Method Validation

[Sallybeetle]

I will be performing a method validation for a product with a new (added) active ingredient, but the same excipients and original active ingredients. The product / method were fully validated with the current active ingredients and excipients.


Do I have to do a full validation of only the new active ingredient in the presence of the original active ingredients / excipients?

Would the original active ingredients have to be present during validation?

Would I have to perform all of the validation calculations for the original active ingredients? I can't imagine that the new active would make an original active less linear or accurate.

Of course, I am assuming that the HPLC method will not have to be adjusted to obtain resolution of all the actives.

Thank you very much for any and all advice.

[tom jupille]

I can't imagine that the new active would make an original active less linear or accurate.

FDA auditors can have very fertile imaginations in such matters.

As long as you have to go through all of the sample prep, chromatography, etc., anyway, the incremental effort to crunch the numbers on your other components is relatively small compared to having to re-do the whole thing later (my 2¢ worth, anyway).

[josebenjamin]

Sallybeetle,

I hope I have understood your situation. If you need to validate the new active ingredient, then you have to run a full validation for this new assay, including excipients and older active ingredients. All of this in order to be safe and not have any "handles" where auditors could question the logic of your work.

If you are only interested in the "old actives", but the samples contain this new ingredient, then you could get away just showing that the specificity of your method has not changed. In other words, you will have to show that the new active does not have any intereference with the old ones. This could be easily done showing no extra peaks due to the new component obstructing the quantiation or recovery of the old actives.

good luck,

josebenjamin

Since the excipients have

[pawan ratra]

I would like to share my experience with the similar situation.

I have worked with two products. Product 1 contain A+B and Product2 is the combination of A+B+C+D. I have a very interesting observation during method development. when the pH of diluent is acidic (pH-2.5), the area counts of the peak C and peak D increase with time upto 4 hrs and then stabilized. When the diluent pH is 7.0 the area counts of peak A and peak B increase with time and then stabilized. The ph of dluent has to be maintained about 5.0 to get the stable area counts for all the peaks.
From the above it can be concluded that the addition of one or two active components may give unusual observations. Thus it is required that the complete validation should be performed whenever there is change in the formulation.