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Derek Lowe The 2002 Model

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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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May 26, 2011

Pfizer's Brave New Med-Chem World

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Posted by Derek

OK, here's how I understand the way that medicinal chemistry now works at Pfizer. This system has been coming on for quite a while now, and I don't know if it's been fully rolled out in every therapeutic area yet, but this seems to be The Future According to Groton:

Most compounds, and most actual chemistry bench work, is apparently going to be done at WuXi (or perhaps other contract houses?) Back here in the US, there will be a small group of experienced medicinal chemists at the bench, who will presumably be doing the stuff that can't be easily shipped out (time-critical, difficult chemistry, perhaps even IP-critical stuff, one wonders?) But these people are not, as far as I can tell, supposed to have ideas of their own.

No, ideas are for the Drug Designers, which is where the rest of Pfizer's remaining medicinal chemistry head count are to be found. These are the people who keep trac of the SAR, decided what needs to be made next, and tell the folks in China to make it. It's presumably their call, what to send away for and what to do in-house, but one gets the sense that they're strongly encouraged to ship as much stuff out as possible. Cheaper that way, right? And it's not like there's a whole lot of stateside capacity, anyway, at this point.

What if someone working in the lab has (against all odds) their own thoughts about where the chemistry should go next? I presume that they're going to have to go and consult a Drug Designer, thereby to get the official laying-on of hands. That process will probably work smoothly in some cases, but not so smoothly in others, depending on the personalities involved.

So we have one group of chemists that are supposed to be all hands and no head, and one group that's supposed to be all head and no hands. And although that seems to me to be carrying specialization one crucial step too far, well, it apparently doesn't seem that way to Pfizer's management, and they're putting a lot of money down on their convictions.

And what about the whole WuXi/China angle? The bench chemists there are certainly used to keeping their heads down and taking orders, for better or worse, so that won't be any different. But running entire projects outsourced can be a tricky business. You can end up in a situation where you feel as if you're in a car that only allows you to move the steering wheel every twenty minutes or so. Ah, a package has arrived, a big bunch of analogs that aren't so relevant any more, but what the heck. And that last order has to be modified, and fast, because we just got the assay numbers back, and the PK of the para substituted series now looks like it's not reproducing. And we're not sure if that nitrogen at the other end really needs to be modified any more at this point, but that's the chemistry that works, and we need to keep people busy over there, so another series of reductive aminations it is. . .

That's how I'm picturing it, anyway. It doesn't seem like a particularly attractive (or particularly efficient) picture to me, but it will at least appear to spend less money. What comes out the other end, though, we won't know for a few years. And who knows, someone may have changed their mind by then, anyway. . .

Comments (114) + TrackBacks (0) | Category: Business and Markets | Drug Development | Drug Industry History | Life in the Drug Labs


1. You're Pfizered on May 26, 2011 8:07 AM writes...

My understanding is that WuXi is doing a large % of Pfizer's DMPK work as well.

All you need is to have the primary biological assays run there and you'll pretty much eliminate the need to ship compounds back to the states. The stateside hands could do the scale-ups for advanced testing and in vivo studies.

I wonder if the folks at WuXi have any type of feedback in terms of biological data, or even the type of target they are working on. My guess would be no. This keeps the top tier compounds in each series somewhat anonymous, helping with the IP worries.

I still think the CROs are building up some really nice screening collections from all of these collaborations, but that's the cynic in me.

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2. AlchemistOrganique on May 26, 2011 8:13 AM writes...

Can't wait for the full pacification of Afghanistan...once Wuxi becomes too expensive, Qandahar and Kabul are fertle ground for CROs.

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3. K on May 26, 2011 8:27 AM writes...

Brave or stupid?! I know which my money is on

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4. Lester Freamon on May 26, 2011 8:28 AM writes...

Who actually decides what to screen against/what targets to go after? How are those decisions made?

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5. Pfefecorn on May 26, 2011 8:29 AM writes...

For me, the most important issue on this case is the logical idea between the lines in this process. It seems that Pfizer doesn't believe China and Chinese are capable of doing Med CHem by themselves. If they are re-structuring their Med Chem bench to China, why not send the Drug Designers also? Why keep them here? It seems more like a "We americans are born to think, not to do" mentality rather than a cost reduction. This same mentality is seem in every corner in industry, even between europeans and americans for european industries. It's a shame.

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6. Industry Guy on May 26, 2011 8:34 AM writes...

