Originally Published MDDI August 2002

NEWS & ANALYSIS

Maureen Kingsley

As China's accession to the World Trade Organization (WTO) inches the country closer to an open market, a group of Chinese businessmen and professors is promoting the Yangtze River Basin as an investment opportunity for Westerners.

The not-for-profit, nongovernment Yangtze Council was formed in 1998 to facilitate and promote Western investment in the Yangtze region by offering market-entry and economic-development assistance. The council hopes its efforts will speed the industrial and technological development of inner China and address the disparity that exists between the region and the country's coastal cities.

Council representatives looking to attract medical device manufacturers to the region say that China's healthcare and hospital systems are undergoing major reform. The number of privately owned and foreign-invested hospitals will rise dramatically as a result of China's joining the WTO, subsequently driving up the market for medical devices and diagnostics there, they add. The country already allows private dental offices, so a market for foreign-made dental products exists, as does one for such advanced medical machines as computed tomography equipment.

Representatives of the Yangtze Council make some compelling arguments for the region. Nearly half of China's population lives there, and 40% of the country's urban population is spread across the river basin's 241 cities. The region covers approximately 1,118,700 sq mi, which accounts for almost one-fifth of all the land in China. The Yangtze River itself stretches across three of China's major economic zones. According to council members, the Chinese government plans to spend $200 billion on development of the area over the next five years.

The council favors joint partnerships between Chinese and Western companies as the main way to meet its goals. It also provides what it calls "frank, expert advice" from experienced Chinese investors in cultural, governmental, industrial, and regulatory issues.

See http://www.yangtzecouncil.org for more information.

Copyright ©2002 Medical Device & Diagnostic Industry

Originally Published MDDI August 2002

NEWS & ANALYSIS

Going From Temp to Perm: It's "Heart" Work

What do heart-failure patients, their doctors, and cardiopulmonary equipment manufacturers have in common? All three hope to see FDA approve the use of implantable heart pumps as permanent alternatives to artificial hearts, heart transplantation, and drug regimens for patients suffering from class-IV heart failure. Such pumps as the Jarvik 2000 and HeartMate have traditionally been used as temporary transitional devices in patients awaiting heart transplants, but a study published recently in Circulation: The Journal of the American Heart Association suggests their potential value as permanently implanted devices.

Known in the medical community as left ventricular assist devices (LVADs), the heart pumps have been used for the past four years to keep patients alive as they wait for heart transplants. In light of the Circulation study, however, FDA must decide whether to approve LVADs for what cardiologists are calling "destination therapy."

Clinical trials of LVADs implanted permanently in patients (in lieu of actual heart transplants) are currently under way both in the United States and abroad. One study, known as REMATCH, is spread across 20 transplant centers and is a collaborative effort of NIH, Columbia University, and Thoratec Corp., manufacturer of HeartMate. It is likely that this trial's outcome will help determine FDA's final decision on marketing LVADs as permanent devices.

Copyright ©2002 Medical Device & Diagnostic Industry

Originally Published MDDI August 2002

COVER STORY

When properly applied, double-redundant and fail-safe design methods focus validation practices on machine enhancement and reliability, reducing dependence on operator vigilance and intervention.

Ray Johnson

As the technology of packaging machinery advances, there is a greater challenge to design fail-safe systems.

Validation has been an FDA-mandated requirement in the medical device industry for many years. At first, the regulation caused immense confusion, and the initial focus by many was on generating documentation. As the practice of validation has advanced, however, a greater emphasis has been placed on the process of validating machinery and equipment.

The art of validation continues to develop and expand. As the validation testing and qualification processes mature, a greater understanding of manufacturing risks emerges. One aspect, positive, fail-safe machine design, has always been a feature of good manufacturing practices (GMPs). But as the technology of processing and packaging machinery advances, there is now a greater risk of failure and a correspondingly greater challenge to design fail-safe systems.

The regulatory bodies continue to be vigilant where customer's lives may be threatened. This vigilance is particularly important where the customer has to place absolute trust in the product. For example, ensuring product and package integrity is critical in cases of packaging where information essential to identifying the product is included on the package—or in the case of sterile products, where the packaging is part of the product.

In the medical manufacturing industry, the consumer has no alternative but to place absolute faith in the package and the product. Errors such as packaging mix-ups or faulty packs that lead to nonsterile products can easily go undetected by the consumer. Such a high level of consumer trust in the product places a high responsibility upon the manufacturer—a reliance that can only be met through GMPs, process and product controls, and process validation.

Validation has been an evolutionary process for most companies in the medical device industry. Firms have generally taken a responsible stance in implementing validation, thereby ensuring the robustness of their processes, packs, and products. A large number of companies have followed guidelines on testing and qualifying packaging machines, and there is no doubt that the validation process has substantially improved the design, quality, and performance of such machines and processes.

In the drive for near-zero defects and the need for absolute control of the packaging process, however, questions are being raised regarding faults that occur at a very low and unpredictable frequency. Such undetected faults are aberrations that are more likely to occur today as a result of technology advances. This is an issue of grave concern, because such faults potentially impact the integrity of the package—and therefore, the product.

DOUBLE-REDUNDANT AND FAIL-SAFE DESIGN

Double-redundant and fail-safe design reduce dependence on operator vigilance.

To address these concerns about undetected faults, double-redundant and fail-safe design is becoming a requirement in the area of medical device processing machinery. In this process, manufacturers carefully examine the risks of undetected errors occurring to ensure that systems are modified so that either the mistakes cannot occur or there is zero risk of them going undetected. But many medical manufacturers and their machinery suppliers have thus far failed to realize the need for or consequences of not embracing double-redundant and fail-safe design in their packaging machinery and processes.

