The last time I checked, “terrorism” was defined, more or less, as the unlawful use of violence to achieve a political objective. So it is silly to describe drug counterfeiting as “international health care terrorism” (see “Flipping the Bird,” below).

Counterfeiting is a crime, certainly, but a crime most likely motivated by economics and not politics. For this reason, it is also important to distinguish between the deliberate sale of substandard product and inadvertent contamination or production problems. The former will never be amenable to inspections and standards. The latter may be.

Yesterday, the FDA issued a press release about the recall of two lots of antibiotic:

[The company] Medicis today announced that it is voluntarily recalling two lots of the antibiotic SOLODYN® (minocycline HCl, USP) Extended Release Tablets. Medicis has received a report that one bottle contains AZASAN® (azathioprine tablets) instead of SOLODYN® … AZASAN® is an immuno-suppressive agent used in transplant patients to prevent kidney rejection and for the treatment of rheumatoid arthritis.

Whether this happened in China or in a US plant, it just ain’t terrorism. It isn’t counterfeiting either.  Let’s maintain the useful distinction.

On Friday I offered “public comment” to the concept of placing a 1-800 number is all DTC television ads.  While to many this idea sounds like a no-brainer — it ain’t so easy.  Some things to consider:

* The use of the terms “adverse event” and “side effect” being used inter-changeably.  Just what do consumers think they mean?  The committee seemed to think that the FDA should look into this.

* How can poly-pharmacy patients report an adverse event when they can’t be sure what’s caused it?

* Will an 800 number (presented via a super, audio, or both) cause a “power of suggestion” situation, thus producing a kind of adverse event “placebo effect.”

These general themes led the committee to worry (and rightfully so) that information reported via an 800 number would likely provide the FDA with data of questionable quality and utility.  A serious “signal-to-noise” issue. Of particular worry was how the FDA would then use this information relative to communicating “early safety signals.”  Talk about unintended consequences!

A post below raises the prospect that discussion of prescription drug counterfeiting might be “just another scare tactic of Big Pharma.”  That could be true, if such a discussion served mainly as a trojan horse argument against the reimportation of medicines from countries with highly developed health systems. Readers can make up their own minds whether that’s what is going on here.

But ask yourself this. If you were an uninsured patient unable to afford medication in the US, would you rather get your prescription filled in a Canadian pharmacy or go without? Me too.

And, as long as we are talking about scare tactics, I’m sure it won’t escape anyone’s notice that this blog is sponsored by a company that is in the business of supply chain management and product security.

That isn’t to say there aren’t real issues. Phony drugs in the developing world are a big problem. And as the US supply chain moves increasingly to some of these same countries, Americans, too, should be concerned. But they should also be wary of anyone who benefits from ginning up a drug scare.

Focusing on prescription drug counterfeiting as international health care terrorism is often trivialized by pols and pundits as “just another scare tactic of Big Pharma.” That argument has never held up under the facts (stubborn things those facts) — and here’s a new truth that should further force those who deny the threat of counterfeits to reconsider their position — efforts to control the spread of bird flu in poultry in Southeast Asia are being hampered by the use of ineffective and often fake agricultural vaccines. This according to Robert Webster, a British virologist, animal flu specialist, and director of the World Health Organization’s Collaborating Centre for Studies on the Ecology of Influenza in Animals and Birds. As a result the threat of the virus evolving and being able to pass to humans, triggering a potentially catastrophic pandemic grows. It’s time to wake up and address prescription drug counterfeiting as what it is — international health care terrorism.

Peter Pitt asks “Where are all the dead bodies?” in a recent post to this blog. “Have you noticed that folks in Washington, DC have stopped asking this question?” says Pitt.

Pitts has misquoted Minnesota Gov. Tim Pawlenty (a Republican) who testified before Congress in support of the re-importation of Rx drugs from Canada. In response to PhRMA’s and FDA’s criticism of re-importation as “unsafe,” Pawlenty said “My first response to that is show me the dead Canadians. Where are the dead Canadians?”

Now that re-importation of FDA-approved drugs from Canada is no longer an issue, Pitts’ focus is on the real danger: adulterated counterfeit drugs. He cited recent revelations about the possible deliberate adulteration of heparin somewhere along the supply chain, possibly in an effort to reap extra profits the same way cocaine dealers do it — by bulking up product with supposedly inactive ingredients. In the heparin case, however, the “inactive ingredient” may have been responsible for causing 81 deaths — and counting!

I say “and counting” because the FDA’s warnings about and recalls of heparin are going unheeded at many hospitals that have stocks of the product. Could it be that protecting “profit” is on their minds as well? Heparin, after all, has been a very good money maker for the health industry — including physicians and hospitals.

On top of all this we now hear that Baxter International has been accused of failing to co-operate with Chinese authorities trying to investigate the alleged heparin contamination. Baxter, in turn, points the finger at the FDA for failing to inspect the Chinese plant at the center of this brouhaha.

