Pharmaceutical Analytical Method Validation and Gauge R&R

[v9991]

I have seen couple of templates of R&R studies they are primarily seem to be analysis of same-set-of-parts analyzed by multiple personnel.

Data is assessed to outline the variation of Equipment-appraiser-R&R-part & total; all of them are assessed wrt Measurement unit, tolerance analysis, study variaion, % contribution.

Now for analytical method validation in pharma and biotech industries...as per ICH Q2 ( ref. pg. 11, 12 onwards for brief methodology and acceptance criteria)

i have one particular question....how do these two correlate....
for eg., is it adequate to comply with ICH Q2 standards or is there a opportunity &^ need to adopt R&R analysis of the data.

I am sorry for asking a very-broad & generic question,
CAN I REQUEST for understanding the application of R&R analysis for Accuracy studies.
3-concentrations (70% - 100% - 130%); 3- preparations analysis; analyzed on 5 different days;
Traditionally, the acceptance criteria is that, values observed should be within the specification limits i.e., 98-102% of target concentrations for test parameter of assay.

similarly there are other parameters viz., robustness, ruggedness, etc.,
thank you...

 

[Stijloor]

A Quick Bump!

Can someone help?

Thank you very much!

 

[v9991]

A Quick Bump!

Can someone help?

Thank you very much!

are these assessment criteria similar ?
pharmacopoeia/ICH vs R&R

 

[Bev D]

The general answer is NO. the common Gauge R&R is really only intended to assess precision and NOT accuracy. additionally the mathematical incorrectness of the %tolerance calculation would drive your stats group crazy and lead to rejection by your regulatory body.

there are several appropriate techniques for analytical method assessment,, you should use those.

 

[v9991]

thank you,

...other parameters viz., robustness, ruggedness, etc.,

...

robustness :- where minor deliberate changes are made to the method and system suitability is verified.
ruggedness :- where the equipments - analysts are varied and equivalence is established.
how about using R&R for above scenario?

 

[Bev D]

Again no. Youden, bland Altman, non-inferiority, mcnemer's test, confidence intervals etc are methods to use depending on what you are doing.

 

[v9991]

considering that i apply R&R , precision i.e, repeatability & reproducibility.
the general acceptance criteria is <10; accepted with caution 10-30 and not acceptable >30%

are these ranges applicable and valid for complex analytical methods, such as ones of pharma, which involves multiple steps i.e., weighing-dilution(s)-measurement and comparison with (primary or reference) standard

 

[Bev D]

no. remember these ranges are rules of thumb (with no empirical or statistical basis) for a ratio that is mathematically invalid. Just because an approach is commonly used doesn't mean its acceptable.

 

[v9991]

no. remember these ranges are rules of thumb (with no empirical or statistical basis) for a ratio that is mathematically invalid. Just because an approach is commonly used doesn't mean its acceptable.

thank you Bev D;

1) so, can you also please comment on the another point i mentioned...viz., direct measurements viz., using of measurements such as verniers, temperature sensors, pressure sensors
VERSUS indirect/complex techniques involving such as ones i tried to list out..."weighing test - dilution - absorbance/response of UV - compare with standard response"!
2) another point on these accpetable ranges for RU&R, given the complex techniques, i am planning to characterize these ranges based on multiple data & batches; and arrive a given range for, at-least each for given product AND at-best the given test technique/method

how does the above approach sound?

 

[v9991]

The general answer is NO. the common Gauge R&R is really only intended to assess precision and NOT accuracy. additionally the mathematical incorrectness of the %tolerance calculation would drive your stats group crazy and lead to rejection by your regulatory body.

there are several appropriate techniques for analytical method assessment,, you should use those.

thank you Bev D, can you pl. kindly point out the "mathematical incorrectness" part for me please.