MD+DI Online is part of the Informa Markets Division of Informa PLC

This site is operated by a business or businesses owned by Informa PLC and all copyright resides with them. Informa PLC's registered office is 5 Howick Place, London SW1P 1WG. Registered in England and Wales. Number 8860726.


Articles from 2011 In April

For the Weekend: Contemplating the Warp Speed of Technological Advancements

 Here's a fun read as we head into the weekend: Boing Boing's Cory Doctorow has a column in Make magazine in which he waxes philosophic about the breakneck speed of our advancing technology, and  how "giddy" it makes him feel to contemplate how quickly some of the formerly state-of-the-art gadgets he keeps around his office have been left in the dust.

Doctorow recounts a discussion he had with a friend in the 1990s, in which they imagined the prospect of one day having access to 1 TB of RAM. As he writes:

And we started to laugh. This substance that cost more than its weight in gold — that solved all our problems — sometime in our lifetimes would be so cheap and abundant that we would have literally unimaginable amounts of it. 

The piece is definitely worth a read, as is the rest of the content on Make's Web site (and if you don't check Boing Boing compulsively already, then you're missing out). This sentiment must resonate with those of you in the device industry. Just think: when MDEA Lifetime Achievement Award winner Alfred Mann was starting out 42 years ago, this was the kind of computing technology people were fantasizing about:

  My my, all those circuits! 

– Thomas Blair

Robotic Surgery Successfully Used to Treat Cancer of Larynx

 Oh, robots. What can't they do? When they're not vacuuming our floors or creepily impersonating our pets, they're delicately cutting tumors off of our larynxes

Doctors at the Mayo Clinic were able to use robotic surgery to successfully treat supraglottic squamous cell carcinoma, a cancer that settles in above the vocal cords in a way that's traditionally been tricky to reach. A study of the procedure demonstrated that it was effective in removing the cancer.

Of course, the robot isn't actually removing the cancer on its own; a surgeon still has to operate it.

From the press release:

...the robotic arms that enter the mouth include a thin camera, an arm with a cautery or laser, and an arm with a gripping tool to retract and grasp tissue. The surgeon sits at a console, controlling the instruments and viewing the three-dimensional surgical field on a screen.

Doctors are optimistic that robotic surgery will give them a big boost in the fight against throat cancer.

– Thomas Blair

Alfred Mann Wins MDEA Lifetime Achievement Award

Serial entrepreneur, inventor, and philanthropist Alfred Mann has become something of a legend in the medical device industry. So it’s only fitting that on June 8, Mann will the recipient of the MDEA Lifetime Achievement Award. “I’m really honored to receive this award,” Mann says. “Over my career, I’ve received a number of awards but this one is especially important,” he adds.

Mann, who at 85 years old still spends 70–80 hours per week at work, was selected by the MD+DI editorial advisory board and UBM content team because of his storied career in the life sciences industry. In all, he has dedicated the past 42 years of his career to developing new medical technologies.

He initially got involved in the medical device space after founding Spectrolab in 1956. Now a part of Boeing, Spectrolab was and still is a provider of solar panels that are used to power spacecraft. “One of our good customers was Johns Hopkins University, whose Applied Physics Laboratory was trying to advance medical products by using the methods developed in the military and aerospace programs,” Mann says. “In 1969, [Johns Hopkins] came asking me to develop a long-lived cardiac pacemaker with some of the Spectrolab technology.” At that time, pacemakers were large and heavy, and they only had enough power to last about a year and a half before needing to be replaced. “Johns Hopkins persuaded me to start a company to develop a long-lived pacemaker. The company, known as Pacesetter Systems, had the goal of developing a smaller device with a rechargeable battery, which we did,” he says. “Our second patient, who was implanted with the new pacemaker technology in 1973, is still alive today and is using the same pacemaker after 37 years.”

Mann’s involvement in the medical device field expanded in the early 1980s as he began looking for ways to diversify the business of Pacesetter Systems. “We undertook development of implantable and external insulin pumps and continuous glucose sensors for treating diabetes. That project was later spun off and became a company known as MiniMed. The devices we produced have really revolutionized the treatment for Type-1 diabetes.”

Mann’s interest in the disease continues to the present. “I’ve been involved with developing technologies to treat diabetes for a long time,” he acknowledges. “There wasn’t really a family connection that inspired me to work on improving the treatment of the disease. But the more I understood the disease and the need to develop new technologies in this area, the more I wanted to help in this field.” Mann says he became worried about 15 years ago that an increase in incidence of Type-2 diabetes was imminent. “And that has happened. There are now 300 million people in the world the disease,” he says. “We’re looking at a half a billion people with diabetes in the world within a couple of decades.” In late 2010, UnitedHealth Group projected that half of all adults in the United States have either diabetes or prediabetes by 2020.

Most recently through his work as the leader of biopharmaceutical firm Mannkind Corp., Mann has been involved with a therapy that mimics the insulin kinetics of a healthy pancreas. “If you take an injection of today’s regular commercial insulin, it doesn’t peak for roughly two to three hours,” Mann explains. “A normal person digests a meal in roughly three hours. So you have all of that late excess insulin, which causes severe low blood pressure, a condition known as hypoglycemia, which can be a problem in the short term.” Approximately 15 years ago, Eli Lilly and Novo Nordisk created rapid-acting analogs of insulin, which sped up the breakdown of insulin hexamers in all current insulins. “These rapid-acting analogues last for five to seven hours and peak in 30–90 minutes. That’s much better but it’s still too slow. I’ve been very involved with a unique insulin product that mimics the insulin kinetics of a non-diabetic person. That insulin created at Mannkind is an ultrarapid-acting form of insulin that peaks in 12–15 minutes and is gone within three hours.”

