Wednesday, January 28, 2009


FDA Whistleblowers Appeal for Help

It has been reported over the last couple of days that FDA senior management - presumably the Office of Chief Counsel - has escalated its crackdown on nine scientists who have revealed perceived and serious irregularities in the FDA's medical device approval process. According to the most recent report from the New York Times, the scientists charge that "agency officials have acted illegally and that patients are routinely put at risk from high-risk medical devices that are approved for sale even though manufacturers have never proven that the products are either safe or effective."

Given that the Supreme Court, in Riegel v. Medtronic, upheld preemption against civil liability in the class III medical device arena, these charges become especially ominous. If, indeed, FDA cannot be relied upon - and the possibility of lawsuit is removed - patients are effectively left without protection or recourse.

Earlier reports, including some references in the very recent GAO assessment, suggest the reviewers' charges may, indeed, be well founded. It is also extremely unusual for the FDA's Office of Criminal Investigations to initiate action against FDA personnel. Established after the generic drug scandal, the OCI generally handles issues of manufacturing fraud, gross misbranding, and counterfeit medications. For the OCI to be deployed as an internal "enforcement squad" also deserves serious attention.

There may, indeed, be criminal action to be investigated, but it remains unclear whether the perpetrators are the the reviewers or their managers or a more complex mix. The case has already been brought before the House Energy and Commerce Committee.

It is the opinion of this writer that there should, indeed, be the fullest and most transparent investigation of all parties involved in this dispute. And that if, indeed, the OCI is using, or has used, its resources to investigate FDA reviewers that fact itself deserves serious scrutiny through Congress and, potentially, an independent special prosecutor, Acting Commissioner Frank Torti, and Health and Human Services Direct Tom Daschle. If it is necessary, the intervention of the White House, as requested by the reviewers, does not appear unwarranted.

We have learned that during the Bush administration there appear to have been close consultations between the President's advisors and the FDA's Office of Chief Counsel, particularly regarding preemption initiatives. A recent report in the Wall Street Journal, for example, noted that the Office of Chief Counsel, responding to FDA career staff who questioned preemption arguments, replied that the 2006 labeling guidelines would not go through without the preemption preamable, "this per the White House."

The New York Times article can be found at:


  1. The purpose of the FDA's Office of Criminal Investigation (OCI) is outlined in the following policy:

    The Office of Criminal Investigations (OCI) has the primary responsibility for all criminal investigations conducted by the FDA, including suspected tampering incidents and suspected counterfeit products. Similarly, OCI has primary responsibility and is the primary point of contact for all law enforcement and intelligence issues pertaining to threats or perceived threats against FDA regulated products.

    Note it is not supposed to investigate criminal activities by FDA personel.

    The Office of Internal Affairs (OIA) is a subdivision of OCI. In 1998 a MOU was signed between the HHS Office of the Inspector General (OIG) and FDA that transferred some investigative responsibilities of FDA employees to OIA, although it was supposed to done jointly. This type of agreement was unique in all of the federal government. From the beginning this responsibility was apparently abused to retaliate against whistleblowers, e.g. Leo Lutwak - 1998.

    Due to this as well as conflicts of interest of OIA investigating senior FDA officials the HHS IG issued a letter to suspend this agreement on Sept 6, 2007. (Shortly after allegations of serious criminal activities by FDA officials were made by reviewers in the Center for Drugs.) This rescinding of the MOU was praised by Senator Grassley and reported by Ed on Pharmalot along with the relevant documents and Commissioner Von Eschenbach's reply on Nov 29, 2007.

    OIA retained the responsibility to investigate other actions by FDA officials that did not rise to the level of serious criminial activity.

    In December 2007 Commissioner Von Eschenbach appointed William McConagha, a lawyer, to be the agency's assistant commissioner for integrity and accountability.

    FDA policy and procedure manuals indicate that his responsibilities are to advise the Commissioner on inquiries and investigations by OIG. In other words he is de facto the Commissioner's lawyer in defending FDA officials from criminal investigations by OIG's Special Investigative Unit (SIU).

