Protocol for Stability Testing: A well-designed stability protocol should contain the following information:
Protocol for Stability Testing
Stability studies at developmental stages are generally carried out on a single batch while studies intended for registration of new products or unstable established products are done on the first three production batches, while for stable and well-established batches, even two are allowed. The selection of batches should constitute a random sample from the population of pilot or production batches.
(b) Containers and closures:
The testing is done on the product in immediate containers and closures proposed for marketing. The packaging materials include; aluminum strip packs, blister packs, HDPE bottles, etc. This may also include; secondary packs, but not shippers. Products in all different types of containers/closures, whether meant for distribution or physician and promotional samples, are to be tested separately.
(c) The orientation of storage of containers:
Samples of the solutions, dispersed systems, and semi-solid drug products for stability studies must be kept upright and positioned either inverted or on the side to allow for the full interaction of the product with the container closure. This orientation helps to determine, whether the contact between the drug product or solvent and the closure results in the extraction of chemical substances from the closure components or adsorption of product components into the container closure.
(d) Frequency of testing:
The frequency of testing should be such that it is sufficient to establish the stability profile of the new drug substance. For products with a proposed shelf life of at least 12 months, the testing frequency at the long-term storage condition should be every 3 months over the first year, every 6 months over the second year, and annually thereafter throughout the proposed shelf life expiration date. In the case of accelerated storage conditions, a minimum of three-time points including; the initial and endpoints, for example, 0, 3, and 6 months is recommended.
When testing at the intermediate storage condition is necessary as a result of significant change at the accelerated storage condition, a minimum of four test points including; the initial and final time points, is recommended, for example, 0, 6, 9, and 12 months.
(e) Sampling Plan:
The sampling plan for stability testing involves planning for the number of samples to be charged to the stability chambers and sampling out of the charged batch to cover the entire study.
The first step should be the development of the sampling time points followed by the number of samples needed to be drawn at each pull point for a complete evaluation of all test parameters and finally adding up to get the total number of samples. For example, there would be a requirement of about 100 tablets per pull out in long-term or accelerated stability studies including; 10 each for assay, hardness, and moisture determination, 6 each for dissolution and disintegration, and 50 for friability.
This multiplied by the total number of pull-outs will give the total number of tablets required for a study. This is followed by the development of a sampling plan, which includes; the selection of the containers representing the batch as a whole but in an unbiased manner.
(f) Test parameters:
The stability test protocol should define the test parameters that would be used for the evaluation of the stability samples. The tests that monitor the quality, purity, potency, and identity which could be expected to change upon storage are chosen as stability tests. Therefore, appearance, assay, degradation products, microbiological testing, dissolution, and moisture are standard tests performed on stability test samples.
Microbiological tests include; sterility, preservative efficacy, and microbial count as applicable.
The batches used for the stability study must meet all the testing requirements including; heavy metals, residue on ignition, residual solvents, etc. Some of these are required at the time of product release but not required to be repeated during stability testing.
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