Earlier this year, CardioFocus wowed the market when it won pre-market approval from the FDA for its HeartLight system, an endoscopically guided light energy device for the treatment of atrial fibrillation. The minimally invasive ablation therapy is considered a major advance in treating afib because it allows surgeons to see the actual tissue they’re ablating. To date, more than 3,400 patients worldwide have been treated using the HeartLight device.
“We’re still somewhat of a small company,” vice president of engineering Jerry Melsky says. ”Our core technology is delivering laser energy to the body in unique ways.”
That core tech is employed in HeartLight as a continuous, near-infrared laser light projected by the catheter, which heats the atrial tissue around the heart’s pulmonary vein, forming scar tissue that results in electrical isolation. The catheter works to create “conduction block” by allowing the physician to place overlapping arcs of laser light into the atrial wall around the vein. Complete isolation is often obtained with several 20-30 second energy deliveries, promising a great advantage in accuracy, speed and effectiveness in comparison with other catheter methodologies.
Such state-of-the-art advances don’t happen overnight. In fact, CardioFocus has been working on the technology for more than 20 years, and found a partner in Minnetronix 16 years ago. You could say the two companies grew up together, sharing successes and challenges. What happened behind the scenes holds lessons for start-ups and established companies on the CMO and OEM sides of the aisle.
In the beginning
Minnetronix co-founder Dirk Smith says the relationship has been quite a journey. “CardioFocus hired us initially as a design company, and then they had to wait and see how things played out,” he says. “It’s very much evolved into a full design-to-manufacturing-to-service-and-field-support relationship.”
Melsky says CardioFocus was founded on the idea of making modifications to optical fibers, so that light-based energy could be put into various parts of the body for a few therapeutic outcomes. “Way, way back, we were doing a lot of different things with laser energy, and in the mid-‘90s we got very focused on making a device to treat atrial fibrillation and making the gadget that goes inside the body [the catheter and the laser fiber] as a single piece.”
Minnetronix started working with CardioFocus around 2000, already armed with the core laser ablation technology in an early lab stage, explains Smith. “They came to us very much as technologists, asking us to help design and build a human-use laser.” The core technology, however, is all from CardioFocus, says Minnetronix’s Smith. “They have a good team of optics experts and systems engineers.”
That initial project involved an instrument to power and control the laser, Melsky adds. “We needed an electronic box that had a diode laser in it as part of the system. We had a choice of whether we were going to build up in-house capability to do that, or whether to go to a supplier to help us with that. It seemed to make more sense, from a value proposition, for us to stay focused on the devices that go in the body and to bring in this other expertise at building an electronic box with a user interface to actually supply the laser energy to our device.”
Minnetronix was brought in and spent a number of years working on getting CardioFocus into pre-clinical and clinical studies. For several years thereafter, CardioFocus continued advancing its technology, adding imaging and other advanced optics. Then it came back to Minnetronix for the next step. From there, says Smith, “We worked with them on the current product, basically, to do requirements through design of the product and then on into production of pre-clinical, clinical, and for-sale production devices.
Melsky says the relationship has been a good one for both sides. “We were able to tap into a lot of their expertise,” he says. “One of the things that was really important to us was they had capability not just to do product development work, but also to do the manufacturing piece, and even beyond the manufacturing piece to do fulfillment of this piece of capital equipment.”
What Minnetronix brought to the table, Smith notes, was experience with integrating complex medical devices, electronics and software expertise, plus systems engineering and the regulatory and Quality System experience to go with it.
The technology is fairly complex, notes Jim Reed, vice president of new business development & marketing at Minnetronix. “A lot of things are happening at the same time: A balloon displaces the blood out of the atrium of the heart, a visible laser shows where the ablation will occur, and an invisible laser does the ablation, which you can’t actually see. The system therefore has to create an artificial visual line on that display to show where you have ablated. That allows you to get a complete annular ablation around that vein to make sure it’s completely isolated.” Both lasers, the feedback loops for safety, the expanding and vacating balloon, visual signal processing, and visualization all have to operate in concert.
