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Canon Launches ChineseTrade Show and Magazine

Originally Published MPMN September 2004

INDUSTRY NEWS

Canon Launches Chinese Trade Show and Magazine

Susan Wallace

Two new products will be launched by MPMN's publisher, Canon Communications llc (Los Angeles; www.devicelink.com). They are a quarterly Chinese-language magazine, China Medical Device Manufacturer (CMDM), and the MEDTEC China conference and exhibition. Both will serve China's fast-growing medical manufacturing industry. 

Canon will receive active support for both initiatives from the China Association for Medical Devices Industry (CAMDI). CAMDI represents nearly 4000 member companies and has strong ties to the country's State Food & Drug Administration (SFDA). 

The premier issue of CMDM is scheduled for January 2005. The initial circulation will be 6000. The MEDTEC China show will debut in the fall of 2005. 

William F. Cobert, president and CEO of Canon, says, "China's medical manufacturing market is growing at an astonishing rate, and much of its infrastructure is already in place." He continues, "Through these major product line extensions, we will expand our global reach and be in a strong position to assist our core customer segment--high-technology OEM suppliers--in serving the Chinese market."

According to Frost & Sullivan's 2002 Country Industry Forecast: Chinese Healthcare Industry, China's total healthcare market grew well over 100% in the five-year period ending in 2001. During the same time frame, the share of the medical device and equipment segment of this market increased from 5% to nearly 17%.

"We enthusiastically support Canon's new products in China," says CAMDI's chairman, Jiang Feng. "Our member companies need a dedicated industry journal and exhibition to meet the sharply growing demands of China's healthcare marketplace."

In addition to MPMN, Canon produces 19 trade magazines, 18 U.S. and international trade shows, industry directories, medical device engineering and design awards, and Internet sites.

Copyright ©2004 Medical Product Manufacturing News

Thermoplastic Supplier Provides Custom Polymer and Process Development Services

Originally Published MPMN September 2004

INDUSTRY NEWS

Thermoplastic Supplier Provides Custom Polymer and Process Development Services

Corinne Litchfield

Foster Corp.'s laboratory and processing equipment are available for customers needing polymer R&D assistance.

Companies purchasing small quantities of materials can often believe they are shortchanged in terms of customer service. Sometimes they may feel they have been coerced into buying more than they need. 

Foster Corp.'s Applied Polymer Development (APD) group (Putnam, CT; www.fostercorp.com) has a better idea. The firm now offers custom polymer and process development services, unrelated to the amount of material purchased, to medical device manufacturers around the globe. By forgoing quantity requirements, the company can provide R&D assistance on a contractual basis to both small- and large-scale manufacturers.

Small-volume material-supply purchasers are sometimes required to buy minimum lots substantially greater than what they need for their consumption, and technical support may be minimal. The typical transaction between a materials supplier and customer is made in dollars per pound of material purchased. Rather than tell potential customers to return once they have a price-per-pound amount, APD assists customers with the development process on a contractual basis. 

"There's an increasing demand for companies to do R&D regarding material solutions before they can determine how much material is needed," says Dan Lazas, APD's business manager. The company's polymer engineering skills, laboratory, and processing equipment are available to clients needing services ranging from experimental design to comprehensive material support. Services are offered on time-based rates or project fees, and are tailored to meet the client's application and budget requirements. 

Copyright ©2004 Medical Product Manufacturing News

Companies Join Forces to Advance Drug Delivery via Biodegradable Polymers

Originally Published MPMN September 2004

INDUSTRY NEWS

Companies Join Forces to Advance Drug Delivery via Biodegradable Polymers

Corinne Litchfield

Site-specific drug delivery is made possible by using biodegradable polymers to surface coat medical devices, such as the drug-eluting stent shown at right. An uncoated stent is shown on the left.

From dissolving sutures to orthopedic implants, the use of biodegradable polymers in medical devices has surged in the past 30 years. Current applications include devices that not only deliver medication to a specific area but that are also resorbed by the body over time. SurModics Inc. (Eden Prairie, MN; www.surmodics.com), a provider of surface-modification and drug-delivery solutions, has obtained an option to acquire an exclusive license from OctoPlus (Leiden, Netherlands; www.octoplus.nl) for two classes of biodegradable polymers. "Our customers are increasingly interested in exploring the use of biodegradable polymers for site-specific drug delivery--whether as coatings on medical devices, or as devices that are fully biodegradable," says Bruce Barclay, president and COO of SurModics. 

With the addition of OctoPlus's products, SurModics has five distinct families of polymers for use in site-specific drug delivery. The two polymer classes from OctoPlus, known as PolyActive and OctoDEX, now join SurModics's previously announced Bravo, Encore, and Accolade lines. SurModics's Bravo polymer matrix is already in use in the drug-eluting stent marketplace. It is also used in an ophthalmic drug-delivery system under development at InnoRx Inc. "We believe [PolyActive and OctoDEX] have the ability to demonstrate both excellent mechanical properties and tunable drug elution as a medical device alone or from the surface of medical devices," states Barclay. 

