Mending Broken Hearts : Expansion at Irvine Firm That Turns Animal Tissue Into Valves for Humans May Portend a Bright Prognosis for the Local Industry

In the bright, white assembly room, about 100 women in sterile hairnets and gowns sit in rows along the workbenches, silently hand sewing small wire forms and fabric pieces to tissues from pig hearts or heart sacs of cows.

These women are making artificial heart valves for humans.

With angle-arm magnifying lights illuminating the task, each woman repeatedly pokes her small needle, threaded with fine Dacron, into the animal tissue, then draws the thread through with forceps, taking four to eight hours to complete each one.

Eva Duran, a final inspector who checks their stitchery by microscope, looking for wrinkles, tears or other hazardous flaws, scraps one in 10. “I look at each one as if it’s going into a different person--and it has to be the best that it can be,” she said.

Baxter International employs 350 of these assemblers at its valve-making plant in Irvine. The company’s Edwards CVS Division is also building a $20-million state-of-the-art valve factory nearby that could more than double its work force and production there.

Officials estimate that the annual worldwide demand for artificial heart valves runs at about 200,000; Baxter aims to be filling half of the demand in five years.

For Baxter, the Deerfield, Ill.-based global health-care company whose Edwards unit initially captured the market in the 1960s with the first mass-produced artificial valve, the expansion marks a corporate commitment to win back lost ground.

And, for a company whose history was marred eight years ago by deaths from faulty valves, the gleaming, unopened facility marks its best effort to meet, and even exceed, toughened regulatory standards.

The Food and Drug Administration hasn’t completed its inspection of the facility. Anita B. Bessler, the division’s president, said: “We expect to be fully approved and operating by the end of the year.”

More broadly, Edwards’ expansion suggests the possibility of a modest comeback for Orange County’s heart valve industry.

Twenty years ago, with Edwards, Shiley Inc. and other firms anchored here, the county led the world in production of artificial valves. By the early 1980s, the county had ceded its distinction to the St. Paul-Minneapolis area.

Edwards chose to reinvest here, partly because of the abundance of assembly workers.

Though Edwards won’t disclose its pay levels, officials say the plant pays 15% to 20% more than other local firms. Labor-market sources suggest that assemblers can start at more than $7 an hour. For those who stay, benefits are good, they say, and the typical manufacturing employee has an average 11 years’ experience with the company.

The job demands unusual dexterity, attention to detail and, above all, patience. It takes assemblers six months to train, 1 1/2 years to become proficient, and for every two trainees Edwards hires, only one usually makes it, officials said.

Lan Le, who arrived from Vietnam in 1975, trains assemblers, many of them recent immigrants. “Some people come in for just a couple days and feel frustrated handling the tissues. Some learn and find that it’s interesting for them, so they stay.”

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Edwards’ history parallels the industry’s rampant growth--and serious setbacks--in Orange County. In 1960, Lowell Edwards, a retired aerospace engineer, started producing the first artificial, mass-market valve. Resembling a Ping-Pong ball in a wire cage, the valve quickly dominated the market.

In 1966, Edwards’ company was bought by American Hospital Supply Inc., which, in turn, merged with Baxter nine years later.

However, Edwards got in trouble in its bid to recover its market share from feisty Minneapolis-St. Paul rivals St. Jude Medical and Medtronic Inc. The two had come out with carbon valves with two leaflets that were believed to allow better blood flow than Edwards’ standard.

To catch up, in 1986, Edwards bought Hemex Scientific, a company producing bi-leaflet valves in Austin, Texas, and Shelkshine, Scotland. Two years later, Edwards halted production of the Hemex valves, after federal regulators received reports of 12 valve malfunctions, with six resulting in deaths. In every instance, the gatelike bi-leaflets broke off.

About 20,000 of the devices were sold worldwide between 1982 and 1988, with most implanted in people overseas. The company was also sued by a New Orleans man, who sought $1.5 million for pain and suffering he underwent when he learned he would likely have to undergo open-heart surgery again to remove his valve.

The company says the number of “adverse incidents” from the device remains low and within FDA performance minimums. The company says litigation has been minimal. It’s modified the design, and now sells a bi-leaflet valve overseas but not domestically.

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Edwards’ product problems were vastly overshadowed--and outnumbered--by Shiley’s. Don Shiley, a former Edwards’ employee, started Shiley Inc. in his Tustin garage in the mid-1960s. Pfizer Inc. bought the company in 1979. Nine years later, Shiley stopped selling its Bjork-Shiley valve, which plaintiffs’ attorneys have blamed for hundreds of deaths.

Pfizer and Shiley have since agreed to pay $215 million to settle a class-action lawsuit brought by valve recipients. They also paid $31 million to settle government charges that they made false claims about the valve and to cover government expenses. They didn’t admit wrongdoing. Pfizer sold most of Shiley’s operation to Fiat S.A. of Turin, Italy, in 1992.

Shiley’s catastrophe, coupled with problems associated with other transplanted items, prompted the FDA to slow its approval of new devices. And the agency began requiring manufacturers to keep track of all patients who receive their items, in case a life-threatening problem should develop. Observers at the time cited manufacturers’ difficulties in alerting all individuals implanted with Shiley or Edwards’ faulty valves.

