Testing of therapeutic goods

TGA Laboratories test therapeutic goods for quality. A risk-based process is applied to determine how products are tested.

Samples for testing are obtained from manufacturers, wholesalers, chemists, hospitals, retail outlets or the general public. On average, around 2000 samples of products are tested each year.

Compliance testing and problem investigation can involve analysing the presence of contaminants, strength and potency, mechanical properties, electrical properties, and software analysis. Some products, such as biological medicines, are tested frequently as they are complex to manufacture and are often used in healthy individuals (such as vaccines) or in patients being treating for cancer or autoimmune disorders. The TGA also has expertise in identifying counterfeit medicines and in assessing the quality of herbal products and traditional complementary medicines.

Testing measures the compliance of a particular sample against specified quality criteria, or for medical devices, compliance with the Essential Principles. For regulated products, the quality of the sample is assumed to represent the batch from which the sample is drawn, providing there are assurances that the sample has been stored in accordance with label instructions.

The samples tested may not be representative of other batches of the product. For this reason, laboratory testing cannot be seen as a replacement for other regulatory controls (such as Good Manufacturing Practice (GMP) compliance and assessments for market authorisation). Nevertheless, it provides an immediate assessment of the quality of the portion or sample tested and this information is useful in supporting other regulatory measures.

Methodology

The integrity of our laboratory testing is maintained through the use of our quality management system and associated laboratory operations manuals and standard operating procedures. We continuously monitor research into new and improved methods of testing to ensure we are using the most current methodology.

Systems are in place to track samples and ensure their appropriate testing. Each piece of equipment used in testing is maintained and calibrated regularly and the quality system is audited by the independent body the National Association of Testing Authorities, Australia (NATA). Each section of our Laboratories Branch is required to maintain NATA accreditation by demonstrating its technical competence to operate in accordance with ISO/IEC 17025.

All laboratory testing is recorded and monitored by a Laboratory Information Management System (LIMS). The system provides an integrated approach to sample management from the selection of products for testing to the reporting stage. The LIMS system underpins our internal quality system and makes a significant contribution towards meeting the requirements of NATA accreditation.

Testing categories

Responsive testing

When an issue with a product is identified, we prioritise testing of these products to ensure potential public safety concerns are addressed quickly. Issues may be identified through complaints, adverse event reporting or by areas of the TGA. When goods are found to be non-compliant, we may do further testing or the product may be recalled.

Programmed testing for compliance and monitoring

Goods on the Australian market are selected for compliance and monitoring testing to verify that they are of acceptable quality as defined by official standards or agreed specifications. Programmed testing is performed to investigate a potential risk of non-compliance and to monitor continuing compliance if required. For example, a new medicine may be tested when it is a condition of registration (e.g. batch release), and surveys may be conducted in response to intelligence obtained from various sources (such as previous testing results, GMP inspectors, the medical, scientific or engineering literature and regulatory control agencies in other countries). This type of testing is governed by a risk management framework which is based on ISO 31000 - Risk management - Guidelines.

Maintenance testing - accreditation; harmonisation and quality assurance; standardisation and method development

Maintenance testing is carried out to ensure we stay up to date with developing technologies and methods. This long-term, supporting activity is essential to ensuring the responsiveness, robustness and reliability of our testing capability. As a result, there is an active program of developmental research into new and improved methods of testing as well as training of staff in new technologies. 

Laboratory support to external agencies

We undertake testing for external agencies such as the World Health Organization (WHO) and other regional governments. Our laboratories are designated as a WHO Collaborative Centre for both Quality Assurance, and Quality Assurance of Vaccines and other Biologicals.

Testing of biological medicines

The Laboratories Branch tests biological medicines to ensure they comply with their approved specifications and Australian Certified Product Details. This testing is done through risk-based approach and projected product surveys.

Batch release of vaccines is unchanged, and sponsors are still required to submit batch release documentation and samples before supplying a batch of vaccine in Australia. 

Also see Guidance for sponsors: Testing of biological medicines.

Product Survey Testing

During product surveys, the Laboratories Branch tests individual batches of biological products to ensure they comply with their approved specifications and Australian Certified Product Details. 

The type of testing varies for different products and is focused on quality attributes including:

• identity
• strength
• purity
• potency

Testing can take a few days or several weeks; it all depends on the complexity of the tests and how many tests are required.