"We are very pleased to enter into this agreement with SurModics, a well-established player in the medical devices arena," says Dr. Joost Holthuis, CEO of OctoPlus. "This partnership strongly complements our activities in developing state-of-the-art controlled-release drug-delivery systems. By combining the strengths of our two companies, we will maximize the scientific and commercial potential of our proprietary biodegradable polymers in the rapidly growing drug-eluting medical devices field."

PolyActive and OctoDEX are currently under clinical and preclinical evaluation by OctoPlus for use as pharmaceutical formulations. PolyActive, a biodegradable multiblock polymeric drug-delivery system, has been used in two FDA-approved products. Its biodegradability, safety record, and tunable release properties make it suitable for the controlled release of proteins and hydrophobic small-molecule drugs. OctoDEX is a delivery system for the controlled release of proteins and large particles such as liposomes and antigens. Both PolyActive and OctoDEX have undergone extensive safety testing. Further, OctoPlus has demonstrated that these polymers can be made into durable films. Applied to medical devices, they can be used to deliver large and small molecules with tunable elution rates and varying linear- or pulse-release profiles. 

Copyright ©2004 Medical Product Manufacturing News

Walking the Talk

Originally Published MPMN September 2004

EDITOR'S PAGE

Walking the Talk 

It's that time again. The presidential election is starting to heat up and the candidates are doing their very best to convince us that they can make our lives better. And of course, they're all promising that they'll make sure 
everyone who wants to work has a job. Nice words, but whether it will happen remains to be seen.

In the meantime, some medical device suppliers are doing more than just talking the talk. They are taking the initiative and making a difference in the lives of one group of people who may not otherwise have jobs--the disabled. In the United States, there are more than 32 million people with disabilities who want to work.
 
Employ + Ability Inc. (Braintree, MA) welcomes them. In fact, the company's mission is to provide jobs with benefits to disabled people. Ninety percent of its workforce are people with mental or physical disabilities.

"The focus at Employ + Ability is on the ability of the employee, not the disability," says Louis DeHaan, the company's CEO and president. "[Our mission] is really putting people in positions where they can succeed and improve their ability." 

The FDA-registered company makes more than 10 million hot- and cold-therapy products annually, ranking it one of the largest manufacturers of these products in the country. Employ + Ability also assembles Class II medical devices, including pregnancy test kits, as well as makes and packages single-use medical kits.
 
The company receives no state or federal funding. Instead, it relies on the revenue generated from sales to cover operating costs. Any charitable contributions received are set aside for capital expansion and the creation  of new jobs. The company does solicit private investors, whose donations cover the cost of full-time employment of a person with disabilities. 

Another company, Opportunity Medical (Highland Park, IL), also employs the disabled. It has joined Workability International, a consortium dedicated to increasing employment for the disabled worldwide. The group believes that people with disabilities should have the same right to work, and equal opportunity and pay for equal work.

Opportunity Medical is a contract manufacturer of sterile, disposable medical products. They also offer secondary services such as pad printing, precision drilling, manual assembly, heat sealing and shrink wrapping, and sterilization and validation.

Hiring disabled people is a strategy that has paid off for both firms. Their clients are some of the leading medical device companies. Opportunity's customers include Baxter, Cardinal, Tyco, Medline, and Searle/Pharmacia. Employ + Ability produces and fills orders for Inverness Medical, Johnson & Johnson, Tyco Healthcare, and US Surgical.

These two companies should be commended for their efforts. Their success proves that disabled workers are a valuable and effective resource. And it works both ways. With these jobs, the disabled can reduce or eliminate their public assistance for disability entitlements. 

Susan Wallace, Managing Editor

Copyright ©2004 Medical Product Manufacturing News

Temperature Sensors Go Platinum

Originally Published MPMN September 2004

HOTLINE

Temperature Sensors Go Platinum

Surface-mounted temperature detectors use thin-film technology

Corinne Litchfield
The small package size of the platinum RTDs make them suitable for use in applications where space is an issue.

A surface-mount resistance temperature detector (RTD) series developed by Heraeus Sensor Technology (North Brunswick, NJ) is suited for use in biomedical applications. The 0805 RTD provides the stability of a thin-film platinum RTD in a standard surface-mount package. 

Surface-mount thermistors can shift in resistance properties, but the platinum RTDs' resistance remains stable, resulting in high accuracy, according to Bob Gliniecki of the company's U.S. distributor, DWM & Associates. Thin-film resistance elements have a sensitive platinum film deposited onto the ceramic former, thus offering small dimensions and the possibility of high nominal resistances. The small package size provides a fast thermal response time and is suitable for products where space is an issue. Possible biomedical applications include temperature compensation in personal glucose testers, SIDS breathing sensors, and patient temperature monitoring and management. 

