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Articles from 1999 In December

Location, Location, Location State on a Mission: California's Biomedical Pursuit

Medical Device & Diagnostic Industry Magazine
MDDI Article Index

An MD&DI December 1999 Column

Amid economic resurgence, rival cities in the Golden State are competing—sometimes in odd ways—to attract healthcare technology companies.

According to a recent analysis, California is home to the highest concentration of biomedical companies in the world. A study this past summer by the California Healthcare Institute (La Jolla, CA) reported that biotechnology, medical device, and diagnostics companies in the state now employ more than 200,000 workers, trailing only electronic equipment manufacturers as a source of jobs and surpassing iconic industries such as aerospace and the movie business. Fully one-third of the country's biotechnology companies and 28% of medical device and diagnostics firms, said the institute, are located in California.

You might think that such spectacular economic bounty within the borders of one state could be divvied up without much contention. In fact, a fierce struggle for regional dominance is transpiring among three metropolitan areas, each eager to stake the biggest claim in the biotech gold rush. The cities in question—San Diego, San Francisco, and Los Angeles (with Orange County)—may take their names from two saints and the Queen of the Angels, but the competition is far from beatific.

The latest move was on the part of San Francisco, as the city broke ground on a massive new project along its eastern waterfront that is intended both to foster academic research and to attract biomedical companies. At the heart of the development is a $1.4 billion satellite campus for the University of California-San Francisco, which will ultimately contain approximately 3 million square feet of labs and other facilities dedicated to bioscience research. Adjacent to the new campus will be nearly six million square feet of research, office, and manufacturing facilities. City, university, and economic development officials have promised to sweeten the pot for future tenants by providing a range of incentives, including tax credits, access to research equipment, expedited city permitting, and negligible EIR requirements.

One reason San Francisco is willing to undertake such commitments is that, in the eyes of some biomedical industry executives, it has fallen behind San Diego as a desirable place to conduct business. An industry survey conducted by A.T. Kearney Inc. found that San Diego is seen as extending a fuller, more balanced spectrum of benefits to both early-stage and mature companies. That is, it has the world-class research institutions, venture-capital resources, and infrastructure critical to start-ups and developing firms while also offering the land availability, tax profile, regulatory climate, and labor and operating costs conducive to manufacturers. (Los Angeles/Orange County is ranked a distant third, despite boasting a greater number of total companies than either rival.) San Diego also comes out ahead for relative ease of transportation and more affordable housing—motivating the San Francisco developers to include more than 6000 housing units, of which nearly one-third will be sold below market rate.

However, in their zeal to match the perceived advantages of San Diego, the organizers of the San Francisco project have done a very strange thing: they've named the enterprise "Mission Bay." When I heard the name I had an odd feeling of displacement, accompanied by the image of a leaping killer whale. Sure enough, the first dozen items called up by a Web search for the term all identified Mission Bay as part of San Diego—or more precisely, according to one source, as "a coastal embayment approximately five miles north of downtown San Diego" (and next to Sea World). As a matter of fact, the current Mission Bay is actually owned by the City of San Diego!

The idea here seems to be a modified field-of-dreams strategy: if you name it the same, they will come. Can San Diego's own "Golden Gate medical enterprise zone" be far behind?

Jon Katz

Copyright ©1999 Medical Device & Diagnostic Industry

After Abbott, A Tougher FDA Is Emerging : Targeting Device CEOs Gets Their Attention—and a Fix : FDA Approvals Chief Departs : Why Don't Device Firms Use Innovative Reviews? : FDA Abandons Internet Promotion Guidance

Medical Device & Diagnostic Industry Magazine
MDDI Article Index

An MD&DI December 1999 Column


James G. Dickinson


  • Targeting device CEOs gets their attention and a fix
  • FDA approvals chief departs
  • Why don't device firms use innovative reviews
  • FDA abandons Internet promotion guidance

The warm and fuzzy climate of FDA's regulatory relationship with medical device manufacturers may be turning a bit chilly. Initiated by the Clinton Administration's "reinventing government" program and the agency's own complementary "reengineering" initiative at CDRH, and fostered by the FDA Modernization Act (FDAMA), the atmosphere of friendly cooperation is looking bleaker in the wake of November's record-setting consent decree with Abbott Laboratories.

The $100 million decree exceeds the previous record of $61 million—also against a device company—dating from the 1993 C.R. Bard settlement. Abbott announced it was taking a $168 million charge against its assets to allow for lost sales and administrative costs it will incur in implementing the manufacturing and personnel changes required by the decree—including FDA's costs for verifying corrections.

There's always a great temptation to view such events as isolated occurrences, confined to their own particular set of circumstances. But that's not the way FDA's highest management is viewing the Abbott consent decree, FDAMA or no FDAMA.

What they're saying—though not for attribution—is that this case sends a signal to industry as a whole about the seriousness with which FDA views promises made to it by manufacturers within the inspection setting.

A senior official close to the Abbott case has told this reporter that Abbott could have gotten out of its GMP problems five years earlier for about $20 million, but that its management decided instead to "play hardball" with the agency, making promises it had no intention of keeping. In successive inspections of Abbott's in vitro diagnostics facility, promised corrections were found not to have been carried out. Although this lack of response was not unique to Abbott, FDA officials say privately that the company's management was especially tough to deal with.

The Abbott consent decree prompted FDA commissioner Jane Henney to make the first public statement of her term on an enforcement matter. "This action underscores FDA's strong commitment to the enforcement of laws designed to protect patients and consumers," an agency statement quoted her as saying. "These violations do not necessarily mean that Abbott's diagnostic products will harm patients, but the firm's failure to follow good manufacturing requirements decreases the level of assurance," she added.

What Henney calls the "level of assurance" is what other firms besides Abbott have been taking lightly, agency leaders say. It isn't enough that no patients are being injured by a company's failure to dot regulatory i's or cross regulatory t's—FDA's investigators have to be happy with a company's quality system. This toughening attitude comes at an odd time in FDA's history, when the Republican Congress has once again ratcheted down the agency's enforcement budget while earmarking increased funds for product approvals.

