Annex 6 - Manufacture of Medicinal Gases

The concept paper explains that the current Annex 6 version dates from 2010 and does not fully reflect:

• Current industry practice and technological advancements (e.g., new safety equipment and computerized systems).
• Lessons learned from the COVID-19 pandemic and stakeholder feedback that highlighted areas needing clarification.
• Practical regulatory expectations, such as documentation and quality assurance for critical supply processes (e.g., liquid oxygen for hospitals).
• Potential gaps in addressing specific gas production scenarios such as qualification, release procedures, and unique contamination risks.

The overarching intention is not to rewrite the entire annex, but to remove grey zones and inconsistencies so that regulatory expectations align with real-world medicinal gas operations.

Manufacturers of medicinal gases in the EU or in a PIC/S member state.

The concept paper proposes a limited scope revision of the GMP Annex 6, focusing on the following expanded themes:

• Premises & manufacturing environment

Assess how general GMP requirements for premises and environmental controls apply when manufacturing medicinal gases under pressure in closed systems, to ensure appropriate interpretation of contamination control and clean areas under GMP.

• Technology & safety integration

Reflect modern safety technology use in medicinal gas operations. For example, exclusive use of gas-specific couplings and the elimination of containers lacking residual pressure valves (which are risk mitigators).

• Inspection & validation of equipment/containers

Clarify and possibly adjust inspection checkpoints and frequency for complex containers, including cylinders with integrated pressure regulator flowmeters and cryogenic vessels, which might not be sufficiently addressed in the current annex.

• Documentation requirements

Increase clarity and expectations for documentation in key supply chain activities — notably the filling and supply of liquid oxygen to hospital evaporators, which are critical to continuous patient care.

• Batch release and Annex 16 link

Consider if there should be specific provisions for medicinal gas batch release consistent with Annex 16 requirements, particularly regarding QP availability and potential for remote or retrospective certification models.

• Qualification expectations

Address gaps surrounding qualification practices for facilities and storage containers, including mobile and stationary tanks and reusable containers with complex cleaning requirements.

The concept paper also outlines a proposed timeline from public consultation through draft guideline release (Nov 2026) to final adoption by 2027.