Corante

About this Author
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

Chemistry and Drug Data: Drugbank
Emolecules
ChemSpider
Chempedia Lab
Synthetic Pages
Organic Chemistry Portal
PubChem
Not Voodoo
DailyMed
Druglib
Clinicaltrials.gov

Chemistry and Pharma Blogs:
Org Prep Daily
The Haystack
Kilomentor
A New Merck, Reviewed
Liberal Arts Chemistry
Electron Pusher
All Things Metathesis
C&E News Blogs
Chemiotics II
Chemical Space
Noel O'Blog
In Vivo Blog
Terra Sigilatta
BBSRC/Douglas Kell
ChemBark
Realizations in Biostatistics
Chemjobber
Pharmalot
ChemSpider Blog
Pharmagossip
Med-Chemist
Organic Chem - Education & Industry
Pharma Strategy Blog
No Name No Slogan
Practical Fragments
SimBioSys
The Curious Wavefunction
Natural Product Man
Fragment Literature
Chemistry World Blog
Synthetic Nature
Chemistry Blog
Synthesizing Ideas
Business|Bytes|Genes|Molecules
Eye on FDA
Chemical Forums
Depth-First
Symyx Blog
Sceptical Chymist
Lamentations on Chemistry
Computational Organic Chemistry
Mining Drugs
Henry Rzepa


Science Blogs and News:
Bad Science
The Loom
Uncertain Principles
Fierce Biotech
Blogs for Industry
Omics! Omics!
Young Female Scientist
Notional Slurry
Nobel Intent
SciTech Daily
Science Blog
FuturePundit
Aetiology
Gene Expression (I)
Gene Expression (II)
Sciencebase
Pharyngula
Adventures in Ethics and Science
Transterrestrial Musings
Slashdot Science
Cosmic Variance
Biology News Net


Medical Blogs
DB's Medical Rants
Science-Based Medicine
GruntDoc
Respectful Insolence
Diabetes Mine


Economics and Business
Marginal Revolution
The Volokh Conspiracy
Knowledge Problem


Politics / Current Events
Virginia Postrel
Instapundit
Belmont Club
Mickey Kaus


Belles Lettres
Uncouth Reflections
Arts and Letters Daily
In the Pipeline: Don't miss Derek Lowe's excellent commentary on drug discovery and the pharma industry in general at In the Pipeline

In the Pipeline

« The Uses of Disorder | Main | The Failure of Modern Medicine? »

June 14, 2011

A Shortage of Cancer Drugs?

Email This Entry

Posted by Derek

There have been several headlines about a shortage of classic chemotherapy drugs recently. How do these things happen? This post at Marginal Revolution is the best short overall look at the problem that I've seen so far:

Currently there are about 246 drugs that are in short supply, a record high. These shortages are not just a result of accident, error or unusual circumstance, the number of drugs in short supply has risen steadily since 2006. The shortages arise from a combination of systematic factors, among them the policies of the FDA. The FDA has inadvertently caused drugs long-used in the United States to be withdrawn from the market and its “Good Manufacturing Practice” rules have gummed up the drug production process and raised costs.

As Alex Tabarrok says there, one pebble, or a few, won't dam up a stream. But if you keep throwing them in, something's going to happen, and I think that we've reached that point here. . .

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


COMMENTS

1. Nick K on June 14, 2011 1:55 PM writes...

The Law of Unintended Consequences strikes again.

Permalink to Comment

2. Anonymous on June 14, 2011 2:12 PM writes...

Funny, "I told you so" just isn't that satisfying when people are dying.

Permalink to Comment

3. Nick K on June 14, 2011 2:15 PM writes...

The Law of Unintended Consequences strikes again.

Permalink to Comment

4. cynical1 on June 14, 2011 4:47 PM writes...

Did you even read the links in that post? According to the American Society of Health-System Pharmacists, "Inability to fully comply with GMP, which results in production stoppages or recalls, was considered a major cause." And exactly where do you think all those problems with manufacturing are happening? I'm guessing the same place that puts lead in children's toys, cadmium in charms, and melamine in baby food. Maybe the record number of shortages are linked to a record number of incompetent overseas production facilities. Of course, it's just easier to blame the FDA. Personally, I'm glad there's an agency such as the FDA that regulates the crap that is being imported or manufactured domestically. If it doesn't meet spec., I don't want it in my arm. Maybe you might consider unmitigated greed as the real cause for the shortages. Give me a break.........

Permalink to Comment

5. Phil on June 14, 2011 9:02 PM writes...

@4: No matter how feasible, unsubstantiated claims are still unsubstantiated claims.

FTFA: "A Teva spokesman said its California plant that makes injectable drugs, which was closed last year due to quality issues, is now back up. But the plant will not reach full capacity until the end of this year."

It's not just overseas facilities.

To address your point about greed, FTFA again: "But underlying all of this, he said, is a dearth of financial incentive to make the lower-cost cancer drugs, especially when new cancer drugs command huge premium prices."