Mann expected FDA to approve the AFREZZA inhaler that dispenses the novel insulin in January 2011. That, however, didn’t happen. “While we were conducting our trials, we developed a better delivery device. This new inhaler is much more convenient, discreet, and less expensive. It is also more efficient for delivery,” Mann says. “We were able to make it much more convenient and discreet and less expensive. It also actually has a better profile for delivery.” Mann decided to launch with the new device since a later transition might be confusing to patients. “FDA told us what we needed to do for the substitution and we did it all,” he says. “In January, they came back to us and told us they wanted to see two new trials with the new device to bridge the extensive trials that were conducted with the earlier clinical device.” Mann explains that FDA is asking for a 12-week human trial. To recruit the 900 patients for that trial will probably take at least a year, he estimates. Because it will take FDA an expected six months to do their review, the company does not expect the product to be ready for the market until the end of 2012 or early 2013.

Mann’s work with medical devices extends far beyond improving pacemakers and diabetes treatment. Among the companies he has founded are cochlear implant maker Advanced Bionics, visual-prosthesis manufacturer Second Sight, hearing-aid manufacturer Implantable Acoustics, drug-therapy specialist NeuroSystec, electrostimulation firm Bioness, and Infusion Systems, a manufacturer of drug-delivery systems. In addition, he heads Quallion, which develops advanced batteries for medical, aerospace, and military applications.

When asked which medical technology he is the most proud of, Mann says he has a hard time picking one. “I’ve been involved in projects that have, for example, enabled a deaf child to hear, a blind person to see, and a crippled person to walk,” he explains. “The technologies such as pacemakers and glucose sensors that I’ve been involved with are obviously very important, too.”

In all, Mann has founded 17 companies and maintains an affiliation with nine of them. “What drives me is trying to find solutions that enable people to live longer and more fruitful lives,” Mann says. “I get such satisfaction from helping improve patients’ lives. It’s absolutely rewarding,” he explains. “You see a kid who can’t hear and give him a cochlear implant. Doesn’t that make a difference? It’s hard not to be overwhelmed by such experiences. I’ve been involved with many device advances. There are so many of those developments that are very satisfying to me.”

Mann is also a major supporter of institutional research. He has founded and endowed the Alfred Mann Foundation, a nonprofit research organization dedicated to advancing medical technology. That organization employs more than 100 people. He has founded Alfred E. Mann Institutes for Biomedical Engineering at the University of Southern California, at Purdue University, and at the Technion–Israel Institute of Technology. The institutes are business incubators for medical device development that are principally endowed by Mann. “What I’m trying to do by supporting research at universities is to have some of my work to continue to solve other problems. The institutes at the universities are looking at a number of applications,” he says. “For example, one of the programs is working to develop a micro-mass spectrometer that could be used for detection of cancer. There’s also some work underway to develop surgical glues that are vastly better than what exists today,” he says. “There’s also research on a fascinating new cancer therapy that may be able to cure major cancers.”

Mann plans on further supporting medical research by donating his estate to charity. One of the primary focuses of the charity will be supporting the Alfred E. Mann Institutes for Biomedical Engineering.

Earning bachelor’s and master’s degrees in physics from the UCLA, Mann’s graduate work focused on nuclear and mathematical physics. He holds honorary doctorate degrees from the University of Southern California (USC), The Johns Hopkins University, Western University, and the Technion Institute.

In addition, Mann serves as a trustee for USC, is a member of the board of overseers of the Keck USC School of Medicine, and has served as the chairman of the Southern California Biomedical Council—a nonprofit organization devoted to supporting the biomedical industry in the Los Angeles metropolitan area. He is a research professor at USC and is on the USC Viterbi Board of Councilors. He is also an adjunct professor in the UCLA Department of Bioengineering.

Mann will accept the award at a ceremony at MD&M East in New York this June.

—Brian Buntz


Magnetic Nanobeads Could Polish Off Rust from Microfluidic Sensors

Diagram illustrates how a sensor technology might work using ferromagnetic iron oxide nanobeads. (Graphic courtesy of Oregon State University)

Researchers at Oregon State University (OSU; Corvallis) have discovered how to use magnetic 'nanobeads' to help detect chemical and biological agents. When it is developed into a handheld sensor, this microfluidic sensor technology could benefit a range of applications, including portable diagnostic devices.

The key to the technology is minuscule pieces of rust composed of ferromagnetic iron oxide nanoparticles. While these particles can selectively detect chemicals, they can also be incorporated into a system of integrated circuits to instantly display the findings.

"The particles we're using are 1000 times smaller than those now being used in common diagnostic tests, allowing a device to be portable and used in the field," remarks Vincent Remcho, a professor of chemistry and associate dean for research and graduate programs in the OSU College of Science. "Just as important, however, is that these nanoparticles are made of iron. Because of that, we can use magnetism and electronics to make them also function as a signaling device, to give us immediate access to the information available."

This technology, according to Pallavi Dhagat, an assistant professor in the OSU school of electrical engineering and computer science, should result in a powerful sensing technology that is fast, accurate, inexpensive, mass-producible, and small enough to hold in your hand.

Existing assays are often cumbersome and time consuming, using biochemical probes that require expensive equipment, expert personnel, or a complex laboratory to detect or interpret. The OSU scientists' approach, in contrast, involves attaching nanoparticles to these biochemical probes. When a chemical of interest is detected, a ferromagnetic resonance relays the information electronically to a tiny computer, which displays the information to the user. Although no special thin films or complex processing steps are required, the sensor's detection capability is sensitive and accurate.

