Renewal Applications: Centers of Excellence in Regulatory Science and Innovation (U01)

The Office of the Chief Scientist (OCS) in FDA's Office of the Commissioner (OC) is publishing this Funding Opportunity Announcement (FOA) to provide support for the Agency's Centers of Excellence in Regulatory Science and Innovation (CERSIs). Regulatory Science is the science of developing new tools, standards, and approaches to assess the safety, efficacy, quality, and performance of FDA-regulated products. The CERSIs, interacting collaboratively with the FDA, foster robust and innovative approaches to advance the field of regulatory science as follows: A. SCIENTIFIC PROGRAMMATIC AREAS FDA has identified the following priority areas based on the Agency's current unmet regulatory science needs. As these priorities evolve, the list will be updated periodically. See FDA's Regulatory Science Research Priority Areas for updates. 1. High priority topics, with needs across product lifecycle and relevant subpopulations (sex, gender, age, race/ethnicity): a. Tobacco, including, but not limited to toxicity, addiction, health effects, behavior, and communications. See link on CTP research priorities for more information. b. Reducing healthcare-associated infection: i. Better understanding of the effectiveness of sterilization and reprocessing of medical devices ii. Further development of pathogen reduction technologies for whole blood and blood components iii. Promote development of innovative antimicrobial approaches c. Issues related to opioid use, misuse and dependence 2. Develop and evaluate methods to improve quality and safety of FDA-regulated products for use by patients and consumers, including methods to improve predictive value of nonclinical evaluation a. Methodologies for development, manufacturing/quality control of complex generic drugs, biosimilars, biological products and medical devices b. Biocompatibility and biological risk evaluation of medical devices and their component materials c. Evaluation of innovative methods such as: i. Microphysiological systems (MPS) (organ on a chip) ii. Computer modeling and simulation (e.g., in silico clinical trials and biocompatibility modeling) iii. Discovery and validation of minimally invasive biomarkers particularly for diseases and medical states where few markers exist (such as traumatic brain injury), including predictive microbiome biomarkers and use of current methods such as EEG and bio-imaging. 3. Develop methods and tools to improve and streamline clinical and post-market evaluation of FDA-regulated products, including a. Scientifically valid approaches to incorporating patient input (e.g., patient preference, patient reported outcomes) into regulatory decision-making b. Complex adaptive, Bayesian, and other novel clinical trial designs c. Approaches to leveraging large, complex data to inform regulatory decision-making, including use of "real world" data sources and mobile technologies d. Evaluation of product safety and efficacy in special populations, such as maternal, pregnant and lactating women, perinatal, pediatric, and geriatric individuals e. Subpopulation evaluations based on age, sex, gender, race and ethnicity, including evaluation of: i. Safety and efficacy ii. Effective comprehension and usability of FDA communications See links on Office of Women's Health (OWH) Research Roadmap and Office of Minority Health (OMH) Research and Collaboration Program for more information. B. FUNDING 1. Initial CERSI Award: FDA provides funding at the time of initial award of a cooperative agreement for CERSI activities associated with FDA's regulatory science priorities (see Part 2, Section I.A) based on availability of funding and the scope of the applicant's application. 2. Post-Award Research Projects: In order to accelerate innovation and to address new developments in emerging regulatory science, as well as urgent unmet needs, FDA anticipates funding for additional research projects to be conducted in collaboration with the CERSIs after the initial CERSI award of a cooperative agreement. These post-award research projects are intended to rapidly and proactively further the regulatory science efforts of FDA in response to public health needs that may not be known or identified at the time of the initial CERSI award. These studies will be conducted collaboratively with FDA. In some cases, FDA will serve in an advisory role for these projects and in other cases, FDA will participate in the projects in hands-on collaboration with the CERSI. In the latter case, internal support for the FDA portion of the project will be provided by the Agency separately from the cooperative agreement support provided for the CERSI. (It is also possible that a CERSI project could be supported, in part, by a third party.) Applicants are expected to leverage the funds provided by FDA for the cooperative agreement to expand support for their CERSI activities (e.g., non-FDA federal funds, non-federal funds, CERSI institutional funds, "in-kind" support such as institutional accommodations). C. PROGRAM CHARACTERISTICS The CERSIs promote innovation in regulatory science predominantly through cutting-edge scientific research that supports FDA's regulatory needs (see Part 2, Section I.C.2); they may also provide training in regulatory science (see Part 2, Section I.C.3). An overview of the CERSI program is provided in this section. See Part 2, Section IV.2 on PHS Research Plan for information that should be provided in your application for evaluation by FDA. 1. The core program infrastructure provides for effective execution of the CERSI's cooperative agreement, including coordination, management and oversight of program activities, financial transactions, reporting obligations, and interactive meetings. In some cases, the CERSI partners with another institution working collaboratively on the program (i.e., subaward). The CERSI also interacts collaboratively on projects with FDA and with investigators within the CERSI's institution and sometimes with investigators at other institutions. The CERSI is expected to function independently and network with other CERSIs in the program when possible (e.g., synergizing, collaborating and sharing expertise and program goals). 