Getting Approval: The FDA and Bringing New Devices to Market

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By Matt Skoufalos

The length of time it takes to bring a medical device to market in the United States has been a subject of scrutiny and criticism among various manufacturers and industry watchers for years.

“On the one hand, there are concerns over the seemingly slow pace of introduction of new devices and drugs to the U.S. medical market,” wrote researchers Kyle Fargen, et al., in “The FDA Approval Process for Medical Devices,” a 2013 study published in the Journal of Neurointerventional Surgery.

“Simultaneously, the FDA faces criticism for allowing drugs and devices to enter the market prematurely,” the authors wrote. “Ironically, the FDA is being criticized at both ends of the spectrum while remaining substantially under-funded for the difficult tasks that it must oversee.”

In 2013, Fargen, et al, argued that the amount of time it takes to develop new pharmaceutical products for approval by the U.S. Food and Drug Administration (FDA) may run on a 12-year timeline, while the development path for a medical device can run some five to nine years shorter than that, thanks to “separate fast-track routes of obtaining approval.”

Comparatively, in “Innovation under Regulatory Uncertainty: Evidence from Medical Technology,” a 2017 study published in the Journal of Economics, Harvard Business School professor Ariel Dora Stern discovered that being the first manufacturer to market in the medical device world can add an average delay of more than seven months and several million dollars to the FDA approval process over subsequent comparative entrants in that same category. Stern argued that clerical inefficiencies at the agency, not technological complexities, were to blame for putting technological pioneers at a disadvantage.

“Considering potential explanations, I find that approval times are largely unrelated to technological novelty, but are meaningfully reduced by the publication of objective regulatory guidelines,” she wrote. “Small firms are less likely to be pioneers in new device markets, a fact consistent with relatively higher costs of doing so for more financially constrained firms.”

The criticism of being both too tedious in its evaluation of new technologies and not critical enough in follow-up comparisons neatly illustrates the tensions of the balancing act that the FDA must negotiate in addressing issues of quality control and consumer safety. As the agency pivots to address these concerns while fulfilling its charge, device manufacturers and technology developers have responded to these conditions in various ways while working to bring products to market.

FDA classifies medical devices based on “the degree of control necessary” to ensure their safe and effective use: the greater the potential risk of its malfunction, the higher the risk classification of a device, and the more closely it is scrutinized. Class I devices include dental floss and band-aids; they are considered low-risk, according to the agency, accounting for 47 percent of all medical devices. Ninety-five percent of these are exempt from the regulatory process for reasons of being lowest risk. Such devices don’t require FDA review as long as they are “suitable for their intended use, adequately packaged and properly labeled,” registered and listed with the FDA, and manufactured under a quality control system, the agency notes. Another 43 percent of medical devices – things like condoms – are Class II devices, which require a greater degree of regulatory control, particularly at the manufacturing level, in order to offer maximum safety and effectiveness.

Class III medical devices, such as implantables, account for just 10 percent of all FDA-approved medical devices in the country, yet pose the greatest potential risk of patient harm, and therefore face the tightest regulatory oversight. Under section 510(k) of the U.S. Food, Drug and Cosmetic Act, any medical device manufacturer must notify the FDA and receive the approval of the agency prior to taking any such technology to market in the United States. Taking its name from the Act, that procedure is known as a 510(k) or premarket notification (PMN); through it, manufacturers must prove that their planned technology is as safe and effective – the standard is “substantially equivalent” – as another FDA-approved device. Products “that contain new materials or differ in design from products already on the market” must apply for pre-market approval (PMA), a much higher standard of review than the equivalency test of the 510(k) designation. PMA requires that manufacturers offer valid scientific evidence of the safety and effectiveness of their devices, including data from human clinical trials.

For manufacturers that prefer to launch their products in Europe, the CE Mark, which is the official stamp of approval from the unified regulatory bodies of the European Union, offers an alternative pathway to device approval. Like the U.S. Food, Drug, and Cosmetic Act, the EU Medical Device Directive (MDD) offers standards against which the safety and effectiveness of medical devices may be judged. The MDD rates devices according to five classes of risk; each product must meet technical and safety standards as well as a risk analysis. Under EU law, the CE Mark must be renewed annually, and for manufacturers that follow a full quality assurance pathway, the CE Mark is a self-certification, meaning that they must provide a Declaration of Conformity affirming that the product is manufactured to those specifications.

Tony Roder, Regulatory Affairs Executive for GE Healthcare, said that for manufacturers bringing medical devices to market in a global economy, there are always variations in regulatory approvals from one country to the next. In the 175 national markets in which GE competes, there are few standardized classification schemes aside from those shared by EU countries, he said. Aside from that, each process has its own timeline, which only increases with the severity of the potential for patient harm associated with increasing risk. The PMA process can take more than twice as long as the 90-day 510(k) timeline, whereas the CE mark process for a given technology can be completed within mere days depending upon the thoroughness of the technical documentation available.