Under the agreement, Abbott is allowed to continue manufacturing and distributing diagnostic products that FDA agrees are "medically necessary." These include assays for hepatitis, retrovirus, cardiovascular disease, cancer, thyroid disorders, fertility, drug monitoring, and congenital and respiratory conditions. The company said the decree "does not affect Abbott's MediSense, i-STAT, hematology, or Murex products; the clinical chemistry products Abbott Spectrum, Aeroset, and Alcyon; or any other Abbott divisions or products." All other Abbott in vitro diagnostic devices could remain available for 30 days, in order to "permit users to standardize and obtain alternate test methods," FDA said in a statement.

The agency also recommended the use of additional quality control material (reagents used to help verify the proper functioning of test kits) made by other firms to ensure that Abbott's tests function properly. After 30 days, Abbott won't be permitted to make or distribute non­medically necessary tests.

"Abbott has agreed to comply with FDA's quality systems regulation for these products according to a schedule approved by FDA," the agency's statement said. "The firm has also agreed to pay $15,000 per manufacturing process, per day (up to a $10 million cap), for failure to adhere to that schedule." In addition, if the medically necessary products are not in compliance within one year, Abbott has agreed to pay another fine equal to 16% of the noncompliant products' sales revenues.

The consent decree requires Abbott's corrections to be overseen by an outside expert who will certify to FDA that corrections have been made. FDA will also reinspect Abbott's facilities to verify that the products have been validated and that the manufacturing processes conform to the quality system regulation. If the inspection does not reveal any significant problems, the affected products will be allowed back on the market, FDA said.

The decree states that, "Once corrective action is complete and Abbott has been allowed to resume manufacturing and distribution, the company will hire an independent auditor to conduct audit inspections of its in-vitro diagnostic device manufacturing operations at least twice a year for at least four years." The decree will still allow Abbott to export affected products as long as they meet export requirements outlined by the Federal Food, Drug, and Cosmetic Act.

When CDRH upped the ante last year in its war against medical device industry inattention to the new QSR, it elicited an unusually synergistic reaction from the industry itself. FDA's move involved redirecting its QSR warning letters from the customary recipients in companies to the highest management authority of all—in most cases, the chief executive officer. Philosophically and legally this made good sense, since the new regulation's systems focus involves multiple layers of company structures and directly scrutinizes the corporate culture for which CEOs are ultimately responsible.

The first of the new-style warning letters caught the eye of Nancy Singer, special counsel at the Health Industry Manufacturers Association (HIMA), who re- cognized the trouble they could cause.

Singer set about organizing an industrywide, self-help response that would capture and hold the commitment of highest management while advancing FDA's goal of establishing an effective systems approach to quality assurance and quality control. FDA was significantly motivated, Singer knew, by its resource limitations. The days of nit-picking, "gotcha" enforcement on a violation-by-violation scorecard approach had necessarily yielded to a partnership strategy under QSR—as embodied in the QSIT program, which practically dragoons industry management into active participation.

However, as FDA's flurry of warning letters showed, industry was not yet on board. Despite plenty of FDA letters, notices, and meeting presentations, the word had not permeated up all corporate structures.

Assembling a panel of 30 industry representatives in addition to HIMA's Bernie Leibler, Singer and Guidant Corp.'s Michael Gropp put together, with FDA input, a 14-page document titled Points to Consider When Preparing for an FDA Inspection under the QSIT Management Controls Subsystem. It was posted on HIMA's Web site in mid-September.

The document provides a brief history of the new QSR regulatory landscape and then focuses on FDA's primary concern and the source of its main current frustration: management responsibility. (During the first QSR inspections in late 1998/early 1999, 57 of 200 FDA-483 observations had involved management deficiencies or outright failures.) Of the top 10 deviations noted by FDA investigators, HIMA's document points out, management controls subsystems accounted for 40%.

The HIMA document stresses that responsibility belongs with top management, naming criminal-case examples that cited CEOs, presidents, executive vice presidents, QA vice presidents, production VPs, corporate regulatory affairs VPs, and general counsels. It also presents ways in which company managements should respond to FDA QSIT inspections. The document can be found on HIMA's Web site at

After six years at CDRH, director of device evaluation Susan Alpert, MD, moved to FDA's Center for Food Safety and Applied Nutrition (CFSAN) in October as director for food safety, joining another CDRH alumnus, former deputy center director Joe Levitt, who is CFSAN's director. In a statement, Levitt said Alpert's appointment "means FDA will be bringing a clinical perspective to all facets of its public health mission of ensuring that Americans continue to enjoy a safe food supply."

A successor to Alpert at CDRH had not been named as this issue went to press.

A panel of senior CDRH officials say they need to hear from industry on why more use isn't being made of innovative programs designed to speed reviews and free CDRH staff for more focused work. "We probably have the largest menu of options for submission we've ever had in the device program," outgoing Office of Device Evaluation director Susan Alpert told attendees at the Regulatory Affairs Professionals Society (RAPS) annual conference in Washington, DC. "We don't understand the reasons why people aren't taking advantage of the options available. Maybe we're not telling industry enough about how we think the programs work, about their benefits."

CDRH director David Feigal said one example of the problem is in third-party reviews. Although some 1200 devices are eligible for such reviews, he said, only 32 have been submitted for them, even though the process takes only half the time of a standard review. "You need to tell us what we can do," Alpert exhorted the RAPS attendees. "Why don't you use third-party reviews? We need you to communicate to us what we can do to make these programs more useful to you."

Expanded use of the alternative programs is important, said Alpert, because in the last fiscal year CDRH was essentially unable to further reduce review times. Preliminary figures, she said, indicate a reduction in 510(k) submissions along with a reduction in the amount of FDA review time and total review time. A total of 44 premarket approval (PMA) applications were approved, with FDA requiring an average of 9 months out of a total review time of 12 months. Alpert indicated that the agency is working on PMAs submitted in late 1998 and 1999, and that there were four modular submissions in the last fiscal year.

"We're proud of these numbers," Alpert said, "but they are flat from last year." With CDRH committed to meeting the FDAMA mandates of 90-day reviews for 510(k)s and 180-day reviews for PMAs, she said, it's necessary that the number of each coming to the agency be reduced through greater use of available options.

During a question-and-answer period after the formal presentations, one attendee said the special 510(k) has worked well in his experience, but the abbreviated 510(k) has been "a mess" because there are consensus standards that are in conflict with older guidances, and companies find that reviewers continue to turn to the guidances. In response, Alpert said the agency does not have the resources to read every guidance looking for conflicts with the consensus standards, and she asked for industry's help in pointing them out.

