Some of the important issues facing the sterilisation of medical devices include the sterilisation of combination products, and improvements in the processes being employed. This article outlines recent developments in X-ray sterilisation and low- and medium-energy electron beam capabilities, and reports industry association news.
Sterilisation of combination products
A number of combination products have been the subject of recent submissions to the United States (US) Food and Drug Administration (FDA) (www.fda.gov
). These include prefilled syringes, pharmaceutical preparations in implantable forms and in association with delivery systems, and implantable devices. These submissions propose sub
25 kGy irradiation treatments for sterilisation. The challenges that some of these products represent include
- the need to minimise the energy input during sterilisation to minimise drug degradation
- tight control of bioburden to facilitate low dose sterilisation
- the combination of ultra-clean processes and low energy terminal treatments.1
A recent overview in Medical Device Technology2 gives a useful synopsis of the FDA position in relation to the regulation of combination products and also provides an interesting contrast with the European environment for these products.
As part of ongoing activity towards a review of the current regulatory requirements for sterility assurance levels (SAL), a survey is being conducted by Association for the Advancement of Medical Instrumentation (AAMI ) (www.aaim.org
). It is hoped that this will determine the current status of products being manufactured with a SAL of greater than 10-6
. It should also provide further data, derived from the practical use of sterile products as measured by patient outcome and infection rate, on those products currently benefitting from sterilisation doses of less than 25 kGy. The data and practical experience gained from the survey are expected to lend further support to those manufacturers who are currently restricted by product incompatibility with the radiation doses necessary to satisfy the current requirements for SALs. A review of the findings was expected at the AAMI Working Group 90 meeting held in Washington, District of Columbia, USA, in November 2009. No information on the outcome is available at the time of writing.
In the final quarter of 2009, the first industrial scale X-ray sterilisation system in Europe at the Leoni Studer (www.studerhard.ch
) facility in Switzerland commenced its commissioning trials; the facility is expected to be fully operational in quarter two of 2010. This system is based on the IBA Rhodotron (www.iba-worldwide.com
) delivering accelerated electrons at 7 MeV into a target, which converts the electron energy into X-rays. The X-rays are directed onto pallets of medical devices undergoing the sterilisation process. The system boasts a throughput potential in excess of 124 000 m3
per year, and a dose uniformity ratio (maximum to minimum dose spread) of better than 1.5 for product with a density of 0.3 g/cm3
; and the treated pallet is relatively independent of effects from neighbouring pallets. Economic performance of the system versus alternative sterilisation methods (gamma radiation) has always been a challenge for X-ray technology and with this system IBA claims to have achieved parity. However, in the final analysis it is effectively a comparison between cost and supply chain issues of electricity versus cobalt 60.
Low- and medium-energy electron beam
Getinge Linac (www.linactechnologies.com
) recently announced the installation
of one of its Sterbox medium energy (5 MeV, 5 kW) machines for the sterilisation of medical devices. Believed to be the first truly in-line configuration, this machine, installed for a US manufacturer, is sterilising small medical devices that are fed directly from a blister packaging machine to the electron beam sterilisation unit, which operates at equivalent speed to the packaging system. The main benefits of this approach are the reduction of the inventory and the lead times of material awaiting sterilisation, and tight control of maximum to minimum dose spread associated with irradiating a small target. Shielding for the system is by prefabricated lead blocks, which, in principle, makes the system removable. A second machine is reported to be ready for installation at the same site.
Lower energy machines employing electron energies in the KeV range are increasingly being found in pharma-ceutical environments in conjunction with isolator technology where up to three accelerators oriented radially around delivery lines can be used to sterilise the surfaces of items entering aseptic manufacturing environments. These machines employ electrons accelerated to KeV energies and consequently can be self shielded. The low energy levels employed mean that material penetration by electron is limited to a few microns therefore material compatibility issues are minimised. Approximately 27 of these machines are now installed and systems for application to medical device manufacture are under development.
