Medical Device Link.

Originally Published EMDM May/June 2001

Industry News

A palace guard leads the opening ceremony of the International Meeting on Radiation Processing, held this year at the Palais des Papes in Avignon, France.

Ionization equipment manufacturers and subcontractors joined researchers from around the world at the majestic Palais des Papes in Avignon, France, in March for the 12th International Meeting on Radiation Processing. The biannual meeting provides industry professionals and members of academe with an opportunity to share news on scientific advances, new applications, and evolving standards. The unusual conference venue prompted chairman Théo Sadat of Thomson CSF Linac to welcome delegates to industry's "first high-tech meeting in the new millennium . . . in a historic 700-year-old building." Following a dramatic opening ceremony with a medieval accent, delegates rolled up their sleeves and got down to the business of the 21st century. In the Conclave Room, where cardinals once sat to elect a pope, and elsewhere within the palace, discussions turned to polymeric grafting, e-calibration of dosimeters, and substantiating a 25-kGy sterilization dose.

Better Polymers through Grafting

Grafting polymers by means of a radiation or UV source holds enormous potential for a range of industries including the biomedical sector, according to Adolphe Chapiro, former president of the Groupe Français d'Etudes et d'Applications des Polymères (Strasbourg, France) and noted scientific author. Calling it a powerful means to alter a polymer's properties and to create new materials, Chapiro noted that the technology permits bulk or targeted modifications. "In grafting polyethylene to acrylic acids, for example, you retain all of the properties of polyethylene while fostering strong adhesion to metals," he said. "For implant applications, a biocompatible polymer can be grafted onto the surface of another polymer that is not suited for invasive use [but which may be desirable for other properties]," he added. Although there have been few industrial applications of this technology thus far, Chapiro noted that animal trials have shown great promise.

By combining grafting with the charge-transfer (CT) complex engendered by ionized curing, a much stronger bond between materials can be created, noted Jack Garnett from the department of materials and chemistry at the University of Western Sydney (Australia). Chairing a session devoted to curing processes, Garnett told attendees that the use of photoinitiators (PIs) to promote UV-initiated and E-beam curing, as is common today, limits the effectiveness of the process. "These additives increase the cost of UV curing materials and may lead to contamination of the cured film with PI fragments," he said. Recently discovered UV- or gamma-initiated CT complexes—defined as an aggregate of two or more molecules in which the charge is transferred from a donor to an acceptor—eliminate the need to add PIs. However, he added, this may adversely affect a material's adhesion to a substrate. To remedy this, Garnett recommended concurrent grafting and curing, which can be accomplished by using either a UV or radiation source. The combination of grafting, which produces a chemical bond, and curing, which creates a physical bond, results in strong adhesion, he said. Radiation processing has an advantage over UV in this regard, he added. "With ionizing radiation systems, you produce radicals as well as positive and negative ions," Garnett explained. "This provides additional mechanistic pathways to achieve grafting."

Compact Radiation Units Introduced

A compact irradiator designed for low-volume applications was presented by MDS Nordion (Kanata, ON, Canada) at the Avignon meeting. By rethinking the structure and operation of conventional gamma sterilizers, MDS was able to substantially reduce the cost of the unit. The Brevion is affordable for a category of customers that, until now, may not have considered investing in an on-site gamma unit, according to Daniel Levesque, director of sales Europe, industrial irradiation, at MDS Nordion.

Unlike traditional gamma systems, the Brevion transports totes to the irradiator source via tracks. To reduce downtime during batch changes, MDS developed a cartridge concept that enables a single unit to process two source passes. As one batch of irradiated products slides out from the sterilizer, the track system automatically positions the second batch for processing. Changeovers are performed in less than 5 minutes, and typical processing time is 3 to 5 hours. Because there is no maze or storage conveyor and the unit is shipped largely preassembled, installation costs have been slashed by 75% compared with conventional units. Setup time is less than 4 weeks. The primary markets for the Brevion, according to Levesque, are medical device manufacturers processing small product volumes and contract service providers in developing countries with a small but growing device industry.

A compact E-beam system developed by Mitsubishi Heavy Industries Ltd. (Nagoya, Japan) was also presented at the meeting. The C-band 5712-MHz accelerator is reportedly the first of its kind to achieve 10-MeV acceleration energy. It measures 60 cm in length and weighs 20 kg. The machine is suited for sterilization and nondestructive inspection applications.

Coming Soon: On-Line Dosimetry Calibration

"Industry wants high-quality, rapid-turnaround calibration services, and, of course, everyone wants them as cheaply as possible," said Marc Desrosiers, research chemist at the National Institute of Standards and Technology (NIST; Gaithersburg, MD, USA) at a session devoted to developments in dosimetry. NIST, he added, will soon be giving the people precisely what they want.

