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Articles from 1997 In April


New Resins

Medical Device & Diagnostic Industry Magazine | MDDI Article Index

An MD&DI April 1997 Feature

MEDICAL PLASTICS

A crop of new plastics offer improved features for medical manufacturing.

There is a bewildering array of medical plastics available for manufacturers today, and the choices are still expanding as materials developers find innovative ways to deliver greater strength, flexibility, resistance to sterilization or bodily materials, or just simple aesthetic appeal.

Several materials companies have recently released new medical plastic compounds that promise important advantages for manufacturers.

AlphaGary Corp. (Leominster, MA). New medical-grade compounds that are free of bovine materials are now available from AlphaGary for extrusion and molding. According to the manufacturer, the materials, which are made with vegetable-derived stabilizers and lubricants, exhibit greater clarity and continued high performance in heat stability and melt viscosity as compared with compounds containing animal-fat microingredients. The materials are suitable for a variety of applications including Class VI radiation-resistant tubing, film, or fittings and connectors, drip chambers, and oxygen therapy equipment.

Bayer Corp., Polymers Div. (Pittsburgh). Bayer has recently announced that it is offering the first lipid-resistant polycarbonate. Makrolon DP1-1805 is highly transparent, bonds well with PVC tubing, and is designed to alleviate the problem of cracking in high-stress applications where there is contact with intravenous fluid products, particularly lipid emulsions. Selected tints and colors of the new polycarbonate meet FDA biocompatibility requirements. The material can also withstand radiation, EtO, and steam autoclave sterilization.

A lipid-resistant polycarbonate from Bayer resists cracking.

GLS Corp. (Cary, IL). GLS Corp. has just released a translucent thermoplastic elastomer compound for medical applications, Dynaflex G-2755 grade, made with one of the company's polymers. The 100% recyclable compound typically has a 52 Shore A hardness, a 415-psi tensile modulus at 300% elongation, and a 790-psi tensile strength at break.

GLS Corp.'s thermoplastic elastomer compound is 100% recyclable.

Unichem Products, a div. of Colorite Polymers (Ridgefield, NJ). A recent release, Flexchem is a medical-grade PVC compound that is designed to replace silicone rubber in applications where a high degree of resilience is required. Flexchem compounds rebound readily after compression, making them suitable for tubing that is designed for repeated pinching and releasing, like the tubing for peristaltic pumps. According to the manufacturer, the compound costs only half the price of silicone rubber. The USP Class VI compound contains ingredients that are appropriate for use in medical applications, and can be supplied in colored, white, or translucent formulations.

Dow Plastics, a business group of The Dow Chemical Co. (Midland, MI). Dow Plastics has developed a new resin that exhibits improved mold release. The company says that the Calibre 2071 polycarbonate resin was designed to respond to a substantial need in the medical device industry for a material that will produce parts that can be easily ejected from their molds. Using only minimal force when releasing newly formed parts would allow manufacturers to reduce wear on molds.

Norton Performance Plastics Corp. (Wayne, NJ). Norton has recently announced a new Tygon 2075 tubing material that is plasticizer-free, so no plasticizer can contaminate the fluid that is being delivered. The material is also flexible and can produce tubing with smooth inner surfaces, high resistance to aggressive chemicals, and good clarity. It can be sterilized with radiation, EtO, or steam methods.

The company has developed the material primarily for endoscopy, administration of chemotherapy agents, or other applications that involve circulating blood or bodily fluids. In endoscopic devices, the tubing's smooth, nonwetting surface prevents fluid adsorption or the trapping of fluids in crevices, ensuring complete delivery of irrigation fluid volume. In chemotherapy, aggressive drugs can be handled in the tubing without risk of altering the dosage or preservative content.

Gamma-10 Plastics, Inc. (Minneapolis). A new family of polypropylene medical resins that can withstand repeated high doses of gamma radiation as well as other methods of sterilization has been introduced by Gamma-10. Several of the new resins are gamma and E-beam stable even at very high doses, and all of the materials can be sonic welded, heat sealed, or heat welded.

Some of the resins, which can be supplied with customized melt indices or gamma capabilities, were developed for the manufacture of medical parts that must undergo radiation sterilization, such as syringes. The resins do not degrade or discolor after radiation dosing. Two of the materials, which are film grade, are designed for straight-line tearing for medical pouches, drapes, and tapes.

Raychem Corp. (Menlo Park, CA). Raychem has introduced MicroFit tubing, a very small, medical-grade tubing offered in two materials, MT1000 and MT2000. According to Mark Burns, product manager at Raychem, "The microtubing line features the industry's highest shrink ratio and accommodates the drive toward producing smaller, more compact medical devices." The tubing has a shrink ratio of 3:1 and fits diameters from 0.007 to 0.045 in.

Raychem's MicroFit tubing is suitable for use with compact devices.

MT1000 tubing uses a tough, semirigid fluoropolymer that is suited for applications requiring high-temperature autoclaving and cut-through resistance. The tubing can be sterilized by radiation, ethylene oxide, steam, and dry heat with no significant change in properties.

MT2000 tubing is a tough, modified polyolefin that demonstrates flexibility, lubricity, and good electrical insulation performance. The low shrink temperature enables the tubing to shrink faster than other similar materials, reducing the risk of damage to temperature-sensitive substrates.

Leslie Laine is a senior editor for MD&DI.


Copyright © 1997 Medical Device & Diagnostic Industry

Polymeric Biomaterials

Medical Device & Diagnostic Industry Magazine | MDDI Article Index

An MD&DI April 1997 Feature

MEDICAL PLASTICS

A limited number of biomaterials are available for long-term implantable applications.

The traditional definition of biomaterial is a systemic, pharmacologically inert substance designed for implantation or incorporation into the human body. Materials used must nearly duplicate the properties of the tissues they replace in order not to trigger an immune response in the body. Polymeric materials typically used for such applications include polyurethane, polypropylene, and polyimide. Typical applications include catheters, contact lenses, and hip joints. On yet another level, pacemaker leads and blood vessel replacements present additional challenges.

"More and more researchers are selecting core materials for their mechanical properties and then modifying the surface to fit a particular environment," says Karin Caldwell, a biomaterials researcher at the University of Utah (Salt Lake City). She explains that most manufacturers now choose a core material that exhibits the rigidity, tensile strength, or other characteristics they desire, then modify it to work within the environment the device is being designed for.

And, although many polymer manufacturers have begun to restrict their materials for use in only critical medical devices, some companies continue to develop and manufacture new biomaterials for long-term implants, namely, those specifically intended to remain in the body for longer than 29 days.