Potentially capable of detecting almost anything of interest in air or water, the technology also has "green" benefits, the scientists say. The use of rusty iron should help address issues of safety in the resulting product.

Roche’s HPV Test Gets Record FDA Approval

Roche’s HPV Test Gets Record FDA Approval

Roche's Cobas 4800 system for HPV testing.

In just 10.5 months, Roche secured FDA approval for its human papillomavirus (HPV) test—and that’s a record for any HPV test today, says Christoph Majewski, head of HPV at Roche Molecular Diagnostics (Pleasanton, CA). The Cobas HPV test is the only FDA-approved test that performs 16 and 18 genotyping simultaneously with high-risk pool testing of the other 12 HPV genotypes.

The Centers for Disease Control and Prevention (CDC) estimates that about 20 million Americans are currently infected with HPV and an additional 6 million are infected annually. Nearly 12,000 U.S. women are diagnosed with cervical cancer each year, and HPV is suspected to be responsible for a large number of these cases.

Roche’s Athena clinical trial showed that 1 in 10 women, age 30 and older who tested positive for HPV 16 and/or 18 with the Cobas test, had cervical precancer despite receiving normal Pap test results. “By providing simultaneous 16 and 18 genotyping, doctors will be able to make immediate decisions about which women are at the highest risk for cervical cancer and therefore should be followed up with immediately,” says Majewski. “We hope that 16 and 18 genotyping will become the new clinical standard in cervical cancer screening, which is preempted by the guidelines that AACCP [American College of Clinical Pharmacy] had issued a few years ago. We hope that by providing this type of testing, we may be able to reduce the rate of cervical cancer further in the population.” Majewski also anticipates that the test could lead to earlier identification of genotype 18, which frequently leads to adenocarcinoma, a cancer that is often underdiagnosed. The fully-automated Cobas 4800 platform provides sample preparation, amplification of target DNA by a polymerase chain reaction and nucleic acid hybridization to detect 14 high-risk HPV types. The assay allows the lab to obtain four different results (12 high-risk HPV genotypes, genotype 16, genotype 18, and beta-globin) from one sample at the same time.

Majewski explains the two patient populations for this test. “In the United States, there are predominately two algorithms that are recommended by the clinical opinion leaders. One is ASC-US triage—the follow up of an equivocal cytology with an HPV test in women. This algorithm is recommended for women between 21 and 30 years,” he says. One of the concerns within the medical community has been that when cotesting younger women (the prevalence of HPV is high in this population), many samples turn out to be positive and result in unnecessary follow up. Majewski believes that the results of the Athena trial prove that in the future, 16 and 18 genotyping could help prevent this issue.

“The second algorithm recommended is basically the adjunct testing, which is the simultaneous use of HPV and cytology. That algorithm is recommended for [women] 30 years and above,” says Majewski. “Both age ranges are offered in our labeling and packaging inserts, because the assay is [FDA] approved for both of these applications.”

The company has high expectations for the success of the test, which will be available at its warehouse on May 1. Although there is additional market opportunity for the test overseas (the system received the CE Mark in December 2009), the biggest potential is in the United States, where currently 80–90% of HPV testing occurs, according to Majewski. He estimates the U.S. market for Roche’s test to be about $300 million. The Cobas 4800’s competitors in the HPV testing market are Qiagene’s Digene HC2 HPV DNA test and Hologic’s Cervista test.

Stretchable Electronics Bend and Fold Like a Rubber Band

John Rogers University of Illinois Urbana-Champaign
In the following conversation, John Rogers, Lee J. Flory-Founder chair in engineering at the University of Illinois at Urbana-Champaign, discusses the application of stretchable electronics technology to balloon catheters and envisions its role in future medical device applications.

MPMN: Describe your stretchable electronics concept. How is stretchability achieved, and what technological hurdles must be overcome to fabricate stretchable electronics?

Rogers: How to create flexible, stretchable electronics is an interesting question and a challenging problem because if you think about conventional electronics, they are all built on the rigid, planar surfaces of semiconductor wafers based on silicon or gallium arsenide. What we were interested in is building circuits with the kinds of performance capabilities associated with state-of-the-art silicon-type devices, but in formats that can be bent and stretched and folded and even manipulated like a rubber band or a balloon. Our feeling is that if you can accomplish that outcome, it affords new opportunities for integrating electronics directly with the human body for all kinds of purposes, ranging from physiological status monitoring to new kinds of surgical and therapeutic devices.

Balloon Catheter Stretchable Electronics
Stretchable electronics technology can accommodate the curvilinear shapes exhibited by such medical devices as balloon catheters, enabling a single device to perform a range of diverse functions, including monitoring and ablation.

How to achieve stretchable electronics is a materials-level challenge that we have been thinking about for a while. It turns out that there are some relatively simple ideas in elementary mechanics that allow you to achieve stretchable silicon devices. One of them is that if you make anything thin enough, it becomes flexible just by virtue of the fact that bending stiffness decreases rapidly with thickness. A very, very thin sheet of silicon is flexible because of those mechanics, and a wafer is not--it's a rigid, nonbendable type of material. Thus, step one is to make the silicon very, very thin--maybe a factor of a thousand or ten thousand times thinner than a silicon wafer.

Making a silicon substrate very thin is a pretty easy way to get bendability. But stretchability is a little bit different, and it's really what you need if you want to accomplish biointegration. You can bend a flexible sheet of silicon or even a sheet of plastic. You can also wrap them around certain kinds of curvilinear shapes such as cylinders and cones, but you can't wrap them around a sphere. And you certainly can't wrap them around a body part. Their mechanics are not really matched to the soft, elastic nature of tissues in the body. Thus, you need to go beyond flexible.

