FDA Takes on Swine Flu “Cures” on Updated Webpage

May 31, 2009

FDA has been issuing warning letters to companies trying to cash in on concerns regarding the swine flu. And they are doing it on an updated website that is much more user friendly as far as researching older warning letters by year and by subject. And FDA is asking for email responses Within 48 Hoursinstead of the usual 15 days from the internet purveyors of dubious flu remedies. This is a definite change that I am a little surprised to see.

It is typical for people to try and make a fast buck whenever a new health issue concerns the public. FDA has traditionally sought to prevent magical mystery cures without any foundation in fact. So it is no surprise that FDA is on the lookout for companies on the internet trying to profit from people’s fears. To review the warning letters on FDA’s handy-dandy new website look for FDA Warning Letters under Important References on the right.


Is FDA infected with a “caution syndrome?”

May 23, 2009

The Food and Drug Administration is now looking forward to a new era with the appointment of Margaret Hamburg as Commissioner. Although just about everyone has greeted her arrival warmly, now we will see political pressure from, well, just about everyone. Although many people are familiar with the Vioxx story and the Coast IRB fiasco, there are those who feel quite strongly that FDA is getting too cautious in its approval of new drugs and that the caution stifles innovation. A good place to look at this viewpoint is at Forbes.com (not surprisingly). I am putting a link under “Interesting Articles” for ‘Caution Syndrome’ infects FDA by David Gratzer. There, you will find links to several other articles that, in the opinion of this Blog, are deregulatory in nature and not in the best interests of consumers. However, they are well thought out and not as strident as other discussions about the new administration. I urge you to take a look.

As you may have figure out by now, I have a different opinion. I believe that FDA has been far too lax in its enforcement of the regulations. However, complaints of overly bureaucratic, timid, I don’t want to do anything wrong regulators are sometimes justified. What we need to do, in addition to my comments below in my remarks on Dr. Hamburg’s confirmation, is demand that FDA have the same standards that FDA expects of industry. FDA should have not only professional reviewers and inspectors but highly trained and professional Managersto oversee their work. FDA needs clear regulations that make sense and can be enforced. The most obvious example to me are the GCP regulations that govern clinical trials.

These regulations are long overdue for updating. The clinical research industry (yes, it is an industry) has changed significantly since the 1970s when the regulations were first put into place. Many clinical trial vendors are not regulated at all. The regulations that are in place are vague and lack guidance documents to steer researchers in the right direction. Clinical trials have no requirement for quality assurance activities and quality control is poorly defined (‘monitoring’ is quality control).

Clear, updated regulations along with a professional FDA are what is needed for the development of new health products. More deregulation would be a step in the wrong direction. If you don’t believe me, walk to your medicine cabinet and pull out something that you use, for whatever reason. Can you look at your cholesterol medication, pain reliever, or allergy medication and determine where the ingredients came from? Do you know if they were ever tested for safetyand effectiveness just by looking at them? Can you tell if the dose is correct? Do you know if this a counterfeit drug? If you answered ‘no’ to any of those questions, then you understand why we need a strong, effective FDA.

You can read additional posts on FDA Commentaries here:



A new commissioner for FDA

May 21, 2009

The May 20th confirmation of Dr. Margaret Hamburg as the new Food and Drug Commissioner has been widely anticipated with strong support from many different sectors. A number of sworn enemies of each other are speaking highly of their hopes for a new day at FDA. Perhaps its appropriate to look at what took place during the “old days” at FDA.

When George W. Bush was inaugurated as President in 2001 the Food and Drug Commissioner was Dr. Jane Henney, a public health professional with a long career in academia and at FDA. She was not known for strong leadership, at least not among FDA field employees that I knew (I worked in the FDA field at the time), but she was credible and competent. There was also a Republican controlled Congress that opposed abortion rights for women and adamantly opposed approval of a drug known as RU-486. FDA under Henney took a long time to approve the drug, largely because of political pressure from anti-abortion activists. Finally, in September 2000, the drug was approved and anti-abortion groups continue to blame Henney to this day. When there was speculation in January that Barack Obama might appoint Henney to return as Commissioner one group had this to say:

“Washington, DC (LifeNews.com) — Leading pro-life advocates are not happy that incoming president Barack Obama is considering Jane Henney to become the next head of the Food and Drug Administration. Henney is a former FDA chief who oversaw the approval of the dangerous RU 486 abortion drug during the end of the Clinton administration.”

(Links referred to in this post have been retired, CA 21 SEP 11)

A link to the LifeNews article is on the right under “Dr. Hamburg & FDA Commissioners.” Henney submitted her resignation to Bush who immediately accepted it. However, there was a major problem. A potential commissioner nominee’s position on the approval of RU-486 would be a litmus test for the necessary Senate confirmation. It was going to be very difficult to have a new commissioner confirmed. This didn’t appear to concern President Bush who held off on appointing anyone and instead let Acting Principal Deputy Commissioner Bernard A. Schwetz, DVM, run the agency for a year. In the next seven years there were five Commissioners or Acting Commissioners of FDA, providing little continuity of leadership.