Five types of RTD elements are available in the SMD 0805 series. Key operating characteristics of the elements include low drift, long-term stability, and interchangeability. 


DWM & Associates (US distributor for Heraeus Sensor Technology)
1901 Rte. 130 
North Brunswick, NJ 08902 
Phone: 732/940-4400 
Fax: 732/940-4445
E-mail: sales@dwmai.com 
URL: www.dwmai.com 

Copyright ©2004 Medical Product Manufacturing News

Forming Technology Improves Thermoforming and Blow Molding Process

Originally Published MPMN September 2004

HOTLINE

Forming Technology Improves Thermoforming and Blow Molding Process

Deep-drawn and thin-wall rigid and flexible products are available

Melody Lee
Melt-Phase technology forms containers with deep draws and seamless walls.

By merging the strengths of traditional thermoforming and blow molding, PBM Plastics (Newport News, VA) offers a new forming technology. Melt-Phase creates containers with deep draws, seamless walls, and precision flanges. According to the company, the process creates previously unheard of shapes and abilities for use by plastics engineers. 

The materials created using Melt-Phase offer engineers chemical-resistant qualities and heat resistance up to 500°F. Draw ratios of up to 8:1 and walls as thin as 1 mil are possible. More than 10 layers may be included in a single liner. Flexible liners or rigid containers can also serve as barrier protection.

An alternative to typical glass test tubes and containers can be made using the Melt-Phase technology. The new material is made with high-heat and chemical-resistant crystalline and amorphous plastics. The disposable products are fully autoclavable. 

Another example of a product created by the Melt-Phase process is a sterile guard used in cleanrooms and medical applications. The cover is available either transparent or in a number of colors and is designed for difficult shapes. 

PBM Plastics also worked with another company to create a liner for a personal medical dispensing system. The OEM needed to integrate a liner into the device to collapse and release more than 99.5% of the contents. An accordion bellow design with a rigid flange allowed controlled collapse while providing a barrier material for long shelf life. 

The process has also been used to make nonsolid bladder systems, filtration sleeves, and medical dispensing and collecting devices.

PBM Plastics
240 Enterprise Dr. 
Newport News, VA 23606-1300 
Phone: 757/888-6800 
Fax: 757/888-6373 
E-mail: cvaughn@pbmplastics.com 
URL: www.pbmplastics.com 

Copyright ©2004 Medical Product Manufacturing News

HOTLINE: Inverter Lights up System Display

Originally Published MPMN September 2004

HOTLINE

Inverter Lights up System Display 

The unit is a compact, cost-effective power source

Rita Emmanouilidou
The DMA-series inverter from Endicott Research Group is a compact, high-efficiency power source for two-tube LCDs.

An inverter is designed to power LCDs backlit by two cold cathode fluorescent lamps or tubes that are used in low-temperature environments and require high starting voltages.

Measuring 4.28 in. in length, 0.880 in. wide, and 0.50 in high, the DMA series from Endicott Research Group (Endicott, NY) offers up to 12 W of output power, two outputs, and integrated input and output connectors. The unit also features external control and pulse with modulation dimming. It can be supplied with a fully compatible locking or nonlocking input wire harness featuring #24 AWG wire.

The DMA series is the main power source that lights up a sharp display used in a hemodialysis delivery system. The display enables a clinical technician to visually access data pertaining to the patient treatment. The 2008K system from Fresenius Medical Care (Lexington, MA) is the latest evolution of the company's dialyzer. It features a new LCD touch screen that "makes it more user-friendly, while at the same time optimizing the latest computerized electromechanical products available," says spokeswoman Luisa Ravalico.

"In the older screen version, features were selected by using the cursor; the new touch screen allows the user to physically touch it and move it into the required fields, thus making it faster and easier to work with." The touch screen also simplifies the troubleshooting and calibration procedure by offering step-by-step directions as well as a real-time-status screen. 

"We originally purchased the DMA-series inverter as a standard component, but eventually, based on ERG's and Fresenius's knowledge and expertise, it evolved into a customized product for our equipment," says Ravalico.

Endicott Research Group
2601 Wayne St.
Endicott, NY 13761 
Phone: 607/754-9187 
Fax: 607/754-9255 
E-mail: sales@ergpower.com  
URL: www.ergpower.com 

Copyright ©2004 Medical Product Manufacturing News

HOTLINE: Inverter Lights up System Display

Originally Published MPMN September 2004

HOTLINE

Inverter Lights up System Display 

The unit is a compact, cost-effective power source

An inverter is designed to power LCDs backlit by two cold cathode fluorescent lamps or tubes that are used in low-temperature environments and require high starting voltages...
Read more...