This is a problem, but it's not as simple as pure greed. As Derek had pointed out many times, developing drugs is very expensive. When the payoff isn't there to offset the investment, no one will do it. No one CAN do it.

Permalink to Comment

6. processchemist on June 15, 2011 1:22 AM writes...

No one remember the classical Baxter eparine case? Obviously GMP is costly, but FDA and EMEA controls (in this last case operated by the national authorities) are the only way to assure the quality standards required by a drug. And it's not a matter of specs: GMP certifies the manufacturing unit AND any single process for any API produced there. Specifications and "USP" or "EP" or "BP" compliance of the product can't account for contaminants invisible to the pharmacopeia analytical methods ( a classical example: beta-lactamic APIs, where only NMR can really say something about the real potency of the product).
Obviously who sells generic drugs has the interest to acces to the cheapest asian supplier, but this is not the interest of the patient.
And in the generic arena, controls have a great importance, because where margins are tight the pressure to cut costs is higher....

Permalink to Comment

7. simpl on June 15, 2011 5:07 AM writes...

One of the less pleasing sides of our merger was the pressure from financial analysts to get rid of older, low-margin drugs. Not only did that result in logistic and production turbulence for years, but the security of the products on the market was lower. If a product's sales cover production costs and contributes to overheads, it pays its way and provides a service.
This is not only a US problem by the way, but interesting that the time to resolve in US is so long. A pharma multi (with multiple plants to produce drug product) should be able to turn things around in a few months. Consultant syndrome may have lead to low stocks of active ingredient in some cases.

Permalink to Comment

8. anchor on June 15, 2011 6:29 AM writes...


Derek: The road block to the availability could be FDA, with regulatory stranglehold is far from the reality. It is possible FDA is a problem and by blaming them, they are giving a free pass to the drug companies. At the end of the day we are talking about “dollars invested and dollars made” and it is as simple as that. Unlike statin and diabetes drugs that have "large patient population", cancer (a heterogeneous disease) does not. I mean at the end of the day the drug companies have to decide "if it was worth" making these drugs on an ongoing basis to reach out to few thousands of patients, who are benefited (cost vs. benefit, i.e. benefit to the company). That is the hard truth, no matter how you dissect. That these drugs benefit only few people are the reason why they are expensive (recouping the cost!). I think, it was the late George Young who once said, “When they say it’s not about the money, it’s always about the money.” How true!

Permalink to Comment

9. processchemist on June 15, 2011 6:58 AM writes...

@anchor

"The road block to the availability could be FDA, with regulatory stranglehold is far from the reality."

Maybe you're talking about the new drug approval process, hardly can be said that cGMP is something "far from reality". Can be cumbersome, but it's the only system capable to assure adequate drug product safety.
Usually, scarcety causes rising in prices. With higher prices maybe some little western producer can valuate the oppurtunity to file an ANDA, or to start again the production, if has a Drug Master File already registered.

Permalink to Comment

10. MTK on June 15, 2011 9:05 AM writes...

Just as a check I did a cursory glance at all the 2010 FDA warning letters related to cGMP compliance of a pharmaceutical. (They're all online and you can search for it. There's also a ton of other warning letters besides pharmaceutical cGMP.) Anyway, I really didn't see any indication that India and China were overrepresented. Most were US facilities with Italy, Spain, Belgium, UK also there. Of course that may represent inspection rates also.

In any event, on the surface, it doesn't seem like off-shoring has an effect here. In fact, when you think about the most serious cGMP problems, in terms of shutting down production, I think of some of the problems that Lilly and Schering had a few years back and both were in the US. Those things halted production for a long time. The other thing is that oncology drugs often require high-containment facilities which cost a lot and require some expertise, not exactly the best candidates to take off-shore.

Permalink to Comment

11. johnnyboy on June 15, 2011 9:51 AM writes...

@ 10 - yes, but you also have to take into account the not-so-off-shore offshoring, ie. Puerto Rico. I seem to remember that a lot of the FDA-identified manufacturing issues of the last few years involved plants in PR, where a lot of big pharma have facilities. I imagine the reason for setting up plants there involve low labor costs and tax incentives. Of course when FDA findings force plant closures, those cost savings no longer look very advantageous. More short-sighted thinking from top-level management (I'm really getting tired of typing that phrase).

Permalink to Comment

12. processchemist on June 15, 2011 9:53 AM writes...

@MTK

"Of course that may represent inspection rates also"

Yes, it does.
Now in the EC only APIs from inspected manufacturers are allowed to be imported: the new laws produced an immediate scarcity of some generic APIs. Before the new law, a statement of cGMP compliance from the producer/seller was enough. Now many brokers and buyers have discovered that almost no one of their asian suppliers was FDA or EMEA inspected.
The scarcity is caused by the fact that in the past years western manufacturers (inspected) dropped some (many) products, unable to match the prices from asian producers.

Permalink to Comment

13. processchemist on June 15, 2011 10:00 AM writes...