The need for these design criteria in medical manufacturing emerged as a result of two basic factors in industry as a whole: the limitations of statistical analysis and machine complexity.

STATISTICAL ANALYSIS

If a fault is discovered, the machine rejects the product or stops the processs.

Sample inspection or statistical controls cannot detect spurious machine events or aberrations in a process. A well-recognized and legitimate method of controlling a machine or process is to apply statistical tools that will predict the standard deviation of a batch. Using such tools on a reasonable sample, it is possible to predict to a high probability whether the entire batch is going to be within the specification. Of course, these statistical tools must be applied with care—the incorrect use of statistical tools in applications where there are multiple variables can be dangerous and should only be approached with absolute care. But statistical analysis is essential and valuable in the field of validation, and a sound mathematical basis for ensuring process stability and capability.

Statistical analysis assumes stable conditions; however, the potential aberrations in modern packaging machines render a statistical analysis inadequate for predicting all errors. Furthermore, statistical tools rely on the sample being representative of the population, which may or may not be the case. Therefore, any spurious events or aberrations in the packaging process will not be predicted with the measurement of a supposed representative sample batch—unless the person taking the sample just happens to include the fault in one of the sample batches. The problem, of course, is that in validation you cannot rely upon luck.

MACHINE COMPLEXITY

The second factor affecting the potential for undetected faults is the rise in machine complexity. Thirty years ago, packaging machines were primarily mechanically driven and most processes were linked from a single drive motor through drive shafts, cams, and belts. If there were any failures on these machines, they were almost all mechanical in nature. Mechanical failures are unlikely to be spasmodic; indeed, nearly all would be permanent such that the machine could not run without intervention and repair. Such failures simply do not repair themselves, in other words, and the fault would be certain to be detected through normal GMP batch inspections.

But today, with the need for flexibility and controls that allow rapid pack changeover, machines are designed in a much more complex manner. Instead of the central drive system being composed of cams and pulleys, packaging machines now have servomotors, electronically controlled pneumatic systems, and other devices that are linked through a computer network to provide the synchronization necessary to harmonize each element of machine operation. Such machines have the essential benefits of greater flexibility (almost all changeovers are electronic), higher speed, lower maintenance, and better overall reliability. They also have the added benefit of improved GMPs, since there is a significant reduction of wear parts and parts requiring lubrication.

The flexibility and speed inherent in modern machines rely upon the control system to ensure all independent elements act in concert. The coordinating element is typically a programmable logic controller (PLC). Properly applied, the PLC ensures that commands are given to each element in the correct sequence and at the correct time.

If the PLC fails to detect the correct performance of any element to which it has sent a command and the fault remains in place, however, the fault may go undetected. The process of batch quarantine prior to sample inspection, and subsequent release after inspection, may miss the intermittent failures, thereby leading to the release of bad product into the marketplace.

APPLYING DOUBLE-REDUNDANT AND FAIL-SAFE DESIGN

In the world of machine manufacturing, there is no such thing as perfection. It is possible with new packaging systems for machine faults to be transient—in other words, the faults are only present for a small number of machine cycles and are then corrected. There is little chance that such transient faults will be detected and effected products eliminated before they are released to market without a more sophisticated level of design and controls.

There are examples in other industries where double-redundant and fail-safe design has been introduced as a regular manufacturing component. Examples include dual-brake circuitry on cars, dual-control systems on aircraft, and perhaps the simplest case of all—the backup parachute.

There has long been a need for dual circuitry in machine safety systems where there is a high potential risk to operator life. There is also a widely accepted belief, however, that no matter how careful the design, quality, and assembly procedures, errors may still occur, albeit infrequently. Thus, where lives are directly at risk, double-redundant or fail-safe design is mandatory. Since errors in the medical packaging industry also threaten lives, double-redundant and fail-safe design is no less vital.

Figure 1. Validation and risk analysis cycle. (click to enlarge)

Figure 1 illustrates a well-proven system for minimizing the risk of aberrations or transient errors. The first requirement is that validation be specified as a primary requirement, not an afterthought that is performed after the packaging process is in place and FDA is knocking on the door. In this way the machine or process is designed to be validated from the outset. This simple stipulation immediately improves the robustness and repeatability of the machine. The second step is intended to remove weaknesses in the design that may lead to transient faults or aberrations.

Risk analysis, also known as failure mode effects analysis (FMEA), enables manufacturers to identify whether transient mistakes can lead to a reduction in product integrity. The process of designing a machine where all risks are eliminated is called fail-safe design. The act of designing out a potential mistake usually requires the addition of a double-redundant system.

Process design for the medical packaging industry must include double-redundant and fail-safe design to eliminate all potential faults. The FMEA risk analysis of the process involves detailed analysis of each machine element and the potential consequences of its failure. If failure is possible, and if it will give rise to an undetected faulty package, then either the machine must be redesigned or a double-redundant system added to ensure the system is checked for correct operation each machine cycle. Machine elements with the potential for failure are termed system defects. The double-redundant system-defect subsystems do not contribute to the overall machine performance, but are put in place solely to ensure that what is expected to happen actually does happen, in every case.

Any single event that is likely to lead to an undetected reduction in pack integrity should be designed out. Single-event possibilities should be monitored by independent systems so that two independent errors have to occur in a way that produces a plausible result before undetected errors can occur. If this concept is applied along with fail-safe philosophy, the chances of two such failures arising in this manner are as close to impossible as can realistically be achieved.

