FDA issues draft guidance to help medical gas manufacturers comply with new tailored GMPs

The US Food and Drug Administration (FDA) has issued draft guidance to assist manufacturers in complying with the updated Good Manufacturing Practices (GMPs) for medical gases, which will take effect on 18 December 2025. These GMPs are tailored to the manufacturing, processing, and storage of medical gases.

Under the revised GMPs, medical gas manufacturers will be subject to medical gas-specific CGMP regulations under a new part 213 rather than the general CGMP regulations under parts 210 and 211.

The guidance states that “the regulations implementing the statutory requirements for medical gas are located in part 213. They cover the same categories as the general cGMP drug regulations in parts 210 and 211 for finished pharmaceuticals, but reflect differences in how medical gases are manufactured, processed, packed, and held.”

The draft guidance highlights the need for more specific GMPs for medical gases. The agency has received numerous reports of incidents involving medical gas mix-ups, which resulted in at least eight patient deaths and 16 serious injuries between 1996 and April 2004, according to a notice announcing a proposed rule on 10 April 2006. Since nursing homes and hospitals are not required to report adverse events related to medical gas mix-ups to FDA, “it is likely that the actual number of these events exceeds the number reported.”

The GMPs for finished pharmaceuticals under parts 210 and 211, fixed via regulations issued in 1978, “did not consider the differences in the manufacturing processes for medical gases compared to other drugs,” according to a Federal Register announcement. The announcement notes that medical gases are typically produced in a closed, sealed, pressurized system, are not expected to expire or degrade under normal storage conditions, and are stored in cylinders that are reused multiple times.

The FDA highlights in its announcement that the production of medical gases involves multiple entities that handle these gases after they leave the original manufacturer. These entities may further process, package, or store the gases. In these situations, the potential risk to patient safety from mix-ups or the unintended use of rejected or quarantined products is generally higher than the risk associated with contamination.

The guidance covers how medical gas manufacturers can comply with the new 21 CFR 213 addressing the manufacturing of these products, including the responsibilities of the quality unit; quality agreements with suppliers; equipment maintenance and cleaning; controlling incoming designated medical gas components and containers; sampling and testing of in-process materials; packaging and labeling control; laboratory controls; batch production and control records, and returned and salvaged medical gases.

The chapter on controlling incoming containers and components states that “the quality unit must examine medical gas containers and closures, including valves, for conformance with appropriate written procedures and specifications, and approve or reject them, before manufacturing or filling (§§ 213.22(a), 213.84(a) and (c) and 213.89). A manufacturer should reexamine a medical gas container or closure when it is exposed to adverse storage conditions that could cause deterioration or contamination of the medical gas. Manufacturers must also protect against container and closure leaks (§ 213.84(b)).”

The draft guidance replaces an earlier version issued in June 2017.

Stakeholders can comment on the guidance on www.regulations.gov through 30 January 2026 under docket number FDA-2003-D-0431

Draft guidance; Federal Register notice

FDA issues draft guidance to help medical gas manufacturers comply with new tailored GMPs

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