The expert in medical studies was shocked when he heard the rumour. During the more than fifteen years that Anders Fuglsang has been conducting inspections for the WHO, EU and pharmaceutical companies at clinics around the world, he has not experienced a similar scandal.
“It’s unprecedented”, says Anders Fuglsang, “and the consequences for patients can be very serious”.
Data for more than 2,000 medicines are currently being reviewed by the European Medicines Agency, EMA, and the pharmaceutical companies that have brought the medicines to market. The fraud potentially affects 61 medicines for Danish patients. 23 of these medicines are approved in Denmark, but only fifteen of them can be found in various strengths and forms on the shelves of Danish pharmacies, according to the Danish Medicines Agency.
THE FACTS
The issue involves generic medicines, i.e. counterfeit medicines that must be as safe and effective as the expensive original medicines. Or at least that’s how it should be, but that’s now being questioned.
The EMA suspects that an Indian clinic has falsified data to such an extent that the authorities have raised serious doubts about the quality, safety and efficacy of the medicines. These include medicines for patients with lung cancer, HIV and diabetes, several of which are in the Danish market.
Eva Aggerholm Sædder, senior consultant at the Department of Biomedicine at Aarhus University, has seen the list of suspected fraudulent medicines.
“It’s very serious, both for patients and for confidence in medicines, there’s no doubt about that,” she says.
The scandal was already lurking in November 2020.
Two inspectors from the Spanish Medicines Agency arrived in the Indian city of Pune. Corona had locked everything down and Indian pharmaceutical companies were producing medicines at full speed for the rest of the world.
In a grey concrete building called Majestic Plaza, the Synapse Lab clinic is housed on a few floors. Since 2007, employees have behind these walls been producing data that has approved thousands of medicines in the EU. Synapse Lab is a clinical research organisation or CRO, and this is roughly how they work:
A pharmaceutical company comes up with a copy of a painkiller that they want to launch in a country. The patent for the original drug has expired and the cheaper copy may be approved if the company can provide data showing that the new copy is as effective and safe as the original painkiller.
The CRO, in this case Synapse Lab, tests the generic drug among subjects in two groups. One group takes the original pill and the other group takes the new and hopefully accurate copy. Both groups have blood samples taken during a given period of time.
And this is where the Spanish inspectors encountered problems, explains Anders Fuglsang.
The inspectors returned from India with findings that led to the following in the inspection report: “The severity and scope of the inspection raises serious concerns (…) and the overall reliability of the data generated by this CRO”.
The Spanish inspectors returned exactly two years later, in November 2022, and this time they no longer had any doubts. The essence of their criticism was summarised in five points, of which one sentence in particular has caught Anders Fuglsang’s attention. Overlapping plasma time concentrating profiles.
In practical terms, this means that the EMA suspects the clinic of reusing data from test subjects in medical studies, explains Anders Fuglsang.
“This means that the EMA is concerned about quality, safety and efficacy. The data is unreliable. Maybe these medicines don’t have the pharmacological properties they should have,” he says.
In July this year, the Spanish inspectors alerted the European Medicines Agency, EMA, and the industry in Europe. Pharmaceutical companies have now been given a deadline by the European Medicines Agency. By 15 September, they must submit new data to the EMA showing that their medicine is safe and effective.
“All medicines are in acute potential danger of being withdrawn from the market because pharmaceutical companies have to prove that the data behind their medicines is valid”, says Anders Fuglsang.
In short, the fraud means that neither the pharmaceutical companies nor the patients can rely on their counterfeit medicine being as safe and effective as the original medicine, experts tell Danwatch.
Data fraud on this scale may have consequences for both healthcare finances and patient safety, says Eva Aggerholm Sædder.
“It’s terrible. If a patient’s treatment fails or potentially very serious adverse effects are identified, it has huge consequences. This is something that needs to be analysed in depth,” she says.
Anders Fuglsang agrees that the fraud should cast doubt on patients’ safety.
“Very much in doubt”, says Anders Fuglsang, “we should fear that the medicine does not have sufficient effect or that it has too many adverse effects. The evidence for bioequivalence, i.e. that the medicine has the same effect and safety as the original medicine, has been manipulated,” he says.
The EMA has asked pharmaceutical companies to submit different or new data showing that their medicine is as effective and safe as the original medicines. If not, experts suspect they will be asked to withdraw the products from the market. Eva Aggerholm Sædder explains that this fraud can also have societal consequences.
At a time when shortages of many types of medicines are pushing up prices, we rely on cheap generic copies. If the fraud means that thousands of generic medicines are withdrawn from the market, there will be an even greater shortage of medicines and confidence in cheaper medicines will suffer, explains Eva Aggerholm Sædder.
“In Denmark, we have a unique system where generic medicines have a huge impact on how much money we spend on medicines, which are constantly increasing in price. The new medicines reach consumers quite quickly, but it costs money, so we need to be able to trust a product when we use it. A scandal like this has a major impact on that trust,” says Eva Aggerholm Sædder.
The Spanish Medicines Agency has known about the problems with Synapse Lab since 2020, and although that seems like a long time, it doesn’t mean the authorities could have intervened earlier, she says.
“We don’t know what type of irregularities the inspectors saw three years ago. It may be that the fraud has increased in scale, which is why they have not intervened until now,” says Eva Aggerholm Sædder.
One of the pharmaceutical companies, Sandoz, which has used Synapse Lab and is currently facing doubts about the data that has had several hundred of its drugs approved, is awaiting the authorities’ assessment. The CEO of Sandoz, Carsten Glerup, does not wish to be interviewed, but writes in an email to Danwatch:
“We have with the utmost seriousness noted the alleged concerns about the data quality at Synapse Labs. Together with the European trade association for pharmaceutical manufacturers, Medicines for Europe, Sandoz and other affected companies are working closely with the European Medicines Agency, EMA, to investigate the situation and ensure the necessary measures are taken to maintain patient safety. As soon as the conclusions from these investigations are available, we will be able to share further information.”
Another pharmaceutical company that markets some of the medicines on the list, Accord, has not responded to our inquiry.
The experts believe that there is a risk to Danish patients, but the Danish Medicines Agency rejects this. The Danish Medicines Agency does not wish to be interviewed, but writes in an email that it does not believe that the fraud at the Indian clinic poses a risk to Danish patients.
“A suspicion has been raised (in the EMA ed.) and a process is underway. However, as the quality of the manufacturing has not been questioned, it has been assessed that there is currently no patient safety risk associated with the affected medicines and therefore there is no need to withdraw the medicine while the case is being investigated”.
“In situations where the formulation of the medicine is more complex, for example if it had a slow-release effect, we would consider that there could potentially be some impact on patients if the two products are not absorbed into the bloodstream in the same way. This is not the case for any of the medicines involved in this case. This includes the medicines for the treatment of lung cancer and HIV”.
The Danish Medicines Agency is now awaiting the EU process.
THE FACTS
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Louise Voller