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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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August 28, 2009

REACH for the Sky!

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Posted by Derek

I wrote years ago on this blog about REACH, the European program to (as the acronym has it) Register, Evaluate, Authorize and Restrict Chemical substances. (I'm not sure where that second R got off to in there). This is a massive effort to do a sort of catch-up for chemicals that were introduced before modern regulatory regimes, and it involves fresh toxicological investigations and an absolute blizzard of paperwork. This program was launched in 2006, after years of wrangling, and the last few years have been spent in yet more wrangling about its implementation.

The worried voices are getting louder. Thomas Hartung (a toxicologist at Johns Hopkins and the University of Konstanz) and his co-author, Italian chemist Costanza Rovida, now say that the program is heading off the cliff. (Their full report is here as a PDF). In Nature, the authors have a commentary that summarizes their findings. They estimate that around 68,000 chemical substances will fall under the program, and when they run the numbers on how those will need to be tested, well. . .

"Our results suggest that generating data to comply with REACH will require 54 million vertebrate animals and cost 9.5 billion Euros over the next 10 years. This is 20 times more animals and 6 times the costs of the official estimates. By comparison, some 90,000 animals are currently used every year for testing new chemicals in Europe, costing the industry some 60 million Euros per year. Without a major investment into high-throughput methodologies, the feasibility of the programme is under threat — especially given that our calculations represent a best-case scenario. In 15 months' time, industry has to submit existing toxicity data and animal-testing plans for the first of three groups of old chemicals."

These are staggering numbers. There are not enough labs, not enough toxicologists, and not enough rats (well, usable rats) in Europe to even come close to realizing such an effort. It turns out that the biggest expense, on both the animal and money counts, is reproductive toxicity testing, which is apparently being mandated into the second generation of rodents. That works out to an average of 3,200 rats sacrificed per chemical evaluated, so you can see how things get out of hand. The authors are calling for an immediate re-evaluation of the reproductive toxicity testing protocols, arguing that the cost/benefit ratio is wildly out of whack, and that the rate of false positives (especially involving second-generation studies) is high enough to end up scaring a lot of people for no sound reason at all.

I'm absolutely with them on this. The program seems like one of these "No cost is too high for absolute safety" ideas that make politicians and regulators happy, but don't do nearly as much good for society as you'd think. (It's worth noting that Hartung and Rovida actually support the idea of REACH, but think that its implementation has gone off the rails). One beneficial side effect, as the authors mention, is that the whole mess will probably end up advancing the state of the art in toxicology a good deal, partly in ways to figure out how to avoid the coming debacle.

Not suprisingly, the European Chemicals Agency is disputing the study, saying that they don't anticipate the numbers of chemicals registered (or the costs associated with studying them) to differ much from their estimates. If I can suggest it, though, I would like to mention that the history of large regulatory programs in general does not provide much support for that optimistic forecast. At all. To put it in the mildest possible terms. We'll see who's right, though, won't we?

Comments (19) + TrackBacks (0) | Category: Regulatory Affairs | Toxicology


COMMENTS

1. T on August 28, 2009 9:16 AM writes...

Ridiculous. A typical European 'initiative' getting completely out of hand, with no one willing to refocus/stop it for fear of losing face. If the numbers (animals & money) weren't so horribly large it would be funny.

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2. NorthernChemist on August 28, 2009 10:12 AM writes...

To put the accuracy of the ECHA's estimates into perspective, the number of pre-registrations made by the deadline of December 1st 2008 was 2.6 million - compared with their original estimate of 180-200,000.

http://www.rsc.org/chemistryworld/Issues/2009/January/ReachEntersSecondPhase.asp

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3. NH_chem on August 28, 2009 11:24 AM writes...

In dealing with a customer and REACH issues, there are many things open to interpretation. One company can see it one way, one the other. There is no real direction. The idea of REACH is good but the implementation is poor. In fact, it has created a money making opportunity for many cleaver people and companies.

To all those dealing with REACH issues, GOOD LUCK!!!

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4. Lucifer on August 28, 2009 2:42 PM writes...

Europe lost their marbles decades ago.. it is just more obvious now.

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5. Mutatis Mutandis on August 28, 2009 2:54 PM writes...

In the US, the EPA has similar problems with a huge backlog of untested chemicals. However, they are investigating advanced in-vitro toxicology options (including the use primary cells, in-vitro models for organs, high-content screening and microarray screening) in the hope of reducing the number of compounds that need to go through to animal testing. This may indeed advance the state of the art in toxicology beyond what is now common in the pharmaceutical industry.

The EU should consider a similar programme. Besides, shouldn't the industrial nations cooperate on this? No point in paying twice for the same result...

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6. ChangJ on August 28, 2009 5:49 PM writes...

Working with one of the first materials to go through REACH and having talked to a lot of chemical companies about it, my concern is less on cost of registration (which is saying a lot) and more on future innovation.

Many many large and small companies just do not have the capability (both human and money) to do the large scale of testing required for this. This is killing their ability to create new chemicals and the ability to use those chemicals.

In 10 yrs when people wonder why we barely see anything new anymore, this will be one of the biggest reasons.

