USP Initiatives for the Safe Use of Medical Gases

Medical gases (e.g., oxygen, carbon dioxide, helium, nitrogen, nitrous oxide, medical air, and combinations of these) are drugs regulated by section 201(g) of the Federal Food, Drug, and Cosmetic Act. The United States Pharmacopeia (USP) sets standards for all medical gases, including those that address quality, strength, purity, packaging, labeling, and identification. The proper handling of medical gases has been called into question during the past several years because of incidents resulting in patient harm and even death that have been documented by the US Food and Drug Administration, by the Joint Commission on Accreditation of Healthcare Organizations (JCAHO), and by USP through its Medication Errors Reporting Program. In most cases, the deaths and injuries occurred to patients who were thought to be receiving medical-grade oxygen but instead were receiving a different gas (e.g., nitrogen or argon) that had been mistakenly connected to the oxygen supply system.

In April 2001, FDA issued a Public Health Advisory addressing the reports from hospitals and nursing homes concerning deaths and injuries to patients resulting from medical gas errors (1). In the advisory, FDA pointed out that incorrect gases were administered to patients who should have received oxygen. The advisory also described recurring errors caused by a lack of training of personnel who connected gas to the systems and who failed to carefully examine the labels on the gas containers. In response, FDA made several recommendations to help prevent future errors:

• In hospitals and other patient-care facilities, medical-grade products should be stored separately from industrial-grade products.

• All personnel who handle medical gases should be trained to recognize various types of medical gas labels and should be trained to examine labels carefully.

• Personnel should understand how containers are connected to oxygen supply systems and be instructed about the serious consequences of changing or forcing connections.

• Facilities should emphasize repeatedly that the fittings on medical gas containers should not be changed under any circumstances.

• Once a cryogenic container is connected to an oxygen supply system and before the product is introduced into an air-supply system, a knowledgeable person should ensure that the correct container has been connected properly.

In 2001, the USP Medication Errors Reporting Program received a report from a community hospital indicating that mislabeled gas cylinders were delivered to the hospital. According to the report, four yellow air tanks with air tank fittings (valves) were delivered from the supplier and were mislabeled as nitrogen. An alert respiratory therapist recognized the distinctive air-tank fittings and alerted the appropriate personnel, thus preventing these mislabeled products from reaching patients. As a result of this error and others reported to FDA, USP posted an article on its Web site alerting practitioners about the possibility of medical gas mix-ups and cited the FDA Public Health Advisory (2).

Taking into account the seriousness of the situation, USP and FDA staff met to discuss the errors and establish what USP could do to prevent further medical gas errors. Part of USP's public health mission is to assure consumers that prescription and many nonprescription medications and related items used in the medical field are of high quality, that ingredients and strength of these products are consistent, and that these items are properly labeled and stored. After the meeting with FDA, USP staff published an article, "Proposed Standards for Medical Gases: A Public Health Initiative," in Pharmacopeial Forum(PF), USP's bimonthly journal of standards development and compendial revision (3). The article elicited numerous public comments and recommendations for USP, FDA, and JCAHO regarding the safe use of medical devices. They included:

• Revising USP–NF monographs on medical gases to require specific colors for medical gas containers and connections (see next bullet point also). Harmonizing this requirement with United States and Canadian medical gas suppliers was considered favorably. (For more information, see the Compressed Gas Association's Web site, www.cganet.com/FDA_materials/Medgasmixup.asp)

• Requiring specific colors for hookups, perhaps by means of plastic tabs or rings, on hospital or nursing home walls where medical gas connections are made. This action may involve coordination with JCAHO and the American Society of Healthcare Engineers.

• Revising the names of medical gases to include the term medical in the title (e.g., "Medical Oxygen USP," "Medical Air USP"). This task would be the responsibility of the USP Nomenclature Expert Committee and would result in changes to monograph titles in USP–NF and, therefore, a change in the labels. In addition, there would be revisions to the relevant section in USP–NF General Notices.

• Revising USP–NF monographs by inserting information in the Packaging and Storage section to preclude errors.

• Revising existing USP–NF medical gases monographs to bring the specifications (i.e., tests, procedures, and acceptance criteria) more in line with modern industry practices. (The monographs currently are under review.)

