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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