The organization is currently testing a system that will allow companies to calibrate dosimeters via the Internet. "The company would have to be equipped with an electron paramagnetic resonance (EPR) spectrometer connected to a PC and a batch of presupplied alanine dosimeters," he explained. The Internet calibration program on the NIST server will control the evaluation and guide the technician through the various steps. A provisional certificate will be issued within a matter of minutes; after appropriate quality checks have been conducted at NIST, an official certificate will be delivered.

An obvious advantage, noted Desrosiers, is the elimination of the current 3- to 5-day turnaround time. "Calibration services will be offered on demand 24 hours a day, 7 days a week, and the results will be available in minutes." Because the process requires no oversight from NIST staff, fees will be drastically reduced, he added.

On-line calibration against the US national standard gamma-radiation source is currently undergoing testing. NIST expects to make the subscription-based service available to customers worldwide starting in 2002.

Substantiating the 25-kGy Sterilization Dose

Both ISO 11137 and EN 552, standards related to the validation and routine control of radiation sterilization, permit the use of 25 kGy as a sterilization dose provided that it can be substantiated that it achieves a sterility assurance level of 10^-6. Unfortunately, neither document provides guidance on how to show substantiation. Craig Herring, senior fellow, sterilization science, at Ethicon Endo-Surgery Inc., a Johnson & Johnson company, presented a paper in which he described a process called Method VD_^max that aids manufacturers in the substantiation of 25 kGy.

"The process is markedly similar to Method 1 in ISO 11137, which was done deliberately to avoid confusion," said Herring. "If you test 0/10 or 1/10 positive, then the dose is substantiated. If you show 2/10 positives, a confirmatory test is required; a 3/10 positive rate means that the dose is not substantiated," he explained. The method was tested in a parallel study against Method 1 at three different J&J facilities, said Herring, using three different categories of products: disposables, implants, and sutures. A total of 421 dose audits were conducted over a 3-year period without any failures, reported Herring. "Only a handful of products required confirmatory tests, all of which ultimately proved to be positive," he added. The procedure will be described in AAMI/FDSB-1 TIR 27, which will be available this summer from the Association for the Advancement of Medical Instrumentation (http://www.aami.org).

Norbert Sparrow

State-of-the-Art Prosthetic Leg Incorporates Magneto-Rheological Technology

Many of the innovations developed in the medical device industry find applications in other industries as well. Likewise, technology developed elsewhere, even for the most seemingly unrelated applications, often finds use in medical devices. When Biedermann Motech (Schwennigen, Germany), a manufacturer of spinal implants and prosthetic components, was seeking a way to improve stability, gait balance, and energy efficiency for amputees using its Smart Magnetix prosthetic leg, it found an award-winning solution in technology taken from Lord Corp.'s (Cary, NC, USA) truck-seat damper.

The unlikely collaboration culminated in the two companies sharing an award at the Annual International Symposium on Smart Structures and Materials held in Newport Beach, CA, USA. The award, presented in March, recognizes companies or individuals who develop technologies that mimic biological systems for commercial or industrial applications.

Magneto-rheological technology allows the prosthetic leg to closely re-create a natural gait.

Lord Corp., a materials technology company, modified the magneto-rheological (MR) technology found in its truck-seat damper and designed it into the Smart Magnetix prosthetic leg. Its combination of MR, electronics, and software enables the device to respond 20 times faster than prior state-of-the-art designs and therefore it achieves the closest neural human reaction time of movement for the user. In other words, the newly designed prosthetic more closely mimics the process of natural thought and locomotion than previous prosthetic designs.

Lord's MR technology is based on proprietary and patented MR fluid formulations; damper, mount, brake, and clutch designs; and sophisticated computer-control algorithms. When exposed to a magnetic field, MR materials change consistency from a fluid to a near-solid state. The materials consist of micron-sized, magnetically active particles dispersed in a carrier medium. In the presence of a magnetic field, the particles align and resist flow, leading to high forces when required to move. The materials in MR particles respond to the applied magnetic field within milliseconds, allowing for real-time control of the fluid rheology.

"Slopes and stairs have traditionally been a nightmare for an amputee," says Lutz Biedermann, president of Biedermann Motech. "But Lord's controllable material has made it possible for patients to achieve confidence in their steps. Biedermann Motech is finally able to provide a solution for stable and reliable support without noticeable differences in movement or limitations for the user."

Smart Magnetix provides fast adaptation to control knee movement, yet is robust and affordable for the amputee.

