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Steven K. Galson, MD, MPH

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Close the FDA Approval Gap

Posted: 07/15/10 04:01 PM ET

The extensive review this week by a panel assembled by the Food and Drug Administration of the diabetes drug Avandia highlights the critical importance of government regulation and oversight of the drug industry.

Questions have been raised about the safety of Avandia since 2007, and a process to assess these risks versus patient benefits was undertaken by the objective professionals at FDA. But one important question underscores all such inquiry: What happens when the drug safety cop is taken off the beat?

Even though our system of pharmaceutical review and approval is regarded as the most effective in the world, there exists an incredible -- and potentially deadly -- loophole: unapproved drugs.

Recent news stories regarding the recall of 1,500 lots of Johnson & Johnson's children's and infants' Tylenol, Motrin, Zyrtec and Benadryl due to bacterial contamination, and the subsequent suspension of the their manufacture, reinforce the importance of the US Food and Drug Administration's (FDA) regulatory oversight over drug products--even years after they have been approved for sale. But due in large part to grandfather provisions going back 50 years, unapproved drugs - those that have been marketed prior to the establishment of today's FDA - are actively promoted, prescribed and taken by millions of patients in the U.S. These drugs escape FDA scrutiny otherwise imposed for all approved prescription and over-the-counter medications.

Most alarming is the fact that unapproved drugs account for nearly 72 million prescriptions per year. Unapproved drugs lack the specific quality controls of an FDA-approved drug, including manufacturing oversight that ensures the appropriate amount of active drug in each tablet, the purity of ingredients and consistency from dose-to-dose. And perhaps equally troubling is the fact that - unlike every other medication available for human consumption in the United States - unapproved drugs are not required to be accompanied by dosing information supported by human clinical studies.

The consequences of this approval gap can be tragic. Hundreds of deaths have been linked to the more than 500 unapproved drugs that FDA eventually banned. Yet to this day dozens of unapproved drugs are marketed under the regulatory radar. As recently as this past March, FDA took action against manufacturers of unapproved sublingual nitroglycerin tablets for treating certain heart conditions. FDA stated that it had seen "significant quality and efficacy problems" with unapproved nitroglycerin products and, as a result, recalled them from the market. Meanwhile, an FDA approved version had been available for years right alongside the unapproved, unregulated, and we now know, unsafe versions.

And the front-line gatekeepers of the nation's prescription drug delivery system--America's pharmacists--are themselves largely unaware of this dual standard for safety among the products on their shelves. A 2006 nationwide study of 500 pharmacists found that 91% of them incorrectly assumed that all of the products they dispense are FDA-approved.

They should be approved, of course. That's why in June of 2006, when I was head of the FDA's Center for Drug Evaluation and Research, we launched an initiative to finally address unapproved drugs. The Agency issued a Compliance Policy Guide (CPG) to review the safety and efficacy of unapproved drugs that continue to be available, in an attempt to bring these products into the modern world of drug safety with clinical, regulatory and manufacturing oversight.

Certain medications that have never undergone FDA evaluation should continue to be available for patients--when no substitute exists--so long as there are no known safety concerns. Many patients simply have no alternative treatment. But as soon as an approved version becomes available, FDA needs to act immediately and enforce its policies by withdrawing all unapproved formulations from the market. Regulatory oversight alerted us all to the risks associated with certain products manufactured by J&J. If no one is watching, how can we be sure it will never happen again?

 
 
 
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10:53 AM on 07/19/2010
As founder and president of Legitscript, a service that monitors the online sale of prescription drugs, I concur with Galson’s premise: that the availability of unapproved drugs is a significant issue. LegitScript works hard to identify pharmacies that sell unregulated pharmaceutical products (including unapproved drugs), which have been associated with the deaths of hundreds of patients over the years. As Galson notes, it is important not only for patients to be aware of this, but pharmacists as well.

The problem goes well beyond the Internet. In his article (Close the FDA Approval Gap), Galson reports a key fact: that “unapproved drugs account for nearly 72 million prescriptions per year.” This illustrates the fact that the dispensing of unapproved prescription drugs is not merely an occasional oversight.

Galson, who played a key role in the 2006 launch of the FDA’s “Unapproved Drugs Initiative”, which is meant to better protect American patients from unapproved drugs, correctly states that the “FDA needs to act immediately and enforce its policies by withdrawing all unapproved formulations from the market” as soon as approved versions become available if this problem is to be fixed.

