Medical Device Link.

MANUFACTURING

The Panel on Gamma and Electron Irradiation has recently published a Method for Statistical Process Control of Radiation Sterilisation Facilities.^1,2 This is part of an ongoing programme of work on the utilisation of measurement uncertainty data and statistical methods. The task of producing this document has been undertaken by the Irradiation Panel’s Dosimetry Working Group, which includes recognised dosimetry experts and professionals. Working together with several operators of radiation plants, it has developed concepts that have been trialed and proven in a number of plants. The revision to ISO 11137 Sterilisation of Health-Care Products, Radiation, Parts 1, 2 and 3, which is expected to be published in 2006, includes specific requirements to take measurement uncertainty into account when product is released.

Taking better control

Control of the radiation sterilisation process has historically been based on analysis of individual dose measurements to ensure they are within defined upper and lower limits. However, this approach disregards the statistical nature of the process and can result in unnecessary investigations or product rejection when dose readings fall outside defined limits. The Irradiation Panel’s Statistical Process Control Method takes account of dosimetry and process uncertainties to define a target dose for each type of product. The process can then be monitored to ensure that variations about this dose are within the range that would be expected from prior knowledge of plant and dosimeter performance.

The Statistical Process Control Method uses a probability-based approach to determine the appropriate target dose for running the sterilisation process. The target dose is defined as the dose required to be delivered at the minimum dose location within an irradiation container. This approach takes into consideration the total standard uncertainty associated with the delivery and measurement of the sterilisation dose and maximum acceptable dose. These uncertainties are determined during the calibration of the dosimetry system, during Operational Qualification and during Performance Qualification. The method uses standardised control charts to record the doses measured during routine processing. This allows data from multiple products to be recorded on a single chart and control limits to be predefined. The points plotted represent standardised values of measured dose, the target dose and a measure of the expected variability in the dose. The process is considered to be in control if the doses measured are within the range of doses that would be expected, based on the statistical variability of both the irradiation process and the dose measurement. The logic and the methodology described in the Method enables the concepts to be applied to gamma and electron-beam sterilisation processes.

New requirements

The revision of ISO 11137 referred to above has been underway for several years and the changes included in the revised standard as a result of the review process are comprehensive. Part 1 addresses requirements for development, validation and routine control of a sterilisation process for medical devices. Part 2 outlines the requirements for establishing the sterilising dose to be applied to products. Part 3 contains guidance on dosimetric aspects associated with defining and controlling the radiation sterilisation process. Areas where there are future requirements include the scope of dose-setting methodologies, guidance on dose audit requirements, the establishment of product families and the application of dosimetric control. Readers are advised to carefully scrutinise the standard when it is published later in 2006. Understanding the requirements of this standard is essential for those involved in the manufacture of sterile medical devices. The Irradiation Panel via its members continues to have a close involvement in the development of this and other standards that affect plant operation and the delivery of sterile product.

The Panel on Gamma and Electron Irradiation
212 Piccadilly, London W1J 9HG, UK,
www.irradiationpanel.org