    However, the CDRH reviewers after sending a letter to Commissioner Von Eschenbach on May 31, 2008 were referred by Von Eschenbach to William McConagha who instead of referring the matter to OIG apparently referred it back to the FDA officials who were the subject of the complaint.



    This is not the only time this has happened within FDA. Similar things have occurred with FDA reviewers from the Center for Drug Evaluation and Research.

    In my mind this raises the possibility of obstruction of justice, witness tampering, and agency wide racketeering by current and former FDA officials.


  2. Thanks for this Salmon.

    I deliberately avoided the phrase, "goon squad."


  3. Alice in WonderlandJanuary 29, 2009 at 11:37 AM

    Actually, the “crackdown” should include an investigation of pockets…who’s in whose. From what I understand, if an American citizen is harmed by a FDA approved device, and he/she complains to the US Supreme Court, odds are the Court is going to rule in favor of the device maker for the mere reason the device has the good FDA seal of approval. Sounds cozy to me. Therefore, let’s just skip the step about going to the Supreme Court and due process; it’s a waste of time and money. The patient, if still living, or their spouse, should go home and lick his/her wounds, dream about the America that was, and try to get some rest.

  4. Exactly! Alice!

    The justices going after FDA is like them going after their half brother who is cooking crack in mom's garage. It pisses off the rest of the family if said "half brother" has to go to jail. Nevermind that you are only trying to keep the house from being blown up or that you fear for mom's life when the junkies start stealing from or threatening mom when half bother screws his customers.

    So, like, Don't Ask_Don't Tell.

  5. Sorry, Alice. I tried. Got Riegel'd.

  6. Did anyone else notice what FDA did in honor of the Fourth of July last summer.

    On July 1st FDA issued a new policy on prior approval for outside activities for employees (including writing personal op-ed pieces) where if the FDA employee says anything that places FDA in an unfavorable light will be denied.

    Here's the relevant text:

    Outside activities requiring prior approval:

    2. Teaching, speaking, writing, or editing that relates to official duties, or would be undertaken as a result of an invitation by someone that is a prohibited source of the FDA (see definition of prohibited source, below).

    • Advance approval is required for outside activities listed above in the definition, paid or unpaid, unless specifically exempted from the advance approval requirement under this MAPP.

    • Outside activities, although not an employee entitlement, will ordinarily be approved when they do not adversely affect performance of an employee's official duties, constitute a potential conflict of interest or appearance of a conflict of interest, or create an adverse effect on the image of FDA.

    It's right on FDA's public website. It's MaPP 4641.3.R

    You can get to it via the following link:


  7. Salmon - Wow! David Graham spoke at our university in May, not long after the Vioxx withdrawal. He was clear that he was speaking for himself, not FDA (chuckle when he said that). I would not say he created a particularly attractive picture of FDA, at least the OND senior management.

    He was clear about what he is usually clear about.

    Do you think that sort of talk would be prohibited under these guidelines? And could a new Commissioner erase them?

  8. A note of caution, or perhaps patience. It appears that the FDA employees claiming that device reviews have been mishandled may have decided to share confidential documents and correspondence regarding specific devices with the press. The FDA and its employees are bound by law to keep its dealings with the private sector confidential. If they violated this law, then they broke the law.

    News reports suggest that the agency's failure to complete reclassification of medical devices under its review is a part of the problem. I have seen no specific information reported anywhere regarding which devices the concerned FDA employess claim were allowed onto the market over their objections. Have any of these devices been reported to have serious problems?

    Bottom line, we don't really know what this is about yet, and while the FDA has many problems that need fixing, shouldn't we wait until the facts are out before deciding who is right on this one? Reportedly, Congress is involved and has been inforemd by the employees. They haven't yet acted. No hearings. Why? If they thought this was a big problem, they could stop it by exposing it.

    Just because nine FDA employees think that some of their bosses decisions are wrong, doesn't mean they are.

    I think it also important to note that the Bush administration is over. The Bush White House isn't pulling the strings anymore at FDA. Although Bush administration hold overs are still in place, Frank Torti is Obama's pick for Interim Commissioner, and we should assume he and the new administration have talked, and continue to talk.

