More than a dozen institutions have been using poor-quality, unauthorised drugs to treat cancer patients.

A huge scandal is brewing in Italy as a joint investigation by Politico and the Bureau of Investigative Journalism (TBIJ) has revealed that

more than a dozen Italian hospitals imported cancer drugs that were unauthorised in the European Union.

The article highlights that at least 16 hospitals in Italy have been treating cancer patients with a poor-quality imported drug that is not approved for use in the European Union. Gaps in national and EU medicines regulations have allowed Italian hospitals to legally request shipments of Celginase — a low-cost cancer medicine shown to be substandard — even when better alternatives have been available, Politico points out. Neither Italy’s drugs regulator nor the country’s ministry of health are responsible for checking the quality, efficacy or safety of this drug before allowing it into Italian hospitals, Politico writes in the article, noting that nor does it fall within the remit of the European Medicines Agency (EMA).

Hundreds of vials of the drug have arrived from India over the last seven years, with many of them still sitting on hospital shelves today, Politico says, adding that

it is unknown how many cancer patients could have experienced adverse side effects or lower chances of remission as a result. The drug in question is used to treat one of the most common forms of childhood cancer and is manufactured in India for as little as 13 euros a vial, compared to 2500 euros for other standard drugs.

Published academic studies have found it did not meet minimum manufacturing standards or consistently reach the clinical activity threshold to treat cancer.

In January, the Bureau of Investigative Journalism and the American health news site STAT revealed that poor-quality brands of cancer drugs, including Celginase, have been shipped to more than 90 countries since 2016,

putting an estimated 70,000 children around the world at risk.

In 2018, an apparent nationwide shortage of the widely used drug Oncaspar led to children in Italy receiving another brand, which was later found to be substandard, the article says. The hospital concerned said its request to import the drug in question was authorised by the Italian drugs regulator, and that not doing this would have reduced the chances of children’s recovery. But Politico has confirmed that Celginase has been purchased by Italian hospitals even when Oncaspar has been available.

In Italy, if a drug is in shortage, doctors and pharmacists can ask the Italian drugs regulator to greenlight the import of that same drug from another country, as highlighted in the article. A different law permits a drug that is not approved in the EU but is elsewhere in the world — such as Celginase — to be imported for a named individual patient if a doctor deems there is no valid alternative therapy available. As Celginase and Oncaspar are not exact equivalents, using this loophole, doctors have been able to request Celginase imports even when Oncaspar is available. This is how some hospitals have replaced good-quality medicine with cheap, substandard products for treating childhood cancer.

Crucially, this process bypasses the country’s drugs regulator. In Italy, permission is instead given by the ministry of health’s customs agency, which is required only to check that the paperwork has been correctly filled out by the hospital and the drug arriving is the one requested. Politico points out that the agency is not required by law to check the quality of imported drugs nor ask for data from the overseas regulators that approved them. Instead, the responsibility for using these drugs lies with the individual doctor who requests them. The Italian drugs regulatory agency said that doctors should use qualified and reliable import intermediaries who can guarantee the quality and safety of the drug, particularly with suppliers in non-EU countries.

Through freedom of information requests to the Italian customs agency of the ministry of health, TBIJ and Politico found that at least 16 hospitals, including the Istituto Nazionale Tumori in Milan and San Camillo Forlanini in Rome, imported hundreds of vials of Celginase into the country over a seven-year period. The Istituto Nazionale Tumori said that shortages required them to source Celginase. It added that the patients who received the drug are either responding to it or are in remission, and that the Italian drugs regulator has never provided information showing that Celginase could be harmful. San Camillo Forlanini did not respond to a request for comment.

The European Medicines Agency (EMA) also has no power over imports of unapproved drugs from non-EU countries, according to its former head Guido Rasi. Most of the Celginase imported into Italy from India came via Switzerland. The Swiss customs agency said that it does not have specific data on the products in question. It did not know if Indian drug imported via Switzerland might have gone to any other EU countries besides Italy, but said Celginase was not used in Switzerland.

The Italian drugs regulator says that in February 2023, it exchanged information with the World Health Organization (WHO) on data around a potential lack of efficacy of the Indian-sourced drug, adding that there appears to be no evidence from the WHO of low-quality, dangerous or ineffective products imported from India.

Changes to the EU law are in the works to attempt to address some of these anomalies in the regulations, Politico underlines. The planned revision would oblige drugmakers to flag any potential shortages six months in advance — up from two months — and it could require companies or wholesalers to keep larger stockpiles.

For now, however, the paradox remains that while Europe’s medicines are among the most highly regulated in the world, drugs that are shipped in from abroad can fail to meet even minimum standards.

The manufacturer of Celginase did not respond to a request for comment.