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

Roshan Ramanathan; Scott Stibitz; Douglas Pratt; Jeff Roberts

doi:10.1016/j.vaccine.2019.06.009

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

Vaccine. 2019 Jul 18;37(31):4256-4261. doi: 10.1016/j.vaccine.2019.06.009. Epub 2019 Jun 21.

Authors

Roshan Ramanathan¹, Scott Stibitz¹, Douglas Pratt¹, Jeff Roberts²

Affiliations

¹ Office of Vaccines Research and Review, Center for Biologics Evaluation and Research (CBER), US FDA, 10903 New Hampshire Avenue, Silver Spring, MD 20993, United States.
² Office of Vaccines Research and Review, Center for Biologics Evaluation and Research (CBER), US FDA, 10903 New Hampshire Avenue, Silver Spring, MD 20993, United States. Electronic address: jeff.roberts@fda.hhs.gov.

PMID: 31235375
DOI: 10.1016/j.vaccine.2019.06.009

Abstract

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.

Keywords: Clinical development; Controlled human infection models; Regulation; Vaccine; Vaccine licensure.

Publication types

Review

MeSH terms

Communicable Disease Control / legislation & jurisprudence*
Communicable Disease Control / methods
Communicable Disease Control / standards
Drug Development / legislation & jurisprudence
Humans
Legislation, Drug
Models, Theoretical*
Quality Control
United States
Vaccines* / administration & dosage
Vaccines* / immunology
Vaccines* / standards

Substances

Vaccines