‘It’s heartbreaking’: bad cancer drugs shipped to more than 100 countries

Cancer is one of the biggest killers worldwide, linked to around 10 million deaths every year — roughly one in six. The burden of cancer is growing, particularly in low and middle-income regions. In sub-Saharan Africa, for example, instances of cancer have doubled in the last 30 years.

Much of the global demand for treatment is met by so-called generic drugs. These are versions of a drug that can be made once the original maker’s exclusivity rights have expired, and are typically made far more cheaply. The bad drugs described in this investigation were all generics.

Generics are widely used in all countries but are most crucial in those with fewer resources, where costlier treatments might be beyond reach.

If generics were not available in sub-Saharan Africa, for instance, “any cancer treatment would be likely inaccessible to most of the population”, said Claudia Martinez of the Access to Medicine Foundation, an NGO part-funded by the Bill and Melinda Gates Foundation.

In chemotherapy drugs, the active ingredient, which fights cancer cells, is also highly toxic. Patients need to receive enough of it to treat the cancer, but not so much that they overdose and suffer damaging side effects.

As such, hospital pharmacists calculate doses carefully and, in doing so, rely on the amount of active ingredient being exactly what’s stated on the label.

Over the past six years, these brands of drugs have been shipped to more than 100 countries in every populated continent on the planet. They range from low and middle-income nations like Nepal, Ethiopia, North Korea and Pakistan, to wealthy countries such as the US, UK and Saudi Arabia.

The worst-performing drug in the study is made by Indian manufacturer Venus Remedies. It is a drug called cyclophosphamide, which is often used to treat cancers, including lymphoma and breast cancer.

A table showing data on subpar cancer drugs shipped to Pakistan. — The Bureau of Investigative Journalism

All eight samples of this Venus Remedies drug failed, with six containing less than half the amount of active ingredient claimed by the manufacturer. One contained just over a quarter of the stated dose, which, according to several cancer pharmacists, would be as effective as no treatment at all.

The drug has been shipped to six countries, with its largest importer being Ethiopia. Although Pakistan does obtain cyclophosphamide from Indian vendors, Venus Remedies is not the main supplier.

Wondemagegnhu Tigeneh, a clinical oncologist in the Ethiopian capital Addis Ababa, told TBIJ that he has treated patients with chemotherapy drugs he believes did not work.

“I have a suspicion that the active ingredient was lower than expected,” he said, remembering a drug he gave to a recent patient who had responded well to the first three rounds of treatment. But on the next round, their progress suddenly stopped.

Because he has no means to test them, Tigeneh can never be sure of the quality of a given drug. But in his 20 years treating cancer, he has learned to notice tell-tale signs. Sometimes, for instance, there is a complete absence of side effects such as nausea or hair loss.

“That makes it difficult to trust that particular drug,” he said.

Then there are the patients whose disease he struggles to get under control, such as a patient whose response to treatment halted without warning.

Rather than reducing the size of the tumour enough to enable surgery, his team has been forced to move on to a second-line treatment. If that fails, the next stage is palliative care. “

It’s very sad,“ said Tigeneh. “We didn’t used to see things like this.”

Cancer patients in Ethiopia have far better access to treatment facilities now than they did 20 years ago. It doesn’t seem, however, that the standard of medicines has kept pace.

A 2020 study of cancer drugs in Ethiopia included 20 samples of cisplatin, which were all found to be substandard, averaging just over half of the stated content. One researcher who tests the quality of drugs in the country told TBIJ that they find bad medicines wherever they go.

Venus Remedies told TBIJ that the study results were “not scientifically plausible” given the company’s “validated manufacturing systems and quality controls”.

It said it has received no complaints or concerns about the batches in question and shared the results of its own testing that indicated they were of a good standard.

Professor Marya Lieberman works in her lab at the University of Notre Dame, in India, the US, in this photo taken in July 2024. — Barbara Johnston/University of Notre Dame

It said storage conditions in the supply chain, which can affect drug quality, might have affected the researchers’ test results. However, the absence of similar quality issues across the entire data set suggests this is not the case.

Venus Remedies is one of three companies or regulators that queried the methodology used by the lab, saying it deviated from international standards or could give erroneous results.

However, Lieberman said that, although her results are not intended for regulatory purposes, her researchers’ methods are based on those used by regulatory labs and were verified for suitability, accuracy, and precision. Both the findings and methods have been scrutinised by independent academics.

Some 2,000 miles south of Addis Ababa, in Malawi, specialist cancer care has only been available for around 15 years. In one of the poorest countries in the world, patients depend on healthcare being free at the point of need. That means clinics have to rely on generic drugs.

A pharmacist specialising in cancer care in central Malawi told TBIJ of seeing patients at his hospital overdose on methotrexate, a drug used to treat leukaemia and lymphoma.

Malawi has also imported two of the brands of methotrexate the researchers in this investigation found to contain too much active ingredient: Zuvitrex, made by Zuvius Lifesciences; and Unitrexate, made by United Biotech.

Neither company responded to multiple requests for comment.