Unique industry collaboration
The International Irradiation Association (iiA) (www.iiaglobal.org
) promotes the safe and beneficial use of irradiation and represents the interests of industry members. The Association has now formally assumed responsibility for the management and organisation of the International Meeting on Radiation Processing (IMRP) Conferences. The last IMRP Conference, held in London in September 2008, was jointly hosted by Isotron (www.isotron.com
) and REVISS (www.reviss.com
) and was generally acknowledged to have been a successful meeting. The Proceedings of this Conference, which capture the technical content of the meeting, have been published in Radiation Physics and Chemistr
y and can be viewed online.3
Abstracts of all submissions and full copies of the presented papers can be found on the iiA website (www.iiaglobal.org
The next IMRP Conference is to be held on 13–16 June 2011 at the Hilton Montréal Bonaventure Hotel, Montreal, Canada. Building on the success of IMRP London 2008, the 2011 programme will offer expanded application and technology strands over three days of presentations and poster papers. Delegates will have the option of taking part in in-depth tutorials and workshops on the first day of the conference. Preparation for this meeting is gaining momentum. The event is themed “Where Science and Business Connect,” and will continue the tradition established by earlier IMRP Conferences by reflecting the industry’s unique combination of scientific and business perspectives on important current issues affecting all players. The Programme Committee has been established under the Chairmanship of Eamonn Hoxey (Johnson & Johnson EMEA, www.jnj.com/connect) and Deputy Chair, Richard Wiens (MDS Nordion, ww.mds.nordion.com) and includes passionate and committed experts from around the world. Central organisation is being provided by an organising committee chaired by iiA’s General Manager, Ruth Brinston.
iiA continues to be active in a number of other areas. Two North American industry organisations, Gamma Irradiation Processors Alliance (GIPA) and Food Irradiation Processors Alliance, formalised their long-standing informal relationships by announcing their affiliation to iiA in the summer of 2009. GIPA, assisted by iiA, has consistently been making representations and contributions to the US Nuclear Regulatory Commission (www.nrc.gov
) study (being conducted by ICF International, www.icfi.com
) on the lifecycle costs of cobalt-60. iiA understands that the deadline for completion of this study has been extended, but there are still concerns over the calibre and quality of the information being obtained.
iiA is developing a strategic plan to enhance its input to the problem of denial of cobalt shipment around the world.
Currently, it contributes views to the discussions being co-ordinated by the International Atomic Energy Agency (IAEA) (www.iaea.org
) via the International Sealed Source Producers Association (www.isspa.com
), which enjoys the status of a nongovernmental organisation with IAEA.
In spring 2009, iiA announced a change to its Board with the retirement of Bob Morrisey (Wiscasset Group) and Jean-Louis Bol (IBA Industrial), and the appointment of Arnold Herer (IBA Industrial, www.iba-worldwide.com
) to represent electron beam interests, and David Liu (Johnson & Johnson, www.jnj.com
). The organisation also undertook a survey of its members to update the Board on their views in order to inform the development of iiA’s strategic planning and its detailed activity programme. The strategy was reported to the iiA membership in November 2009 and is currently only available to members. It will be placed on the iiA website in early 2010.
Industrial sterilisation is a relatively mature technology; however, as evidenced by above developments, the industry continues to develop its technologies and to re-evaluate some of the long-standing assumptions around the requirements for sterility assurance. As an industry association that was reborn only a few years ago, iiA continues to develop its structures, membership and technical agenda to ensure that it reflects and campaigns on the critical challenges and issues facing sterilisation industries today.
1. A. Lolas, “Regulatory Approaches for Novel Processing and Innovative Products, IMRP Conference September 2008, London, UK.
2. M.E. Donawa, “US Regulation of Combination Products,” Medical Device Technology, 20, 6, 22–25 (2009).
3. Radiation Physics and Chemistry, 78,
7 and 8 (2009), www.sciencedirect.com