Prednisone Calibration Failure

[Tom Morgan]

Subsequent to a failure of a single vessel during calibration, an investigation is performed. No specific cause/problems are identified. The failing vessel (only) was retested twice (with tablets from the same bottle) and passed both times - with results that fit with the tight grouping of the original 5 passing vessels.
Should all six stations (vessels) be retested before returning to service or is the successful retesting of the failing location adequate for "calibration"? And, what is the rationale for your position?
Thanks for your replies and perspective.

[qureshi]

Please keep the USP informed of the observations and for further discussion on this topic refer to my post http://www.dissolution.com/vbulletin/showthread.php?p=3693#post3693 and corresponding thread.

Saeed

[johnt]

I have always been of the belief that when the suitability is tested all six vessels need to be done. My reasoning is that when you do a dissoution test all six vessels are used therefore during the official suitability needs to be done with all six vessels.

[ewething]

I strongly suggest to re-test all six at once. There may be an issue with the drive belt or that specific spindle that may or may not repeat itself within that same position.

I have heard that worn drive belts could could cause a failure in one position during one test and then in another during another test.

Good luck!

[vjf]

In our lab we automatically re-test all six vessels. After a failure we have a check list of 10 things that must be checked and found within specifications before the test is repeated.
Note: There have been a number of instances that everthing is in spec and we still have a failure. We check all 10 again and run the test again.

[qureshi]

As I said before, please keep the USP informed. This will help them addressing the issue that "out of spec" values not necessarily reflect sub-standard instrumentation. These (your) observations are providing support to our own findings which are published stating "The results indicate that failure to meet the USP Dissolution Apparatus Suitability Test may not truly mean that the apparatus is "out of compliance" [Eur. J. Pharm. Sci. (1999) pp. 249-258].

[blincoln]

I don't buy into repeating all six vessels due to one failure. If we were suppose to repeat all six vessels then the calibrators' specifications should be represented with USP S1, S2, and S3 tolerances. The calibrator certs are for individual tablets, not for n=6 testing.

If the recommendation is to repeat all six prednisone tablets, then you would have to repeat all six non-disintegrating tablets, if they were previously tested. Now its becoming rediculous. Check your standards, recheck the mechanical operation with a QA station and apply a sound analytical investigation. Remember, a good dissolution bath and test will differentiate between good and bad product. Actually, I think the calibrators should come with a money back guarantee (LOL)!!!