FDA Issues Directive for Thorough Methanol Testing in Alcohol-Infused Products

The US Food and Drug Administration (FDA) has released a set of final guidelines aimed at providing assistance to manufacturers and compounders in the critical task of testing alcohol-based products, including both ethanol and isopropyl alcohol, for the presence of methanol. This comprehensive guidance, issued on October 17, 2023, came into immediate effect.

One notable aspect of the updated guidance is its deliberate shift in focus from the context of the COVID-19 pandemic. This expanded directive extends its scope to encompass not only hand sanitizers but a wider array of products that employ pharmaceutical alcohols (PAs). In doing so, the FDA has signaled its concern about the potential vulnerability of other drug products that incorporate ethanol or isopropyl alcohol, collectively referred to as pharmaceutical alcohol. These particular substances serve as key active ingredients in various pharmaceutical products, making their potential susceptibility to methanol contamination a matter of significant concern.

The agency explained that the demand for pharmaceutical alcohol as the active ingredient of those products had also increased as a result of the heightened demand for hand sanitizer products during the COVID-19 pandemic. The significant strain placed on supply chains during the pandemic heightened the vulnerability of key ingredients to economically motivated adulteration. This economic incentive to adulterate supplies raised the risk of methanol contamination. It's important to note that while the COVID-19 Public Health Emergency concluded on May 11, 2023, the FDA determined that the recommendations from the 2021 guidance remained applicable even in non-pandemic contexts.

The FDA continues to actively issue warning letters to companies found to be manufacturing products that contain unacceptable levels of methanol, as part of their commitment to ensuring public safety.

In accordance with the final guidance, manufacturers and compounders are expected to adhere to the established methanol limits as specified in the United States Pharmacopeia (USP) monographs for alcohol, which encompasses both ethyl alcohol (ethanol) and isopropyl alcohol. The set limit stands at 200 parts per million (ppm), and any products exceeding this threshold will be categorized as adulterated, highlighting the gravity of methanol contamination.

The guidance further underscores the critical importance of drug manufacturers being fully aware of the entities involved in producing all the ingredients within the supply chain, including pharmaceutical alcohol. This emphasis on transparency and traceability is designed to promote stringent quality control measures and prevent the inadvertent incorporation of methanol into the final products. Additionally, the guidelines stress the importance of thorough testing throughout the production process, and they highlight the potential hazards associated with neglecting this essential aspect.

The origins of the methanol contamination issue can be traced back to the spring of 2020 when numerous hand sanitizer products were found to be labeled as containing ethanol but were subsequently tested positive for methanol contamination. Tragically, consumption of some of these contaminated hand sanitizers led to methanol poisoning, resulting in serious health risks. In certain cases, manufacturers even labeled their products as containing methanol, despite the fact that methanol is unequivocally deemed an unacceptable ingredient in any drug product, as clearly stated by the FDA.