You do that by configuring your circuit into an open-mesh design that allows individual devices to be interconnected using springy-type wires that can deform and move. When these wires are bonded to an underlying rubber sheet, the entire mesh can accommodate stretching in a way that isolates strain away from the device nodes in the mesh and allows the interconnects to move, providing a reversible linear elastic response to applied force.

That's what we've done in our latest project. We've exploited these two ideas--thinness and mesh geometry--to integrate a range of sensor and electronic functionalities onto the surface of an otherwise conventional balloon catheter. When a balloon catheter is inflated, it undergoes hundreds of percent of strain deformation, but we've designed the circuit so that it can move with the balloon without constraining its motion and without compromising the performance characteristics of the electronic devices.

MPMN: How do your stretchable electronics perform such functions as mapping regions of the heart and ablating abnormalities in conjunction with a balloon catheter? Why is this functionality important for doctors?

Rogers: We're materials scientists and engineers, but we work closely with clinical cardiologists to define the most useful levels of functionality that we can possibly provide in this format. Conventional balloon catheters are just dumb devices. They're completely nonfunctional; they merely effect a mechanical intervention. They do not perform sensing or actuation in the sense that we're talking about now. Thus, the idea was to take a balloon and add the most useful functionality as defined by our collaborators.

We designed the system to afford functionality for interventional procedures that are used to treat certain classes of arrhythmias. Such procedures currently involve two steps. The first involves mapping the electrophysiology associated with the beating heart to identify regions of the tissue that are behaving in an aberrant or abnormal fashion. The second is an ablation, or resection, step, which essentially eliminates aberrant tissue to address the arrhythmia. One way to eliminate the tissue is to use radio-frequency energy to burn it thermally and destroy it. Currently, these two procedures are performed using separate point-type catheters--one for mapping and one for zapping.

The mapping process itself occurs in a point-by-point fashion, whereby a surgeon moves the mapping catheter from one place to another along the interior surface of the heart, measuring single-point ECG traces at each location. In this point-by-point way, you can stitch together an overall map for identifying spatial regions that need to be dealt with. And once that's done, you come in with another point-type catheter that provides ablation functionality. You go back through in a point-by-point fashion and ablate away aberrant tissue.

This procedure works extremely well, but the problem is that it's time-consuming. It also requires a fair amount of skill on the part of the surgeon, and its resolution--the repeatability of being able to identify just the aberrant tissue and remove just that tissue--can be challenging. And in these procedures, morbidity is most closely tied to the duration of the procedure. Thus, our cardiology colleagues have told us that anything we can do to make it more precise, faster, and less dependent on the skill of the surgeon would be valuable.

So that's what we did. Our circuit provides multipoint mapping functionality and--using the same catheter--the ability to perform multipoint ablation. Our vision is that you have a soft balloon catheter that you insert into the interior of the heart. Then you inflate it to push the sensors and the ablation electrodes against the soft, beating inner surface of the heart. First you map, and then you zap using the same catheter in the same position, and then you're out. It's much different from what's done today. Conceptually, it's the same kind of process, but it's carried out in a more advanced engineering mode.

MPMN: In addition to mapping and zapping, can your stretchable and flexible electronics be customized to perform other functions?

Rogers: We have design rules for making this kind of flexible mesh array, and we can incorporate just about any kind of semiconductor device technology into this platform. Thus, we have incorporated sensing and ablation electrodes, but we've also developed temperature, flow, and tactile sensors to accommodate this platform. Temperature sensing is important because the ablation process is intrinsically based on temperature. The ability to sense temperature allows you to monitor in situ what you're doing to the tissue with the ablation electrodes. Flow sensing is important because the rate of cooling and the contact of the electronics to the tissue can be impeded by the flow of blood through that interface. Thus, being able to measure local surface-level blood flow is also important. And tactile sensing is important for measuring exactly how hard you're pressing the balloon against the tissue.

To show that we could do it, we even demonstrated devices that had tiny LEDs mounted on them. In this case, clinicians did not tell us that they needed LEDs; our goal was merely to demonstrate a capability--basically to put a stake in the ground and say, "Look, any kind of semiconductor device technology you're interested in, we can do it. And here's an example."

MPMN: What are your future plans for this flexible, stretchable electronic technology?

Rogers: In future cardiology applications, such as the treatment of arrhythmias, it's a straightforward path for us. We're going to populate the surface of a balloon catheter with many more sensors to get a better, high-definition view of what's going on and improve precision. I think that we can also scale our technology in a straightforward manner. These advances are kind of obvious. The other thing we're interested in is getting this technology into a form that can be useful for patients. Thus, we intend to move it from the research lab and animal demonstrations into something that can be useful for people that are suffering from this kind of heart disease.

To that end, we have begun a startup company called mc10 (Cambridge, MA). This company also has close ties with Massachusetts General Hospital (Boston) and the Sarver Heart Center at the University of Arizona (Tucson). This startup is pursuing commercialization. And in my lab, we're pursuing higher levels of integration.

But more generally, I think that while this kind of technology allows you to perform different kinds of procedures on the heart, it enables almost any kind of interface with the body to take on a new complexion. Thus, we're building devices that can map electrical activity in the brain, for example. The focus there is on diagnosing and treating epilepsy.

I think that stretchable electronics are suitable for a whole host of different application areas. We're pushing in a variety of directions and trying to do as much as we can in close collaboration with surgeons so that we can direct our technologies to the things that are most important. I'm not a doctor; I'm trying to feel out the situation. But we are engaged in robust collaborations in the areas in which we're working.