In other comments, Alpert said the Office of Device Evaluation recognizes industry's interest in reimbursement issues and would like to help the parties involved communicate with each other. She suggested that representatives of the Health Care Financing Administration be invited to meetings at which clinical trials are discussed so the trials can be designed to meet the needs of all parties and interests.

Office of Compliance director Lillian Gill told the group that her priorities for next year include evaluation of the QSIT and MRA programs, various grassroots initiatives, Y2K, HACCP, and more advertising and promotion guidance.

FDA has abandoned its efforts to develop an agencywide Internet advertising and promotion guidance because of the Web's "constantly evolving nature," Center for Biologics Evaluation and Research labeling policy associate director Toni Stifano told an industry meeting in Washington, DC. Speaking at the RAPS annual conference, Stifano indicated that the agency still holds a "significant interest in the multifaceted utility of the Internet." She said the agency's top management decided to continue to apply existing laws and regulations with regard to enforcement actions on a case-by-case basis.

According to Stifano, FDA will now focus its Internet enforcement on three areas: unapproved products, health fraud, and prescription drugs sold without a prescription.

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Copyright ©1999 Medical Device & Diagnostic Industry

Radio-Frequency Sealing for Disposable Medical Products

Medical Device & Diagnostic Industry Magazine
MDDI Article Index

An MD&DI December 1999 Column

An extensive variety of polymers can be processed with RF to form seals that are as strong or stronger than the material itself.

For years, the medical industry has used radio-frequency (RF) sealing to manufacture bags for IV fluids and for blood and urine collection. As the industry has grown apace with an aging population, the demand for more bags and disposable devices has created increased interest in this processing technology. This article explains what RF sealing is and how it operates. Also reviewed are machine sizing and tooling requirements, product-handling systems, and various ways to maximize sealing efficiency.

It is not clear exactly when RF technology was first employed in plastic sealing, but estimates point to somewhere around 1945. Plastic raincoats, three-ring binders, and novelty items such as wallets were some of the first products sealed with radio waves. Later applications included medical bags, swimming-pool liners, various automotive products, tents and awnings, and, in the last 10 years, packaging.

In the medical industry, RF energy is used to seal together two or more layers of film—typically PVC, EVA, Saran, or polyurethane—to form a container or pressure device. Bags for IV fluids, chemotherapy, blood, enteral feeding, ostomy and urology, laparoscopy, enema, ileostomy, and fluid filtering are all made with RF sealing. In addition, the process is used to produce blood-pressure cuffs, hot and cold packs, leg-compression sleeves, aircasts, body bags, wheelchair pads, immobilizing pillows, breather bags, implants, IV arm boards, stretchers, centrifuge devices, sterilization indicators, tourniquets, catheters, and fluid-pump cassettes, among other disposable devices. Although these products are extensive and varied, the technique for sealing them is essentially the same.

Medical bags are typically processed via radio-frequency sealing.

The RF sealing process is similar to microwave heating of food, and indeed may have stimulated the development of microwave ovens. For example, just as not every material will heat in a microwave, not all plastics can be heated with radio frequency. Polystyrene, polypropylene, and polyethylene are common materials that do not respond to RF energy.

ABS (acrylonitrile-butadiene-styrene) Good
Acetal (Delrin) Poor
Acrylics Fair
Barex 210 Excellent
Barex 218 Excellent
Butyrate Good
Cellulose acetate Good
Cellulose acetate butyrate Good
Cellulose nitrate Fair
Cellulose triacetate Fair
CPET Not sealable
Ethyl cellulose Not sealable
EVA (ethyl vinyl acetate) Good
EVOH (ethyl vinyl alcohol) Fair
Nylon (polyamide) Good
Pellethane (not recommended for tear seal) Good
PET (polyethylene terephthalate) Good
PETG (polyethylene terephthalate glycol) Excellent
Phenol-formaldehyde Good
Polyethylene (all types) Not sealable
Polymethyl methacrylate Fair
Polypropylene Not sealable
Polycarbonate Poor
Polystyrene Not sealable
Polyurethane Good
Polyurethane foam Fair
Polyvinyl acetate Good
Polyvinyl chloride
 Flexible, clear
 Flexible, glass-bonded

Rubber Not sealable
Saran (polyvinylidene chloride) Excellent
Silicone Not sealable
Teflon (tetrafluoroethylene) Not sealable

Table I: Radio-frequency sealability of plastic sheeting.1

Because of the significant investment many medical manufacturers have made in RF systems, there is a strong incentive to retain RF compatibility when new materials—such as those formulated to replace PVC—are created. There are many new polyolefins currently being developed for medical products that can be sealed with RF. In fact, one way to determine if a plastic is a good candidate for RF sealing is to see if it heats up in a microwave (Table I).


RF sealing is the use of radio waves—typically at 27.12 MHz—directed through two or more layers of a dielectric plastic in conjunction with pressure so that molecules of all layers of the plastic combine when the material becomes molten. The changing polarity of the radio waves being passed through the plastic causes polarized molecules in the polymer to vibrate back and forth, inducing friction at the molecular level and producing heat. This heat, when created with sufficient energy, causes the plastic to become molten and, under pressure, the layers seal together by free exchange of molecules. The RF energy is then shut off while the tooling holds the plastic sheets together for a very short time to cool under pressure.

What results is a seal with equal or greater strength than the material itself. The seal is consistent, nearly clear, and uniform in appearance and measure. Adding a thin, raised exterior edge to the die will result in a tear seal, which is a thinning of the plastic layers to approximately 0.001 in., which allows an operator to strip the outside waste from the very edge of the seal. This configuration is very common in the production of medical bags and is also used in clamshell sealing.


A basic RF sealer comprises a radio transmitter and an air-operated press that opens and closes the power applicator. The transmitter is called an RF generator because it generates radio-frequency-wave power rather than transmitting radio signals. The generator includes three components: the power supply, the oscillator, and the controls. The power supply converts power from an ac line source into high-voltage direct current. An oscillator tube/resonator combination then converts the direct current into 1000 to 1500 V of alternating current operating at a frequency of 27.12 MHz ±0.6%. The controls regulate and monitor the operation of the generator as its output heats the plastic in the seal area.

The sealing appliance is almost always an air-operated press with interchangeable electrodes (tooling or dies) that are typically made of brass. Bag tooling comprises a top die and a bottom nest with raw-material locators, and mandrel assemblies for tube seals.

