New applications of the VDmax approach to substantiation of preselected sterilization doses

The VD_max approach for substantiation of 25 kGy has been in use for more than 10 years. VD_max methods are included in ISO 11137-2:2006 and AAMI TIR33:2005. ISO Technical Specification, 13004, is under development that will include sterilization doses from 15 to 35 kGy.For substantiation of a sterilization dose for very low bioburden products, less than or equal to 0.3, values of VD_max have now been derived and tabulated for a sterilization dose of 12.5 kGy.Products have been encountered that have both low bioburden and a relatively low maximum dose. In several situations, existing tabulated VD_max values could not be effectively used; in one such situation, the average bioburden was too high to substantiate a 15 kGy sterilization dose and the use of a 17.5 kGy sterilization dose was not practicable due to the likelihood of exceeding the product's maximum acceptable dose. For this product, values of VD_max were derived and tabulated for substantiation of a 16.1 kGy sterilization dose.Values of VD_max have been derived and tabulated for the substantiation of sterilization doses linked to a sterility assurance level (SAL) of 10^?3. To offer a potential alternative to aseptic processing, the notion of using an “aseptic processing equivalent dose”, 10^?4 SAL, has been investigated along with the use of alternate model populations for calculation of VD_max values.