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7. ChristianK on August 28, 2009 6:18 PM writes...

If there aren't enough rats the number of registered chemicals will automatically be lower than 68,000.

Some chemicals will simply be replaced by alternatives without being tested at all which will bring the total price down.

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8. Tom Womack on August 29, 2009 3:52 AM writes...

If you're doing reproductive testing, surely you have to do it into the second generation because otherwise DES comes out as safe; subtly screwing up forming gametes is not terribly hard.

If you believe the compounds are generally entirely safe, go for the fragment-screening approach and dose a ten-compound cocktail per rat ...

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9. Morten G on August 29, 2009 4:11 AM writes...

I would have thought you figured this was a good thing Derek since banning a bunch of compounds is going to produce a lot of work for synthetic chemists to come up with alternatives.

And Womack is right, if the compounds are generally safe (maybe some in vitro pre-screening?) then using a cocktail could cut costs tremendously. And you could check for cocktail effects at the same time.

Very ambitious project...

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10. dearieme on August 29, 2009 4:33 PM writes...

Before I retired I was asked to give some undergraduate lectures on hazards. On the subject of REACH I pointed out that it looked certain to be absurd but that there wasn't yet any experience of it that I could recount. So, to give them a flavour of what to expect, I introduced them to the European Commission's cucumber regulations.

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11. srp on August 30, 2009 3:30 AM writes...

I'm not sure we in the US are in a position to laugh at the EU. We now have a law ostensibly designed to protect children from lead poisoning that will essentially outlaw all children's clothing and products produced in the past (including older children's books), wipe out the vast home-based craft industries making goods that might be used by children, and require destructive testing of all finished products used by children (thereby outlawing customized items). Humorously, this law was precipitated by a scare over lead components from Chinese suppliers to big toy companies (that had already been addressed by those companies), but the big toy companies will barely be affected by the law while their small competitors will be destroyed or driven underground.

So REACH may be crazy and impractical, but it isn't uniquely stupid.

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12. Bored on August 30, 2009 8:23 PM writes...

If no cost were truly too high for absolute safety, we would never be allowed to leave our houses made of concrete and steel. Automolbiles would be banned, as would nearly every man-made chemical and every electrical or mechanical device ever invented. There is a power lust behind this, somewhere. To paraphrase Ben Franklin, those who give up freedom for safety deserve neither.

"Life is pain. Anyone who tells you otherwise is trying to sell you something."

- from "The Princess Bride"

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13. Mutatis Mutandis on August 31, 2009 5:57 AM writes...

Let's not exaggerate: The sad fact is that there is a long historical record of people being killed by the use or manufacture of seemingly innocent products, for example pottery with poorly made lead glazes, or fire-resistant panels containing asbestos. And the history of products sold for medical applications has its own nasty surprises -- I've read that in the 1930s, barely sub-lethal doses of thallium compounds were sold over the counter for hair removal.

Investigating the safety of the many chemicals that have never been properly tested makes excellent sense. The problems seem to be due more to a failure to prioritize properly and to employ innovative toxicology approaches.

Permalink to Comment

14. passionlessDrone on August 31, 2009 8:03 AM writes...

Hello friends -

I believe that a similar effort in the US was stalled, largely as a result of the inability to determine which type of rat to use. The arguments seemed to go:

1) If we don't have a robust rat, they won't reproduce, and then it is difficult to look for problems.

and

2) If you select a highly robust rat, we will miss problems that are going to affect species that are not as robust.

Ten years in, and a model cannot be agreed on. Does anyone have any more information on that?

Nice post. Thank you.

- pD

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15. Henry on August 31, 2009 2:43 PM writes...

"and not enough rats (well, usable rats) in Europe to even come close to realizing such an effort."

Globally, there are several million people working in finance who contributed to the economic collapse.

I would think that the data generated from using twenty thousand US bankers and stockbrokers would be far superior to the data generated from the cheese eating form of rat.

Save a rat, test a banker!

(It's amazing no one else thought of this)

Permalink to Comment

16. Bored on August 31, 2009 7:24 PM writes...

Henry,

Bankers, yes, but there would be greater satisfaction in using politicians. Besides the obvious fact that politicians outnumber rats, politicians could be freely sacrificed without a peep from the PETA freaks.

When we run out of politicans, we start using "Czars" from the Obama administration, who are starting to outnumber rats as well.

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17. AR on September 1, 2009 10:55 AM writes...

Sorry, Bored. Can’t use politicians – safety studies need colony breed rats. Have to stick to Ivy League business school graduates.

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18. Bored on September 1, 2009 3:14 PM writes...

AR-

Ah, but you see there is another advantage to using politicians over rats in lab experiments: There are some things that rats won't do.

And if there were ever an example of colony breeding, it is Washington D.C.

Permalink to Comment

19. Occupational Toxicology on September 16, 2009 10:28 PM writes...

Derek, Excellent post. REACH has definitely "gone off the rails." As always, coming up with regulations is the easy part, but implementation is the real work. In addition, the law of unintended consequences kicks into full speed. I wonder the amount of hazardous air emissions that have been created by professionals just traveling to conferences to figure all this information out.

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