The FDA has warned a domestic drug manufacturer about potential contamination of its products with highly toxic diethylene glycol (DEG) and ethylene glycol (EG) – compounds commonly found in automobile antifreeze.

A historical parallel can be drawn back to the 1937 tragedy involving a DEG-contaminated elixir of an oral antibiotic, sulfanilamide, which caused over 100 deaths in the U.S. This disaster led to the passage of the Federal Food, Drug, and Cosmetic Act (FDCA) in 1938, a landmark law that gave the FDA authority to oversee drug safety and required manufacturers to prove their products are safe before marketing them.

While this tragedy led to stronger regulations, history continues to repeat itself. Decades later, DEG and EG contamination remains a serious concern, with recent FDA enforcement actions highlighting ongoing failures in testing and supplier oversight.

Understanding the Sources of DEG/EG Impurities

Glycerin and propylene glycol—two widely used excipients in drug manufacturing—are also among the most common sources of DEG and EG contamination and should be tested for these impurities.

DEG and EG can make their way into these materials as process impurities or through economically motivated adulteration, since DEG and EG closely resemble glycerin in taste and appearance but are far less expensive.

Glycerin has a versatile role in the pharmaceutical industry. It can be used as a humectant, levigating agent, plasticizer, solvent, and sweetening agent. In cough syrups, for example, it provides a soothing, mucus-protective lubricating layer in the pharynx. Glycerin is also used as a sweetener in syrups and lozenges, an excipient in eyewash solutions, and is commonly found in eardrops, topical gels and creams, suppositories, and gel capsules.

The FDA has approved glycerin as a food additive and considers it “generally recognized as safe” (GRAS) for a wide range of uses. However, its widespread use does not eliminate the need for vigilance; it merely strengthens it.

Given that excipients can make up as much as 90% of a drug formulation, the risk of contamination, particularly with toxic substances like DEG or EG, carries serious implications for product safety and public health.

So, what other drug components are High Risk for DEG/EG contamination?

The FDA defines high-risk drug components as those historically found to be more susceptible to DEG and EG contamination. While the guidance does not provide a comprehensive list, it explicitly identifies glycerin, propylene glycol, maltitol solution, hydrogenated starch hydrolysate, sorbitol solution, sorbitol sorbitan solution, non-crystallizing sorbitol, polyethylene glycol and diethylene glycol as high-risk ingredients.

Among these, glycerin and propylene glycol are the most frequently used excipients in both prescription and over-the-counter (OTC) drug products. Regarding FDA-regulated products, glycerin is found in 14,631 OTC products and 2,347 prescription medicines, while propylene glycol is present in 7,243 OTC products and 8,012 prescription medicines (Table 1).

Table 1 | Number of National Drug Codes (NDCs) that contain high-risk excipients. An NDC is a unique three-segment identifier; this analysis considers only the labeler and product code segments as listed in the National Drug Code Directory.

Present-Day DEG/EG Contamination

Dextrum Laboratories was issued an FDA Form 483 on August 29, 2024, following an 11-day for-cause inspection of its Miami, Florida, manufacturing site. The firm, which performs contract manufacturing of nutritional products, dietary supplements, and other products, including oral cough and cold drug products, was cited once again for serious lapses in quality control.

Among other deficiencies found during the inspection, FDA investigators maintained that the firm “did not complete or provide testing results for a total of (b)(4) retained samples of raw materials containing high-risk drug components,” including a failure to test glycerin for diethylene glycol (DEG) and ethylene glycol (EG)—a critical safety concern.

Figure 1 | Dextrum Laboratories Inc. Form 483 in Redica Platform

What makes this finding especially alarming is the pattern of repeat violations within an unusually short span of time. The same site received an FDA Warning Letter just eight months earlier based on a July 2023 inspection with similar observations.

