Diethylene glycol: Unnoticed threat in the landscape of fixed-dose combination medications

Abstract

Diethylene glycol (DEG) and ethylene glycol (EG) are organic compounds often found in various consumer products, including antifreeze and industrial solvents used in pharmaceutical preparations, as well as serving as raw materials for polymer manufacturing. Since September 2022, seven consecutive episodes of DEG and EG contamination have been reported across at least nine countries. A notable commonality among the affected products is that at least 14 of them are fixed-dose combinations (FDCs). However, the evidence supporting the efficacy of most of these combinations is insufficient, which renders their prescription, dispensing, and use irrational. Moreover, these products are not without risk, as they can cause adverse reactions. Several factors contribute to the prevalence of these irrational FDCs, including low production costs, consumer popularity, and a tendency to authorise locally manufactured products. As a result, many countries’ pharmaceutical markets keep marketing authorisation for irrational FDCs. The persistent reports of DEG or EG contamination – especially those involving irrational fixed-dose combinations – present a crucial opportunity to enhance quality control measures. In addition, it is imperative to reevaluate the marketing authorisations of these products that lack evidence of safety and efficacy, adapting the national medicines lists and clinical guidelines to WHO recommendations. Strengthening regulatory frameworks and implementing stringent manufacturing and quality assurance standards are essential to prevent contamination incidents and ensure the safety of pharmaceutical products.