Current regulatory approaches to ensuring drug safety: controlling ethylene and diethylene glycol impurities

In recent years, there has been an increase in cases of drug contamination with ethylene glycol (EG) and diethylene glycol (DEG) – toxic polyatomic alcohols that pose a serious threat to human health even at minimal concentrations. These hazardous substances may be present in medications as impurities due to the adulteration of raw materials or the use of substandard excipients. In response to this global threat, international regulatory agencies and national pharmacopoeias have introduced requirements mandating testing for EG and DEG impurities. This article provides a detailed review of current regulatory approaches to controlling these impurities at global and national levels. Special attention is given to the analysis of key regulatory documents and recent initiatives. The article examines WHO medical alerts (2022–2024), which mandate the testing of all batches of potentially hazardous excipients, as well as FDA warning letters (2023–2024) addressed to manufacturers violating GMP rules in raw material quality control. It also describes the FDA’s industry guidance on testing excipients most susceptible to EG and DEG contamination, along with the WHO methodology for monitoring these impurities in finished dosage forms. A particular focus is placed on harmonized pharmacopoeial requirements, including general chapters from various pharmacopoeias (US, Russian, European, Belarusian, EAEU, Uzbekistan, and Kazakhstan) that regulate the determination of EG and DEG in ethoxylated substances and establish maximum permissible limits – no more than 0.1% for each. Notably, the article mentions a new general pharmacopoeial monograph introduced in the Pharmacopoeia of the Republic of Uzbekistan, which allows for the control of EG and DEG impurities in finished dosage forms. Special emphasis is placed on risk minimization strategies at all stages of drug manufacturing and the need for a comprehensive approach to drug safety. The analysis of international experience and modern regulatory practices helps identify key directions for ensuring drug safety, including harmonizing standards, strengthening quality control, and implementing advanced analytical methods.