Chromatography Forum

Phase I drug. Already has API HPLC stability-indicating method. Forced degradation was performed on API (acid/base, oxidation, light, thermal/humidity). Excipient compatibility was performed too (thermal/humidity).

Now drug product stability-indicating method is under development based on API method.

In this case above, is the forced degradation mandatory for drug product? can we skip it since we've already performed API forced deg study and 6 month excipient compatibility study?

Thanks!

Apple

Dear Apple,

You have to perform the force degradation studies for the drug product separately. Both the drug product and API is required to be subjected to the forced degradation.

Regrads

Thanks Sunjay.

Is there any exception? Because we are debating this issue now. Some people think with API's forced deg and excipient compatibility study results, forced deg for DP can be skipped because of the tight timeline.

Although I lean toward doing it, I don't have firm reasons why it is mandtory. Does ICH guideline or FDA guidance requires forced deg study for both API and DP?

Thanks agian!

Apple

I would say it would be safer to do forced deg. on both API and drug product... you may get some nasty surprises down the line if you don't!

The ICH doesn't require "forced degradation". There is however the requirement for "stress testing"for APIs and drug products.
Even for phase I you will need some stability results. I am also not quite sure, what extend of documentation is required.

Alex

I agree with Rob, especially when there may be any (unpredicted?) interactions between API and inactive ingredients after a long time.

Phase I drug. Already has API HPLC stability-indicating method. Forced degradation was performed on API (acid/base, oxidation, light, thermal/humidity). Excipient compatibility was performed too (thermal/humidity).

Now drug product stability-indicating method is under development based on API method.

In this case above, is the forced degradation mandatory for drug product? can we skip it since we've already performed API forced deg study and 6 month excipient compatibility study?

Thanks!

Apple

Hi,

It is better to do the forced degradation of the drug product along with the API as it gives better insight into the molecule. It also helps to build confidence in the analytical method used for the same. The regulatory agency will also ask for the data if not submited during the IND filing and this comes out as a deficeincy letter . So why to delay things , just do it and be on safer side.... isn't it??

Regards,

Yogesh