The press consists of a steel frame with an air-operated, moveable platen assembly that squeezes the sealing die against the plastic film resting in the bottom die nest. A closed path is created where the top die presses through the material and against the bottom nest. The polymer heats as the RF current flows from the generator along the path through the seal area—where the brass tool contacts the plastic—and back to the generator. The actual operating sequence is as follows:

1. Press lowers and closes current path.
2. RF energy flows through the path and heats the seal area.
3. Seal is accomplished and energy flow is stopped.
4. Seal cools under pressure.
5. Press opens and releases the finished product.


When processors calculate the power level (in kilowatts) required for a given sealing application, they first convert the seal area into square inches. If a tear seal is involved, the linear inches of the tear seal must be assumed to each be the equivalent of a 0.125-in. bar seal. Thus, a bag with 24 in. of perimeter tear seal will have 3 sq in. in tear seal alone. To this must be added the area of the corresponding bar seal as well as any internal seal areas to determine the total seal area. This total is then divided by three to determine the power required to seal the application in minimal time, with power to spare. Some manufacturers will simply use 5 sq in. per kilowatt, but this method does not allow for the fastest possible cycle times nor for the predictable decrease in power of the oscillator tube over time (Figure 1).

Figure 1: Typical RF power output for minimum cycle time.


Tooling for the RF sealing of medical bags consists of an upper die, typically made from brass, mounted to an aluminum tool and jig plate, and a bottom die or nest that is typically made from aluminum. Dies have also been constructed solely from aluminum, steel, or copper beryllium, and any metal that conducts electricity will work. The nest usually has a buffer board or sheet attached in the seal area to minimize the heat-sinking effect of the metal nest and provide an insulated landing for any tear-seal tool edge.

The reason for most tools being brass is threefold: the metal conducts electricity very well, it transfers heat very evenly, and it is easy to machine, and therefore, repair. The key considerations in RF tooling are to maintain parallelism (uniform thickness throughout the tool, within 10% of the preseal thickness of the plastic) and to remove any sharp edges and corners. Because RF voltage increases per area when applied to sharp edges and corners, the higher the voltage, the greater the chance that the material will break down and arc across, ruining the plastic and possibly harming the die. A good arc suppressor in the generator will stop the RF output before die damage can occur, but arcs—even if stopped within milliseconds—can damage the film and the buffer.

Bags with tubes sealed into them will require double-cycle tooling, which includes mandrels that are inserted into tubes and placed between layers of film. Often, these mandrels will incorporate a stripper to help get the bag and tube off of the mandrel after sealing.

Tooling can be made to seal more than one piece per cycle, depending on the power level of the sealer and the die platen dimensions. Typically, tooling changes require from 10 minutes on a two-station shuttle to 30 minutes on multiple-station turntables. Optional quick-change features can substantially reduce changeover time.


To determine the maximum amount of RF energy that can be fed into the seal area, generator output is increased until the arc suppressor fires. The RF output is then reduced until firing only occurs due to an irregularity, such as the presence of foreign matter, material imperfections, or improperly located material. At this point, the system is operating at optimum energy levels and below the arc-through threshold. When maximum power output is insufficient to trip the arc suppressor, the output level needed to minimize sealing time is probably unavailable. If the available RF output falls well below the power requirement for setup, the temperature requirement for a seal will never be attained. When this occurs, higher-output equipment or tooling that requires less power is indicated.

Sealing can be made more efficient by controlling heat loss. The heat is generated in the plastic; therefore, the tooling actually sucks heat out of the material since the tooling temperature is below the melt temperature of the plastic (240°–320°F). Heat losses can be minimized by warming the tooling to approximately 120°–150°F and/or by insulating the tooling surfaces from the product with a buffer. Both methods reduce the heat-sink effect of the tooling, while allowing for efficient cooling after the RF is turned off.

Tooling that is run at temperatures higher than ambient needs to be leveled on the press at the temperature at which it will be run. The natural tendency of metal plates to expand when heated tends to warp platens at higher temperatures. Leveling adjustments are built into most RF platens to address the expansion and avoid warping. RF output can also be enhanced by increasing press pressure so that the material will bond before its interface reaches the temperature needed for a full melt, but this parameter has the smallest effect when compared with energy and time.


An automated RF bag sealer is capable of completing 8 to 10 cycles per minute (cpm). On soft PVC film applications without tube seals, throughput can occasionally increase to as much as 20 cpm. However, 8–10 cpm remains the average for fully automated product feeding, with 5–7 cpm for manually loaded turntables and shuttles. Actual production output will depend upon how many items are being sealed at one time and on the speed of the operators. Most items occupying 1 sq ft or more are sealed 2-up employing a power output from 12.5 to 20 kW. Smaller items are typically sealed 4-up or 6-up using a 4–10-kW power output.


Bags with tubes sealed into them are best made on what is called double-cycle equipment. For each press closure, there are actually two separate RF seal cycles. The first cycle seals the perimeter of the tube or tubes. The second cycle seals the bag perimeter and any internal bar seals. The best equipment to perform this task would include completely independent controls for tuning, preheating, welding, cooling, power, and arc-suppression sensitivity, which would ensure full control in tuning each seal exactly as desired. In addition, a system to balance the top and bottom of the tube seal is often necessary for even flow of RF current around the tube.

On the first cycle, RF energy is applied to the mandrel inserted inside the tube and between the sheets of film, while the upper and lower half-circle dies (or cradles) are both grounded. This way, the seal will be even all the way around the tube. On the second cycle (the press has not yet opened), the mandrel is disconnected from the RF and from the ground (i.e., is electrically neutral). Through the double-cycle RF switch, the upper die is then connected to the RF and the bottom die remains grounded, allowing the perimeter and any bar seals to be accomplished. The double-cycle process eliminates the need for a second unit to seal tubes and avoids the double handling that would ensue. It also produces a more attractive product, with no obvious seal overlaps that could weaken the integrity of the bag.

Product feeding time is shortened through the use of an automated product in-feed system. The two most popular configurations are a shuttle system and an indexing turntable. A shuttle system has two complete in-feed stations. In operation, one station is loaded while product in the other is being sealed; moving the newly loaded station into the sealing position moves the sealed station out. Shuttle systems are usually placed at the end of two conveyor belts to handle the flow of presealed film and finished product.

