MANUFACTURING
Rising horizons
The International Meeting on Radiation processing (IMRP) takes place every two years. It is a unique forum that features contributions from basic research and technical developments
through to the business of operating commercial successful radiation processing. The programme of the next IMRP, which is being held on 21–25 September 2008 in London, UK, (www.imrp2008.com), plans to lift the horizon on radiation processing and its future developments. This article provides an update on some of the significant developments occurring in this field and gives an overall outlook on what is new in radiation sterilisation.
Combination drug–device products
New generation combination products that contain a drug or other biological active component are demanding fresh thinking and novel approaches to terminal sterilisation, which must be addressed much earlier in the research and development process. Two workshops have been held to explore the technical challenges and practical aspects associated with the radiation sterilisation of these products. Hosted by the International Irradiation Association (iiA), these took place in December 2006, in San Diego, California, USA, and in June 2007, in Washington, District of Columbia, USA. Presentations from these two workshops are downloadable from the iiA website (www.doubleia.org). Some of them are reviewed below.
At the June 2007 meeting, there were two notable presentations of vital interest to standards development and those interested in advancing the use of radiation processing:
- “Sterility Assurance Versus Safety Assurance” by Robert Morrissey (Vice President, now retired, Operations Preparedness and Technology, Johnson & Johnson, New Brunswick, New Jersey, USA) and Cathie Nutter (retired scientific reviewer, Office of Device Evaluation, Center for Devices and Radiological Health, United States (US) Food and Drug Administration (FDA)). In their ten observations, the presenters noted that sterility assurance levels (SALs) evolved from the food industry and the US spacecraft sterilisation programme and that the choice of SAL 10-6 has been arbitrary. Those who define sterility in terms of a single SAL think that a product with a 10-6 SAL is intrinsically superior to a product with a 10-3 SAL. However, no relationship has been established between a given SAL and product safety. SALs should be based on the intended benefits derived from the use of the product.
- “Center for Drug Evaluation and Research (CDER) Review of Sterilisation of Combination Products” by David Hussong (CDER, Office of Pharmaceutical Science, FDA, Rockville Maryland, USA). In his conclusions, Dr Hussong observed there is room for improved knowledge of irradiation sterilisation of products with low bioburden and new processes are encouraged; innovation needs to focus on demonstrating that the product is safe.
New guidance
Several initiatives are currently underway. An Association for the Advancement of Medical Instrumentation (AAMI) Technical Information Report (TIR) task group is developing a modified Method 2 that is suitable for low bioburden or “ultra, ultra” clean products, pharmaceutical items and combination drug–device products.
The American National Standards Institute/AAMI document, ST 67, Sterilisation of Medical Devices, Requirements for Products Labelled “Sterile,” is coming up for review (www.aami.org). This document provides guidance on selecting an appropriate SAL for a terminally sterilised medical device or maximum contamination rate for an aseptically processed medical device. In Europe, EN 556 specifies SAL. It can be anticipated that considerable discussion and debate will go into developing a revised document that reflects current realities with the convergence of health care products and the need for an international harmonised standard.
A supportive industry
Sharing sterilisation experiences is a hallmark of the radiation processing industry. At the June 2007 workshop, Byron J. Lambert (Advisor Sterilisation and Material Engineering, Abbott Vascular, Temecula, California, USA) gave a presentation titled, “Compatibility of Drug–Device Materials Subject to Radiation Sterilisation.” This provided guidance on material compatibility, protocol guidance including case studies, and the latest industry work on AAMI TIR 17 and Working Group 96, Compatibility of Materials Subject to Sterilisation.
Dusan Razem (Ruder Boškovic Institute, Zagreb, Croatia) has produced a comprehensive review on the “Effects of Irradiation on Controlled Drug Delivery (CCD)/Controlled Drug Release Systems (CCR).” In this, the significance of CDD/CDR systems is considered with a special emphasis on the role of irradiation for sterilisation and crosslinking developments over the past 15 years. The review is available at www.sciencedirect.com/ref and is published in Radiation Physics and Chemistry, March 2008.
Advances in facility technology
The use of high energy X-rays to sterilise products is gaining renewed interest. This is because of the arrival of new higher powered electron beam accelerators with greater conversion efficiencies and IBA SA (Louvain-La-Neuve, Belgium) continues to lead the development of this technology. Designers of gamma irradiators are equally meeting the challenge with innovative designs and proposed modifications to existing equipment thus enabling the sterilisation of combination drug device products. The latest ground breaking developments are expected to be unveiled at IMRP 2008.
The International Atomic Energy Agency (IAEA) Safety Series No. 107, Radiation Safety of Gamma and Electron Facilities, 1992 is being revised. The proposed new guide includes X-ray and the current thinking on the safe design and operation of irradiation facilities. This document has been approved and submitted to the IAEA publications committee for release in 2008.
Progress in mathematical modelling and process control
Mathematical modelling has emerged as one of the next frontiers of advancement in the use of radiation processing. It is discussed in the following documents:
- “Review Monte Carlo Modelling Codes” by the Irradiation Panel. This includes an introduction to six software packages that are of potential interest for modelling irradiation facilities and predicting dose distribution. It is available on the Panel’s web site: www.irradiationpanel.org/
publications/publications.asp - “Selected Applications of Mathematical Modelling Technologies to Industrial Irradiation Processing” was presented at the June 2007 workshop by Michael Saylor, President, Special Process Services LC, Vienna, Virginia, USA. It is downloadable from www.doubleia.org.
New presentations from the Radiation Processing Simulation Modelling Users Group (RPSMUG) meeting, which was held on 24 October 2007, are published on its web site: www.rpsmug.org/index.htm. They include:
- “Electron Beam Benchmarking Status Report” by Josef Mittendorfer (President, High Tech Consulting, Wels, Austria). This reports on the electron beam experiments performed at Mediscan, Kremsünster, Austria, and results of the mathematical modelling exercises.
- Benchmarking for a gamma irradiator by Kevin O’Hara (Senior Physicist, MDS Nordion, Ottawa, Canada).
- “ASTM 2232: Standard Practice for Selection and Use of Mathematical Methods For Calculating Absorbed Dose in Radiation Applications,” presented by Doug Weiss (Corporate Process Technology, 3M, St Paul, Minnesota, USA). This is up for revision.
Usefulness of meetings
The radiation processing industry is one in which many individuals from around the world gather together to help shape and expand the use of radiation processing in health care, advanced materials and consumer items and to deal with global trade issues. It is where the exchange of ideas and sharing of results leads to the development of plans and critical initiatives to further the technology until the industry comes together again.
The conference proceedings of IMRP 2006 have been published in Radiation Physics and Chemistry, Vol. 76, Issues 11–12, November/December 2007.
Ruth Brinston is Manager responsible for operational aspects at iiA, 1283 Collins Avenue, Ottawa, Ontario K1V 6C7, Canada, tel. +1 613 260 9589, e-mail: ruth.briston@doubleia.org, www.doubleia.org. The European address for iiA is c/o Isotron plc, Ground Floor Stella. Windmill Hill Business Park, Whitehill Way, Swindon SN5 6NX, UK, Arne Miller is Radiation Research Department Manager, Risø National Laboratory, Roskilde, Denmark, Cathie Deeley is International Marketing Manager, REVISS Services (UK) Ltd, Chesham, UK, and Deputy Chair, IMRP 2008 Programme Committee.
