Chromatography Forum

We have Validate the Analytical method.

But During manufacturing of the Large scale up batch due to process problem one excepient ratio changed from 0.5% to 1.0%.

During method development we have done the excepient compatibility by spiking the drug in indivdual excepient and found there was no interference of this excepient.
In my view this increase in the ratio will not affect the Analytical method .

Kindly tell me whether i have to revalidate the method or not ?

If yes which parameter i have to revalidate?

Please suggest the web site from where i can get the Clarity on this Issue?
Please give me the Regualtory Expert E mail Address for getting Clarity?

We have Validate the Analytical method.

But During manufacturing of the Large scale up batch due to process problem one excepient ratio changed from 0.5% to 1.0%.

During method development we have done the excepient compatibility by spiking the drug in indivdual excepient and found there was no interference of this excepient.
In my view this increase in the ratio will not affect the Analytical method .

Kindly tell me whether i have to revalidate the method or not ?

If yes which parameter i have to revalidate?

Please suggest the web site from where i can get the Clarity on this Issue?
Please give me the Regualtory Expert E mail Address for getting Clarity?

carry out the specificity in validation again. refer ICH guidelines or USP.

Excipients amounts may give problems in specificity, recovery and stability in analytical solution. So you have to at least demonstrate that all of the above parameters are not affected by change in the excipient ratio.

I do not remember exactly and do not have the copy of the guide either. If this excipent is one of the analytes, then probably you need do some test. IF not, then there are two possiblities. 1) if it does not control drug release, you do not have to revalidate; 2) if it does control drug release but relative change is less than 10%(I do not remember exaclty), you do not have to revalidate, otherwise you have to.
There is some guide. Hope you can find it, Good Luck

Do you mean the excipient peak changes from 0.5% to 1% relative to the nominal conc of the active analyte? Personally, if the excipient to drug ratio does not change significantly, then I don't think you need to do anything (assuming you did not add a different type of excipient). How do you define "significantly" here? You may want to look at your formulation development data, talk to your formulator or use SUPAC as a guidance. In terms of specificity, you should assess whether a 1% peak will interfere with peaks of interest. As pawan ratra suggested, using significantly higher excipient may affect recovery, stability and even precision.

Dear All,

In the formulation Lubricant (Magnissium Stearate) quantity has been changed from 0.5% to 1.0%.We have done the Assay, RS and the Dissolution we found no change in results.



Aruna