Friday, January 23, 2009

FDA on GAO's High Risk List

The Government Accountability Office has added the FDA to its list of organizations that are considered to be at risk. Concerns listed included:
  • Protecting Public Health through Enhanced Oversight of Medical Products
  • Inspecting Foreign Manufacturers
  • Monitoring Post market Safety
  • Reviewing Promotional Materials for Medical Products
  • Overseeing Clinical Trials
The full report can be found at  -

Here is a quote from the report
Many have begun expressing concern about FDA’s ongoing ability to fulfill its mission of ensuring the safety and efficacy of drugs, biologics, and medical devices. Reports issued by both FDA’s own Science Board in 2007 and the Congressional Research Service in 2008 point out that the demands on the agency have soared in recent years for a variety of reasons. These include the complexity of new products submitted to FDA for premarket approval, the emergence of challenging safety problems, the globalization of the industries that FDA regulates, and new statutory responsibilities. The Science Board also found that FDA’s resources had not increased in proportion to the growing demands placed on it, putting public health at risk. Similarly, in 2006, citing serious resource constraints, the National Academy of Sciences’ Institute of Medicine expressed concern for the future of drug safety. HHS’s Office of Inspector General (OIG) included the oversight of drug and medical device safety as one of its top management performance challenges for fiscal year 2007.
Our work examining a variety of issues at FDA echoes the conclusions reached by others that the agency is facing significant challenges that compromise its ability to protect Americans from unsafe and ineffective products. FDA has recently announced plans that may help it address some of it resource challenges, such as embarking on a major multi year hiring initiative and investing in an information technology modernization effort. However, to make a meaningful difference, these initiatives will require effective implementation, and their success cannot yet be evaluated. Although such initiatives may hold promise, we nonetheless believe that FDA needs to enhance its oversight of medical products to better protect public health.


  1. Reading between the lines and having been at FDA and involved in the IOM interviews this is my persepective:

    >Inspecting Foreign Manufacturers

    The pharmaceutical industry needs the belief that things are safe. It they outsource and move offshore they need some visible indicator. This does not mean that it will be rigorous.

    >Monitoring Post market Safety

    Let's get these unsafe drugs onto the market. Let's shift the focus from prevention (pre-market review) to post-market then when we detect the problems we already know we can a) drag it out because we're not certain then b) say we need to look at class and see if we can keep it on the market c) sell another drug for an orphan indication that will treat it and make a bundle off of the huge increase in stock price for the small company we've invested in. (ex. Zyprexa - Lilly / United Therapeutics- treatments for pulmononary arterial hypertention). (I can name several others as a clue here are the orphan /other indications: herediatary angioedema, huntington's chorea, hepatitis).

    >Reports issued by both FDA’s own Science Board in 2007 and the Congressional Research Service in 2008 point out that the demands on the agency have soared in recent years for a variety of reasons. These include the complexity of new products submitted to FDA for premarket approval, the emergence of challenging safety problems, the globalizaiton of the industry FDA regulates, and new statutory responsibilities.

    FDA's science board is made up of individuals from Lilly, Glaxo,and I believe Harvard and Johns Hopkins. All I believe with close ties to the pharmaceutical industry.

    Of course with new biologics including therapeutic proteins, monoclonal antibodies, RNA inhibitors etc.. Chips to test for genetic polymorphisms associated with diseases and drug toxicities like Stevens Johnson Syndrome, we'll need people at FDA quickly to review our products because we don't want any delays in getting them to market.

    We need people at FDA to ID them postmarketing through surveillence so we can collect their DNA for developing new products (for the mutuations we don't already know about) and can change labeling per FDAAA 2007 and sell genetic testing for everybody (for the ones we do know) and the orphan drugs for treatment.

    As for globalization well if clinical testing, development and manufacturing is moved offshore then we need an appearance that we're doing something about oversight. Plus we need to bring standards up somewhat otherwise if we don't we will have a mess but this way we can also decrease it from the levels we have in the US, EU etc..

    >The Science Board also found that FDA’s resources had not increased in proportion to the growing demands placed on it, putting public health at risk.

    Of course we need money to pay for this and rather than use our own from increase User Fees lets' push to use taxpayer's dollars.

    As for GAO their evaluation is based on the problems at FDA that have already become widely known publicly. But the pharmaceutical industry and FDA will look at it and say how do we make lemonade out of lemons.

  2. Thanks for this, David, and Salmon for comments. These reports seem to be becoming an industry in themselves. How many confirmatory studies do we need?!

    I assume the new administration/HHS would be more likely to do something, but I am still uncertain re: Congress. Many of these problems have been around for a very long time, through both Dem and Rep Congresses. Despite much talk, there has been almost no action on the funding side. Dingell appeared to be wanting to go that way up to the elections. Now that they are over, I guess we will see. The econ crisis obviously won't help.

    As far as the industry and lemonade, I have just reread the DRI brief in Levine that Dan Troy wrote. The FDAAA is continually referenced to support how thorough and empowered the current FDA is. The bill certainly served needs. It remains to be seen whose.

