Who cheats on tests? Some foreign drug makers do.
Several dozen companies have been caught in the act, fabricating data used by Health Canada and other regulators to approve drugs for sale in the Canadian, U.S. and European markets.
Western inspectors have found pages of important data buried under rubble. They've found evidence of erased computer records and falsified human blood tests. And those are just the examples they've witnessed.
The data fraud is happening across the international pharmaceutical manufacturing industry.
"Data integrity is a fairly new issue and it's an emerging issue," said Etienne Ouimett, Health Canada's director of drug establishment inspections.
And because 80 per cent of drugs on the Canadian market and almost half of those sold in the U.S. are imported, Health Canada, the U.S. Food and Drug Administration and other health regulators are increasingly trying to crack down.
Raw data crumpled on the floor
In April, the FDA and the World Health Organization independently discovered problems at one private research company in Bangalore, India. Semler Research Centre was testing pills, in humans, for a variety of international drug companies.
WHO inspectors
reported finding evidence of "deliberate sample manipulation," which they concluded was "a common practice" and an "indicator of fraud."
FDA inspectors
reported observing Semler employees tampering with bioequivalence tests. These are experiments designed to prove that new versions of old drugs have the same metabolic effect on the body.
The regulator says it caught Semler employees deliberately switching blood samples, to make it look like the the test drug was having the desired effect.
The inspectors also reported finding raw data ripped up and crumpled on the floor.
So far, the FDA has found no evidence of serious safety concerns with drugs approved using Semler data. But the agency demanded all of the tests be repeated by an independent group.
Canadian connection
Health Canada has identified one Canadian drug company that used data from Semler to have a drug approved for sale here. That company is Marcan Pharmaceuticals and the drug is moxifloxacin, an antibiotic used to treat sinusitis, bronchitis, pneumonia and other bacterial infections.
Marcan's version of moxifloxacin is marketed in Canada under five different brand names and it's an instructive example of the maze that awaits anyone who tries to
track the manufacturing chain of a single pill.
Health Canada says Marcan has been able to demonstrate the safety of moxifloxacin using other data.
But the Semler story is just the latest episode in a burgeoning data manipulation problem that international agencies are working together quietly to try to control.
Dozens of drugs are no longer being imported to Canada because of unreliable data, and more than two dozen suppliers of finished medicines and raw pharmaceutical ingredients are on a Health Canada watch list for data integrity violations.
Manufacturing shrouded in secrecy
But it's almost impossible to find out which drugs are being quarantined and who sells them.
Those details, along with information about where the drugs are made, are not routinely available to Canadians. Health Canada lists some of the examples on a
data inspection tracker. But the list doesn't name all of the drugs affected or describe the nature of the data integrity problems.
And the entire drug manufacturing chain is shrouded in secrecy, protected by a curtain of corporate confidentiality that Health Canada refuses to lift.
It's an uncomfortable consequence of the global supply chain's growing complexity.
Everything from raw materials to human safety testing is contracted out to third parties in India, China and around the world.
These days even the regulators admit it's difficult to connect the dots.
"We know where our shirts are made, we know where our shoes are made but we don't have that level of detail over where our medicines are made"- Behrat Mehta, PharmaCompass
"Companies may one day buy an ingredient from the U.S and the other day buy the same ingredient but produced by a manufacturer in France," said Health Canada's Etienne Ouimett. "And depending on who provides the best service for money they may turn to a fabricator in Switzerland and then turn to a packager in another country."
Matthew Herder, health policy researcher at Dalhousie University, said this means as drug companies become global enterprises, "we're taking on greater and greater risks of what we really know in the manufacturing of those drugs."
Health Canada can only inspect a fraction of the hundreds of foreign manufacturing sites and instead gets much of its on-site inspection information from its "trusted partners," including the FDA and the European Medicines Agency. And those reports reveal the challenges inspectors face trying to uncover data fraud.
Storage room door screwed shut
In one case, during an FDA inspection of an Indian company last year, an employee ran away with a USB thumb drive when he saw FDA inspectors. Fifteen minutes later, a manager came back with what the company claims was the same USB drive. But "it is impossible to know whether management provided the same USB thumb drive that the analyst had removed," the inspectors reported.
In another case, in June of last year, a Chinese drug company refused to let Italian inspectors see ingredients and finished drugs being kept in an "unofficial and non-controlled storage area." The company had even screwed the door shut. Inspectors concluded the material was to be used "outside of a quality assurance system" and that there was a serious risk of data falsification.
At a manufacturing plant in Tarapur, India, in February, French inspectors found raw data about some antibiotics discarded in a pile of rubble on the other side of a wall.
The same company claimed it had manufactured the active antibiotic ingredient in-house, when instead it had purchased the product from a Chinese company not approved to sell pharmaceuticals in the European union.
The data manipulation doesn't necessarily mean the drugs are dangerous. The problem is, without reliable data, their safety can't be proven.
"If you can't trust that the drug contains the active ingredient at a concentration that it's supposed to contain, if it's too low, it can be ineffective. If it's too high, depending on what the drug is, it can actually be dangerous," said Barbara Unger, a pharmaceutical industry consultant in California.
Last year, the FDA caught an Indian drug manufacturer manipulating tests for genotoxic and carcinogenic impurities.
Tragic proof
In another case, when the FDA responded to complaints from U.S. manufacturers about impurities in raw ingredients from a Chinese company and asked to see the data, inspectors discovered it had been deleted and the audit trail disabled.