The TGA doesn't test products to check their efficacy (effectiveness) as this requires clinical trials in humans. All biological medicines are registered prescription medicines and are individually evaluated for quality, safety and efficacy (effectiveness) before they can be included on the Australian Register of Therapeutic Goods and supplied to consumers.

We have published some detailed reports of specific batch release testing projects

Evaluating vaccine batch release documentation and data

Testing is not performed on every batch of a biological medicine before they are released.

For vaccines, where batches have not been tested, release for supply is subject to an evaluation of manufacturing, testing and shipping documentation and data provided by the company supplying the product.

These processes are modelled on the World Health Organization (WHO) Guidelines for Independent Lot Release of Vaccines by Regulatory Authorities.

For biological medicines (other than vaccines) that have not been tested, release for supply may be subject to evaluation of documentation, or on the condition that an annual report is provided to the TGA with information on the batches released.

An evaluation of documentation and data can include a review of:

• certificates of analysis for the raw materials, drug substance, and finished drug product
• raw data and test results from testing of raw materials, drug substance and finished drug product
• shipping documentation, including temperature logs for transport of the product(s) from the manufacturing site to Australia
• release certificate(s) from another comparable National Regulatory Authority
• examination of a physical sample of the product to assess:
  • visual appearance, and
  • labelling compliance.

Laboratory testing of unregistered therapeutic goods

Most therapeutic goods are required to be approved and included on the Australian Register of Therapeutic Goods before they can be imported, manufactured, supplied or exported unless there is an exemption. (See: Accessing unapproved products)

Unregistered products tested by the TGA are typically:

• products that are the subject of a complaint from consumers and/or healthcare professionals;
• goods that have been intercepted by Australian Border Force officers while being imported to Australia; or
• goods purchased or seized by TGA officers from retails stores or manufacturing facilities.

The nature of these products and goods means many have no official packaging, labels or distinguishable product name.

Unregistered products are generally tested to determine if they contain any undeclared pharmaceutical ingredients or other prohibited substances.

A product may 'pass' laboratory testing (if it does not contain any undeclared pharmaceutical ingredients or other prohibited substances) however still be found to be an unregistered therapeutic good and therefore declared a Prohibited Import under the Therapeutic Goods Act 1989.

In most cases a product found to be considered a therapeutic good, and is imported or supplied in Australia without appropriate authorisation, will be destroyed.

Goods declared to be Prohibited Imports are seized and destroyed under the Customs Act 1901. Where appropriate the TGA may pursue criminal or civil court action in relation to these goods.

Testing standards and what happens when products fail

Our laboratories test therapeutic goods to ensure they comply with applicable standards and legislation. For most medicines these are 'default standards' provided by the British Pharmacopoeia, European Pharmacopoeia, and United States Pharmacopeia - National Formulary. 

In some cases specific Australian standards may apply, these are known as Therapeutic Goods Orders (TGOs). For those medicines that do not have a pharmacopoeial monograph or TGO, specified acceptance limits are agreed mutually and recorded as the product's Certified Product Details with which the product must comply.

Medicines are typically tested using methods to assess quality including:

• identity - are the ingredients in the medicine the same as indicated on the label
• content - does the amount of the ingredient(s) match the amount approved and claimed on the label
• purity - are there any process related impurities or degradation products, above the approved amounts
• activity/potency/ efficacy - does the medicine function as intended (in laboratory models^[1])
• microbiological quality - is the medicine free from bacteria and other contamination.

Medical devices are tested to ensure they perform as expected and in accordance with the Therapeutic Goods (Medical Devices) Regulations and the Essential Principles.

Most registered prescription medicines tested by the TGA meet their specifications. In a typical year the TGA tests around 1000 prescription medicines and on average only 0.5% fail. Failure rates are generally higher for over-the-counter medicines, complementary medicines and medical devices. 

When laboratory testing identifies problems with therapeutic goods, our response varies in accordance with our risk-based approach to regulation. We assess the significance of any non-compliance and decide if action needs to be taken. This action may include:

• issuing new safety advice and information
• requiring changes be made to the product labelling
• monitoring the product over time to identify any further issues
• recalling the product
• restricting access to the product
• cancelling the product from the ARTG.

Test methods

TGA Laboratories Branch has made the following test methods available for the use of sponsors and manufacturers:

• Test method: UPLCC01 - Cannabinoids