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July 10, 2007


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Giuseppe Balacco

The answer is very simple. The purpose of any pharmaceutical industry is to bring a drug to the market. For this purpose thousands of compunds are synthetized. What's important is that the one compund going to the market is carefully certified. Validating all the products is a waste of time and money. It's also true that acquiring a spectrum and storing it without giving a look to it is a worse waste of time. You are simply worried because you want to sell your software. The more time researchers spend in quality assurance, the less drugs they invent!

Ryan Sasaki

Thanks for sharing your thoughts Giuseppe.

I agree that the purpose of pharma companies is to bring drugs to market.

Perhaps validating all products is a waste of time and money...but in doing so companies can build a meaningful knowledge base of their compound library...but even more importantly they can probably reduce the number of incorrect structures in their registration database.

I am not simply bringing up this issue because I want to sell our software. In fact, many, many companies already have our software deployed to all of their chemists in an open access environment and along with it the ability to electronically assign all of their NMR data. Some of these medchem groups are actually doing this, others want to start doing it, it's just that these groups seem to be in the minority.

From my experience as a chemist in the pharma industry, I learned very early on that there is an incredible amount of time, money, and effort spent on quality assurance. I'll counter your point by saying the less time researchers spend on quality assurance, the lower quality products they'll produce.

Andrew Anderson

Ryan, nice topic! One that's especially interesting to me, in light of my previous career as a spectroscopist supporting medicinal and combinatorial chemists. I'll keep my comments focused by responding to the first responder, Giuseppe. Two of Giuseppe's comments resonate quite negatively, at least in my mind:
1) "Validating all products is a waste of time and money" This is only true, if you have a very narrow view of what "validation" is. No, a full fledged proof of structure isn't needed in discovery. But, confirming that the chemistry you performed worked IS necessary. Why? Because if you synthesize the wrong structure, and you steer the SAR of a project in the wrong direction, you screw the project. I've seen this happen, and it's not fun...

2) "The more time researchers spend in quality assurance, the less drugs they invent!" I simply don't agree with this statement. Yes, successful discovery organizations foster an environment of creativity. And yes, GxP requirements are of course not appropriate for discovery. But, as a scientist, I can't accept that no validation is a good thing. Let's take Giuseppe's statement further, and suggest that chemists stop describing their syntheses in a lab notebook. Furthermore, let's suggest that there be no registration process at all...just mix and test! How long would it take for a drug to be discovered in that environment?

My summary assessment of the problem is, like most things in life, a careful balance must be struck between a quality and speed.

Finally, one more comment: as blog readers/responders, let's dispense with the accusations of hidden agendas. Yes, Ryan and I have "day jobs." But I am not responding to this BLOG to enhance my potential to sell more software. I'm motivated to respond because I'm interested in the discussion, period. I won't speak for Ryan, but I'm confident he'll confirm what his interests and worries are.

Giuseppe Balacco

Let me explain my position. I am convinced that keeping a lab notebook is fundamental. I am convinced that following a few rules is fundamental, because it allows every researcher to read and understand what's written in somebody else's notebook. I am also convinced that acquiring and assigning NMR spectra is a must. The concept of "validation" is something that I can't accept, however. What happens when the "validator" gives a false positive? What happens after one year of using a software validation? It happens that the chemist has forgotten how to read an NMR spectrum.
The point "a wrong structure can steer the project in the wrong direction" proves nothing. Obviously, only a compound with high pharmacology activity has such a potential, and not all compounds have this high activity. The subject of my first post was the thousands of compounds with no potential, whose only future is the "mythic" corporate database.

Ryan Sasaki

Thanks for your response and clarification, Giuseppe. However, I think you may be misunderstanding my point somewhat.

Please note, I am not proposing "automated" validation of NMR data by a software (or taking the data out of the hands of the chemist). Not in this particular post. I am specifically talking about the chemists themselves doing complete assignments in an electronic format. In many labs, that is not necessary and the confirmation of a registered compound has the potential to be only loosely based on the data. Again, some chemists will fully assign their data but others will only look for one peak, or might depend solely on the mass value.

If a mandate is in place at the top, that medicinal chemists HAVE to assign their data electronically and link to that data in their notebooks...isn't that a step forward in improving the quality of the compounds in the registration database?

Wouldn't full electronic assignments between a spectrum and a structure, in your words, "allow every researcher to read and understand what is written in somebody else's notebook" even clearer? If you agree that acquiring and ASSIGNING NMR data is a must...then I think you agree with my overall point...Chemists should be asked to fully assign their NMR data to ensure quality.

Whether or not that is done on paper or electronically depends on preference...but I think in this day and age, having this information in a digital format is the way to go. It's easier to store, link to, and retrieve.

As a software company we have worked very hard for years to try and make the process of assigning multiplets to atoms in a chemical structure as easy and seamless as possible. The goal is to make it faster than it can be done on paper. I think we are close if not already there.

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