SOP on Stability Studies of Drug Products
1.0 Purpose: Product stability is significantly influenced by the method / process of formulation, packaging and thereafter during storage by a variety of factors, such as temperature, humidity, light etc. It is therefore necessary to know the influence of these factors, and then establish the shelf-life of the Drug Product under recommended storage conditions.
2.0 Scope: This SOP provides general guidelines for conducting, evaluating and reporting stability studies on finished Drug products.
3.0 Responsibility:
3.1 Quality Control Chemist – to perform the test.
3.2 Quality Assurance Manager – to review
4.0 Materials and Equipment: As required.
5.0 Procedure: The stability studies protocol includes:
5.01 Selection of Batches: A minimum of 3 batches should be selected for accelerated and long time stability studies. The batches should be packaged in the container-closure systems intended for the marketed product. Two of the three batches should be a minimum of pilot scale and the third batch may be smaller.
5.02 Test procedures: Test procedures should include all parameters that are susceptible to change during storage and that are likely to influence quality, safety and / or efficacy. These include, as appropriate, physical, chemical, biological and microbiological characteristics.
5.03 Acceptance Criteria: The acceptance criteria should be numerical limits, ranges, and other criteria for specific tests, and should include limits for individual and total impurities and degradation products.
5.04 Sample Requirements: Sample quantity is based on amount needed for each test.
5.05 Test Frequency: Test frequency should be adequate to demonstrate any degradation and to provide enough data points for statistical evaluation. The commercial batches testing is expected initially, at 1, 3 & 6 months in case of accelerated studies and in case of long term studies initially, at 6, 12, 18, 24, 30 and 36 months. For intermediate studies initially, at 3, 6 and 12 months.
5.06 Storage Conditions: Stability studies should be carried out under storage conditions for a length of time that covers the conditions for storage, and subsequent use. The effect of temperature and moisture should be evaluated as appropriate. Stability studies include long term and accelerated storage conditions.
Long Term Studies: 300C 20C Temperature; 65% 5% Relative Humidity
Accelerated Studies: 400C 20C Temperature; 75% 5% Relative Humidity
5.07 Duration of Studies: Accelerated studies are carried out for 6 months, and long term studies for the expiration dating period for finished drug products.
5.08 Evaluation: Any evaluation should consider not only the assay, but also the levels of degradation products and other appropriate attributes.
A significant change at the accelerated conditions is defined as:
5.08.1 A 5% potency loss from the initial assay value.
5.08.2 Any specified degradant exceeding its specification limit.
5.08.3 The product exceeding its pH limits.
5.08.4 Dissolution exceeding the specifications for 12 dosage units.
5.08.5 Failure to meet specifications for appearance and physical properties (e.g. Colour, phase separation, caking, hardness etc.)
5.09 Stability Report: The results may be presented as both a table and graph for each batch. The results of testing both at time of manufacture and at different times during storage should be given. A standard report form should be prepared in which the results for each pharmaceutical preparation can be summarized.