It seems no one wants to say “the buck stops here, we are responsible.” IMHO, if the drug industry is going overseas to produce 80% of the ingredients in our drugs, then THEY are ultimately responsible for the supply chain that THEY set up. After all, the FDA didn’t tell them to do it!

Have you noticed that folks in Washington, DC have stopped asking this question?

The Lancet 2008; 371:1551
DOI:10.1016/S0140-6736(08)60663-7

Editorial

Combating counterfeit drugs

Last week, the US Food and Drug Administration (FDA) told a Congressional hearing that it believes a contaminant found in batches of heparin, which have killed at least 81 patients, might have been deliberately added. The source of the contaminant—oversulfated chondroitin sulphate—has been traced back to a Chinese supplier of drug manufacturer Baxter International. Why the stocks might have been intentionally contaminated is unclear, but the fact that oversulfated chondroitin sulphate is structurally similar to heparin but about 100 times cheaper, raises the very real possibility that it could have been added by counterfeiters.

If counterfeiting is behind the heparin case, it would not be that surprising; trends indicate that counterfeit medicines, defined by WHO as drugs that have “been deliberately and fraudulently mislabelled with respect to identity and/or source”, are a growing, global problem. The FDA alone has seen an 800% increase in the number of new counterfeit cases between 2000 and 2006. In developing countries, where drug regulatory systems can be weak or non-existent, around 10–30% of medicines might be counterfeit. Antimalarials have been a particular target for counterfeiters, and fakes have flooded the market in many Asian countries.

The substances used to adulterate medicines can vary from chalk, to antibiotics, to highly lethal substances that cause alarming spikes in mortality rates. Subtherapeutic levels of the genuine medicine, such as an antimalarial, can also lead to death or the development of fatal drug resistance. But these deaths, mainly in developing countries, are largely hidden in public-health statistics.

This situation is only likely to worsen as counterfeit drugs are becoming more difficult to combat. Criminals are using more sophisticated techniques to bypass standard laboratory testing such as the addition of cheaper substances that mimic genuine drugs. Holograms on drug packaging, designed to make counterfeiting more difficult, are also being copied with increasing accuracy making boxes of fake products hard to detect by the human eye. These deceptive measures have unfortunately led to a booming, lucrative trade. The Center for Medicine and the Public Interest estimates the sales of counterfeit drugs will reach US$75 billion in 2010. So what is being done to address the problem?

At the international level, the World Health Assembly adopted a resolution against counterfeit and substandard drugs in 1988, and at the end of 2006, the International Medical Products Anti-Counterfeiting Taskforce (IMPACT) was set up by WHO to mobilise action. However, despite these moves, few concrete steps have been taken by countries and political will to adopt anti-counterfeiting measures is lacking.

Most WHO member states are doing a poor job of reporting counterfeiting cases. Incredibly, between 2002 and 2004, WHO received no reports of counterfeit drugs. In many countries, counterfeiting medicines is not even considered a crime and when it is, the penalties for those found guilty often do not tally with the severity of the action. For example, in the UK, the prison sentence and fine for counterfeiting a T-shirt with a trademarked logo can be greater than for counterfeiting a medicine. Tougher prison sentences and heftier fines need to be introduced by governments to deter counterfeiters.

Countries must also strengthen their ability to regulate the drug supply. According to WHO, only 20% of its member states have well-developed drug regulatory systems, and around 30% have no or weak drug regulation. Twinning food and drug authorities in rich countries with ones in resource-poor countries might help nations that are struggling to regulate the market. Drug authorities also need to work effectively with customs, the police, scientists, health workers, WHO, and INTERPOL. This type of collaborative approach has proved successful in tackling counterfeit antimalarials in southeast Asia.

The pharmaceutical industry also has its part to play. It should be legally required to report suspected cases of counterfeiting to the relevant national drug authority—a practice which is currently voluntary. Companies must also be encouraged to lower the prices of their products in developing countries to reduce the economic incentive for counterfeiters.

There is no magic bullet to deal with counterfeit medicines. Countries need to adopt multipronged, multidicisplinary approaches to combat the problem. WHO and donor countries should provide support to developing nations to strengthen their drug regulatory systems. But individual governmental commitment to this goal is essential. Without it, public safety will continue to be compromised.

We don’t know the prevalence of counterfeit or substandard drugs (more on the distinction in a later post). The recent deaths caused by the Baxter brand of heparin illustrate the potential risks of adulterated product. But is that case the tip of the iceberg or an exception to the rule… the rule of a safe, well-controlled supply chain?

The high rates of counterfeit pharmaceuticals in developing countries have been well documented. Phony anti-malarials alone undoubtedly cause untold deaths. But a widely cited estimate that the counterfeit industry will be worth $75 billion by 2010 comes from a report by the Center for Medicines in the Public Interest. The report (which CMPI was kind enough to send) provides little information on how this extrapolation was derived, other than to say it was based on the “author’s calculations.” Nor does break down the number between wealthy countries with well-controlled drug supplies and countries with endemic counterfeiting and poor health infrastructure. So what is the situation in the US and similar nations? The authors of a PLoS Medicine article suggest that pharmaceutical manufacturers in the US and the UK deliberately fail to report incidences of counterfeiting. As a first step toward understanding the extent of this problem, an international and publicly accessible registry should be established to track counterfeit products. Governments should mandate that industry report all known or suspected cases.

