Is medical device manufacturing finally coming clean?
The trend toward smaller and less invasive devices will call for stricter contamination control. It could be time to take a page out of the semiconductor playbook.
BY HANK HOGAN
It's safe to say that sterilization and regulation are the two dominant issues steering the contamination-control practices of the multibillion dollar medical device industry. That may change, however, as new technologies, such as automation, enclosures and innovative manufacturing techniques based on lasers and other tools are increasingly deployed.
The result could mean a significant transformation in the contamination-control practices and methods employed by medical device manufacturers. And these changes are slowly, but surely, beginning to take shape.
Maintaining status quo
Typically, today's medical devices are manufactured in a manual process, with cleanroom classification running between ISO Class 7 (Class 10,000) to ISO Class 8 (Class 100,000). The size of the cleanrooms, because of the nature of the manufacturing, tends to run in the range of several tens of thousands of square feet, with contamination control consisting of a few scattered HEPA filters as part of fume and ventilation control—not for particulate suppression.
Usually, the cleanrooms depend upon general airflow to sweep away airborne undesirables, along with other fundamental contamination-control procedures consisting of gowning for operators and periodic scrub downs of surfaces and machinery.
But what some industries would consider a lax approach in contamination control is dictated by the fact that medical device manufacturers have the sterilization step ahead; therefore, the biological burden created by the manufacturing process doesn't have to be as low as what is required of the final product.
"We are still really concerned about the cleanliness of the cleanroom, obviously, but currently with our regulations for our company, our cleanrooms are not like a Class 100 or a Class 1000 cleanroom; they are much dirtier than that," says Aaron Kendrick, facilities manager with Guidant Corp. (Indianapolis, Ind.), a major medical device manufacturer that puts an emphasis on cardiovascular products.
This isn't to say that temperature and humidity controls don't have to be in place and that potential biological contamination from operators doesn't have to be controlled. According to Yan Cardineau, director of operations in the Arizona device manufacturing division of Medtronic, Inc. (Minneapolis, Minn.), "Sterilization is validated based on a certain amount and type of bioburden. If you lose control, then basically you have to put everything in quarantine and study what the implications are."
From a practical point of view, however, few manufacturers want to go through a recertification with regulatory agencies. In turn, they are reluctant to implement manufacturing changes. So, the manufacturing process that's certified and used may be the manual one put in place for the original prototype development and initial certification submission—which has implications for the quality and reliability of the product, as well as the repeatability of the manufacturing process itself. It also has an impact on the contamination-control challenges.
"It's a very manual, intensive task that we perform, and because of that, you've obviously got a lot of people," explains Willy Voxwels, standards and facilities manager with Guidant. The problem, he adds, is that the people involved in the manufacturing process "...are probably the highest contributing factor to both particles and bioburden."
Could the state of affairs be changing?
The size of the United States' medical device market, according to figures compiled and published by the Washington-based Advanced Medical Technology Association (AdvaMed), was $69 billion in 2002. For that same year, AdvaMed put the worldwide consumption of all health care technology at $175 billion. Those numbers, according to AdvaMed, are certainly large enough to fund and perhaps warrant changes and improvements in manufacturing technology and practices.
Industry observers believe that changes will come in the form of small enclosures housing more highly automated tooling in cleaner environments-perhaps like the interconnected minienvironments that are driving state-of-the-art semiconductor manufacturing.
Bill Baumgartner, industry analyst with The Freedonia Group (Cleveland, Ohio)—an international business research company—predicted in a November 2003 study that use of cleanroom consumables in the medical device and supplies market would increase more than 10 percent annually, reaching $55 million in 2007 from a base of $34 million in 2002.
This growth, Baumgartner notes, "Will result from increased manufacture of medical devices and disposable supplies, as well as expanded penetration of the market by cleanroom technologies."
