Reporting impurities (duplicate sample prep)

[mojo]

For related substances methods with duplicate sample preparations, how do you report the results? We are debating this at the minute. Some people belive that you should report the highest individual from either sample, but this can produce a positive bias for the total related substances. Others think that we should average the results.

[Alex Buske]

That depends on your protocols. If they state " the result for a single impurity is calculated as the mean of two runs" or something similar, then the average can be used (basically the only way to get usable stability data)..
I f you just have the specification "no imp. more than 0.5%" than averaging might not apply.

Alex

[krickos]

Some people belive that you should report the highest individual from either sample, but this can produce a positive bias for the total related substances.

That seems like a dangerous path ie omitting reporting results based on the result from case to case, would love to see someone explain that to a FDA inspector.

Agree with Alex here, ie you should have a standard operating procedure (SOP) with regard to sample plan and how many samples that get analysed based on batch size (number of containers, blisters or whatever you produce).

Then of course different test procedure might require one or more sample preparations from one sample.

What we tend do is:
If for example 2 samples per batch/lot and procedure requires duplicate sample preparations we usually report both sample average and batch/lot average.

[shahis77]

GENERALLY SINGLE INJECTION IS REQUIRED FOR DETERMINING THE IMPURITY.........WHAT I DO IS AFTER IMPURITY PROFILING I COMPARED THE RESULTS TO MY ASSAY VALUE OR DISSOLUTION VALUE .....THEY ARE ALMOST SAME .....IF THE IMPURITY VALUE IS COMING OUT TO BE VERY DIFFERENT THEN WE GO FOR SEPARATE INJECTION WITH FRESH SAMPLE......AVERAGE OR BEST RESULT IS NOT THE WAY TO REPORT IMPURITY