Trauma Surgeon Reflects on Experiences with R&D, FDA and Zimmer Biomet Partnership

Thomas “Toney” Russell, M.D., an orthopaedic trauma surgeon and President & CEO of Innovision, developed the N-force fixation platform to meet his own clinical needs in optimal fixation of fractures in the extremities and pelvis. N-force, comprising fenestrated screws, washers and calcium phosphate materials, works by injecting bone substitute material (the calcium phosphate) directly through the fenestrated screw to support fixation and fill the bone void.

Russell has worked with various device companies throughout his career, such as Richards Medical, Smith & Nephew, Knee Creations and Zimmer, making intramedullary nails, external fixators and plate systems. Despite his experience, N-force was a large regulatory undertaking due to concerns posed by FDA ’regarding the delivery of calcium phosphate through a metal screw.

After receiving multiple 510(k) clearances for N-force, Innovision faced the next set of challenges: sales and marketing, which it addressed by signing a distribution agreement with Zimmer Biomet in October 2015.

ORTHOKNOW caught up with Russell to learn more about the N-force’ regulatory pathway and his take on the future of implant delivery.

ORTHOKNOW: What’s the backstory of your company and the N-force?

Russell: For fractures, you reach the point where you realize you can’t fix everything with metal if the bone quality is not good enough. Implants are designed to work best in normal bone, but we’re getting more patients with compromised bone due to osteoporosis and severe injuries.

In the last 30 years, we’ve learned that bone mineral is pretty sophisticated material. During that time, calcium phosphate technology has evolved, permitting control of the reactivity and flow characteristics of the bone substitute material, where [the materials] will intrude into the bone trabeculae; then, the body remodels them into bone. The problem was that we didn’t have a way to get this material easily into the bone. The research I’d done was based upon ways to get the material in the right place and in the right quantity.

That’s how the N-force was developed. I had a clinical need for fracture fixation devices through which I could accurately place bone substitute materials within the bone.

There had never been an implant like this cleared by FDA. It took six years of working with FDA to develop initial protocols for regulatory clearance of devices for augmentation of metal implants with specific cleared biomaterials.

ORTHOKNOW: What were your biggest challenges in working with FDA? How did you handle them?

Russell: We did a risk mitigation analysis, which took about two years to develop with FDA. Of all of the risks, there were a few things about which FDA was concerned. The first was implant strength. They challenged, ”You have to design implants that deliver these biomaterials to be equivalent in ASTM (American Society for Testing and Materials) testing to the predicate devices on the market.” We worked on different ways to equal out the stresses, and then developed a process to manufacture that reproducibly.

Then, we had to prove that the material would flow in the screws. We worked with a group at ETEX (a bioresorbable bone substitute materials manufacturer acquired by Zimmer in 2014), and developed protocols. We had to show that it was a low-pressure injection; all of the previous techniques involved high pressure to get materials in. With low pressure, we minimized the chance of embolism. We designed that characteristic in the screws through fluid dynamic analysis and thermodynamics. We had to re-engineer the material itself, so we changed the implant design and the material to make it optimized for the flow.

FDA said, “You’re injecting materials that harden around the implant; they could turn into bone. How are you going to get the metal out?” So, we designed a self-extraction feature in the hydraulic grooves that cut a path through the biomaterial once it hardens. If you have to take it out for some reason, you can do so without destroying the calcium phosphate around the bone.

ORTHOKNOW: Why was FDA so skeptical?

Russell: FDA thought that this was impossible because, from a mechanical standpoint, once you insert holes or perforations in a cylindrical structure, it weakens the device. Also, bone substitute materials are Non-Newtonian fluids that resist flow and movement down a closed cylinder, but we were able to engineer it. Once we received regulatory clearance, we performed a small release to several centers and collected experience with approximately 200 screw insertions. We learned more about the bone substitute materials and conducted more cadaver research, leading to another generation of bone substitute material and mixing system to increase surgical efficiency, as well as a better sheath injection system for version 2.0 of the N-Force. We then went back to FDA and repeated the protocol testing to receive our next 510(k) clearance.

