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Impurities in new drug product

Posted: Wed Aug 08, 2018 2:29 pm
by chunduri.2009
Hello Every one,
In Q3B ich guidelines can any one help me out the exact difference between reporting threshold, identification threshold & qualification threshold ?

Re: Impurities in new drug product

Posted: Thu Aug 09, 2018 3:29 am
by dap
Hello.
Reporting th means disregard limit.
Identification th means unidentified impurity limit.
Qualification th means identified impurity limit.

Re: Impurities in new drug product

Posted: Fri Aug 10, 2018 5:30 pm
by chunduri.2009
Sorry I can not understand your point,
if possible could you please elaborate it.
Thank you,
Siva Kumar ch

Re: Impurities in new drug product

Posted: Fri Aug 10, 2018 6:43 pm
by mattmullaney
Hi chunduri.2009,

From ICH Q3B(R2),

http://www.ich.org/fileadmin/Public_Web ... deline.pdf

Degradation Product: An impurity resulting from a chemical change in the drug
substance brought about during manufacture and/or storage of the new drug product by the effect of, for example, light, temperature, pH, water, or by reaction with an excipient and/or the immediate container closure system.

Identified Degradation Product: A degradation product for which a structural
characterization has been achieved.

Unidentified Degradation Product: A degradation product for which a structural
characterization has not been achieved and that is defined solely by qualitative
analytical properties (e.g., chromatographic retention time).

Identification Threshold: A limit above (>) which a degradation product should be identified.

Qualification: The process of acquiring and evaluating data that establishes the
biological safety of an individual degradation product or a given degradation profile at the level(s) specified.

Qualification Threshold: A limit above (>) which a degradation product should be qualified.

Reporting Threshold: A limit above (>) which a degradation product should be
reported.

Appendix 1 of Q3B(R2) contains a plot which may help with explaining these definitions and their relationship.

A caveat can be the toxicity of the degradation product under consideration (upon its qualification).

Please, do you have further specific questions?

Re: Impurities in new drug product

Posted: Mon Sep 03, 2018 7:50 pm
by Geof235
Hi,

I’ve always explained it like this

Reporting threshold: this is the limit at which a peak is to be reported (typically 0.05% relative to sample concentration) basically any peaks greater than 0.05% needs to be calculated and reported as unknowns

Identification threshold: this is the limit where if a peak is observed (typically between 0.1% - 0.2%) you must identify the chemical structure.

Qualification threshold: this is the limit where if a peak is observed (typically greater than 0.2%) you must not only know what the chemical structure is, but you may also have to isolate it and perform a toxicological study or some other study to evaluate if the impurity is toxic or harmful