The Polymer Technology Group (Emeryville, CA). The firm produces the polycarbonate-based polyurethane Bionate, achieving oxidative stability by replacing susceptible ether groups with carbonate linkages adjacent to hydrocarbon groups. Such biomaterials are used in applications that have a potential mode of degradation, such as pacemaker leads. The company also uses the polycarbonate urethanes as base polymers for its surface modification technology, known as surface modifying end groups (SMEs). The SMEs are incorporated during polymer manufacture and can permanently modify surface properties, such as blood compatibility, abrasion resistance, coefficient of friction, and resistance to degradation in implants. The resulting material contains covalently bonded surface-active end groups and provides a measurable difference in interfacial tension compared with identical polymers that do not have SMEs.

One of the Polymer Technology Group's services is the continuous casting of polyurethane films or membranes for use in medical devices.

Applied Silicone Corp. (Ventura, CA). The company has introduced an implant-grade liquid silicone rubber system. The HS-series system is supplied in two-component kits that contain equal amounts of pure dimethyl silicone elastomers engineered for use in liquid-injection molding systems that produce high-strength molded parts. The liquid silicone rubber is a pumpable, colorless, translucent paste, so that when the two components are mixed together in equal portions the liquid cures to a tough, rubbery elastomer using addition-cure chemistry.

According to the company, these liquid silicone rubbers provide improved clarity and cure faster at elevated temperatures than peroxide-catalyzed systems. In addition, they produce no peroxide residues and no volatile by-products. They are designed specifically for long-term implantable devices, including catheter strain relief junctions, encapsulated electronic parts, and needle septum ports. The company recommends that device manufacturers use airless mixing, metering, and dispensing equipment for production operations to ensure the best combination of the two components. The company cautions manufacturers against using this material with polymer systems that contain traces of amines, sulphur, nitrogen oxide, organotin compounds, or carbon monoxide because the combination can interfere with curing.

The company has also released a high-consistency addition-cure silicone elastomer system for extrusion or molding. The health-care-grade high-consistency addition-cure extrudable systems are two-part platinum-catalyzed silicone elastomers designed for use in applications that require high-strength extruded or molded parts. The extrusion materials are formulated for rapid extrusion vulcanization in short-dwell cure ovens. The molding materials are formulated for extended-mix-life transfer and compression molding operations. Both contain 100% (by weight) of dimethyl silicone elastomer when cured. The products, which are supplied in equal amounts, are strained through a 25-µm screen to ensure freedom from particulate contamination. Both systems contain no volatile cure by-products and no peroxide residues.

Glasflex (Stirling, NJ). Glasflex produces an implantable-grade polymethyl methacrylate (PMMA) suitable for such applications as intraocular lenses and cement spacers for orthopedic prostheses. The material, a virgin methyl methacrylate monomer, is tested for residual monomers, molecular weight distribution values, spectral curve requirements, and other physical and chemical properties to ensure biocompatibility. The company's intraocular lens materials are available in UV-absorbing or UV-transmitting formulations with either a finite or infinite molecular weight. Using UV absorbers, cross-linking agents, and other specialized chemicals, the company develops proprietary implantable PMMA materials.

Thermedics (Woburn, MA). The firm manufacturers a line of elastomeric polyurethanes developed for tissue and blood-contact situations. Tecoflex aliphatic polyurethane was originally developed for use in the company's artificial heart program. Because it produces minimal tissue reaction and blood clotting, its use has been expanded for other implantable devices requiring biocompatibility. The aliphatic resins are reaction products synthesized of methylene bis(cyclohexyl) diisocyanate, poly(tetramethylene ether glycol), and 1,4 butane diol chain extender. According to the company, the resins can be used in many soft elastomer medical applications, such as indwelling catheters, because of easy processing and high tensile strength. Other common uses for the materials include gastric feeding, vascular access, cardiac pacing, and dialysis devices. In such applications, the materials exhibit minimal acute or chronic inflammation in short- and long-term use compared with other materials. The polyurethanes can be loaded with radiopaque materials for detection on x-ray or fluoroscope and col-ored for product identification or coding. They have relatively low melt temperatures and can be extruded or molded in a variety of durometers (hardness). The materials are tailored for prototyping and casting complicated configurations. Accord-ing to the company, the materials' composition eliminates the danger of forming methylene dianiline, a known carcinogen, which can occur in improperly processed or overheated aromatic polyurethanes.

Limited availability of materials poses a challenge for manufacturers of long-term implantables. Much research is under way to graft materials onto core polymers to increase the choice of materials for these critical applications. Currently, hydrophilic polyethylene oxide, which is unique in its ability to provide a stealth coating, is being used to covalently link to polypropylene oxide, producing a seaweedlike surface, the University of Utah's Caldwell says. Other researchers are seeking to develop polymer networks that do not absorb blood proteins for such applications as contact lenses.

Sherrie Steward is a senior editor for MD&DI.


Copyright © 1997 Medical Device & Diagnostic Industry

BUGABOO

Medical Device & Diagnostic Industry Magazine | MDDI Article Index

Originally published April, 1997

An MD&DI April 1997 Column

EDITOR'S PAGE

At last month's annual HIMA meeting in St. Petersburg, FL, the challenges posed by cost-effectiveness were the subject of much discussion, by both speakers and attendees. The crucial question, as always for the device industry, was whether innovation would be retarded, not by FDA this time, but by health-care providers and payers insisting that device companies demonstrate the cost-effectiveness of their products.

As venture capitalist Ross Jaffe put it, circumstances for developers of devices have shifted from "Field of Dreams" expectations--if you build it, they will buy--to the "Missouri Complex"--if you want them to buy, you'd better show them good data on cost-effectiveness. His fellow speaker, venture capitalist Jonathan Osgood, noted that as a result of this change, "the structure of your clinical trials will have to change to reflect demands for clinical outcomes data."

Osgood wasn't troubled by this. Indeed, he was upbeat about the prospects for the device industry. But many device companies are worried about the cost of developing these data. HIMA president Alan Magazine told me later that the Wilkerson study commissioned by HIMA two years ago found that 93% of medical devices had markets worth less than $150 million. Because of this limited payoff, he said, smaller device companies are increasingly abandoning the development of some devices rather than incur the substantial costs of outcome studies.

But is innovation in fact being dampened by this trend? This was the subject of much debate in a "Socratic Dialogue" among eight panelists and their audience. Most of the panelists felt that innovation was as plentiful as ever, if not more so, but several in the audience disagreed. No one, however, could offer evidence either way.

