Title: Nitrosamines Forum for Advancing Critical Translational Science (NA FACTS) FOA Title & Number: Identification and Evaluation of Possible Approaches to Addressing Nitrosamine Impurities in Drugs (U01), RFA-FD-24-020 Project Summary 1 The Health and Environmental Sciences Institute (HESI) will address the need to implement feasible and 2 sustainable safety assessment methods that protect public health from nitrosamine (NA) risks while ensuring 3 uninterrupted access to essential medications by establishing the Nitrosamines Forum for Advancing Critical 4 Translational Science (NA FACTS). NA FACTS will form two multi-stakeholder advisory teams, each with 5 distinct tasks. One advisory team will be tasked with identifying, prioritizing and preparing a report with 6 recommendations on in vivo and in vitro research priorities for assessment of NA impurities in drugs (Specific 7 Aim 1). This advisory team may identify and initiate a select number of new projects within the existing HESI 8 Genetic Toxicology Testing Committee (GTTC) Nitrosamines Research Program (NRP) and establish a 9 competitive seed funding mechanism to catalyze a limited number of additional new programs (Specific Aim 10 3). A second advisory team will be tasked with designing and convening a workshop to assess the feasibility of 11 establishing a public-facing (Q)SAR database that builds on NA classification (Specific Aim 2). The NA FACTS 12 Principal Investigator (PI) and Key/Senior Persons will provide FDA with a report synthesizing the 13 recommendations from the prioritization exercise and the outcomes of this workshop. The summary reports 14 for Aims 1 and 2 will be publicly posted with FDA approval. Specific Aim 4 (assessment of opportunities to 15 ensure that research and practices identified in Aims 1-3 can continue following closure of the cooperative 16 agreement) will be fulfilled as a component of Aims 1-3 above. Specifically, HESI personnel will utilize the 17 networks and topical areas developed in Aims 1-3 to focus this effort. HESI personnel will also apply their 18 decades of expertise to assess and evaluate stakeholders’ interest in supporting or leading continued work 19 related to Aims 1-3 at the close of this cooperative agreement. HESI personnel will work with the NA FACTS 20 team and existing GTTC NRP to facilitate discussion of possible resource models and program mechanisms 21 that could support sustained activity (e.g., stakeholder contributions of funding or expertise/data/studies, 22 grants, etc.). HESI foresees ongoing success advancing this important work given the organization’s 35 years of 23 designing innovative scientific, resource sharing collaborations, which includes the establishment and growth 24 the GTTC NRP.

Title: Nitrosamines Forum for Advancing Critical Translational Science (NA FACTS) FOA Title & Number: Identification and Evaluation of Possible Approaches to Addressing Nitrosamine Impurities in Drugs (U01), RFA-FD-24-020 Project Narrative To address the ongoing public health risk from nitrosamines impurities in human drugs, the Health and Environmental Sciences Institute, through the Nitrosamines Forum for Advancing Critical Translational Science (NA FACTS), will form two advisory teams each with distinct tasks. One advisory team will (a) identify, prioritize and prepare a report with recommendations on research priorities for assessment of NA impurities in drugs, (b) initiate a select number of new projects within the Nitrosamines Research Program, and (c) ensure research priorities continue to be addressed beyond the cooperative agreement. A second advisory team will convene a workshop and publish a report on the feasibility of and the mechanisms and resources needed to establish a public-facing (Q)SAR database that builds on NA classification.