What is Preclinical Testing of Vaccines​?

What is the Main Purpose of Preclinical Testing?

Pre-clinical testing must be performed before clinical trials. The purpose of pre-clinical trials is to use human cell cultures or animals to evaluate the potential toxicity of a new therapeutic drug before the “in vivo” test is performed by human participants.  The main goals of preclinical studies are to determine a starting, safe dose for first-in-human study and assess potential toxicity of the product, which typically include new medical devices, prescription drugs, and diagnostics.

According to the US Food and Drug Administration (FDA), before a new medicinal drug is approved for use, a series of tests need to be carried out. In the first phase, basic research identifies hypothetical targets to treat a certain disease and then small molecules or biological compounds are screened to find any which show potential to treat the disease.

Before the new vaccine can be tested in humans, preclinical testing is required to prove its safety. In most cases, preclinical testing is very extensive in order to obtain sufficient data to not only reliably show the safety of the new vaccine, but also to show its potential efficacy, toxicity and pharmacokinetic properties. In addition, preclinical trials allow scientists to model potential drug-target interactions.

New vaccines, such as those developed for COVID-19, must undergo a rigorous preclinical testing phase as part of a broader vaccine development cycle. Usually, pre-clinical testing is performed first, followed by clinical trials of the vaccine, followed by regulatory review and approval, and finally development of vaccine production and quality control.

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Overview of Preclinical Drug Development Process

• Drug Discovery

• Screening

• Pre-Clinical Testing

• IND Application

• Phase I Clinical Trials

• Phase II Clinical Trials

• Phase III Clinical Trials

• New Drug Application (NDA) / Biologics License Application (BLA)

• Phase IV and Beyond

Here, we will discuss the steps that led to the vaccine’s approval for preclinical testing and the content involved.

Ways of Preclinical Testing

Before any new vaccine enters preclinical testing, it has been developed in the laboratory, usually as part of a four-step process including pathogen life cycle and epidemiology, immune control and escape, antigen selection and vaccine formation, and finally clinical Before testing.

First, scientists must understand the structure and behavior of the pathogen they are targeting. Issues related to entry pathways, interactions with cell receptors, replication sites, and disease-inducing mechanisms are all resolved before the first step in vaccine development. In addition, the data collected is related to the demographics of the people most affected by the pathogen.

Next, study the human body’s immune response to the invasion of target pathogens. Since then, scientists aim to develop a specific antigen that will target pathogens, maintain immunogenicity and stability, induce an appropriate immune response, and be suitable for large-scale production.

Finally, the newly developed vaccine is ready to enter preclinical testing, which will study its immunogenicity, safety and effectiveness in humans.

Pre-clinical Testing Protocol

Preclinical testing is conducted in human cell cultures, in which scientists use in vitro techniques to study how vaccines affect these cells, or use animal models in which an animal is selected and the effects of the vaccine are studied in vivo. The data collected in pre-clinical testing details the development and production of the new vaccine. It is important that the data collected from preclinical studies should be sufficient to support further clinical trials of the vaccine. Without strong evidence, the vaccine cannot transition from the preclinical stage to the clinical stage where human participants will be tested.

If preclinical testing does not meet the requirements of animal models, you must first provide clear reasons for testing on animals, rather than using human cells in vitro. Research using animal models must also follow Good Laboratory Practice (GLP) guidelines and national guidelines related to animal testing.

This stage of vaccine development is critical to determining the biological, chemical, and physical characteristics of the vaccine being developed. This is also the basic stage to emphasize any potential risks associated with vaccine use. The results of pre-clinical testing can help guide the development of subsequent clinical testing.

Preclinical testing should include toxicity, potency and immunity tests. The World Health Organization (WHO) recommends that toxicity testing should include the following: assessing the initial safe dose and subsequent dose escalation plan; assessing single and repeated doses and establishing a set of safety parameters; proving the potential reversibility of virulence; proving the vaccine strain’s The level of inactivation; to prove the reversibility of the toxoid; and to evaluate the potential of the vaccine antigen to cause the release of antibodies that cross-react with human tissues.

In addition, performance testing should be conducted. These tests are used in routine batch inspections. Analysis suitable for efficacy testing includes challenge models (for example, in mice for rabies and pertussis vaccines), and evaluation of infection units of live attenuated organisms (for virus vaccines). The World Health Organization recommends that the selected potency determination should mimic the expected function of the vaccine in the human body.

Finally, it is also recommended to conduct immune tests in preclinical trials. Usually, immunogenicity data comes from animal models to help scientists calculate the appropriate dosage and route of administration that should be tested in subsequent clinical trials. Preclinical immune testing should assess the relevant immune response caused by the vaccine.

In general, the main purpose of preclinical testing in vaccine development is to ensure that the vaccine is safe enough to be tested in humans, and to evaluate the potential efficacy of the vaccine, so as not to waste time and money on clinical trials that may not be used for vaccines. .

Article Source:

Cunningham, A., Garçon, N., Leo, O., Friedland, L., Strugnell, R., Laupèze, B., Doherty, M. and Stern, P., 2016. Vaccine development: From concept to early clinical testing. Vaccine, 34(52), pp.6655-6664.