety - A regulatory science perspective.

In 2013, the Global Coalition for Regulatory Science Research (GCRSR) was established with members from over ten countries (www.gcrsr.net). One of the main objectives of GCRSR is to facilitate communication among global regulators on the rise of new technologies with regulatory applications through the annual conference Global Summit on Regulatory Science (GSRS). The 11th annual GSRS conference (GSRS21) focused on "Regulatory Sciences for Food/Drug Safety with Real-World Data (RWD) and Artificial Intelligence (AI)." The conference discussed current advancements in both AI and RWD approaches with a specific emphasis on how they impact regulatory sciences and how regulatory agencies across the globe are pursuing the adaptation and oversight of these technologies. There were presentations from Brazil, Canada, India, Italy, Japan, Germany, Switzerland, Singapore, the United Kingdom, and the United States. These presentations highlighted how various agencies are moving forward with these technologies by either improving the agencies' operation and/or preparing regulatory mechanisms to approve the products containing these innovations. To increase the content and discussion, the GSRS21 hosted two debate sessions on the question of "Is Regulatory Science Ready for AI?" and a workshop to showcase the analytical data tools that global regulatory agencies have been using and/or plan to apply to regulatory science. Several key topics were highlighted and discussed during the conference, such as the capabilities of AI and RWD to assist regulatory science policies for drug and food safety, the readiness of AI and data science to provide solutions for regulatory science. Discussions highlighted the need for a constant effort to evaluate emerging technologies for fit-for-purpose regulatory applications. The annual GSRS conferences offer a unique platform to facilitate discussion and collaboration across regulatory agencies, modernizing regulatory approaches, and harmonizing efforts.

Knock-in mouse model for resistance to thyroid hormone (RTH): an RTH mutation in the thyroid hormone receptor beta gene disrupts cochlear morphogenesis.

Thyroid hormone and the beta isoform of its receptor, Trb, are essential for normal development of the mammalian auditory system. We have analyzed auditory system function and structure in a mouse strain with a targeted Thrb mutation, Thrb(PV), which leads to the loss of binding of thyroid hormone (T3) to the Trb protein. Heterozygosity for the orthologous human THRB(PV) mutation and other similar mutations in human THRB cause resistance to thyroid hormone (RTH), which is occasionally associated with mild sensorineural hearing impairment. Auditory brainstem response analysis of heterozygous Thrb(PV)/+ mice demonstrates that they develop normal hearing. In contrast, Thrb(PV)/Thrb(PV) mice have severe hearing impairment that is already present at 3 weeks of age. This hearing loss is associated with disruption of postnatal morphogenesis of the tectorial membrane and organ of Corti. Comparison with the previously described phenotype of a Thrb -/- knockout strain suggests that Thrb(PV) disrupts the function of other genes that are critical for development and/or maintenance of these structures.