    Devices really are different from drugs and biologics; consequently, the review and approval process is logically and necessarily different from those applied to drugs and biologics. Many devices really don't need years of clinical trials and lengthy FDA reviews to establish safety and efficacy. Some do. This seems to be about the judgments made by some managers about where that line is, and there is no evidence (that I am aware of) that this diagreement has allowed unsafe devices onto the market. We need to know if it has. We also need to know if it has not, because if the latter is true, then this is just an internal disagreement about process and policy.

    Given the FDA's steady descent into general incompetence over the last several decades (probably accelerated somewhat during the Bush years), I don't think anyone will be surprised to find out that they have also failed in some systemic ways with devices, but we don't know the facts yet, and assuming that the complaining employees are correct is premature. Many (and maybe most) of the career middle and senior managers at FDA that these employees report to, and seem to be complaining about, have been at FDA for a very long time, some for decades. Where are they in this dust up?

    I agree we need a full, objective investigation of this issue, and complete transparency regarding its findings. But we should remember that the FDA is the mess it has become in large part because there have been too many knee-jerk "fixes" applied to it before we understand what needs to be fixed. I reiterate again, we are now in the Obama Administration and the complaints of the FDA nine are public enough to have shown up on the new administration's radar. (If it hasn't shown up and prompted senior administration officials to inquire about it and weigh in, if warranted, that is a problem all by itself.) I think a very relevant question at this moment should be - is the new administration taking charge at FDA - or is the agency effectively on its own?

  9. Steve - Very much appreciate your post. Speaking for myself, I assumed action probably was illegal - like Pentagon papers. As far as impact of faulty devices, I would not expect to have heard such reports in the near term. But, I agree, we need more of the facts, which is what I hope we will have.

    I think your last question - " I think a very relevant question at this moment should be - is the new administration taking charge at FDA - or is the agency effectively on its own?" -
    is absolutely on point and something I have been wondering a lot myself.

  10. I think it is worth noting that the same individual who was appointed by the FDA to
    "intvestigate the problem" was himself accused by the reviewers of being centrall instrumental in creating it.

    At the very least, doesn't smell good.

  11. Under the new policies David Graham would no longer be able to come and give the same talk. It has nothing to do with whether it's legal or illegal to release the information. You simply can't say anything that makes FDA looks bad.

    Now I don't know about the 9 CDRH reviewers but even in CDER we heard about stuff over there years ago, and even we could read stuff in the press that apparently wasn't on the up and up.

    Congress right now is very busy with other things, heck they need to get a new Sec of HHS and new Commissioner in there first. Things are so bad systemically at FDA that just having hearings on one small aspect of it like a few devices isn't going to do it. This is simply another small cut. The final thrust is yet to come.


  12. "Just because nine FDA employees think that some of their bosses decisions are wrong, doesn't mean they are."

    Agreed. I kept my mouth shut for years because I said well I think they're wrong, but it's their decision and I gave them my advice. However when you see the same things pop up over and over and you're batting 1.000 and management is batting 0.000 and they're making the same mistakes over and over. Plus when you bring up data and science and things are just ignored and covered up with threats and retaliation piled on top. Well that's when I began to change my mind and began to talk to congress. But even that wasn't enough for me make my opinions publicly known. It took truly believing that I was looking at intentional maiming and even murder.


  13. As for illegal actions.

    I was sent an e-mail by FDA management threatening me with a year in jail for speaking to congress. Even though that's explicitly allowed under the FD&CA as well as 5 USC 7211 and other laws. They even sent the same e-mail to the congressional staffers threatening them with a year in jail for receiving my petition.

    Finally when I said I was going to the FBI about racketeering activities among other things they fired me with the first reason given that I said I was going to the FBI. Excuse me isn't there something called witness tamperiing?

    Now I don't know about the validity of a lot of the things I read in the press, but I do have personal experience.


  14. Steve,

    My understanding as for the confidentiality is that it likely falls under the trade secrets act as that's what companies always quote on the front page of all drug submissions.

    However, I've also been told that the trade secrets act does not hold if it's being used to hide criminal activity. In fact I believe that was the justification that Alan Jones used for going public. Perhaps a lawyer who's reading this who's more familiar with the area can comment.


