James Zellner, Technical Sales Representative
The FDA defines photostability as the ability of a drug substance or product to resist chemical changes when exposed to light and considers photostability testing as an “integral part of stress testing”. Much of the FDA’s standing on photostability and the associated studies to perform comes from the ICH Q1B Guidance for Industry Photostability Testing of New Drug Substances and Products. The FDA has officially adopted this document as guidance, so it should be used to design photostability studies.
ICH recommends a systematic approach to photostability testing, which, as appropriate, may include testing of the drug substance, exposed drug product (out of its primary packaging), drug product in any intermediate packaging, and, finally, drug product in its final packaging. Later, if there are changes to either the formulation or packaging, ICH states these studies should be repeated to demonstrate that no change to product stability occurs.
When conducting a photostability study, Q1B is specific in what types of light, wavelength, and exposure should be used. For visible light, this consists of not less than 1.2 million lux hours and a near UV exposure of 200-watt hours/ square meter. Exposure should be measured via chemical actinometric systems and/or calibrated radiometers/ lux meters. Throughout the exposure period, the temperature of the photostability chamber must be maintained to avoid additional stressors on the product that may lead to inaccurate photostability conclusions. Sample sizes should be adequate to demonstrate that no variability exists between individual product units. While there isn’t a specific number used in Q1B, 20 units are cited as an example for a solid dosage form. “Dark control” samples are included for comparison. During light exposures, the test samples are arranged in the chamber to ensure uniform exposure of the product to the light source and continue until the appropriate amount of lux/ watt hours is achieved.
At the conclusion of the exposure period, many tests may need to be performed to assess photostability. The drug substance or product should be assayed for stability of the API (active pharmaceutical ingredient) using a formulation-specific, stability-indicating analytical method. As with other guidance, FDA expects this to be done via a chromatographic method that is reliable, meaningful, uses a reference standard, and is highly specific. The assay method should have, during its development, been created using both visible light and UV stressors to ensure the potential degradants created during this exposure are separated from the API. Testing to assess photostability should not be limited to the assay. Appearance, color and clarity of solution (in the case of a liquid product), and dissolution/disintegration (in the case of a solid product) are examples of other tests that may need to be assessed to fully understand the photostability of the drug product. The appropriate tests to include depends on the drug substance or product being tested. Dark control samples are tested using the same scheme as the primary samples to compare.
Evaluation of the test results should include a determination of whether changes observed, if any, are acceptable. The results from stability studies should be considered when evaluating photostability data. If the substance or product is not stable when exposed to light, an assessment of the product or packaging systems is needed. Special labeling or packaging may be required to mitigate the effects of light exposure.
Contact ARL today to learn more about Photostability Studies and Testing. 800-393-1595 or info@arlok.com.