NICHD: R&D: PRECLINICAL SAFETY AND TOXICOLOGY STUDIES FOR REGULATORY REQUIREMENTS: NON-SEVERABLE

Within the Division of Population Health Research (DiPHR), the Contraceptive Development Program (CDP) at NICHD supports research to identify and develop compounds that can safely and reversibly modulate human reproductive physiology such as ovulation, sperm production, or sperm function with the goal of enabling individuals to better manage fertility and optimize reproductive outcomes. The Biological Testing Facility (BTF) is a critical component in this process designed to allow rapid evaluation of new composition-of-matter, drug formulations, delivery systems, and devices for fertility management and endocrine activity. The BTF provides overall project management and the capabilities to support all phases of preclinical activities pursuant to development of new fertility management methods: these include, but are not limited to administrative support, manuscript support, fertility management, target discovery database, in vitro and in vivo assays, plasma and microsomal stability studies, absorption, distribution, metabolism, excretion and toxicity (ADMET), pharmacokinetic (PK) and pharmacodynamic (PD) profiling, animal studies, manufacture of active pharmaceutical ingredients (APIs), process and product development, formulation, clinical lot production, preclinical enabling studies and associated tasks leading to the filing of investigational new drug (IND) applications. Compounds formulated by the BTF are, or will be, tested including but not limited to non-human primates. Compounds formulated by the BTF that are prepared under current Good Manufacturing Practices (cGMP) will allow clinical evaluation in the CDP’s Contraceptive Clinical Trials Network (CCTN). The CCTN investigators have developed protocols to evaluate the drug candidates identified as high priority by the Program. The BTF has been working with the CORs for the Chemical Synthesis Facility and the CCTN and with the investigators in the CCTN to develop and test the appropriate formulations for clinical batches of the candidate compounds. The next clinical study for each candidate drug is dependent on timely receipt of clinical batches to begin the process of recruitment and enrollment. Drugs that are currently in ongoing clinical trials require stability testing of the clinical formulations. The Biological Testing Facility plays a critical role in the drug development mission of the CDP. Scope and Objectives: Research and development encompassing all phases of preclinical studies including but not limited to preclinical computational screening and modeling, target discovery, database improvements and updates, discovery and optimization of active pharmaceutical ingredients, metabolic profiling, in vitro assays and in vivo studies, safety toxicology studies, Good Laboratory Practice (GLP) and/or non-GLP toxicology and FEED studies, pharmacokinetic, and pharmacodynamic studies of active pharmaceutical ingredients and/or new chemical entities (NCEs) in appropriate concentrations and formulation that will be suitable for use in clinical trials of a potential fertility management products using in-house or appropriate subcontract facilities as described in the Background will be supported by this task. The task requires that the contractor provide documentation and reports of studies to support regulatory filings acceptable to stringent regulatory agencies. The drug products formulated in appropriate concentrations shall be characterized for in vivo safety, efficacy, and/or toxicology studies in all areas and species. The goal of these studies is to carry out research and to develop preclinical package acceptable to the regulatory agency in filing an investigational new drug (IND) application that would support testing in clinical trials and toward filing a New Drug Application (NDA) for approval of a new method. Project Number: 75N94020D00003-0-759402500002-1 | Fiscal Year: 2025 | NIH Institute/Center: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | Principal Investigator: Deborah Bunin | Institution: SRI INTERNATIONAL, MENLO PARK, CA | Award Amount: $1,497,846 | Activity Code: N01 View on NIH RePORTER: https://reporter.nih.gov/project-details/75N94020D0000307594025000021