This is the death song for Pfizer....SAR changes too rapidly to have it outsourced efficiently. By the time the results are in, they are just getting starting materials on the last order which then has to be changed of course. They may eventually make something useful but the timelines will be stretched out and thats the last thing a company like Pfizer needs is longer timelines to market.

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7. susurrus on May 26, 2011 8:41 AM writes...

They should apply Six Sigma to their process. Then they would be a textbook example of how a company can completely rid itself of innovation.

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8. anon on May 26, 2011 8:51 AM writes...

short on PFE
Long on WuXi

WuXi will eventually realize they don't need PFE anymore to tell them what to do for projects. They'll just run their own projects instead. What are the odds of a lower success rate.

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9. Jose on May 26, 2011 8:53 AM writes...

IF this was 20-30 years ago, when the drug discovery & development process was operating fairly smoothly and producing blockbusters on a semi-regular basis, then this whole strategy wouldn't be so off target. But holy hell, they're taking a process with too many holes no-one understands, and are INTENTIONALLY adding millions of far worse holes that are all nearly impossible to pin down or keep track of?

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10. silicon scientist on May 26, 2011 8:53 AM writes...

Isn't this similar to the industrial/economic model put forth by Thomas Friedman, accepted as common wisdom in Washington, and exemplified by Apple? We in the US and post-industrial world come up with the "big ideas" while the developing world acts as our hands to make the stuff as cheaply as possible.

Almost every major industry is running on the Pfizer model. I hope it works out, but I'm fairly certain we're in for a world of hurt.

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11. Hap on May 26, 2011 9:07 AM writes...

Considering how many Chinese scientists we've been training (and how many of them have done well), I don't understand why anyone at Pfizer would think that the Chinese can't do drug development. If your company's contribution to the process is late-stage development (and perhaps bad management), why do you think that your company won't be elided when Chinese companies decide that if they're going to be developing the drugs, they might as well make the money from them, too?

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12. BFS on May 26, 2011 9:19 AM writes...

[Y]ou feel as if you're in a car that only allows you to move the steering wheel every twenty minutes or so."

It's more like steering an aircraft carrier which doesn't have the ability to turn on a dime.

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13. karass on May 26, 2011 9:25 AM writes...

This discussion is too biased. To rationally understand issues lemme take the other side. Please comment so neophytes like me can comprehend better:

The Assumption:
* Molecule synthesis and assaying are modular operations which can be outsourced across geography, culture, and language barriers. Some of this is already true as evidenced by reagents purchased from abroad or outsourced assays.

* "Drug Designing" is where the knowledge is and is to be kept in house. like apple's design team. Implicit here is that Drug Designing is modular and separable from synthesis. Probably true if med. chemists of equal caliber are on both sites.

The pros and cons.

Pro: If Wuxi does the assaying too and submits results immediately, with tight feedback loops this thing might actually work

Pro: This has never been done right. Given how bad every other thing has fared in drug discovery, it may be worth a shot. The lower costs could help.

Con: IP will not stay secure.

Con: Infrastructure issues (reagent availability) still poor in China

Con: Geopolitical risk

Con: Loss of US capability in synthesis?

Con: You train your future competition, unless you create your branch at the outsourced site. Assuming the future competition is after than the CEO's time, this is probably not his/her worry

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14. ex-Pharma on May 26, 2011 9:27 AM writes...

Lets hope that all the sacked chemists go work for small, lean biotec's that can still turn on a dime and appreciate good ideas. Beat Pfizer to the best compounds/targets and sell it back to them for billions.

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15. Zippy on May 26, 2011 9:28 AM writes...

Sounds like consultants were involved.

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16. RD on May 26, 2011 9:33 AM writes...

Well, that'll learn'em for leaving us off patents in the past.

Speaking for myself, I never liked the idea of Drug Design *telling* medicinal chemists what to make. For one thing, most drug designers have forgotten how to do synthesis. And it never seemed reasonable to ask chemists to check their brains at the door to my office.

OTOH, there are some medicinal chemists who are openly hostile to drug design and go to Rube Goldbergian lengths to avoid having to make what a drug designer suggests. Some of them do it because they've been burned before; some of them do it because they see every patent as "mine, mine, mine!", and don't want to acknowledge they got help from anyone. So, good designs don't get made or they get made two years later when the chemist has an epiphany and claims to have come to the conclusion all by themselves. Many are the days when a drug designer wishes they could just order up some analogs from a WuXi.

