Case Study: The Impossible Impurity

A client requested the generation of a specific API degradant listed in a recently drafted USP monograph. The FDA had found the client’s ANDA CMC section deficient because their HPLC method was not proven to separate and measure the degradant, and the client had not been able to access the degradant through purchase or synthesis attempts. Forced oxidative degradation was performed on the API, the true degradation markers were identified, and the degradant presented in the monograph was shown to be impossible to form based on steric grounds. The report provided to the client justifying the actual chemical pathways of degradation was used to address the deficiency and successfully resolve the FDA reviewer’s concern.