December 2022: A routine inspection resulted in a Form 483 with ten observations.
July 2023 (7 months later): A for-cause inspection uncovered similar issues, leading to another Form 483 and eventually a Warning Letter in December 2023.
August 2024 (8 months later): A for-cause inspection resulted in a Form 483, again citing repeat deficiencies.

The Form 483 issued August 2024 states:

“Component testing is deficient in that each component is not tested for conformity with all appropriate written specifications for purity, strength, and quality. Specifically, your firm committed to providing DEG and EG testing results for all retained samples dating back to January 2023, yet failed to fulfill this commitment. After reviewing the list provided by your Quality team, it was identified that you did not complete or provide testing results for a total of (b)(4) retained samples of raw materials containing high-risk drug components. These samples, spanning from January 16, 2023, to July 28, 2023, include critical components such as (b)(4), and (b)(4).”

This pattern is not isolated. Redica Systems’ data shows that 10 FDA inspections at this site since 2001 have resulted in a Form 483. But the recent shift—from routine oversight to a rapid sequence of for-cause inspections—suggests heightened concern from the agency.

When FDA returns multiple times within short intervals and continues to observe the same deficiencies, it becomes harder to view the issues as isolated lapses. Instead, it suggests that promised corrective actions aren’t fully taking hold. At that point, further enforcement becomes not surprising, but expected, and it is virtually guaranteed that further enforcement action will take place.

Recent Global DEG/EG Poisoning Incidents

A 2023 World Health Organization (WHO) report details numerous DEG/EG poisoning incidents since 1990, and hundreds of instances of DEG/EG contamination, primarily in Asia and Africa.

At the same time, the WHO issued worldwide health alerts regarding EG and DEG-contaminated medications in Indonesia, Gambia, and Uzbekistan. The contamination events, spanning at least seven different countries, have been linked to more than 300 fatalities, most of them in children under the age of 5.

The report notes a troubling increase in the number of reported incidents over the last 3 years with contaminated syrups detected in all regions except the WHO Region of the Americas, which includes North America. As of October 2023, the highest number of incidents was recorded in the African region.

Foreign inspections conducted by FDA have led to the issuance of Warning Letters to firms highlighting issues related to DEG and EG contamination. . In 2020 alone, three such letters were issued, to:

Sunstar Guangzhou Ltd. (China)
Huaian Zongheng Bio-Tech Co., Ltd. (China)
Dental-Kosmetik GmbH & Co. (Germany).

Each focus on testing incoming glycerin raw material lots for the presence of DEG and EG prior to releasing the lots for use in drug product manufacturing.

Additionally, each of the three warning letters included the following language:

“The drug products you manufacture contain glycerin as an ingredient. The use of glycerin contaminated with diethylene glycol (DEG) has resulted in various lethal poisoning incidents in humans worldwide. See FDA’s guidance document, Testing of Glycerin for Diethylene Glycol, to help you meet CGMP requirements when distributing glycerin for use in drug products, including testing for DEG and recommendations for supply chain integrity.”

Updated FDA Guidance on Testing for DEG/EG Contamination

In response to reports of fatal poisonings linked to drug products manufactured with DEG- or EG-contaminated components, and an alarming rise in such reports in early 2023, the FDA issued a draft guidance for industry in May 2023. Titled “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 testing requirements to prevent contamination in high-risk ingredients.

Figure 2 | Testing Guidance for Industry as found in the Redica Systems Platform

At the time of issuance of the guidance, FDA said it “had no indication that any contaminated products connected to the recent international incidents have entered the U.S. drug supply chain.”