Turntable or rotary systems are typically built to accommodate from four to eight stations, allowing more operators access to the tool nests. Typically fed precut film and tubes so that machine speed can be maximized, these systems can be set to run in an automatic mode in which the operators must keep up with the set pace. Tooling is more expensive for rotary systems than for shuttle units, as more nests are required (Figure 2).

Figure 2. A common configuration for semiautomated RF sealers is this 12-kW, four-position, double-cycle medical turntable.

With total automation, the operator is eliminated as a variable. Fully automated systems use mechanical means such as web indexers, feeder bowls, and pick-and-place robots to load the die nests. These systems are best suited to long, dedicated runs of products with seals that are the same size and shape, as they do not lend themselves to frequent changeover.


With RF sealing, everything between the upper and lower dies heats evenly, at least in theory. In actual use, however, the dies heat-sink the plastic on contact, such that a temperature profile would indicate the hottest spot is at the interface of the two materials. This works to great advantage in bonding, since the interface is where the most heat is required.

Other methods, such as thermal, impulse (a switched thermal), or ultrasonic sealing, do not share this advantage. For example, temperature profiles taken during thermal and impulse processing indicate that the hottest spot is where the dies touch the outside of each layer of plastic—a condition that often causes degradation of the outside of each layer before the interface reaches melt temperature. (Thermal and impulse sealing functions best with certain very thin [<0.006 in.] films and with polyethylene, polypropylene, or polystyrene.) Ultrasonics, on the other hand, works like a jackhammer, pounding the plastic from 20,000 to 40,000 times per second, with the resulting friction creating heat and thus melting the plastic. Again, the temperature profile is less desirable than that with RF. These alternative processes are limited in area of seal, lack repeatability of acceptable seal quality, and do not have the ability to produce tear seals. They are often employed in small-area spot sealing or in applications for which product appearance is not important, such as polybagging or tack sealing to locate parts.


Few products are as well suited for a particular manufacturing process as are medical bags for RF sealing. No other bag-sealing method yields the consistency, capacity, and quality afforded by RF technology. Depending on the type of bag produced, the required quantity, the manufacturing environment (e.g., labor costs), and the unit price, there are several processing options available to the RF sealer, ranging from completely manual to fully automated techniques.

In addition to choosing the most efficient RF sealing technique for a particular job, bag makers should work with reputable RF companies to ensure the proper design of equipment and tooling. It is also important to remember that RF interference can affect many sensitive electronic devices within a manufacturing facility, and appropriate shielding meeting or exceeding OSHA, IEEE, and FDA regulations should be verified during equipment selection. The fact that, in many cases, data feedback from sealing equipment can help validate the manufacturing process and eliminate costly product testing is another important consideration.

Although RF sealing is a long-established technology, new product developments and option packages have solidified its performance, reliability, and safety. At first glance, RF sealing may seem complicated—the term "black magic" has even been used to describe it. However, RF sealing merely obeys the laws of physics, and is in fact a predictable, dependable, and robust manufacturing process.


1.For more information on the mechanical and chemical properties of the materials listed in Table I, see the Plastics Encyclopedia, Thermoplastics and Thermosets, 8th ed. (San Diego: Condura Publications, 1986).


Dittrich, HF. Tubes for RF Heating. Eindhoven, Netherlands: Philips Technical Library, 1971.

Farkas, RD. Heat Sealing. New York: Reinhold, 1964.

FCC Rules and Regulations, CFR 47, Part 18. Washington DC: U.S. Federal Communications Commission, 1985.

Metaxas, AC, and Meredith, RJ. Industrial Microwave Heating. London: Peter Peregrinas Ltd., 1983.

Ott, HW. Grounding and Shielding Techniques in Instrumentation, 3rd ed. New York: Wiley, 1986.

Ott, HW. Noise Reduction Techniques in Electronic Systems. New York: Wiley, 1976.

Safety Levels with Respect to Human Exposure to Radio Frequency Electromagnetic Field—300 KHz to 100 GHz, ANSI Standard C95.1. New York: ANSI, 1982.

Sobotka, H. Industrial RF Heating Generators. Eindhoven, Netherlands: Philips Technical Library, 1963.

Terman, FE. Electronic and Radio Engineering. New York: McGraw-Hill, 1943.

Von Hippel, AR (ed.). Dielectric Materials and Applications. Cambridge, MA: MIT Press, 1966.

Westman, HP. Reference Data for Radio Engineers, 5th ed. New York: Howard Sams & Co., 1974.

Zade, HP. Heat Sealing and High Frequency Welding of Plastics. London: Temple Press, 1959.

Steve Myers is general manager at Callanan Co. (Elk Grove, IL), a wholly owned subsidiary of Alloyd Co. and a supplier of RF welders and sealers to the medical device industry.

Photos courtesy of Callanan Co.

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Copyright ©1999 Medical Device & Diagnostic Industry

Improving Quality through Automated Assembly

An MD&DI December 1999 Column

Spurred by FDA's 1997 GMP changes, medical product manufacturers are bringing automation techniques to the forefront of the production process.

Over the past few years, customers in virtually all industries have been demanding higher quality from manufacturers. As end-user expectations have risen, manufacturers have responded by placing a higher emphasis on achieving consistent quality results.

Within this push toward quality, the medical and biomedical industries have led the way in many respects, partly in response to the more stringent regulatory requirements in these industries and partly because of the inherent business benefits of maintaining higher quality.

Adding to the medical industry's quality emphasis were the regulatory changes brought on by FDA's 1997 revised GMP guidelines.1 The practical advantages of lowered litigation risks and reduced return and rework costs also have made quality a core strategic imperative. Due in part to this increased pressure to deliver higher quality, manufacturers have increasingly turned to automation in their facilities. The expanded use of advanced automation techniques has given medical manufacturers a robust new set of capabilities for cost-effectively building repeatability, consistency, and quality directly into the production process.


Leading up to its 1997 revisions to the GMP guidelines for medical manufacturing, FDA studied the causes of production defects and field failures in medical products. Exhaustive analysis indicated that the majority of product problems could be traced back to inherent flaws in either the product design or the manufacturing process design. For the most part, the studies also found that any attempts to inspect-in quality for such products merely led to high systemic costs because of the resultant need for massive inspection programs and the waste associated with lowered product yields.

