LONDON: Vital chemotherapy drugs used around the world have failed quality tests, leaving cancer patients in more than 100 countries at risk of ineffective treatments and potentially fatal side effects.

The drugs in question form the backbone of treatment plans for numerous common cancers including breast, ovarian and leukaemia.

Some drugs contained so little of their key ingredient that pharmacists said giving them to patients would be as good as doing nothing.

Other drugs, containing too much active ingredient,put patients atrisk ofsevere organ damage or even death. `Both scenarios are horrendous,` said one pharmacist. `It`s heart breaking.

Doctors from multiple countries told TBIJ of the drugs in question not working as expected,leaving patients suddenly unresponsive to treatment. Other patients suffered side effects so toxic that they could no longer tolerate the medicine.

The variance found in the levels of active ingredient was alarming. In some cases, pills from the same blister pack contained different amounts.

These findings expose huge holes in the global safety nets intended to prevent profitseeking manufacturers from cutting corners, and to protect patients from bad drugs. All the while, patients and governments with stretched resources are paying the price for drugs that don`t work.

Generic drugs 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 crucialin those with fewer resources, where costlier treatments might be beyond reach.

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.

Research from landmark study, published today (Thursday) examined the amount of active ingredient in seven common types of cancer drug: cisplatin, cyclophosphamide, doxorubicin, ifosfamide, leucovorin, methotrexate and oxaliplatin. All of them are classed as essential medicines by the World Health Organisation (WHO).

Working with collaborators in Cameroon, Ethiopia, Kenya and Malawi, researchers at the University of Notre Dame, Indiana, analysed drug samples from the four countries.

Of 189 samples that had not expired at the time of testing, about one fifth failed. This consisted of 20 different brands of generic drug made by 17 manufacturers.`We were all taken aback when we saw the results,` said Marya Lieberman, the professor who led the research.

More than 30 manufacturers made products to a good standard.

The majority of failed drugs had too little active ingredient (for most this meant less than 88pc of the amount stated on the label) while some contained too much (more than 112pc). Both thresholds were decided by researchers based on internationalstandards.

Tracking the threat 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 lowand middle-income nations like Nepal, Ethiopia and even 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.

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 importerbeing Ethiopia. Although Pakistan does obtain cyclophosphamide from Indian vendors, Venus Remedies is not the main supplier.

Venus Remedies told TBIJ that the study results were `not scientifically plausible` given the company`s `validated manufacturing systems and qualitycontrols.`Itsaidithasreceived 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.

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.

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 afforda-ble medicine.

But while the majority of Indiamade 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 $500m 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. And as recently as August 2024, it was reportedthattheregulatorhadfound more than 50 drugs on the market to be substandard or fake, including some paracetamol and antacids.

Questions have also 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 interestisin 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 afterthe 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 leukemia 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.

Meanwhile, these medicines continue to fill pharmacy shelves.

Zuvius Lifesciences and GLS Pharma have supplied their failed brands to over 40 countries.And 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 severalessentialcancer 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`.

This report has been published in collaboration with The Bureau of Investigative Journalism. The article has been edited for the print edition. A detailed version can be accessed on Dawn.com and TBIJ`s website.