 

Forming Technology Improves Thermoforming and Blow Molding Process

Deep-drawn and thin-wall rigid and flexible products are available

By merging the strengths of traditional thermoforming and blow molding, PBM Plastics (Newport News, VA) offers a new forming technology...
Read more...

 

Temperature Sensors Go Platinum 

Surface-mounted temperature detectors use thin-film technology 

A surface-mount resistance temperature detector (RTD) series developed by Heraeus Sensor Technology (North Brunswick, NJ) is suited for use in biomedical applications... 
Read more...

Copyright ©2004 Medical Product Manufacturing News

Wireless Medical Devices: Satisfying Radio Requirements

Originally Published MDDI September 2004

Integrated Circuits



Understanding radio protocols and requirements is the first step in successfully using wireless communication in medical applications.

Carl Falcon

A wide variety of medical applications, such as implantable devices and telemetry equipment, are increasingly using wireless communication. And at the heart of this trend is the need for low-power radio application-specific integrated circuits (ASICs). In order to select the appropriate radio ASIC, it is critical to first understand the protocols and requirements needed for the particular medical device. This article provides an overview of the protocols commonly used in medical radio applications. It also reviews the essential factors to consider when selecting a frequency band, topology, and transmission protocol.

Common Medical Radio Requirements

Medical radios are usually driven by two primary requirements. First, medical radios must consume very little power so that they can last on battery power for months or years. Second, medical radios must often be added to other low-cost, small-sized components such as sensors. This consideration requires that these radios be low cost, have a simple design, and need few external components.

Medical applications are usually indoors, which typically translates into a relatively short range over which data must be transmitted. In addition, the radios need to transmit only a small amount of data, and those data are transmitted only infrequently. 

A short data range means that the radio design can be kept simple and that the transmitter power can be kept low. The infrequent data transfer means that medical radios can sleep a large portion of the time. Both the short data range and infrequent data transfer of these radios help to minimize power requirements. 

Of course, the requirements of a medical wireless system go beyond low power and low cost. Table I lists additional requirements that should be considered when reviewing possible wireless system architectures.

Selecting a Frequency Band

Table I. Wireless system requirements (click to enlarge).

Several licensed frequency bands exist specifically for medical applications. In addition, many low-cost applications operate in the unlicensed frequency bands known as the industrial, scientific, and medical (ISM) bands. No license is necessary to operate a device in this band. 

Most radio ICs are transceivers, which means the IC can both transmit and receive data. A transceiver is often paired with a simple microprocessor or other support circuitry that directs the baseband operations, such as controlling the flow of information between the real-world interface and the transceiver.

Figure 1. A simple medical wireless system (click to enlarge).

In the simple wireless system shown in Figure 1, the analog data from a sensor measurement is first converted from its continuous-time analog signal into a discrete-time digital signal. A baseband processor then adds some error-detection information and formats the data for transmission. The baseband data are sent to the transceiver, encoded onto a radio-frequency (RF) signal and broadcast by the transmitter, detected by the receiver, and finally decoded back into digital data. Low-power transceiver ICs usually operate between 300 MHz and 1 GHz. The frequency spectrum between these limits contains many bands where both licensed and unlicensed medical and industrial equipment can operate (see Figure 2). Table II details the common North American and European frequency bands that are suitable for certain medical applications.

Figure 2. The 300 MHz to 1 GHz frequency spectrum (click to enlarge).

In the United States, the Federal Communications Commission (FCC) has set aside a few frequency bands for medical data transmissions only. In 1999, FCC set aside the medical implant communications service (MICS) frequency band. The MICS band, located in the frequency range of 402–405 MHz, is reserved specifically for wireless data communications between implanted medical devices and external equipment. 

Wireless medical telemetry enables monitoring equipment to remotely and unobtrusively observe several patients at one time. Such telemetry systems transmit real-time physiologic data, so it is critical to ensure that data are not lost or delayed. More and more radios for nonmedical applications are operating in the ISM bands, 

increasing the likelihood of signal loss and interference. FCC, therefore, has set aside frequency bands specifically for wireless medical telemetry services (WMTS). The radio spectrum designated for WMTS includes the 6 MHz between 608 and 614 MHz.

Topology

Table II. Medical frequency bands (click to enlarge).

Wireless receivers and transmitters are often arranged in a star configuration, in which a centrally located transceiver communicates with one remote location (a point-to-point topology) or with several remote locations (a point-to-multipoint topology) simultaneously. In a point-to-point architecture, only one transmitter and receiver pair is communicating at any given time on a specific carrier frequency. The central node takes the role of a master coordinator, while the remote location is a subordinate. Point-to-point communications can be simplex (one way only), half duplex (first one direction and then the other, sequentially), and full duplex (simultaneous communication in both directions).

