Guidance issued on process control for sterilization using ionizing radiation

New part included in the BS EN ISO 11137 series of standards

A new technical specification has been issued as Part 4 to the ISO 11137 series of standards for radiation sterilization using gamma, electron beam or x-ray irradiation. This new part of the series provides guidance on process control. The series has the general title of Sterilization of healthcare products – Radiation and the four parts now consist of:

• BS EN ISO 11137‑1:2006 +A2:2019 Requirements for development, validation and routine control of a sterilization process for medical devices;
• BS EN ISO 11137-2: 2015 Establishing the sterilization dose;
• BS EN ISO 11137‑3:2017 Part 3: Guidance on dosimetric aspects of development, validation and routine control; and,
• PD ISO/TS 11137‑4:2020 Guidance on process control.

The new Part 4 document is an ISO Technical Specification (TS). It has not been adopted as a European Technical Specification but has been adopted in the UK by BSI as a Published Document (PD). As a guidance document, it is not a candidate for harmonisation to support the European Regulations for medical devices and, as such, it has not been a priority to adopt it in the European standards system.

In the ISO 11137 series of standards, measurements of radiation dose from operational and performance qualification studies are used to establish  a process that will operate consistently to meet the requirements for the minimum and maximum dose of radiation that can be delivered to products. These measurements are made with calibrated dosimetry systems traceable to standards recognized internationally and with a known level of uncertainty. The measurements are used to establish a relationship between the:

• processing parameters of the irradiator;
• dose measured at the routine monitoring position (monitoring dose); and,
• range of doses delivered to a product.

The measurements of dose also characterize the variability associated with the process itself.

The requirements for the development, validation and routine control of a radiation sterilization process are specified in ISO 11137‑1.  PD ISO/TS 11137‑4 has been prepared to provide additional guidance on establishing and routinely controlling the irradiation process. It addresses setting process target doses and verifying the process is in a state of control. Process target dose is a new term that means the dose the irradiation process parameters are set to deliver at a specified monitoring location. PD ISO/TS 11137-4 also provide guidance on the application of dose measurement as a tool in monitoring an irradiation process using statistical process control (SPC).

SPC is a specific form of data trending to demonstrate the performance of a process over time.  In radiation processing, SPC can use the collection and analysis of multiple dose points over a series of similar measurements. SPC allows for monitoring of process doses to identify patterns of response and potentially predict failures before they occur. For example, doses can remain within prescribed limits, but if the doses are  trending in one direction consistently, this can trigger an investigation before a dose is measured that is out of specification.

PD ISO/TS 11137-4 provides a significant amount of information that will be of value to operators of radiation sterilization facilities and manufacturers of medical devices that use contract irradiators to sterilize their products.

It is worth noting that, in addition to the standards comprising the parts of ISO 11137, the portfolio of standards on radiation sterilization also include PD CEN ISO/TS 13004:2014 Sterilization of health care products. Radiation. Substantiation of selected sterilization dose: Method VD_max^SD. PD CEN ISO/TS 13004 supplements ISO 11137-2 by adding additional doses that, in addition to 15 kGy and 25 kGy, can be selected and substantiated when establishing the sterilization dose.

Author: Eamonn Hoxey, of E V Hoxey Ltd, UK, is a writer, trainer and consultant on a range of life science areas including regulatory compliance, quality management, sterility assurance and standards development