In a recent publication, USP describes prednisone based performance verification test (PVT) as,
“Lot P1 demonstrates sensitivity to test performance parameters (vessels and degassing)”.
It appears that that the use of PVT has been reduced to establishing the appropriateness of vessels and degassing of the medium rather than a performance evaluation test for the apparatuses or procedure as it is supposed to. Even claims for sensitivities of the two suggested parameters may be of questionable merit. Because;
1. In a recent study from the FDA laboratory it has been demonstrated that dissolution test does not appear to show sensitivity to vessel dimensions, stating “Geometric characteristics varied within and among the sets of vessels, but the overall averages and standard deviations of dissolution results (six vessels) showed no statistical significant differences among the vessel sets”.
2. To be sensitive to a parameter (vessel geometry) there must be a link of dissolution results (response) to vessel geometry (action). For example, a mercury thermometer is based on heat based expansion. Thus, the higher the temperature higher the expansion. How does vessel geometry (or variation in its contour) relate/link to dissolution results?
3. Even if the contour of a vessel has any effect, then shouldn’t its control be established using appropriate physical measurements? It is like suggesting monitoring or controlling the room temperature based on measuring the humidity in the room. This appears to be quite impractical and an irrelevant approach.
4. With regard to sensitivity to de-aeration, objective and practice also appears irrelevant for number of reasons. For example: (1) conducting a dissolution test using de-aerated medium should make the test physiologically irrelevant as physiological environment does not dictate de-aerated medium. (2) For testing of products which are not sensitive to de-aeration, performing PVT with a de-aerated medium would be irrelevant. (3) Often dissolution tests are conducted for longer than half an hour. Usually during the testing, dissolution media become equilibrated with the dissolved gasses (air) and do not remain de-aerated. So, how would the analyst to maintain a consistent de-aeration level which apparently would be impossible.
In short, it appears PVT in its current form does not appear to provide any useful purpose but a financial burden on the pharmaceutical industry. Therefore, its use may easily be discontinued.