As a result of the research findings, FDA's revised GMP guidelines focused on design procedures and production methods. Similar to ISO 9000 trends in other industries, the 1997 revisions expanded the scope of quality management to encompass the underlying process issues that ultimately lead to the desired quality results.

Spurred by the GMP changes, many manufacturers have selected advanced automation as an effective methodology for improving quality in the manufacturing process. Manufacturers are realizing that automation allows them to preserve flexibility, improve throughput, and reduce cost.


Manufacturing products of consistent quality requires the ability to perform detailed production tasks with high repeatability—the bedrock of process control. Unfortunately, human labor is inherently incapable of performing a given detailed task with near-perfect consistency and uniformity. Even a well-designed human-executed task will vary in results, thereby impacting the ability to control output quality. When many different detailed tasks are strung together—as is the case with most complex assembly processes—the per-task error potential is multiplied by the number of tasks, making overall quality control an even greater challenge. In addition, human-based assembly processes are subject to such random variations as periodic staff changes and other human-related factors that require close monitoring and continuous retraining.

Within any labor-intensive production model, significant costs must be allocated for ongoing training and product inspection to achieve even a suboptimal balance of throughput and quality. Exhaustive testing can generally sort product output to achieve required quality levels; however, this invariably reduces overall yields and greatly increases costs, while rarely achieving the high process uniformity that is required by both the new FDA guidelines and the competitive requirements of today's global market.

Automated techniques, on the other hand, are inherently well suited to achieving and maintaining process uniformity. Instead of constant tinkering with human process variables, an up-front investment in appropriately designed automation techniques can establish repeatable detailed-task methods and effectively integrate individual tasks into a well-balanced production line.

From a cost standpoint, the increasing use of automation techniques is validating FDA's finding that designing-in product and process quality can ultimately lower production costs. Even manufacturers in geographic areas with relatively low production costs, such as the Far East, are rapidly turning to automation techniques because of the combined benefits of quality improvement and cost reduction.

Figure 1. This modular automation system enabled the manufacturer to achieve improved product uniformity and a 96% yield from production.

For instance, a Singapore-based major manufacturer of disposable blood pressure monitors recently installed a modular automation system (see Figure 1). The system was developed and cleanroom tested in the United States in 1995. It was then shipped to Singapore, where it was retested and validated by the manufacturer, and started into three-shift production by early 1997. Since the changeover, the facility has achieved a substantially improved product uniformity, a 96% yield from production and a radical reduction in rework costs, a 96% reduction in labor hours, and a work-in-process inventory reduction of over 90%.


Of course, the effective use of automation in medical manufacturing depends on the specific product types and the required production volumes. A production system may be a single continuous automated process or a number of distinct and separate islands of automation. Individual automated processes may be linked via synchronous or asynchronous methods. Likewise, the indexing of individual tasks can be done in a broad-front parallel manner or sequentially, in either a linear or rotary fashion.

For example, some product lines require manufacturing in huge volumes at low cost and have the luxury of almost no product alterations over many years. In these instances, the automation methodology typically consists of highly integrated continuous-motion or broad-front indexing systems that produce high volumes per system. The downside of such systems is inflexibility—even modest product design changes can render an entire system obsolete. This type of automation has been used successfully for decades on products that experience long lifetimes and little change. But today's shrinking product life cycles make the monolithic automation approach less desirable for most applications.

Standard disposable syringes provide an example of a long-life product. Their basic product designs did not change substantially over a period of several decades. With the advent of safety syringes, however, the number of design variations multiplied, and, in turn, manufacturers began competing based on product differentiation. As a result, process flexibility and the ability to extend and alter the automation equipment quickly became more important.

Synchronous indexing equipment of rotary or linear design, or pallet-based flexible automation systems are often used for product lines manufactured in large volumes but with short life cycles. A pallet-based system can be partly synchronous and partly asynchronous, or it can use either one-up or multi-up configurations on individual operations. Such systems boost overall throughput by enabling each specific operation to run at its optimal speed.

Examples of product families that require a high level of production flexibility can be seen in the new biodiagnostic technologies, which have made great strides over the past decade. A stream of new and ever-better devices is constantly arriving on the market, with successor designs rapidly replacing existing products. These production environments demand high levels of modularity and flexibility. A flexible modular system can assemble, process, test, and package a complex biodiagnostic device by bringing together a number of readily replaceable and modifiable modules in what is essentially a plug-and-play format (see Figure 2). Ideally, the individual modules also consist of standardized components that enhance both the reconfiguration and the ongoing maintenance of each process operation.

Figure 2. By bringing together individual modifiable and replaceable modules, a flexible automation system like the one pictured here can assemble, process, test, and package successive designs of a complex biodiagnostic device.

The virtues of modularity include the ability to incrementally increase production without duplicating the entire production line. For instance, if a particular operation bottlenecks as production volumes increase, modular automation allows the manufacturer to institute parallel systems or multi-up processing for that process only, to cost-effectively bring it up to speed with the rest of the production line. In addition, the inherent flexibility of a modular production line permits extensive reuse of existing equipment as product designs change and evolve. The result is a combination of shorter time to market and lower overall production costs.


Cleanroom manufacturing techniques were pioneered in response to the demands of the medical and semiconductor industries. Increasingly, as product designs shrink and become more complex, the manufacturing process becomes more sensitive to the presence of contaminants and debris. For the most part, traditional cleanroom efforts have focused on creating a controlled environment that encompasses the entire production line, including equipment, human operators, and the surrounding air space. In these scenarios, large banks of HEPA filters are used in combination with elaborate facility designs to bring the whole production area up to the most stringent compliance level for airborne particulates required by any operation (e.g., Class 10,000, Class 1000, or Class 100).

In contrast, the new wave of advanced modular automation equipment provides a more cost-effective set of alternatives in which smaller HEPA filters are integrated directly into individual pieces of equipment, thereby targeting the particulate-management investment required by each operation (see Figure 3). Creating very clean conditions within specific machine envelopes can reduce by half the cost and size of filtering equipment. In addition, it enables manufacturers to avoid much of the expense associated with designing and maintaining an entire cleanroom environment to meet the requirements of an individual process operation.

Figure 3. HEPA filters are integrated directly into individual pieces of cleanroom equipment to target the particulate-management requirements of an operation.

