From Our Perspective: FDA Actions to Continue to Ensure the Safety of the Nation’s Drug Supply
[August 8, 2023] - The agency has not identified any diethylene glycol (DEG) and ethylene glycol (EG) contamination within the U.S. and will continue to enforce U.S. safeguards designed to prevent contaminated products from entering U.S. commerce.
In August 2023, FDA issued warning letters to companies that failed to provide adequate documentation to the agency about required testing designed to prevent DEG/EG contamination or that failed to respond to FDA’s requests for information. Warning letters inform firms about conditions at their facilities that appear to violate the FD&C Act but do not necessarily indicate that a product is contaminated with DEG or EG. As a precautionary measure, FDA placed certain firms that received warning letters, and their products, on either import alert 66-40 or import alert 66-79.
In May 2023, FDA announced the availability of an immediately-in-effect final guidance, Testing of Glycerin, Propylene Glycol, Maltitol Solution, Hydrogenated Starch Hydrolysate, Sorbitol Solution, and other High-Risk Drug Components for Diethylene Glycol and Ethylene Glycol. The guidance outlines recommendations to help pharmaceutical manufacturers, repackers, other suppliers of high-risk drug components, and compounders prevent the use of drug components contaminated with DEG or EG.
By Dr. Patrizia Cavazzoni, Director, FDA Center for Drug Evaluation and Research
Originally published on March 3, 2023
One of FDA’s top priorities is ensuring the safety, quality, and effectiveness of the drug products available to the American public. Manufacturers of drugs intended for the U.S. market, including over-the-counter monograph drug products, are obligated to ensure that their products comply with Current Good Manufacturing Practice (CGMP) requirements and appropriate quality specifications. FDA’s CGMP regulations for drugs contain minimum requirements for the methods, facilities, and controls used in the manufacturing, processing and packing of a drug product. The CGMP regulations help to ensure that a drug product is safe for use, and that it has the ingredients and strength it claims to have. This is important because consumers generally cannot detect through smell, touch, or sight that a drug is safe or if it will work.
Throughout history there have been occasional incidents where diethylene glycol (DEG) and ethylene glycol (EG) have been used inappropriately as inexpensive, odorless, sweet-tasting solvents in the manufacturing of medications. On October 5, 2022, the World Health Organization (WHO), the agency that leads the United Nations international efforts to promote public health, announced contaminated medications, including children’s cough and cold syrup had been found in The Gambia with unacceptable amounts of the contaminants DEG and EG. Since those initial reports, the WHO has announced that cases of DEG and EG contamination have been reported in at least seven countries and are associated with more than 300 deaths in three of those countries. Most of the deaths have occurred in young children under the age of five. This current outbreak is becoming one of the largest epidemics of DEG poisoning in history.
FDA Acts to Ensure the Safety of the Nation’s Drug Supply
Although we have no indication that any products described in the 2022 and 2023 WHO alerts have come into the U.S. drug supply chain, we are investigating the potential impact on FDA-regulated drug products. We are making every effort to prevent contaminated drug products from entering the U.S. market.
We have implemented strict safeguards to prevent DEG/EG adulterated products, including those listed in the WHO alerts, from being imported into the U.S., and we are also working with the Centers for Disease Control and Prevention (CDC), regulatory authorities in other countries, and the WHO to support investigation efforts to determine the root cause of the reported contamination. We are closely scrutinizing multiple liquid formulations of FDA-regulated drug products, including syrups, solutions, and suspensions, made with glycerin, propylene glycol, polyethylene glycol, maltitol solution, hydrogenated starch hydrolysate, or sorbitol solution.
FDA has also contacted drug product manufacturers and foreign regulatory counterparts to remind them that products intended for sale within the U.S. must meet CGMP requirements and appropriate quality specifications. This includes testing raw materials and finished product batches before release to ensure that a product is safe for use, and that it has the ingredients and strength it claims to have. We have also previously published a guidance document, Testing of Glycerin for Diethylene Glycol, [Updated Guidance as of May 2023] intended to inform stakeholders, including pharmaceutical manufacturers, pharmacy compounders, repackers, and suppliers of the potential public health risk of glycerin contaminated with DEG. This guidance document also emphasizes the need for precautions with other components of drug products, such as propylene glycol, that have demonstrated a history of contamination with DEG.
It’s important to note that all FDA-regulated drug products imported into the U.S. must comply with the same standards as domestic products. FDA has multiple tools for assessing the quality of imported drugs and protecting consumers and patients, which include site inspections, remote record requests, import entry review, detention, import refusal and sampling and testing. FDA works with foreign authorities to identify potential risks that could impact U.S. consumers and surveys world events that could impact FDA-regulated products.
Information for Consumers
- Only take medicines which were made to be sold in the U.S., especially for children. Drug standards and regulations vary from country to country, and FDA only has direct regulatory authority over the manufacture and distribution of products marketed and sold inside the U.S. Drugs sold outside of the U.S. may not meet FDA standards for safety and effectiveness. FDA generally does not evaluate medications manufactured solely for marketing and use in other countries for safety and effectiveness.
- If you have unexplained symptoms that may be related to DEG/EG poisoning, see your health care professional immediately, and tell them about any recent use of OTC products -- particularly imported products. Health care professionals and patients can report potentially linked adverse events to FDA's MedWatch Safety Information and Adverse Event Reporting Program.
- FDA does not recommend over-the-counter medications for cough and cold symptoms in certain very young children because they can cause serious and potentially life-threatening side effects. FDA-regulated manufacturers voluntarily label these cough and cold products to state: “Do not use in children under four years of age.”
We understand consumers may be concerned about the WHO’s reports of drug products contaminated with DEG and EG, and I want to reiterate that we have no indication these contaminated products have entered the U.S. drug supply chain. We will continue to monitor the situation and keep the public and health care professionals updated of any changes in status to the U.S. market.