Chromatography Forum

We have an HPLC method that is completely validated for assay and impurities of our final product (a freeze-dried powder).

We now want to use the same method for analysis of an intermediate in the manufacturing process. The intermediate is a bulk solution (water solution) containing the API and excipients. To what extent do we need to revalidate the method for assay of the API in the bulk solution?
We need to follow FDA regulations.

Hi

On top of my head (might have missed something) and presuming that the bulk solution is diluted to a target concentration that is the same as for the final product sample concentration:

a. "only" new other player in sample seems to be purified water for injection. Maybe some assessment at least have to be written generally, see d below.

b. As sample preparation obviously changes significantly I would at least consider doing accuracy again as well as intermediate precision.

c. Consider if variation of bulk solution concentration can wounder outside validated range of analytical method without be outside process validation. You might want to increase range.

d. Robustness, new sample solution will require new short time stability of sample solution study. But might be avoided if existing and new sample solution is equivalent enough.
Is the stability of the bulk solution know? May have impact on how fast samples need to be prepaired.

If your intermediate is equivalent to the reconstituted final product, I wouldn't see where re-validation is necessary. If you reconstitute your final product with water to the same concentration as the intermediate bulk, it's the same thing since the API and excipients are already there in the dried final product only minus the water for reconstitution. Or am I missing something.....