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January 27, 2005
Hope in a Drum
Having a project die after it goes into clinical development is never a good thing (unless you count the money saved by finding out that it was a loser and not taking it on even further.) There's a minor problem associated with this situation, though, that I've never heard discussed very often. What do you do with all those batches of compound that you made?
And there tend to be quite a few of them. As a compound goes on into the clinic, the serious scale-up chemists get to work on it, because there are a lot of compound-intensive tests that have to be done. Toxicity testing in animals moves to larger species and longer dosing times (four weeks, then ten to twenty weeks), and those things really chew up piles of compound.
Medicinal chemists like me start out making 15 milligrams of something, and we'll move up to a few grams when we have a winner. I've helped out on campaigns for the first rounds of real toxicity testing, making (say) a hundred-gram batch of compound, but only once or twice in my career. It's very rare for me to use over a hundred grams of a reagent, much less make a hundred grams of some product. So it's quite a sight to see rows of brown-glass screw cap bottles, each with 100 grams of final compound in them.
Or, for that matter, to see a two-kilo drum of the stuff with a snap-on closure on it like a batch of driveway sealer. What do you do with all this material after the compound has hit the wall? You already know that you're not going to take it into the clinic again. You don't need that much to stock the repository to run it through future assays. It's probably not much use as a starting material for other reactions. What good is it, then?
Every place I've worked has shelves of these things. My impression is that none of us have figured out what to do with them. In the end, it's just too painful to mark them down as chemical waste for the guys in coveralls to haul away.
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