Getting FDA’s OK to go inside the body


The challenge: Secure Food and Drug Administration approval to put a new type of device or material inside the human body.
The approach: Both CardioMEMS and AcryMed combined rigorous trials with early and constant communication with the FDA.
The result: CardioMEMS’ EndoSure Wireless AAA Pressure Measurement System received FDA approval in November. A catheter using AcryMed’s SilvaGard coating was approved in December.

By David Forman

Developing a new product - matching design and functionality with a real market need - is difficult enough. But when it comes to working inside the human body, it’s doubly so. Devices and materials used in vivo must undergo rigorous clinical trials in what is essentially a make-or-break process. Two recent success stories, one a MEMS company and the other a nanotech company, highlight some of the practices companies use to navigate the trials process.

Both companies - CardioMEMS of Atlanta and AcryMed of Portland, Ore. - saw their products receive FDA approval late last year. CardioMEMS makes implantable MEMS medical sensors. AcryMed makes antibacterial nanoparticle coatings for medical devices. In both cases, said executives at the firms, getting in touch with the FDA early on proved critical, as did clear communication and a collaborative attitude.

CardioMEMS’ implantable sensor is designed for use with stents that treat an aneurism of the lower abdominal aorta. In the condition, a weakened aortal wall begins to bubble out, a potentially catastrophic problem if it bursts. Currently, stents with a fabric coating are implanted within the artery to create a sort of tube-within-a-tube. When functioning correctly, the blood flows through the tube and the pressure on the arterial wall is alleviated.

However, leaks appear periodically when blood finds its way around the stent, putting pressure back on the damaged wall. Currently, patients must undergo CT scans on a regular basis to test for leaks. With CardioMEMS’ sensor, however, a doctor merely has to move a handheld antenna over the patient’s abdomen to determine whether there is any pressure on the sensor, which has been implanted into the aneurysm sac during the same procedure in which the stent was placed in the body.

CardioMEMS’ wireless pressure sensor is implanted in a patient along with an arterial stent. By measuring pressure, it can determine whether the stent is leaking. Photo courtesy of CardioMEMS
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In addition to the challenge of developing an innovative technology that combines MEMS sensors, wireless connectivity and proprietary software, “we also had to demonstrate to the FDA that the product is both safe and effective since we are a medical device company,” said David Stern, CardioMEMS’ chief executive.

To streamline the process, Stern said his company stayed in constant communication with the FDA and hired a director of regulatory affairs to be responsible for the effort. Clinical tests began in March 2004 in Brazil and ultimately also included Argentina, Canada and the United States.

For starters, CardioMEMS’ sensor is built on a ceramic silica substrate, he said. To prove its product’s safety, the company had to do extensive research to show that all the materials it used were biocompatible and also extremely stable.

Meanwhile, interesting questions popped up - like, how do you confirm that the device is always functioning correctly? After all, if the stent is doing its job, there may be little or no pressure in the aneurysm sac. It is important that physicians do not misinterpret a “zero” pressure reading as a non-responsive sensor.

Stern explained that as long as the antenna is receiving a frequency signal from the sensor, the physician can be assured that the device is working properly. Just the same, the company still developed a simple test to use during the follow-up pressure measurements: The patient coughs and the sensor responds by showing a pressure change.

AcryMed found success with a similar strategy even though it is ultimately AcryMed’s customers who must file for FDA approval rather than AcryMed itself. The company’s SilvaGard coating is intended to prevent the buildup of films on medical devices. Such “biofilms,” said Bill Gibbins, AcryMed founder and chief technology officer, can provide bacteria with a safe haven from which to launch repeated infections against their hosts.

“It turns out organisms are more coordinated (than we thought),” Gibbins said. “They will turn on a gene that makes them sticky and form a tightly adhering colony on a surface. ...When a critical mass forms, it will release a chemical signal to make a polysaccharide coating that blankets the organisms.”

Catheters coated with AcryMed SilvaGard, at left, both look and act different from the uncoated ones at right. The yellowish coating helps prevent the buildup of biofilms that can lead to infections. Photo courtesy of AcryMed
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If you can keep biofilms from forming on devices, said Gibbins, you can keep many infections from forming, too. The company’s SilvaGard, a silver nanoparticle technology, is designed to do just that.

The surfaces of implanted medical devices are perfect for the formation of biofilms, Gibbins said, and the longer they are implanted, the likelier they are to create infection-related problems. “If a Foley (bladder) catheter is implanted three to five days, there is less than a 5 percent chance of an infection,” he said. But after that, he said, the infection rates begin to rise precipitously.

Since he knew his licensees would need FDA approval, Gibbins made sure his company was also working closely with the agency from the start. Concerted efforts included developing specifications for using devices, making sure their materials would meet with approval, establishing a baseline for what kind of antimicrobial performance to expect and determining whether there were any known side effects - of which they found none. In December, I-Flow Corp. of Lake Forest, Calif., received FDA clearance for its ON-Q SilverSoaker antimicrobial catheter, the first medical device to use AcryMed’s SilvaGard.

The payback for both CardioMEMS and AcryMed is not just the initial product, but also the momentum of a successful FDA clearance. Stern said CardioMEMS is now transitioning production of its sensors to a large-scale commercial fab, and the company plans to commence clinical trials on a second product within months. Meanwhile, Gibbins said AcryMed has received inquiries from more than a dozen new potential customers.