Reporting Impurities

[michaelcarolus]

Hi All

I need some advice on how to report impurities for a drug product.

I have to a stability indicating HPLC method that measures impurities for a drug product. The method specifies the following:
Reporting Threshold = 0.1%
LOQ = 0.05 %

I would like to know if I should only report impurities > 0.1% or should I report all impurities > LOQ.

Thanking you in advance
Mike

[danko]

As I see it, you should report impurities ≥ 0.1
LOQ is 0.05, which is ≈ 0.1 - the significant digits taken into account.
So, it’s the same thing. It would have been another story if the reporting threshold was 0.10

Best Regards

[michaelcarolus]

Hi Danko

Thanks for your response. If the reporting threshold was ≥ 0.10% and the LOQ was 0.05%, what would you report.

Regards
Mike

[HPLCaddict]

Just a bit of nitpicking: "reporting threshold" is a fixed term, defined in ICH guidelines. For drug substances, it's either 0.03% or 0.05%; for drug products either 0.05% or 0.1%; it depends on the maximum daily dosage which of the two values you should use.
These limits are defined in the ICH guidelines (Q3A and Q3B), they are fixed! There cannot be a reporting threshold of 0.10%, nor any higher values.
There can be something like a "disregard limit" or similar, which can be defined in-house. But this is something different than "reporting threshold" and these two should not be mixed up.
Generally, anything below the reporting threshold doesn't need to be reported (that's why it's called "reporting threshold" ). If it's above the LOQ, it could be quantified, of course, but it doesn't need to be reported in the CoA. Impurities below the reporting threshold also do not count to "total impurities".

[michaelcarolus]

Hi HPLcaddict / Danko

Thanks for your comments. We were having this debate in our lab regarding reporting of results. My view is that we only need to report results above the Reporting Threshold as per ICH. However, the analyst, wanted to report all results above the LOQ. My suggestion is that we detect all peaks above the LOQ. We will then "filter" the results and ONLY report results greater than the Reporting Threshold. This will then we recorded on the COA or Stability summary data sheet.

Thanks again for all the comments

Mike