As evidence, he points to such examples as Gish Biomedical, a manufacturer of disposable devices used in cardiovascular surgery, orthopedics and oncology, which Baumgartner says increased its cleanroom manufacturing space by 40 percent in 2003. He expects that demand for cleanroom consumables will benefit from this expansion initially, but that will change as the use of isolators and enclosures—or minienvironments—become more widespread. As these enclosures become more automated, the rise in demand for consumables will drop.
There are some signs of a trend toward automation and the implementation of new manufacturing technology. Medtronic, for instance, not only makes medical devices in its Arizona cleanrooms but, on the same campus, makes semiconductor devices.
Some of Medtronic's medical products consist of sealed hybrid electronic devices that are implanted to intelligently regulate heartbeat and other functions. These hybrids are assembled from components in the same or similar cleanrooms used for the manufacture of the final device. Medtronic produces more than a half-million hybrids a year at its Arizona facilities, and those go into the shell assemblies that are the final product.
According to Medtronic's Cardineau, roughly half of the manufacturing process for its devices is automated or semi-automated. The company is able to do this because the volume makes the capital expenditure required for automation worthwhile while it reaps benefits beyond increased efficiency and shorter cycle time.
"One is reliability," comments Cardineau. "The product that we make and the return rate that we have is the best in the industry by far. The level of quality that we have in the processing and the degree of automation in process controls and inspections is extremely robust; and that definitely helps us gain control over operators going to sleep or not being trained or certified properly."
From a contamination control point of view, a greater degree of automation means fewer people in the cleanroom; in turn, one of the largest sources of contamination has been reduced.
Cardineau notes that machinery still needs to be cleaned periodically, but the reduced cleanroom traffic helps decrease the contamination burden. The Medtronic cleanrooms in Arizona are currently ISO Class 8, with no plans to go to a tighter classification.
Whether other manufacturers will follow Medtronic's lead will likely depend on whether automation makes economic sense. The industry is highly competitive and can work for and against the adoption of new approaches.
On one hand, there are economic pressures for greater efficiency. On the other, there's a need to get to market as soon as possible. Introducing a manufacturing change, with all that it entails for recertification, can slow down the time it takes to get a product into manufacturing volume. So, it's becoming a case where manufacturers need the automation in place during the initial process development and certification.
Finally, new manufacturing technologies could have an impact on contamination-control requirements within the medical device industry. For its medical device customers, Resonetics Inc. (Nashua, N.H.), a contract manufacturer specializing in laser micromachining, drills holes 25 µm or smaller in diameter through stents and other products, and also etches precise patterns in films.
Glenn Ogura, Resonetics' vice president of marketing, notes that the company's cleanrooms run from ISO Class 6 (Class 1,000) to ISO Class 7 (10,000) and use such familiar methods as bunny suits, HEPA filters, and laminar flow workstations. The biggest reason for reaching this level of cleanliness has more to do with laser micromachining than demands from the company's medical device customers.
"If particles land on a catheter tube, then it is possible that the particle will shadow the intended target area, resulting in incomplete laser drilling," says Ogura.
To avoid this problem, parts are cleaned by plasma, ultrasonic cleaning or simple alcohol wipe. They are also placed in a self-contained enclosure, such as a glovebox, which is purged with nitrogen or placed in a vacuum chamber.
Contamination-control procedures must be followed once the laser begins drilling, stripping, etching or cutting. And as the material vaporizes, some can resettle onto the medical device. Techniques such as vacuum nozzles, gas assist or sacrificial layers are used to minimize the debris.
As is the case with automation, it's unclear just how soon medical device companies will turn to such technologies as laser micromachining. There's a definite trend toward smaller and less invasive devices as well as three-dimensional surfaces and devices. This move implies the need for more precise machining of surfaces, in turn, boding well for new manufacturing techniques.
But the need to satisfy regulatory agencies and to pass a certification process means that such new manufacturing approaches will probably become widespread only when they're incorporated early in the development cycle.
As Ogura notes of his customers, "Once the [regulatory] paperwork is submitted, they are very reluctant to change anything."
HANK HOGAN is a special correspondent to CleanRooms magazine living in Austin, Texas. He can be contacted at: firstname.lastname@example.org