Chromatography Forum

No, the fragrance peaks are too small to influence the quantitation of the active peak. Our QA agrees with you that such peaks are negligible, but my supervisor says "a peak is a peak, no matter how small".

We've discussed dilution of samples and standards so such peaks are not larger than 3x the noise, but I feel that doesn't help the science either, and would require dilution of each sample (another step for QC to potential screw up, plus more solvent waste). We've also discussed using a less sensitive wavelength for this, but again, doesn't help the science, just a way to "skirt" the regulations. In the one instance we can saponify the fragrance component and then that area is flat, but that's also an extra step (plus neutralization) for QC, and would also require some validation, tech transfer, etc.

We also have same preparation but different set of conditions that had been previously validated but that requires a column change and solvent change (uses THF), not really something we want to throw onto QC, like running one "flavor" by a different set of conditions.

Our test methods do not state anything about peaks that are below a certain threshold need not be integrated or determined either.

The ICH guidance for drug product impurities specifies a threshold of 0.05%. Thus any peaks below would not be reported, and hopefully for you not require integration. I would focus on using the guidance as justification for not reporting peaks smaller than 0.05% rather than ways to make the peaks disappear.

I wouldn't want to be the one trying to explain to the FDA auditor why the methods were updated and impurity peaks previously observed or no longer present.

You wouldn't need to add to the test methods just a general SOP.

I that that 0.05% ICH guideline is more for an impurity in an API for the API manufacurer. And my supervisor does agree with that.

The ICH drug product reporting threshold is 0.05%, so the guidances must be the same for APIs and drug products.

So If the FDA does not require a GMP drug product impurity to be reported at levels less than 0.05% than why would a body wash have a stricter guidance?

But it all depends on the size of the fragrance peak.