How do unsafe cancer drugs reach patients?

A major new investigation by the Bureau of Investigative Journalism has revealed that bad cancer drugs have been shipped to more than 100 countries around the world. How did they get there?

Well, before they reach a patient, most cancer drugs have already undergone a long, complicated journey.

Once the raw materials have been sourced, a typical drug will be manufactured, packaged, shipped, locally distributed and finally put to use. It will travel through factories, storage facilities, transport systems, hospitals and pharmacies. And at every stage of this process, the drug’s quality must remain unharmed.

Relatively innocuous events – a change in temperature, poor handling – can have critical effects. And unlike wealthy nations with robust tracking systems, low and middle-income countries often lack the infrastructure to monitor the journey.

What are the risks in drug manufacturing?

Ensuring that cancer drugs are sterile is the ultimate responsibility of the manufacturers. Every action must be tightly controlled. Staff working without proper disinfection processes can carry contaminants. Even a technician moving too quickly in a clean room can create air movement that spreads bacteria. Everything is sanitised right down to the pens and paper.

The process is unforgiving: if raw ingredients aren’t tested adequately, if equipment isn't cleaned properly, and if water isn't filtered thoroughly, these lifesaving medicines can become lethal.

How does the UK ensure safety of medicine?

About 80% of NHS prescriptions in England are generic drugs – identical copies of branded drugs that can be made once a drug’s patent expires – and about two-thirds of those come from abroad. To try to ensure that these drugs are safe, the following measures are in place:

• Every batch undergoes two rounds of quality testing: at the manufacturing site, then on entering the UK
• During each of these rounds of tests, 20 different markers of drug quality are checked
• Only specific experts, for example those registered with professional bodies like the Royal Society of Chemistry, are qualified to verify each batch
• The Medicines and Healthcare products Regulatory Agency (MHRA) regularly inspects manufacturing facilities, both in the UK and abroad.

What about in other countries?

Such testing systems are the gold standard. Many low- and middle-income countries, however, face significant challenges.

In Nepal, for example, limited resources and expertise mean that there is no effective testing and monitoring of cancer medicines imported from India and Bangladesh. Many countries also lack the ability to track drugs through supply chains and, like Nepal, do not have any verified experts or facilities to check drug quality.

These shortcomings, combined with corruption issues and porous borders, all mean that bad and potentially counterfeit drugs can enter healthcare systems.

What are the consequences of unsafe cancer drugs?

Time is of the essence for any cancer patient undergoing chemotherapy, so for that reason alone a substandard or ineffective drug will affect their treatment. But drugs that have not been manufactured properly can be toxic or contaminated – and put a patient in immediate danger.

There are numerous examples of this having happened during recent years. In 2019, five young patients from Saudi Arabia developed a high fever, and one died, after taking an Indian-made medicine given at the same time as chemotherapy drugs. In the same year, four children died and more than a hundred fell ill in Colombia when given the same type of drug. In 2022, children in Yemen and Lebanon received methotrexate, a critical chemotherapy drug used to treat leukaemia and other cancers, that had been contaminated with a deadly bacteria.

In 2023, TBIJ uncovered a dozen poor-quality brands of a childhood cancer drug used in Brazil.

The World Health Organization (WHO) maintains a rapid alert system for dangerous drugs. After a concern has been raised – generally by a health ministry, regulator or hospital – and assessed by the WHO, an alert is then sent out to all member governments. However, this system only catches problems after harm occurs.

In addition, many regions lack facilities to test drugs. Only seven countries in sub-Saharan Africa, for example, have laboratories that have been approved as meeting WHO standards.

But the WHO has put several mechanisms in place to keep a check on drug safety in low and middle-income countries:

1. Global Benchmarking Tool (GBT): a tool that assesses and rates national regulatory systems on a scale of 1 (least mature) to 4 (most mature). In 2023, 70% of WHO member countries were rated level 1 or 2, meaning they have limited capacity to check drugs coming into the country.

2. Essential Medicines List (EML): a list of medications that are considered to be the safest and most effective for meeting the most important health system needs. While generic versions of drugs on this list could still be fake or substandard, the existence of the list helps countries prioritise limited resources.

3. Prequalification Programs (PQP): These lists contain laboratories, specific drugs and sources of active pharmaceutical ingredients that the WHO has inspected, evaluated, and confirmed to be acceptable for use. This helps governments and national regulators procure safe medicines.

4. Good Manufacturing Practices (GMP): a certification which ensures that pharmaceutical products are consistently produced and controlled to quality standards. Most countries will only accept the import and sale of medicines that have been manufactured by internationally recognised GMPs. It is used by pharmaceutical regulators and the pharmaceutical industry in over 100 countries.

5. WHO Certification Scheme: A CoPP (or a Certificate of Pharmaceutical Products) can be requested by a country that wants to import a medicine and is issued by the exporting country according to the WHO guidelines. It acts like a passport for medicines, proving the item is approved and safely made in the exporting country.

These measures certainly provide some protection against dangerous drugs, but the protections they offer simply aren’t enough. Without the level of oversight seen in countries like the UK, these measures often fail to prevent substandard drugs from reaching patients. For example, a paper published this year revealed the results of testing of 84 drugs intended for shipment from India to Nigeria. All 84 held CoPPs. All 84 failed testing.