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Australian regulatory guidelines for sunscreens (ARGS)
7. Stability testing
7.1 Stability test requirements
Therapeutic sunscreens marketed in Australia must be labelled with an 'expiry' or 'use by' date. That date must be supported by experimental data that support the shelf life of the sunscreen product in the container intended for marketing (or at least a container made of the same materials and with similar shape, size and wall thickness to that of the market container) under the recommended storage conditions (that is, 'Store below 25°C' for product to be stored in air-conditioned premises or 'Store below 30°C' for product to be stored at room temperature). The data must substantiate the physical, chemical and microbiological stability of the product for at least the claimed shelf life.
Sponsors of all therapeutic sunscreen products are expected to have performed stability testing on each product to at least the standard set out in these Guidelines. The claimed shelf life and storage conditions for each product should be derived from the results of the stability testing on that product. Generation of adequate stability data to support the assigned shelf life for a therapeutic sunscreen is the responsibility of the sponsor.
While the stability data supporting the shelf life of a sunscreen product are not required to be submitted to the TGA at the time of listing, they may be requested for review by the TGA at any time. Sponsors should, therefore, ensure that the data are available in a form suitable for submission to the TGA if and when requested.
Stability testing guidelines for sunscreens Guidelines for Stability Testing of Sunscreens April 1994 were developed by the Australian industry peak bodies and accepted by the TGA. They are now incorporated below with some minor amendments to improve clarity and consistency with the stability guidelines for medicines adopted by the TGA (see ARGOM chapter on Quality). This section (7) now supersedes the Guidelines for Stability Testing of Sunscreens April 1994.
7.2 Establishing stability before listing or registering
Prior to listing and market launch, the shelf life must be established with real time testing for the whole of the required shelf life or with adequate certainty using accelerated testing (that is, 6-9 months at 10°C or 15°C above the stated maximum storage temperature - see Table 2) or justified on the basis of supporting stability data for a closely related formulation.
Pre-listing or pre-registration stability testing should be carried out using at least two batches of the formulation intended for marketing manufactured in a manner that closely mirrors the production-scale manufacturing process. A formulation very similar, but not identical, to that intended for marketing formulation may be used provided any differences are very minor and unlikely to affect the physical, chemical or microbiological stability or in-use performance of the product.
The batches tested in stability studies may be pilot-scale but should have been manufactured in a manner sufficiently similar to that of commercial production scale batches that they adequately reflect the properties of the product intended for the market.
7.3 Confirming stability and shelf life
If the shelf life assigned at the time of listing is based on data generated using pilot-scale batches and accelerated studies, the shelf life should subsequently be confirmed by real time studies covering the whole of that shelf life using at least two production-scale batches stored at the maximum recommended storage temperature. These production scale batches should be tested initially at manufacture and then annually until the end of the shelf life.
7.4 Stability protocol requirements
Physical testing should include at least the following quality parameters: appearance, emulsion stability, absence of crystallisation, odour, viscosity, compatibility with the immediate container and the condition of the inside surface of the container in contact with the product.
Chemical stability testing should include: pH (if water is the continuous phase) and the content of each of the active ingredients assayed using a validated, stability-indicating analytical procedure (for example, HPLC). Active ingredients should remain within the limits 90% to 120% of label claim.
Overages of active ingredients in the formulation are acceptable provided they do not result in concentrations exceeding the limits provided in subsection 9.1.
For water-containing sunscreens, microbiological stability should be confirmed by means of preservative efficacy testing at the start and end of accelerated stability testing and at the end of the shelf life during the subsequent real-time stability testing.
The temperature of storage used in stability studies should be controlled, monitored and logged to ensure the integrity of the results.
The frequency of testing for accelerated studies should be adequate to allow regression and statistical analysis to support extrapolation of the data. Appropriate testing time points would typically be 0, (1 or 2), (3 or 4), (5 or 6), 9 and 12 months (followed by 24 and 30 months, depending on the shelf life required to be justified).
The accelerated stability data should only be extrapolated as in subsection 7.5 if their accuracy, reproducibility and fit around a straight time-line are adequate. A minimum of 4 time-points with a reasonably even spread over the time period concerned are needed for meaningful line-fitting and 95% confidence interval calculations.
7.5 Shelf life determination
For a product exhibiting no discernable changes or trends, a 2-year shelf life for storage conditions of 'store below 30°C' (that is, storage at room temperature in Australia) may be supported by stability data covering 6 months storage at 40°C, and a 3-year shelf life for storage conditions of 'store below 30°C' may be supported by data covering either 9 months at 40°C or 6 months at 45°C.
A shelf life of greater than 3 years should be supported by data from storage at 40°C covering at least half of the shelf life (for example, 2.5 years accelerated data would be required to support a 5-year shelf life).
For a product exhibiting no discernable changes or trends, a 2-year shelf life for storage conditions of 'store below 25°C' (that is, the product should be stored in air-conditioned premises) may be supported by stability data covering 6 months storage at 35°C, and a 3-year shelf life for storage conditions of 'store below 25°C' may be supported by data covering either 9 months at 35°C or 6 months at 40°C.
A shelf life of greater than 3 years should be supported by data from storage at 35°C covering at least half of the shelf life.
Generally, the maximum shelf life permitted for any therapeutic good is 5 years.
|Temperature above labelled storage conditions||Time period||Test time points||Possible shelf life prediction|
|+10°C||6 months||0, (1 or 2), (3 or 4), 6 months||2 years|
|+10°C||9 months||0, (1 or 2), (3 or 4), (5 or 6), 9 months||3 years|
|+15°C||6 months||0, (1 or 2), (3 or 4), 6 months||3 years|