What was clear, however, was that the term cost-effectiveness has been poorly defined to date. As panelist Earl Steinberg said, "Most people don't understand what cost-effectiveness is and most consumers don't care." The amount of wrangling by the panelists over what it does mean, and the number of times audience members mixed it up with regulatory issues, buttressed his point.

I don't mean to minimize the importance of cost-effectiveness requirements to device companies. But I don't think it's likely that such requirements will be the undoing of innovation. Innovators will be more challenged in developing their products than in the past, but I believe that there will be highly motivated partners--large companies, financial sources, suppliers, and customers among them--ready to step in and help them over the hurdles.

During the Dialogue, moderator Arthur Miller asked whether, given the current managed-care environment, Medtronic cofounder Earl Bakken would go into his garage to pioneer something like the pacemaker today. Somehow, the question was never answered. But I think he would, since that is what innovators are driven to do.

But would he come out of his garage with a commercially viable product? Again, I think the answer is yes--but the process of getting it onto the market would be dramatically different. The medical device industry will inevitably change, and soon. But for the foreseeable future, its reliance on innovation will not.

John Bethune
[email protected]

Coating and Surface Treatment Technologies

Medical Device & Diagnostic Industry Magazine | MDDI Article Index

An MD&DI April 1997 Feature

MEDICAL PLASTICS

Advances in surface modification help manufacturers improve the physical and mechanical characteristics of their devices and enhance biocompatibility.

The last several years have witnessed an intensification of interest in the discipline known broadly as surface science. Combining aspects of materials analysis, biochemistry, molecular and cell biology, pharmacology, and toxicology, the field is increasing in prominence based on the fact that most biological reactions occur at surfaces. Any fundamental understanding of the biocompatibility of a medical device, for instance, must take into account the basic phenomena of interfaces and surfaces and the properties of proteins and cells at interfaces, as well as the characteristics of local and systemic biological reactions. Principles worked out in surface science laboratories are becoming the basis for ways of improving the function and durability of materials featured in a wide range of medical products.

A variety of methods have been developed to modify the surfaces of polymers or other biomaterials used in the device industry. Examples include conventional coating processes such as spraying or dipping; vacuum deposition techniques; and such surface-modification technologies as diffusion, laser and plasma processes, chemical plating, grafting or bonding, hydrogel encapsulation, and bombardment with high-energy particles. Traditionally, the goal was to achieve improved physical or mechanical properties in a component or device--for example, by adding a nonstick coating to a catheter for easier insertion. Increasingly, however, surface modification also aims at inducing a specific desired bioresponse or inhibiting a potentially adverse reaction. Several companies offer different surface treatment techniques suitable for device manufacturing with medical-grade plastics. The highlighted companies have contributed information about a particular technique and are not necessarily the only ones providing that type of surface treatment.

Ion-Beam Processing--Spire Corp. (Bedford, MA). Among available surface engineering methods, those employing ionized-particle bombardment have been particularly useful in biomaterial surface modification, in part because of their ability to influence surface properties without altering bulk attributes. Offering reliable, low-temperature processing at reasonable cost, ion beam­based surface treatment employs two primary techniques for treating medical devices: ion implantation and ion beam­assisted deposition (IBAD).

In the ion implantation process, accelerated ions are directed at the surface of a material and create significant changes as a result of interaction with substrate atoms. Since the ions typically penetrate to depths of less than 1 µm and low substrate temperatures are maintained, modifications are confined to the near-surface region. For polymers, proper selection of implantation parameters can produce a cross-linked surface layer with significantly improved hardness and wear resistance. The most common application in this regard is the treatment of artificial joint components made from ultra-high-molecular-weight polyethylene (UHMWPE), with benefits limited only by the shallow depth of implantation. Because ion implantation of silicone rubber or polyurethane has the effect of increasing water wettability and critical surface tension, its use on catheters made from these materials can help reduce biofouling and cumulative thrombus formation.

IBAD is a thin-film vacuum deposition process that combines physical vapor deposition with concurrent ion-beam bombardment. The technique permits the deposition of extremely homogeneous, adherent, low-stress films of virtually any coating material--including metals and ceramics--onto most substrates. Like ion implantation, IBAD is a low-temperature process that is similarly controllable and reproducible. IBAD applications include deposition of infection-resistant coatings or sealant coatings, production of flexible biosensor circuits on polymer substrates, and enhancement of polymethyl methacrylate cement adhesion to UHMWPE orthopedic components.

Light-Activated Surface Modification--BSI Corp. (Eden Prairie, MN). A number of the methods used to treat polymeric devices yield little or no direct substrate bonding and employ coatings that are extremely substrate specific, that tend to abrade or delaminate, or that are unable to bind active biomolecules. An alternative process that can result in durable, cost-effective, generic surface modification is the use of light-activated chemical immobilization of molecules having predefined characteristics. Through the use of photoreactive reagents, the technique can achieve true covalent bonding of a wide variety of molecules to most commonly employed biomaterials.

The process produces extremely thin coatings (typically from 200 to 500 nm) that can be put down with minimal loss in activity of the functional coating molecule. Control of the final coating thickness depends on photoreagent concentration, duration and intensity of photoexposure, coating application procedure, and number of successive coating layers applied. Some of the types of active molecules that can be immobilized for surface treatment purposes are synthetic hydrophilic polymers; hemocompatibility factors; cell attachments, proteins, and peptides; and synthetic and naturally derived polysaccharides. Material characteristics that can be modified include lubricity, hemocompatibility, antimicrobial properties, cell growth and tissue integration, protein and cell adhesion, and wettability.

Plasma Surface Engineering--Talison Research (Sunnyvale, CA). Adding sufficient additional energy to a gas produces a plasma--a substance sometimes referred to as the "fourth state of matter." In the case of cold gas plasma--the type commonly used for surface modification--the process involves excitation of a gas at reduced pressure by radio-frequency (RF) energy. Plasma surface engineering can be divided into three distinct modalities: ablation, or removal of materials from a surface; alteration, or chemical modification of a surface by activation or grafting of specific functional groups; and accretion, or addition of a new chemical layer (for example, a plasma- deposited film) to a surface.

The effect of a plasma on a polymer surface is determined by the gas chemistry and the process parameters of the reactor system. As with ion-beam systems, plasma treatments impact only a few molecular layers on the surface of a material. The type and degree of modification depend on the composition of the substrate, the process gas employed, the amount of reactive gas flowing through the system, and the level of applied RF power. Typical applications for plasma surface engineering include application of hydrophilic coatings to contact lenses, modification of catheter components to enhance adhesion for bonding or coating, treatment of diagnostic devices for chemical functionalization, and preparation of implant components to receive biocompatible coatings.