• Adding information about color coding to an existing general chapter or creating a new general chapter.

• Adding information to General Chapter ‹661› Containers about the characteristics of cryogenic vessels for medical gases and the labeling requirements for application to all medical gases.

Since these recommendations were proposed, USP has initiated several monograph revisions, including:

• In PF 28 (4) (July–Aug. 2002), a revision to the identification test in the medical gases monographs proposed replacing the rudimentary test requiring a burning wood splint, sometimes in conjunction with a floating balloon, with a more specific gas chromatography test. This proposed new gas chromatographic procedure was not adopted at that time.

• In PF 30 (2) (Mar.–April 2004), the use of a gas chromatographic identification test with USP reference standards rather than the certified standards was proposed. In this way, the retention time could be matched for identification.

USP also organized several meetings with the Compressed Gas Association and FDA to move the revision process forward and to determine what improvements have been initiated to address the patient safety issues acknowledged by all parties.

In 2003 FDA released a draft guidance on current good manufacturing practices requirements for medical gases (4). An attachment in this guidance cites in detail the adverse events resulting from medical gas errors. This guidance also identifies several associated CGMP violations, including:

• mislabeling;

• inadequate training of medical gas filling and delivery personnel;

• inadequate finished product testing;

• inadequate quality control.

The most recently proposed revisions to USP monographs for medical gases appeared in PF 31 (4) (July–Aug. 2005) and include changes to the packaging and labeling sections of the monographs. Specific modifications include standardizing the colors and couplings of containers as recommended in the FDA draft guidance.

USP standards are enforceable by FDA and have been recognized by other regulatory agencies around the world. They play an important role in labeling, packaging, storage, and finished product testing. USP monographs, if they are consistently observed and applied, can help reduce medical gas errors. However, adoption of the revisions proposed in 2005 regarding helium, nitrous oxide, nitrogen, and nitrogen 97% was postponed after USP received industry inquiries. As a result of the postponement, USP formed an ad hoc advisory panel on medical gases that convened its first meeting on Aug. 9, 2005 at USP headquarters. Attendees included members of the Aerosols Expert Committee, representatives of the Compressed Gas Association, and other medical gas industry representatives. Although they were unable to attend, FDA representatives were invited to participate in these discussions. Issues related to the revised medical gases monographs included identification, assay, and color-coding of containers and connections. Industry representatives also were very interested in discussing and debating issues regarding the need for updated medical gases monographs and in working to further improve the safety of medical gases.

USP will continue to work with the medical gases industry to ensure that all revisions of USP standards for medical gases are in line with industry practices and advances in technology. The USP advisory panel will continue to enlist the expertise of the medical gases industry, FDA, and practitioners to provide for the safe use of these products in our healthcare institutions and in-home care.

Kahkashan Zaidi, PhD,* is a senior scientist in the Department of Standards Development; Paul D. Curry, Jr., PhD, is vice-chairman of the Aerosols Expert Committee; and Shawn C. Becker, BSN, RN, is the director of Patient Safety at the US Pharmacopeia, 12601 Twinbrook Parkway, Rockville, MD 20852-1790, tel. 301.816.8269, kxz@usp.org

References

1. US Food and Drug Administration, Guidance for Hospitals, Nursing Homes, and Other Health Care Facilities—Public Health Alert (FDA, Rockville, MD, April 2001), www.fda.gov/cder/guidance/4341fnl.htm (accessed Oct. 11, 2005).

2. United States Pharmacopeia, "USP Practitioners' Reporting News. Medical Gas Errors," www.usp.org/patientSafety/newsletters/practitionerReportingNews/prn882001-06-19.html. (accessed Oct. 11, 2005).

3. S. Becker and G. Bormel, "Proposed Standards for Medical Gases: A Public Health Initiative," Pharm. Forum. 28 (4), 1312 (July–Aug. 2002).

4. FDA, Guidance for Industry. Current Good Manufacturing Practice for Medical Gases, (FDA, Rockville, MD, May 2003) www.fda.gov/cder/guidance/3823dft.pdf (accessed Oct. 11, 2005).