Perhaps I should clarify who these people are. My career has been in drug discovery, so I’ve been a customer for everything from 100 milligrams of a competitor compound to a few hundred grams of an intermediate. The orders that have to be dealt with by fork lifts and railway cars are beyond my scope – but they’re beyond the scope of many contract synthesis companies, too, so I feel reasonably safe in talking about only this end of the business. So, what do chemists like me want, anyway?

That’s not hard to answer. The biggest fear that someone has when ordering a non-catalog compound is that it’s not going to show up on time. There is perhaps one bigger fear, namely that the compound might not show up at all, but you try to minimize those by dealing with people you have reason to trust. (That said, there are plenty of situations where late delivery might as well be never, which is one of those details that has to be made clear right from the beginning). But it’s safe to say that most people who contract out have a very definite timeframe in mind.

But will they be honest about what that is? Up to a point, sure. Everyone builds some wiggle room into their deliver-by dates – you suppliers know that we do, the same way that we customers know that you’ve done the same thing to your dates. As long as no one gets excessive about it, that system works fine. But the flip side of the “gentleman’s agreement” is that the compound still does have to show up during the time that it can still be useful. More than once, I’ve been the unhappy owner of an intermediate that arrived well after the time that anyone wanted it. On one memorable occasion, no one could even figure out what the stuff was for. The person who’d put in the request had left the company, so we did have that excuse, but it’s safe to say that this is the situation we’re all trying to avoid.

The problem with timeliness being such a concern is, naturally, that some suppliers will promise delivery dates that they know are going to be tough to meet, just because they worry that if they don’t agree to the timeline, then someone else will. That’s a line that every contract shop has to walk, and I certainly can’t tell anyone how close to come to it. My friends in the business have told me some eyebrow-raising stories about the last-minute heroics that they’ve had to pull once in a while, and it’s a shame that these tales (necessarily!) often have to stay buried. They say that people who respect the law and who like to eat sausage should never watch either one of them being made, and the same probably applies to fine chemicals.

Of course, our customer’s-side indifference as to how the compound got to our bench depends on that compound having the same structure that it has on its label. And that’s the second biggest worry on our end. I think it’s safe to say that everyone who has spent money contracting out intermediates has had a bad experience with purity at some point. If a contract synthesis outfit is looking to distinguish itself, that might well be the place to do it. Get a reputation for delivering snow-white compounds, every time, and word will definitely get around. We’ve all taken delivery of things that turned out to be rather far from snowy.

And it’s easy to understand how that happens, since organic chemistry isn’t quite an exact science. Unfortunately, analytical chemistry is a lot closer to being one, and many of these situations could be avoided with more attention to detail. The worst examples don’t even call for expensive LC/MS equipment. My personal favorite from my experience could have been spotted by a retired ballet teacher or even a reasonably well-trained parrot: a bottle of liquid delivered with two prominent phases, the upper layer being (mostly) the product and the lower layer being mostly water. I can understand how selling water at custom-chemical prices is a tempting business model, especially when ordered by weight, but it’s not a very sustainable one.

Fortunately, that’s the worst I’ve ever seen, by a wide margin. The great majority of my contract experiences have been good ones. With that in mind, one thing that suppliers may not have realized is how exciting it can be for a medicinal chemistry team to receive a large bottle of a key intermediate. Just the thing that they need, the compound that they’ve been waiting for – and they didn’t have to take the time to make it themselves. For groups that typically have to bring up their own material, it’s a great thing.

We customers certainly aren’t blameless every time something goes wrong, either. Probably our biggest offense is not providing enough details about the synthetic routes. All too often, people find themselves relying on published procedures (patent and open literature), which are just not as robust as they should be. Anyone who’s contracting out a synthesis that they’ve done no work on themselves has to realize that they’re taking a chance – well, actually, they’re asking someone else to take a chance for them, and they should adjust their thinking accordingly.

You’ll probably have noticed that there’s one variable that I haven’t mentioned at all: price. That’s partly because it’s such a fundamental part of the field – a discussion of fish need not bring up the fact that they spend all their time in the water. If going outside weren’t less expensive, we wouldn’t do it. But that said, price plays a smaller role than you might think in the decision of which service to use. A higher-than-usual quote does stand out, but if it’s accompanied by some compelling reasons for the price, it can still win out. And a quote that comes in far lower than the others is frankly suspicious, so taking those together, there’s not as much room to discriminate on price as first appears.

We’d rather make outsourcing decisions on the basis of reliability, but that’s not a figure that can be written down in an E-mail quote. And that’s what makes contract synthesis such a tough business: a reputation for good service is so valuable, but it gets risked every time a new order comes in. None of us – on either side of the deal – are earning our livings the easy way!

Derek B. Lowe has been employed since 1989 in pharmaceutical drug discovery in several therapeutic areas. His blog, In the Pipeline, is an awfully good read.