Conventional stepper motor–powered prosthetic devices lack the same degree of stability that Biedermann Motech's battery-operated and electronically controlled MR damper knee mechanisms can provide. Biedermann Motech's Smart Magnetix system adapts to all possible movement changes in milliseconds. Lord's MR damper is designed to perform in combination with sensors and software to detect and adjust to changes in walking speed, uphill and downhill motion, high and low loads, ramps, stairs, and terrain differences. The system analyzes the patient's gait to adapt knee motion appropriately and with fine control within milliseconds. MR technology provides infinitely variable, real-time damping control. The MR dampers are highly adjustable and instantly responsive to the changing needs of the device user. In contrast, conventional hydraulic shocks are not real-time adjustable, and controllable hydraulic shocks with stepper motors adjusting the valving provide less adjustability, speed, and control.

MR technology was invented in the 1940s, but the first fluids and devices had limited life and stability in applications such as shocks, dampers, brakes, and clutches. Without digital processing and fast, inexpensive computing, MR technology was never commercialized until Lord Corp. began developing the technology 15 years ago. Recognizing the need for flexible, less complicated control capabilities, it has gone beyond the original idea of MR technology to develop stable, wear-resistant suspensions that can withstand the rigors of primary and secondary suspension applications. The company has commercialized several applications that match the lifetime performance of more complicated and expensive controllable hydraulic and electromechanical systems.

For more information, contact Biedermann Motech, Bertha-von-Suttner-Str. 23, D-78054 VS-Schwenningen, Germany; phone: +49 7720 85100; fax: +49 7720 851066; Internet: http://www.biedermann.com. Or, contact Lord Corp., 111 Lord Dr., Cary, NC 27512-8012, USA; phone: +1 919 4685979; fax: +1 919 4695777; Internet: http://www.lordcorp.com.

MEDTEC Ireland Serves Industry in Transition

The medical device industry has been a key contributor to Ireland's buoyant economy. For the device sector to continue to thrive, however, most analysts agree that companies must place a greater emphasis on R&D and product development. The practical implications of this transition will be among the topics addressed at the MEDTEC Ireland 2001 Regional Conference and Tabletop Exposition. The event is scheduled on 19 and 20 September at the Radisson SAS Hotel in Galway.

Innovation and Product Development in the Medical Device Industry in Ireland and Challenging Conventions will lead the first day's sessions in a track devoted to design issues. The development and manufacture of value-added products will be illustrated through case studies presented by Tom Fitzmaurice of Medtronic. Alun Wilcox of PDD Product Innovation Consultants, a London-based design bureau, will take the debate a step further by challenging industry to question conventional thinking. Well-versed in wireless technologies and telemedicine, he will address the importance of humanizing technology. New design tools and processes, which may help medical manufactures to achieve that goal, will be highlighted in papers presented by members of Germany's Fraunhofer Institute and the Galway Mayo Institute of Technology.

Running parallel to those sessions during the conference's first day is a manufacturing track that will report on developments in material science and supply-chain management techniques. In the afternoon, the focus shifts to packaging and such areas of interest as barrier packaging, process validation, and the relative merits of thermoforming and pouch packaging. A track devoted to biocompatibility and bioengineering will include papers on finite element modelling, developments in surface treatment technology, and novel biomedical implants.

On the second day, attendees will be able to choose between a slate of sessions devoted to quality systems and broader regulatory issues or a track on plastics processing and new manufacturing technologies. In the latter category, Breda McCollum of Donegal Healthcare Ltd. will describe some simple problem-solving tools that can help to resolve injection moulding issues. The use of lasers in joining miniature components will be explored by Richard Sherlock, who has been involved in several device projects through his work at the National Centre for Laser Applications at the National University of Ireland in Galway. Addressing time-to-market issues, a supplier of housings and subassemblies to the telecommunications sector will explain how accelerated ramp-up times common to that industry can be successfully transferred to the device arena.

On the regulatory front, several experts will discuss ISO 9000:2000, designing for compliance with US FDA's quality system regulation, meeting risk management standards, and a host of related topics.

In addition to the conference, leading suppliers to the device industry will participate in the accompanying tabletop exposition. More than 80 companies will be on hand to discuss their products ranging from IV components to adhesives to tubing.

MEDTEC Ireland is organized by Canon Communications llc. To request additional information, contact Mark Temple-Smith, P.O. Box 975, Bottisham, Cambs CB5 9SF, UK; phone: +44 1223 813660; fax: +44 1223 8136611; e-mail: mark@cancom.com.co.uk; Internet: http://www.medtecireland.com.

In Quest to Eliminate Biofilm, Baker's Yeast Rises to the Challenge

The study of yeast cells may point a way toward eliminating the formation of biofilm on medical devices and implants, according to microbiologists at the Whitehead Institute for Biomedical Research in Cambridge, MA, USA.