Antimicrobial/Antibiotic Coatings--STS Biopolymers, Inc. (Henrietta, NY). Despite the efforts of countless researchers to combat it, device-associated infection remains a major problem in medical care. Infection at indwelling catheters, for example, can result from contaminated disinfectants, from the hands of medical personnel, or as a result of autoinfection from a patient's own microflora. Such infections are not easily treated, since proliferating bacteria on the surface of the catheter can secrete a polysaccharide biofilm or "slime" difficult for systemic antibiotics to penetrate. One way of addressing device- related infection is to incorporate antimicrobial agents directly onto the surface of the device. Silver compounds (silver chloride or silver oxide) are a popular choice for infection-resistant coatings, but many commercially available silver-coated catheters are of marginal effectiveness because the hydrophobic polymer matrix limits the silver ion concentration near the device surface. A process has been developed, however, that incorporates silver compounds in a nonreactive hydrogel polymer system that provides greater aqueous diffusion from the coating and thus a greater concentration of silver ions at and just above the device surface. The coatings can be formulated for short-, intermediate-, or long-term effects; offer controllable lubricity and elution; can be applied inside lumens; and demonstrate superior adhesion, durability, and flexibility. Polymer substrates that can be treated with the technique include polyurethanes, polyolefins, polyesters, PVC, polyamides, polyimides, and silicones.

Thromboresistant (Heparin) Coatings--Baxter Healthcare Corp. (Irvine, CA).Even with the use of systemic anticoagulants, the functioning of devices such as cardiopulmonary bypass circuits, hemodialyzers, ventricular-assist devices, and stents has been associated with thrombus formation, platelet and leucocyte activation, and other complications related to the deleterious effects of blood/material interactions. Of the various biologically active substances used to improve the hemocompatibility of synthetic surfaces, heparin is perhaps the most promising. In a number of studies, heparin-coated devices have been shown to enhance various aspects of blood compatibility.

Although many techniques have been developed to immobilize heparin onto biomaterial surfaces, one of the most effective is based on the concept of "universal coating," in which the physiochemical properties of heparin are modified by incorporation of a specific binding agent onto the heparin molecules. The resulting heparin coating material has a high affinity to a variety of synthetic surfaces and retains all biological properties of the unmodified heparin. Experiments have shown that the use of immobilized heparin provides greater benefits than does administration of systemic heparin: for example, the availability of heparin-coated bypass circuits has enabled surgeons performing open-heart surgery to decrease levels of systemic heparin, which has helped reduce patient blood loss and transfusion requirements while guarding against thrombus formation.

Jon Katz is the editor of Medical Plastics and Biomaterials.


Copyright © 1997 Medical Device & Diagnostic Industry

Safety Is Key to Product Quality, Productivity

Medical Device & Diagnostic Industry Magazine
MDDI Article Index

An MD&DI April 1997 Column

Safety programs in the medical device industry maintain a relatively low profile compared to those established for quality, largely because manufacturers are primarily concerned about meeting FDA regulations--particularly in recent years. Even so, safety is an enormous consideration that can affect productivity and product quality.

"When you're looking at how to set up and run equipment safely, you're addressing quality," says Stephen Sheng, regulatory compliance manager for International Medication Systems, Ltd. (South El Monte, CA), a maker of pharmaceuticals and plastic injection moldings used in medical devices. "If a person is injured, you've lost production time and you're affecting quality," he adds.

However, compliance with FDA quality requirements--particularly good manufacturing practices--does not satisfy safety and health requirements laid down by OSHA. While FDA regulations focus on products as the means to ensure public safety, OSHA regulations seek to ensure the safety of the people making those products. As a result, companies often assign specific staff to develop and operate in-house safety programs aimed at ensuring compliance with state and federal regulations and identifying ways to keep workers on the job.

At Advanced Technology Laboratories (ATL; Bothell, WA), Cathy McCaffrey works with a full-time nurse and risk manager to establish and maintain a safe workplace environment. As the company's environmental and safety manager, McCaffrey focuses on regulations set by the Washington State Industrial Safety and Health Act. These regulations, which are implemented by the Washington State Department of Labor and Industries, are much more stringent than those of the federal government, she says.

States often use federal regulations as the core of their own safety and health programs. "The states usually add on what they think are appropriate requirements," says Robert James, now a consultant in Hempstead, MD, who served 26 years with Becton Dickinson (Cockeysville, MD), most recently as director of regulatory affairs and quality systems. Doing so allows compliance staff to focus on requirements specific to their company and locality.

But developing an effective safety program can be challenging, and no single safety program can fit all medical companies because work processes vary depending on the products and the approaches to manufacturing. Requirements for the storage of flammable and combustible liquids and the use of personal protective equipment, for example, may not apply if such chemicals or noise levels are not encountered by workers.

And there may be other concerns unique to a company, even concerns specific to medical device companies. ATL workers service used diagnostic ultrasound scanners. These scanners often include probes designed for use intraoperatively and in body cavities. "Although the risk of infection is not great, we have a strong infectious pathogen program that includes decontaminating scan heads sent back for service, before they are handled by our employees," McCaffrey explains.

Because of such special circumstances, companies must first examine their operations, processes, and work environments in the context of safety regulations. A formal audit of worker practices is the first step in establishing a compliance program, a step taken by Sheng when he set up such a program several years ago at International Medication Systems. After the operations analysis, he says, management must be informed of the results and enlisted to implement a program aimed at resolving any problems.

Workers must then be trained in how to perform their work safely. OSHA requires that educational materials, including labels and data sheets, be prepared and distributed to workers to warn of occupational hazards.

Records of safety information and instructions, worker training, and audits are essential to achieve government compliance, as inspectors inevitably request such documentation. When establishing and administrating safety programs, manufacturers must ensure that efforts meant to satisfy certain government regulations do not violate others. "Sometimes, when you change a process, you want to make sure the quality of the product has not been affected," Sheng says. Companies can do that by integrating safety and quality teams. McCaffrey at ATL works closely with specialists focused on FDA concerns, as well as concerns dictated by other federal and state agencies.

Done well, safety programs can generate benefits other than just meeting the letter of the law. They can increase morale among the workforce and create the opportunity to improve the lives of employees. "We have a very good 'return to work' program," McCaffrey says. "If employees are injured, we modify their duty so they can return sooner. The nurse works with them during this phase, while keeping in contact with the doctors." One reason for the program is productivity, she says, but more important is the mental health of the employee. "Statistics show that the longer someone is sitting at home, the more likely they are to get depressed," McCaffrey says. "We want them back here."--Greg Freiherr

True Multiplexed Analysis by Computer-Enhanced Flow Cytometry

Medical Device & Diagnostic Industry Magazine | MDDI Article Index

An MD&DI April 1997 Feature

IN VITRO DIAGNOSTICS

A personal computer and a novel assay format convert a common laboratory instrument into a state-of-the-art diagnostic device.

