The biggest hurdle in my mind is changing the mindset from research to developing a definition of the product/therapy. There are many technical issues such as scale up, closed system development, serum free media, quality control, etc but none of these can be successfully addressed until you understand the critical aspects of the therapy you are about to test in a clinical trial. It is very easy for a Cell Therapy to unknowingly drift in characteristics as you go through development into manufacturing. The last thing you want to discover is what once gave you promising preclinical or early clinical results, no longer performs in the same way.