In considering fail-safe design, the objective should first be to make it impossible for the error to occur. If this cannot be achieved, then it is necessary to ensure that the error does not go undetected. If the error is detected, the only way to ensure it has not induced a product or package failure is to stop the machine or to remove potentially affected items from the machine with an automatic ejection system.

POSITIVE FAIL-SAFE DESIGN PHILOSOPHY

Fail-safe design and FMEA analysis can be applied to software as well as to mechanical systems. Such analysis dictates the use of a "positive" fail-safe philosophy throughout the software design—especially for elements such as inspection systems or shift registers that sequence faults through the packaging machine. The positive philosophy is a method of processing good signals only. Any type of reject or failure would result in an absence of signals, indicating failure or "bad" product. In this way, an overall system failure or aberration that would result in an absence of signals would lead the machine to treat the occurrence as a failure by default.

A classic example is a shift register that tracks bad product through a machine to the eject station for automatic rejection. If the shift register is designed to process negative or bad signals (as many systems are—one failure leads to one signal) and the shift register loses the contents of its memory, all good and bad product will pass by the reject station. If the shift register is designed to process only positive or "good" signals (i.e., positive philosophy) and loses the contents of its memory, all good and bad product will be automatically ejected at the reject station, and then presumably after a number of consecutive faults, the machine will be programmed to stop.

How does it work in practice? The machine should be designed with a sensor to detect any product present just prior to the reject station. If the control system sends a positive "all clear" signal associated with the product, then the reject station is signaled to hold back and allow the product to pass. But if the reject station receives no positive signal as a result of a problem (i.e., heat was out of limit, pressure was too low, etc.), then it automatically ejects the product.

If there is a system failure such as a power loss or the control system becomes locked in some undefined state (like the blue screen that sometimes appears on desktop PCs), then no signals will be sent to the reject station and all product will be automatically rejected. Even in the case of a well-meaning employee placing a stray product back into the process, the reject station will sense the product's presence but the control system will not send an associated positive signal. As a result, the product will be automatically ejected.

The reject station would be fail-safe using positive-signal processing. But what happens if the air line or pneumatic cylinder that controls the reject station fails? In that case, when the reject station senses the presence of a bad product and the control system does not send a positive "hold back" signal, the product that should be ejected in the next step instead may go out the door with the good product. If this could occur, an eject verification sensor must be added in the reject chute as a double-redundant system. If the reject station does not take bad product out of the process for any reason, the eject verification sensor will not see the bad product pass through the reject chute and therefore will signal a system defect and stop the machine. The addition of the eject verification sensor makes the reject station fail-safe and double redundant.

VALIDATION TESTS, MANDATORY PLANNED MAINTENANCE, AND SOPS

Risk analysis alerts manufacturers to transient mistakes that may reduce product integrity.

The risk analysis and fail-safe design process readily identify the required validation tests. Maintenance issues that can impact validation are also identified as a result of the process, as are the standard operating procedures necessary to maintain package integrity.

Part of the operation qualification of a packaging machine involves challenging system-defect devices. An error is artificially induced for each element that has been designated as a risk, and the machine response observed. For example, with the reject station, the air to the reject mechanism is turned off and a bad product is introduced into the process. The expected response is that the eject verification sensor will not detect the ejected product and signal that a system failure has occurred.

Under all circumstances, the machine or process is expected to detect the fault and either stop the process immediately or reject the offending product. These tests are an essential part of the validation process and should always be performed to demonstrate that fail-safe design methods are working. Typically, if fail-safe design methods are used, a significant proportion of the validation testing procedures are created to ensure that the double-redundant systems are working.

In endeavoring to determine whether or not mistakes can be made, it is best to assume that if something can happen, it probably will. No matter how elaborate or complex or expensive the system is, failure can—and often does—occur. With this in mind, consider the following simple examples of components included in most packaging machines.

Pneumatics. Pneumatics are widely used and are often critical to the integrity of the pack or process. This especially applies in the case of sealing machines. Pneumatics are prone to wear, however, and can often work intermittently. It is possible for solenoid valves to stick for one cycle or for a cylinder to spasmodically fail to reach its desired position. The result could be a single faulty pack, or a single missed reject. If such events occur infrequently, they are most likely to go undetected, and as a result even an ostensibly validated process will fail.

This risk can be designed out, however, by ensuring that the correct positions of the pneumatic components are independently monitored and the positional information is sent back to the control system. Such a system would require the failure of both components (the primary device and the secondary sensing device) before product integrity could be impacted. In designing the system, the secondary positional sensing element must be positive fail-safe. The controlling system should monitor the status of the secondary element such that it cannot be overridden. The validation test should challenge both the operation of the secondary element and its positive fail-safe nature.

Servomotors. Servomotors operate by receiving instructions from a motion controller to move to a predetermined position. The controller observes the motor's position from feedback, usually in the form of pulses from an independent motion detector, known as a resolver or shaft encoder. Information is constantly updated so the controller always knows the position of the motor. The controller sends constant commands to the motor to move to the correct position at the correct time. If not robustly designed, however, the return signal could degrade or be inaccurate, in which case the servomotor will move to the wrong position. Depending on the nature of the motor's design, it is possible for such a fault to rectify itself during the next machine cycle, leaving just one potentially faulty product.

