WHO, UN report uncovers supply chain weaknesses that contributed to patient deaths

A recent report from the World Health Organization (WHO) and the United Nations Office on Drugs and Crime (UNODC) highlights significant weaknesses in the global pharmaceutical supply chain that have resulted in patients – especially children – consuming medicines contaminated with harmful levels of toxic chemicals, such as diethylene glycol (DEG) and ethylene glycol (EG).

The report examines eight case studies highlighting systemic failures that led to patients ingesting contaminated medicines. It looks at four historical cases dating back to 1996 in Haiti, China, Panama, and India. Additionally, it reviews four more recent cases that occurred since 2022 in The Gambia, Uzbekistan, Indonesia, and Cameroon. The report also provides recommendations for regulators, law enforcement agencies, and manufacturers on how to improve pharmaceutical supply chains.

“Reports suggest that these cases are isolated, unusual, and anomalies, often reported following a cluster of obviously linked adverse events in patients. Recent developments indicate that this issue is more common than first thought,” WHO wrote.

Several of the case studies include allegations of corruption. In two instances, government employees were convicted for receiving bribes, while in another case, businessmen were found to have offered and facilitated bribes to government officials.

In Haiti, between November 1995 and July 1996, approximately 100 children under the age of 13 died after ingesting two locally produced pediatric syrups that were contaminated with high levels of DEG. The affected children typically presented at hospitals with acute renal failure. This situation triggered a multinational investigation to determine the cause of these deaths.

Suspicion centered on two locally manufactured paracetamol syrups, which were later found to contain high levels of DEG. In June 1996, the sale of these two syrups was prohibited, a public awareness campaign was initiated, and a recall was conducted.

The authors said there are some common themes reflected in the case studies. One of the reasons is economically motivated. The report notes that “in the drive to produce low cost medicines some manufacturers may resort to high-risk cost saving behaviours, which compromise the quality of the [finished pharmaceutical product]. The price differential has motivated some excipient traders and distributors to supply non-pharmaceutical grade excipients misbranded or mislabelled as pharmaceutical grade for the sake of profit.”

The report cites weak regulatory oversight as another reason for concern. It states that “weak regulatory oversight both in the country of manufacture and the importing country contributes to reducing the risk of sanction. If a [finished pharmaceutical product] is produced for export only (not authorised for placing on the market in the country of manufacture), regulatory oversight may frequently be even less stringent. Exports are often to low and lower middle-income countries where regulatory requirements are less stringent, some with very weak regulatory oversight and sanctions, and others with no facilities to submit the medicines for laboratory analysis.”

Another issue is the presence of weak procurement systems among pharmaceutical manufacturers. In these situations, few steps have been taken to authenticate the source or origin of the excipient. The report notes that “decisions to purchase excipients had been based on price and availability. During this research invoices from intermediaries supplying pharmaceutical grade excipients have been examined and relate to fictitious addresses, rented offices, or mobile telephone numbers that when rung are not answered.”

Additionally, the low frequency of adverse event reporting by companies was cited as a contributing factor in these incidents. The report indicates that while most countries have pharmacovigilance systems to track adverse events in patients, the levels of reporting can be quite low.

The report offers a slate of recommendations for national regulatory authorities (NRAs), WHO, inspectors, enforcement, testing labs, and manufacturers:

For NRAs, it is recommended that their regulatory framework provide financial and other incentives for pharmaceutical manufacturers that demonstrate a consistent history of compliance with GMP, in order to encourage a “sustained culture of compliance.”
The report recommends the establishment of a publicly available enforcement policy that includes sanctions for failing to test excipients for their identity and purity, specifically for the presence of DEG and EG. Additionally, it suggests improving information sharing among NRAs, police, customs, and other relevant government departments. This enhanced communication is aimed at ensuring rapid information exchange and timely investigations related to substandard and falsified medical products.
The report recommends that the WHO perform a formal, evidence-based, expert-led review of the list of high-risk excipients. This review should be published and shared with all Member States and stakeholders. Additionally, WHO should assess the current starting material and certification scheme, aiming to simplify the system by utilizing new technologies and incorporating high-risk pharmaceutical excipients.
For inspectors, the report recommends that high-risk pharmaceutical excipients as defined by the WHO should be prioritized during inspections to the same degree as active pharmaceutical ingredients.
In the testing area, the report recommends that all NRAs train and equip medicine quality control laboratories to test for the presence of DEG/EG in finished pharmaceutical products and excipients.
For finished pharmaceutical product manufacturers, the report recommends prioritizing that sourcing high-risk pharmaceutical grade excipients comes from approved vendors acting for the original manufacturer of the excipient. Manufacturers should also enter into a contractual agreement with their supplier stipulating the source and specification of the excipient.

WHO report

WHO, UN report uncovers supply chain weaknesses that contributed to patient deaths

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