Networks that are more complex may have multiple transmitters and receivers that can communicate with one another as peers. Within a network, one of the central nodes is designated as a coordinator. The coordinator is tasked with waking up other subordinate devices on the network out of a low-current sleep mode just before data are to be transmitted. Coordinator transceivers can also talk to one another as peers.

Figure 3. Network topologies (click to enlarge).

Mesh networks allow wireless devices to talk indirectly to one another even when the two devices cannot see each other. A transmitting device can pass data to its neighbor, which in turn can pass data onto its next neighbor, and so on. In this way, a mesh network can be used over a far-flung network, say, between the top and bottom floor in a high-rise building. Figure 3 illustrates two different network topologies.

Selecting a Transmission Protocol

Transmission protocols define the way data are to be encoded, transmitted, received, and decoded. Protocols also define any error detection methods as well as techniques to minimize interference and distortion. Protocols are usually optimized for the given application to reduce the overhead associated with error correction and thus result in lower-cost and lower-power operation.

Figure 4. Various protocol features mapped to unlicensed frequency spectrum (click to enlarge).

Medical equipment manufacturers concerned about the interoperability among radios from different manufacturers should consider using an open-standard protocol such as Bluetooth or ZigBee. Figure 4 maps several open standards against the unlicensed frequency bands. Open-standard protocols can also allow for a complex networking of transmitters and receivers such as those operating in a mesh-type network. 

However, standard protocols give up some flexibility, and considerable overhead is required to ensure compatibility and interoperability. Bluetooth and ZigBee radios are also designed for higher-frequency bands, such as the 2.4 GHz ISM band. The wireless local-area-network (WLAN) and wireless personal-area-network (WPAN) open standards were developed to address high-speed data transmission requirements. Because medical applications typically require only low data rates, the WLAN and WPAN standards (e.g., IEEE 802.11a, b, or g) are rarely appropriate for small implantable medical devices. 

Table III. Open-standard protocol versus proprietary protocol (click to enlarge).

In some cases, proprietary protocols can fit a given medical application better than a standard. Often, proprietary protocols are the only ones available for MICS band operation. A proprietary protocol can offer more flexibility and provide lower-power operation if interoperability is not a concern. A proprietary protocol can also be less expensive overall.

A few considerations should be taken into account when choosing a protocol and an associated frequency band. Among these considerations are:

• Geographic location. The medical frequency bands used worldwide do not necessarily coincide from country to country (see Table II). The 2.4 GHz band is generally available in most locations, but it may be restricted depending on the country. Other, lower-frequency bands are restricted to a geographic location.
• Interoperability. If the application requires that devices from several manufacturers must work together, then a specific communications standard must be used. That standard will define the frequency range. The newly adopted IEEE 802.15.4 standard, commonly known as ZigBee, addresses the 868 MHz, 902–928 MHz, and 2.4 GHz ISM bands and ensures interoperability between various radio devices. 
• Interference. Multiple wireless standards often coexist in unlicensed frequency bands. For example, 900 MHz cordless phones operate in the 902–928 MHz band. In addition, the 2.4 GHz band is usable in most locations, making it a popular choice for a variety of wireless communications protocols. Significant microwave oven operation also can plague that band.

Low-data-rate radios can usually host both the protocol and application control in a simple 8-bit microcontroller. Typical applications use only between 4 and 30 Kbyte of code and less than 300–4000 bytes of RAM, depending on whether the radio is a full-function controller or a reduced-function device.

By comparison, more-sophisticated radios, such as Bluetooth, require a dedicated core to manage the baseband protocol stack. They also need a separate host device to manage the logical link control and adaptation protocol, protocol interfaces, and applications. In order to achieve this, between 100 and 200 Kbyte of code and about 150 Kbyte of ROM may be required for a full software stack.

A clear understanding of the trade-offs between open standards and proprietary protocols can be developed by comparing two similar radio transceivers that operate in the same 868 MHz (EU) and 902 MHz (U.S.) unlicensed medical bands. Table III shows how two different transceiver designs operating in the same frequency bands address the wireless system requirements noted in Table I. Transceiver A follows a more-complex open-standard protocol (IEEE 802.15.4), while Transceiver B follows a simpler but proprietary protocol. 

Environmental Requirements

Figure 5. Carrier modulation (click to enlarge).

In a medical environment, data transmissions through a wire or along a circuit board trace are always vulnerable to interfering signals, coupled noise, electromagnetic interference, and noisy or shifting power and ground planes. 

A common method of overcoming transmission problems is to use the digital data to modulate a much higher frequency signal, called a carrier signal. Carrier modulation techniques convert the digital signals into frequencies that are inherently more immune to noise. 

Because the shifting carrier signal is an ac signal with no ground reference, the carrier signal is not affected by unstable or noisy ground planes. The carrier frequencies can be tuned specifically to avoid electrical noise, and the receiver circuits can be designed to reject out-of-band noise. The receiver can also be designed to reliably detect very small changes in frequency that can yield long data ranges with very little power.

