Stability testing specifications setting

Specialized LIMS— This type of LIMS is based on the fact that certain laboratories have a range of well-defined processes (e.g., stability testing) that are performed according to a specific set of regulations and by using well-established tests. The tests are done according to industry-wide accepted protocols. Specialized LIMS are tailor-made for certain types of laboratories. Therefore the performance can be optimized for clearly defined work process. 

Specifications set for each test attribute should be evaluated at each test point. Specifications can be set for release of the product and for shelf life as discussed in ICH guidelines Q6A and Q6B. The shelf life of the product is determined by all available stability information. Justifiable differences between shelf life and release acceptance criteria are appropriate. 

The product being crystallized was subject to a familiar set of constraints in the pharmaceutical industry. In early clinical trials, it was established that for bioavailability the active drug had to be supplied with a high specific surface area (2.3 -4.0 m /gm). On the other hand, it had to be highly crystalline, since (accelerated) stability testing had shown that partially (or totally) amorphous product, often encountered in the production of small (high surface area) particles, was subject to unacceptable... 

In summary, results of stability testing are related to the specifications that are set for both drug substances and products, because the allowable levels of degradation products and shelf life assay values for parent drug are assessed from the results of stability testing. 

Section (g) of this section indicates that the drug product used for investigation does not need to follow cGMP providing that the company will meet their specifications set by stability testing of clinical materials. However, many companies choose to follow cGMP for their late-phase clinical studies. 

For impurities, a specification for individual and total impurities must be set. It is recommended that numerical data are reported for individual (known and unknown) and total impurities in place of conforms or complies. Detailed information is discussed further in Q3A and Q3B. For stability testing of drug products, impurity specifications are set only for degradation products. 

In the United States, new dmg applications must be submitted to the Food and Dmg Administration (FDA), together with the appropriate chemical, manufacturing and control data, such as methods and specifications, the results of stability tests, proper labelling, details of pharmacological activity, the pharmacokinetic profile, toxicology studies and impurity limits [14]. In 1987, for the first time, the FDA published a set of guidelines on the submission of new chiral dmg applications. Each new dmg submission should show the molecular stmcture and the chiral centres of the dmg. The FDA also emphasizes the need for toxicological studies for each... 

The equipment is quite adequate for screening purposes. In its simplest form (i.e., a glass tube in an oven), it is a relatively low cost technique that can be assembled with standard laboratory equipment. However, the simple test set-up provides no quantitative thermal data for scale-up purposes, but only T0 values. The more advanced instruments like the SEDEX and SIKAREX, which are also isoperibolic calorimetry equipment, acquire specific thermal stability data that can be used for scale-up. Furthermore, the small autoclave tests provide gas evolution data. 

The frequency of OQ/performance verification depends not only on the type of instrument and the stability of the performance parameters, but also on the acceptance criteria specified. In general, the time intervals should be selected such that the probability is high that all parameters are still within the operational specifications. Otherwise, analytical results obtained with that particular instrument are questionable. The OQ/performance verification history of the type of instrument can be used to set reasonable test intervals. Here the importance of proper selection of the procedures and acceptance limits becomes very apparent. 

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