This sort of excess can be just as harmful as a deficit. A bad overdose can leave a patient with lifelong side effects or even kill them. As Nabhani-Gebara said, “More is not better.”

The Malawian pharmacist said patients at his hospital have suffered severe vomiting and nausea after overdosing on methotrexate, while others had to be moved onto a second-line treatment, which may not be as effective.

For some patients, the side effects were so severe that they had to pause treatment entirely, giving the cancer a chance to grow.

When a sample of the methotrexate in question was tested as part of a research project taking place at the time, it was found to be too high in active ingredient. “It’s very worrying,” the pharmacist said.

He told TBIJ that he and his colleagues have, on occasion, had to stop using an entire batch of chemotherapy medicine and send samples to the national drug regulator after the medicine changed colour — a sign that something is wrong with it.

“We had patients scheduled for clinic,” he said, “and then we had to break the news to them that we don’t have medicines.”

Countries all over the world have systems in place to stop bad drugs from reaching patients. However, there are huge disparities in their effectiveness.

According to Chaitanya Kumar Koduri of the US Pharmacopoeia, an organisation that sets standards for medicines in the US and internationally, “70pc of countries cannot take care of their own medicine quality”.

Most governments have a national regulator, but their remit and resources vary hugely. Even the better-funded regulators are far from foolproof.

The US Food and Drug Administration (FDA), for instance, is struggling to keep up with inspections of manufacturing plants domestically and in India and China and has admitted that its inspections have not been a reliable indicator of drug quality.

The FDA recently announced it would expand unannounced inspections at foreign manufacturing facilities, saying this will help expose those who falsify records or hide violations.

It told TBIJ “that inspections and reviews will continue to ensure [drug] safety and efficacy”.

Maximilian Wilfinger tests chemotherapy drugs in Marya Lieberman’s lab at the University of Notre Dame, Indiana, the US in this file photo taken in August 2024. — Matt Cashore/University of Notre Dame

One of the countries where medicine regulation ranks the lowest, according to the WHO, is Nepal. It is also one of the biggest importers of the failed chemotherapy brands in this investigation.

Despite there being more than 20,000 brands of medicine on the market, the country’s drugs regulator has set a target of testing just 22 drugs in the next 12 months — none of them chemotherapy drugs.

Narayan Prasad Dhakal, the regulator’s director general, told TBIJ that its lab cannot currently test cancer drugs and admitted that the situation around quality testing is “a concern”. He also said that while his department has the power to recall cancer drugs based on external evidence, it has never done so.

The issue is especially fraught for patients who may have travelled from remote, rural areas to get treatment that may not even work.

Laxmi Kumari, whose two-year-old son is being treated for cancer in Kathmandu, Nepal’s capital, has had to procure chemotherapy drugs from private pharmacies.

The treatment has cost the family nearly 200,000 Nepalese rupees (£1,160), equivalent to several months’ average salary in Nepal, and yet they have no reassurance that it will be effective.

“We have no way of knowing the quality of the medications being used in his treatment,” said Kumari. “We rely entirely on what the doctors recommend.”

“Neither patients nor their families have any way of knowing the quality of these drugs,” said Smriti Pokharel of the Wish Nepal Foundation, which helps children from low-income families access cancer treatment.

“Even doctors face challenges in verifying their quality. No one seems willing to take responsibility for ensuring proper treatment for cancer patients.”

Generic drug manufacturers are operating in a global market that healthcare professionals and experts agree is driven by one thing: price. It’s a market in which those operating under a less watchful eye can find ways to undercut their competitors.

This could mean scrimping on the amount or quality of the active ingredient — the most expensive component — or using cheap or outdated machinery. Research shows that the majority of substandard drugs occur due to problems with manufacturing, quality control, packaging or storage.

The results can be fatal. Four children died in Colombia after being given contaminated cancer drugs in 2019. Three years later, another batch of bad medicine caused the deaths of at least 10 children in Yemen who were being treated for leukaemia.

The price-driven market creates a dangerous dynamic in which the number of companies making a particular drug shrinks and shrinks until global supply is precariously dependent on just a handful of manufacturers. Should one company slip up, thousands of patients can be left without the drugs they depend on.

It’s a situation that played out in the US recently. Between 2018 and 2022, Intas Pharmaceuticals, the parent company of Accord Healthcare — which made the worst-performing cisplatin tested in this investigation — grew its market share of cisplatin from 24pc to 62pc.

It also increased its share of methotrexate fivefold in the same time period. All the while, prices of both these chemotherapy drugs dropped.

Then, at the end of 2022, a surprise inspection by the US drug regulator revealed a “cascade of failure” at an Intas factory in India, where staff were seen shredding and pouring acid on quality records.

The shutdown that ensued sent shockwaves across the US, with nearly every major cancer centre reporting shortfalls in chemotherapy drugs during the spring or summer of 2023, according to The New York Times.

Accord Healthcare said the batch of cisplatin that failed our testing had met all established quality standards and shared data from internal and external studies indicating its quality. It said it has not received any market concerns related to this batch.