This potential risk can be addressed in one of two ways: either by choosing an inherently fail-safe servomotor and control system, or by adding secondary monitoring systems to separately detect the correct position of the machine on every cycle. Again, the testing procedure should challenge the robustness of such systems under the fault conditions that have been identified in the risk analysis.

Temperature Controllers. Most temperature-control systems are considered robust. It is only when risk analysis or FMEA is applied that the scope for potential errors is realized. For example, a heat-sealing-type packaging machine must hold its sealing temperature steady within a predetermined operating range or otherwise signal a system defect. All such machines should have double-redundant and fail-safe design to ensure that no product is packaged outside of the operating range.

In the case of a heating system with multiple heater cartridges but only one feedback temperature probe, however, there is a risk that a single element could fail without being detected by the temperature probe. By ensuring that all heaters are connected in series—so that if one heater fails, all will fail—the temperature probe is then sure to detect the failure and the risk can be eliminated. Alternatively, current-monitoring devices for each cartridge can be used to eliminate this potential risk.

CONCLUSION

Double-redundant and fail-safe design methods are becoming essential features of packaging machines in a validated environment. Properly applied and embraced, they will further increase the reliability of the machines and the quality of the products emerging from the medical device industry.

More importantly, double-redundant and fail-safe design methods will help focus validation on machine enhancement and reliability, and reduce dependence on operator vigilance and intervention. This approach is the only certain way to eliminate the transient faults and aberrations that have arisen from the increased complexity of modern machine design.

Ray Johnson is president of Doyen Medipharm Inc., Lakeland, FL.

Copyright ©2002 Medical Device & Diagnostic Industry

A new material designed for nonlubricated applications reduces wear on moving parts. Polyamide-imide also provides a margin for continued operation of lubricated systems if lubrication is lost. Torlon 4435, designed by Solvay Advanced Polymers (Alpharetta, GA; 770/772-8200), exhibits wear resistance to both low-pressure and high-velocity conditions, and high-pressure and low-velocity conditions. Torlon's durability is due to its ability to maintain mechanical properties at high temperatures. The polyamide-imide material features a glass transition temperature that allows parts to operate at temperatures of up to 260ºC. The 4435 grade, a thermoplastic material, can be formed into a net shape by injection molding. Torlon is also available in grades applicable to moderate environments.

Parylene has been used in a wide range of medical device and component applications since the 1970s. These include catheters and mandrels, stents, needles, cannulae, cardiac assist devices, prosthetics, and electronic circuitry.

The need to sterilize such products raises a number of questions regarding the poststerilization characteristics of the coating material. This article describes a series of laboratory tests that were conducted to determine the effects of common sterilization methods on selected parylene coatings used for medical device applications.¹

PARYLENE FILM AND THE USE OF STERILIZATION

The raw material for parylene films is a powder known as dimer.

Certain medical components require a protective coating to isolate them from contact with moisture, gases, corrosive biofluids, or chemicals. Coatings are also used to protect patients from contact with surgical items or implanted devices that may not be biocompatible. Vacuum-deposited parylene is often the protective medical coating of choice. Additionally, parylene may be used to deliver other functional properties, such as electrical insulation, particulate tie-down, or increased lubricity.

The thin, transparent polymer film is characterized by pinhole-free coverage of both planar and irregular surfaces. Because it is deposited from a gaseous state, parylene provides uniform coverage across a substrate, even on corners, edges, and in crevices. (See sidebar for a description of parylene variants and the vacuum coating process.)

Sterilization is intended to destroy all microbial contaminants on the surface of a medical device, and the process can be accomplished by a number of chemical or physical means. The challenge in sterilization is to render a surface sterile without degrading the function or useful life of either the sterilized item or its coating.

STERILIZATION TEST METHODS AND SAMPLE MATERIALS

To measure the effects of each sterilization process on a parylene-coated object, it was necessary to compare quantitative test results for coated and sterilized samples with similarly coated samples that had not been sterilized.

The physical-property measurements identified for the sterilization tests were tensile strength, tensile modulus, coefficient of friction, moisture vapor transmission, and dielectric strength. Standard statistical tools were used to determine sterilization-related differences (changes) between the control and test samples. The sterilization procedures tested included steam autoclave, gamma and e-beam irradiation, hydrogen peroxide (H₂O₂) plasma, and ethylene oxide (EtO). Three laboratories performed the various post-sterilization tests.

Parylene-coated test samples included borosilicate glass plates and polished 16-gauge 304-stainless-steel coupons. The glass plates were treated with a release agent to allow the film to be separated after sterilization for moisture vapor transmission and tensile strength measurements. The coated steel coupons were used for voltage breakdown tests.

The steel and glass coupons were prepared in four coating runs (two Parylene N and two Parylene C), with consistent run-to-run fixturing. All of the specifications for each coating run were recorded and provided to researchers. These included such factors as chamber volume, dimer charge, polymer density, deposited mass, and average film thickness.

Dielectric Strength. Breakdown voltage testing was peformed in accordance with ASTM 149, Method A, at a ramp rate of 500 V/sec. Groups of five replicate breakdown voltages were recorded in ac kilovolts, and the results were coordinated with precise film-thickness measurements.

Dielectric strength was defined as the voltage gradient, or electric field strength, at which the breakdown occurs, and was calculated from the raw voltage breakdown data. In most cases, voltage breakdown resulted in a clearly visible puncture hole through the coating, and film thickness at each breakdown point was recorded with an accuracy of ± 0.1 µm.

Moisture Vapor Transmission. Moisture vapor transmission (MVT, also called permeability) calculations on sterilized coating samples followed the provisions of ASTM F1249, a dynamic flow method using a dry gas carrier, with a pressure-modulated infrared detector to measure transmitted moisture.

