Thursday, August 6, 2009


Hamburg Outlines New Approach--Law Enforcement

The below, from todays WashPost, will be welcome news to most people here.


FDA Poised for More Aggressive Approach

By Lyndsey LaytonWashington Post Staff WriterThursday, August 6, 2009 4:05 PM

Margaret A. Hamburg, commissioner of the Food and Drug Administration, said Thursday that her agency will take a faster, more aggressive approach to enforcing regulations and laws.

"The FDA must be vigilant, the FDA must be strategic, the FDA must be quick and the FDA must be visible," Hamburg told the Food and Drug Law Institute in a noontime address.
Hamburg said she was making changes to FDA's internal processes to streamline and speed up the way it enforces regulations governing the safety of food, drugs and medical devices.

"In some cases, serious violations have gone unaddressed for far too long," Hamburg said. "These include violations involving product quality, adulteration, and misbranding; false, misleading, or otherwise unlawful labeling; and misleading advertising."

Hamburg, who has been on the job for eight weeks, said the FDA has often been hampered by lengthy internal debates and prolonged negotiations with violators, she said.

"Frankly, I can see in some past responses, there's a lot of back and forth, a lot of stall and delay, [the attitude of] 'let's wait and see what the company does,' " Hamburg said. "We need to be as clear as we possibly can about our expectations and standards, and when there are ongoing problems or when a problem emerges that has as serious impact on health, then we have to aggressively act."

For example, the FDA will no longer issue multiple warning letters to violators before taking enforcement action, Hamburg said. And if there is a "significant" threat to public health, the FDA might act before it even sends a formal warning letter, she said.

Hamburg said she thinks tough enforcement will act as a deterrent to companies who might otherwise violate the law. "Ultimately, the FDA's success should be measured not by the number of warning letters or injunctions or seizures but by our impact on the health and welfare of the public. Enforcement of the law is not simply an end in itself -- enforcement is critical to the agency's public health mission."


  1. First let me say that I applaud what Margaret Hamburg is doing and forgive me for spouting off about the negative aspects of what implied by the article but...

    The article serves to further highlight the weak foundation that the FDA stands on.

    When we see that with each new administration there is a new “approach” to Federal law enforcement it doesn’t make me feel confident in the stability and the honesty of the FDA as an organization.

    This kind of fluidity in an organization with such responsibility is fertile ground for massive corruption in the least and criminal culpability in the worst. There is a weakness in basing policy on political or personal preference because preferences can be influenced and changed to suit the most influential.

    So I am struck by just that – why has the FDA decided to now enforce the law? Why did it decide before that law enforcement was unnecessary? And most importantly, at its core, what truly influenced this about face?

    Of course the easy answers are political partisanship and industry protectionism. But specifically how are these forces applied to the FDA? How do they finally manipulate the day to day operation of the FDA? Even more importantly – Why are these things allowed and what is the ultimate consequence for the American public?

    Are we safer or are we less safe in the long run?

  2. Bravo Commissioner Hamburg. Hopefully, this is a new day and soon will gone the days of Vioxx, Trasylol, Paxil, Rezulin, Baycol, Bextra, Zelnorm, Fen-Phen, HRT, etc, etc, etc.

  3. In response to David,

    I think you actually _under_estimate how much the FDA has become politicized. The answer to why the FDA has changed is a very simple one: the Obama administration.

    The politicitication of FDA has always been part of its history, but it became much more intense during the Reagan administration, part of the overall deregulatory agenda of "Reaganonomics." There was a bit of temporizing in late Clinton, but Bush II pushed politizing FDA further than ever--with the appointment of Troy, the refusal to appoint a permanent Commish through most of the admin., and the coordinated attack on critical regulatory initiatives.

    An excellent read on all of this is Phil Hilts's book on FDA--One Hundred Years of Regulation.

    As in the past, I think trying to find the answers to such questions inside the FDA itself distracts us from the key players. Look at Congress; look at different administrations. The FDA is their creature.