@MTK

"The other thing is that oncology drugs often require high-containment facilities which cost a lot and require some expertise, not exactly the best candidates to take off-shore"

That was my thought too, until about 5 years ago, when I met at CPHI an indian entrepreneur with manufacturing sites in China. He was dealing with taxanes, camptotecins, vinblastine, cabergoline and so on. At my question: "How can you keep prices so low with these products, that require high containments facilities?" the answer was: "I have no high containment! Life is cheap in the countries where I work!".

Permalink to Comment

14. RickW on June 15, 2011 11:10 AM writes...

Derek, I'm really disappointed in this post, which seems beneath you. The post you linked to is nothing but raw meat for the FDA haters. You know as well as anyone why cGMP regulations exist. If you look at the document that is linked in the Marginal Revolution post, there are many reasons for drug shortages. One of the powerpoint presentations in the Appendix gives the number of shortages due to regulatory issues as 1% (although that seems low to me). The document also seems to favor more FDA authority, as it would require manufacturers to notify the FDA if they plan to leave the market, if there is a shortage of raw materials, and so on. "best short overall look" my eye.

Permalink to Comment

15. Anonymous on June 15, 2011 11:30 AM writes...

@11,

Those PR plants have been operating for quite some time. Few of those are due were opened recently. in fact, the biggest problem there is that they're losing they're plants to other areas of the world.

@13,

That's sad, but I guess that's the cruel truth.

I will say, however, that at my old pharma job we once rejected without any hesitation the low bid for an oncology drug intermediate due strictly to containment concerns. This company was outside the US and presumably complied with their nation's laws, but we felt it would be unethical of us to take the cost advantage presented on the backs, or lungs, of worker safety.

Permalink to Comment

16. SteveH on June 15, 2011 2:07 PM writes...

Ah, more FDA-bashing! The heady smell of lessez faire capitalism in the air! The working of the perfect, free market (in the case, of pharmaceuticals) would remove low-quality, poorly-produced, ineffective drug products from the marketplace only through the deaths or debilitations of thousands of patients/consumers - your neighbors, your friends, your parents, your spouse, your child, or you. When you or yours is ill, do YOU have the time or expertise to investigate the QA/QC of the drug that the doctor needs to administer right away? Isn't it better to have a system in place to make sure those drugs are okay, BEFORE you need them? One thing is certain about commerce - if there is money to be made, corners WILL BE cut. It'll be cold comfort to think that a drug manufacturer might get sued for producing a shoddy product, after you've buried someone you love. Ask a parent whose child was killed in a crib accident if they wished that there had been tighter regulations on the companies that made the cribs.

Permalink to Comment

17. Anonymous on June 15, 2011 4:21 PM writes...

6, Process Chemist,

The only useful tests for potency of beta lactams are biological, nmr is no better than HPLC, and may be worse for many contaminants. Until the 1970s the compendial assays fore beta lactams were usually biological.

Aside from CE, TLC, and Iatroscan most chromatography is constrained by the simple limitation that you only see what elutes, and the expense of the detector doesn't fix that. However, when validated, it's an excellent process control and QA tool.

The problem with cGMP is that important criteria can be subsumed by trivial detail that is easily monitored. I've met some excellent auditors who understand that risk is an important consideration, and the FDA "accepted" that they needed to incorporate risk into assessments a few years ago, but still appear to focus on individual non-compliances.

In my limited experience, many auditors appear to be people who aspired to be school prefects so they could bully others whilst hiding behind a clock of authority. Pulling up socks really didn't change student's learning skills.

Permalink to Comment

18. ccm on June 16, 2011 8:55 PM writes...

@SteveH

I don't think anyone is suggesting doing away with the FDA, or even any requirements that actually affect product quality. Working in a QC lab, though, I can tell you that there are a number of expectations that really don't have anything to do with the quality of the products. For example, how many "deaths and debilitations" would be caused if I were to print out a chart from the website of a chemical distributor with the molarities of various concentrated reagents (an "uncontrolled document," oh horrors!), or if I slapped a post-it on the front of a waterbath that said "in use, do not change temperature"? An FDA inspector would take issue with either of those, though. The pebble analogy is a good one. Individually, none of the more inane requirements is much of a burden, but as a whole, they do "gum up" the processes. And if every pharmaceutical manufacturer (every compliant manufacturer, anyway) is similarly slowed, I don't think it's unreasonable to say that they might cause systemic cost increases. That's not likely to be the entire problem as far as the shortages go, but it's a start.

Permalink to Comment

19. Dan Spinato on July 1, 2011 1:21 AM writes...

This only means one thing: cancer is becoming a widespread disease.

Permalink to Comment

POST A COMMENT




Remember Me?



EMAIL THIS ENTRY TO A FRIEND

Email this entry to:

Your email address:

Message (optional):




RELATED ENTRIES
XKCD on Protein Folding
The 2014 Chemistry Nobel: Beating the Diffraction Limit
German Pharma, Or What's Left of It
Sunesis Fails with Vosaroxin
A New Way to Estimate a Compound's Chances?
Meinwald Honored
Molecular Biology Turns Into Chemistry
Speaking at Northeastern