Reed says Minnetronix was able to develop a system that performs all of those functions simultaneously, in an intuitive, user-friendly and – importantly – safe way, “because you’ve got lasers and fluid and pressure, and temperature controls, all being handled at the same time.”
The challenge for both companies was huge, says Reed. “CardioFocus was a startup and now, after years of development, clinical trials, and the regulatory processes, they have this game-changing PMA device.”
Rising to the challenge
Smith points to the safety of the laser as a key focus during development. “This is a high-powered laser, and safety is really critical. They can burn tissue very quickly with this device.” One of the first steps was matching CardioFocus’s patented technology with the thermal safety of the laser.
Melsky likewise praises Minnetronix’s technical team. He says the electrical hardware and software design was integral to the product, but even more than that, he says the CMO showed strength in creating a unified product.
For example, he says “Their team was deep enough and capable enough that they were willing to go outside of their core competencies in certain areas, and we were pushing them into doing certain things with regard to integrating a laser into the electronic box. And they were able to rise to the challenge and to do that piece.”
The optics integration was another big step, Smith says. The team worked to implement the imaging system to make sure it could display both still images and video quickly enough for surgeons to use.
Melsky also recalls the development of the optics, which he says wasn’t in Minetronix’s core competency. “We had asked them to integrate this piece of optics into the system. The optics really needed a little bit of an alignment or an alignment check at the end of the manufacturing process. Initially Minnetronix said it didn’t have any expertise for the alignment.”
But CardioFocus insisted it was a key step, critical because Minnetronix was responsible for putting components together; there was no good way to get a good output other than to do the alignment once it’s all put together, says Melsky. “They were able to rise to the occasion in putting procedures together so that they could do the alignment.” And it turns out Minnetronix was able to improve on the original requirements by streamlining the manufacturing. “So they’re not doing the alignment anymore, they’re doing an alignment check.”
An additional challenge was the user interface. “When you put as complex a system as this is together, the user interface has to translate that complexity to intuitive use for the user,” Smith says. The goal was to create a simple user interface to control a complex system.
Another story highlights how Minnetronix was able to go above and beyond. “The endoscopic visualization system in HeartLight requires a specialized light source that delivers light to the optical fibers in the catheter,” Melsky explains. CardioFocus had been buying a xenon arc light from a supplier that discontinued the product. “There was nothing else on the market even remotely like this light source,” Melsky says. The company asked Minnetronix to build the light source “almost from scratch;” Melsky admits it was an unusual request, but says Minnetronix rose to the occasion and built a replacement light source.
Smith attributes many of these achievements to Minnetronix’s dedication to quality and design controls. “An important focus area with this and other products is the technical file and documentation.” Minnetronix managed the technical documentation on the instrument and the capital equipment through verification testing (although, Smith notes, a third company worked on catheter design). It also managed usability requirements.
Product quality was high on the list of attributes that made Minnetronix a good partner, Melsky says. “The stuff that they’ve delivered to us has always been high-quality, both in the development and in the manufactured items.”
Melsky says CardioFocus felt comfortable with Minnetronix precisely because of its familiarity with quality management and FDA regulations. “Sometimes the first questions we ask suppliers are, ‘Are you FDA registered? Have you been audited? Can you show us your recent audits?’” It was critical that FDA and other bodies had vetted the company. “They had top-notch systems in place.”
Finding a partner who knows medical devices and the regulated nature of the medical device industry is a big deal. “We’ve looked at other suppliers where they do some medical, and maybe some military, and often what we find is they have certain aspects of their system where the level of scrutiny and quality control really isn’t up to snuff for the medical device industry.”
Minnetronix prides itself on the fact that it was able to hand CardioFocus the subset of documentation needed to apply for the PMA, “essentially complete and ready to go to FDA,” says Reed.
All of this is not to say the relationship never had ups and downs. Both companies went through trials and errors, something inevitable with long partnerships. As Smith says, “There’s definitely a growth curve, and our company grew up through this process. Industry has seen regulatory changes and technology changes. For example, the electronics and software – the microprocessors – that we put in that first laser have changed so much in the last 15 years.”