New and improved in vitro diagnostics (IVDs) can detect disease at the molecular level. These increasingly sophisticated assays are becoming indispensable to the diagnosis of many medical conditions, including cancer, autoimmune disorders, allergies, and cardiovascular disease.

However, the clinical impact of available IVDs may be curtailed by the current cost constraints in the health-care industry. Health-care payers often consider use of an assay justified only when the test results are presumed critical, not merely useful. The best interests of the patient are served when all relevant diagnostic tests are performed while at the same time costs are minimized to satisfy payers.

This article describes the design and mechanics of a diagnostic system tailored with these requirements in mind. The FlowMetrix system (The Luminex Corp., Austin, TX) allows simultaneous quantitation of multiple analytes with a minimum of reagents and time.

HOW IT WORKS

The FlowMetrix system incorporates three familiar, mature technologies--bioassays, microspheres, and flow cytometry--with novel hardware and software. Both immunoassays and nucleic acid­based tests are compatible with this platform.

Figure 1. Classification of 64 FlowMetrix microspheres by color. Microsphere sets are classified by their distinct red and orange emission signals. Each of the 64 sets comprises thousands of individual microspheres with a characteristic, identifying red-orange emission profile.

For years, IVD developers have been trying to achieve multiplexed analysis, but all systems developed previously functioned by splitting the sample into minute volumes, one for each test. The FlowMetrix system leaves the sample intact and adds microspheres, each of which carries an individual assay. Panels are created by combining up to 64 different microsphere-based assays into a single sample test. Multiplexed assays can be run on sample volumes as small as 5 µl.

Each assay is individually constructed around a single microsphere set with its own identifying fluorescent color. Each set of microspheres is manufactured with unique relative proportions of red and orange fluorescent dyes (Figure 1). During analysis, which takes place in a conventional flow cytometer enhanced with proprietary hardware and software, the microsphere components of each of the 64 different assays are classified according to these unique colors. The emission spectra are so tight in wavelength that, while the human eye cannot distinguish one set of microspheres from another, the processor can discern the ratio of red to orange signals from each individual microsphere.

At the same time, the relative intensity of a green fluorescent dye is also measured. This green color, associated with soluble reporter molecules bound to reagents at the surface of the 64 distinct microsphere sets, provides the qualitative and quantitative assay results. Because the intensity of a reporter molecule is read only at the surface of each microsphere, any reporter molecules remaining in solution do not affect the assay value, which makes the no-wash assay format possible.

The potential of this system can be seen in the example of a proposed emergency room test panel. A single sample of blood from a critically ill patient, added to a well containing the appropriate FlowMetrix reagents and microspheres, could be assayed for bloodborne viruses, cardiac markers, therapeutic drugs and drugs of abuse, allergic sensitivities, and hormones, as well as toxic substances (see Table I). Results would be available after a 15-minute incubation and a 10- to 20-second analysis in the enhanced flow cytometer.

Cardiac Markers Drugs of AbuseTherapeutic DrugsToxic SubstancesHormonesTumor MarkersInfectious DiseasesEnzymesAllergies and AnaphylaxisBlood Types
Creatine kinase (CK)

SGOT

CK-MB

Troponin

CK-MB isoforms
Opiates

Benzodiazepines

Barbiturates

Cocaine

Amphetamines

Propoxyphene
Digoxin

Phenytoin

Theophylline

Procainamide

Tricyclics

Neurontin

Isoniazid

Carbamazepine
Acetaminophen

Salicylates

Alcohol

Phenothiazines

Cholinesterase

Hypervitaminosis A & D
Thyroid

hCG

Catecholamines
PSA

Acid phosphatase

Ca-125
HIV I and HIV II

Hepatitis A, B, and C

Sepsis markers
Amylase

Lipase
Antibiotics

Stinging insects
A, B, O

Rh

Table I. Proposed test panel for emergency room patient screening.

Urgent genetic analysis is another possible application. Potential organ donors can be screened rapidly for the major transplantation antigens.

ASSAY DEVELOPMENT

As described above, each assay in a test panel must be individually developed on a uniquely colored set of microspheres. For instance, an assay for serum levels of human chorionic gonadotropin (hCG) has been developed by covalently attaching a "capture" monoclonal anti-hCG antibody to a uniquely colored microsphere set. After a short incubation with patient serum, a second anti-hCG antibody tagged with a green fluorescent reporter molecule is added (see Figure 2). This "sandwich" technique allows a sensitivity of 10 mIU/ml, comparable to that of other serum assays for hCG.

A similar process is repeated for each assay component of each panel. The assay type is indicated by bead color, and the assay result is determined by the intensity of the green reporter molecules. This format is applicable to both immunometric and competitive immunoassay methods, and both formats may be performed simultaneously in the same tube.

Figure 2. Immunometric "capture-sandwich" assay for human chorionic gonadotropin. Figure 3. Competitive DNA hybridization as a multiplexed tissue-typing tool.

Assays for serum analytes of widely differing concentrations are multiplexed using a single sample preparation dilution. Both the sensitivity and the dynamic range of each assay can be adjusted by controlling the number of target microspheres, the density of target on each microsphere, and the brightness or concentration of the green color attached to the reporter molecule. When assays for analytes of widely differing concentrations are multiplexed, the concentration of reactants for each assay is optimized separately.

For example, a competitive inhibition assay measures serum levels of IgG, IgA, and IgM in the same tube. The primary parameter used for multiplexing was the concentration of reporter for the IgG, which is about 10 times greater than that for IgA or IgM because in serum the concentration of IgG is about 10 to 20 times greater than that of IgA or IgM.