    Re: how, leadership and appointments within FDA, and its institutional culture relative to industry, make an enormous difference. It is very easy to "manipulate" day to day operations depending on who is in charge and how the mission of the agency is defined.

  4. An interesting question is whether the FDA can become "depoliticized," returning to a more neutral, steady-state regulatory agency which we have not seen in some time.

    There will always be degrees, but if each party flips whatever the last party did, we are in sorry shape indeed.

    But given the extremes of Bush II, a forceful pushback was inevitable and mandatory.

  5. Obama also talked tough about pharma. now he is doing back-door deals with them to push his health care agenda.
    If the commissioner really took quick action big pharma would be shut down to-morrow.
    What enforcement? Quit the stupid warning letters, quit the piddly fines and use the money to hire some FDA folks who understand the difference between a clinical trial and conflict of interest.
    its obvious the WLF have not had their input yet with the new commissioner.
    I wish her luck, liked her speech.

  6. Not sure what Anon. really intends to say other than enforcement has been down the toilet over the past several years. But that was not always the case, even during the era when WLF has existed. Check out the history when Goddard was Commish and some of the Kessler period.

    It may be hard to remember, but there was a time when FDA really did do enforcement. And pharma _gained_ as a result, because they were less likely to be taken in by the outlaws. That's well documented too.

    Echoing David, I'd also ask that people don't use Anonymous. Too generic. Why not call yourself Wyeth or something.

  7. Yes Justice -
    To add - If you pick a name like Bob or Jane or Rainy or whatever you want, you can be just as anonymous as Anonymous.

    With a consistent name the PharmaLittle community can come to know you as a kind of a person or at least a personality. It really adds a dimension to this invisible world that makes it more interesting.

    And when we have long discussions, which happen occasionally, it makes it much easier to see the thread of thought that a particular pseudo-person might have. Otherwise multiple Anonymous posts become confusing when the rest of the group is trying to understand the evolution of the discussion.

    If you are from the PharmaLot era, you might remember how we would have some very long and exciting discussions. Ed Silverman, the moderator would often have to remind us of this –

    “…my basic philosophy is that this is like a big lawn party in which different groups hold simultaneous discussions about different, if related topics. One can stop by to listen or participate, while flitting among groups.”

    He would also have to remind us not to “throw the wine glass” occasionally. But the whole idea is to construct a kind of civil community with recognizable members.

    Having said that, if you somehow feel safer as Anonymous that's OK too, I'd rather you joined the discussion than not for sake of a name.

  8. By the way for those PharmaLot aficionados to the left and up a bit on this page you will see that there is window to a PharmaLot search engine. You can enter a word or term and it will search and find all articles and participant comments ever posted on PharmaLot with your term.

    Same thing goes for the PharmaLittle site in a window located above that.

  9. I hope my post was not offensive. I understand the nature of the blog, so do not want to intrude. i never throw the wine glass, always ask for a refill. I am not high tech and it is easier to select anon in the select profile.

  10. To Anonymous - I am not offended nor do I think you intruded. There is no such thing as intrusion on the internet. It's free to all.

    Sorry for not explaining how you can pick a name (if you want). In the "Comment as" box you can select Name/URL. Then type in any Name. You don't need to type anything in the URL box. That's for those that have there own site and wish to publish the address.

    Simple as that, happy posting and Cheers.

  11. It has been a while since I've posted here so to those who remember me from here and pharmalot, Hello!

    Last week the FDA held and advisory committee hearing for the new atypical antipsychotic asenapine (Saphis - Schering Plough).

    This is a me too of olanzapine (Zyprexa), Quetiapine (Seroquel), and clozapine (Clozaril).

    Last Tuesday July 28th the FDA posted a 1067 page background package containing a number of reviews. The beginning of this package contains memos to the file basicly dismissing safety and efficacy concerns raised by reviewers and signed off on by their management.