One of the hardest issues in any relationship is communicating disappointment. At one point during the companies’ long relationship, CardioFocus expressed frustration over Minnetronix’s ability to provide accurate timing and cost proposals. “We were frank with them,” says Melsky. “It seemed like every project that we had done with them had run over.”
They were looking at about a $2 million dollar project to redesign the whole box, he explains. According to Melsky, Minnetronix surprised the company by offering to do the project on a fixed-cost basis.
“They might shoot me for saying that,” laughs Melsky. “I think we both learned a lot from that experience. I’m not sure they’d be willing to do that again, but it was an interesting experiment.”
The reality was that the fixed-cost proposal proved to be a poor decision. “There really isn’t any such thing as a fixed-price contract,” says Melsky, “because there isn’t any such thing as a fixed deliverable specification.”
Melsky says CardioFocus started out thinking they knew what they wanted, but eight months into the program, the company realized that the user interface wasn’t working. “We needed to change our thinking.” And, he says, it’s perfectly legitimate that that as expectations change, as the specs change, the supplier will need to update their quote.
From the Minnetronix side, Smith says the development cycle for complex PMA devices is by nature long and always includes unanticipated challenges and opportunities. “While we follow a standard methodology for every design, each product and each company we work with is unique and every development effort has its own challenges and critical elements. Part of the fun and reward of working with companies like CardioFocus is that they’re doing something that no one has done before, and developing a totally new therapy requires flexibility and adaptability.
“Developing safety-critical devices is complex, particularly for PMA devices which evolve over many years; working closely with our customers to help them identify and focus on the most critical and necessary objectives is essential,” he adds.
The combined team had to adjust not only to changing specifications and pre-clinical testing results, but also with the evolving processes around testing and verification, including human factors and usability. “The way that we perform usability testing on this product now, and really how we conduct overall verification testing, is significantly more sophisticated than even 10 years ago, based largely on new regulatory standards and guidance documents,” Smith says.
What makes a good OEM?
Smith says that when Minnetronix started with CardioFocus, it was one of hundreds of startups around the country. “We had no idea of their probability of success.”
And yet, being able to provide long-term support is critical for Minnetronix as a CMO that works with some of the largest medical device companies in the world.
As Reed says, “We do a lot of work with startups as well as operating companies. We hope those startups will eventually become a company like CardioFocus and our goal is to help them cross that finish line.”
Over time, says Smith, you develop a sense of what good startups bring to the table. Essentially, Smith says, OEMs that know what they need and when they need it are in a better position. CardioFocus is the same company it’s been for more than 16 years, he says, but what they need from a CMO has changed dramatically along the way. That’s very common, he says, particularly in the medical sector, where timelines and product lifecycles can span decades.
A good partner is one that looks beyond its immediate needs, as well as what fits at the moment. “It’s important to play chess, not checkers,” he notes. Smith advises companies to look at today’s needs as well as next year’s – and then 5 years down the road. “They’re almost for sure going to change over time.” It’s important for companies to think about that and pick partners who can accommodate them for their whole company life cycle, not just the particular problem they face in the moment.
What makes a good CMO?
Melsky says an outsourcing partner should have specific technical capabilities, but there’s more to it than that. “I get a call every day from somebody who’s seen our box, saying, ‘That looks like the kind of stuff we make.’ They say, ‘Hey, why don’t you consider us?’”
It was critical to Melsky to find a company that could cover development at a very early stage, from ideation for the new product all the way through to a manufactured product – and one that could actually do the manufacturing.
“Over the years, we’ve talked to different folks about being a supplier for us, doing things similar to what Minnetronix was doing.” Many of them, he said, had development capabilities and were willing to make a few units, but they weren’t able to do full manufacturing. Alternatively, others were highly capable in manufacturing but couldn’t cover the development side.
“Having somebody that was going to take it all the way through from the concept state into full production, that was very important for us,” Melsky explains, noting that a lot of issues occur at the hand-off from development into production.
“Another big thing for us is their response to problems that come up,” he adds. “They’ve always been very responsive when we’ve had a new issue that we’ve discovered. They’ve always been very responsive in trying to help us sort through what the problems are and giving us rapid proposals for addressing problems.”