Sensitivity and specificity for the multiplexed assays are comparable to results from conventional immunoassays. For a ToRCH assay, five microsphere sets are conjugated with antigens to Toxoplasma gondii (toxo), rubella togavirus, cytomegalovirus (CMV), and herpes simplex virus (HSV) types 1 and 2. Human serum is buffered at a 1:400 dilution in phosphate-buffered saline for 15 minutes, then reacted with green fluorescent goat-anti-human IgG for 15 minutes, and analyzed with the FlowMetrix system in about 15 seconds. The system counts 100 microspheres of each microsphere set. Specificity was demonstrated in a competitive format by the addition of each soluble antigen, resulting in the corresponding decrease of the appropriate bead-based signal. Human serum calibrators and controls from commercial sources were used to define the limits of the assay sensitivities. Human calibrators negative for all ToRCH antigens were negative on all microsphere sets. Human calibrator sera positive for all the ToRCH antigens were positive on all microsphere sets. A serum control (Blackhawk Biosystems) defined to have only minimal reactivity to each of the five ToRCH antigens was used to compare the sensitivity of this system to that of conventional analyzers. This control was tested using the IMX machine for toxo, rubella, and CMV, and the DiaMedix machine for HSV. At a 1:400 dilution, all five microsphere sets demonstrated reactivities of 3­6 standard deviations above background. The ranges of reactivities for this same control serum run on these two enzyme-based diagnostic instruments ranged from 1.1 to 2.7 times above the limit of detection. These results indicate that the FlowMetrix system ToRCH assay is as sensitive as the IMX and DiaMedix ToRCH assays.

For development of nucleic acid­based tests, the principle is the same as that underlying immunoassays. In these tests, however, the ligand-ligate interaction occurs not between an antigen and an antibody but between oligonucleotides in a hybridization event. This reaction follows normal DNA or RNA amplification, which may be accomplished by any commercially available process.

In a test for organ transplant compatibility, different colored beads are conjugated with distinct oligomers representing different alleles for each histocompatibility gene. Oligonucleotides complementary to 14 different allelic sequences of the HLA-DQA1 locus were covalently attached to 14 different microsphere sets. Fourteen green-labeled oligonucleotides complementary to the 14 allelic sequences were also included in the reaction mixture. In the absence of inhibitor, hybridization yielded 14 bright green fluorescent microspheres. The polymerase chain reaction (PCR)-amplified patient DNA competes most effectively for binding to the microsphere bearing the complementary capture probe, displacing the reporter molecule and thereby lowering the intensity of green fluorophore at the microsphere surface (see Figure 3). Sequence identity, and thus histocompatibility allele, are thereby determined.

In a preliminary trial, this HLA-DQA1 tissue-typing system detected the single base differences between alleles with 100% accuracy. The test was run on 34 homozygous and heterozygous samples of all alleles of the DQA1 locus purchased as individual clones from the UCLA tissue-typing repository. The absolute DNA sequences of the different allelic pieces of DNA were provided by UCLA. The sequences had in most cases been determined by restriction fragment length polymorphism (RFLP) analysis. The FlowMetrix results corresponded to the UCLA data in all cases.

ADVANTAGES

Responding to the current economic forces in the diagnostic industry, the FlowMetrix system is inexpensive: hardware and software necessary to adapt a conventional flow cytometer to the FlowMetrix system costs less than $5000. The system is completely controlled by a personal computer provided with the system and requires no modification of the flow cytometer. A single switch transfers normal instrument function to the FlowMetrix mode. The FlowMetrix system consists of a Becton Dickinson FACScan interfaced through a supplied switch box to a Pentium-based personal computer running in the Windows 95 or NT environment. The PC is loaded with a proprietary signal-processing module board and software that provides both control of all FACScan functions and real-time data acquisition and analysis of the microsphere-based assays.

Operating costs are also low, because microspheres are inexpensive and the microassay format requires very low reagent volumes, typically 100 to 1000 times less than enzyme-linked immunosorbent assays (ELISAs). For example, 500 µg of a mouse monoclonal antihuman IL2 is sufficient to coat 1440 ELISA wells. If these wells are developed in triplicate, as is common practice, about 500 data points result. The same quantity of antibody would coat 5 × 108 microspheres for use in a FlowMetrix assay. Using 1000 microspheres per data point, as is normally required, would generate 500,000 data points in this system.

Figure 3. Competitive DNA hybridization as a multiplexed tissue-typing tool.

Another advantage of the multiplexed format is that cross- reactions or interference can be easily identified and corrected. During assay development, each reporter molecule is individually tested against the complete panel of microspheres constituting the multiplexed assay, leaving out the microsphere known to be reactive with the reporter molecule. Green fluorescence detected at the surface of any microsphere indicates a degree of cross-reactivity.

Interfering substances that can affect an assay result are also easily identified. For example, human antimouse antibodies (HAMAs) present in patient serum in response to monoclonal antibody therapy can be detected by incorporation of a microsphere bearing an irrelevant mouse immunoglobulin.

GETTING STARTED

Installation begins with connection of a specially configured personal computer via cable to the digital interface port of the flow cytometer. Windows-based software then guides the user through the process of assay design and analysis. Procedures are described for creating antigen-antibody, small-molecule, and nucleic acid­based assays from development of the first assay to full-panel development. Luminex supplies the microspheres; customers create the assays. Complete panels will also soon be commercially available.

CLINICAL APPLICATIONS

Flow cytometers are found--and often underutilized--in more than 5000 clinical laboratories and biomedical research departments. With the FlowMetrix system, this instrument can perform most immunodiagnostic tests as well as the increasingly important nucleic acid­based tests now coming onto the market.

The system's speed derives not only from its ability to simultaneously perform multiple assays but also from its rapid throughput. A typical cycle time is approximately 30 seconds. The large menu of possible tests, randomly accessed, allows hospitals as well as smaller labs to function more effectively and efficiently. Point-of-care testing could also bring these advanced capabilities to the smallest clinic. Allergists, for example, could test patients for serum IgE and IgG against a regionally specific panel of suspected allergens.

PERFORMANCE SPECIFICATIONS

A number of multiplexed assays are being developed for the clinical market, including ToRCH, nucleic acid­based tissue typing, serum proteins and hormones, and a fertility panel. Quantitation at the femtomolar level and a dynamic range of 3­4 logs have already been achieved. Intra- and interassay precision of 4­5% is easily achieved because each assay point is a calculated average of over 100 data points representing the number of microspheres in each color set counted per assay.

CONCLUSION

With an inexpensive computer enhancement, the technology described above enables a standard laboratory instrument--the flow cytometer--to perform most common immunodiagnostic and nucleic acid­based assays. In the microassay, no-wash format, reagent costs and sample handling are reduced. The high throughput inherent in the system can be further expanded with off-the-shelf sample delivery instrumentation. Perhaps most importantly, assays can be bundled into panels and performed simultaneously, with the results reported in real time. This system responds directly to the needs of the IVD industry and the increasingly difficult economic and technical environment in which it operates.

Ralph L. McDade, PhD, is vice president, development, and R. Jerrold Fulton, PhD, is vice president, research, for The Luminex Corp. (Austin, TX).


