Chromatography Forum

Hi every one,
We are using some chromatic method to evaluate the impurities of ’ X’ product. All the analytical methods were validated according to ICH and USP guidelines. We are receiving the API from ‘A’ source for ‘X’ product. Recently we changed the API from ‘B’ source. The ‘B’ source chemical synthesis is different from ‘A’ source. Now my question is if we change the API source is there require to re-validate the chromatographic method again? Anyone can help me in this situation. If anybody having the information about the validation please forward to me. My mail ID is brbabu_1979@yahoo.com.

Thanks in advance
Babu

I'd have to think that if the synthetic route has changed, then there's at least a reasonable probability that the impurity profile has changed. Your method may yet be suitable for the new process, but if I was in your position and dealing with API's, I'd want to prove it. I think at least some revalidation would be necessary. I'd start with a check on specificity and proceed from there.

well a intresting topic that I could dwell upon for a long time, but will try to keep it short.

This is like the "other way around" of getting a new related substance method (like a new pharmacopiea method) for your drug substance, ie you have to document and state that the method is suiteble for detecting the impurities typically present in your drug substance.

In this case you are aware of the impurity profile of source A (API manufacturers are required to keep an impurity profile) so you should not have a issue to obtain the impurity profile from source B. Based on this information and what methods that are in use (company specific or pharmacopieas) you should be able to make some estimate on what is needed to do.

Also check with your QA/regulatory department. When switching drug substance source it is not uncommon that regolatory authorities requires batch data comparison on 2-3 batches from each source or sometimes even a comparison on impurity profiling.

As for synthectic different routes, that asessment should be left to organic chemists and actual data evaluation, cause:
1. Two seeminly different routes, one using destillation an other extractions for clean up and different solvents for crystallisation may show the same total impurity content but different amounts on individual impurities.
not to forget, different last crystallization, drying procedure and potential milling may change properties such as particle size distrubution if that is important for you product.
2. Two seemingly identical routes may show complete different impurity profiles depending on source and quality of structure adding raw materials.

Thaks juddc and krickos for your replays. I agree with you guys. Do any guidelines say do some partial validations please help in this case?

Thanks
Babu

Thaks juddc and krickos for your replays. I agree with you guys. Do any guidelines say do some partial validations please help in this case?

Thanks
Babu

From the ICHQ2R1 guideline:

Furthermore revalidation may be necessary in the following circumstances:
- changes in the synthesis of the drug substance;
- changes in the composition of the finished product;
- changes in the analytical procedure.
The degree of revalidation required depends on the nature of the changes. Certain other changes may require validation as well.

So yes depending on your findings it may require a revalidation, but not necessary a full one.

Thank you very much and appreciated krickos for your replay. These would be very helpful for me. I also feel that partial validation is required. I will look up at the synthesis part and will determine the plan of validation.

Thanks
Babu