Understanding Gamma Sterilisation - Pharmaceutical Technology

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Understanding Gamma Sterilisation
Single-use systems used for the production of culture media and the filling of sterile APIs and drug products must be sterilised prior to use. This column will address some of the questions on how single use systems are sterilized by gamma irradiation and what documentation may be requested by regulators to support a sterile API, drug product or vaccine application.


Pharmaceutical Technology Europe
Volume 24, Issue 2

The VDmax method still requires at least 40 systems; 30 for bioburden testing (10 from each of three lots) and 10 units for sterility confirmation after low dose exposure. That's a lot of systems and a primary reason to consider simply irradiating at >25 kGy and claiming microbial control wherever a validated sterile claim is not required.

Once the mean bioburden and minimum validated sterilising dose is established, and the product goes into production with a sterile claim, quarterly dose audits are conducted to confirm that the levels of bioburden and/or their sensitivity to gamma irradiation have not changed over time. These quarterly dose audits require an additional 20 units from a current lot each time; 10 for mean bioburden analysis and 10 for irradiation at the low verification dose and sterility testing. If any of the irradiated units are found to be nonsterile, the test must be repeated at a higher verification dose, which will then qualify a new, higher production sterilisation dose for subsequent batches to return the process to a <10–6 SAL.

Addressing technical difficulties with testing of single-use systems

Because of their size and complexity, single-use systems can present some technical difficulties when assessing bioburden and sterility after irradiation. Fortunately, the standard provides some practical strategies by allowing for the grouping of similar products into families so that validation only needs to be performed with a "worst case" or representative unit. Product families are defined by common nature and source of raw materials, components and product design and size, along with assembly process, equipment and environment, etc. A single Master Product can then be identified or constructed to be the representative or "worstcase" version of all the products in the family. Sterilisation of comparable products in the family can then be rationalized as equivalent to the validated Master Product.

While this reduces the number of different systems that need to be qualified, bioburden recovery and sterility testing of large complex systems can still present formidable technical challenges. Therefore, it is common to only validate sterility of the internal product fluid contact pathway (with closures at any ports or openings) The system exterior and inner packaged space, which receives the same radiation dose, can be considered microbially controlled, but not validated as sterile.

To further ease the technical challenge of aseptic handling for bioburden and sterility testing, the Master Product can also be broken into smaller subunits, termed Sample Item Portions (SIP). These can be tested separately and have their mean bioburden and sterility results combined to establish the validated sterilising dose for the fully configured system.


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