  15. Salmon,

    In your experience do you think that potential cures to some disease have been covered up? Or are we really not there yet? Is the public right to be cynical?

    Is there more an emphasis on making disease "drugable" rather than really treatable?

  16. Salmon,
    What role do see U.S. Pharmacopeia (USP) playing in the reorganization of FDA?

    Yesterday USP posted its recommendations to the new administration, here:
    Click on the "Press Releases" tab.

  17. Anonymous,

    Personally I have never seen a cure kept under wraps in favor of maintaining noncurative treatments. However as I've lived and seen more things nothing surprises me as to what people will do to make a buck. However I have seen companies with less desirable drugs knock better drugs. Plus I have seen companies with a treatment for a disease hold back on developing and marketing a better drug until they've milked everything they can out of the first on. Plus I've seen many development strategies that maximize profits that are not designed to maximize benefit. So if anything I would expect that the scenario of keeping a cure under wraps hypothetically could occur.

    As for confidentiality I personally have done my best to comment based only on information that's publicly available. Sometimes that information is hard to find and I've come across it serrendipitously. Plus I have enough experience to know how to read between the lines in regards to certain aspects about drugs.

  18. Nancy,

    I had not read the article on USP and FDA but thanks to your link I have.

    In general the various letters and proposals appear largely acceptable, and reasonable, and might be useful. However as with everything the devil is in the details. True USP does have metric expertise that Janet Woodcock has gutted at the Agency through starvations, and they can move faster than FDA in some ways. However companies also use USP to game the system submitting changes to standards when it will effect a generics approval at the last minute. Also sometimes USP standards are not really that up to date. For example companies come in and say all the time that the amount of drug in the tablet should only be +- 15% of labeled content because that's what the USP standard is. Well my opinion if you can't manufacture something generally to within +-2% (sometimes 5%) with current technology then you're totally out of control.

    USP has recently been involved in setting up the US diagnostic something to validate genetic tests prior to submission to FDA. It could be good or it may not be devils in the details.

    USP is run by Roger Williams. He was head of the Office of Pharmaceutical Sciences at FDA up until about 8-9 years ago. So he's a physican clinical pharmacologist who was overseeing the Chemistry and Manufacturing as well as generic drugs and clinical pharmacology. I believe Roger helped write the white paper suggesting the FDA's Office of Clinical Pharmacology pursue Question Based Reviews. Well that was useful as many people in clinical pharmacology were not trained to think clinically and it helped them. However it was abused so that now companies simply write their summaries like that and it allows the simply cut and pasting of misleading information, especially for the computer jocks.

    Roger got run out of the FDA. Knowing the person who instigated this I wouldn't be surprised if it was it was on trumped up allegations. In addition over the past 8 years there has been a wholesale gutting of oversight of manufacturing quality issues. So if the head of that group were standing in your way then you need to find a way to get rid of them. However all this is just idle wondering.

    All in all I think it would be useful for whoever comes in as commissioner to at least listen to what Roger has to say and see what the details are.

  19. Salmon, you raise some interesting questions.

    We have FDA employees who were forced out of their jobs for trying to ensure that safe and effective products were approved. FDA's track record seems to indicate that employees who were forced out of their jobs were the ones who should have been retained and rewarded. This leads to my first question: What types of employee behaviors are rewarded at FDA?

    My second question has to do with the oversight of manufacturing quality.

    The immediate-release formulation of Seroquel was approved in 1997. The approval documents are posted on the FDA Web site. According to Chemistry Review #2, the original formulation of Seroquel was not approved "because of lack of evidence of the stability for the tablets with a ___ coating. Zeneca plans to amend the NDA and propose the ___ coated tablets as the to-be-marketed formulation.

    Based on the information in Chemistry Review #3, what changes did AstraZeneca make to the tablet coating in order to meet the approval standards?

    Seroquel SR (sustained release) was not approved. FDA reportedly requested that AstraZeneca change the intagliation from "SR" to "XR" (extended release) during the approval process. I was unable to find on the FDA Web site the approval documents for Seroquel XR. Why was the intagliation changed? How do "sustained release" tablets differ from "extended release" tablets?


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