Biological Testing Facility (X01 Clinical Trial Not Allowed)

Background Nearly half of all pregnancies in the United States are unintended. There is a critical need for fertility regulation methods that fit the needs of women and men throughout their reproductive lives. This notice of funding opportunity (NOFO) supports the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) in its mission to develop novel, safe and effective contraceptive methods for men and women. Purpose and Scope The NICHD has a state-of-the art Biological Testing Facility (BTF) for advancing male and/or female non-hormonal contraception development with the capabilities and capacity for preclinical and Investigational Device Exemption (IDE) or Investigational New Drug (IND)-enabling studies (e.g., fertility studies, pharmacology, toxicology, reproductive tract histopathology, sperm morphology). The long-term objective is the enablement of an IND/IDE study of a preclinical candidate, which offers a safe, non-hormonal based therapy for male and/or female contraception that acts prior to fertilization and does not act via the hypothalamic-pituitary-gonadal axis. The purpose of this NOFO is to provide investigators with a mechanism to request services from this facility that would advance their contraceptive development program. This NOFO aims to position innovative and validated methods for future clinical development. Applicants do not need to have current NIH funding to apply, but priority may be given to programs receiving NIH support at the time of application submission. Potential services available to support that goal include but are not limited to fertility studies, pharmacology, toxicology, reproductive tract histopathology, and sperm morphology and motility in pursuit of an IND or IDE application for FDA submission. The facility has the capability to advance multiple projects simultaneously across the entire development continuum. It is envisioned that a primary purpose of this resource will be for the advancement of late stage preclinical compounds and devices, and those projects will be granted highest priority. Interested parties are encouraged to reach out to the Scientific/Research Contact to discuss potential services prior to application submission. Applicants with chemical(s) hits and/or leads, or device(s) where the target and/or mechanism of action is unknown will be deprioritized; however, they are strongly encouraged to contact the Scientific/Research Contact for discussion. Important Notes Researchers granted access to resource services will be required to work with NICHD staff for all communications with the facility over the course of the project. Services provided will not exceed 12 months in duration unless approved prior to application submission. Applicants may request the service for multiple compounds (e.g., an efficacy study of multiple compounds) but must justify the value of doing so. There is no budget associated with this PAR. If you are considering applying for a service request that you estimate would exceed $200,000, please reach out to the Scientific/Research Contact(s). Resource access is awarded depending on availability of funds and in consultation with the Contractor. More than one X01 request can be submitted per cycle. Requested services may not overlap with efforts already funded through the PHS. Types of Activities The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) uses the Biological Testing Facility (BTF) for the interest of but not specifically limited to the support of the following activities: Preparation and delivery of vehicle and compound formulations at concentrations suitable for efficacy, safety and toxicological evaluation for oral, injectable, implant, transdermal or other route of administration. In vitro assays and in vivo model studies (rodent, rabbit, monkey) of new chemical entities (NCEs) or devices, including but not limited to: pharmacokinetics (PK), pharmacodynamics (PD), absorption, distribution, metabolism, excretion (ADME), plasma and microsome stability, maximum tolerated dose, toxicology, oral bioavailability, efficacy in mating trials, measurement of drug concentration in rete testis, transport across blood testis-barrier, effects on sperm morphology, motility, capacitation. Reproductive tract pharmacology, toxicology, and histopathology The long-term objective is the enablement of an IND/IDE study of a preclinical candidate, that offers a safe, non-hormonal based therapy for male and/or female contraception that acts prior to fertilization and does not act via the hypothalamic-pituitary-gonadal axis. Target Validation An important component of any early stage product development project is to conduct the necessary research to demonstrate that if the proposed modulation is successful (e.g., inhibition of a specific enzyme), the desired result will be achieved (e.g., infertility). This is commonly referred to as "validation". When a specific and defined molecule is targeted for modulation (e.g., inhibition of a specific enzyme), the specific molecule is referred to as a "target" and the validation process is referred to as "target validation". If the proposed research is focused on a defined molecular target (e.g., an inhibitor of a specific molecular target), the target must be validated prior to X01 submission, and the basis of validation must be justified by applicable data and/or literature citations in the application. If more than one specific molecule is targeted (e.g., two related enzymes), the same principles apply for the two molecules (i.e., demonstration that a well characterized modulation of both molecules will achieve the desired result). NICHD Data Sharing Expectations and Requirements X01 recipients that access the BTF will be required to adhere to the separate award conditions that are associated with the BTF’s plan for data sharing and any limitations to the extent of or timelines for data sharing to ensure that the proper balance is maintained between maximizing the timely sharing of scientific data and the protection of intellectual property (IP), following the NIH guidelines for data sharing and IP. Applicants should discuss projects with the COR/Scientific Program Lead/Program Officer and other proposed collaborators early to avoid agreements that prohibit or unnecessarily restrict data sharing. Considerations for Proprietary Data NIH recognizes that the extent of data sharing may be limited by restrictions imposed by licensing limitations attached to materials needed to conduct the research or by existing or anticipated agreements, such as those with the original compound supplier. Additionally, timelines for sharing may be delayed by plans to seek IP claims, such as patent filing. For example, in this initiative, many of the chemicals to be investigated and much of the data to be generated may be proprietary, intended to become proprietary, or confidential to the original compound supplier, and the supplier may have significant business value that needs to be protected or withheld from the public domain. These considerations will be addressed in the data use agreement, as outlined above. See Section VIII. Other Information for award authorities and regulations.