This TGA behind-the-news article was published on 30 June 2011. Behind-the-news articles are published in response to issues that are of interest to the community at a point in time, for example, subjects that have been in the media.

On this page: The objectives of regulating prescription medicines | The process of evaluating a new prescription medicine | The safety and side effect profile of new medicines | Post-market safety monitoring

The objectives of regulating prescription medicines

The TGA aims to ensure that the community has access to therapeutic advances within a reasonable timeframe. No medical product is completely risk free, and prescription medicines are the medicines that have the highest risk.

Before a prescription medicine can be marketed in Australia, the TGA assesses the risks and the benefits from the available evidence. If the risk:benefit profile is considered favourable, then the medicine is registered for use in Australia.

It is important for patients and carers to understand that although the available evidence about a new prescription medicine has been carefully evaluated by the TGA, the medicine should not be considered as 'safe' under all circumstances; rather, the known benefits are considered to outweigh the likely risks for the target group of patients (population). However, there may be individuals within that target population for whom the benefits do not outweigh the risks. In addition, once a medicine has been used outside of the controlled conditions of clinical trials, new safety issues may emerge.

For most new prescription medicines, clinical trials aimed at demonstrating the effectiveness and safety of the medicine will have involved approximately 500-3000 patients. As a result, the full range of potential side effects will only become known once the medicine is used in larger numbers of patients in the real world everyday clinical setting.

This is why the TGA does not stop regulating medicines once a medicine has been registered. Since 2009, all new prescription medicines have risk management plans, which outline how identified potential risks are going to be managed. In addition, there is a reporting system for adverse events. These reports are actively monitored by the TGA, and signals of concern are followed up with appropriate regulatory action.

The process of evaluating a new prescription medicine

The TGA requires the same standard of evidence for the assessment of a prescription medicine as comparable overseas agencies.

Three types of data are required for prescription medicines:

• Chemical data that describes the ingredients of the medicine
• Nonclinical data from laboratories
• Clinical data from clinical trials.

These data are evaluated at the TGA by experts in the relevant scientific and clinical fields. The TGA is also able to seek advice from advisory committees made up of Australia's most eminent experts in the relevant fields. A senior regulator then considers all of the available information and decides whether the known benefits outweigh the potential risks of the medicine and thus, whether the medicine should be registered for supply in Australia.

The safety and side effect profile of new medicines

Both nonclinical and clinical data provide information about the safety of medicines.

Nonclinical data from laboratory studies

Nonclinical data indicate:

• The organs (liver, kidney etc) that are most likely to be affected by the medicine
• Possible effects on the reproductive organs and possible effects in pregnancy
• The likelihood of the medicine being carcinogenic (cause cancer).

The observations made in nonclinical studies are often consistent with those made in clinical trials. In these cases, the nonclinical data give support to the association of the clinical finding with the medicine.

In other cases, the relevance of nonclinical results to clinical medicine is unclear until there has been greater exposure in the human population. In these situations the nonclinical data indicate potential risks.

Clinical data from clinical trials

Clinical data from clinical trials give information about adverse events that occurred:

• In a small population
• In a population exposed to the medicine for a limited period of time.

Clinical data from clinical trials do not detect all possible adverse effects of a medicine because:

• They usually do not continue for long enough to detect reactions that take a long time to develop.
• They do not include enough patients to detect reactions that occur rarely.
• They do not include all of the different types of people who might eventually use the medicine and who might be more susceptible to some reactions, such as older people, children, pregnant women, or people with other medical conditions.

Post-market safety monitoring

The TGA, like other medicines regulatory agencies around the world, monitors the safety of medicines to contribute to a better understanding of their possible adverse effects when they are used outside the controlled conditions of clinical trials.

Post-market safety monitoring includes:

• Activities to identify and investigate safety signals
• Communication of this information to health professionals and the public
• Appropriate regulatory action, such as suspending or cancelling registration, or narrowing the population in which the medicine can be used.

The TGA monitors the safety of medicines marketed in Australia using:

• Risk management plans
• Adverse reaction reports
• Reviews of published literature
• Sharing of information with other regulatory agencies.

Risk management plans

Risk management plans have been required by the TGA for all new prescription medicine applications since 2009. Risk management plans are designed to define and pro-actively manage risks related to a medicine over its entire life cycle. Periodically, risk management plans need to be updated to reflect new knowledge and understanding of the safety profile of a product. The TGA can require pharmaceutical companies to implement a particular risk management plan as a condition of registration.

Risk management plans consist of an overview of safety information and a plan of activities that will be undertaken to characterise and minimise risks associated with the medicine, including:

• Pharmacovigilance activities, designed to investigate particular risks, or to fill gaps of knowledge, such as further studies or active monitoring for certain adverse events.
• Risk minimisation activities, such as educational materials and activities for health professionals and consumers, designed to reduce the potential for harm to patients.

The adverse event reporting scheme

Reports of suspected adverse reactions provide important information for the TGA safety monitoring program. Anyone can report a suspected adverse reaction to any medicine. Reports by consumers and health professionals are voluntary, whereas pharmaceutical companies are obliged to report any adverse events of which they are aware.

The adverse reaction reports are placed in a database, and the database is analysed regularly by scientific and medical staff at the TGA. The TGA reports are also sent to the World Health Organization database of individual case safety reports (VigiBase), and the TGA often uses the data in VigiBase in its investigation of potential safety signals associated with medicines registered in Australia.

The TGA cannot give medical advice and strongly encourages consumers to talk with a health professional if they think they might be experiencing an adverse reaction.

The Advisory Committee on the Safety of Medicines (ACSOM)

When making its decisions about the safety of medicines, the TGA uses its own expertise and seeks advice from the Advisory Committee on the Safety of Medicines (ACSOM). This committee was formed in January 2010 and comprises experts in clinical medicine, pharmacoepidemiology, pharmacy and consumer issues.

ACSOM advises and make recommendations to the TGA on:

• The safety of medicines
• Risk assessment and risk management of medicines
• Other matters related to the detection, assessment, understanding and prevention of adverse effects.

What happens once a safety concern has been identified?

If the TGA identifies a safety concern relating to a medicine, it can take regulatory action to ensure that the medicine continues to have acceptable safety, efficacy and quality for its intended use. The TGA also seeks to ensure that health professionals and the public are aware of the safety concern and any changes to the availability and recommended use of the medicine.

Actions the TGA can take in response to a safety concern include:

• Informing health professionals and consumers through alerts and articles in Medicines Safety Update.
• Requiring changes to product labelling, such as adding warnings, precautions and adverse reaction information to the Product Information or Consumer Medicine Information.
• Suspending or cancelling the registration of the product, or narrowing the population in which it can be used.
• Requiring the sponsor to undertake post-marketing studies to investigate the safety concern if more information is needed before a judgment can be made about the need for further action.