The safety of vaccines

Lesson 9

How vaccines are proven safe and the research methods used.

Learning outcomes & key terms

1. Students can explain the purpose of a clinical trial

2. Students can list and describe the three phases of a clinical trial

3. Students can briefly describe the regulatory approval process

4. Students can describe the function of post-marketing surveillance, and understand that even after a vaccine meets all the regulatory requirements, data on safety and effectiveness of vaccines is continually monitored


Observation and treatment of patients in the medical clinic, as opposed to theoretical or laboratory studies



Results of clinical trials, testing and observation that are combined to assess how safe and effective a vaccine is



The best


In Vitro

Taking place in a test tube or culture dish


In Vivo

Taking place in a living organism



A substance that has no therapeutic effect used as a control in testing new drugs. It can be prescribed for the psychological (in the mind) benefit to the patient rather than for any physiological (in the body) effect.


National Immunisation Program (NIP)

The vaccines that the government fund for eligible Australians to receive free of charge

Science understanding

Science as a human endeavour

Scientific understanding, including models and theories, is contestable and is refined over time through a process of review by the scientific community.

Advances in scientific understanding often rely on technological advances and are often linked to scientific discoveries.

People use scientific knowledge to evaluate whether they accept claims, explanations or predictions, and advances in science can affect people’s lives, including generating new career opportunities.

Values and needs of contemporary society can influence the focus of scientific research. 

How are vaccines developed in the modern world?

Vaccine development

How does a vaccine go from first idea to being in use within the community?

Firstly, a need arises. A problem emerges in the community and the need for healthcare is recognised

There are many experts from several different organisations involved in development and testing process, including government regulatory bodies and independent scientific and committees

All vaccines must undergo this very rigorous testing and evaluation process to make sure they work in the way they should, and that there are no unintended safety issues

In Australia, vaccines must go through several phases of testing in the laboratory, in animals, and then in humans before it can be approved

The vaccine development process

Vaccine development timeline

1. A pharmaceutical company develops the vaccine

The four phases of vaccine testing

1. Preclinical trials

A potential vaccine candidate is identified by scientists

Laboratory tests and animal studies are used to assess whether the vaccine causes the right immune response in animals to protect against the disease, and whether the vaccine is safe

If all the safety requirements are met and the vaccine candidate causes the right immune response in animals, the vaccine candidate can progress to Phase I clinical trials in humans

2. Phase I clinical trials

The vaccine is given to dozens of healthy volunteers who are monitored very closely

This phase is used to assess the right dose needed and to test for safety.
Generally, this takes at least 1 year to complete

Not all vaccine candidates pass this phase. If they do, they then progress to Phase II clinical trials

3. Phase II clinical trials

The vaccine is given to a couple of hundred healthy volunteers

The volunteers are monitored closely for unexpected reactions (for safety), and their immune response to the vaccine is measured with regular blood tests to make sure the vaccine works in the body as it should

If the vaccine is found to be safe, it can move into the next stage of testing in humans, Phase III clinical trials

4. Phase III clinical trials

Thousands to tens of thousands of people take part in Phase III clinical trials

The trial participants are divided into two groups – those who receive the test vaccine (the test, or “intervention” group) and those who receive a placebo or control (the control group). The participants usually don’t know whether they are given the vaccine or the placebo / control

All participants are closely monitored for safety and tested regularly for the disease the vaccine is designed to protect against

The data are collated and compared between the vaccine group and the placebo / control group

Phase III trials typically take 4-5 years to complete – with COVID-19, they were done in about a year

2. The vaccine is assessed and approved for use by the regulatory authorities

In Australia, once the preclinical and clinical trials are complete, the company that developed the vaccine then shares their trial data with the Therapeutic Goods Administration (TGA), and applies to have their product licensed (allowed to be used) in Australia

Specialist technical experts at the TGA review the data to make sure the trials were conducted properly, and that the vaccine is safe and effective

The Advisory Committee on Vaccines (ACV) is an independent committee of medical and scientific experts who also review the trial data and help advise the TGA on whether a vaccine should be licensed in Australia

This process can take a couple of years

3. The vaccine is used and monitored

Once a vaccine is licensed for use in Australia, it is monitored for safety and effectiveness – its use in many thousands (of real-world people) is monitored, including special at-risk groups that weren’t included in phase 3 work 

The TGA laboratories test the quality of the vaccines

In Australia there are two main mechanisms for vaccine safety monitoring:

1. Passive surveillance, where people who have suffered a serious side effect from the vaccine (called an “adverse event”) can report it to the TGA, where the data is compiled and publicly available through the Database of Adverse Event Notifications (DAEN)

2. Active and enhanced surveillance, where participating medical clinics send an sms to vaccine recipients (or their parents / carers) to ask if they had any reaction to the vaccine. AusVaxSafety tracks the responses to these sms messages and also collates data from specialist immunisation clinics

This combined data is used to actively look for potential safety issues with vaccines.
Another form of active surveillance is when the researchers who performed the Phase I, II and III clinical trials continue to study the vaccine’s safety and effectiveness (known as Phase IV trials)

Another form of active surveillance is when the researchers who performed the Phase I, II and III clinical trials continue to study the vaccine’s safety and effectiveness (known as Phase IV trials)


If a potential safety issues is identified (called a “safety signal”), an independent group of experts (The Advisory Committee on Vaccines) review the data, assess the risk, and recommend what should be done

The TGA also monitors international data, looking for safety signals that may emerge in other countries that haven’t occurred yet in Australia through the International Coalition of Medicines Regulatory Authorities (ICMRA)

Proving that a vaccine is safe and effective involves a lot of people looking at the data

In Australia, vaccines must pass through a rigorous process of testing before it is approved and made available to the public

There are a number of organisations involved in assessing and approving which vaccines are funded to in Australia:

Therapeutic Goods Administration (TGA) – responsible for assessing vaccines and other medicines before they can be used in Australia, and monitoring vaccines for safety after they are approved

Advisory Committee on Vaccines (ACV) – An independent committee of medical and scientific experts that advises the TGA on whether to register a vaccine for use in Australia

Australian Technical Advisory Group on Immunisation (ATAGI) – Advises the Federal Minister for Health on what vaccines should be funded by the government on the National Immunisation Program and other immunisation issues

National Centre for Immunisation Research and Surveillance (NCIRS) – Independent research organisation the provides scientific expert advice on all aspects on immunisation and vaccine preventable diseases

Internationally, the World Health Organization (WHO) also has an advisory group, The Strategic Advisory Group of Experts on Immunization (SAGE), that advises the WHO on global vaccine-related strategies and policies

If the usual vaccine testing process takes so long, how did COVID vaccines happen so quickly?

Under normal circumstances, the phases of vaccine clinical trials are done sequentially, as resources become available

In the COVID-19 pandemic the process was accelerated by doing some of the phases simultaneously, and by making more resources readily available to undertake the trials. Furthermore, the similarity of the coronavirus that causes COVID-19 to other previous coronaviruses that caused Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) meant that prior work done on vaccines for those coronaviruses were applicable to COVID-19, thus reducing the time needed for preclinical work

See the World Health Organization video explaining the difference between the usual and COVID-19 vaccine development processes

Class activity

Go to the AusVaxSafety web site and click on COVID-19 vaccines

Look at the “Data at a glance” information

Discuss as a class

1. Where are most of the people completing the survey from? Why do you think that might be?

2. Look at the number of people reporting at least one adverse event, and the number reporting having to visit a GP or ED. What do you think these statistics mean? Are you surprised by the results?

3. Who do you think would be interested in this information? Why would this information be useful to those people?


Vaccines must pass preclinical trials and then three phases of clinical trials to be considered for use in Australia

Once the preclinical and clinical trials are complete, the data are examined by regulatory authorities and independent experts to make sure the trials were done properly, and the vaccine is safe and effective

Once the vaccine is determined to have met all the safety criteria it is licensed for use by the Therapeutic Goods Administration

After the vaccine is licensed for use, there are systems in place to continue to monitor the vaccine’s safety and effectiveness


1) How many phases on testing must a new vaccine pass to be considered for use in Australia?
a) Three
b) Four
c) One
d) Five


2) What is the name of the regulatory authority in Australia that approves vaccines for use?
a) The Therapeutic Goods Association
b) The Food and Drug Administration
c) The Advisory Committee on Vaccines
d) The Therapeutic Goods Administration


3) Pre-clinical testing of vaccines involves:
a) Laboratory tests only
b) Laboratory tests and animal studies to test for safety and immune responses
c) Animal and human studies to test for safety and immune responses
d) Laboratory and human studies to test vaccine effectiveness


4) Safety data on vaccines is collected
a) During phases I, II and III of the clinical trials
b) During preclinical testing
c) After the vaccine is introduced in post-market surveillance
d) All of the above