Galson has the right idea. It is likewise important to note that this problem cannot be solved without leadership from the FDA. Patient advocates, pharmacists and pharmacies alike should welcome a renewed commitment from the FDA to educate patients and pharmacists about unapproved drugs, and to enforce the nation’s drug safety laws accordingly.
10:55 PM on 07/18/2010
I've posted several comments critical of the criminal FDA and Mr. Galson and nothing is going through. I'm pretty certain I'm not the only one.
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HUFFPOST SUPER USER
vippy
Carpe Diem!
08:41 PM on 07/18/2010
It is a joke saying the FDA is the best in the world. No one else has so many recalls as we have.
Pure greed on the part of our corporations sanctioned by our FDA. FDA is not our friend!
10:23 PM on 07/16/2010
I'd love to see research into some of the widely used herbal medications like black cohosh, which women take for menopause-related symptoms - all with no evidence that it works, or what other
harm it might be causing.
11:13 PM on 07/18/2010
If your biggest concern is a natural herb that's been used for eons than I'd bet you're a Big Pharma blogger.
09:00 PM on 07/16/2010
Is it safe to say that if a drug-maker truthfully acknowledges all of a new drug's potential side-effects, and the FDA approves that drug, that that drug-maker is protected from lawsuits which might be brought when one of those side-effects produces a serious, even fatal reaction? Does that make any sense?
When a patient buys and consumes a drug, is he saying that he knows it might kill him but it might not and therefore he accepts any consequence effected by that drug? Does that make any sense?
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Sammi Hologram
01:57 PM on 07/16/2010
Always enjoyable to read ambiguous propaganda aimed at outlawing vitamins (with the ultimate objective of having the exact same vitamins magically re-materialize as prescription "drugs").

Not convinced? visit the official fda.gov website and read why red yeast rice (a simple, inexpensive grain that is the source of lovastatin) is now illegal and Mevacor (whose active ingredient is lovastatin) is now available exclusively via prescription - here it is in black and white from the FDA's site:

http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2007/ucm108962.htm
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maveet
AussieByChoice
03:16 AM on 07/18/2010
Thank You. FDA is anything but unbiased and uninvolved in keeping us from getting the very basic and fundamental building blocks: vitamins, minerals, lipids, things such as this yeast, or black cohosh mentioned above, or on and on. FDA and CDC are NOT neutral bodies working on our behalf. CDC, in part, acts to keep certain conditions, like ME/CFS, lost in a miasma of conflicting and confusing criteria. This serves its Public Health mandate, by keeping the huge extent of the endemic problem invisibile, and Pharma, by allowing the so-called "cure" or management of said conditions, to be recommended pharmaceuticals. Thus, the recommended treatment for ME/CFS, proven to be a neurological problem, are SSRI's and Anti-inflammatories. See...we can cure you. Bah! In my case, both those drugs crashed my system prior to the ultimate collapse. And experts in the field know that the protocols which work at all tend to be the basics: Vits, minerals, lipids, and a variety of others.

FDA, CDC: think MMS and its relationships to Big Oil.
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maveet
AussieByChoice
03:47 AM on 07/18/2010
The Committee for Justice and Recognition of Myalgic Encephalomyelitis
http://c4jrme.110mb.com/
The History, Science and Politics Affecting Patients Disabled by M.E. around The Globe.
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Rubyfoo
01:54 PM on 07/16/2010
If you want a medical scandal, look at the one where a drug approved by the FDA for one disease can be prescribed by doctors for anything they like. Yes, that diabetes drug can be prescribed for shingles if a pharmaceutical company can pay a medical opinion leader to put their name on a research paper supporting that use, most likely written by an ad agency.
09:01 AM on 07/16/2010
Dear God in heaven, when will we ever abandon this worthless, dangerous drug paradigm?! Drugs are almost totally unnessesary and usually cause more harm than good. Naturual medicine nearly always offers a nutritional remedy for disease when allopaths cry "there's nothing we can do". Well, in a sense they are right. There is nothing they can do with their pititful drugs. Mask a symptom until you die? That's about all. "Here, let us manage your disease. No reason to actually get rid of it. We wouldn't make any money that way". The Medical Mafia, get rid of it.
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tegraphile
09:45 AM on 07/16/2010
Please tell me how you propose to cure Type 1 diabetes. I'm very interested to see how natural medicine will solve what years of research has not.
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A Scientist
Progressive from the south, yes we do exist!
10:25 AM on 07/16/2010
Good point. Perhaps Conk would also like to inform us how exactly to treat chronic rheumatoid arthritis as well. I'm pretty sure those suffering from this debilitating condition appreciate having their symptoms "masked" with COX-2 selective inhibitors.
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07:44 AM on 07/16/2010
Abolish the FDA.
02:31 AM on 07/16/2010
I'm with Dylan Ratigan, those who work in regulatory bodies, can not take jobs in the industry they regulate, or be a lobbyist for 7 years after they work in that regulatory agency.

This is the only way to end the corporate corruption.