This is the first reason Dr. Hamburg is being greeted with such enthusiasm in some quarters. FDA Desperately needs strong, capable leadership. It also needs leadership that will be able to stand up to the multiple interest groups that all too often determine the Agency’s agenda. When I first joined FDA in 1987 we prided ourselves in being a “Science Based Agency.” That is just what we need, for FDA to make decisions based on science, not political pressure.

Although President Bush failed to appoint an FDA Commissioner after taking office he did appoint a new Chief Counsel, an appointment that didn’t require Senate confirmation, a gentleman named Daniel Troy. As a crusading pro-industry attorney Troy had taken FDA to the Supreme Court, and won, on behalf of free speech for tobacco companies. Troy would dramatically change how FDA regulated industry during his tenure and “Warning Letters,” the basic enforcement tool used by FDA plummeted. With weak leadership in the Commissioner’s office and Mr. Troy blocking enforcement of the regulations, morale at FDA sank and public health suffered.

And that is the second major reason people are hopeful that Dr. Hamburg will be an effective Commissioner. Her record as the New York City Health Commissioner and as the senior scientist for Nuclear Threat Initiative have given her solid credentials for leadership. People want the regulations for the safety of our food and drugs to be enforced. Between Vioxx and E. coli in spinach, there is a very real concern that FDA isn’t doing its job.

But why are so many different people from different interest groups happy to see her?If you look at the different links under Comments on Dr. Hamburg (to the right) you will see positive comments from the Center for Science in the Public Interest, a consumer advocacy organization, and PhRMA, the industry organization for Big Pharma. My suspicion is that EVERYONE knows that FDA is in trouble and they all want to influence the direction the Agency takes. Dr. Hamburg has genuine public health credentials, seems to be well liked, and was a shoo-in for confirmation from the start. So why not say nice things? I certainly wish her well. However, I also have a sense of which way the Agency should go:

1. The Agency should stop the politicalization of the past eight years. Drugs should be approved on the basis of science, not politics.

2. Congress should fully investigate whether there should be a single food safety organization and a separate health products safety organization. This is how it is done in much of the world and it is a very good idea here. (See previous posts)

3. The Agency should participate fully in international food and drug safety efforts. Congress should give guidelines from the International Conference on Harmonization the weight of regulations, not recommendations that industry can ignore. They should start with E6, the Combined Guidance on Good Clinical Practice and rejecting the Final Rule that broke with the Declaration of Helsinki in the months before the November presidential election.

4. The Agency should overhaul its inspectional force which is using a 100 year old model based on geography instead of technical expertise. This is particularly important for the management of the field organization, the Office of Regulatory Affairs. FDA’s field managers and field investigators should have the necessary expertise and training in an increasingly complex, globalized economy. FDA should use project management coordinating product reviewers, compliance officers and field inspectors. FDA inspections are rarely coordinated the way most people think.

5. Congress should abolish user fees that started with the Prescription Drug User Fee Act and independently finance FDA activities. Inspections and reviews should take place because there is a public health need, not a fee paid by a company requesting an FDA approval.

Finally, it is important to restore trust in public workers for the excellent work they do on behalf of all of us. Public workers perform work that we need as a society. Too many functions of government have been privatized and we have suffered for it. Professional service from career public servants is something to be commended, not disparaged. I’ll end with a quote from a civil servant in a different agency that sums up a lot:

“A strong civil service is the backbone of democracy. Civil servants sustain government function and institutional knowledge during and through the political transition that occurs when a new president is elected.”

Dr. Matthew C. Larsen
Associate Director for Water
U.S. Geological Survey

FDA clinical trial standards: Is there a serious problem with Phase III studies?

May 14, 2009

One of the first things I look at when I audit a clinical trial is whether or not the participants met the stringent inclusion/exclusion criteria required by the study’s protocol. An increasing number of Warning Letters that FDA writes to researchers is for violation of protocol requirements. Now, there is a well thought out explanation for why the stringent enrollment standards written in clear English by Dr. John M Grohol in the World of Psychiatry. I have put a link under Interesting Articles on the right (Phase III Trials).

Dr. Grohol maintains that trials are designed to exclude the majority of people who might use the drug after approval in part because the stringent criteria will make FDA approval easier by selecting participants where the drug will prove to be effective. I’m an inspector, not a research scientist so I can’t tell you if he is right. But he does have a pretty good argument worth reading. On the other hand, year after year FDA cites researchers for recruiting ineligible subjects. Why would drug companies write protocols their researchers can’t follow?

FDA has come in for some serious criticism because it insists on placebo controlled clinical trials as their “gold standard.” It seems to me that if we are going to have effective reform for health care, then we should take a long close look at how we design clinical trials and decide which drugs are approved for which indications. Just a suggestion.