These measurements were made on 3-in. free-film samples lifted from coated glass coupons. Laboratory results took into account any sample-to-sample variations in coating thickness.

Tensile Properties. Tensile properties were measured in accordance with pull tests as defined by ASTM D882. Tensile tests were made on 1 ¥ 10 in. free-film- strip specimens that were removed from glass plate carriers. This method generated data for peak load (lb), peak stress (psi), Mod E (psi), yield at 10% (psi), and elongation to break (%).

Coefficient of Friction. Coefficient of friction (COF) values for sterilization samples were determined according to ASTM D1894, which involves use of a weighted sled and strain-gauge measurements. The COF is the relation of the frictional force--as measured by the strain gauge of the test apparatus--to the sled weight. Two force values were recorded: starting (static) COF, and sliding (dynamic) COF.

GENERAL TEST RESULTS

Sterilization Method	Parylene N					Parylene C
	Dielectric Strength	MVT	Tensile Strength	Tensile Modulus	COF	Dielectric Strength	MVT	Tensile Strength	Tensile Modulus	COF
Steam	None	Δ43%	None	Δ12%	Δ38%	None	Δ5*	Δ17%	Δ9%	None
EtO	None	Δ21%	None	None	Δ33%	None	8%	None	None	None
E-beam	NA	None	None	None	None	NA	None	None	None	None
H2O2 plasma	None	None	None	None	Δ48%	Δ9%	None	None	None	Δ188%
Gamma	None	None	None	None	None	None	Δ5%	None	None	None
* 5% values are not likely to be statistically significant. NA=not applicable.
Table I. Effects of various sterilization methods on parylene.

Parylene coatings respond to these sterilization methods in a variety of ways (see summary of responses in Table 1). With regard to tensile properties, Parylene N and C were largely unaffected by any of these sterilization techniques. Only steam appears to have had any effect, causing an annealing impact on samples coated with Parylene C, seen as an increase in film crystallinity with a slight change in the tensile properties. Similarly, the tensile modulus property of Parylene N exhibited a minor change.

H₂O₂ plasma sterilization treatment appeared to alter dielectric strength, with a minimal change in Parylene C, and no change in Parylene N.

As with many polymers, parylene subjected to radiation sterilization techniques exhibits an accumulated-dose effect. Consequently, device manufacturers considering E-beam or gamma sterilization should conduct further testing to determine the effects of repeated radiation sterilizations at the anticipated dosage level in the intended application.

There were some subtle differences in the responses of the two parylene variants to these tested sterilization methods. For example, E-beam and gamma irradiation sterilization had no impact on either Parylene N or C tensile properties. H₂O₂ plasma sterilization mildly affected the coefficient of friction value of Parylene N, and the dielectric strength and COF of Parylene C. EtO affected MVT and COF in Parylene N, but only MVT in Parylene C.

In summary, the test results were quite favorable for each type of sterilization method tested. Individual film performance and sterilization impact must be addressed specifically by application.

CONCLUSION

The multilaboratory sterilization test information presented here is an important asset for the continuing development of parylene coating technology for medical device applications. The data generated will be useful for medical manufacturers in the selection of sterilization processes for given products and application settings.

---

FOOTNOTE

1. Parylene (poly-para-xylylene) is a generic polymer coating. Although several suppliers manufacture proprietary versions of the precursor dimer, di-para-xylylene, these sterilization tests were sponsored exclusively by Specialty Coating Systems (SCS; Indianapolis) and were confined to coated test-film samples made from SCS dimer. Thus, test results should not be regarded as being applicable to the dimer or coated products of other suppliers.

Lonny Wolgemuth is medical product manager at Specialty Coating Systems (Indianapolis), a Cookson Electronics Company.

Copyright ©2002 Medical Device & Diagnostic Industry

. AorTech International (Scotland, UK; +44 1698 746699) has selected PEEK-Optima polymer for the frame of its next-generation synthetic trileaflet heart valve. The valve, undergoing trials in the United States and in Europe, is expected to be on the market by 2005. PEEK-Optima, manufactured by Invibio Inc. (Greenville, SC; 866/468-4246), is a polyaromatic, semicrystalline polymer that has undergone extensive biocompatibility and biostability testing to ensure its suitability for implantation. The AorTech valves are designed to overcome the clinical problems of mechanical and bioprosthetic valves: mechanical valves require daily anticoagulant treatment, and bioprosthetics have a limited life span. Each AorTech valve is specified to meet desired tolerances and machined to deliver precise qualities. The company has designed testing equipment to monitor valve performance at varying heart rates, blood pressures, and temperatures.

Originally Published MDDI August 2002

COATING TECHNOLOGY

Return to Article: Assessing the Effects of Sterilization Methods on Parylene Coatings

Transparent parylene film is applied to substrates in a vacuum chamber by means of vapor deposition polymerization. A dry, powdered precursor known as dimer is converted by heat in the coating system to form a dimeric gas, and heated further to generate a monomer gas that is passed to a deposition chamber. Within the chamber, it polymerizes at room temperature as a conformal film on all exposed substrate surfaces.

Parylene deposition has no liquid phase, uses no solvent or catalyst, and generates no gaseous by-products. Consequently, there are no cure-related hydraulic or liquid surface-tension forces in the coating cycle, and coated objects remain free of mechanical stress. The resulting film is a high-molecular-weight, linear, crystalline polymer with an all- carbon backbone. With the absence of polar entities, and substantial crystallinity, the finished film is stable and highly resistant to chemical attack.

