By Anonymous on Wednesday, February 11, 2004 - 08:10 pm:
The USP states, "Adjustments of operating conditions to meet system suitability requirements may be necessary."
How much adjustment can be made to a chromatographic system in order to meet system suitability and still consider the method which is being run identical to the procedure which was originally validated?
When changes are made (i.e., replacement of a pump in an HPLC,modification of a mobile phase, use of equivalent columns, ...) is system suitability sufficient to assure consistent operation?
By tom jupille on Wednesday, February 11, 2004 - 11:26 pm:
Those questions open a large "can of worms".
While there have been proposals for de-facto "adjustment" limits, as far as I know, the FDA has never made an unequivocal statement of what the limits are.
Ideally, the allowable limits of adjustment should be documented as part of the validation package; if your method was properly validated, it will include information about robustness. That information should establish the range of conditions over which the method is valid. Unfortunately, many older methods are lacking this information. Those methods should probably be revalidated anyway.
In the specific case of hardware substitution (e.g., a pump or detector), if you still meet system suitability, then the results are, by definition, suitable for the intended purpose. This assumes that system suitability criteria were properly established during validation. As with robustness information, too many older methods are lacking in this area.
By Steven on Thursday, February 12, 2004 - 10:56 am:
Pharmacopeial Forum Vol.29 No. 1 Jan-Feb 2003 pg 171 has an in-process revision to the Chromatography. This revision defined allowable adjustments being considered. This revision is not in USP 27 or the first supplement so it is not official yet, but you could probably use it as a guideline.
By Anonymous on Wednesday, March 10, 2004 - 12:01 pm:
Steve,
How can I get access to this guideline? Thanks.
By Uwe Neue on Wednesday, March 10, 2004 - 03:06 pm:
It is not only a can of worms, but it also smells rather rotten.... The change of the column is guaranteed to change the selectivity of the separation. It can not be put into the same category as a change of the flow rate.
By labcat on Thursday, March 11, 2004 - 01:23 am:
It is also like a walzer... continuosly changing. Once we couldn't increase the injected volume, then we could increase it to twice the volume specified, now we are not allowed any more... until when?
Column diameter could change +/- 50%, now 25%. But how is it possibile to decrease column diameter from 4mm to 3mm, without decreasing flow rate, as "multiple adjustments are to be avoided"?