    Some of the most significant is that this drug causes dose and time dependent hepatotoxicity, acute cardiac conduction problems, and long term pulmonary arterial hypertention (PAH) like phen-fen and probably vioxx. (PAH) will also be misdiagnosed as SIDS in neonates exposed in utero or via breastfeeding.

    There is an actual review recommendaton stating that the drug is unsafe and that there's no way to label it appropriately. There are also statements or indications in the reviews that the sponsor specificly tried to prevent FDA from figuring this out by withholding information including patient deaths, lab values from studies, and by inappropriately disigned studies.

    For the full reviews see:

    if the link does not work see

    and click on the first pdf file.

    or for specific discussions, page numbers, and evidence see:

    since Tuesday July 28th.


  12. Hi Salmon,

    Great to see you here, by any name, and thanks for the info provided.

    Here's my latest "bugaboo"--I'd be interested to hear whatyou think. As you know, Trilipix is being very actively DTC'd. It is the active metabolite of Tricor, so same old stuff. Somehow, Abbott put together some data and got FDA to agree that Trilipix could market itself as the first fibrate which, on label, is approved for use with a statin. Tricor, of course, did not have that indication, even though it's the identical stuff.

    In the meantime, FDA (via FDAAA) is requiring Abbott to do a phase IV safety study on precisely the issue of this drug, and other fibrates with a statin--something that Baycol should have taught us enough. There is apparently an Abbott/AZ plan (or propaganda about a plan) to create a combined Crestor/Trilipix pill. Of course, all that could be distraction. Bayer put out similar smoke when they knew that Baycol + fenobribate was taking people out ( 1 in 10 such pts were rhabdo'd).

    Meanwhile again, every Trlipix ad includes the required disclaimer that the drug has not been shown to prevent MIs or strokes better than statin alone.

    So why would anyone take, or anyone rx, a drug that's only contribution is to increase risk?

    And why should Abbott be able to market the hell out of this stuff when the completed phase IV study will almost certainly show what we already know--increased rhabdo risk without cardio benefit?

  13. Well. To tell the truth I'm not up on the statins in general and certainly can't comment on specifics.

    However as to your claim that a metabolite is the same as parent drug. No way. Sometimes the metabolite is a better drug but companies got wise to that and so they check them early. Since then what I've seen that many times these metabolites are actually more toxic but with similar efficacy so the companies come in with a study showing comparable efficacy and say approve us we're essentially the same drug. People fall for it and then a less safe drug goes out on the market. Example Effexor (venlafaxine) and Pristiq (desvenlafaxine). For years it's been claims that they are equally potent in vitro and so the same but just look at the difference in side effect profiles. Pristiq is nasty.

    Lots of times though the metabolites do have less problems with certain drug interactions.


  14. Help out this non-chemist...If the active ingredient in two drugs is the same--which is the case for fenofibrate (Tricor) and fenofibric acid (Trilipix)--why would there be a different safety profile in vivo? Isn't the same essential thing ending up in the corpus?

    Perhaps I misused the term "metabolite."

  15. You can read Margaret Hamburg's speech in its entirety at:

  16. In light of Salmon's comments on the continuing going's on at the FDA: if these drugs being approved and brought to market under these "malignant" forms of corporate misbehaviour cause death then they should be brought to justice by being tried for murder under the terms of depraved indifference for human life, which seems to me what it is.

    I am also finding it hard to believe that doctors themselves are not coming forward as they are clearly being used as accessory to murder.

    Or is it that by approving these drugs, which the studies indicate are dangerous, is a new approach to controlled euthanasia? Is the objective to really make the sick patients who take them sicker? What is the thought process behind that? Is that well too bad your sick and need to depepnd on these drug treatments, all bets are off we are allowed to make you sicker and you have to pay us for it?

    We have heard time and time again how difficult it is to get the drugs just right and precisely targeted while minimizing the impact on other organs and systems. Yet it is not so complicated at all, if we take a look at the entire facts and abide by the results fo the clinicaltrials and review all the raw data.