The static and dynamic coefficients of friction for parylenes are in the range of 0.25 to 0.33. This dry-film lubricity is an important chracteristic for certain device applications, such as catheter and guide-wire coatings.

PARYLENE VARIANTS

There are four primary variants of the polymer: Parylenes N, C, D, and HT. Although they all have the same essential coating properties and are applied in the same manner, each has a unique molecular form that results in specialized performance characteristics. Parylenes N and C are the most commonly used variants in medical coating applications. Table I describes the key properties of these parylenes.

Property		Parylene N	Parylene C
Dielectric constnat	60 Hz	2.65	3.15
	1 KHz	2.65	3.10
	1 MHz	2.65	2.95
Dissipation factor	60 Hz	0.0002	0.020
	1 KHz	0.0002	0.019
	1 MHz	0.0006	0.013
Secant modulus (psi)		350,000	400,000
Tensile strength (psi)		6000-11,000	10,000
Yield strength (psi)		6100	8000
Elongation to break (%)		20-250	200
Yield elongation (%)		2.5	2.9
Density (gm/cm3)		1.10-1.12	1.289
Index of refraction (nD23)		1.661	1.639
Water absorption (% after 24 hr)		<0.1	<0.1
Rockwell hardness		R85	R80
Static coefficient of friction		0.25	0.29
Dynamic coefficient of friction		0.25	0.29
Melting point (°C)		420	290
T5 point (°C)		160	125
Gas permeability at 25°C (cm3(STP)•mil/100 in2/d•atm)	N2	7.7	1.0
	O2	39	7.2
	CO2	214	7.7
	H2	540	110
Moisture vapor transmission at 90% RH, 37 °C 0.21			1.5
Table I. Key physical and mechanical properties displayed by Parylene N and Parylene C.

Parylene N offers the highest penetrating power of the variants. Because of its greater molecular activity in the monomer phase, it can be used to coat relatively deep recesses and blind holes. This form of parylene also provides slightly higher dielectric strength than C, and a dielectric constant that is independent of frequency. The lower dissipation factor and dielectric constant of this parylene form enable it to be used for protecting high-frequency substrates where the coating is in the direct electromagnetic field.

Parylene C differs from N in that it has a chlorine atom on the benzene ring, providing a useful combination of electrical and physical properties. Among these are very low permeability to moisture and corrosive gases. Compared to Parylene N, C displays less crevice-penetrating ability.

Copyright ©2002 Medical Device & Diagnostic Industry

A team of scientists has developed biomaterials based on human keratin proteins. The research, funded by Southwest Research Institute (San Antonio, TX; 210/684-5111), focuses on chemical modification of human hair keratins to create keratin-based hydrogels, elastomers, and coatings. Keratins, proteins that make up structural elements of vertebrate tissues, feature homologs numbering more than 100. Human hair keratins provide a structural diversity ideal for biomaterials and are highly tolerated as implantable materials. Once the human keratins are modified, they are processed into biomaterials with tailored chemical, physical, and biological properties. Testing of the biomaterials has revealed the potential of keratins to enhance tissue growth and promote tissue repair. Applications include wound healing, coatings for medical implants, soft tissue augmentation, cellular and protein therapy delivery, and matrices and scaffolds for tissue engineering.

Originally Published MDDI August 2002

ELECTRONICS

Understanding the New EMC Standard for Medical Devices: What Manufacturers Need to Know Now

Meeting the new requirements set forth in the latest edition of 60601-1-2 might prove challenging for OEMs.

Don Sherratt

A test technician prepares for an EMC test in a 10-m semianechoic chamber. Use of a semianechoic chamber is necessary for the immunity testing required under EN 60601-1-2:2001 for applicable medical devices destined for the European Union.

In 1993, the International Electrotechnical Commission (IEC) published the first edition of 60601-1-2, the international electromagnetic compatibility (EMC) standard for medical devices. Soon after, the European Committee for Standardization (CENELEC) adopted it as a European Norm (EN) standard—with only minor changes. It should therefore come as no surprise that IEC's latest revision of 60601-1-2, published in September 2001, was adopted by CENELEC shortly thereafter and published as EN 60601-1-2:2001 It will appear in the Official Journal of the European Community in August 2002.

IEC (EN) 60601-1-2:2001 is considered a major rewrite of the original and will have profound effects on compliance with regard to two important EU directives: the Active Implantable Medical Devices Directive (90/385/EEC) and the Medical Devices Directive (93/42/EEC), as well as CB Scheme requirements and related standards. While the phaseout date of the 1993 EN standard will be two years from now, manufacturers that export their products globally—or who plan to—and wish to remain competitive should immediately begin developing strategies to address the new standard's impact on product design and development.

To help manufacturers prepare for this transition, this article addresses the most significant differences between the first and second editions of IEC 60601-1-2, and outlines key steps to compliance.

Tougher criteria, higher limits

The most significant revisions to IEC 60601-1-2 include increased testing limits for electrostatic discharge (ESD), radiated radio-frequency (RF) immunity, surge immunity, and electrical fast transients (EFTs). There are also required tests for conducted RF immunity, magnetic field immunity, voltage dips, harmonic distortion, and voltage flicker. In addition, the standard contains more-comprehensive pass/fail criteria, which require that clinical utility be maintained during immunity tests and that the manufacturer define acceptable criteria of clinical utility.

