FDA Safeguards Drugs from Ethylene Glycol and Diethylene Glycol Contamination

US: The FDA has released new guidance for the testing of high-risk drug components for Diethylene glycol (DEG) and Ethylene glycol (EG). The guidance recommends that pharmaceutical manufacturers, compounders, repackers, and suppliers immediately start evaluating high-risk drug components for the presence of DEG and EG. The high-risk ingredients specified in the guidance include Glycerin, Propylene Glycol, Maltitol solution, Hydrogenated starch Hydrolysate, Sorbitol solution, and other components. This recent publication aims to raise awareness among manufacturers of their duty of care to consider the possible contamination of pharmaceutical materials with these harmful substances. This is not a new issue; it can be traced back to 1937 when DEG was deliberately added as a solvent to the elixir of sulphanilamide resulting in hundreds of children dying from kidney failure.

Kidney disease continues to be a major health concern in the United States. According to recent statistics, an estimated 2 in 1,000 Americans are living with end-stage kidney disease (ESKD) which requires kidney transplant or dialysis. Sadly, kidney failure has resulted in hundreds of deaths per year, with an age-standardized death rate of 15.6 deaths per 100,000 population. Patients from minority and low-income backgrounds are disproportionately affected by the disease. Chronic kidney disease (CKD) is the ninth leading cause of death in the US and affects more than 1 in 7 citizens, making it a serious public health problem. It is important to raise awareness about kidney disease and its risk factors to prevent further cases and fatalities.

Although there is no evidence of contaminated products in either the US or UK supply chains, it's worth noting that the UK's Medicines and Healthcare products Regulatory Agency (MHRA) has followed the FDA's lead by providing guidance to the UK pharmaceutical industry. While the UK has not experienced any contamination issues thus far, it's important to consider the lack of testing measures in place for Sorbitol Liquids and Maltitol Solution in the corresponding PhEur monographs. Despite the FDA implementing a specific test for EG and DEG in their USP monograph, this has not been adopted in the UK. This raises the question of why such measures haven't been implemented for these products within the UK market.

Butterworth Laboratories routinely conducts tests to determine the presence of EG and DEG in Glycerin, Propylene Glycol, Maltitol Solution, Noncrystallizing Sorbitol Solution, Polysorbate 20, and Polysorbate 80. While it's not uncommon to find low levels of DEG and EG in Glycerin and Propylene Glycol, it raises the question of why these substances are also found in Maltitol Solution, Hydrogenated Starch Hydrolysate, and Sorbitol Solution. It's important to consider whether this is due to degradation or by-products of the manufacturing process.