4/5 December 2019
In June, the FDA published a new guidance for industry draft document. It is intended to help manufacturers of medical gases with detailed recommendations on how to introduce and implement GMP regulations. The FDA regards medical gases as finished pharmaceuticals that may present a major risk for patients when produced incorrectly. These recommendations apply to all gases that meet the FDA definition of a drug, a medical gas and to those listed in the U.S. Pharmacopoeia.
The new document replaces the previous version from 2003. This was as well only available as a draft version. The document is very comprehensive and is divided into the following chapters:
The first chapter mainly lists the quality unit requirements for manufacturers of medical gases. The FDA demands the functions for approvals and failure investigation, but also for quality agreements and supplier qualification (of suppliers and service providers). In small companies, these roles can also be performed by one individual. The main focus of the "Building and Facilities" chapter is on the requirement of a quarantine area. As it is common practice to refill labeled containers, this is the only way to prevent container mix-ups.
The "Equipment" chapter discusses the filling equipment requirements and their qualification. The FDA is critical of valves that may cause contaminations of gases. The topics of cleaning, equipment maintenance and calibration are also covered.
The chapter on container and container closure systems is very extensive. Apart from the general requirements that the containers must have no adverse effect on the product, there are test descriptions for valves, connectors and pressure displays for instance. A smell test which can be used to check for residual gas (except for carbon dioxide, nitrogen oxides and toxic gases) in the container is described as well. To check for corrosion on the inside of stainless steel cylinders, the "hammer test" is mentioned, where a hammer or a similar tool is used to softly knock against the outside of the cylinder.
The chapter on "Production and Testing", however, is surprisingly short. Apart from the requirement that the manufacturing process of a medical gas must be validated, it explains the temperature dependency of the pressure display during filling as well as yield calculation.
The labeling of the gas containers is regarded critically, as incorrect procedures may cause product or container mix-ups. In some cases, the FDA even describes a 100-percent control of labeling here. Laboratory tests of medical gas have the same requirements as drug tests, as specified in 21 CFR 210 part i.
Furthermore, the FDA advises against the production of medical gases by purifying industrial gases, as these may contain increased levels of contamination that are not completely covered by tests.
It was possible to comment on the new draft guidance on Current Good Manufacturing Practice for Medical Gases Guidance for Industry until the end of July.