Blood Will Tell

For more than 20 years, I’ve been intrigued by the increasingly creative technology and inspiring designs that have emerged in the medical device industry. In 1999, when the U.S. Food and Drug Administration (FDA) approved the first intervertebral body fusion device (IBFD) manufactured from a non-metallic material, the market and patient care changed direction. This shift continued when the FDA reclassified IBFDs from a class III into a class II designation in 2007. Then came rhBMP-2 Infuse Bone Graft in 2002, another breakthrough. Today there are three major categories for bone grafting options: ceramic, allograft and bone morphogenetic proteins. Each is yet another example of how technology is advancing.

Now I smell blood. As tissue-based applications, materials and devices continue their upward market trajectory and increasing popularity with surgeons and patients, once again I’m enjoying my view of history in the making.

I turn to Michael Bauer, M.D., president of MJ Bauer and Associates, for an expert preview of how that history will develop. A nationally recognized medical expert in tissue banking, infectious disease consulting and laboratory medicine, Bauer is a certified tissue bank specialist. Bauer’s Denver-based company provides professionals who serve as laboratory directors of record as well as medical directors of tissue banks. He is my go-to source for all things blood-, tissue- and stem cell-related. From his perspective, we’re on the cusp of a third wave of innovation, one that continues the convergence between medical device and tissue.

The first wave was the use of tissue-based substances to speed healing.

“It’s kind of becoming standard now to have some kind of tissue component available that’s rich in some kind of bone-stimulating protein, something to help the bone heal and now in addition to that, we’re seeing an increased demand for wound coverings,” Bauer said. “No matter what they say, it’s going to be tissue, whether it’s liquid tissue or frozen tissue.”

From a regulatory standpoint, the FDA has a well-defined process for evaluating and granting approval to those kinds of applications, Bauer said.

The second wave is amnion-based fluids, materials that are rich in growth factors and bone proteins such as the substances now being added to pastes and putties.

“Amniotic fluid was designed by God for one thing, and that’s to grow things,” Bauer said. “Everything you could possibly dream you might need for wound care or healing—everything—is in that material.”

Several companies now have such products, he said.

“We’ve got a number of amnion banks that are popping up across the country,” Bauer said. “It’s truly the ‘soup of the day.’ I can’t think of a traditional processor that’s not thinking of bringing amnion in-house now, whether or not they actually do so.”
Despite ethical grey areas and questions from a regulatory standpoint, most of his clients continue to focus resources on these amnion-based fluids, he said.

“Most of those who have offered such a product are under an untitled letter with the FDA, which just means FDA doesn’t know what the heck to do with them,” Bauer said. “In some places, FDA has told them to cease and desist. Other places they’re under advisement—‘One slight misstep we’re going to shut you down.’ That’s not intimidating anybody. Everybody’s still moving forward.”

The third wave is one that could turn the tide of modern medicine but is awash in controversy: stem cells.

“In my opinion, the sky’s the limit,” Bauer said. “That’s the third wave and cutting edge of where orthopedic tissue transplantation is heading right now.”

Stem cells have the potential to speed healing from months to weeks. But there are questions about the long-term effects of implanting cells that can literally become anything in the human body. Just as surely as they can become bone, which is the goal of orthopedic applications, they may also find and create cancer, Bauer said.

“[The stem cells would] go wherever they want to go then wherever they land, if there’s a need they’d differentiate into whatever’s there,” he said. “It’s not that it would cause cancer, but it could be ‘pouring fuel on the fire,’ so to speak.”

Proper regulation and transparency are critical for this third wave.

“Until someone actually makes it very clear what’s in their stem cell ‘soup,’ all bets are off,” he said. “The problem with stem cells is FDA doesn’t know what to do with them. They know they’re not a device, but we all think there’s going to be a middle of the road for stem cells, more like bone marrow cells, red blood cells, or white blood cells used to fight infection.”

But not everyone will wait for guidance from regulatory agencies at the expense of innovation.

“If FDA takes too much time, there probably are some big banks out there that might try to go down a device pathway for their more complex products like stem cells,” Bauer said. “One company did that with one particular cell and it’s still on the market.”

Questions about the path to market and monitoring of new products loom large for companies and individuals considering a foray into stem cell-based products.

“The regulatory landscape is huge—people that are getting into it right now, that’s their biggest challenge,” Bauer said. “They need to turn to some experts who can guide them down the tissue pathway and help them with all of their descriptions and marketing materials to make sure they stay on the ‘tissue’ side of the debate.”

Innovators should evaluate their product to best determine which route to follow—tissue or medical device.

“If I started my own bank tomorrow, I’d start with tissue; what can I produce that can be recognized as tissue; then I’d start down the device pathway with a more complicated product,” he said. “I’d release it early on as tissue and hope that FDA leaves it alone and lets it go while I’m getting it ready to be a device.”

Over the long term, Bauer sees options that start out as tissue developing into medical devices.

“No matter what, I think device is going to be the goal for all the cellular-based stuff,” he said. “It’s so complicated, [regulatory agencies are] going to want to see safety profiles, clinical outcomes, controls for cancer—when it becomes live cell-based materials, it will be as complicated as a device pathway.”

Bauer is hopeful that regulations will catch up with the speed of innovation, and says there’s already an appropriate blueprint for the FDA to follow.

“I believe that stem cells are tissue,” he said. “I believe they’re just like blood. If I could just wave a magic wand, I’d say, ‘Guys, you need to just adapt all of your blood regulations for stem cells; let’s just transfer it all over.’ Allow FDA to look over everyone’s shoulder to make sure there really are cells in there. FDA needs to do what they do with blood banks.” 

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Dawn Lissy is a biomedical engineer, an entrepreneur, and an innovator. Since 1998, the Empirical family of companies has operated under Lissy’s direction. She has been responsible for all Empirical operations, including designing test fixtures and protocols, running test protocols, and writing complete reports. She holds an inventor patent for the Stackable Cage System for Corpectomy and Vertebrectomy. She is a member of the Biomedical Engineering Society, Society of Women Engineers, the American Society of Biomechanics, and the ASTM. She holds an M.S. in biomedical engineering from The University of Akron, Ohio. She can be contacted at [email protected].