Chromatography Forum

Hi,
Are there any guidelines for acceptance criteria for method validation parameters?

Thank you

Hi Tubish8,

Yes, some such criteria are noted by the International Conference on Harmonization (ICH):

http://www.ich.org/fileadmin/Public_Web ... deline.pdf

Thank you Mattmanulley,
But I need acceptance criteria especially for accuracy and robustness.

Good evening, Tubish81,

I see. Accuracy is dependent upon the expected goal for the method, often for a potency method, it may be 98.0 - 102.0 percent for a major component, for example. Perhaps this will help:

https://www.fda.gov/downloads/drugs/gui ... 134409.pdf

and/or this, a discussion in this Forum a while ago, HPLCAddict made the following salient points:

I [HPLCAddict] don't think that there are any official guidelines out there which give definite acceptance criteria for accuracy. And this is actually good, because acceptance criteria for accuracy (and any other validation parameter) can be wildly different depending on the purpose of the respective analytical method. Regarding the +-2% you mentioned, this is quite a common criterion for validation of assay tests in the pharmaceutical field. But for related substances, things are VERY different! Just think of it: at the 0.1% level defining an acceptable range of +-2% would mean you'd have to hit the 0.098-0.102% range with your recovery - impossible! I'd say there's no pharmaceutical related substance method out there which is precise and accurate enough to distinguish between these concentrations. An actually it doesn't have to.

I've seen a lot of validations of related substances methods, and usual acceptance criteria for accuracy via recovery are 90-110% or even 80-120%, especially if you look at lower concentrations close to the LOQ.

I agree with HPLCAddict wholeheartedly. Perhaps also this will help:

http://www.eoma.aoac.org/app_f.pdf

As to Robustness, this would have to be determined during method development on a case-to-case basis, that is, there are no pre-set criteria (perhaps your firm suggests some in an SOP?). As for criteria to examine in robustness, there is a list in this text you may follow (in Chapter 2):

Validation Of Analytical Methods For Pharmaceutical Analysis by Oona McPolin,
ISBN-13: 9780956152817, Pub. Date: 05/05/2009, Publisher: Mourne Training Services.

The company I worked for made....wait for it....consumer products. Some of these were over the counter pharmaceuticals. We generally followed guidelines of FDA ORA-LAB.5.4.5 Appendix I, Feb. 24, 2009 revision. Maybe someone can find and post the current links, I just have the PDFs saved.

This states for accuracy: "Acceptance Criteria: 97.0% - 103.0% recovery for each spike level for APIs; 95.0% - 105.0% for finished dosage forms. (see note a.)" Our products were finished dosage forms, so I actually had to show this to our QA Director who wanted 98.0-102.0% for everything, but even though we always seemed to meet 98.0-102.0%, I didn't want to be held to higher standards than the FDA required.

Note a states "If acceptance criteria are not met, due to situations described in this paragraph, the occurrence should be evaluated in the form of a discussion between analyst(s), lab managers, and QA managers, with the purpose of the analysis and the requirements of the customer being taken into account. The specified acceptance criteria can then be modified, if sufficiently justified."

"But for related substances, things are VERY different! Just think of it: at the 0.1% level defining an acceptable range of +-2% would mean you'd have to hit the 0.098-0.102% range with your recovery - impossible!" I had to fight with my own boss on this one, as I couldn't find what the FDA requirements actually would be for a certain trace analysis method I'd developed, I wanted to open the range to 90-110% or 85-115%, but he demanded that I find the documentation; I couldn't find such information, legal documents were not my field or my interest, so the procedure was never validated.

Is there a way to attach PDF documents here???

@ Consumer Products Guy,

Okay then, here's a link to ORA-LAB.5.4.5, 29 Sep 2014 (current?):

https://www.fda.gov/downloads/sciencere ... 092147.pdf

The acceptance criteria remain the same as in the 24 Feb 2009 revision. Table A5 of the AOAC reference (from 2016, Appendix F.) posted above agrees with the recovery criteria FDA specifies at the 0.1% level, and though it is not a legal document, it makes a good deal of sense.

Bosses...no comment to that other than there are too many of those and not enough leaders.

@ Consumer Products Guy,

Okay then, here's a link to ORA-LAB.5.4.5, 29 Sep 2014 (current?):

https://www.fda.gov/downloads/sciencere ... 092147.pdf

The acceptance criteria remain the same as in the 24 Feb 2009 revision. Table A5 of the AOAC reference (from 2016, Appendix F.) posted above agrees with the recovery criteria FDA specifies at the 0.1% level, and though it is not a legal document, it makes a good deal of sense.

Bosses...no comment to that other than there are too many of those and not enough leaders.

Thanks Matt.

My pleasure Consumer Products Guy. Thank you in return for the pointer to the document!