There are a lot of open questions about the influenza antiviral drug oseltamivir ("Tamiflu"), among them whether it works at all for bird flu (highly pathogenic influenza A/H5N1), and if it does, whether resistance will develop making it ineffective. But all the questions have a common assumption: that the patient is actually taking Tamiflu. How would you know if you were or not? Because the bottle says so? Not necessarily. In December 2005 U.S. Customs and Border Protection (CBP) Officers seized 51 shipments they said were counterfeit Tamiflu pills at their air mail facility in San Francisco. These were ordered by individuals over the internet and each had a treatment course of 10 to 15 pills. I'm not sure how it was determined these were counterfeit, but it is obvious this could happen if demand skyrockets during a pandemic or incipient pandemic. It would be nice to have a quick test to see if the pills actually contain any active ingredient. A paper just published by CDC scientists in Emerging Infectious Diseases presents what seems to be a simple and accurate test that can be done in the field.
The test uses a common dye, Congo Red which forms a complex with a protonated amine group on oseltamivir phosphate, the pro-drug that is in purchased Tamiflu tablets. The drug is quite soluble and under the right acidity a colored complex is formed with Congo Red dye. They describe in detail in their paper how to perform the test and show that it is accurate and repeatable compared to a more sophisticated laboratory method (High Performance Liquid Chromatography, HPLC). It is also quite selective, not being confused by other common drugs such as cipro, Tylenol, ampicillin, antimalarials and many others. Now what about testing it against Tamiflu purchased over the internet?
We conducted a search for Tamiflu products on the Internet using the keywords "Tamiflu," "prescription," and "cheap or inexpensive." Approximately 40 online sources were compiled and sorted according to price. We acquired the 6 cheapest products that did not require a prescription and tested for active ingredient by using both colorimetric methods and HPLC. All the products were in capsule form and allegedly contained 75 mg of oseltamivir base (98.5 mg oseltamivir phosphate) as described in the package insert. (Green MD, Nettey H, Wirtz RA. Determination of oseltamivir quality by colorimetric and liquid chromatographic methods. Emerg Infect Dis. 2008 Apr; [Epub ahead of print])
No scandal this time. All six batches tested had active ingredient within 15% of label amounts stated on the label and most were within 10%. So the stuff was real, not counterfeit. More importantly, the developing world now has an effective and inexpensive tool for detecting counterfeit Tamiflu in the field.
Dealing with influenza on a global scale is complicated and has a lot of moving parts. This is just one of them. But it's now a solvable problem, one less than we had a year ago. We're grateful for small things, too.
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Hmm, the main news interest here would seem to me to be that these 6 cheapest no-prescription products actually did contain active ingredient - I had assumed that most or all of these would be cons. Were I either a little bit less pathologically law-abiding, or a little more confident that Tamiflu would actually work by the time a pandemic reached me, I'd get my credit card out... I wonder just how much of the "counterfeit drugs" propaganda is just that, designed to put people like me off buying it?
now, who sells the test-kits ?
1g Congo Red for ~$1, I found
and why didn't they tell us earlier ?
(in 2005, when there was a run on Tamiflu)
Mathematician: I agree that is an interesting nugget of news in this paper, and, like you, I was surprised. But the method is also of interest, perhaps equally so. To see this, assume for a moment that the only way to do this required expensive equipment and skilled personnel. We would be in a different position.
anon: No one sells the kit but now the method is out there. It doesn't look to difficult from the description. Why don't you make a kit and sell it?
A question: what do the Reveres think about employers stockpiling Tamiflu for their employees? HHS is thinking about issuing a new guidance to business on that. Good idea? Bad idea?
The pharmaceutical industry in the US engages in a lot of fear mongering to protect their patented products. Too bad the entertainment industry can't do the same. They could claim that if you download a pirated copy of the latest Britney Spears album it wouldn't be Britney singing (but I digress). Do you remember last year when Governer of Califoria Arnold Schwarzenegor wanted to buy pharmaceuticals from Canada? He could save the state of California 40-50%. However the FDA argued that he couldn't because Canadian pharmaceuticals were not FDA approved and therefore were unsafe. Since Canadian pharmaceuticals are made on the exact same assembly lines at the exact same factories as US pharmaceuticlas you have to wonder how they thought anyone would believe them. To make matters worse you have the FDA acting as a proxy agent for big pharma. They are supposed to be working for US consumers. Its doubtful that they will make a statement confirming the efficacy of imported Tamiflu. What is even worse is that there is a Tamiflu factory in Bangledesh that makes non-FDA approved generic Tamiflu. If the pandemic arrives in the US and there isn't enough Tamiflu to go around the FDA does not have any plans to allow the importation on non-FDA approved Tamiflu even if it would save lives.
rob: Much depends on if there is enough Tamiflu to go around (else big companies will use more than their fair share) and how the distribution program for employees is implemented. Will there be adequate guidance on how to use, when to use, adverse reactions, for whom to use, who will get [everyoe?] or will there be certain subgroups to get first, etc.
Greg: Yes, we've covered this aspect here quite a few times. FDA doesn't check China quality when Big Pharma buys it to put and sell in their drugs (at extra profit) but won't allow the very same drugs as in the US to be imported from Canada. Disgrace.
Rob and Revere,
Not surprisingly, Roche has developed employee education templates, and has distributed Tamiflu directly to employees who go through the steps outlined in the template.
You can read about it at http://tinyurl.com/2cve5n , part of Roche's pandemictoolkit.com site.
(Conflict of interest disclaimer: I have never worked or consulted for Roche or any other pharmaceutical company, nor do I own any of their stock.)
My only problem with this is the "fair share" thing. If the pandemic isnt here and they are allowed to stockpile it, why shouldnt they? Fair share is defined by whom?
Lets face it, Rummy the Rich is going to get richer and they have a product thats for sale and it may or may not work anyway. So if it keeps you alive then its good stuff? So far no one can point to Tamiflu and say it kept me alive as best I can determine.
Counterfeit? Order the stuff yourself thru your pharmacy and pay the price. I have and its not cheap but I have enough now for all my employees and their families to take two passes at the pandemic. I figured two waves and by then taken as a prophylactic we would be just about done anyway.
Too bad the entertainment industry can't do the same. They could claim that if you download a pirated copy of the latest Britney Spears album it wouldn't be Britney singing (but I digress).
That'd backfire--it would make me MORE likely to get a Britney album!
A question: what do the Reveres think about employers stockpiling Tamiflu for their employees? HHS is thinking about issuing a new guidance to business on that. Good idea? Bad idea?
Really? And would your Congo Red dye not also "confirm" as authentic a product containing only, say, 1% of the real stuff??