Introduction

This document is intended to be used in conjunction with ISO 11137‑1. One of the activities encompassed within process definition in ISO 11137‑1 is the option to select and substantiate a sterilization dose to be applied to health care products.

ISO 11137‑2 includes Method VD_max^SD for the substantiation of 25 kGy as a sterilization dose (termed Method VD_max²⁵) for product with an average bioburden less than or equal to 1 000 and Method VD_max¹⁵ for the substantiation of 15 kGy as a sterilization dose for product with an average bioburden less than or equal to 1,5.

This document extends the methods of selection and substantiation of a sterilization dose specified in ISO 11137‑2. It provides a methodology for the substantiation of selected sterilization doses of 17,5 kGy, 20 kGy, 22,5 kGy, 27,5 kGy, 30 kGy, 32,5 kGy and 35 kGy, each of which is valid only for a specified upper limit of average bioburden.

NOTE Selected sterilization doses of 25 kGy and 15 kGy are not included in this document. The seven methods in this document follow the same technical steps as the methods given in ISO 11137‑2 for selection and substantiation of sterilization doses of 25 kGy and 15 kGy. However, the descriptive text in this document has been modified to better communicate the methods and hence the text occasionally differs from that in ISO 11137‑2.

The method described in this document is for substantiation of a selected sterilization dose to achieve a sterility assurance level (SAL) of 10⁻⁶ or less at that dose (e.g. Method VD_max²⁰ for a selected sterilization dose of 20 kGy). The application of the method is not limited by production batch size or production frequency, and the number of product items irradiated in the verification dose experiment remains constant. The method is founded on and embodies the following three principles:

— existence of a direct link between the outcome of the verification dose experiment and the attainment of an SAL of 10⁻⁶ at the selected sterilization dose;
— possession of a level of conservativeness at least equal to that of the standard distribution of resistances (SDR);
— for a given bioburden, use of a maximal verification dose (VD_max) corresponding to substantiation of a selected sterilization dose.

This approach to sterilization dose substantiation was first outlined by Kowalski and Tallentire^[⁷^] and, from subsequent evaluations involving computational techniques (Kowalski, Aoshuang and Tallentire^[⁸^]) and field evaluations (Kowalski et al.^[⁹^]), it was concluded that the method is soundly based. An overview of the method and aspects of implementation are provided in Kowalski and Tallentire.^[¹⁰^][¹¹^] Application of the Method VD_max^SD approach to doses other than 25 kGy is discussed in Kowalski and Tallentire^[¹²^][¹³^].

The method described here and designated Method VD_max^SD procedurally comprises elements that closely parallel those of dose setting Method 1 described in ISO 11137‑2. One key area of difference is the number of product items used in the verification dose experiment. In the computer evaluations referred to above, changing the verification SAL value had little effect on the substantiation outcome and this finding led to a sample size of 10 product items being chosen for subsequent field evaluations and, ultimately, for inclusion in this document.

Manufacturers of health care products who intend to use this specification are reminded that the requirements contained in the ISO 11137 series apply to the manufacture and control of production batches destined for radiation sterilization. In particular, one requirement states that products have to be manufactured in circumstances such that the bioburden is controlled. The control of the quality of raw materials, the manufacturing environment, the health, hygiene and attire of personnel and for establishing the basic properties of packaging material should be maintained.

BS ISO 13004:2022

Sterilization of health care products. Radiation. Substantiation of selected sterilization dose: Method VDmaxSD

Current

Published:

31 Oct 2022