Strategies for Non-clinical safety assessment of vaccines

Setting the scene

Over the past century, vaccines have made a large impact on public health, as recently demonstrated by the treatment of the worldwide Covid-pandemic. Since, in general, vaccines are administered to healthy individuals, including infants and children, it is important to demonstrate the safety of vaccines with proper in vitro testing and in vivo animal testing prior to starting clinical studies with the vaccine candidate. Therefore, over the past decade, there has been an increased focus on nonclinical safety assessment of vaccines, including testing for potential toxicity.

Non-clinical guidelines for vaccines

Over time, the extent of nonclinical safety testing has been greatly increased and current regulatory guidelines (see inset) require a comprehensive package of safety studies to be performed. These guidelines are aligned with overall principles of toxicological evaluation (i.e., detection of potential for systemic and local toxicity) but allow for appropriate flexibility in study designs according to the type of the vaccine candidate, the specific disease for which the vaccine will be used, the human population to be treated and the dosing regimen to be applied in the clinical use (see inset).

Most important general guidelines describing nonclinical studies supporting clinical trials for vaccines are:

  • EMA (European Medicines Agency). Note for Guidance on Preclinical Pharmacological and Toxicological Testing of Vaccines. CPMP/SWP/465/95. guideline/2009/10/WC500004004.pdf; 1997.
  • WHO. Guidelines on Nonclinical Evaluation of Vaccines. World Health Organization Technical Report Series, No. 927, Annex 1 ANNEX%201Nonclinical.P31-63.pdf; 2005.

In addition, there are many guidelines, focusing on type of vaccine (e.g. live attenuated, inactivated, toxoid, recombinant protein, conjugated, RNA, DNA vaccines), specific diseases (e.g Covid, Influenza, Hepatitis, Yellow Fever, Rabies, Tuberculosis) and human population to be treated (e.g.adults, pediatric, juveniles)

Strategy for nonclinical safety/toxicity testing

Prior to starting clinical studies with vaccines, adequate information about the pharmacology and toxicological effects of the vaccines should be available. The program of safety studies to be performed varies depending on the type of vaccine, disease to be treated and intended use in humans (e.g., number of injections). It is important to have an optimized strategy and planning of the proper non-clinical studies to best and quickest transition into clinical studies. Nonclinical testing of vaccines is different from testing of small molecules and the appropriate (combination of) studies has to be deducted for each specific vaccine candidate based on applicable guidelines and experience.

Regulatory toxicology studies for testing the safety of vaccines are performed in vitro and in animal studies and need to be performed in compliance with Good Laboratory Practice (GLP). Venn experts can help you in selecting CRO’s, in monitoring the progress of your studies, reviewing reports and in drafting regulatory documentation.

Next step - clinical (challenge) studies

A clinical development approach that has become more commonplace in recent years, is to test different dosing regimens in a Human Challenge Study. In example, different adjuvants and dosing approaches (with or without booster) are tested in these challenge trials, to obtain the best possible dosing regimen for phase 2 / 3 field trials. In the design of your nonclinical safety/toxicity testing program, you also have to take into account these options to allow you to take the most out of the challenge trials and optimalise your development program.

Venn experts can help you to select the appropriate studies and define a Drug Development Plan for your vaccine candidate.

Why Venn’s Non-Clinical team

The IND filing and first clinical studies for your lead vaccine can be a lengthy and costly process. Developing the right strategy and study designs is the first step in the direction toward an optimized nonclinical program. The combination of specific scientific non-clinical expertise combined with detailed knowledge of regulatory requirements for vaccine development, commitment to your projects and the constant pursuit of quality excellence make Venn a reliable source for Non-Clinical Consultancy Service for your vaccine projects.

Share this article

Other recent articles

Ready to see how Venn Life Sciences could speed up your drug development program?
Get in touch.

Contact Venn