Carrier Modulation Techniques

A number of techniques can encode digital data by varying either the amplitude, the frequency, or the phase of a carrier signal. Examples of each technique are shown in Figure 5. These modulation techniques include: 

Figure 6. Multipath propagation example (click to enlarge).

• Frequency shift key (FSK) modulation, which uses two different carrier frequencies to represent the logic high and logic low of digital data.
• Amplitude shift key (ASK) modulation, which uses one frequency but varies the amplitude of the RF carrier to represent the logic high and logic low of digital data. A variation of ASK is called on-off shift key (OOSK) modulation, where one of the two amplitudes is zero. The OOSK signal is a series of alternating-frequency bursts and quiet periods representing the logic high and logic low of digital data. ASK is more susceptible to noise than FSK, but it is often easier to implement and detect. 
• Phase shift key (PSK) modulation, which encodes the digital data by altering the phase of the carrier frequency. Biphase shift key (BPSK) modulation shifts the phase of the RF carrier by 180 in accordance with a digital bit stream. The receiver performs a differential coherent detection process whereby the phase of each bit is compared with that of the preceding bit. 

Table III also shows that Transmitter A uses the biphase modulation technique, while Transmitter B uses an on-off amplitude modulation technique. BPSK is more difficult to implement but can offer a 6-dB advantage in signal-to-noise ratio over OOSK for a given carrier level.

Multipath Propagation Problems

Once the digital data have been encoded as an RF carrier signal, environmental obstacles can affect the data signal path.

Figure 7. Multipath detection with a diversity antenna (click to enlarge).

Multipath propagation occurs when an RF signal takes different paths when propagating from a transmitter to a receiver. While the signal is en route, obstacles such as walls, chairs, desks, and other items get in the way and cause the signal to bounce in different directions. A portion of the signal may go directly to the destination, and another part may bounce from a chair to the ceiling, and then to the destination, as illustrated in Figure 6. Therefore, some of the signal encounters a delay, increasing the length of path to the receiver. 

Multipath delay causes the information symbols represented in a radio signal to overlap, which confuses the receiver. This is often referred to as intersymbol interference (ISI). Because the shape of the signal conveys the information being transmitted, the receiver will make mistakes when demodulating the signal's information. If the delays are great enough, bit errors occur. The receiver won't be able to distinguish the symbols and interpret the corresponding bits correctly. 

Radio Interference Problems

The proliferation of many types of common wireless devices in the unlicensed ISM bands can corrupt the data signals of medical radios operating in the same band. Airborne radiolocation systems also share these bands.

When these unwanted RF signals transmit at the same carrier frequency as a medical radio signal, they can cause an interruption or corruption of that signal. Corrupted signals arrive with errors, missing bits, or not at all, and the receiver cannot recover the data. Depending on the sophistication of the receiver-transmitter set, the transmitter may be asked to resend the data, which in turn adds overhead to the network and causes delays.

Multipath and Interference Reduction 

Depending on the application, radio interference may be a minimal concern if the environment is relatively quiet. However, indoor short-range radios must be able to account for multipath problems, especially in the ISM bands.

Both active and passive techniques are used to account for multipath fading. Passive techniques generally cost much less. These techniques rely on diversity antenna systems—two antennas for each radio—which increases the odds of receiving an uncorrupted signal.

Diversity antennas are physically separated from both the radio and from each other to ensure that one of the antennas will encounter fewer multipath propagation effects than the other antenna (see Figure 7). The receiver uses two separate receiver paths to filter the signal and then decides which signal is the best choice for demodulation. 

Active techniques employ spread-spectrum technology to address multipath fading and RF interference. Two commonly used techniques are direct-sequence spread spectrum (DSSS) and frequency-hopping spread spectrum (FHSS). DSSS mixes a data signal with a constantly changing pseudorandom noise signal that spreads a continuous data signal over a wide range of frequencies. This leaves enough room for lower-frequency elements of the DSSS signal to reflect off obstacles much differently than the higher-frequency elements of the signal.

FHSS transmits an intermittent data signal for a short period at one frequency and then hops to other frequencies in a pseudorandom pattern. FHSS avoids interference from other radios by hopping on narrow channels over a wide range of frequencies; transmitting on strong, clear channels; and avoiding noisy or faded ones. Frequency hopping is generally regarded as having better noise immunity than DSSS; however, the data rate is lower. 

Data Integrity Checks

Error detection and correction are also important in mitigating the effects of interference and multipath fading. The receiver can check for the presence of errors through an error detection process. Basic designs use a simple checksum, but a cyclic redundancy code (CRC) check is necessary for more-reliable data transmission. With the latter process, the transmitting transceiver adds a CRC to every data packet that is sent. A data packet containing an error will not compute correctly. The drawback of added overhead is more than offset by ensuring the received data are accurate. For low-data-rate radios, a CRC of 16 bits is adequate; for high-data-rate radios, a CRC of 24 bits is ideal.