Electrostatic Discharge. The standard outlined in IEC 60601-1-2:2001 for measuring ESD is IEC 61000-4-2. It defines the range of test levels in relation to different environmental and installation conditions and establishes the appropriate test procedures. The objective of the standard is to establish a common reproducible basis for evaluating the performance of equipment when subjected to ESD. Table I compares the old ESD measurement limits to the new ones.

IEC 60601-1-2:1993	IEC 60601-1-2:2001
IEC 801-2	IEC 61000-4-2
±3 kV for conductive parts ±8 kV for nonconductive parts	±2, 4, and 6 kV for conductive parts ±2, 4, and 8 kV for nonconductive parts
Table I. A comparison of ESD requirements between the old and new standards.

These new requirements will likely demand that insulation thicknesses and creepage and clearance distances be greater than before to prevent arcing through and tracking over insulation. They might also require enclosure materials to possess increased antistatic properties, or that equipment specifications detailed in user manuals mandate higher relative humidity levels for operating environments.

Radiated RF Immunity. In the first edition of the standard, RF immunity requirements were defined by IEC 801-3. In the updated version, they are defined by IEC 61000-4-3 and are outlined separately for life-supporting and non-life-supporting medical electrical equipment. The frequency range of the requirements has been widened and allows for devices specified for use only in shielded locations. Other noteworthy differences include an intentional RF receivers' operation-mode exemption and a mandate that patient-coupled equipment must meet the same requirements as other equipment. Table II presents a comparison of the two standards.

There are different test methods defined in the new standard for measuring RRFI of different medical electrical equipment; manufacturers should discuss the most acceptable methods with technical experts at their testing lab.

IEC 60601-1-2:1993	IEC 60601-1-2:2001
IEC 801-3	IEC 61000-4-3
3 V/m at ISM frequencies from 26 MHz to 1 GHz with 80% AM for non-life-support equipment 3 V/m from 26 MHz to 1 GHz with 80% AM modulation for life-support equipment	3 V/m at ISM frequencies from 80 MHz to 2.5 GHz with 80% AM for non-life-support equipment 10 V/m from 80 MHz to 2.5 GHz with 80% AM modulation for life-support equipment
Table II. A comparison of RF immunity requirements between the old and new standards.

Electrical Fast Transients. IEC 801-4 determined the EFT immunity requirements and test methods in the previous standard, but it will be replaced by IEC 61000-4-4 in the new edition. The new standard defines the test voltage waveform, range of test levels, test equipment, test setup, and test procedure, as outlined in Table III. One notable change is the lack of differentiation between permanently and temporarily installed equipment. There also are significant differences in the requirements for testing ranges and repetition rate, and pass-fail criteria are much tighter under the new standard.

Manufacturers should also be aware that the new standard requires that handheld equipment or parts of handheld equipment be tested with an artificial hand to simulate the capacitive coupling effect of the operator, as specified in CISPR 16-1. The artificial hand is connected to the ground reference plane during the tests. This requirement is new for medical electrical equipment and might result in dielectric stresses on signal or patient cables carrying high-frequency or high-voltage signals. To reduce the potential for this occurrence, manufacturers should keep in mind the type of cables used in interconnecting leads and note that patient leads might need to be changed.

IEC 60601-1-2:1993	IEC 60601-1-2:2001
IEC 801-4	IEC 61000-4-4
±1kV for mains-plug-type equipment ±2kV for permanent equipment ±0.5 kV for signal lines 2.5-kHz repetition rate	±2kV on power lines ±1kV for signal lines 5-kHz repetition rate
Table III. A comparison of EFT requirements between the old and new standards.

Surge Immunity. IEC 61000-4-5 is the new standard that specifies test levels relating to different environmental and installation conditions. It establishes a common reference for evaluating the performance of equipment when subjected to high-energy disturbances on the power and interconnection lines, and specifies sweeping phase angles over particular voltage ranges. The determination of compliance is based on the response of the equipment, considering each surge individually, and taking into account the effects of any coupling between cables that are tested directly and those that are not. Table IV presents a comparison of the old and the new requirements.

These new requirements could necessitate circuit redesign and component changes in medical devices. While the upper voltage requirement remains the same, the new lower voltage requirement means more than one level of surge protection will be needed and will have to begin at ±0.5 kV.

New tests, methods, and prerequisites

IEC 60601-1-2:1993	IEC 60601-1-2:2001
IEC 801-5	IEC 61000-4-5
±2kV common mode ±1kV differential mode	±1.5, 1, and 2 kV common mode ±0.5 and 1 kV differential mode
Table IV. A comparison of surge immunity requirements between the old and new standards.

In addition to a significant difference in test limits, the new standard also specifies changes in the classification of products and outlines the methods and new equipment necessary to determine emissions and immunity compliance.

Product Classification. The new standard stipulates that nonmedical equipment used in a medical system need only meet the applicable CISPR requirements—in most cases CISPR 14, 15, and 22. Most medical electrical equipment or systems will remain subject to the requirements of CISPR 11 and must be defined as Group 1 or 2 and Class A or B. Manufacturers should keep in mind that hospitals are often considered residential or domestic; therefore, Class B limits are often imposed.

Harmonic Distortion. There are two new requirements for determining emissions compliance. The first, IEC 61000-3-2, Limits for harmonic current emissions, addresses the effect on the sinusoidal waveform of the main supply of products with a rated input current up to and including 16 A per phase that are intended to be connected to the public mains network.

In addition to changing the power filter to accommodate the frequency range increase, it may be necessary for manufacturers to redesign the power supply circuit so that it will not affect the sine wave quality of the public mains network or the product harmonics on the public mains network.

