A rough guide to vaccine testing and approval processes

06 April 2021

Outlining the main stages of development and delivery of a new vaccine. By Professor Shanthi Ameratunga. 

Professor Shanthi Ameratunga

A new vaccine’s development and approval processes generally follows principles similar to those used to test, evaluate, approve and implement therapeutics (pharmacological drugs for clinical conditions).

These procedures are designed to follow rigorously developed scientific guidelines to ensure that the products administered to patients have a high probability of being safe and effective. The information submitted for review by regulatory
authorities in a country are typically considered alongside other factors before approval for clinical use. 

The CDC (US Centers for Disease Control and Prevention) outlines the main stages of development and delivery of a new vaccine as follows:
• Exploratory stage
• Pre-clinical stage
• Clinical development
• Regulatory review and approval
• Manufacturing
• Quality Control.

After investigators have determined the potential effectiveness of a vaccine through pre-clinical research involving human cell cultures or animal models, they move to the clinical development stage to investigate how well the vaccine works in humans. 

The clinical development stage involves a sequence of three to four phases, each responding to different, but linked, questions that build on the results of previous phases.

All trials are expected to follow strict ethical guidelines relating to research participation, including fully informed consent.

Phase I: In this phase, small groups of people (usually healthy volunteers) receive the trial vaccine. The aims of this phase are to assess the tolerability of different doses to avoid serious side effects and a greater understanding of how humans react to the vaccine/medication potentially provided in different formulations or combinations.

Phase II: This phase usually involves larger groups of participants than in Phase I, and is designed to gather more evidence regarding the safety and side effects of the vaccine in people similar to the populations of particular interest or concern in relation to the disease. The preliminary information gathered in this phase informs the methods of the next important phase.

Phase III: This phase usually involves thousands of people with characteristics similar to the population the vaccine is intended for. The intention of this phase is to demonstrate the efficacy of the vaccine, typically using a double-blind randomised controlled trial design, where the effect of the new vaccine is compared with the effect of not getting the vaccine (determined in a ‘control’ group receiving an alternate or inert product).

The ‘control’ group (determined in a randomised way) in randomised controlled trials helps reduce common biases that can lead to confounded or misleading results. The Phase III trials (which take longer than Phase I and II studies) are designed to demonstrate that the vaccine is safe and effective, at least in experimental conditions. Study participants are monitored carefully with a systematic protocol of testing and research evaluation, as these form the basis for applications for regulatory review, approval and licensing in various settings.

Phase IV: Many vaccines continue to be evaluated in studies after they are approved and licensed for public use, to ensure the evidence of safety and effectiveness in the rigorous pre-licensure phases remains valid when the vaccine is used in the field. 

It is important to note that a vaccine licensure process will consider many issues over and above the evidence of vaccine safety and efficacy to determine the approach to funding and delivery of a vaccine, and these are active  considerations in New Zealand with respect to the Covid-19 vaccines. Particular issues of note include:
• Clinical and public health significance of Covid-19 including those most at risk of severe disease (these raise important health equity and access considerations)
• Risks and benefits of the vaccine relative to the risk of transmission and occurrence of disease
• Cost-effectiveness of the product
• Feasibility of safe and effective delivery and administration of the vaccine to ensure equitable access to effective vaccines.

All new medicines (including Covid vaccines) are evaluated by Medsafe for approval and recommendation for use in New Zealand. Medsafe reviews the regulatory information provided by manufacturers and the international evidence to ensure the products approved “comply with international standards and local requirements for quality, safety and efficacy”. 

* Professor Shanthi Ameratunga was previously MDANZ’s Clinical and Scientific Advisor

* This article was originally published in the Autumn 2021 edition of In Touch magazine. 

For more information please contact: 
Melanie Louden 
Communications and Marketing Advisor 
Muscular Dystrophy Association of New Zealand 
027 509 8774 
[email protected]