Some medical applications require an aseptic environment within the manufacturing process to produce sterilized products without poststerilization. Implantable devices, for example, must often be manufactured in an aseptic environment, which adds significant cost and complexity beyond that required for cleanroom certification. The design of such an environment poses far more stringent requirements for the automation manufacturer. Once designed, however, the automated approach to aseptic production is generally more reliable and maintainable than attempts to control septic factors with human labor.


As manufacturers shift toward an emphasis on process over inspection, traceability mechanisms and integrated process control become ever more important. Accountability for all product components, whether in accepted assemblies or not, has been a critical feature of medical assembly for many years. Integrating automated assembly techniques with integrated bar code readers or laser markers, for example, provides tighter control over accountability tasks such as tracking component ID codes and lot codes, automating serial number assignments, and labeling assemblies.

Using built-in networking and communications capabilities, automated environments can also be effectively brought within the scope of overall process control and production monitoring systems. In response to pressure from the GMP guidelines, medical manufacturers are increasingly deploying advanced supervisory systems—which far exceed individual machine process control—to provide sophisticated quality analysis and management on a plantwide basis. The use of automation in conjunction with such comprehensive supervisory systems directly facilitates overall production flow while it simultaneously employs statistical process control techniques to guide product improvement programs. As with many innovations that began in the medical industry, the use of sophisticated supervisory controls as a valuable tool for managing quality is now spreading to other industries.


In today's manufacturing environments, automation techniques have provided a foundation for migrating and replicating standardized production methodologies within distributed manufacturing facilities around the world. In the past, with a heavy reliance on human labor processes, bringing a duplicate facility on-line in a different country would be fraught with difficulties, including training issues, the translation of procedures and assembly guidelines, and the differences in labor methods and skill levels, to name just a few. With the trend toward higher levels of automation and the incorporation of user-friendly, multilanguage operator interfaces, many of these redeployment challenges can be resolved simply by replicating the equipment layout within the new location. Automation equipment manufacturers are enhancing this global deployment capability through the incorporation of metric dimensions, easy conversion to different power parameters, and built-in compliance with multiple international safety specifications.


Given impetus from FDA's renewed focus on improving the level of process quality, the medical industry is responding with the increased use of advanced automation techniques. Not only has the deployment of automation helped to provide greater process consistency and repeatability, it has also lowered overall production costs while maintaining the flexibility to incorporate product design changes.

In addition, the example of the medical industry in the use of advanced automation techniques has become something of a beacon for other industries that, while often lacking the same stringent regulatory mandates, are nevertheless under heavy competitive pressures to improve quality levels. A wide range of industries, such as semiconductors, electronics, automotive, and even consumer products, are achieving significant gains by following the lead of the medical and biodiagnostic industries in adapting novel automation systems to enhance product quality.


1. Federal Register, 61 FR: 52654, October 7, 1996.

Charles Wyle is product manager in the medical division of Ismeca USA Inc. (Vista, CA), where he specializes in the automation requirements of high-volume medical device manufacturing. He designed his first automation equipment in 1949, and has concentrated on medical systems for more than 25 years. Ismeca develops and manufactures custom-designed assembly and processing automation for medical industries around the world.

Photos courtesy of Ismeca USA Inc.

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Copyright ©1999 Medical Device & Diagnostic Industry

MD&DI's Top 20the products that drew the greatest reader response from July 1998 to June 1999.

Medical Device & Diagnostic Industry Magazine
MDDI Article Index

An MD&DI December 1999 Column

A line of perfluoroelastomer O-rings is used for a variety of critical sealing applications. The O-rings provide overall chemical resistance and are capable of continuous service at 200° and 250°C peak temperatures. Typical sealing examples include mechanical seals, filters, flanges, valves, sensors, analytical instrumentation, semiconductor chambers, slit valves, vacuum components, wet stations, and furnace doors. MARCO RUBBER & PLASTIC PRODUCTS INC., North Andover, MA.

An injection molding machine is designed for small liquid silicone rubber (LSR) parts. The precise injection head is simple to use and clean. The machine can handle the extreme precision required for silicone intraocular lenses implanted permanently inside human eyes. KUNTZ MFG. CO., INC., Santa Ana, CA.

A tubing system consists of thin-walled tubing used for medical catheter systems, which have varying flexibility and performance characteristics from one end to the other. The ratio between stiff and flexible segments can be as high as 50:1. The company's proprietary manufacturing process allows the manufacture of this tubing with wall thicknesses as low as 0.0025 to 0.003 in. The PTFE inner liner capability allows for better tracking over a guidewire or other delivery device. HV TECHNOLOGIES, Trenton, GA.

A handheld infrared heat tool weighs 10 oz and can be used to shrink heat-shrinkable tubing and materials. The Glo-Ring's circular quartz elements open and close to encircle the workpiece, resulting in quick, even heating and shrinking. The elements attain their maximum operating temperature of 815°C in about four seconds and come in four OD sizes ranging from 0.5 to 3 in. The elements plug into the heat sinks for easy changing or replacing. Heat to the elements is controlled by a variable temperature control on the handpiece. The Glo-Ring can be used in the hand or in its stand. It is CE marked and meets all applicable EU safety standards. THE ERASER CO., Syracuse, NY.

A material is designed for one-step separation of plasma from red blood cells in a vertical format. The Hemasep V medium permits vertical separation of plasma components from small sample volumes of whole blood in under 10 seconds. Separated plasma will wick onto most lateral-flow materials, including the company's Predator membrane or Biodyne nylon 6,6 membranes. PALL CORP., Port Washington, NY.

A contract manufacturer has introduced an injection molding press for insert molding using a wide variety of materials. The tabletop Model 6010 offers the ability to switch from manual operation for process development and barrel purging to automatic for close control of process parameters. With a 5-tn clamp and 10,000-psi injection pressure, the press is well suited for production, short runs, and prototyping of materials that do not require screw-type
machines. Catheter and Disposables Technology, Plymouth, MN.

A digitally controlled fluid motion module designed for precision fluid dispensing and metering of chemicals and reagents can be used in kidney dialysis, chromatography, and syringe-filling applications. The pump, also available in a diposable model, features pulseless continuous flow, 100% volumetric efficiency, zero leakage, and near zero dead volume. It offers digital control and continuous delivery at 0.1% accuracy of flows from microliters to 1.2 L/min. ENCYNOVA INTERNATIONAL INC., Broomfield, CO.