Edwards, previously accustomed to notifying only surgeons of product failures, now must communicate directly with hundreds of thousands of its valve recipients.

Julie Vassily, the division’s manager of marketing services, said, “The FDA can come here any time they want and check our registry and if it isn’t [up-to-date] . . . they can shut us down.”

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Still, toughening regulation, delayed product approvals and soaring liability costs have combined to make it extremely difficult for small entrepreneurial firms to enter the business, giving Edwards and other big manufacturers the chance to solidify their market positions.

For such companies willing to take the gamble, the rewards can be enormous, said Pieter Halter, president of Medical Data International, an Irvine market consulting firm. He said, for instance, that in the United States, the largest market, heart valves sell for $3,500 to $4,000 apiece--and manufacturers can enjoy profit margins in the range of 80%.

Edwards, for instance, is now the world’s leading manufacturer of valves made from pig or cow parts, so-called tissue valves that can be used as an alternative to the traditional mechanical valves. The company is also the only manufacturer approved to market a bovine valve in the United States, though FDA approval is limited to replacement of the aortic valve.

Surgeons often favor mechanical valves for patients because they’re supposed to last a lifetime. Trouble is, recipients must take anticoagulant drugs to prevent potentially life-threatening blood clots. And the medicine leaves them prone to bleeding.

Tissue valves don’t require anticoagulant drugs. However, they have a limited life and are often used for the elderly who aren’t expected to outlive the valve.

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Tissue valves also present surprising challenges to the manufacturer.

Edwards must obtain pig hearts in a range of sizes. Cuong Ton-That, the slightly built manager who runs Edwards’ tissue assembly, said, “Me, for instance--I’m small, so I’d need a valve from a medium-sized pig.”

However, the smallest sizes can run scarce throughout the year, forcing Edwards to load up on its supply around the holidays, when dinner tables groan with platters of tender suckling pig.

Summertime often brings another problem: Pig hearts available from a given slaughterhouse might fall short of specifications if farmers, worried about rising prices of feed grain, slaughter their pigs earlier than expected.

Edwards resolves that problem by maintaining relationships with 15 slaughterhouses.

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For the future, whether Edwards makes mechanical valves, tissue valves or some device not even thought of yet, the company is taking pains to cater to its best customers--cardiac surgeons. The company has designed its new factory with them in mind.

A museum, just inside the entrance, showcases models of artificial valves that illustrate the industry’s historical development. Adjacent to the museum, there’s a glass-enclosed viewing area where surgeons will be able to watch the factory in operation, once it’s open.

Visitors who would like a close-up view of assemblers’ hands as they work can watch a live video-screen connected to zoom-lens cameras, stationed above the workbenches.

Dr. Delos Cosgrove III, a leading surgeon at the Cleveland Clinic and inventor of two valve-related Baxter products, recently visited the museum, where he was surprised to find a failed valve design from decades ago. It reminded him of a recent technique he developed for transplanting a frozen human valve into a human heart.

Though the original design was a blind alley, Cosgrove said, past ideas can provide inspiration for future solutions. “If we know of an idea that was tried and know the reasons it didn’t work, we now may have the understanding to make it work.”

Cosgrove even sends many of his residents to Edwards’ facility each year to watch the assemblers.

“Those ladies are terrific,” said Cosgrove. “They have an enormous amount of training, they are very, very diligent, and you see those valves come out, day after day, and one looks just like another.”

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Valve Job Options

Malformed or damaged heart valves may cause serious illness and death. Baxter Healthcare Corp.’s Edwards CVS Division produces three replacement heart valves: a mechanical version, one that utilizes a pig’s aortic heart valve and another fashioned from cow’s pericardial tissue.

Details on the valves:

Mechanical Valve

Name: Starr-Edwards

Introduced: 1960

Sizes: 21-31 millimeters for aortic type; 26-34 mm for mitral

Advantages: Lasts a lifetime; usually installed in younger patients. Not susceptible to calcification.

Disadvantages: Since it is entirely artificial, patient’s body senses it as a foreign object and blood may clot around it. To prevent this, patient must take anticoagulant medication daily and be monitored to sustain proper dosage.

Tissue Valves

Name: Carpentier-Edwards Bioprosthesis

Introduced: 1972

Sizes: 19-31 mm for aortic type; 25-35 mm for mitral

Advantages: Anticoagulants not needed.

Disadvantages: Difficult to find pigs with valves in the exact sizes required. Normal degenerative process of calcification may damage valve tissue. Usually implanted in older patients who produce less calcium and are less likely to outlive valve.

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Name: Carpentier-Edwards Pericardial Aortic Bioprosthesis

Introduced: 1991

Dimensions: 19-29 mm

Advantages: Made from tissue cut into leaflets and fashioned into a valve; no need to look for cows with proper-sized valves. Anticoagulants not needed.

Disadvantages: Normal degenerative process of calcification may affect valve tissue. Usually implanted in older patients who produce less calcium and are less likely to outlive valve. Currently available for aortic valve replacement only.

Source: Baxter Healthcare Corp. Edwards CVS Division

Researched by JANICE L. JONES