In a point-to-point topology, a simple handshake protocol between the receiver and transmitter known as automatic retransmit request (ARQ) requires the receiver to send an acknowledgment if data have been received with no errors. If an acknowledgment is not received by the transmitter, the transmitter resends the data.

With complex network topologies, such as point-to-multipoint or peer-to-peer topologies, the protocol must enable one receiver to accommodate multiple transmitters broadcasting at the same time. The primary scheme is called carrier sense multiple access with collision detection (CSMA/CD). CSMA/CD is a set of standard rules that determine how network devices should respond when two devices attempt to use the same channel. The handshaking process between receiver and transmitter is similar to ARQ. After detecting a collision, a transmitter waits a random delay time and then attempts to retransmit the data. If the transmitter again detects a collision, the device waits twice as long to try to retransmit the message. This is known as exponential backoff.

Because of data retransmissions, the data rate throughput is slow when multipath propagation is significant. The reduction in throughput depends on the environment. Radio signals in homes and offices may encounter 50 nanoseconds of multipath delay. Metal machinery and racks in a plant, however, provide a lot of reflective surfaces for RF signals to bounce from and take erratic paths. Signal delay in a manufacturing plant could be as high as 300 nanoseconds. It is essential to be aware of multipath problems in warehouses, processing plants, and other areas full of irregular, metal obstacles.

Conclusion

Understanding the protocols and requirements needed for the particular medical application is a crucial step in selecting the appropriate low-power radio ASIC. The protocols and requirements should be reviewed and considered carefully to ensure that the proper frequency band, topology, and transmission protocol are used for a device. A thorough understanding of the environment is also critical to identifying and implementing modulation techniques to reduce multipath propagation, noise, and interference, and to ensure data integrity.

Bibliography

Code of Federal Regulations. Title 47 Telecommunication, Part 15. Washington, DC: National Archives and Records Administration, August 20, 2002.

ETSI EN 300 220-1, “European Standard (Telecommunications series),” V1.3.1, September 2000.

ETSI EN 300 328, “Candidate Harmonized European Standard (Telecommunications series),” V1.4.1, November 2002.

ETSI EN 301 839-2, “Candidate Harmonized European Standard (Telecommunications series),” V1.1.1, April 2002.

Falcon, Carl. “Adding a Low Data Rate Radio ASSP to an ISM Application.” Microwave Journal, October 2003.

Sklar, B. Digital Communications, Fundamentals and Applications. Englewood Cliffs, NJ: Prentice Hall, 1998. 

Carl Falcon is a strategic marketing manager for AMI Semiconductor (Pocatello, ID). 

Copyright ©2004 Medical Device & Diagnostic Industry

Forging New Regulatory Pathways at FDA

Originally Published MDDI September 2004

Q&A



FDA's Office of Combination Products is poised to determine how the agency will handle the products resulting from the increasing convergence of the drug, device, and biologics industries.

Erik Swain

Mark Kramer

Mark Kramer heads an office in FDA that is very small but could have tremendous influence on the future of device regulation. The Office of Combination Products (OCP) was created in 2002 as a result of the Medical Device User Fee and Modernization Act. Its main duties include assigning combination product reviews to a center and coordinating timely premarket reviews involving more than one center. It also must ensure the consistency and appropriateness of combination-product postmarket regulation.

The seven-person staff is also responsible for developing rules and guidance documents specific to the assignment of combination products. Perhaps its most significant policy initiative to date came in May 2004. It proposed a rule that outlined how such assignments will be made and defined key terms in the process. The full text of the proposal can be found on-line at www.fda.gov/ohrms/dockets/98fr/oc03366.pdf.  

Of particular interest is the policy's scheme, called the assignment algorithm. This algorithm establishes a framework for selecting the lead review center for products for which a primary action cannot be determined. OCP is currently reviewing feedback from industry and other stakeholders. After considering the issues cited, it will publish a final rule. 

Kramer, OCP's director, spoke with MD&DI's East Coast editor Erik Swain about the reasoning behind the proposal, the duties that the office performs now, and the role the office may play in the future. 

Q: How has the role of OCP evolved since it was created?

A: Our statutory roles are the same. However, because of an increasing awareness within the agency and within industry about what the office does, we get a fair amount of requests coming in for help in forging regulatory pathways for products. That's not one of our statutory roles, but it's an area where I think we provide the most added value. We help work through difficult regulatory issues involving some challenging products. Some seek resolution of problems, others ask for specific advice, and some may just want help thinking strategies through.

Q: Are combination products the wave of the future, as some are claiming? 

A: By all accounts, it seems they are the wave of the future. Not to the extent that everything will become a combination product, however. Device and drug companies are looking toward improvement of existing technologies, such as developing a drug coating for a device to make it safer or more effective, or developing a delivery device for a drug to make it easier to use. 

