Stability studies are one of the important quality parameters of pharmaceutical products. It sets the drug shelf life, determines proper storage conditions, and the labelling instructions for end-users. Stability studies for the Saudi market (SFDA-GCC) are to be studied in accordance with the International Conference on Harmonisation (ICH) Q1A(R2) and the World Health Organization (WHO). It is one of the key compliance elements for drug file approval in the SFDA and the GCC countries.
In this article, we will detail the minimum requirements for SFDA drug registration. In the drug file, the requirements fall under the three CTD sections:
The summary should clearly outline the number of batches manufactured, placed into stability study, and the time point at which the drug product analysis is done under long-term and accelerated conditions.
Stability batches containing information related to (Storage Conditions, Testing Frequency, and Type of tests) should be outlined, as indicated on the below table;
A discussion of the stability result for the batches studied at the time of submission should be mentioned for no significant change in the overall concentration of the batches.
The conclusion should be clear for no significant changes in any of the product parameters, either during the long-term or during the accelerated stability testing and accordingly, the shelf life and storage condition are proposed.
A stability testing protocol is required to confirm the proposed shelf life. It should contain information on the stability batches studied, test details, storage conditions, and sampling plans. SFDA might require stability commitments in cases such as:
Three primary stability study batches are required. Two of the three batches should be at least pilot-scale batches (pilot-scale batch size is 10% of the proposed production size). The third one can be a lab-scale (lab-scale batch can be smaller than 10% of proposed production but NLT 25% of the pilot-scale)
The frequency of testing at the long-term storage condition should normally be every three months over the first year, every six months over the second year, and annually thereafter throughout the proposed shelf-life (e.g., 0, 3, 6, 9, 12, 18, 24, 36 months).
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 six-month study are recommended.
For Saudi Arabia, stability is required in Zone IVa for long-term stability testing. Alternative storage conditions can be used if justified.
Long Term Testing Conditions:
| Climatic Zone | Temperature | Humidity | Minimum Duration required at submission |
| Zone I | 21ºC ± 2ºC | 45% rH ± 5% rH | 12 Months |
| Zone II | 25ºC ± 2ºC | 60% rH ± 5% rH | 12 Months |
| Zone III | 30ºC ± 2ºC | 35% rH ± 5% rH | 12 Months |
| Zone IVa* | 30ºC ± 2ºC | 65% rH ± 5% rH | 12 Months |
| Zone IVb | 30ºC ± 2ºC | 75% rH ± 5% rH | 12 Months |
| Refrigerated | 5ºC ± 3ºC | No Humidity | 12 Months |
| Frozen | -15ºC ± 5ºC | No Humidity | 12 Months |
* Stability zone for Saudi Arabia
Accelerated Testing Conditions:
| Climatic Zone | Temperature | Humidity | Minimum Duration |
| Accelerated Ambient | 40ºC ± 2ºC | 75% rH ± 5% rH | 6 Months |
| Accelerated Refrigerated | 25ºC ± 2ºC | 60% rH ± 5% rH | 6 Months |
| Accelerated Frozen | 5ºC ± 3ºC | No Humidity | 6 Months |
Stability data should include the type of batches used for the study (i.e. production, pilot or lab), storage condition, stability entering date, and product manufacturing date. The data should be tested for stability-indicating parameters covering physical, chemical, and microbial parameters. In general, appearance, assay, and impurities should be evaluated for all dosage forms, as well as the preservative and antioxidant content and other parameters to be evaluated as per the dosage form.
In-use stability is performed to know that the product stored at °C/ % RH show acceptable quality throughout the in-use period. An in-use program is required for liquid multi-dose sterile products, multi-dose products with a protective outer package, and products that are constituted or diluted.
A minimum of two batches, at least pilot-scale batches, should be subjected to the test. One batch should be tested initially and the other at the end of its shelf life. If the test result is unavailable at the end of the shelf life, then one batch should be tested at the final point of the submitted stability studies (with a commitment to submit the results at the end of the shelf life as soon as they become available).
In-use stability should be tested for physical, chemical, and microbial properties of the product, which is susceptible to change during storage. Testing should be performed at the initial time point, intermediate time points, and at the end of the proposed in-use shelf-life on the final remaining amount of the product in the container.
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