Applicable to biological medicines, excluding vaccines, anti-venoms and toxins
This guidance applies to sponsors of biological medicines, and outlines:
These policies and processes have been in place since 2007 and are published as part of TGA's ongoing transparency initiatives.
While the following products are included in the definition of biological medicines, this guidance does not apply to:
Requirements for vaccine testing
Post-registration testing of vaccines complies with internationally accepted guidelines (most recently published in Annex 2 of the WHO Technical Report Series (TRS 978) (pdf,439kb)).
Applicable to biological medicines, excluding vaccines, anti-venoms and toxins
Our testing program uses a risk-based strategy to prioritise testing. This allows us to focus on high risk products, while testing lower risk products less frequently, or with less labour-intensive methods. Products that have not yet established a track record of quality and safety, such as new products, and products associated with adverse drug reactions or manufacturing failures are considered high risk products.
Applicable to biological medicines, excluding vaccines, anti-venoms and toxins
Please note: A change in process has been implemented regarding physical samples for batch release for biosimilars and biological medicines during the COVID-19 pandemic. See: Physical samples for batch release not required: a reminder for sponsors of biosimilars and biological medicines
We assign products to one of five risk groups based on the outcome of a risk assessment.
We assign the risk group once the second round of evaluation is completed. We will advise you both during and after registration of:
Your product will fall into Risk Group 1 if it is a new biological medicine not currently on the ARTG.
If your product falls into Risk Group 1, you will be required to supply us with:
Samples submitted may be unlabelled, or carry overseas labels
We take no regulatory action based on the testing results of pre-registration samples.
We may contact you to discuss the results and methodologies.
We conduct pre-registration assessment and testing to develop and validate test methods in our laboratory, to ensure prompt and efficient batch release testing.
We may consult you regarding testing procedures during this time.
Your product will fall into full batch release (Risk Group 2) if it is:
You must quarantine all batches of products on batch release until you receive an email notification from TGA releasing each batch for distribution.
The quarantine period for each batch depends on our testing timeframes.
Products are generally kept on full batch release until we have confirmed batch consistency. This is usually achieved by testing at least five independent active substance batches.
For urgently needed products, you may request early release of your product based on the data you supplied on the understanding that:
If your product falls into either full or grouped batch release (Risk Group 2 or 3), you are required to:
In some cases, we may also require you to send raw data for specified assays, including:
You are to provide us with batches of drug product from different, independently manufactured, active substance batches. This means:
Send all required materials with sufficient lead-time to allow for the appropriate testing. New products require at least two months lead time due to the need to develop and validate new test methods. Established products require two weeks lead time as they have established test methods.
Email us to make arrangements for the delivery of the requested items and to send the relevant documentation.
Under the appropriate storage conditions, send samples and materials required to:
Therapeutic Goods Administration
Laboratories Branch, Biochemistry Section
136 Narrabundah Lane
Symonston ACT 2906
We assess the submitted data and test the samples as quickly as possible to ensure you can distribute your product as soon as possible. Our testing timeframes vary.
To reduce testing timeframes, we recommend you notify us prior to sending samples so we can schedule testing at the earliest opportunity.
Our testing time varies depending on the tests involved, for example:
We publish a summary of all TGA test results twice a year on our database of TGA Laboratory testing results.
We deal with any excursions from specification in consultation with you and, if necessary, other Branches of the TGA. In such cases:
We inform you of our test results in a test report letter.
More information is provided in test methods and handling of results.
We place products on full batch release (Risk Group 2) to:
Your product will fall into Grouped batch release (Risk Group 3) if it is:
You must quarantine all batches of products on batch release until you receive an email notification from TGA releasing each batch for distribution.
The time a product is on grouped batch release is the same as for products on full batch release (Risk Groups 2).
For products on grouped batch release:
However:
For products on grouped batch release, we perform delayed testing.
Samples are:
We inform you of our test results in a test report letter.
We publish a summary of all TGA test results twice a year on our database of TGA Laboratory testing results.
We deal with any excursions from specification in consultation with you and, if necessary, other Branches of the TGA. In such cases:
More information is provided in test methods and handling of results.
We place products on grouped batch release (Risk Group 3) to:
We process products on grouped batch release (Risk Group 3) to:
Your product will fall into Protocol batch release (Risk Group 4) if it is:
You must quarantine all batches of products on batch release until you receive an email notification from TGA releasing each batch for distribution.
For new low risk products, monitoring continues until consistency has been demonstrated (usually 5 independent active substance batches).
For products with identified problems, monitoring may continue until there is adequate resolution, even where:
Once all problems have been resolved, we will email you a letter changing the conditions of registration under section 28 of the Act.
If your product falls into protocol batch release (Risk Group 4), you are required to provide us:
We will usually assess the data and notify you of the outcome within 5 working days.
We place products on protocol batch release to:
Any issues for products on protocol batch release do not warrant testing of samples, such as:
Your product will fall into our post-market monitoring program if it:
If your product falls into the post-market monitoring program, we require you to:
You are required to complete an annual product report for biological prescription medicines. We use information in the annual report to update information in the risk assessment tool.
