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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: Twitter: Dereklowe

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August 3, 2007

Not Necessarily So

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Posted by Derek

My travel schedule has left me little time for blogging this morning, so I wanted just to report that I'll be revisiting some of the recent topics around here. My post on virtual companies led to a number of examples being sent to me - I want to look them over and report back. It's my guess that many of these deal with generic drugs or abandoned products, but we'll see. I still don't see how this model would work on a large scale (Pfizer, anyone?), but perhaps there's room for it on a smaller one.

And my post on abandoning the likes of tin, HMPA, and other nasties in med-chem research bought in quite a few counterexamples. I put a note up on that entry to direct new readers of it to the comments, so as not to miss them. I think that different companies treat these issues differently - in some shops, the med chem labs are encouraged to do whatever it takes to make the compounds, with the expectations that process chemistry will straighten out the kinks. Other companies, though, frown on that as irresponsibly throwing the problem over the wall to the next group, and want their med-chem people to forestall such problems if they can. I'll do a whole post on that subject next week, if possible, and we'll take an informal head count.

These bring up a general thought: as with any blog, this one is a reflection of my own experience and biases. (That's the whole point of a blog, eh?) I like the fact, though, that there are so many readers around the industry to confirm or disprove things as they come up. It's my hope that the non-industry audience finds the back and forth on these topics worth reading - I have a mixed crowd around here, and I try to keep things readable for anyone interested who happens by.

Comments (6) + TrackBacks (0) | Category: Blog Housekeeping


1. Green Koala on August 3, 2007 9:53 AM writes...

Just got caught up on your blog, and have a couple of comments on the topics you note here from a few days ago.

Virtual companies:
There are a ton of these cropping up all over the world currently. While in large pharma, I would have never been exposed to such operations, except in licensing discussions. In the small biotech world, depending on the nature of the business, one can come across these start-ups or operating entities on a very regular basis. They span the gamut of drug research, including early discovery, lead optimization, and pre-clinical development, not just clinical development as you mention. But typically, they are similarly modeled; that being, a central small (let's say 5-person) organization with an experienced skill set in each of the critical areas of discovery or development, which outsources essentially all of the day-to-day, week-to-week, etc operations. And currently one can find CROs that do the individual pieces (e.g. HTS on a library, med chem, ADME, in vivo, tox, process chem, CMC writing, regulatory filing, clin trials, etc.) from one end of the spectrum to the other; and, some CROs focus on defined chunks of the process, such as early discovery or clinical development. All available. There are some financial and practical reasons they are more palitable to the VC community as well, thus these types of companies are tending to be funded more than other traditional biotech ventures, where many have not worked as well one would have hoped. Whether these models work in getting additional and better drugs to the market and whether it is a cost-efficient alternative to the status quo average, will take time.

Nasty med chem entities:
Here's one for you. In developing a drug discovery candidate early in my career, we needed to install a prodrug moiety, which after much effort, could only be synthesized using 3 full equivalents of a Ag salt (!). Imagine the cost of goods calculation on that. Scaled up nice for tox studies (yes, we checked for residual metal). The process group got it, and quickly did an excellent job on a tight timeline and found conditions without the metal. I've seen numerous examples of excellent process chem work; and that is why I still say that, in general, process chemists are much better synthetic organic and physical organic chemists than we med chemists ever were or wish to be (of course we rule in other areas).

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2. Zoomer on August 3, 2007 4:31 PM writes...

I have very little scientific background and got started reading your blog because of a work-related project. I find it fascinating and quite well balanced among the scientific, business, industrial and personal worlds. Thanks!

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3. srp on August 4, 2007 7:11 PM writes...

I like the inside-baseball stuff, because I'm interested in how specialists see their jobs, especially what makes their jobs hard (the binding constraints, etc.) Sometimes I don't know what the commenters are talking about, but I can usually get the general idea from context.

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4. Not a scientist on August 5, 2007 3:07 PM writes...

Same here, not a scientist, so the technical discussion is pretty interesting.

Perhaps the problem with drug development is that the org charts should be turned upside down.

Management makes a plan, and then scientists set out to get data.

Everyone is entitled to their own plan, but not everyone is entitled to their own facts. When the data start rolling in, usually the options are pretty clear. Modify, continue or stop.

If you look at the Vioxx litigation documents, many e mails were to the effect "I'm not telling senior management, I don't want to risk my neck!"

Well, why? Because the facts did not conform to management plan. A plan made in the absence of facts.

So, let management be the dispatcher -- a reactive position, reacting to facts. Not commanding officer position, commanding what the facts must be.

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5. tom bartlett on August 6, 2007 8:06 AM writes...

"in general, process chemists are much better synthetic organic and physical organic chemists than we med chemists ever were or wish to be"

Agreed-- in companies where they are ALLOWED to do their jobs, instead of getting wrapped up in TQM or other management nonsense. In my previous Big Pharma job, the process guys were a joke-- because their leaders were a joke. They always ended up using our Discovery processes, little modified. In contrast, I've seen beautiful process work in various ACS meeting technical presentations.

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6. MTK on August 6, 2007 2:08 PM writes...

Besides the different philosophies in terms of what should med chem do vs. what should process do, there are also several models for process groups within the industry. For example, some companies have separate groups for early supplies, i.e. preclinical and Phase I, and late supplies, Phase II and beyond. Other companies have one group take it all the way from discovery to manufacturing.

In addition, some process groups throw out the med chem route from Day 1 while others have decided that a new route isn't worth the effort since most compounds will never get past Phase I and need a good efficient route. In that case, the argument is to use the med chem route with a few modifications first.

My point is that I wouldn't be too hasty to judge the quality of any process group unless the structure, philosophy, and goals of the group are understood. Even just tweaking the med chem route can be a very challenging task when you've got to make about 100x more than has ever been made under very tight and firm deadlines.

One thing that many people fail to recognize is how firm deadlines can be for process chemists. If you miss your slotted time for a tox study, even by a a few days, you may not get back in for months. Try that for pressure.

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