The growing threat posed by dangerous fake drugs has been highlighted by a leading medical journal.Between 2000 and 2006 the US Food and Drug Administration (FDA) saw an eight-fold increase in the number of new counterfeit cases, said The Lancet.

In developing countries with weak regulatory systems, around 10% - 30% of medicines might be counterfeit, the journal added.

Antimalarial drugs were a particular target for counterfeiters and fake drugs had flooded the market in many Asian countries.

Worldwide sales of counterfeit drugs were forecast to reach 75 billion US dollars (£38.22 billion) in 2010.

Counterfeit medicines are defined by the World Health Organisation (WHO) as drugs that have been “deliberately and fraudulently mislabelled with respect to identity and/or source”.

Counterfeiting may have caused the deaths of at least 81 patients in the US who died after being treated with contaminated heparin, a widely used blood thinning drug.

Last week the FDA told a Congressional hearing it believed a dangerous contaminant found in batches of the heparin may have been deliberately added. The contaminant, traced back to a Chinese supplier, was structurally similar to heparin but 100 times cheaper.

Substances used to adulterate medicines varied from chalk to antibiotics to highly lethal substances, said the editorial.

The counterfeit drug trade was becoming more difficult to combat, it pointed out. Criminals were using more sophisticated techniques to bypass standard laboratory tests, for instance by adding cheaper substances that mimicked genuine drugs.

At a recent London policy conference on parallel trade, Heinz Kobelt (Secretary General of the European Association of Euro-Pharmaceutical Companies – EAEPC) discussed his association’s credo of “know your customer.” This was during a discussion of how parallel trade can actually help to enhance drug safety and security. (More on that absurd canard in a moment.)

But, during the ensuing Q&A it turns out that “know your customer” actually means “don’t ask/don’t tell” when it comes to one of their most important and largest category of customers – wholesalers, specifically those shady entrepreneurs who go beyond legal EU parallel trade into the clearly illegal realm of marketing non-approved drugs to North America.

Case in point: Rimonabant.

Licensed and legally marketed in the EU under the brand name “Acomplia,” this medicine is not approved for use in the United States. But type “Acomplia” into any US search engine and you’ll find no shortage of Canadian internet pharmacies ready, willing, and able to sell it to any American with a credit card.

How is this possible? Because these pharmacies are buying their supplies from European wholesalers – wholesalers who are getting their supplies (legally) from within the EU and then selling them (illegally) outside the confines of the Treaty of Rome.

When confronted with this shady behavior, Mr. Kobelt was at a loss for words, finally saying that it was an issue that should be brought up with the wholesalers.

Heinz – you can’t have 57 flavors of “know your customer,” choosing to “know them” only when it’s convenient is a policy that is neither sound nor honest.

As to parallel trade enhancing safety and security, here’s how Heinz spins that one.

During his presentation he pointed out (correctly) that the recent spate of counterfeit drugs that had infiltrated legitimate UK pharmacies had been discovered by a parallel trader. And that’s true. But what he didn’t mention is that those same products had already passed through three other parallel traders without being found.

Some victory for drug safety and parallel trade.

Something else that Heinz didn’t share was that, when the parallel trader found the counterfeits, rather than calling the UK authorities as required (the MHRA in this instance), he called the company whose drug had been counterfeited – so that he could get his supplies replaced.

Parallel trade and altruistic commitment to drug safety? Sure.

Chinese regulators accused Baxter of failing to co-operate in an investigation over deaths linked to impurities in blood thinner heparin.

The charge, swiftly denied by Baxter, marked a fresh escalation in Sino-US trade tensions since reports of at least 81 deaths linked to contaminated heparin in the US have triggered withdrawals in 11 countries.

The State Food and Drug Administration, China’s drugs regulator, said on Tuesday that Baxter had not provided all samples and information requested during a visit last month to its New Jersey plant. The SFDA reiterated its position that there was no proven link between the deaths in the US of patients and “a heparin-like substance” found in the drug.

Baxter replied: “We have been co-operating with all parties in the heparin situation including SFDA and the Chinese government. We plan to continue co-operating with them to help move the investigation forward. We will seek to understand any concerns to the contrary.”

Here’s the rest of the story, courtesy of the Financial Times:

http://www.ft.com/cms/s/0/3587b9b0-1ba7-11dd-9e58-0000779fd2ac.html

Per the larger issue of “tainted” vs. “counterfeit” ingredients, consider the comments of Robert Parkinson, Baxter’s chief executive, who said that the issue in question “appears to be the target of a deliberate adulteration scheme.”

Translation:  Counterfeiting.

There are a lot of issues here that need to be addressed – most notably criminal opportunism.

Consider the Chinese proverb, “Flies never visit an egg that has no crack.”

We must seal the cracks.