    For those of us who believe in an agency that can handle its mission, we have a lot of work to do. And, as all know, beyond bucks there is culture, management, and "old habits" associated with entrenched power.

  3. Related to this issue, there are interesting threads on Fierce Pharma and Eye on FDA which include a statement by Frank Torti, Acting Commish.

    Along with emphasizing science rather than politics in regulatory policy (breath of relief), he notes the need to get a permanent Commish in place asap - among other reasons, so that person will have the clear power and manadate to set direction.

    Fierce Pharma, via Eye on FDA, summarizes:
    He asked Congress to help reshape the agency and provide the necessary resources and powers to get the job done. He emphasized the role of "scientific thought and process" in regulatory decisions, perhaps in response to those agency scientists who recently accused management of engendering a "culture of corruption" where science takes a backseat. And he specifically said that politics should have "no standing in regulatory decisions."

    Thanks and free subscriptions in the mail.

  4. I suppose this means more money for the agency who disrupted and then ignored the carefully titrated treatment for epilepsy patients by jumping on the QbD (quality by design) bandwagon. Allowing a reformulation that caused hospitalizations and months of additional tests and treatments for those who now have a diminished quality of life, a few less teeth, new scars, and a new found level of disability which has caused some to no longer be able to work and support their families. Some who work the medical field- if you think our losses were the losses of people with little significance. Seizing unexpectedly by taking a product we were told was equal to Pfizer's prior formula.
    "New Look" Dilantin indeed.

    I know that the request for product samples to be sent to Puerto Rico was also sent to the FDA. And still, nobody found our damages significant enough to do anything to remedy the situation. So yeah, let's go and toss them some more tax payer dollars. My dollars, even though I was financially devastated by FDAs actions and then their lack of action.
    Sorry, I can't help but to be a little pissed as Pfizer sits fat enough to purchase Wyeth at 60 billion is it? While those of us struggling get flipped the finger by the company we relied on and their regulators.
    One party covering the other to the demise of a group who cannot regain their losses physically or financially, who has been flat ignored by the DOJ for over a year.

    It is fortunate that the GAO realizes the problem. Until we are made whole again somehow- it is all insignificant chatter. There comes a point when you begin to feel like a fool for being upstanding tax paying citizens.

    "However, the criteria Pfizer used was not requested by the FDA to show bioequivalence and was different from the FDA criteria, according to an FDA spokeswoman. She adds that the FDA was unable to review the study protocols before Pfizer proceeded and the agency doesn’t know why Pfizer chose different acceptance criteria. Nonetheless, the agency did approve the new Dilantin."

    We know how and why it happened. The comments after this article lay it all out pretty well.


  5. JaT - Good to see you here.

    As you probably know, Warner-Lambert was "busted" for Dilantin manufacturing defects several times in the '90s (I understand, a different issue).

    Still, impressive enough that Sidney Wolfe called it the worst example of persistent corporate deliquece he had ever seen. Coming from him, that means something.

    Public Citizen's statement can be found here:

    Re: the FDA, if Torti means what he says, and there are others who follow, it will be more than more money that changes. The talk, at least, is about genuine change in the agency's culture. Possible? There are a few instances over the FDA's history when it's happened (and then reverted), although only a few.

  6. Hi JiM,

    Nice to find you here as well. Thank you for your effort toward allowing for these vital conversations to continue.


  7. Paul Valéry said, "History is the science of what never happens twice."

    Professor Justice, sounds like you might have a little FDA history for us to dissect.

  8. Someone (not Valery) said that going after the FDA is like shooting an elephant - slow moving, and bleeds profusely when hit.

    Marx said, "History repeats itself - first as tragedy, and then as farce." FDA may have mushed the two acts together.

    Anyway, Nancy, I was thinking of the Goddard era, brief but effective, and at least some things about the Kessler era, more re: tobacco than pharma. And, whatever else, Larick backed up Frances Kelsey when she didn't give thalidomide the green light in the U.S.. Every now and then, spine happens.

  9. p.s. not to get overly metaphysical, but _nothing_ ever happens twice, even the stuff that chemistry studies....

  10. Ah, Heraclitus, apostle of change! Yes, the physical world is continually changing. However you came up with the theory that there is one constant--the pattern of change itself. Examples of this can be found in modern day chaos research.

    As people at the FDA reflect on past mistakes, their actions will eventually validate Valéry’s theory. The good people at the FDA will not repeat the past mistakes that created tragedy and farce, and the other people will leave at the pleasure of the President.

    Speaking of, has anyone checked out the new White House Web site? The site is very well-designed with a Comments section, here:

    Dr. Torti, Acting FDA Commissioner, is requesting feedback via email, to:

  11. Great post, Nancy. I think the blog has reached new hights we reference to chaos theory! And, indeed, just because nothing is precisely what it was doesn't mean one can't learn from whatever was....