A manufacturer of adhesives for microelectronic, semiconductor, and fiber-optic applications has produced a comprehensive guide to selecting adhesives for medical devices. The eight-page technical paper explains the potential uses of the company's USP Class VI—compatible adhesives. The 100%-solid, nontoxic adhesives have been used for bonding plastic tips to tubing, bonding fiber-optic bundles for light guides, and adhering diamond scalpel blades for surgical procedures. The company also formulates electrically conductive, thermally conductive, insulating, and potting compounds. EPOXY TECHNOLOGY INC., Billerica, MA.

Corona treatment increases the wettability of polymer surfaces, providing improved adhesion for printing, coating, and bonding. Suitable for use with injection-molded, blow-molded, or extruded parts, MultiDyne systems can be operated manually or incorporated into existing or new production lines. The units feature a durable, one-piece ceramic treating head appropriate for a variety of uses, including treating areas near metal inserts. Among the common medical product applications are petri dishes, test panels, tubing, and other disposable labware products. SOFTAL 3DT INC., Germantown, WI.

A manufacturer of specialty wire products designs, develops, and manufactures custom braid-reinforced tubing. The company's capabilities include producing thin-wall reinforced tubing, bonding layers of thermoplastic to fluoropolymers, and braiding all types of round or flat wire. NEW ENGLAND ELECTRIC WIRE, Lisbon, NH.

Hydrophobic air vent caps are available for sterile air transfer in patient care and particle/bacteria removal in biomedical applications. Filter materials used have a pore size rating of 0.2 µm in air. Hydrophobic filter media allow free air passage while blocking flow of aqueous solutions. Filters range in size from 1/4-in. ID to 110-mm ID and are also available in standard threaded bottle cap format. PERFORMANCE SYSTEMATIX INC., Caledonia, MI.

A line of precision-skived, ultrahigh-molecular-weight polyethylene (UHMW-PE) porous films is well suited for applications requiring high strength and chemical resistance. The D/W 402P UHMW porous films have a tensile strength in excess of 1000 psi. Pores, averaging 16 to 18 µm in diameter, are uniformly distributed in the x, y, and z directions. The films are available in thicknesses from 4 to 100 mil and widths in half-inch increments from 1/2 to 28 in. DEWAL INDUSTRIES INC., Saunderstown, RI.

A manufacturer of precision medical instruments and components produces Class III electrosurgical instruments that are biocompatible and engineered for reuse after autoclaving. A featured product is the LLETZ Loop molded electrode, available in seven loop sizes. Its molded construction encapsulates a 0.008-in. tungsten wire-loop cutting element. Stainless-steel blades as well as ball, needle, and other configurations are available. The manufacturer provides turnkey design, development, and production of all types of medical device components, including those requiring exotic metals or complex manufacturing techniques. INSTRUMED, DIV. OF NATIONAL WIRE & STAMPING, Englewood, CO.

A line of fluorescing adhesives cure upon exposure to visible and UV light. The MD 1000 series reduces cure time up to 50% when matched with UV curing lamps with the appropriate spectral output of UV and visible light. The adhesives fluoresce brightly when exposed to low-intensity black light, permitting manual or automated inspection of the adhesive bond line before and after the curing process. The company also offers UV curing equipment for these adhesives. DYMAX CORP., Torrington, CT.

A company offers thin, flexible, biocompatible coatings that can be permanently adhered to metal or plastic substrates. Slip-Coat hydrogel coating becomes slippery when in contact with body fluid, allowing for easy and safe manipulation of invasive devices. Medi-Coat coating contains active agents entrapped in a nonreactive polymer matrix. This controlled elution allows high concentrations at the device surface with low systemic concentrations. Echo-Coat echogenic coating improves the visibility of invasive devices during ultrasound procedures. STS BIOPOLYMERS INC., Henrietta, NY.

Suitable for either air- or liquid-filtering applications, a plastic net can be engineered to meet the user's thickness, strand density, width, diameter, and elasticity requirements. Naltex is available in thicknesses from 0.006 to 0.200 in. and with strand counts of up to 56 per inch. Netting can be made from polypropylene, polyethylene, polyimide, polyester elastomer, and other specialty resins. The company also extrudes netting in radiation-resistant polypropylene and in resins that meet USP Class VI requirements.Pyrogen testing and in-house precision slitting are also available. NALTEX/NALLE PLASTICS INC., Austin, TX.

A brochure describes a company's capabilities for multilayer, fine-line, and adhesiveless flex circuits, in addition to microvias, beryllium copper conductors, and cantilevered leads. A section on flexible circuit materials outlines conductors, insulators, adhesives, and finish. Tolerances, optimum sizes, flexibility, and temperature ratings are explained and ordering information is provided. The ISO 9002—certified company also manufactures precision parts and a full line of standard and custom RFI/EMI shielding products. TECH-ETCH INC., Plymouth, MA.

A custom manufacturer of close tolerance, single- and multilumen small-diameter tubes produces braid-reinforced tubing to customer specifications. The controlled braiding operation produces close tolerance, wire-reinforced tubes in various configurations. The process utilizes single- or double-ended wires of various materials, including stainless steel, beryllium copper, silver, and polymer monofilaments. Wire diameters start as small as 0.002 in. PRECISION EXTRUSION INC., South Glens Falls, NY.

A company offers a line of standard equipment for dispensing two-part liquid silicone rubber. Multiple-component systems are available with fixed or variable ratios. Standard models include the tabletop laboratory unit, which is suited for rapid prototype and short production runs. Five- and 55-gal versions are also available. The standard models are virtually maintenance free and include extended warranties for pneumatic and hydraulic drive components to suit rigorous production demands at an economical cost. Complete turnkey molding systems are also available. ST SERVICES INC., Albany, NY.

A fast-setting, clear silicone rubber is available for prototype mold making. Parts-In-Minutes RP 6473 Si silicone is a low-viscosity casting compound that produces tough, flexible molds without cloudiness, according to the company. The clarity of the uncured material allows easy removal of air bubbles from the model surface before the silicone gels. After curing for 24 hours at room temperature, the new product exhibits properties including a 30 Shore A hardness, elongation of 300%, and tear strength of 55 to 60 ppi. CIBA SPECIALTY CHEMICALS CORP., East Lansing, MI.

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