Phyiscal method precision acceptance criteria assigment

Currently looking to validate a physical method (monitors the max temp output from an exothermic reaction using a calibrated thermocouple - this is a FP release method). review classifies the method as Class III (USP 1225) an so requires precision date only. If this were an analyte I would assign the %RSD acceptance criteria based on analye concentration, since this is a reaction -

can anyone shed some light on how I should assign the acceptance criteria?

Dear Friend…
In this case, as per my understanding, you are monitoring the maximum temperature released during solidification of bone cement. If I’m right, conduct the precision studies as define below.

  1. Repeatability:

1.a System precision: Prepare a lump of bone cement at 100% test concentration. Prepare six individual lumps / beads from the above lump and monitor the maximum temperature exhibited during solidification of each bed / lump. Calculate the RSD for six maximum temperature values recorded during your study. Here, analyte concentration can’t do matter.

1.b Method precision: Prepare six individual lumps / beds from your bone cement as per you test method. Monitor the maximum temperature exhibited during solidification each lump / bed. Calculate the RSD for six maximum temperature values recorded during your study. Here also, analyte concentration can’t do matter.

  1. Intermediate precision (Ruggedness): Let this test conducted by two different analysts, using two different calibrated thermo coupling instruments in two different dates. Proceed as mentioned in system precision.

  2. Reproducibility: Reproducibility is closeness between inter-laboratory test results. Reproducibility should be considered in case of the standardization of an analytical procedure (for inclusion of procedures in pharmacopoeias). So if your test method is only for your laboratory use, no need to conduct this test.


Thanks for the reply - you are correct in the assumptions on the method and what will be monitiored. I glad to say, as you described, this is exactly how I intend to proceed. My only real query is assigment of an acceptance criteria for the repeatability and intermeadiate precision. How do i correctly assign this acceptance criteria?

I was considering taking the SD/%RSD of the repeatability and then apply a factor of 3 to the intermeadiate precison for acceptance criteria. (+/- 3 sigma)

i.e. - repeatability has a %RSD of 0.5%, therefore my intermeadiate precision acceptance limit would be 3 x 0.5 = % RSD of +/- 1.5%

I would like to reference a specific guide/text to assign this limit but I cannot locate or find this reference.

Is this an acceptabe approach? can you suggest an alternative approach?

thanks in advance - your advice has been invaluable!

Precision and Intermediate precision calls the simulated % RSD,
Keep 0.5% for both the cases.

The application of %RSD and its specification depends on type of data.

USP 1225 or ICH Q2 does not address about % RSD Limits.

USP <1010>, Analytical data-Interpretation and Treatment helps you.

more over, The concept of validation is not required in your case, Because it seems to be a calibration model.

If you can confirm this, we will discuss further…

will you please tablulate the data as an example. so that it is easy to understand and intrepretate

Bujji Reddy K