    As for FDA, the operative word may be "good people," as viewed from a perspective. If the contemporary FDA (of the last ten years or so), got too "cozy," they were following the suggestion of both the Clinton and Bush administrations. For example, it seems unlikely that the whole Rezulin dance would have gone on as long as it did - during Clinton years - if the players at the time were not being specifically instructed to "play nice," not confrontative.

    Great to hear about the Torti site. That probably deserves a thread of its own, which I'll do!

  12. Thank you, Justice. I feel confident that the new administration will encourage FDA employees and stakeholders to play by the rules. I am hoping that an appropriate level of oversight will be achieved in every phase of product development, review and approval, and postmarketing surveillance.

  13. Let us hope. Certainly, there are enough blueprints - all the reports of the past few years, and a number of earlier ones which made the same essential recommendations.

    Still, when push comes to shove, neither admins or Congress (Reps or Dems) have followed through - at least not since '62, and that "required" thalidomide. We will see!

  14. Justice, I'll pick up on the thalidomide tragedy. In 1962 thalidomide, a sleep aid, caused severe birth defects in thousands of European babies. Dr. Frances Kelsey (the FDA officer you praised in a previous post, Justice) was instrumental in blocking the approval of thalidomide in the United States. The Kefauver-Harris Amendment was passed, requiring drug companies to prove that drugs were effective for the conditions for which approval was sought.

    What major changes were made at the FDA between 1962 and 1997?

  15. Wow - a pop quiz!

    Of course, "major change" is in the eye of the beholder. No doubt FDA management would point to numerous particulars.

    Personally, I would say the "major change" was figuring out how Kefauver-Harris should be actualized. The clinical trial/NDA system, in its particulars, was not spelled out in K-H. So that had to be worked through. And, of course, there was the very large Drug Efficacy Review process that also followed from operationalizing K-H.

    Otherwise, I would point to how close we came to Kefauver-Harris being reversed (not an FDA change per se, but obviously related). That was an explicit goal of "the Gingrich revolution" in the mid-90s, and was proposed, in a variety of forms, during the Reagan administration. The goal was to go back to a pre-thalidomide FDA. (The deregulators then are mostly the same folks who are the preemptors now.)

    In the mid-90s, the votes were there to do that. It was mainly the intervention of some key players in pharma itself - who realized the FDA's "seal of approval" was no trivial thing - as well as the House Health Subcommittee which had a bipartion tradition on key issues (and the memory of thalidomide made this a key issue) - that kept the reversal from happening. The Senate's Health Committee had already passed undoing Kefauver-Harris.

    Thus, FDAMA, in '97, was in many ways a "gift" back to deregulators. The looser guidelines on off-label promotion, and the advent of TV DTC, were some of the results.

  16. Two footnotes re: thalidomide that I think are not often enough remembered.

    1. Two companies - I think Hoffman-Laroche (in the process of developing Librium) and Squibb - turned down the option of distributing it. They knew there was no good science for either safety or efficacy of thal. It is a good example of industry regulating itself, which does happen.

    2. Second, terrific as Kelsey was, keeping thal. from being approved required back-up from others at FDA as well, ultimately including the Commish. So it is not only the story of "one person," as it is often retold.

  17. Justice, thank you for pointing out the fact that industry was on top of the situation, and that the save was a group effort. Kennedy was President, and Larrick was FDA Commissioner.

    In an eerily familiar story published in TIME magazine - The Thalidomide Disaster (August 10, 1962) - a U.S. psychiatrist ordered the unapproved drug from a German company. One of his patients who took the drug lost her baby. The article is posted here:,9171,873697-2,00.html

  18. If I am not mistaken, Thalidomide was the drug that prompted the FDA to rule, in 1962, that drugs needed to be tested for teratogenic side effects, or to show possible side effects on pregnant and nursing women. It turns out that one optical isomer is responsible for the birth defects. Thalidomide was mostly marketed to pregnant mothers to relieve morning sickness and to act as a mild sedative.

    This is important to note as Thalidomide is making a come back in the treatment of Multiple Myeloma and also in the area of AIDS.

    More importantly, the entire issue of teratogenicity and any side effects that may be deemed to cause developmental issues in infants and children will be important issues that will need to be revisited.... More to come...

    Yes, we are grateful and give much praise when the pharmaceutical industry works well with governmental bodies. I do believe it happens more than we know. Hopefully we will be able to highlight more of that.

  19. "Those who would learn from history are condemned to make new mistakes"

    just sayin'

  20. I think Former is right re: thalidomide and teratogenicity studies being required.

    Re: history and mistakes, remembering history leads in all kinds of directions. In former Yugoslavia, remembering the Holocaust provided, not a preventative effect, but a model of how "ethnic cleansing" can be done.

    In any event, it is useful to have models for things working well at FDA, and in its relationships with industry. It is a direct counter to folks who would say "it can never work," "industry is industry," "FDA is FDA," etc., and thus avoid engaging the possibilities.


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