Collateral Standards for IEC 60601-1

Collateral Standards

The general requirements of 60601-1 apply to all medical electrical equipment and part 2 standards apply to specific categories of medical electrical equipment. However, there is another level in this hierarchy of standards: the collateral standards. These are applied more selectively than the general requirements, either in terms of the topic they cover or the type of equipment, but they are not as specific as the part 2 standards. In standards jargon they are referred to as semi-horizontal standards.

60601-1-1 Medical Electrical Systems. The document is discontinued as a stand-alone document and is now incorporated into the third edition.

60601-1-2:2007 Electromagnetic Compatibility (EMC). Compliance means that the equipment will neither generate unwanted electromagnetic radiation nor be unduly affected by it. Compliance with 60601-1-2 also means that the requirements of the EMC Directive are met.

60601-1-3:2008 Radiation Protection for Diagnostic X-ray Systems. The purpose of this standard is to ensure that stray radiation is kept to a minimum for the safety of patient and operator.

60601-1-4 Programmable Electrical Medical Systems (PEMS). This is a collateral standard for software. It has been discontinued as a stand-alone document and is now incorporated into the third edition.

60601-1-6:2007 Usability. Increases emphasis on ergonomics. Manufacturers must take the requirements into account during the design phase. Many adverse incidents in the past have been traced to use error; equipment should be as intuitive and easy to use as possible. 

60601-1-8:2007 Medical Alarms. Gives guidance in the prioritizing and management of alarm functions in medical equipment. Alarms can be chaotic if the user does not know what is going off and whether the alarm is trivial or serious.

60601-1-9:2008 Environmentally Conscious Design. The designer should consider contamination of the air, water, and biosphere, the use of raw materials, and transport and packaging in the design of new products.

60601-1-10:2008 Physiologic Closed Loop Controllers. This is design criteria that should be considered when designing medical devices that are used to control the parameters they are measuring. For example, a device can measure the insulin level of a patient and automatically infuse insulin. Such systems have to be stable, reliable, and fault tolerant. Software must be designed methodically and validated comprehensively.

60601-1-11:2010 Home Healthcare Equipment. Puts considerable emphasis on the use of home healthcare equipment by nonspecialist users. Electrical safety is also a factor here and the equipment must be tolerant of poor wiring in the building.

Other aspects covered are the likelihood that the device will be handled roughly, the possibility of it getting wet or dirty, and the ingress of objects into the equipment. Instructions for use must be very clear.

In general, but with significant exceptions, these collateral standards are not pass-or-fail—rather they are concepts to be taken into account in the device design. In all cases the concepts or requirements may be overridden by requirements in the particular part 2 standards for specific equipment categories.

Furthermore, in nearly all cases there are other more-detailed or specific standards that cover the same topics (EMC, software, radiation protection, ergonomics and environmental design), a number of which are referenced in the collaterals. Therefore the collaterals should be read in conjunction with these additional standards.

Return to the main article "Is the Third Edition of 60601 the End of Objective Evidence?"

Outsourcing Outlook: Machining

The heightened demand for miniaturized medical device designs is presenting mounting machining challenges. Neal Day, director of sales at Metal Cutting Corp. (Cedar Grove, NJ), advises OEMs on selecting a partner for machining metal medical devices and components.

MPMN: What technical capabilities should a contract machinist possess?
Day: It all starts with materials. To serve the needs of medical device OEMs, contract machinists should possess comprehensive knowledge of the mechanical properties and machinability of commonly used medtech materials, such as the full range of titanium alloys and stainless steels. However, raw materials alone don't make devices. Knowledge of materials, combined with tooling proficiency, helps ensure that contract machinists will be able to produce prototype parts and subsequent iterations. This capability presupposes versatile CNC multiaxis and live tooling capability to achieve overall cost-effectiveness.

MPMN: What machining experience should the OEM require?
Day: Medical device machining requires suppliers to convert difficult metals into close-tolerance parts with complex geometries. Fabricating such parts demands innovative and experienced tool selection. For example, such desirable metallurgical properties as durability and corrosion resistance result in high tool-wear rates that can affect part accuracy. Thus, OEMs should choose machining suppliers that can repeatably produce burr- and particulate-free components with exact dimensions. To that end, the machining partner must have ISO 9001:2008 or higher standards in place, be able to automatically monitor tool wear and process variables, and provide custom statistical reports. In addition, many components require specific surface finishes and treatments. OEMs should partner with machining suppliers that also offer in-house secondary services such as sandblasting, lapping, electropolishing, and passivation to complement their machining processes.

MPMN: Where is machining headed?
Day: With growing demand for shrinking guidewires, stents, and drug-delivery systems in higher and higher volumes, suppliers may soon be expected to master multitasking tools and bar-fed milling machines. The ability to machine increasingly complex materials with tighter tolerances and specifications will also require suppliers to invest in automation or advanced CAD/CAM technologies. Moreover, contract machinists can serve the future technology needs of medical device OEMs by adopting learning-based software programs to leverage customized processes.

Dalau Inc.Plastic-component machining
A precision machinist of plastic medical device components can turn PTFE, PEEK, polyamide, polyethylene, ETFE, and many engineering plastics in prototype, small-batch, and production-series volumes. Conducting its operations under cleanroom conditions, Dalau Inc. operates turning centers that can process components with diameters ranging from less than 0.040 to 15 in. The company's facility also houses multiaxis CNC machining centers for large-volume manufacturing and Swiss sliding-head machines.
Dalau Inc.
Merrimack, NH

Turning and milling services
Serving the medical device and orthopedic markets, Mack Molding Co. operates Swiss seven-axis lathes and a combination turning and milling machine. Featuring multitasking technology, this machine can perform high-power turning and full-function machining in one setup, enabling users to produce small batches of components rapidly and efficiently. Other equipment performs ultrasonic parts washing, vibratory tumble deburring, comparative measurement, and surface-finish analysis.
Mack Molding Co.
Arlington, VT