The kind of drug design/medicinal chemistry interactions you get appear to depend on the culture of the company. One of the companies I worked for had an excellent interaction because both modelers and chemists grew up together, the other was abysmal because modelers did not adequately justify their aristocratic attitudes towards the "hands on" people. But it doesn't surprise me that corporations are going this route. The issue is IP. You want to hold costs down to a minimum while maintaining your patent advantage, so design stays here, synthesis goes to Chindia.

What might have been better? Drug designers could have stopped coming across as arrogant egotists until their computations actually worked, Chemists could have acted less like selfish brats when it came to patents instead of generating resentment and both the designers and chemists could have worked on the rules of engagement and who gets credit *before* the projects got started so that management didn't have to make those decisions for them and use it as an excuse to gut chemistry. Too late now.

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17. anchor on May 26, 2011 9:39 AM writes...

I am thinking of degree in organic chemistry. I mean, we can fully hold Pfizer, Merck and other arrogant companies responsible for the demise or lack of interest in organic chemistry, here in the US. People will always enroll for a PhD in organic chemistry and I have the feeling that when they see the way it is headed (outsourcing to WuXi, Syngene etc.)they might drop out as there is no future. Alpha professors in academia can always land their students in some companies only to be laid off later, while it is going to be uphill for others (i.e non alpha professors). Very sad state of affairs, I say.

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18. Ellen Clark, Clark Executive Search on May 26, 2011 9:45 AM writes...

I recently had a search for a senior medicinal chemist for a big pharma( not Pfizer). I spoke to many of the Pfizer chemists and they are really pained by all this. At the time they still hadn't heard whether they would be Drug Designers or what. Their whole world is in upheaval.Also during the search I came across a Novartis chemist going to China for a 6 month stint to "train" the Chinese in med chem. It seemed to me she was training herself out of a job.And I know that at least one chemistry VP at WuXi is a westerner and lives in China. So the CRO doesn't trust its own people?

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19. Virgil on May 26, 2011 9:54 AM writes...

Like it or not, this is exactly the model used by numerous small biotech's I have interacted with. They can't afford a full med-chem/SAR arsenal of people and facilities, so they have a couple of "heads only" as you call them (drug designers), and they outsource the wet work to China. Everything that comes in by FedEx gets LC-MS'ed, NMR'd and column chromatographed to make sure it is what they say it is, and then it's off to PK. For most small pharma's, in out-of-town office parks, with limited space, a full-on wet chem lab is just out of the question.

It's actually pretty efficient, in terms of speed. The turnaround is on the order of days-weeks, not months, and certainly appears luxurious to someone like me in academia, who can't afford to do it.

So, it really boils down to whether you think big-pharma should be trying to emulate small pharma, because that's what this looks like from 50,000 feet.

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20. Lousy Peon Bench Chemist on May 26, 2011 9:55 AM writes...

The strikes me as self-perpetuating intellectual elitism. The Drug Designers will presumably be the only chemists allowed regular access to the biological data generated. When a chemical idea works out and produces the intended biological consequences (greater potency, better exposure, etc.), the Designers will pat themselves on the back for being so smart and feel that the whole model is justified.
In my experience, anybody can have a good idea, but it's really important to understand what chemistry is difficult and whether a question can be answered more quickly by choosing a compound that's easier to make. When you distance the planners from the synthesizers you lose this synergy.
I expect this model will be slower, and a lot of bench chemists will wind up feeling undervalued and demoralized. It may work (especially if the rest of the industry follows suit slowing everyone down to the same speed), but I think it sucks.

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21. MedChem on May 26, 2011 10:12 AM writes...

#16, BD

The best way to do it is to train your medicinal chemists to become excellent modelers--designer and synthesizer in one person. It's not hard at all, in the sense that with a good program one can safely ignore most of the complicated calculation and approach it more like art than science.

At my company we pride ourselves for having the best computational scientists. And the chemists in general enjoy great synergistic relationships with them. But that said, it's always the self-taught medicinal chemists skilled in the art of SBDD that come up with all the breakthrough ideas. The most important ingredient is the unique chemistry intuition and experience that I think only a medicinal chemist can truely aquire. As much as I respect my modeler colleagues, the mindset of looking to (or depending on) them for ideas is plain rediculous. And that's the mindset apparently big pharma do-nothing robotic managers have.

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22. Rock on May 26, 2011 10:15 AM writes...

A couple of points of clarification:
Wuxi is running the primary screens in addition to PK etc.
The 'designers' and internal synthesis teams will not even be co-located. The designers are moving to Cambridge.

