Stability testing is to be performed to provide evidence on how the quality of a drug substance or formulation varies with time under the influence of various environmental factors such as temperature, humidity and light, and to establish shelf life for the formulation and recommended storage conditions.
Stability studies should include testing of those attributes of the drug substance that are susceptible to change during storage and are likely to influence quality, safety or efficacy. In case of formulations the testing should cover, as appropriate, the physical, chemical, biological, and microbiological attributes, preservative content (e.g., antioxidant, antimicrobial preservative), and functionality tests (e.g., for a dose delivery system). Validated stability-indicating analytical procedures should be applied. For long-term studies, frequency of testing should be sufficient to establish the stability profile of the drug substance.
In general, a drug substance should be evaluated under storage conditions that test its thermal stability and, if applicable, its sensitivity to moisture. The storage conditions and the length of studies chosen should be sufficient to cover storage, shipment and subsequent use.
Stress testing of the drug substance should be conducted to identify the likely degradation products, which in turn establish the degradation pathways, evaluate the intrinsic stability of the molecule and validate the stability indicating power of the analytical procedures used. The nature of the stress testing will depend on the individual drug substance and the type of formulation involved.
Stress testing may generally be carried out on a single batch of the drug substance. It should include the effect of temperatures), humidity where appropriate, oxidation, and photolysis on the drug substance.
Data should be provided for—
(a) Photostability on at least one primary batch of the drug substance as well as the formulation, as the case may be; and
(b) the susceptibility of the drug substance to hydrolysis across a wide range of pH values when in solution or suspension
Long-term testing should cover a minimum of six months duration if there is no significant change at any time during six months testing at accelerated storage condition or twelve months duration if there is significant changes in the six months accelerated stability testing on at least three primary batches of the drug substance or the formulation at the time of submission and should be continued for a period of time sufficient to cover the proposed shelf life. Accelerated testing should cover a minimum of six months duration at the time of submission. In case of drug substances, the batches should be manufactured to a minimum of pilot scale by the same synthetic route and using a method of manufacture that simulates the final process to be used for production batches. In case of formulations, two of the three batches should be at least pilot scale and the third one may be smaller.
