FDA’s New Medical Gas Guidance Is No Laughing Matter

FDA recently published draft guidance explaining how medical gas manufacturers should comply with new regulations that become effective today, December 18, 2025. As an early gift for the holidays, the industry is getting its own set of Current Good Manufacturing Practices (cGMPs). These cGMPs were first unveiled when FDA published a final rule in June 2024, so the medical gas industry got to peek at its presents before they are formally unwrapped today. While the cGMPs are now in effect, comments on the draft guidance are open until January 30, 2026.

Medical gases include both designated medical gases (oxygen, nitrogen, nitrous oxide, carbon dioxide, helium, carbon monoxide, and medical air that meet USP standards) and other FDA-approved gases, gas mixtures, and combination products used for therapeutic purposes. The medical gas supply chain extends from original manufacturers who produce the gas to transfillers who transfer finished medical gas from one container to another. The guidance addresses challenges similar to some of those faced by the drug industry like filling errors and container integrity, but in a light that highlights the unique ways those problems affect the medical gas industry.

The new regs are needed because of these differences, and because over the years, FDA has received several reports of medical gas errors that resulted in patient deaths and serious injuries. As nursing homes and hospitals are not required to report adverse events associated with medical gas mix-ups to FDA, the agency believes that the real toll of these errors is higher.

Prior to the new regulations and draft guidance, medical gas makers followed 21 CFR §§ 210 and 211, as do manufacturers of finished drug products. The 2024 Federal Register notice explained that as of today, the newly minted 21 CFR § 213 replaces Parts 210 and 211 for these products. FDA designed Part 213 for the specific ways companies make, package, refill, and store medical gases and their containers. Companies produce these gases in closed pressurized systems. The gases themselves don’t chemically degrade under normal storage, though manufacturers may still apply expiration dates when required by specific drug applications or when they choose to guarantee container integrity for a defined period.

What distinguishes Part 213 from the drug CGMP container provisions under Part 211? As these provisions are entirely specific to medical gas makers, the new regulations release the industry from the burden of trying to fit the square-peg needs of their industry into the round-hole regulations that weren’t written for them. Part 213 addresses the unique and specific ways companies actually manufacture these products without necessarily sacrificing quality, patient safety, or efficacy. For example, you’d never hear this about traditional drugs, but the guidance clarifies that outdoor spaces and delivery truck beds can serve as appropriate areas for certain operations.

Additionally, manufacturers reuse containers many times. The guidance clarifies best practices for supplier qualification, container leak prevention, facility maintenance, labeling controls, and handling returned cylinders. The industry had previously struggled with these issues under regulations written for traditional drugs.

FDA also established Part 230 for certifying designated medical gases that meet USP standards. Congress created this category because these seven gases predate FDA’s drug approval system. Before Part 230, manufacturers faced a regulatory paradox: they had to comply with drug regulations but couldn’t submit traditional drug applications for these gases, which have been in widespread medical use since before the Second World War. Part 230 solves this by providing a streamlined certification path that acknowledges that the discovery of new kinds of adverse events is unlikely while also bringing them under oversight specific to the industry. FDA exempted these gases from periodic safety reporting since new safety issues rarely emerge, but companies must report serious adverse events within 15 calendar days when those events meet reporting criteria.

FDA defines “medical gas manufacturer” broadly, capturing the potentially long supply chain. The definition includes any entity that produces gas by chemical reaction, physical separation, air compression, purification, or combining gases. This covers original manufacturers through downstream entities that manufacture, process, pack, or hold medical gases.

The industry has advocated for these changes since the 1970s, and these new rules have been in the offing since Congress ordered FDA to write medical gas regulations in 2017. Some years, holiday presents are worth waiting for.