I would go for 20 years, but Dylan's suggestion of 7 years over 2 is an improvement to end corruption in regulatory agencies.
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Geauterre
Writer, Author, Commentator and Humorist.
01:14 AM on 07/16/2010
Why are Europeans, English, Canadians, French, Italians, Germans, Netherlands, Norwegians, Swedish, etc., etc., etc., so far better off when it comes to their versions of drug, medical device and technological advancements oversight? The answer is simple. They don't play games with corrupt robber barons. We're the ones who are at the forefront of that sort of nonsense, and then we have the gall to claim credit for following up in correcting the disasters we usher in. The only hope we have to diminish this sort of criminal aptitude is through a universal health care, which uses stem cell and genetic therapies. And is that happening? Yes, to a degree . . . so slowly, as those who have so much to gain fight against it every inch of the way!
02:20 AM on 07/16/2010
yes, all our writers say we have the best of everything in the world, but other places are happy , healthy, people feel fine. And never lose the house to illness.
What are we paying so much for.
Good service?
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thinkagain2
10:31 AM on 07/18/2010
we pay for nice packaging and advertising.
12:53 AM on 07/16/2010
Now I know it is Dr. Galson that will be the cause of my becoming disabled when I can no longer obtain the 100 year old drug I need to function. Instead I will have to take the newer "approved" drug that makes my condition worse than taking nothing at all. But that will be okay since I will be sicker, I can be given more new drugs which is much more profitable for the pharmaceutical industry. Of course the manufacturer of the unapproved drug will have the opportunity to spend hundreds of millions of dollars to go through a new drug application process for a drug that doesn't have a high profit margin and won't be able to be patented because it has already been on the market for 100 years. At this point the manufacturer could make the unsurprising business decision that going through a new drug application process is not cost effective. I will become disabled from a very treatable condition so that instead of working a full-time job like I do now and contribution to the social security fund I can apply for disability benefits instead. The pharmaceutical companies can get richer and the social security fund will lose.
02:21 AM on 07/16/2010
now the bill passed and the vultures arrive
didn't Pelosi say we have to pass it to find out?
05:22 AM on 07/16/2010
As a retired pharmacist, I find the insinuation that American pharmacists are unaware of FDA approval status of drugs they dispense does nothing to clarify this issue, since many physicians prescribe medications for conditions that they are not indicated for; shall we imply that physicians are at fault as well? Take gabapentin for example, which was approved for prevention of convulsions but marketed for pain management, although no efficacy or safety studies were done, only anecdotal reports.

According to the NEJM, the price of an old unapproved medication for gout, colchicine, went up a hundred-fold when an "approved" version was given the blessing by the FDA, although no studies were needed to verify the safety or efficacy of the old line medication. The same applies to quinine, which is now also priced a hundred times its price now that it has been reviewed for safety and efficacy. This is a new trick that the FDA, bought and owned by Big Pharma, has learned. Required new testing for old line pharmaceutical remedies, and then manufacturing monopolies charge for the "new, approved" version, which used to cost pennies, several dollars per pill, is the latest scheme that drug companies use to maximize profits..
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Annoula
Enough about me!
01:57 PM on 07/16/2010
"Take gabapentin for example, which was approved for prevention of convulsions but marketed for pain management, although no efficacy or safety studies were done, only anecdotal reports."
Dear colleague:
As you probably know, the practice of what you describe is known as "off-label prescribing". When in the course of his practice, a physician observes that an approved drug has collateral actions, the doctor can still prescribe the drug for that use, even though that is not the indication for which it was developed. Minoxidil, as you probably know, was initially developed to treat hypertension but soon it was seen that it also stimulated hair growth [eventually, after the due trials were conducted it gained, FDA approval for that use and now it is sold as a lotion OTC]. Off label prescribing of a drug is not illegal as long as the dose prescribed is not toxic. Off label marketing, in contrast, is illegal because as you say, is not based on rigurous clinical trials but on mere observations made by physicians in their practice.
12:37 AM on 07/16/2010
As a future pharmacist, I can say that I know that many of the drugs I work with on a daily basis are desi drugs--drugs that were grandfathered into the system. However, insinuating that pharmacists do not know what they dispense is disingenuous. Five-hundred pharmacists barely scratch the surface, and using a statistic that is not powered well enough to characterize all of us perpetuates the image that we're on Big Pharma's payroll.
02:23 AM on 07/16/2010
fan and fave!
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NABNYC
10:57 PM on 07/15/2010
The right-wing and their supporters on the supreme court have been pushing the idea of complete immunity from liability for anyone in the drug business. Here's how it works (as explained in the Roberts dissent in the 2009 Wyeth decision): they argue that if the FDA approves a drug, then no matter how many people die from using that drug, the drug company is immune from liability. They can just say: Well, the FDA approved it, end of story. Now it appears the drug companies want to get the FDA to approve everything they sell. Why not? Immunity from liability is very valuable. With the Citizens United decisions, everyone in government can receive money from corporations who want to buy an outcome. You know, those bribes corporations pay to government employees -- what Roberts call "speech."
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aspiecelia