I think this is a good question and agree that the definitions provided are vague. However, I think that it makes sense for the definition to be vague and the line between significant and non-significant risk to be slightly blurred. This could be frustrating for many of us that there isn’t a clear cut answer but this is why these decisions are looked at my multiple people, the sponsor, IRB, and FDA. As someone mentioned earlier, what about glasses, the wrong prescription could alter morphology of your eyes but that would not require a clinical trial just a change in prescription. If the classification of a product that provides significant risk becomes too specific then products could be overlooked that may need a clinical trial or should be considered to have significant risk. I think that most of what the FDA deems to be a significant risk is correct in combination with people using their judgement to make these classifications. Although the last point on the list “• Otherwise presents a potential for serious risk to the health, safety, or welfare of a subject” could be confusing because the point of this checklist is to see if the product has significant risk. This could be where some of the other views mentioned in the forum on what significant risk should be could help with making the boundaries clearer.