The annual product report requests, for that year:
Under GMP requirements, you are expected to have immediate access to all batch data and deviation reports or justifications. If you submit inadequate deviation reports, we may request more information. Deviations should be relatively few in a well-controlled QA system.
You are able to negotiate the submission date by emailing us.
We attempt to test all biological medicines on the market at regular intervals. We calculate the testing intervals using our risk assessment tool.
For our product surveys, when requested, you are required to provide:
During a product survey, we request samples from all sponsors marketing products:
For example, we would request samples from suppliers of:
We inform you of our test results in a test report letter.
We publish a summary of all TGA test results twice a year on our database of TGA Laboratory testing results.
We deal with any excursions from specification in consultation with you and, if necessary, other Branches of the TGA.
We attempt to test all biological medicines on the market (at regular intervals) using a risk-based prioritisation. The interval is calculated in the risk assessment tool from the inherent risk of the product.
Applicable to biological medicines, excluding vaccines, anti-venoms and toxins
We initiate a risk assessment once the second round of evaluation is completed. For most biological medicines, the risk assessment results in full, grouped or protocol batch release.
We update the risk assessment once:
After demonstrating batch consistency, we generally assign products to the post-market monitoring program (risk group 5). From that time, we update the risk assessment on a regular basis (usually every three years).
We may review and update our risk assessment if there are local or overseas reports of significant or severe problems with:
Events that may result in a risk assessment review may include situations where there are reports of life threatening adverse events or immunogenic reactions.
If the risk assessment tool identifies a change in the risk of the product, this may trigger a recommendation to change the risk group.
We will consider any mitigating or exacerbating factors (in consultation with the sponsor), before assigning the product to an appropriate risk group.
If this risk group is different to the current risk group of the product, we will vary the conditions of registration (under section 28 of the Act) and inform the sponsor by email.
Applicable to biological medicines, excluding vaccines, anti-venoms and toxins
We inform you of our test results in a test report letter.
We publish a summary of all TGA test results twice a year on our database of TGA Laboratory testing results.
For testing biological medicines, we are increasingly using validated TGA in-house orthogonal screening techniques. We apply internal acceptance criteria based on either:
from approved specifications of the tested group of biological medicines
Products whose results are:
In re-testing samples, which do not meet TGA in-house screening acceptance criteria, we use:
If non-compliance is confirmed using compendial or CPD methods, we will inform you and negotiate an appropriate course of action:
Before we use any method, we validate or verify their use according to the following standards:
Screening and CPD methods may require standards and internal controls, which only the manufacturer can supply. Such reagents may need to be verified before use in batch release. In such cases, after completion of the second round of evaluation, we may request:
The Certified Product Details (CPD) of a biological medicine specifies its:
When a new biological medicine is registered, ensure you provide us with an electronic draft of the CPD, as described in Guidance 7: Certified Product Details of the Australian Regulatory Guidelines for Prescription Medicines.
A template to prepare a CPD is available on our website.
Once drafted, send your CPD as a single pdf document to us. You can also use this address as a first point-of-contact on any testing issue.
When we have approved a change to an existing ARTG entry, either through a category 3 application or a self-assessable change, ensure you provide an updated CPD to the:
As laboratory protocols and reference standards may be subject to intellectual property protection, we treat all information supplied in the CPD as official information as detailed in Treatment of information provided to the TGA.
Deviations from approved storage conditions may cause a biological medicine to be of unacceptable quality and therefore not suitable for supply.
There are ways you can gain permanent approval of temperature excursions (of specified and validated magnitude and duration) to allow you to manage them under GMP. See Temperature excursions of biological medicines.
Applicable to biological medicines, excluding vaccines, anti-venoms and toxins
To assess the potential risks posed by a therapeutic good objectively, we use an internal risk assessment tool to address:
The risk assessment tool is also used to assign:
Applicable to biological medicines, excluding vaccines, anti-venoms and toxins
During the evaluation process, we assign your biological medicine to a risk group using the risk assessment tool.
Your application to register a new biological medicine is:
Variations to prescription medicines - excluding variations requiring evaluation of clinical or bioequivalence data: Process guidance outlines the normal Category 3 and self-assessable notification processes.
If you have a significant change in a manufacturing process, you are required to complete a comparability study before and after the change.
We will review the assigned risk group and notify you if any change is required, such as to:
If you make changes to testing methods or specifications you will need to submit an updated copy of the Certified Product Details document to us.
We assess the requirements for batch or protocol release testing during the evaluation process. The Delegate considers all recommendations and their suitability for inclusion in the approval letter.
If test methods used in the analysis of a new biological medicine are complex and approval seems imminent after the second round of evaluation, we may request:
Applicable to biological medicines, excluding vaccines, anti-venoms and toxins
Evaluation and registration of all new biological medicines:
Variation of the entry of the ARTG:
Conditions of registration:
Testing of therapeutic goods:
Applicable to biological medicines, excluding vaccines, anti-venoms and toxins
Version | Description of change | Author | Effective date |
---|---|---|---|
V1.0 | Original publication | TGA | 22/12/2015 |
V2.0 | Original document re-formatted and updated to reflect the latest practices, introducing information on use of TGA in-house orthogonal testing methods. | Biochemistry Section Regulatory Guidance Team | July 2019 |