Laser-processing capabilities
Capable of manufacturing products in high volumes, Laserage Technology Corp. offers precision laser machining, cutting, drilling, and welding of many materials, including nitinol, stainless steel, cobalt-chromium alloys, titanium, platinum, borosilicate, quartz, ceramic, silicone, and bioabsorbable polymers. Certified to ISO 9001:2008 and ISO 13485:2003 standards, the company's facility is equipped with CO2, Nd:YAG, and fiber lasers for welding and cutting device components; an Nd:YAG microwelder for welding small parts and performing rapid prototyping; a DISC laser for cutting device components; and a femtosecond laser for ablating such cylindrical device components as bioabsorbable stents. In addition, the company offers prototyping and engineering support, heat-treating, component finishing, and such secondary operations as nitinol shape-setting, electropolishing, microblasting, chemical passivation, and annealing.
Laserage Technology Corp.
Waukegan, IL

Machining of orthopedic and cardiovascular devices
Specializing in the precision machining of orthopedic implants and cardiovascular devices, a contract manufacturer converts such materials as titanium, stainless steel, cobalt chrome, and PEEK. Offering close-tolerance manufacturing to 0.00001 in., Lowell Inc.'s services range from engineering support through Swiss turning, multiaxis milling, and EDM. The company also provides laser marking, turnkey assembly in Class 10,000 and Class 100 cleanrooms, cleaning, heat-sealing, labeling, and vacuum-packaging services. Equipped with more than 60 advanced CNC machining and turning centers, coordinate-measuring and vision-inspection metrology machines, and material-analysis instrumentation, the company operates an ISO 9001:2008- and ISO 13485:2003-certified facility that employs profile tolerancing to measure and inspect components in three dimensions.
Lowell Inc.

Microprecision machining of custom metal parts
Specializing in small-batch production, Metal Cutting Corp. offers a range of custom microprecision machining services using four-axis CNC machining centers and wire EDM equipment. The company's CNC milling and turning centers and CNC lathes with live tooling capability can produce medical components with diameters as small as 0.010 in., while its high-speed wire EDM machines process parts with diameters as small as 0.0005 in. In-house machining centers can achieve tolerances to ±0.0002 in. and produce such custom features as flares, profiles, holes, forms, single tapers, slots, angles, and points in any metal. Additional services include close-tolerance, burr-free abrasive cutting; precision grinding and lapping; cleanroom metrology; and particulate-free packaging. The company uses in-house digital optical gauging microscopy to confirm that specifications are achieved.
Metal Cutting Corp.
Cedar Grove, NJ

Is the Third Edition of 60601 the End of Objective Evidence?

Is the Third Edition of 60601 the End of Objective Evidence?

Although the transition period for the third edition of the medical electrical equipment standard (IEC 60601-1:2005) doesn’t end until 2012, there are many changes and firsts that design engineers must become familiar with now. Doing so ensures that they design electronic products and components that will come up to scratch and can be sold on the global market. The EU will be the first body to fully adopt the third edition, and will therefore be the primary focus of this discussion.

For many, the third edition represents a much-needed update because the use of medical equipment in clinics and in homes has changed significantly. Electronic medical equipment is omnipresent in people’s lives and the updated standard aims to reflect those changes (see the sidebar on collateral standards).

The end of the transition period is still two years away, but it makes commercial sense to start using this new, more complex, and greatly expanded standard now. Incorporating it into the design process now will help to avoid costly redesigns and potential delays in time to market for products further down the line.

Falling Foul of the Law

Previous versions of IEC 60601-1 only covered products intended for use ”under medical supervision.” However, consumers have never been more aware of the state of their health, and consequently there has been a boom in the home health and self-test electronic products industry. The use and location of medical equipment has changed and it has become necessary to increase the scope of the standard. As a result, a good number of health-related electronic devices that were not covered by previous standards, will be addressed by the requirements defined in the third edition. Manufacturers of active devices, such as seasonal affective disorder lamps, fitness machines, and depilation equipment, must now be careful of the claims they make, because careless marketing language could get a product classified as a medical device. Then it will have to meet the complex requirements of IEC 60601-1 as well as the Medical Devices Directive 93/42/EEC as amended by directive 2007/47/EC. Such categorization could cost extra money and delay in getting the product to market with further external regulatory scrutiny by way of a Notified Body.

Because manufacturers that sell health-related products will be at an increased risk of inadvertently falling foul of the law, it is essential that companies consider early in the design phase how a product will be used and who it will be marketed to. Such consideration ensures that products meet the robust standard as necessary and can be legally sold after the 2012 implementation date.

Reducing Risk

As a harmonized standard (under the Medical Devices Directives 93/42/EEC as amended by directive 2007/47/EC), one of the many new requirements is the incorporation of the concept of risk management. It includes an obligation to keep a detailed risk management file (RMF). Many of the tests that are required to demonstrate compliance with the standard make reference to the RMF.

An increased level of flexibility must be introduced, because it enables the testing process, which is required to ensure compliance with the standard, to be modified depending on how the device complies with some aspects of the standard. For example, some medical equipment may need to be robust enough to withstand battlefield or other extreme conditions.
The testing house selected can therefore toughen the use standards and associated risk (e.g., increase requirements for shock or heat resistance). However, the new element of risk management in the third edition of the standard has raised some concerns. Critics say that the risk management rules are open to interpretation and could introduce a degree of subjectivity, thereby moving away from objective pass-fail criteria. One testing house could determine a pass and another could use the same data to determine a failure.

