Nonclinical evaluation of vaccines
Vaccines are administered to healthy humans, often in the first year of life. The demands for safety and efficacy are therefore very high. Nonclinical testing is a prerequisite to moving a candidate vaccine from the laboratory to the clinic and includes all aspects of testing, product characterization, proof of concept/immunogenicity studies and safety testing in animals conducted prior to clinical testing of the product in humans.
The nonclinical evaluation of vaccines includes the initial testing of candidate formulations in animal models. In vivo and in vitro toxicity studies conducted before the start of clinical trials (preclinical) identify potential safety concerns and serve to avoid possible harm to human subjects. Potential concerns include toxicity due to the active ingredients or excipients, reactions to trace impurities such as production substrates, and interactions between components of other vaccines administered simultaneously.
Studies designed to determine the right dose to induce an immune response in appropriate animal models can provide valuable information on the immune response that can be expected in humans, and guide the determination whether the candidate vaccine will be beneficial to both the human study participant and the wider population once marketed. But it must be recognized that there are limitations in animal testing; susceptibility to infection by viruses, bacteria, and other microorganisms are often highly specific, and the immune responses in an animal model, particularly at the elevated doses used for nonclinical testing, may not be predictive of what will ultimately occur in humans. Nevertheless, few people would accept the administration of a candidate medicinal product without some level of assurance of its acceptability in a living animal. Therefore, nonclinical testing continues to be a balance between the desire to reduce the use of animals for testing purposes against the rights of humans to be administered safe and effective vaccines. International harmonization of testing requirements is therefore an essential tool needed to establish uniform approaches to the determination of the safety and efficacy of medicinal products, as well as to restrict animal testing to those critical areas where it cannot be replaced by alternative means.
Non-clinical evaluation of vaccine guidance
WHO guidance on the nonclinical evaluation of vaccines was adopted by the Expert Committee for Biological Standardization (ECBS) in 2003. This document provides recommendations to manufacturers and national regulatory authorities within the context of this document, refers to all in vivo and in vitro testing performed before and during the clinical development of vaccines.