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23. Lacerta Bio on May 26, 2011 10:17 AM writes...

@Virgil, I was about to say the same thing. Just this morning I spoke with a virtual company that's executing this same model. They have 3 FT guys, one of which is "the chemist." He manages and oversees the Preclinical development taking place across a few CROs around the world, none of which are in the US. Everything is outsourced: chemistry, regulatory, manufacturing...everything.

Also, Hap's comment regarding China and drug development is spot on. This process will help train our future competitors. It's only a matter of time before WuXi starts developing their own internal projects. They can then buy a US-based commercial company and sell their products here.

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24. molecular architect on May 26, 2011 10:31 AM writes...

The real problem with this system will only become apparent as the current "designers" retire. Where will the new ones come from? One doesn't learn med chem in grad school, one learns it by experience. Just look at the hiring patterns in Pharma chemistry groups. Companies tend to hire folks with training in synthetic chemistry, especially total synthesis, not medicinal chemistry PhDs. So, how will new PhDs learn med chem if they cannot work on teams with experienced folks studying SAR?

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25. Rock on May 26, 2011 10:32 AM writes...

A couple of points of clarification:
Wuxi is running the primary screens in addition to PK etc.
The 'designers' and internal synthesis teams will not even be co-located. The designers are moving to Cambridge.

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26. pc on May 26, 2011 10:33 AM writes...

Rumor is that one big CRO in CN has already started venturing into its own drug discovery. Word is that considerable sum of resources have been sunk into this. It's not unlikely 10, 20 years from now western pharma find that their CRO become fierce competitors. What's worse, their Chinese counterparts will have an upper hand in the potentially largest market because of the government's back up.

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27. Anonymous on May 26, 2011 10:41 AM writes...

#21 MedChem: I don't think we have a disagreement on that at all. I agree that some of the best people at drug design are self taught. That's how we all started back in the early 90s when virtual screening was just a twinkle in someone's eye.
However, I have seen a lot of good ideas not acted upon because drug designers don't do synthesis. They have to rely on med chemists. And med chemists are clever enough to know how to get around them. Sometimes, that results in a lot of wasted time and missed opportunities. Why make someone else's compounds even if they're easy and turn out to be active? The funny thing is that I have never heard of an incident where a drug designer excluded the person who synthesized the compound from a patent. The reverse happens all the time.
OTOH, we all can't be good at everything. Some of us need to specialize. Some medicinal chemists may never feel comfortable using Schrodinger GLIDE or library generating software. Drug designers generally avoid lab environments like the plague. Only the few and the brave venture back into the labs to do real science. (personally? I think it would be a good thing if designers spent a year in the lab. It's good brain training) In those cases, two heads may really be better than one. Why not settle the disputes before they get started instead of waiting? I can see a lot of resentment in the comments from medicinal chemistry but it would have been very helpful for them to have walked a mile in our shoes.

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28. A non on May 26, 2011 10:53 AM writes...

I find it interesting how many of these comments assume the "Drug Designers" are modelers. My impression from folks at Pfizer is that this is not universally, or even mostly, true.

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29. huh? on May 26, 2011 11:02 AM writes...

When I interviewed with Pfizer I was under the impression that the Designers were experienced Medicinal Chemists who just didn't work in the lab anymore. I wasn't told they were comp sci or modelers. Why is everyone assuming this? Is this true?

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30. You're Pfizered on May 26, 2011 11:12 AM writes...

I would imagine that the Designers would be as #29 said, experienced medicinal chemists who have moved from the bench. I'd assume that there would be modelers involved as the projects needed since not ever target is going to be able to utilize them.

The one thing that many pharma companies might be overlooking in the CRO game is attrition. The landscape in China is getting to be very, very competitive for scientists. I'm hearing that 15-20% attrition per year is the norm for many companies. I'd assume that those are the bottom performers either. In order to keep more of these guys, they'll have to pay them more, increasing the cost. It will become more and more expensive to do business there.

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31. You're Pfizered on May 26, 2011 11:14 AM writes...

Meant to type that 'those are not the bottom performers either...'

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32. MoMo on May 26, 2011 11:30 AM writes...

AlchemistOrganique! You are a genius! That's what is going on- the cheapest labor in chemistry will always win!