Fungal growth caused by Candida albicans envelops devices in a resilient biofilm coating that impairs their functionality. It also engenders infections of the skin, oral cavities, esophagus, gastrointestinal tract, and genitalia. Patients with weakened immune systems are particularly vulnerable to the organism, which causes thousands of deaths each year. Observing that yeast cells stick to the bottom of plastic laboratory plates, microbiologist Todd Reynolds set out to find the yeast proteins responsible for this adherence. "The system that initiates the formation of a biofilm in baker's yeast potentially can hold true for pathogenic Candida as well," he says. "Once molecules involved in this process are identified, we can search for similar molecules in that fungus," adds Reynolds, "and ultimately find a way to neutralize them." Reynolds published his research in the February 2 issue of Science in an article coauthored by Whitehead Institute director Gerald Fink.

The researchers have identified yeast genes FLO11 and FLO8. The first encodes a cell-surface glycoprotein required for adhesion to agar, and the second gene expresses a protein that turns on FLO11 expression. Disrupting the FLO11 gene, according to the report authors, stopped the yeast cells from radiating out in their characteristic gauzy floral pattern and prevented the formation of biofilms on hard plastic surfaces.

"If there's a comparable gene in Candida and a competitive inhibitor that would interfere with its ability to bind," says Reynolds, "that could substantially inhibit the fungus from setting up a biofilm or even, perhaps, from adhering to human tissue in an infectious situation."

The fungal biofilm discoveries have been exclusively licensed to Cambridge-based Microbia Inc., a startup biotech company cofounded by Fink. Although research is still at an early stage—the company tentatively plans to begin animal trials by the end of 2002—Microbia has discussed the technology with interested device OEMs. "Ultimately, we would want to partner with several individual device manufacturers by product area," says vice president of legal affairs Sarah Cabot.

For more information, contact Microbia Inc., 1 Kendall Sq., Bldg. 1400W, Cambridge, MA 02139, USA; phone: +1 617 4563600; fax: +1 617 4940908; Internet: http://www.microbia.com.

Norbert Sparrow

Embedded Software Connects Devices to Internet

Microchip Technology's PIC18CXXX embedded microchips support Live Devices' software, which enables devices to be connected to the Internet.

A software innovation by LiveDevices (York, UK) that connects devices to the Internet may be a step forward for those looking to provide remote medical diagnostics. From patient monitoring to remote data collection using the Web, the software serves as a more attractive option for device manufacturers than products previously on the market. The software is run on low-cost hardware developed by Microchip Technology (Chandler, AZ, USA), which makes it viable for use in mass quantities of products. The software runs on the Microchip PIC18CXXX family of devices and supports basic Internet protocols. Microchip Technology's hardware is embedded into each device and can be programmed after it has been placed in a circuit board. Depending on the application, the hardware can connect devices to the Internet using an Ethernet connection, dial-up modem, or a wireless RF modem. It can accommodate up to 2 million bytes of program memory and 4 Kbyte of data memory.

If used in a medical capacity, the technology would allow clinicians to control and communicate with a variety of devices using the Internet. The devices can be remote controlled, can be provided with remote alarming, or can output vast amounts of data for storage in a custom-configured database on the LiveDevices server infrastructure. Each device is registered with LiveDevices and has its own account to monitor items like security keys and device status. Short message services (SMS) forwarding allows a device to send a short text message to a pager or mobile phone when necessary.

Live Devices engineering director Andy Hutcheon says the company hasn't dealt with medical devices to date, but that the most obvious use for medical device manufacturers is in the ability to configure a device to collect diagnostic data. "Remote collection of data for monitoring patients or for clinical trials is a distinct possibility for medical devices using the embedded software," says Hutcheon.

In addition to data collection, the technology can eliminate the need to include display controls on a single device. Multiple devices can be controlled via a handheld unit, a Web pad, or a keyboard. Hutcheon cites the example of a prosthetic limb with a digital control system as a candidate for use with LiveDevices' Internet interface. "Perhaps the prosthesis needs to be calibrated to adjust the gait. A technician could calibrate numerous prostheses remotely using a single display interface."

The company's standard software will soon be available for download at http://www.livedevices.com, and can be embedded into products by OEMs at no charge. The industrial software, which includes encryption, security, additional Internet protocols, and technical support, is offered for a fee, as is the use of the infrastructure services.

For more information, contact Live Devices, Innovation Centre, York Science Park, York YO10 5DG, UK; phone: +44 1904 435128; fax: +44 1904 435130; e-mail: info@livedevices.com; Internet: http://www.livedevices.com.

Jamie Graham

Copyright ©2001 European Medical Device Manufacturer