Copyright © 1997 Medical Device & Diagnostic Industry

The New Managed-Care Environment: Can Small-Company "Plankton" Survive?

Medical Device & Diagnostic Industry Magazine
MDDI Article Index

An MD&DI April 1997 Column

It's symptomatic of the topsy-turvy new order in the U.S. health-care market that the goal of a medical device manufacturer could be to sell less. But this and similar concepts were exactly what panelists at a session of the Medical Device Executive Forum (MDEF) conference, which was held February 10­11 in Anaheim, CA, promoted to their audience.

Introducing a bewildering array of market trends and government initiatives was Susan Zagame, vice president for payment and healthcare delivery for the Health Industry Manufacturers Association. After describing a variety of cost-effectiveness approaches being pursued by managed-care organizations (MCOs), Medicare, and other payers, providers, and purchasers, she asserted that for medical device manufacturers, "It's no longer the market of 'If you build it, they will come.'"

To help companies compete in this environment, she offered the following strategies:

  • Expand markets and sell globally.
  • Partner with larger companies.
  • Eliminate the middleman by becoming a distributor.
  • Enter into cost-management with customers, with the goal of selling less, not more.
  • Make marketing messages financially rather than clinically oriented.

Another option for small companies, Zagame said, is to sell out to larger ones. Underlining the value of small companies as a source of innovation, she quoted a colleague who compared them to plankton in the food chain: "If the plankton disappear, the big guys won't have anything to eat."

Agreeing with Zagame's assessment of the marketplace was Leah Amir, manager of health-care economies for Mallinckrodt Medical (St. Louis, MO). "The path of most resistance [for traditional sales executives] seems to be where most sales opportunities are today," she said.

Amir argued that salesforces must be prepared to let customers know when their company's products may not be appropriate or cost-effective. "Say that your product is not for every patient--that's what MCOs want to hear," she said. The ultimate result of this approach, she concluded, is a long-term, committed customer, "which is what we all want."

Health-care providers today, Amir said, increasingly value the clinical and cost-effectiveness information that device companies can provide almost as much as the products. One key type of data that should be provided in the future is outcomes research, according to final panelist Bryan Luce, PhD. CEO and senior research leader of MEDTAP International (Bethesda, MD), Luce described how outcomes research until recently has been largely the province of pharmaceutical companies. The new "spark of interest among device companies" is just in time, he claimed. "Your customers are starting to understand more about outcomes research than you are," he told his audience, "and that is dangerous." The device industry, he concluded, "needs to systematically incorporate outcomes research into product development."---John Bethune

India's Medical Device Market Is Becoming Too Big to Ignore

Medical Device & Diagnostic Industry Magazine | MDDI Article Index

An MD&DI April 1997 Feature

EXPORTING

Significant economic reforms in the 1990s and a growing middle class have greatly increased the purchasing power of the Indian health-care system. In 1996 India's gross domestic product (GDP) grew 6.6%, while the earnings for Indian corporations averaged approximately 20%. These developments, a result of the economic reforms that began in July 1991, are just two reasons why trade between the United States and India has experienced substantial growth in this decade. With the world's second largest national population--930 million--India's health-care sector offers U.S. medical device manufacturers enormous opportunities. Growing between 15 and 20% a year in the 1990s, India's market for medical devices reached $680 million in 1995. Assuming the government of India continues to support improvements in the nation's health-care system (which presently accounts for 6% of the GDP), demand for U.S. medical devices should grow steadily well into the next century.

Most medical devices and supplies bought in India today are imported. U.S. exports to the country reached $57 million in 1996, a 19% increase from 1994, and constitute a 40% share of the device market. The Indian government has gradually reduced its once high tariffs and has delicensed imports. Tariffs on medical goods now range from 15 to 40%, depending on the product. However, public hospitals that provide free treatment to at least 40% of their registered patients are exempt from customs duties. Under current regulations, hospitals can also import used or refurbished medical equipment without a license, but the equipment must have a minimum residual life of 5 years. Furthermore, if medical equipment is imported by state-run hospitals and related public institutions involved in research and development, the products can enter the market duty-free.

Along with imports, local production of medical devices has increased as well. There are more than 90 indigenous medical manufacturers, of which 22 dominate production, and several joint ventures and foreign collaborations with U.S. companies. Foreign investment approvals have increased dramatically since 1991. Over $9.7 billion in direct foreign investment was approved in 1995, more than double the 1994 level and about four times that of 1993. The United States is the leading source of such investment in India, accounting for about 20% of total investment approved in 1995. (Direct foreign investment in India requires approval by the foreign investment promotion board, now part of the Ministry of Finance and the Reserve Bank of India.)

Historically, most Indians had very limited access to any type of modern medical service. Today, however, the situation is much improved, for several reasons. First, there is a growing awareness about health issues within India and an increasing demand for quality care at affordable prices. Second, the government has made large investments in health care, as part of a five-year-plan to provide better health-care facilities. And third, a growing middle class of 50 to 80 million Indians are demanding more sophisticated medical treatment, a demand largely answered by private institutions.

The Indian government provides comprehensive health insurance for government workers, who account for about 5% of India's population. Those in the private sector can purchase various health insurance plans from the General Insurance Corporation, one of two publicly held, monopolistic insurance companies. (Private insurance companies are banned by law.) Although successive administrations have proposed opening the insurance market to foreign investment, the process of doing so will undoubtedly be long and complex. The current United Front government has introduced legislation to establish an insurance regulatory authority to oversee the two insurance monopolies and act as a stage for liberalization of the market, but its chances of passing in the parliament are uncertain at best.

There are four types of Indian health-care facilities that use foreign medical equipment: primary health centers and rural hospitals, government hospitals, private hospitals, and teaching institutions. According to the Confederation for Indian Industries, one of the largest industry associations in the country, there are almost 9500 private hospitals and nursing homes in India, and the number is increasing rapidly. The majority of Indian hospitals are located in major cities such as New Delhi, Madras, Bombay, Calcutta, Hyderabad, and Bangalore. Private hospitals outnumber state facilities by two to one and purchase 40 to 50% of imported devices. Private hospitals tend to invest in sophisticated foreign medical devices because their doctors are mostly trained abroad, particularly in Europe and the United States. India's Apollo Hospital in New Delhi, for example, the world's fourth-largest hospital, is well stocked with high-technology medical equipment from abroad.

India has nearly 450,000 registered physicians, or about 1 per 2000 people, a disproportionately low figure for a country with such an immense population. Although there are twice as many private as public hospitals, nearly half of all physicians work in the public sector. Indian doctors play an important role in purchasing medical devices for hospitals and other health-care facilities, and their influence is growing. But their demands for quality and sophistication in medical products are counterbalanced by another key factor: price. Because most of the population cannot afford to pay for health care, institutions in turn pay careful attention to costs in making their purchasing decisions.