The world’s pharmacy

India, where about 20pc of the world’s generic drugs come from, plays a pivotal role in ensuring people everywhere can access affordable medicine. Sixteen of the 17 manufacturers of failed drugs in this investigation are based in India.

While the majority of India-made drugs are safe, the country’s generics industry has long been dogged by scandal. In 2013, Indian manufacturer Ranbaxy agreed to pay a fine of $500 million after its US subsidiary pleaded guilty to the improper manufacturing, storing and testing of drugs.

In 2022 and 2023, Indian-made cough syrups were linked to the deaths of children in Gambia, Cameroon and Uzbekistan. As recently as August 2024, it was reported that the regulator had found more than 50 drugs on the market to be substandard or fake, including some paracetamol and antacids.

In India, the world’s largest producer of generic drugs, questions have been raised over whether manufacturers are properly punished for producing drugs that aren’t fit for purpose and whether foreign regulators have proper oversight.

“The Indian government’s interest is in trying to protect the industry,” said public health activist and former Big Pharma whistleblower Dinesh Thakur.

Sixteen of the 17 manufacturers identified in this investigation are based in India, and five have been previously flagged by a regulator for producing substandard batches of drugs. One of them, Zee Laboratories, has been flagged 46 times since 2018.

India’s drug regulator told TBIJ that Zee Laboratories has been audited and given a “stop production order”, which was lifted after the company resolved the problems in question. It did not give details about when this was, which issues it pertained to or whether the company faced any consequences.

It’s also unclear whether the manufacturers exposed in TBIJ’s previous investigation into substandard asparaginase have faced any repercussions, despite 70,000 children with leukaemia being at risk.

Three of those companies — Getwell Pharmaceuticals, United Biotech and VHB Medi Sciences — also made some of the substandard drugs revealed by this investigation.

Thakur said there’s only one way to explain the production of weak drugs by big companies: “Somebody’s cutting corners.”

Meanwhile, these medicines continue to fill pharmacy shelves. Zuvius Lifesciences and GLS Pharma have supplied their failed brands to over 40 countries.

In the past two years, Venus Remedies, which made the drug that pharmacists said wasn’t worth prescribing, has been awarded a series of contracts and licences, including from the Pan American Health Organisation to supply several essential cancer drugs to Latin American countries.

India’s drug regulator defended the oversight system, saying that failing drugs are recalled and manufacturers face “either administrative penalties or legal prosecution in court”.

Getwell Pharmaceuticals, GLS Pharma, VHB Medi Sciences, and Zee Laboratories did not respond to multiple requests for comment.

In order to ensure that people across the world have access to safe, effective drugs, the World Health Organisation (WHO) has put in place a series of steps.

It has compiled a list of “essential medicines”, to help countries with limited resources know what to prioritise. It checks certain drugs, active ingredients and their manufacturers to create a pre-approved list that countries can trust.

The WHO also oversees a set of standards for manufacturers and drugs that many countries refer to when importing medicines.

However, these measures have their own limitations.

The list of recommended medicines, for example, only expanded to include cancer drugs in 2019 and experts say that the WHO should include more of them on the list.

Shalini Jayasekar-Zürn of the Union for International Cancer Control, a global membership organisation dedicated to taking action on cancer, says it currently only encompasses two cancer drugs, rituximab and trastuzumab.

“It would be great if the list were expanded to include more essential medicines, especially for cancer,” she said.

While the WHO oversees standards for manufacturers and drugs, it’s up to the countries buying medicines to make sure those standards are met, which is no easy task given the resources of national regulators.

Meanwhile, Thakur said that one WHO scheme — a certificate system that says a given drug meets various standards — has been undermined by companies that have found “workarounds” to get hold of the paperwork without improving quality.

“It’s not worth the paper it’s written on,” he said.

As a result, experts say, is that without the comprehensive oversight seen in countries like the UK, the WHO’s processes don’t stop substandard medicines from making their way onto shelves.

Reflecting on TBIJ’s findings alongside his own experience, Thakur said that the WHO was “clearly not” delivering on its stated purpose: to promote health, keep the world safe and serve the vulnerable.

The WHO did not respond to several requests for comment made by TBIJ.

The cruel irony is that in this race to the bottom, it is the cancer patients who are often left to foot the bill. And those who have the least pay the most: in low-income countries, the cost of 58pc of essential cancer medicines is paid by patients, compared with 1.8pc in upper-middle-income countries.

One cancer pharmacist in Ethiopia estimated that it could take over a year for a patient to save for cancer treatment. If that medicine then turns out to be faulty, they simply might not be able to afford to pay for another.

“Most people believe cancer is incurable,” they said. “When they end up with a medicine that won’t cure them, that’s another tragedy.”

“For me, it’s a question of fairness,” said Lieberman, the lead researcher. “[Patients] have the right to be treated with a medicine that actually is what it says it is. One that has the correct ingredients in it, that hasn’t degraded, and that doesn’t have things in it that will hurt them. It’s too important.”