2. Cutting-edge regulatory science research is the major focus of the CERSI program. Research projects designed to address an unmet regulatory science need at the Agency (see Part 2, Section I.A) are selected and conducted in collaboration with FDA. In some cases, the FDA-CERSI collaborative research projects are conducted with other CERSIs or with partners outside of FDA and the CERSIs. Whether or not FDA directly collaborates in the scientific research, it serves in an advisory role, interacting with the CERSI in project planning, monitoring, and evaluation both to provide scientific input and enhance the utility of the work to meet FDA's public health mission. The CERSI program may include exploratory pilot research projects that are aligned with FDA's regulatory science priorities (see Part 2, Section I.A). These projects are weighed and prioritized in collaboration with FDA against on-going projects that require additional funding. The goal, potential impact and potential for continued funding of an exploratory pilot research project are considered in selecting these projects for the CERSI program. FDA-CERSI collaborative research projects are either funded by FDA upon initial CERSI award of a cooperative agreement or funded by FDA post-award. See Part 2, Sections I.B (Funding) and IV.2 (PHS 398 Research Plan) for additional information. Initiation of new potential research collaborations are stimulated by scientific exchanges between FDA and the CERSIs. These scientific exchanges can also serve to catalyze newly initiated or on-going collaborative research projects. Scientific exchanges may involve FDA staff traveling to the CERSI to meet with CERSI program directors and interested researchers and/or spend time learning about new technologies. Funds for FDA staff travel to the CERSI are provided by the Agency separately from the cooperative agreement support provided to the CERSI. Reciprocally, CERSI staff can visit FDA using funds provided by the cooperative agreement. 3. Regulatory science training is not mandatory, but may be part of the CERSI program. If included, it should represent a minimal cost component of the program to FDA. Training can include proposed courses and other training opportunities for both FDA staff and the CERSIs, as well as broader efforts by the CERSIs to engage other potential partners, domestically and internationally. CERSI training in regulatory science may include: - Fellowships at the CERSIs, and, when feasible, at FDA for individuals with an advanced degree in a scientific field (e.g., M.D., Ph.D., PharmD, MPH), who participate in an FDA-CERSI collaborative research project - Scholar awards (small award/ stipend) at the CERSI for graduate students or postgraduates. It is highly encouraged that these CERSI Scholars participate in an FDA-CERSI collaborative research project, but they could also participate in other regulatory science related research at the CERSI - Incorporation of regulatory science (e.g., address scientific question(s) related to medical product development) into CERSI institution's existing coursework that pertains to disciplines currently in demand at FDA (e.g., mathematical modelers, statisticians, medical officers) - Courses or mini-courses in regulatory science (in-person or online), in particular, for emerging areas of regulatory science (e.g., patient preference and patient reported outcomes, real world evidence, regenerative medicine) - Workshops on topics related to an FDA regulatory science priority that address an unmet Agency need (see Part 2, Section I.A). These workshops may be: 1) collaborative with FDA, 2) collaborative with FDA and other partners, or 3) sponsored by the CERSI on its own. Scientific and educational workshops in partnership with FDA are conducted to bring FDA, CERSI staff, relevant stakeholders and the public together to foster collaborations and stimulate innovation in addressing the Agency's unmet regulatory science needs. - Lectures on an FDA-CERSI collaborative research project or related research of the project principal investigator. They can also be on a topic related to an FDA regulatory science priority (see Part 2, Section I.A). These lectures may be hosted by the CERSI at their academic institution, at FDA or another venue. Lectures can be in-person or webinars. - Competitions for students to stimulate their interest in regulatory science (e.g., America's Got Regulatory Science Talent, regulatory science writing competition) - Certificate or degree program in regulatory science - Other types of training and professional development opportunities intended to advance excellence in regulatory science and address FDA's unmet needs may be included. FDA-CERSI collaborative workshops and lectures are selected for the CERSI program in collaboration with FDA. Any fellowships at FDA are coordinated with FDA to assess the feasibility of having the fellow at FDA and to determine an appropriate mechanism for placing the fellow at FDA. It is expected that coursework for which a fee is charged by the CERSI institution should be self-sustaining and require little to no funds from the CERSI cooperative agreement.