Two companies on Health Canada's watch list have been caught falsifying the source of their active pharmaceutical ingredient. Both claimed to have made the raw material, but actually purchased it from somewhere else.
There's tragic proof that data integrity matters. In 2008, 19 people in the U.S. died and hundreds more were sickened by a contaminated blood thinner made from a raw material the FDA believes had been tampered with at its source in China.
In January, the European Medicines Agency recommended its member states suspend the marketing authorization for 700 drugs because of data integrity violations discovered at one contract research organization in Hyderabad, India.
Risk of drug shortages
But banning drugs can cause drug shortages and that creates new headaches for regulators like Health Canada.
"They have to balance whether the risk to public health is greater if they take these medically necessary products off the market," said industry consultant Barbara Unger.
That means if a company is making medications that are deemed to be "medically necessary," Health Canada will still allow the drugs to be imported into Canada, with conditions, even if there are questions about the integrity of the data used to approve them.
"It's a case-by-case basis because it varies by the nature of the product, by the nature of the data integrity issues," said Ouimette.
"We will work with the company to design the terms and conditions that are such that will mitigate the potential risk of the product coming into the country."
"...a lot of companies are manipulating their documentation"- Behrat Mehta, PharmaCompass
In India, Bharat Mehta is one of the few people speaking out about the data manipulation problem. He spent 15 years in the Indian pharmaceutical industry and now writes an industry newsletter.
He says the reasons for faking data are clear: the companies are being hired to test drugs and ingredients, and they want to get the answer their customers are paying for.
"If you develop a reputation of being a lab which would not be able to demonstrate the equivalence, at some level why would people come to you for business?" he said.
Fake paper trail
The companies also know that Canadian, American and European inspectors want to see a paper trail for the drugs they import.
"There's a very high degree of focus in pharmaceutical quality to be able to back up whatever you say with paper," Mehta said. "And so because of that pressure a lot of companies are manipulating their documentation."
And without knowing who really makes a drug, consumers can't apply pressure or make informed decisions.
"Currently the entire system is extremely opaque," Mehta said. "We know where our shirts are made, we know where our shoes are made, but we don't have that level of detail over where our medicines are made."
"And I think consumers should have access to that type of information so it pushes the industry to hold itself to a higher quality of standards."
That's why many are calling for greater transparency. At Dalhousie University in Halifax, Matthew Herder has been pushing Health Canada to release all industry data.
"If your goal is to encourage better oversight, better data integrity in the research and development process, then I think there's good reason to have a lot more transparency about that complicated group of corporate actors that are involved," he said.
The secret world of drug manufacturing
David Donnelly/CBC
Do you know where your pills are made? Canada? The U.S.? Not likely.
80 per cent of pills sold here are made overseas in places like China and India.
But if you want to find out exactly where, good luck.
Companies refuse to disclose trade secrets and Health Canada doesn’t make them do so. So, when there’s news that foreign drug companies have been caught faking data on safety and effectiveness, how do you know if the pill you take is connected with that company?
You often don’t.
Pakistan's Adviser to the Prime Minister on Foreign Affairs Sartaj Aziz said Pakistan has diplomatically engaged numerous countries over the criteria-based approach for the countries that are not signatories to the Non-Proliferation Treaty (NPT).
"If the group forms such a uniform criteria, then Pakistan has stronger credentials for NSG membership than India," he told Dawn News.
Pakistan has bright chances of getting membership to the Nuclear Suppliers Group (NSG) on merit, he claimed.
"Our strategy was to apply after India did, after which we would have immediately followed. We have had our application in an advance state of readiness for the past three months for this purpose," Aziz said.
He claimed that Pakistan has gradually gathered support for the criteria-based approach.
"Last week, I telephoned the foreign ministers of Russia, New Zealand and South Korea, who will in future head the NSG, and our viewpoint was that they should support the criteria- based approach and we have gathered support for it, China was already supporting it," Aziz said.
He expressed hope that due to "Pakistan's efforts and its strong credentials", if India gains entry into the 48-nation club, Pakistan will also not be left behind.
Responding to a question about nuclear scientist Abdul Qadeer Khan's proliferation network, Aziz said Pakistan has come a long way since then and everyone has witnessed Pakistan safeguarding its nuclear assets.
"If you compare it with India, when our neighbouring country conducted a nuclear test in 1974, it misused the nuclear supplies given to it for peaceful purposes, which led to the formation of NSG. After that nuclear fissile material was stolen from India, but such an instance has never occurred in Pakistan," Aziz claimed.
He said the US has formed a policy to 'build up India' as "their entire attention is towards containing the Islamic world and China".
"We cannot question them but we repeatedly tell them that you (US) are a sovereign country and can maintain any level of relations with any country, but if you increase the strategic and conventional imbalance in South Asia, our problems will increase," the foreign affairs adviser said while referring to the US support for India's inclusion in NSG.
The US has been pushing for India's NSG membership while China has been reportedly backing Pakistan's bid to join the nuclear trading club.
India, though not a member, enjoys the benefits of membership under a 2008 exemption to NSG rules for its atomic cooperation deal with the US.
The NSG looks after critical issues relating to nuclear sector and its members are allowed to trade in and export nuclear technology. The NSG works under the principle of unanimity and even one nation's vote against a country could scuttle its bid.