by
krickos » Wed May 11, 2011 10:58 am
Hi CGP
Will give some comments in reverese order.
3. Seen warningletters/483s citing similar things relating to question 2 like:
-No documentation of verification of suitability when introducing pharmacopiea procedures
-No supporting documentation/changecontrol of significant changes to analytical procedures
However changes (documented)of pharmacopiea procedures whitin the allowed intervalls given in USP (or EP for that matter) has not caused us any trouble so far.
2. Not formally, but I recommend that you write a supporting report with before/after comparision and handle the change according to your in-house standard operating procedure. Technically you may have to repeat some typical validations parameters more or less depending of what you do change, perhaps most common has specificity/resolution improved, is LOQ/LOD-signal to noise ratio stilll accepteble, is peak shape OK.......
Running SSTs and samples for comparision of before/after can sometimes be good enough sometimes a little more may be needed depending on change/changes.
1. First time I encounter such a question and hard to give a straight answer.
Putting the theory of what a retention/guard gap do to the side for a moment, I would do a risk assesment. What is likely to happen if I make this change (cause it is a change) and what validation parameters are then impacted.
Apart from increasing the life time of the analytical column, ideally you get better peak shapes which in turn may have impact (hopefully positive) on selectivity/resolution,peak shape, LOQ/LOD-signal to noise.
I see this as a change outside what was discussed in question 2 and what normally is covered under robustness in a validation. Consequently it should require some additional validation work in my opinion.