Q: Do you see an expanded role for your office in the future? For example, do you see a day when it performs reviews of combination products?

A: As these products continue to proliferate, there will be more work for us to do. But reviewing products would be a fairly fundamental change. We are a small group right now. It's not even conceivable that we could perform that function. Besides, the law provides for that authority to remain in the centers. 

My own personal take is that to do such a thing, we'd have to have the diversity of expertise that the three centers have now––maybe even more. I don't know how realistic that is since resources are tight. Also, if another group of reviewers were created, it could add to the complexity [of the process]. There is logic in having drug-eluting stents reviewed by the same people who review other types of stents. What if a drug-eluting stent were approved, but it used a stent that did not meet the standards of the bare-metal stent reviewers? Having the office review products might seem attractive, but it could create new problems. So, for now, we have no intention to do that. I have seen improvements in the way the centers work together. I believe that we can work within the current paradigm to make combination product reviews as consistent and effective as possible.

Q: There is a perception that CDRH has a less rigorous review process than the Center for Drug Evaluation and Research [CDER] or the Center for Biologics Evaluation and Research [CBER], and therefore firms should do what they can to have CDRH be the lead review center for their combination products. Is this a fair perception, and to what extent does OCP take into account a firm's wishes when assigning a center to a review?

A: The review standards are more similar than they are different. That being said, sponsors do tend to have preferences. During the process used to assign a combination product to a center, a sponsor is required to make its recommendation for a lead center based on the product's primary mode of action. Most sponsors of combination products historically have been device companies, and they tend to prefer CDRH. [These sponsors are] familiar with the process involved in reviewing [a device] application. They are also familiar with the device guidances, regulatory pathways, and statutes. However, when we have combination products developed by a drug company, they are more apt to request CDER or CBER to review [their products]. That's because the whole device process is often foreign to them. They are more familiar with the drug process. We are required to assign the lead center based on the primary mode of action of the product.

Q: What kind of feedback have you received from industry regarding the OCP initiative?

A: It looks favorable so far. Many of the comments have been along the lines of “it needs some refinement, but not a major overhaul.” I've not yet heard that we are totally off base. 

Q: How did you come up with the definition of mode of action?

A: The biologic, drug, and device mode of action definitions are closely tied to the definitions of biologic, drug, and device in the law. There's nothing magical there. The definitions are designed to be mutually exclusive. 

Q: How did you come up with the definition of primary mode of action?

A: Primary mode of action is defined as the most important effect of a combination product. We want to consider what the product does, what is most important about it, and how it works. 

Q: How did you come up with the assignment algorithm? Does it address the concerns of those who may be unsure what OCP would do with products that don't have a single primary mode of action?

A: How we would handle products without a clearly identified primary mode of action was an area of concern. The products that are not usually difficult to assign are the ones where one component is a helper. With a drug-eluting stent, the primary mode of action is the stent. The drug helps the stent do its job better. But there are products without an obvious helper, where the primary mode of action is unclear. The assignment algorithm would allow us to handle them.

Q: The algorithm stipulates that products without a primary mode of action be reviewed by the center that has “the most expertise to evaluate the most significant safety and effectiveness questions” presented by the product. How do you define expertise and how do you decide which safety and effectiveness questions are most significant?

A: If we're not sure of the most important therapeutic action, then the product will be assigned to the center with direct expertise in that type of combination product area. If no center has direct expertise, then it will be assigned to the center with the most related expertise. We would consider the safety and effectiveness questions raised by that product. From there, we can determine which center has the most expertise related to those questions. As far as which safety and effectiveness questions are most significant, it's hard to answer that hypothetically. It has to be evaluated in conjunction with the product as a whole, and not just with what is novel about the product. 

Q: What is the next major challenge for the office after the proposed rule outlining the assignment process gets implemented? Are there any other statutory voids that need filling?

A: We are continuing to work on a number of issues. We've identified areas that need to be clarified, and we are working on them. These include adverse-event reporting and selecting GMP requirements. Should the manufacturer of a drug-device combination follow the QSR, the drug GMPs, or some combination of the two? Also, when are two applications required as opposed to one? There are also cross-labeling issues—when do two different products need to be labeled for use together? We just issued a guidance on dispute resolution. Handling of post-approval changes is also an issue. We have made a lot of progress on many of these issues. It's just a matter of having the time to write regulations and guidances, and get them out for comment. 

Q: What kinds of combination product technologies might we see in 10 years that don't exist right now?

A: I'm not the best person to answer that, but nanotechnology and drug-delivery technology seem to be waves of the future. Also, in contrast to products that combine two different things, such as a drug and a device, there might be products that perform two functions; for example, a single entity's acting as both a device and a drug. 

Copyright ©2004 Medical Device & Diagnostic Industry