WHO TRS 1044 Annex 5: good manufacturing practices for medicinal gases

Edition and status

Annex 5 belongs to the fifty-sixth report of the WHO Expert Committee on Specifications for Pharmaceutical Preparations (TRS 1044, 2022). WHO's publication page dates it 14 November 2022 and lists it as a technical document. The text arose from the increased demand for medicinal gases, in particular oxygen for patients with COVID-19, and states that WHO GMP guidelines are reviewed and updated regularly and published in the WHO Technical Report Series.

In a Member States information session on access to medical oxygen held on 17 June 2025, WHO described its GMP for medicinal gases as directly applicable to medical oxygen, pointing to TRS 1044, Annex 5.

What it covers

The guideline focuses on the production, control, storage and distribution of medicinal gases (section 2.1). Its sections run from quality management, personnel and documentation through complaints, recalls, returns, self-inspection, premises, equipment, qualification and validation, production and quality control to product life cycle and storage and distribution (sections 4 to 17). Requirements include:

• Industrial oxygen should not be used as a medicinal gas (1.2).
• The quality system should ensure that finished products are not released before the authorized person has certified that each production batch was manufactured and controlled in accordance with product specifications (4.5).
• Cylinders, mobile cryogenic vessels and valves should be dedicated to a single medicinal gas or a given mixture (14.18); cylinders should be colour coded according to relevant standards and preferably fitted with minimum pressure retention valves (14.19).
• Checks before filling should include a positive residual pressure in each cylinder fitted with a minimum pressure retention valve, removal of previous batch labels, an external inspection for dents, arc burns, debris or oil and grease, the correct outlet connection for the gas, and valid hydrostatic or equivalent tests (14.26).
• Each filled cylinder should be tested for leaks (14.30), and each batch should be tested in accordance with the marketing authorization, authorized specification or pharmacopoeia, with a record of analysis (15.1). For a single gas filled on a manifold, the gas from at least one cylinder from each manifold filling cycle should be tested for identity, strength and purity (15.3).
• Hospital tanks refilled in place from dedicated tankers need not be sampled after filling if a certificate of analysis of the tanker contents accompanies the delivery (15.10).
• Cylinder labels should carry at least the information recommended in the pharmacopoeia, where applicable, plus items such as the gas name, batch number, manufacturer name and address and test date (6.10).

What it does not cover

The guideline does not cover the manufacture of medicinal gases in hospitals or at home for personal use. It states that its principles may be applied in those cases so that oxygen generated at hospitals or at home is suitable for its intended use and meets the appropriate quality standards (2.2). WHO's technical specifications for oxygen plants are separate documents, such as the 2020 interim PSA plant specifications (superseded by WHO's technical specifications of 31 December 2024) and the 2024 specifications for health facility oxygen systems.

Relation to other documents

• Its introduction names the guidelines of the European Union and of PIC/S as other published guidelines and says its recommendations are harmonized with the principles of similar published guidelines (1.3, 1.5). The EU text is EU GMP Annex 6.
• Its references cite The International Pharmacopoeia, 10th edition (2020). The 13th edition of The International Pharmacopoeia was published in 2025, so check the edition when a specification quotes pharmacopoeia limits.
• For cylinder marking and labels its references cite ISO 32:1977 and ISO 7225:2005.