In our recent webinar, Mapping a Path to Market: Creating a Comprehensive Drug Development Strategy, we discussed five key areas that must be addressed in detail in order to create a comprehensive drug development plan.
During our discussion of manufacturing and quality considerations, an attendee posed the following question: When and why is it critical to use an active pharmaceutical ingredient (API) with higher levels of impurities during preclinical studies?
In my experience, it’s particularly important as you move from microscale to kilogram scale because that often results in products with different impurity profiles. This is something the FDA pays close attention to, and in fact, the FDA has put a few studies on clinical hold because the scaled-up (kilogram-scale) API batches were less pure (< 98+%) than the micro scale API batches used for pre-clinical/non-clinical (99+%) and in vitro pharmacology studies.
My colleague, Nik Burlew, Vice President of Quality Systems at Clinipace, makes the point that this is really one of the most important presentations you make in the Investigational New Drug (IND) application. He notes that it is essential to demonstrate in the IND that the levels of impurities in batches intended for human use in the clinic have been qualified at the same or higher levels in your toxicology studies. If you make a single batch for tox and clinical use, you run the risk of forming impurities (degradation products) during the time after the tox study and before your clinical study. Thus using a “dirty” batch of API for tox can pay off significantly in the long run.
Here are more questions to think about while developing your strategy when it comes to your API: Who is going to make the API? Based on your end goal, are you looking for a manufacturer to get you through Phase II or all the way to the commercial product? Will you need to import API before your IND is in effect? How will you evaluate and qualify your contract manufacturers?
Mark Shapiro is the Vice President of Clinical Development at Clinipace.