Use of controlled human infection models (CHIMs) to support vaccine development: US regulatory considerations

In 2016, the United States (U.S.) Food and Drug Administration (FDA) licensed Vaxchora® for active immunization against disease caused by Vibrio cholerae serogroup 01 in adults. Vaxchora was the first US-licensed vaccine for which the primary evidence supporting effectiveness was derived from human challenge studies. Following this precedent, FDA has received numerous inquiries from manufacturers, academic researchers, funders and other stakeholders regarding how controlled human infection models (CHIMs) can be used to support the development of safe and effective vaccines to address public health needs. The aims of this article are to discuss: (1) Chemistry, Manufacturing and Controls (CMC) for challenge inocula, (2) conduct of controlled human infection studies under US IND and (3) use of CHIMs to support vaccine development. General concepts and regulatory considerations for the safe conduct of CHIMs and use of CHIMs to evaluate vaccine effectiveness are discussed.