comment on the acceptance criteria

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query: comment on the acceptance criteria applied in analytical method validation studies. In particular the suitability of the investigated parameters and the predefined limits should be assessed.

But, do we have any official reference like ICH , USP or any guidelines. if yes please let us know the references.

Background: Can you please help us to find out the rational behind the acceptance criteria used in method validation. yes we are using i.e.; RSD, % recovery , Correlation coefficient, Slope , intercept. confidence intervals and we are using defined criteria in validation of all parameters.
The only reference which I know is USP section <621> on %RSD. Other acceptance criteria are what your method can perform. Usually for HPLC the acceptance criteria for correlation coefficient (function f linearity) is 'not less than (NLT) 0.990'. Other parameters are not set like slope, y-intercept, LOQ... This is the reason behind a pre-validation HPLC run (to be sure the method will pass!).
There are some detectors that MAY BE non-linear like CAD and/or ELSD but this depends on the method, molecule, and the sample matrix.
HPLC chemist wrote:
Other acceptance criteria are what your method can perform.


I would contradict this. Acceptance criteria for validation must be what your method SHOULD perform, not what it CAN perform. It depends on what you want to do with this method. What are the specifications your product must fulfill?
Just as an example, if you have an assay with a specification limit of 90-110 % then a limit of 2% RSD for a 6-fold injection ist fine. If you're testing a pharmaceutical API with an assay specification of 98.5%-101.5%, then 2% RSD for 6-fold injection is way too much.
There actually are little to absolutely none "official" references for acceptance criteria (even USP 621, as quoted, only refers to USP monographs, at leat officially). Bad part: you have to define them yourself. Good part: you can define them yourself.
"State of the art" would be to define an "analytical target profile" or ATP - basically that's just a definition of what the method is supposed to do. Remember that in the end validation is NOT executing a standard validation protocol which is predefined and the same for any validation you perform - it is showing that the method is able to do what it is supposed to do. Meaning that the acceptance criteria may be different for every validation you perform...
We had to cGMP-validate our GC test method for ethanol levels in alcohol gel hand sanitizer maybe 20 years ago. The ethanol levels in such products are about 60 to 70%. But my pointy-haired boss still insisted that we determine the ppm we could detect for "limit of detection/limit of quantitation" even though these were many orders of magnitude below the actual working range of the test. A written point of view in the file would've sufficed.

In the early stages of the project, I discovered this as a small subtle hump on the ethanol peak not observed before, and confirmed this as of isopropyl alcohol by GCMS. Since isopropyl alcohol was not on the ingredient statement, the batch was considered contaminated and had to be destroyed. It was discovered that the contract manufacturer violated the SOP and used isopropyl alcohol to clean out their pumps and hoses, and residual isopropyl remained. Because of that one instance, the head of Personal Care demanded that we adapt the procedure so it would readily show isopropyl alcohol if present, so we had to change polarity of the column. Of course, when following the SOP as written, this contamination never happened again....
HPLCaddict wrote:
HPLC chemist wrote:
Other acceptance criteria are what your method can perform.


I would contradict this. Acceptance criteria for validation must be what your method SHOULD perform, not what it CAN perform. It depends on what you want to do with this method. What are the specifications your product must fulfill?
Just as an example, if you have an assay with a specification limit of 90-110 % then a limit of 2% RSD for a 6-fold injection ist fine. If you're testing a pharmaceutical API with an assay specification of 98.5%-101.5%, then 2% RSD for 6-fold injection is way too much.
There actually are little to absolutely none "official" references for acceptance criteria (even USP 621, as quoted, only refers to USP monographs, at leat officially). Bad part: you have to define them yourself. Good part: you can define them yourself.
"State of the art" would be to define an "analytical target profile" or ATP - basically that's just a definition of what the method is supposed to do. Remember that in the end validation is NOT executing a standard validation protocol which is predefined and the same for any validation you perform - it is showing that the method is able to do what it is supposed to do. Meaning that the acceptance criteria may be different for every validation you perform...


I am glad to see your comment as I fully agree. When setting up a biomarker screening method with 100 analytes. I get the question of LoQ. My reply is that i can give method linearity, precision and rsd but what LoQ criteria to use is not a simple question with a simple answer when the clinically relevant effect to be detected is not known. Unfortunately a lot of people think that LoQ is just a technicallity for the chemist and can be determined using a simple guideline. For example IL6 at baseline may be low with rsd of samples being high but the increase with inflammation is tenfold and easily observed.
Validation studies are a critical part of the process of analytical method validation. They provide the basis for the validation of analytical methods and the assessment of their suitability for a given application. The validation process consists of three main steps:

1. Selection of appropriate analytical parameters

2. Validation of analytical parameters io games

3. Validation of analytical parameters in combination with other parameters
Validation studies are performed to assess the suitability of an analytical method for a specific application. The selection of appropriate analytical parameters is based on a number of factors, including the purpose for which the method is to be used, the intended use, and the expected results. In addition, validation studies should be performed for all parameters that are expected to be used in combination with the method to be validated. Validation studies should also be performed on all samples that are expected to be received by the method under investigation.
We also used ORA-LAB.5.4.5 as a reference for our finished OTC pharmaceutical products.
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