“No matter how many markets you look at, we’re not going to get any globally harmonized risk classification of products,” Roder said. “There’s pathways to get things down-classified but it takes quite a long time, and it can be quite an arduous process to actually get that done.”

In the field of medical imaging, the majority of technologies currently on the market are “established, long-term-accepted, very mature technologies,” Roder said. Device-makers may offer iterative improvements upon them that don’t really reinvent the core elements of the technologies at work therein, but may open them to potentially new clinical applications. That means that the bulk of new products will follow the 510(k) pathway to market, which, for imaging devices “is probably one of the better ones around the globe,” he said. He believes that new EU medical device regulations issued this year are intended to more closely approximate the PMA approach to handling high-risk devices, which involves a greater deal of close collaboration with industry groups to overcome process and systems issues.

“There’s a lot of engagement with industry to proactively resolve issues that are problems for FDA and manufacturers, and alignment issues,” Roder said. “That has less of an impact on medical imaging technology than it does on other devices.”

However, FDA still “struggles a little bit from having to navigate historic or archaic systems,” he said, including mandatory physical copy filing requirements that nonetheless accompany much more comprehensive, fast, and portable electronic filings. Roder also believes that the agency will need to determine how it handles medical devices that inform courses of treatment through the use of big data and similar analytical models, if for no other reason than that’s where the field is headed.

“Where you’ll see a lot of focus in place is what to do with all this information,” he said. “How do you leverage the information that’s generated and gathered by a hospital network or a group of imaging systems? Are there different ways to look at AI? That’s going to drive a necessity to think about things potentially differently and how the regulatory schemes deal with that.”

Mukesh Kumar, CEO of FDAMap.com of Gaithersburg, Maryland, helps a variety of medical device manufacturers earn FDA approval or a CE Mark for products. He believes many of the next technological developments in medical imaging will come in the area of analytical software that provides secondary analysis of medical images. Mature modalities like X-ray, ultrasound, MRI and CT are not evolving as much or as quickly as the software algorithms that enhance or analyze the images they capture, Kumar said.

“When you think about the cutting-edge developments in imaging, most of it is in analysis software,” he said. “Almost all the imaging software is approved as a device.”

He pointed to FDA’s recently announced Digital Health Innovation Action Plan, an initiative that focuses on speeding the pathway to FDA approval for low-risk medical devices intended for education or general awareness – things like health apps, and smart watches, with which FDA doesn’t want to be involved particularly. But the agency document does cite a need to support the “new innovation and manufacturing processes” of new-to-the-market medical device manufacturers in the digital space. Its action plan outlines the benefits of “products that leverage connectivity” for continuous improvement and safety updates while noting that those benefits can be checked by “challenges of cybersecurity and interoperability.”

“Because they can impact the health of millions of Americans, the U.S. public should be able to trust that these products are high-quality and do what they are supposed to do,” the FDA document notes. “FDA recognizes that an efficient, risk-based approach to regulating digital health technology will foster innovation of digital health products. FDA’s traditional approach to moderate- and higher-risk hardware-based medical devices is not well suited for the faster iterative design, development, and type of validation used for software-based medical technologies. Traditional implementation of the premarket requirements may impede or delay patient access to critical evolutions of software technology, particularly those presenting a lower risk to patients. For the American people to see the full potential of digital health technologies, FDA must lean forward and adapt our processes.”

Under that approach, the 21st Century Cures Act is meant to remove FDA oversight from the process of regulating “certain software that supports administrative functions, encourages a healthy lifestyle, serves as electronic patient records, assists in displaying or storing data, or provides limited clinical decision support.” Kumar says he has several clients who are operating in this space, and who welcome the opportunity of getting their products into use as quickly as possible. When they’re not sure the best tack to take, he recommends that his clients have an exploratory meeting with the agency to discuss the best course of action.

“In general, the trend is to go and talk to FDA as many times as you can,” Kumar said. “I see a lot of companies going for an exploratory meeting than they would have five years ago. It’s always very hard to clean up somebody’s mess than to not make a mess in the first place.”

Even with a two- to three-month waiting period to schedule with FDA, the results of a meeting with the governing body can really help shape the development of a product and set it on the path to clearance, Kumar said. In 20 years working with the medical device industry, he said FDA processes “are pretty decent,” and a one-on-one meeting can reinforce their value to device-makers.

“From a company’s point of view, if you do your homework well, then you can play this game better and you can have a much easier process,” Kumar said. “FDA has no stake in this game. But you have to know the rules, and you have to play within the rules.”

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