The third edition introduces the concept of essential performance, which may be a surprise to those purchasing equipment. Essential performance expands the scope of the standard beyond basic safety requirements to ensure that the product does the job from the end-user’s perspective.

Another new requirement is causing some ripples in the medical device world. The lifetime of the equipment must be planned for and documented. A manufacturer must estimate the product lifetime and, by implication, the mean time between failures, the availability of spare parts, and how long the manufacturer will support that equipment. Although this is reassuring for purchasers making a significant investment in expensive medical equipment, it translates to significant challenges from a marketing and sales perspective.

The new requirements help users get a better idea of their return on investment when comparing equipment from different manufacturers. The standard provides the purchaser with knowledge of how long a particular product is predicted to last and for how long they will be able to repair it. Purchasers can therefore assess a product’s long-term potential and cost effectiveness compared with competitive products.

There is a also record-keeping implication as Directive 93/42/EEC requires manufacturers to keep records for the lifetime of nonimplantable products, and for an additional five years after the product has been retired. Records must be kept of implantable products 15 years after production has stopped.

Increased Patient Protection

The standard includes new concepts for means of patient and operator protection. Previous versions of the standard have allowed a current was allowed to appear on the conductive enclosure of the medical equipment in question, exposing the user or patient to a small level of current. Although there are greatly increased figures for earth leakage current in the new standard, the additional current is now confined to the earth continuity conductor of the product. These changes significantly influence the design of many medical devices that have been used for several years—manufacturers that want to continue selling products may need to invest in a redesign. On the positive side, this increased earth leakage current allowance enables the use of more-substantial mains interference filters.

Mechanical hazard protection has also been expanded significantly. The standard now covers trapping points, which had not been taken into consideration before. The addition makes perfect sense when you consider that equipment is used to manage patients, rather than directly treat them. Equipment that is not thoroughly tested for hazards beyond electric shock could cause harm to the patient. When designing equipment such as dentist chairs and patient hoists, more detailed mechanical safety checks must now be conducted.

The standard now also covers batteries and battery charging circuits. The best advice would be to use a power source within the product that already carries a certificate proving compliance with the third edition of 60601. If such battery components are not used then they will require additional testing under the new standard. Such testing can be a lengthy and expensive process because the batteries must be proven safe under all possible environmental conditions in which the device may be used across its expected working life. Such tests must also cover the full range of safety tests such as misuse, temperature, orientation, and ingress of fluids.

A RMF should accommodate designs for which batteries might be left idle for long periods of time. One example of such a   condition is automated external defibrillators units that are stored in public places (e.g., shopping centers, offices, etc.). Users require assurance that the device will work on the rare occasion it is needed. The same requirement might apply to a battery-operated relief kit for asthmatics.

Modernizing the Approach

Although the third edition of IEC 60601 may be viewed by designers of medical equipment as yet another hoop to jump through, it is intended to help them keep pace with a rapidly changing technological world. Applying standards created more than 30 years ago would be pointless and would not adequately protect manufacturers, end-users, or patients.
The good news for device makers is that the third edition includes extremely extensive explanatory material. It aims to give designers and testers an increased insight into the rationale behind clauses, and therefore a more comprehensive understanding of the requirements.

Getting to grips with these significant changes when designing active medical devices may take some effort now, but it should prove to be a good return on investment. Those who wait until 2012 to have their products tested against the new standard will find that testing houses are booked solid as the deadline approaches. If a product isn’t approved in time it will have to be withdrawn from the market until tests are completed. Invest in appropriate redesigns now and have them tested against the new standard to reap rewards further down the line.

Jean-Louis Evans is managing director at TÜV SÜD Product Service.

Small-Bore Connectors Find Their Perfect Mates

The proliferation of luers (left) prompted the development of ISO 80369, which requires the use of specified luer alternatives such as this one by Value Plastics (right).

Promoting patient safety is paramount in medical device design and development. But in the case of tubing connectors, the widespread use of compatible luers for various gas and liquid delivery systems has continued to put patients at risk of life-threatening tubing misconnections. In a global effort to dramatically reduce this risk, however, industry, suppliers, and regulatory agencies have come together to develop the ISO 80369 standard on small-bore connectors for liquids and gases in healthcare applications. And while the imminent approval of the standard's subsections signifies a long-overdue shift in patient care, it also represents a new era of medical device design for many OEMs.

Tubing Misconnections
Because of their ease of use, price, and reliability, tapered luers quickly became the tubing connector of choice in the late 1980s and 1990s. But this proliferation of luers across tubing sets and delivery systems designated for such different functions as enteral feeding, IV administration, and neuraxial access presented the opportunity for fatal tubing misconnections.

"There is not really a problem with luers or tubing connectors themselves," explains Bruce Williams, CEO of tubing connector supplier Value Plastics Inc. (Fort Collins, CO). "The difficulty comes from the fact that they work well and, since they are relatively inexpensive, they are used in many different, and sometimes incompatible, applications. Even though the application may be incompatible, the luer connectors mate with each other as the user expects them to and therefore don't provide an indication that the tubes they've just connected shouldn't be."

Leak-proof, biocompatible tubing connectors are available from Colder Products to replace luers in a range of medical device applications.

As a result of this universal compatibility and lack of error feedback, rushed nurses have inadvertently connected enteral feeding lines to IV catheters and IV lines to epidural lines, according to reports. "It really does put a nurse in a difficult situation," notes Jim Brown, business unit manager for medical markets at Colder Products Co. (St. Paul), a provider of quick-disconnect couplings, fittings, and connectors. "[The lines] all look virtually the same, and if you connect any of those incorrectly, you can cause an irreversible injury or death."