    Once we start holding these companies and their employees criminally responsible for the damages being caused by these drugs, then and only then will we be able to improve the system.

    I suppose we can expect to hear much rhetoric on how if we hold CEO's and their employees criminally responsible for these actions then no one will bother entering in the pharmaceutical industry and innovation will die. It is an empty threat. They are not doing us any real favor or service by being here in the first place. Kind of like "with friends like this, who needs enemies?"

  17. For what it's worth....

    In public opinion polls in some countries, Sweden for example, people rate companies' knowingly suppressing the dangers of a drug as equivalent to murder. In the U.S., it is viewed as equivalent to rape.

    Hamburg's statement, which I recommend reading, references stronger links between FDA enforcement and other relevant government agencies (viz., the Justice Dept).

  18. I have read the Hamburg statement, and I am encouraged by these initial steps to redirect and improve the credibility of the FDA.

    My hope going forward is that more detailed specifics on how further changes will be implemented that would significantly improve the functioning of the FDA. I am thinking specifically about how the FDA will ensure that it is accessing all the raw data on clinical trials for drugs being approved.

    I would also hope the FDA gets more involved in the area of epigenetics. This is becoming a critical area for many of the drugs going through the approval/screening process. The onus should be on the drug frims themselves to provide epigenetic data, there is enough data avaiable to start to extrapolate and provide potential scenarios. The idea is that this could significantly improvide the ability to more adequately convey the risk/benefit profiles of the drugs.

    With a view towards Salmon's comments on some recent goings on at the FDA, it is even more clear that the FDA needs to "review" its reviewing process. I really think ad hoc supplementary reviewers that are anonymous to the process, review the drug files after they have been blinded by the FDA staff. This would delay approval of some drugs. However, the details would be a bit more finessed for "fast track" drugs that are life saving. In fact, this aspect should not be considerred as a "nice to have", it is clearly becoming an imperative.

    I am going to keep watching this space....

  19. Haven't looked at this thread in a while.

    I looked at the labeling for both Tricor and Trilipix and no they aren't the same chemical entity.

    Tricor is fenofibrate and Trilipix is Choline Fenofibrate. Fenofibrate is the methyl ester of fenofibric acid and Trilipix is the choline ester. The active metabolites of both is fenofibric acid which is a carboxylic acid. Carboxylic acids are largely glucoronidated and these glucuronides can be toxic.

    Different rates of absorption, metabolism and presentation to the liver on absorption can result in different toxicity profiles, and a more slowly absorbed compound like Trilipix could be more toxic. Alternatively a faster absorbed compound could be more toxic in ways that I haven't considered with a 30 second look.

    Without looking at the data I can't tell and to tell the truth to go through the amount of data that's in a company submission can easily take 1 year or more even for a whole team of people.

    As for ad hoc reviewers. While it would be nice. It really isn't practical for reasons I won't go into. If you look at reviews on you can gather that there are already at a minimum 4 levels and for consult divisions up to 7 layers of review at FDA. What you need is honesty and ethics at all levels and quality at the primary and secondary levels. From the last couple of NDA reviews I've looked (asenapine and iloperidone) at the big problem seems to be the primary level and sometimes the secondary level also is being inappropriately overruled.

    As the song goes: Who's watching the man , who's watching the man, who's watching me. Or in other words who's watching FDA management who's watching the reviewers, who are supposed to be watching the drug companies


  20. My real question is this. This drug is being heavily DTC'd as we know. Even though FDA has required a significant phase IV study to determine better what the risks of the statin/fibrate combo really are (mainly, the increase in rhabdo).

    Meanwhile again, there is no evidence whatsoever that "adding Trilipix" reduces risk for hard events realtive to a statin alone. That is included in the DTCs.

    So what is the justification for this stuff even existing, let alone being blockbustered?


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