- Annex 12 of EudraLex Volume 4, titled Use of Ionising Radiation in the Manufacture of Medicinal Products, provides specific guidance on the application of Good Manufacturing Practice (GMP) when ionising radiation is used during the production process. This includes both the use of radiation for sterilisation of medicinal products and for other purposes such as decontamination or treatment of raw materials, packaging components, or intermediates. Given the complex nature of radiation processes and their potential impact on product quality and safety, the annex establishes rigorous standards to ensure that such methods are consistently controlled, validated, and scientifically justified.
- The annex requires that all irradiation processes be carried out according to predefined, validated procedures that ensure proper control of the radiation dose and uniform distribution across the product. This includes thorough dose mapping, calibration of dosimeters, and ongoing dose verification to confirm that each part of the load receives the correct radiation level. Both minimum and maximum doses must be established based on product-specific characteristics and justified scientifically, as over- or under-exposure may compromise product efficacy or safety.
- A key feature of Annex 12 is its emphasis on validation and documentation. Prior to routine use, all irradiation processes must be validated to demonstrate consistent performance within defined parameters. Detailed documentation must be maintained for every irradiation batch, including records of dosimeter readings, equipment settings, product loads, and confirmation that the intended dose range was achieved. If irradiation is performed by a third-party contractor, a technical agreement must be established to ensure compliance with GMP, and the contract facility must be audited regularly.
- The annex also outlines the responsibilities of the Qualified Person (QP) in relation to irradiated products. The QP must ensure that all necessary data regarding the irradiation process, including validation records and batch-specific information, are available and compliant before certifying the product for release. It is also the QP’s responsibility to verify that irradiation has not adversely affected the product’s stability, quality, or regulatory compliance. Any deviation from established procedures must be thoroughly investigated and appropriately documented.
- Annex 12 acknowledges that ionising radiation may be used for purposes other than sterilisation, such as bioburden reduction or treatment of excipients, provided that the rationale is scientifically justified and supported by appropriate studies. In such cases, manufacturers must still apply the same level of control and validation as for sterilisation processes. Furthermore, compliance with national and international radiation safety regulations is required to protect both personnel and the environment.
- In conclusion, Annex 12 of EudraLex Volume 4 sets out a robust regulatory framework for the controlled use of ionising radiation in pharmaceutical manufacturing. It ensures that irradiation processes are based on scientifically sound principles, thoroughly validated, and consistently monitored. Through stringent documentation, process control, and QP oversight, the annex safeguards the integrity of the product and ensures patient safety, while enabling the effective use of irradiation technology in line with GMP standards.
Further reading:
- EudraLex – Volume 4 – Good Manufacturing Practice (GMP) guidelines
- EudraLex – The Rules Governing Medicinal Products in the European Union, Volume 4 EU Guidelines for Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use Annex 12: Use of Ionising Radiation in the Manufacture of Medicinal Products
