What about the hypothetical regulatory reality where companies can cite “20 years of clinical practice / OTC marketed sales in another country X” as justification enough for considering a medicine to be GRAS until proven otherwise (similar to how most medicines that preceded the creation of the FDA got grandfathered in as GRAS until proven otherwise)?
There are currently several hundred medicines sold elsewhere in the world and considered essential in most places in the world, that no US company is willing to go through FDA trials for, because there’s already an existing foreign patent on the drug, so it’s not worth it because all the US company would end up being able to produce and market is a generic. (US doctors still supply these drugs clinically from time to time; but to do so, they must get special one-time FDA exceptions to import them, and then use them “investigationally.” This usually takes months of back-and-forth and has extreme labor overheads. It also is vulnerable to foreign-market supply shocks.)
The way to cut this Gordian knot is to just not require trials for these drugs. They were already proven long ago to the satisfaction of some other drug agency; and even if the FDA doesn’t trust the standards of that agency, with at least 20 years of existing use, they can simply refer to longitudinal studies conducted in that country that recorded all-cause mortality of patients on the drug vs not.
There are currently several hundred medicines sold elsewhere in the world and considered essential in most places in the world, that no US company is willing to go through FDA trials for, because there’s already an existing foreign patent on the drug, so it’s not worth it because all the US company would end up being able to produce and market is a generic. (US doctors still supply these drugs clinically from time to time; but to do so, they must get special one-time FDA exceptions to import them, and then use them “investigationally.” This usually takes months of back-and-forth and has extreme labor overheads. It also is vulnerable to foreign-market supply shocks.)
The way to cut this Gordian knot is to just not require trials for these drugs. They were already proven long ago to the satisfaction of some other drug agency; and even if the FDA doesn’t trust the standards of that agency, with at least 20 years of existing use, they can simply refer to longitudinal studies conducted in that country that recorded all-cause mortality of patients on the drug vs not.