Scattered reports of such luer-related tubing misconnections prompted rumblings of change years ago, but the development of concrete, enforced guidelines has been slow to occur. As far back as 1996, the Association for the Advancement of Medical Instrumentation (AAMI) released a standard stating that connectors employed with enteral feeding tubes should not be able to mate with female luer-lock connectors. However, the standard was not strongly enforced and had little impact on tubing connector designs. Prior to and following that standard, the European Committee for Standardization actively discussed how best to prevent misconnections and experienced some success in influencing blood-pressure cuff design away from luer connectors.

"The Institute of Medicine's [1999] report, 'To Err is Human' was the watershed that kind of broke things open, however," says Brad Noe, manager, technical resources/marketing, at BD Medical (Franklin Lakes, NJ) and cochairman of the U.S. technical advisory group to Joint Working Group 4, which is responsible for developing ISO 80369.

Since then, regionalized efforts, the Joint Commission's 2006 Sentinel Alert, and coverage of tubing misconnections in the mainstream media have added fuel to the fire. The culmination of all this activity around 2006 and 2007, Noe says, spurred AAMI to develop a technical advisory group. "Then, it was decided to elevate this on a global basis," he recalls. "The EU efforts, the U.S., and a number of other member bodies within ISO came together and decided that this standard was what we're going to create."

The ISO 80369 Standard
"In a nutshell, the goal is to improve patient safety," Williams comments. "When complete, the standard will provide medical device manufacturers with guidelines to help ensure that the various tube sets used to administer different types of patient care cannot be accidentally connected to equipment, other tube sets, apparatus, etc., in such a way that the patient will be harmed."

ISO 80369 establishes criteria for small-bore connectors and tubing sets based on their application family. Released in January, the parent document, ISO 80369-1, summarizes the strategy and objectives of the subsequent subgroups in addition to identifying their requirements. "We recognized very early on that what is today's technology and solutions may be improved upon," Noe says. "We wanted to allow for latitude for someone building a better mousetrap to not have to go back and reinvent everything. There's consistency and synergies [in the parent document], but there are no restrictions as to what the design criteria could be except within certain tolerances and expectations."

Still in development, however, are ISO 80369-2 through ISO 80369-7. ISO 80369-2 focuses on connectors for breathing and driving gas applications while ISO 80369-3 sets forth the guidelines for enteral feeding connectors. In addition, ISO 80369-4 deals with connectors for urinary collection lines; ISO 80369-5 is dedicated to limb-cuff inflation systems; and ISO 80369-6 focuses on neuraxial use.

ISO 80369-7 states that vascular access in the form of IV lines is the only application family in which luers will still be permissible, however. "We [on the working groups] can all agree on two things," Brown says. "Something has to be done, and luers will be used only when going into the bloodstream; everyone else has to change to a different type of connector."

Though not yet approved, these subgroups are inching toward the finish line. Members anticipate that the documents will gain approval beginning later this year and continuing into 2012. "We're making what most people would think is a snail's pace progress," Noe notes. "But from an international standards emphasis, we're making tremendous progress in moving things forward to get to universal standards."

Luer Alternatives
In addition to the ISO 80369 standard, California legislation dictates that the state's acute-care facilities are not permitted to use interconnecting IV and enteral feeding sets as of January 1, 2013, or 24 months after the approval of the ISO standard--whichever comes first. Likewise, epidural connectors cannot mate with other sets as of January 1, 2014, or 36 months following standard approval.

"For U.S. manufacturers, which are also often global manufacturers, it's kind of a race here--a good one not a bad one--to have product available for consumption in California by that deadline or shortly thereafter," Noe notes. "It always helps to have an incentive."

To ensure compliance with this law and the ISO 80369 standard, medical device OEMs in the specified areas need to start educating themselves about the standard and planning for potential redesigns. "They should be aware of the [standard] so they can address potential issues now," Brown advises. "Ultimately, if you're a medical device manufacturer and you're using small-diameter tubing, you're going to have to look at your connector."

Clinical requirements, flow rates, air pressures, and other performance characteristics will be outlined in the ISO 80369 standard to guide OEMs in their tubing connector designs. Specified engineering controls or forcing functions will ensure that a tubing connector from one application family specified in the standard cannot mate with a connector from any other group, according to Noe.

"The standard will provide the OEM with information and connector designs specific to the applications referenced in the standard," Williams adds. "For example, if the OEM is designing a device for a respiratory application, the standard will provide a connector design that has been evaluated and determined to be suitable for that application. By utilizing the connector specified by the standard, the OEM will be assured that their device cannot be accidentally misconnected to the other applications referenced in the standard."

To assist with product design changes, suppliers such as Value Plastics and Colder offer a variety of tubing connectors and are working on new ones to accommodate the standard as well. Value Plastics notes that recommendations for specific application areas are premature because the ISO 80369 standard is still in development; however, the company offers an array of luer alternatives that includes the SBL, TSC tapered-seal, XQ quick-connect, and BPF blood-pressure connectors. The company is also developing unique connectors designed with sealing and latching features that do not mate with connectors discussed in the standard, according to Willliams. Furthermore, it has established an ISO 80369 news hub on its Web site that provides an overview, meeting notes, archived information, and the option to receive e-mail updates.

Similarly, Colder Products provides various tubing connectors for applications outlined in the standard as well as for other medical devices that can benefit from luer alternatives. For example, the company offers the SMC product line, a standard connector that will meet the specifications established in ISO 80369 for blood pressure cuffs. It also produces the SRC line, which was designed as a reliable, leak-free luer alternative and has been employed in blood-collection applications.

"Once the standard is released, it's a big task for manufacturers to change the connector system, make all the new tooling, implement it, and get rid of all of the old stock," Brown admits. "The standard is just the beginning of it."