BUT GET READY. Here's what will happen. The CRO's in China will cause a a crisis or two in international patent law, if they haven't already or trashed it enough. The smart companies here will abandon this practice as the lawsuits mount, if they havent already. Sorry Joshua Boger, but dont get too cocky and buddy-buddy with the Dragon-you will get burned!
Meantime, China will continue to stomp on others IP, as they are doing now, with NO SHAME as they dump their waste chemicals into open pits for the locals to rummage for scraps of food in. It is happening already.

But what do these US drug company designers do in the meantime? They give away valuable technology to outsiders that can't wait to run off and synthesize their own versions. It is happening already.

But, You get what you pay for and the words "industrial espionage" will be paid for in full, by our leading pharmaceutical executives of this fragmented New World.

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33. Anonymous on May 26, 2011 11:32 AM writes...

#30: There are probably some med chemists who could do this kind of work, especially people who know how to design libraries. But if it's SBDD? That takes some time to learn how to do. However, modelers don't seem to be losing their mojo so I am assuming that companies still think they need them.

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34. xfz on May 26, 2011 11:44 AM writes...

What a stupid style! Bench chemist's hand & drug designer's head??? I bet most of the time good ideas come from bench chemist.

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35. Anonymous on May 26, 2011 11:50 AM writes...

But drug designers *are* the medicinal chemists! Medicinal chemists design molecules. Synthetic chemists make molecules. These may or may not be the same people.

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36. Anonymous on May 26, 2011 11:59 AM writes...

As a 5th year graduate student in Ochem, I cannot stress how depressing my future appears to be...

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37. You're Pfizered on May 26, 2011 11:59 AM writes...


A smart medicinal chemist with 5 years experience in big pharma knows SBDD. The designers at Pfizer have to know not only the types of compounds to make, but how to generally make them, then fix the advanced biological issues that always crop up. Most modeling guys I know have very little bench chemistry experience, if any at all.

They are sharp guys who know their stuff, but not one of them could lead a team of chemists and a medicinal chemistry project, and they'd all tell you that.

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38. Don B on May 26, 2011 12:00 PM writes...

Can someone point to a "suucessful" pfizer drug design in the last 20 years?

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39. Quintus on May 26, 2011 12:10 PM writes...

Seems to me that the managers at Pfizer don't have a clue.
I expect that company will not exist pretty soon. What a bunch of twats

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40. smurf on May 26, 2011 12:15 PM writes...

The compchem people do support work only: they are NOT the drug designer, never will be.

"drug designer" = experienced medicinal chemist, trained in organic synthesis.

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41. Gilbert Pinfold on May 26, 2011 12:17 PM writes...

PFE is the Lindsay Lohan of drug companies. We all watch the stupid, self-destructive behaviors until we realize that this is a company that wants to die...

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42. smurf on May 26, 2011 12:28 PM writes...

The real problem for Pfizer is not the chemistry outsourcing – this can work. The real issue is the design of the early stage screening funnel – Pfizer forgot how to do.

A well designed screening funnel is the product of a partnership between disease experts, assay and reagent generation specialists, chemists and screeners, and this partnership is broken. We now have a dictatorship, not a partnership.

To keep the screening funnel under control such that the results can be interpreted quantitatively is another challenge - good luck to Pfizer, they’ll need it.

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43. CR on May 26, 2011 12:29 PM writes...

I recently heard an upper manager of Pfizer explain this model. The "Designers" are in fact, medicinal chemists (some might be very talented computational chemists (re: modelers), but very few). Overall, Derek's explanation of the process is right on. As many people here have commented, what happens when the synthesizer cannot make the designers compound (or doesn't want to due to patent issues) - I asked this very question - and the manager stated that that would not happen. This is a very collaborative situation and everyone has come on board with this idea. Explaining that fresh Ph.D.'s love to come in and just make compounds - and for most of them that is all they want to do (ridiculous statement) - but for those few that want to become 'designers' they could start learning that process (ie, medicinal chemistry). This was so counter-intuitive to everyone in the room as we all know that everyone should become 'designers' - or as we would all call them 'medicinal chemists'. The room was full of Chemistry directors from most of the other big pharma and nobody believed that would actually happen, though. After the manager gave the presentation, many of us wondered how long it would be until there were zero 'synthesizers' in the US.

@27, Anonymous:
"The funny thing is that I have never heard of an incident where a drug designer excluded the person who synthesized the compound from a patent. The reverse happens all the time. "

The person that synthesized the compound has ZERO patent claim if they just simply made the compound. The designer has made the intellectual contribution, not the synthesizer - so I'm n