Indian health-care providers view the FDA-regulated products of U.S. medical device companies as the best in the world. U.S. manufacturers should seize this tremendous advantage and use it as an effective tool for selling their products in this lucrative and growing market.

Victoria Kader is a senior analyst and Duaine A. Priestley is an international trade specialist at OMMI.

UPCOMING OMMI TRADE PROMOTION EVENTS

To help U.S. companies take advantage of the growing medical device market in India, the U.S. Department of Commerce, Office of Microelectronics, Medical Equipment, and Instrumentation (OMMI) is organizing a trade mission to India in 1998. The mission will include stops in New Delhi, Bangalore, and Madras, three of the most densely populated cities in India. These markets have the highest concentration of health-care facilities in the country and offer the best prospects for sales. U.S. firms will be able to meet with potential Indian purchasers and make helpful government and business contacts. Companies interested in participating should contact Duaine Priestley at 202/482-2410; fax 202/482-0975.

Upcoming OMMI trade promotion programs related to medical devices are listed in the table below. Please call 202/482-2470 for further information.

EventLocationDate
APLC: PragomedicaPragueApril 22-25, 1997
APLC: INMED '97Kiev (Ukraine)May 13-15, 1997
Trade fair: ExposaludSantiago May 13­17, 1997
Trade fair: Hospitalar '97São PauloJune 17­20, 1997
Trade fair: Sinomed '97Beijing June 25­28, 1997
Trade mission to eastern Germany and Eastern EuropeBerlin, Vienna, and Bratislava (Slovakia) September 1997
Trade mission to former Soviet Union Nizhni Novgorod and Kazan (Russia) October 1997
APLC: Hospitalaria '97Buenos Aires November 1997
APLC: Arab HealthCairo December 1997
Trade mission to IndiaNew Delhi, Bangalore, and Madras January 1998
Trade mission to ChinaBeijing, Shanghai, and Guangzhou April 1998

Copyright © 1997 Medical Device & Diagnostic Industry

NIST to Foster Agreement on Voluntary Standards

Medical Device & Diagnostic Industry Magazine
MDDI Article Index

An MD&DI April 1997 Column

Directed by the Technology Transfer and Advancement Act of 1995, the National Institute of Standards and Technology (NIST) has posted on the World Wide Web its plan to coordinate standards and conformity assessment activities among federal, state, and local government agencies and the private sector.

Intended to increase the competitiveness of the United States in the global marketplace, the plan describes an approach for developing a U.S. system of consensus standards and procedures for each of the following: voluntary standards, product certification, accreditation of testing and calibration laboratories, registration of quality and environmental management systems, and formal recognition procedures for private-sector bodies to support global trade. The act's other goal is the development of a system that meshes with those being developed internationally. For more information on NIST's plan to coordinate U.S. standards, visit its web site at http://ts.nist.gov/ts/htdocs/210/plan.htm.---Daphne Allen

Dealing with Change in Device Development

Medical Device & Diagnostic Industry Magazine | MDDI Article Index

An MD&DI April 1997 Column

SNAPSHOT

In more than 20 years of ultrasonic product development and marketing, Jacques Souquet, PhD, has both witnessed and helped cause dramatic changes in the industry. In fact, Souquet, who is the senior vice president of Advanced Technology Laboratories (Bothell, WA) and the recipient of six patents in ultrasonic imaging, can remember the rudimentary beginnings of ultrasound products.

"I have four children," Souquet says. "For kid number 1, my wife didn't have an ultrasound; for kid number 2, my wife had an ultrasound, but at the time you really needed to trust the doctor to tell you 'this is a baby, this is a head, this is the rest of the body.' It was simply a mishmash of black and white and not recognizable. But by kid number 4, the images had gray scale, and you could see facial detail."

According to Souquet, the most important technological change in ultrasonic devices occurred relatively recently. "There is a dramatic impact from the use of software components in ultrasound products, something we weren't faced with even five years ago," he says. This change in technology means that qualifications for ultrasonic device developers are changing. "The mix of competence in companies is shifting to the software area," he adds.

A native of France who has worked in the device industry in France as well as the United States, Souquet notes that like the devices themselves, the marketplace and the ultrasound manufacturing companies have become much more sophisticated than when he began his career.

There are a greater number of competitors in the ultrasound device market, says Souquet. "There are also products that occupy very specific niches in the market. For example, there are now products that are targeted toward only muscular or skeletal applications," he says.

Companies are also developing a more advanced approach to product development. Using the company he now works for as an example, Souquet says that "there has been a shift toward understanding the customer. There is a better fusion of the different groups--marketing works closely with product generation, or engineering, and finance is tied in more closely. There doesn't seem to be the separation that existed in the past, when finance, engineering, and marketing were all distinct, and it was lucky if the three could march at the same speed. Now because product cost is important, understanding customer needs is important, and technology is important, we see fusion of different groups in a company being much better handled."

Weathering the rapid changes of the past two decades has left Souquet with a better understanding of how those who are entering product development can best succeed in a future that promises to hold as many surprises as the past has.

"First and foremost," says Souquet, the successful product designer must "integrate customer needs with technological innovation. We should not develop technology in a vacuum; we have to develop technology that addresses our customers' needs."

He recalls that one of his own successes hinged on following this advice. "About 15 years ago in cardiology imaging, part of the population--it was 30% at the time--couldn't be imaged because we couldn't go through the ribs. And the idea I had was to put a probe on the tip of a gastroscope that we would slide down the esophagus, to get much closer to the heart and to be able to use a higher frequency, which delivers better resolution, and by doing so to image the heart without the problem of getting through fat tissues or between ribs. All of that was delivered because of listening to unmet needs of the customers who, not being technologically versed, didn't know this could be done.

"I am assuming that the person who would get into medical product design would be versed in technology," continues Souquet. "I would advise that person to look at the other side of the coin, and learn better what our medical needs are, so that he or she can apply technological savvy to the things that need to be done, and not develop technology just for the sake of technology."

Souquet says that the successful product developer must also take advantage of future changes. "A young person getting into a business like ours should keep an entrepreneurial spirit to exploit changes in the market," he says, "and should also realize that the future is not simply an extrapolation of the past. To be successful we need innovation and creativity, not just redoing in a better way what was done in the past."

Leslie Laine is a senior editor for MD&DI.


Copyright © 1997 Medical Device & Diagnostic Industry