Here at Nutrasource, we field many inquiries about stability storage testing for many different dosage forms. To provide you with some insight into this important but often overlooked type of product testing, our analytical laboratory, Diteba, provides answers to the most frequently asked questions regarding stability storage and testing.
1. What is an accelerated stability test condition?
The International Conference on Harmonization (ICH) defines this as "studies designed to increase the rate of chemical degradation or physical change of a drug substance or drug product by using exaggerated storage conditions as part of the formal stability studies". Most commonly, it is storage at 40°C +/- 2 degrees and Relative Humidity (RH) of 75% +/- 5 % when the long-term stability storage condition for the product is 25°C +/- 2 degrees and RH of 60% +/- 5%. This and other storage conditions are prescribed in the ICH Guidelines for Stability Testing.
2. Can you perform stability testing for a physical, chemical and microbiological stability study?
Diteba can perform physical and chemical testing for stability studies; however, they do not have microbiological testing capabilities in-house.
3. What are product release specifications and why do I need to know them?
You would need to know the product testing specifications to be tested in a stability testing program. Every product is different and each one typically requires different testing methodologies and equipment. Product specifications are a list of tests, referenced to (stability-indicating) analytical procedures with proposed acceptance criteria, including different acceptance criteria for product release and shelf life specifications.
4. What is long-term stability testing?
ICH defines this as "stability studies under the recommended storage condition for the re-test period or shelf life proposed (or approved) for labelling". Long-term stability testing is also referred to as room temperature stability storage condition testing. The most common storage condition is 25°C +/- 2 degrees and RH of 60% +/- 5%. This and other storage condition are also prescribed in the ICH Guidelines for stability testing. At times, 30°C, 75% RH storage conditions can be substituted depending on the product or compound being testing and the zone you are contemplating have the product sold in. These zones are also stipulated in the ICH Guidelines.
5. How many lots of product do I need for both accelerated and long-term stability testing?
Depending on what stage of the product lifecycle your product is at, you will usually require between 1 and 3 lots of each product stored in each container/closure system proposed for selling to be placed on stability. The ICH Guidelines recommend 3 lots; however, we strongly urge you to consult with the applicable regulatory authority in your region to find out what specific requirements they may call for.
6. What time points do I need to test my product at?
ICH Guidelines recommend that proposed stability testing should show results after 0, 3, 6, 9, 12, 18 and 24 months storage for long-term testing and 0, 3 and 6 months storage for accelerated testing. You may wish to consider longer time points for long-term stability testing (i.e., 36, 48, 60 months) if you feel your product can achieve a longer shelf life.
7. What parameters should I test for in my tablet/capsule product in a stability program?
You will need to determine what the proposed shelf life testing specifications are that will need to be included in a stability testing program. Some typical testing parameters that can be included are: color, appearance, odour, friability, active substance content (potency), degradation result (impurities or related substances), disintegration, dissolution, water content and microbial content. Consult with the applicable regulatory authority to determine what specific tests they may require.
8. Should a stability testing program have a conclusion as to how the product was tested, what the result was and how long its shelf life should be based on the testing completed?
Yes, this should be conducted on a routine basis. As well, a stability testing protocol should be created at the beginning of the stability testing program stating what the parameters of the stability testing program are, the product specifications that are to be adhered to, what is expected to be tested and when this should occur.
9. In a 24-month stability study, is the month 2 time point critical or could it be eliminated such that we just do months 1 and 3?
For long-term studies, the frequency of testing should be sufficient to establish the stability profile of the product. For products with a proposed shelf life of at least 12 months, the testing frequency at the long-term storage condition should normally be every 3 months over the first year, every 6 months over the second year, and annually thereafter through the proposed shelf life.
At the accelerated storage condition, a minimum of three time points, including the initial and final time points (e.g., 0, 3 and 6 months), from a 6-month study is recommended. Where an expectation exists that results from accelerated testing are likely to approach significant change criteria, increased testing should be conducted either by adding samples at the final time point or by including a fourth time point in the study design.
10. Can the testing of stability samples be matrixed so that we can get costs down but still conduct a legitimate study?
ICH Guidelines recommend that for reduced designs, such as matrixing or bracketing, where the testing frequency is reduced or certain combinations are not tested at all, this can be applied if you can justify the matrix or bracketing approach. Your stability schedule should be designed so that a selected subset of the total number of possible samples for all combinations is tested at a specified time point. At a subsequent time point, another subset of samples for all combinations should be tested. The design assumes that the stability of each subset of the tested samples represents the stability of all samples at a given time point. You must be able to identify the differences in the samples for the same drug product, covering different lots, strengths, sizes of the same container/closure system and different container/closure systems.