Specificity Requirements

[usallevyn]

I am getting ready to validate a method. For Specificity, what are the requirements ? My plan is to spike the product with impurites of the active ingredient to demonstrate that the active assay result is unaffected. Is that sufficient?
I do not plan to subject the product to various stress conditions like heat, UV, acid, base and oxidative degradation. Please advise if that is required by ICH.

USP (1225) allows spiking experiments for specificity for ASSAY.

[Rob Burgess]

Do you have all the possible impurities (synthetic and degradant) that may be present? If you do, consider youreslf lucky because from a pharmaceutical viewpoint for new chemical entitities its very unlikely that you have any!

I believe stress testing would be required to show you have specificity from your degradation products, especially for your impurity (related substances) and stability indicating assay method.

There was a paper in the J. Pharm. & Biomed Analysis a couple of years ago that described stress testing and specificity requirements very succinctly.

[usallevyn]

Actually I am working with Allantoin (ACTIVE) and methylparaben, propylparaben and 2-Phenoxyethanol (PRESERVATIVE) in the formulation. We know the degradants of most the compounds. So again I ask, do we still have to perform the stress testing/forced degradation under different conditions.

[Rob Burgess]

I would say yes, becuase you have developed a new method and you don't know if you have specificty between all your components and possible degradants.

[putnam]

Hi!

I would agree with Rob that a stressed degradation study should be performed to determine all possible degradants which may possibly interfere with the analyte.

We also try to show purity of the analyte peak as part of our specificity requirements. We analyze peptides, so DAD is not quite so useful. MS is a possibility, though we usually determine purity chromatographically with an orthogonal mechanism. For instance, we have developed both RP and CEX methods and will usually collect fractions (beginning, middle, and end) of the analyte peak as resolved on one method (say, RP-HPLC) and then run these fractions on the other method (CEX-HPLC) and see if we see any new peaks. This ties up the specificity section of our validation package quite nicely.