Method Equivalency

[putnam]

Hi!

What kind of data would be necessary to declare equivalency between two methods? For instance, to declare a given analytical HPLC method is equivalent to a USP monograph, what sort of information would need to be generated? What sort of statistical work-up would be required?

Many thanks,

Putnam

[gbalock]

Putnam,
Typically we do a n=6 assay using both methods. The criteria are not more than 3.0% difference between the means, and a pooled SD of not more than 3% for an assay. The criteria are a little looser for a dissolution.

[Rob Burgess]

This could be infinitely more difficult if you were trying to declare equivalency for a related substances / impurity method.

[wanda50]

We do assay/rel subs. Our criteria for assay is n=9 with an RSD of 2%; related subs is RSD of 10%.

[Albany-12303]

Regarding assays in finished product, wouldn't a validated house method be considered equivalent to the USP method by the very fact that it is validated? A validated method, whether it is a USP or a house method, is shown to be accurate and precise.

For impurities, though, the situation is different. I do not think that they need to be equivalent. If the house method quantitates a greater # and amount of impurites than that OK too. So some kind of correlation study is needed.

[JM]

Equivalency between two assay methods is quite straight forward by looking at overall RSD between two methods.

For Impurity estimation , one has to prove that in-house method is equivalent or better than the offical method in terms of resolution , no. of impurities , sensitivity etc. It is done by preparing a study report of comparative data of one representative sample using both methods and prove that in-house method is better.if method is equivalent , it is safe to use official methods for regulated markets.

JM

[wanda50]

Even if you want to bring a USP method in house, you need to do a technology transfer. The USP strongly suggests this.

[Albany-12303]

How about replacing a USP TLC method with a validated house method (for impurities)? Does a comparison study even have to be done considering that the FDA has begun disapproving impurity limit tests altogether? - they want to see hard numbers!