Most of the stuff that FDA asks you about is legitimate; it’s just so time-consuming and expensive that most people run out of resources and money before they can complete the work. This has been a high-risk project. Between $10 million to $20 million was what it took to get this project from start to the market. Most companies are not interested in something that takes more than one to two years. The technology has become complex enough that you don’t really get innovation unless you have a long-term project.

FDA has a siloed mentality, and those silos don’t communicate. The real challenge was to develop a dialogue between the two silos of the orthobiologics side and the metal side. That was done with the help of Holly Rhodes with MCRA (Musculoskeletal Clinical Regulatory Advisers), who is a former FDA employee. She served a critical role in knowing how to work with FDA.

ORTHOKNOW: What’s next for Innovision?

Russell: Last October, we signed a distribution deal with Zimmer Biomet, because a small company can only get so far. We got the devices, all of the regulatory approvals and the manufacturing, then Zimmer Biomet got our distribution rights and invested in our company. We’ll be working with them to actually commercialize the devices. There’s a set price for using the materials and the screws. Basically, you have about the same price for each operation, whether you use two or three screws; it doesn’t really matter. That way, the surgeon doesn’t have to worry so much about the cost, and the hospital knows it’s a fixed cost.

We have a 4.0 and a 7.3 design of screws, so now we’re going to take that technology and put it into screws for plates, nails, hip devices, acetabular cups, any place where you’re anchoring a device and the bone quality is poor and you need to get immediate stability. With our technology, they could just put one of these devices in, inject a material and get a stable implant. Technology is about trying to enhance the stability of our future implant designs.

ORTHOKNOW: How do you think price pressure in orthopaedics will impact the adoption of new technologies like yours?

Russell: On the accounting side, [hospitals] don’t want new technology, because it’s more expensive. This is the dilemma in the U.S. We have a segmental system, with a hospital that gets reimbursed by a third party, a rehab hospital that has a different schedule, disability insurance that is another carrier and the social network is Social Security. You have four different groups trying to shift the costs to somebody else. People get hung up on the cost of an implant. The implant took ten years to develop, it has liability insurance, regulatory fees and all these pathways; somebody has to make it, they have to pay employees and pay for the raw materials, then the hospital says, ‘I want it $100 cheaper.’ The cost of hospitalization for one day in the U.S. is $3,000 to $4,000. The cost of one day is more than the cost of the implant. If you have technology that improves people’s recovery faster and gets them back to work faster, that’s something that people should agree to, but it’s a fight right now.

[With bundled payments], whenever surgeons are put into a system where their boss is somebody else besides the patient, then people with agendas can subvert how the physicians practice, not for the benefit of the patient. Who is the patient advocate? I’m concerned about that.

ORTHOKNOW: In your opinion, what does the future hold for the orthopaedic industry?

Russell: In trauma implants, for years people had said that there is one size implant and this is what you need for all hip fractures, for example, no matter how small or big. People still argue that. In the last 30 years, my designs have focused on implant matching—so for younger, active people, I design the nails to be smaller; you take away less bone and still control stability to make them stronger. As you get to larger patients, you need designs that fit the bigger canals, so there’s a lot of engineering to avoid stress shielding and vary the cross-sectional modulus, which is the stiffness of the implant. You can’t just do one operation for every fracture. Just like we do for total joints, you size the person’s anatomy and use the right sized implant that matches it. We haven’t been doing that in trauma until the last ten years or so, and there are still a lot of people who don’t do that.

For the last 30 years in orthopaedics, we’ve had a major innovation every ten years. When I started, 35 years ago, there was no arthroscopy, no spinal pedicle fixation or lateral interbody fusion, no interlocking intramedullary nails for the tibia or femur, no locking plates, no MIS, no bone substitute materials; the list goes on and on. For the next 30 years, we need to figure out how to marry implants with biologics to get a synergistic effect of the two.