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The Blog enters the world of movie reviews

May 11, 2009

When you are the author of an internationally famous Blog on FDA Stuff and you’ve had over 200 hits the past week, you know its time to take on Hollywood. I just saw Duplicity with Clive Owens and Julia Roberts at the Blue Mouse, the last single screen theater in the Northwest. Movies only play at the Blue Mouse after they’ve played everywhere else they possibly could. So if you want to see Duplicity you will probably have to wait to rent it.

When I first began working at FDA (a former employer), I answered the phone at the San Francisco District’s Consumer Affairs Office. One of my first calls was about a drug, now widely available, that would grow peach fuzz where men had grown bald. “When is it going to be approved?” the caller asked desperately. I soon learned that cures for baldness, along with weight loss gimmicks and impotence potions were very big business.

Which leads us to Duplicity. At first I thought it had been written by a computer geek obsessed with Part 11 of the FDA regulations on computerized records. There is a lot of security system hocus pocus that is pretty cool. Then, about three quarters through the movie, the plot thickens, so to speak. Anyway, when you want a fun, lightweight movie to rent, please consider Duplicity. It’s about industrial espionage and products that go bang in the night. Without FDA approval, I might add. I’ve added a link to the Duplicity website under the Blogroll. Have fun.

The Swine Flu and FDA Politics

May 5, 2009

Believe it or not, the recent outbreak of H1N1 influenza is hitting the FDA senate confirmation process moving the hearings up a week, The confirmation is a priority of Senator Edward Kennedy and the Good Lord only knows that FDA could use some leadership. Read what the Wall Street Journal has to say in Interesting Articles.

Hopefully we won’t have a repeat of the flu vaccine disaster of a few years ago. The Atlanta Jounal Constitution reports the flu is spreading, although not as bad as though. See interesting articles

UPDATE: Here is an interesting selection from the Huffington Post on H1N1, Tamiflu, and the FDA entitled “Swine Flu or FDA: Which is more dangerous to your health?” Find it in interesting articles under “Swine Flu & FDA”

Compliance with FDA requirements on annual reports

May 3, 2009

One of the most overlooked requirements by FDA is for the clinical investigator to complete a final report to the sponsor after the completion of a clinical trial. I think that having a short final report helps a clinical investigator in preparing for an FDA inspection. After all, some inspections take place Years after the study is complete. You can find the requirement in 21 CFR 312.64 where it says:

(c) Final report. An investigator shall provide the sponsor with an adequate report shortly after completion of the investigator’s participation in the investigation.

I am offering a humble contribution to this issue in the following document. It is NOT an FDA document but everything in it was taken from different parts of the FDA website.


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SQA Annual Meeting Wrap-Up

May 3, 2009

The 25th Annual Meeting of the Society for Quality Assurance finished on the 23rd of April, so much for live blogging, with an interesting array of speakers from the U.S. Food & Drug Administration, Health Canada, & the Environmental Protection Agency along with QA professionals from academia, industry, and independent souls such as myself. Here are some of the highlights:

The British MHRA (the counterpart of FDA in the UK) is conducting more inspections in the United States. They are interested in how a sponsor manages clinical trial vendor and what the contracts look like.

FDA is working on re-writing the Compliance Program Policy Manuals for both Sponsor/CRO/Monitor inspections and Institutional Review Boards (IRBs). This is particularly important for IRBs since the CPGM has been outdated since 1997, 12 years ago. The CPGM is the document that FDA field investigators use to conduct an inspection and is Must Reading for everyone concerned with FDA inspections. There is a link to the IRB CPGM on the references section to the right.

FDA also presented at a panel on Part 11 (electronic records, electronic signatures). I found that I left the session more confused than when I went in. I will put two guidance documents on the reference section to the right. One is the “Scope and Application” document which the FDA representative said was more important than most guidance documents because it is “interpreting regulations” not just offering FDA’s current thinking, which is how guidance documents are usually described. The other document is “Computerized Systems Used in Clinical investigations” which offers helpful definitions and guidance on SOPs. I am still not sure what the FDA position on hospital or medical center electronic medical records (EMRs) is. If anyone out there has info they wish to share on EMRs, I certainly would appreciate it.

I enjoyed sessions by QA professionals. One interesting suggestion was to create a “story board” for lengthy clinical trials, so the changes can survive SOP changes, protocol amendments and staff turnover. Another interesting suggestion was to give a slide presentation to the Vendor during a qualification audit and not just listen to the vendor’s dog and pony show. Letting the vendor know what your needs are can facilitate a smooth audit and direct it in the appropriate direction.

The one thing I felt was lacking was an overall analysis of what is happening with drug and medical device safety at FDA these days. There are a lot of things going on and it would have been nice to hear a discussion of what is in store. I’m certainly curious.

Finally, I am attaching an article about the Declaration of Helsinki and FDA. I had referenced it in one of my first posts and forgot to put it in. My own viewpoints have changed a little since it came out last year but Gerd Fortwengel, the principal author, did a great job of describing the changes to FDA regulations.


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