Single-use systems (SUS) are widely used throughout the pharmaceutical industry for manufacturing drug substance and drug product. After manufacture and packaging, many SUS are sterilized using gamma rays, typically emitted by radioactive Cobalt-60.
However, industry demand for gamma irradiation (GI) is outpacing the available Cobalt-60 supply despite an increasing number of available nuclear reactor source sites. Also, the cost and enormous complexity of the Cobalt-60 supply chain have decreased drivers for increasing GI capacity.
To ensure sufficient ionizing radiation sterilization capacity, the biopharmaceutical industry is now implementing sterilization by x-ray irradiation (XI) as an additional sterilization technology.
Suppliers have started notifying customers of implementation plans and timelines for XI, which have highlighted end-user challenges due to insufficient standardized risk evaluation guidance to inform the evaluation, qualification/validation, and documentation of these changes.
How to evaluate XI
BioPhorum has published Guidance for risk evaluation of x-ray irradiation of single-use systems. This guidance provides a robust, consistent, and repeatable methodology to assess the inclusion of XI as an alternative sterilization modality to GI-treated single-use products. The guidance is accompanied by an XI Risk Evaluation Tool that defines our approach to evaluating XI for sterilization of SUS.
Our equivalency risk evaluation supports the transition to XI implementation using seven steps: trigger, review data, categorize, evaluate, mitigate, update matrix, and close. Together, these steps provide a standard methodology to assess XI change notifications.
This is supported by a detailed end-to-end risk evaluation flowchart of the XI implementation cycle, which emphasizes key decision points. This templated risk evaluation approach uses established material data to inform likely component sensitivities within the scope of implementing XI in addition to GI and further highlight risks that may require mitigation.
By following the guidance, any risk evaluations completed for materials commonly used in SUS will provide you with rigorous empirical data sets that document this equivalency. Also, if they are written to encompass worst-case conditions, these completed risk evaluations can be leveraged to support future evaluations for similar parts. The approach highlights the use of industry and supplier data to inform case-by-case risk evaluations for SUS components, which can then be combined to encompass the bill of material for complex SUS assemblies or related SUS families.
From a regulatory perspective, the risk evaluation supports interactions with health authorities, with XI considered a like-for-like change from GI. This recommendation is supported by multiple supplier and end-user data packs.
The goal is to proactively evaluate equivalency between GI- and XI-treated products to reduce or mitigate any specific risk assessment needs at the local manufacturing site. While this method may be re-evaluated as additional industry resources become available, it will allow you to begin assessing change notifications immediately and to proactively define an implementation strategy in collaboration with suppliers. Using this method, risks to process execution, product quality and patient safety will remain low.
This BioPhorum XI risk evaluation approach builds on work published by the BioProcess Systems Alliance, which enables the assessment of physical and functional equivalency between products sterilized using GI and XI.
For more information, download the paper here and contact Louisa Mitchell, Global Change Facilitator, at email@example.com