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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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In the Pipeline: Don't miss Derek Lowe's excellent commentary on drug discovery and the pharma industry in general at In the Pipeline

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« Intermediates | Main

September 16, 2010

Six Sigma in Drug Discovery? Part One.

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Posted by Derek

I had an interesting email about a 2009 paper in Drug Discovery Today that has some bearing on the "how much compound to submit" question, as well as several other areas. It's from a team at AstraZeneca, and covers their application of "Lean Six Sigma" to the drug discovery process. I didn't see it at the time, but The title probably made me skip over it even if I had.

I'll admit my biases up front: outside of its possible uses in sheer widget-production-line settings, I've tended to regard Six Sigma and its variants as a buzzword-driven cult. From what I've been able to see of it, it generates a huge number of meetings and exhortations from management, along with a blizzard of posters, slogans, and other detritus. On the other hand, it gives everyone responsible a feeling that they've Really Accomplished Something, which is what most of these managerial overhauls seem to deliver before - or in place of - anything concrete. There, I feel better already.

On the other hand, I am presumably a scientist, so I should be willing to be persuaded by evidence. And if sensible recommendations emerge, I probably shouldn't be so steamed up about the process used to arrive at them. So, what are the changes that the AZ team says that they made?

Well, first off is a realization that too much time was being spent early on in resynthesis. The group ended up recommending that every lead-optimization compound be submitted in at least a 30 to 35 mg batch. From my experience, that's definitely on the high side; a lot of people don't seem to produce that much. But according to the AZ people, it really does save you time in the long run.

A more controversial shift was in the way that chemistry teams work. Reflecting on the relationship between overall speed and the amount of work in progress, they came up with this:

Traditionally, chemists have worked alongside each other, each working on multiple target compounds independently from the other members in the team. Unless managed very carefully by the team leader, this model results in a large, and relatively invisible, amount of work in progress across a team of chemists. In order to reduce the lead time for each target, it was decided to introduce more cooperative team working, combined with actively restricting the work in progress. The key driver to achieve and sustain these two goals was the introduction of a visual planning system that enables control of work in progress and also facil-
itates work sharing across the team. Such a visual planning system also allows the team to keep track of ideas, arrival of starting materials, ongoing synthesis and compounds being purified. It also makes problems more readily recognizable when they do occur.

We have reflected on why chemistry teams have always been organized in such an individual-based way. We believe that a major factor lies in the education and training of chemists at universities, in particular at the doctoral and postdoctoral level, which is always focused on delivery of separate pieces of work by the students. This habit has then been maintained in the pharmaceutical industry even though team working, with chemists supporting each other in the delivery of compounds, would be beneficial and reduce synthesis lead times.

OK, that by itself is enough to run a big discussion here, so I think I'll split off the rest of the AZ ideas into another post or two. So, what do you think? Is the "You do your compounds and I'll do mine" style hurting productivity in drug research? Is the switch to something else desirable, or even possible? And if it is, has AstraZeneca really accomplished it, or do they just say that they have? (Nothing personal intended there - it's just that I've seen a lot of "Now we do everything differently!" presentations over the years. . .) After all, this paper is over a year old now, and presumably covers things that happened well before that. Is this how things really work at AZ? Let the discussion commence!

Comments (1) + TrackBacks (0) | Category: Drug Development | Life in the Drug Labs | Who Discovers and Why


COMMENTS

1. NYSpursFan on September 16, 2010 9:23 AM writes...

Exceedingly interesting hyppothesis. It's certainly true in any PhD program that you're trained to think and act and produce and write as an individual. Then you get a job in industry and are thrown into a "team" environment, which isn't really a team, per se, but a group of individuals. The group is being managed by an "individualist" with no experience or training in group oversight or management. As I think out loud here, there may be quite a bit of truth in this. I also see this in the financial and consulting communities. Perhaps the answer lies in "team" PhDs?

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