Stability data, good laboratory practice

This study was conducted in accordance with FDA Good Laboratory Practice Regulations (FDA, Tide 21 CFR Part 58, Federal Register, 22 December 1978 and subsequent Amendments 11 April 1980 and 4 September 1987) except that data concerning the identity, purity and stability of the test material and stability of the test material/carrier mixture were generated within a GMP environment. 

An important aspect is that of data and model stability. The raw data, for example, assay data, need to be updated regularly as new results become available. This process is tedious and time consuming and once a valid protocol for data acquisition and validation has been established, it is suitable for automation. The automatic procedure requires extensive data integrity checks (e.g., do all data points have valid structures and experimental results, how to handle conflicting results from different experiments) and a formalized automated normahzation process. This involves answering questions such as how to handle isomers, do experimental in vivo results have precedence over in vitro results or should all results be shown, should more confidence be put in results from Good Laboratory Practice (GLP)-studies, and so on. The models are then automatically rebuilt using the updated data and auto-updated as was mentioned in the QSAR section. A model may be promoted to use in the production system if it passes some defined validation tests, specific for each model, which was also mentioned earlier. 

Phase solubility and thin layer chromatography are two very commonly employed techniques which will verify purity. Not only do these techniques indicate initial suitability of a standard, but they also help to monitor changes in standard purity with time which could render the standard no longer acceptable. Of the two, phase solubility is the most reliable from the standpoint of accuracy and the fact that it can be employed in most laboratories. On the other hand, when phase solubility data indicate differences in bulk purity, it is good practice to establish whether the change is purity or stability related. Phase solubility is not readily employed in this capacity however, thin layer chromatography can provide excellent supplemental data. There are additional techniques, but these two can provide considerable information with relative ease and low cost. 

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