(1999; 168 pages) [Spanish]
7.3.5 Stability studies
Many excipient products are very stable and may not require extensive testing to check stability. The stability of some excipients may be affected by undetected changes in starting material specifications, or subtle changes in manufacturing procedures. Excipients may also be shipped in a large variety of different packaging types that can affect their stability (e.g. metal and plastic drums, bags, plastic and glass bottles, bulk tankers).
Some excipients may be similar in chemical structure to other excipients, and some may be mixtures or blends of other excipients. These excipients may be very similar to others within a product group. Minor quantitative differences of some of the components may be the only significant variation from one product to another. For these excipients, a "model product" approach to assess the stability may be appropriate. Stability studies of this type should involve selection of several "model products" that would be expected to simulate the stability of the product group being assessed. This selection must be scientifically based. Data from stability studies of these "model products" can be used to determine the theoretical stability of similar products.
The full stability testing programme, when needed, usually contains the following features and takes into account historical data:
• The programme should be formalized in writing and ongoing studies should be reviewed at least annually.
• The programme should periodically include a sample from at least one commercial size batch.
• Stability samples should be stored in containers that approximate the primary market container. Simulations of all types of containers are not required, unless there are theoretical reasons to indicate that stability may be affected by container type.
• The samples should be stored under conditions similar to those recommended for the marketed excipient product.
• Additional samples may be stored under stress conditions (e.g. elevated temperature, light, humidity or freezing) if such conditions might reasonably be encountered during distribution and storage.
• Stability-indicating test methods should be used.
• Where stability of the excipient appears to be a significant issue in its use in pharmaceutical manufacturing, additional periodic testing of either the specific material or "model products" may have to be performed to ensure that the expected stability does not significantly change with future batches. The frequency of testing should be determined by the impact that the excipient's stability may have on its usage.