Voltage Fluctuations and Flicker. IEC 61000-3-3, Limitations of voltage fluctuations and flicker, is the other new emissions requirement. It specifies the testing and limits of short interruptions or dips in the supply voltage caused by other apparatus connected to the same electrical supply (known as flicker). The new requirement specifies that compliance must be determined for all medical electrical equipment or systems with a rated input current up to and including 16 A per phase and those that are intended to be connected to the public mains network.

If the equipment has long-time and momentary current ratings, the higher of the two ratings shall be used in determining the
applicability of the requirement.

Manufacturers should note that the holdup times for power supplies will need to be improved in machines for which voltage dips and interruptions can cause the product to lose function.

Conducted RF Immunity. There are several new immunity requirements in the new IEC document. The first is a new standard for measuring conducted disturbances induced by RF fields in start frequency: IEC 61000-4-6. Under this standard, equipment is evaluated according to its respective testing category; these categories include life-supporting equipment, non-life-supporting equipment, shielded-location-use equipment, intentional RF receivers, and battery-powered equipment. Manufacturers are responsible for choosing the appropriate test and severity level applicable to the product.

Magnetic Field Immunity. Using IEC 61000-4-8 to determine magnetic-field immunity at various power frequencies is another new immunity requirement under IEC 60601-1-2. Equipment rated for both 50 and 60 Hz is subjected to a magnetic field of 3 A/m at 50 Hz and again at 60 Hz. If a piece of equipment is rated for operation at only one frequency, the tests are conducted at the rated frequency. There is no allowance for loss of performance or interruption of operation in this requirement.

The manufacturers most effected by this new test requirement will be those with equipment containing magnetic-sensing devices, such as hall-effect sensors or bimetal switches. Specific shielding of these components may be required to reduce unwanted operation. Magnetic field immunity levels may also need to be raised for equipment intended for use in the proximity of powerful magnetic fields.

Voltage Dips, Interruptions, and Variations. A third new immunity requirement outlined in IEC 61000-4-11 defines immunity test methods and the range of preferred test levels for voltage dips, short interruptions, and voltage variations of equipment connected to low-voltage power supply networks. The requirement applies to equipment and systems that have an input power rating of up to 1 kVA, or an input current of 16 A or less per phase. There is no allowance for component failures or equipment malfunctions requiring repairs.

There is some leeway within the compliance levels for non-life-supporting equipment, if the manufacturer can justify lower levels based on the hazard the product will pose when exposed to voltage dips or short interruptions in the supply voltage. If a lower compliance level is sought and justified by the manufacturer, it may be necessary to use (or make recommendations for the use of) uninterruptible power supplies, batteries, or power-conditioning equipment.

Crucial next steps

Manufacturers should act now to ensure their readiness for the new requirements in 60601-1-2. The following suggestions are measures that companies can take to help prepare themselves.

Test products currently under development. Manufacturers should begin to identify potential noncompliance in products that are under development by testing them against the current IEC standard in a 10-m semianechoic chamber. Potentially top-money-earning products should be identified and tested immediately to determine what changes—if any—will be necessary before the new edition of the standard is officially established.

Partner with a third-party testing lab as soon as possible. Testing of medical devices or systems requires time to complete the conformity assessment phase. only a few conformity assessment organizations accredited to perform the testing exist to serve hundreds of manufacturers. What's more, few labs are equipped with the full array of test equipment needed to determine compliance with the new standard. To avoid production delays, manufacturers should work with a third-party tester to ensure that their most important products are either compliant—or very close—by November 1, 2004.

Develop tables of acceptable criteria for each operating mode. The tables should identfy possible indicators of performance degradation and describe how such degradation is likely to manifest itself. This information will assist the testing lab in detecting problems objectively so they can be accurately reported to the manufacturer. It would also be wise for the manufacturer to witness the immunity tests so that noncritical errors are correctly interpreted as such. Manufacturers seeking guidance in completing these tables will benefit from an early partnership with their third-party test lab.

Decide whether or not to continue Offering legacy Products. Manufacturers must make decisions soon about legacy products, for which redesigning for compliance could be cost-prohibitive. Older products might need to be replaced with redeveloped models to meet the new standard.

Check CE Marking. Following a successful product conformity reassessment, the declaration of conformity for those devices previously bearing the CE marking will need to be renewed and the technical files will need to be revised, along with the device master records and design history files. The relevant notified body (for devices in Class I, IIa, IIb, or III) will need to be informed of any significant design changes, and it may be necessary to resubmit a summary of changes made, along with a risk analysis and essential requirements checklist.

By keeping abreast of the changes in the new EN EMC standard and preparing products for compliance, manufacturers can avoid critical time-to-market delays and gain a global competitive edge.

Don Sherratt is the director of business and technology for medical devices at Intertek ETL SEMKO in Boxborough, MA.

Copyright ©2002 Medical Device & Diagnostic Industry

Nitinol material is now available in both wire and tubular form from UTI Corp. (Collegeville, PA; 800/321-6285). Nitinol provides shape memory, high elasticity, biocompatibility, and MRI compatibility. Elastic properties give it rubberlike qualities; it can return to its preset shape after deformation. Uniform Tubes, a division of UTI, has developed a tube-drawing process that is compatible with nitinol fabrication. UTI's Star Guide division specializes in precision wire applications for the alloy. Potential applications include guidewires, stents, flexible needles, orthodontic wires, clamps, and sutures.