Key Gaps Highlighted in FDA’s 2023 DEG/EG Guidance

The 2023 FDA guidance identifies several common deficiencies found when the manufacturing processes associated with DEG/EG contaminated products. The guidance aims to help companies avoid these critical mistakes:

Lack of Comprehensive Identity Testing: “The manufacturers of the liquid drug products that contained contaminated glycerin did not perform full identity testing on the glycerin raw material, including tests to quantify the amount of DEG present and to verify the purity of the glycerin received.
Overreliance on COAs: “The manufacturers of the liquid drug products containing contaminated glycerin relied on the certificate of analysis (COA) provided by the supplier of the glycerin.
Unknown Supply Chain: “The origin of the glycerin was not readily apparent from the COA. The COA obtained by the manufacturers of the liquid drug products was often a copy of a COA on the letterhead of the distributor from whom they had purchased the glycerin and not the COA provided by the original manufacturer of the glycerin. The chain of custody or distribution history of the glycerin was also not readily known, often because the glycerin might have been sold multiple times between its manufacture and its use in manufacturing the finished drug product.”

Regulatory Trends: A Pattern of FDA Action and Industry Scrutiny

The release of the updated guidance is just one indication of the FDA’s intensified focus on this issue. Recent regulatory enforcement trends further underscore the agency’s efforts to address this concern:

2022: FDA receives adverse event reports of fatal poisonings linked to DEG- and EG-contaminated drug products.
2023: FDA issues updated guidance, replacing its 2007 version, in response to ongoing safety concerns.
2024: The new guidance ranks as the second most frequently cited in human drug warning letters, appearing in 29 cases (Table 2). Additionally, Form 483 observations referencing “glycerin,” “diethylene glycol,” and/or “ethylene glycol” occur at a rate nearly 5 times higher than before 2022 (Figure 2).
2025: A Continuing Trend? Given that warning letters are typically issued 6-9 months after inspections and we are continuing to see a high incidence of Form 483s mentioning glycerin, diethylene glycol and ethylene glycol, the industry is likely to see even more warning letters in 2025.

With ongoing regulatory scrutiny and past contamination incidents serving as stark reminders of the risks, manufacturers must ensure rigorous testing and compliance.

Table 2 | FDA Guidance Document Testing of Glycerine, Propylene Glycol, Malitol Solution, Hydrogenated Starch Hydrylysate, Sorbitol Solution, and Other High-Risk Drug Components for Diethylene Glycol and Ethylene Glycol was the second most cited Guidance in 2023 and 2024 in Warning Letters with a sharp increase in 2024.

Figure 3 | Percentage of 483s containing “glycerin”, “diethylene glycol”, or “ethylene glycol”.

How the Redica Platform Helps Track Supplier Risks

Understanding the risks associated with DEG/EG contamination is critical for manufacturers, suppliers, and regulators. Companies that fail to comply with FDA guidance risk enforcement actions, supply chain disruptions, and potential liability issues. Proactively monitoring raw materials and supplier compliance can help avoid costly regulatory penalties and protect public health.

The Redica Platform enables pharmaceutical manufacturers to stay ahead of compliance risks by tracking supplier histories, FDA enforcement actions, and raw material testing practices. Through real-time monitoring of 483 observations, warning letters, and global supply chain risks, Redica provides actionable intelligence to help companies mitigate supplier-related quality issues before they escalate.

Protect Your Supply Chain—Schedule a Redica Platform Demo Now.

Conclusions

The same issue that catalyzed sweeping drug safety reforms nearly 90 years ago—DEG/EG contamination—continues to pose a serious global threat. Despite regulatory advances, recent deaths overseas and repeat FDA citations in the U.S. underscore how persistent the risks remain.

The FDA has clearly identified the most common failures: inadequate identity testing, overreliance on supplier COAs, and limited visibility into the supply chain. While no contamination-related deaths have been reported in the U.S. in recent years, the sharp rise in FDA inspection findings citing glycerin, diethylene glycol, and ethylene glycol suggests elevated risk and regulatory concern.

The FDA’s 2024 Warning Letter to Dextrum Labs may well be the first of many. For manufacturers, the lesson is clear: rigorous testing, robust supplier oversight, and full visibility into raw material origins are not optional—they are essential to protecting both patients and brand integrity. The past offers a warning. What happens next depends on how the industry responds today.