EU GMP Annex 12 - Use of Ionising Radiation in the Manufacture of Medicinal Products

What it says

Use of ionising radiation for sterilisation or other manufacturing purposes requires specific process validation demonstrating the delivered dose achieves the intended effect, dosimetry systems calibrated and controlled to verify actual dose delivered to product, and process controls addressing radiation source management and product loading configuration.

Paraphrased for plain-language clarity. Always verify against the current published regulation text.

What it means in practice

• Radiation sterilisation validation must demonstrate not just that adequate dose was delivered on average, but that dose distribution throughout the actual product load achieved the required minimum dose at every point, since uneven dose distribution could leave portions of a load under-sterilised even while the average dose appears adequate.
• Dosimetry, the actual measurement of radiation dose delivered, is the critical verification tool for this process, requiring its own calibration and control given that the entire sterility assurance claim depends on dosimetry accuracy.
• Product loading configuration during irradiation is a specific, controlled process parameter, since how product is physically arranged within the radiation field directly affects dose distribution and therefore sterilisation effectiveness.

What inspectors look for

• Whether dose mapping studies adequately characterise dose distribution throughout actual product loading configurations, not just average dose delivered.
• Whether dosimetry systems used to verify delivered dose are properly calibrated and traceable.
• Whether product loading configuration during routine irradiation matches what was validated, with deviations from the validated configuration properly assessed.

Related regulations