As technology continues to advance all facets of healthcare, software has become an important part of products and is now integrated widely into digital platforms serving a range of purposes. Software as a medical device (SaMD) is one of three types of software related to medical devices. The other two types include software that is integral to a device, and software used in the manufacture or maintenance of a medical device. It is the former that is associated with the most uncertainty, as it’s a relatively new technology and has less clearly defined boundaries than the other types.

Use of SaMD is continuing to increase. It can be used across a broad range of platforms, including medical device platforms, commercial off-the-shelf platforms and virtual networks, to name a few. Such software was previously referred to by the industry, international regulators and healthcare providers as ‘stand-alone software’, ‘medical device software’ or ‘health software’, causing considerable confusion.

Due to the rapid evolution of devices based on this technology, the FDA has recently taken action to modernise its approach to regulation. It released a ‘digital health innovation action plan’, involving piloting a new digital health recertification programme to ensure that patients are able to have access to safe and effective devices as quickly as possible.

These changes by the FDA have been a long time coming, with the former 510(k) process having been in place since 1976. This was heavily based upon the concept of substantive equivalence, the idea of a new device being sufficiently similar to an existing one – a predicate device. If this could be supported by data, this provided manufacturers with a fast-track to market. “While that worked for a lot of medical devices, over the past few years, as innovations have been coming to market, especially around software and digital services, this has pushed the limits of what the original intent was,” explains Sundeep Karnik, a consultant at ZS.

The rule of three

The new regulations bring about three key changes for manufacturers. The first one relates to the selection of the predicate device. “You have to be much more careful when making your selection,” says Karnik. “If you choose a predicate device that was approved for particular patents, you cannot add on new features that are software and digital that are over and above what it originally had.”

The second aspect centres on the concept of ‘substantive’. “Before, you could get around this and say ‘look, my device is substantively equivalent to this device, just give it approval,’” says Karnik. “Now, you can’t simply introduce new software features that are unproven or untested.”

The third element of the new FDA regulations pertains to the data being used in support of a device. “The FDA wants more data than just that of the device performance that you could measure in some animal studies,” explains Karnik. “When there are new software features, these need to be tested in a different way, and the data presented to the FDA also has to be a different kind of data.”

Although these are significant changes, they don’t necessarily mean a longer time to market. “Part of the intent here is to actually make it faster by saying, ‘before you even come here, be careful about what predicates you choose, be strategic about what differences you’re going to try and argue, and be very intentional about what data you’re going to use to support this,’” says Karnick. “If you have thought about it carefully, done all that homework and brought the right information to the FDA, the process should, technically, go faster.”

“Companies will be forced to think more deeply about how either a physician or a patient lives with a particular device.”
Sundeep Karnik

These new regulations mean that manufacturers need to think differently about the products that they want to bring to market. “I think something the industry should think about now is whether they have products that they would have brought to market in the past because it was easier, even though they didn’t really bring much value to customers or the company because it was just the red version of the blue and green one that they already have,” says Matt Singer, also a consultant at ZS.

“The new regulations cause you to rethink some of that less innovative life-cycle management and focus more time on where you can actually differentiate or bring value.”
Matt Singer

“The new regulations cause you to rethink some of that less innovative life-cycle management and focus more time on where you can actually differentiate or bring value.”

This doesn’t automatically mean less revenue, however. “Maybe at the end of the day, it costs the company less money because it’s spread across fewer products than before and is instead focused on the ones that are really going to bring value to the marketplace,” says Singer.

The regulation has a number of implications, particularly for SaMD. “It legitimises that software has reached a majority, and that there is data that supports that it can, and should, be regarded as a medical device,” explains Karnick. “These kind of approvals from the FDA impact the physicians to perceive something approved by the FDA as being ‘real’ and something they need to take action on. It also gives the same message to patients who will be more trusting about using it because the government has looked at it.”

However, the perception of these changes is likely to be substantially different between companies. “If you’re a newer healthcare player, you might look at this and see it as a huge move forward for you, because now the solutions developed have a clearer and faster path to market,” says Singer. “If you are a classical med-tech company, and used to bringing new products to market that typically take three to five years or longer to develop, you might view this as the stakes having been raised a little bit.”

The new regulations also have important implications for patientcentricity, a concept gaining traction throughout the industry. “Most medtech companies have the product at the centre,” says Singer. “They’re very innovative; they have amazing engineers, and research and development departments, which can create incredible products that move medicine forward and make a substantial impact on the health of patients worldwide. The customer at the centre, whether that’s a patient, doctor or hospital, is more cuttingedge thinking, which these changes could accelerate.”

This means thinking in a more holistic way than has been necessary in the past. “Companies will be forced to think more deeply about how either a physician or a patient lives with a particular device,” says Karnick. “Digital and software-based solutions imply a fundamentally different engagement model, one which is integral to the effectiveness of the device.”

Time to get engaged

Historically, most devices have been relatively passive, and those that have been interactive have been limited in their scope. In contrast, newer technologies facilitate a much higher level of engagement with the patient. “If we take a more interactive device, let’s say you have a high-glucose problem, or diabetes, and you have a device that tells you when your blood glucose is high – you would pop a drop of blood on there, it would say your blood glucose was high and then it was up to you what you did with that information,” says Karnick. “But when you start to add software services, now that device is going to provide you with suggestions in real time on how to manage your health or glucose better.”

This influences the approach needed for the entire product development process. “In order for us to be able to provide those kind of suggestions and nudges to people, it means we have to think carefully about what patients need, how we articulate those needs, and create software and features that serve them and measure the impact to inform the value proposition of the device,” explains Karnick.

Although it has been over 40 years since the 510(k) pathway has been updated, it likely won’t be much longer. Being prepared for potential future changes is therefore key. “If you’re focused on solving important customer problems and demonstrating how you do that better than alternatives, you’re going to be a winner,” says Singer. “That is the sustainable advantage that you can have in any market.”

Central to remaining competitive is transitioning away from the traditional way of working towards a newer, more agile approach. “We have to move from the ‘build it and they’ll come’ model to becoming a lot more thoughtful and intentional about what you are going to build and why,” says Karnick. “Once we’ve decided, we then have to move a lot faster than we did in the past, because if we don’t, someone is going to bring it to the market faster – and we’ll be left behind.”

A new approach

The FDA’s Total Product Life-cycle (TPLC) approach enables the evaluation and monitoring of a software product from its pre-market development to post-market performance, along with continued demonstration of the organisation’s excellence.

Excellence appraisal

Identifying the objective criteria and methodology that the FDA will use to pre-certify a company and decide whether a company can keep its pre-certification status.

The FDA is currently basing the pilot programme’s criteria on five excellence principles: patient safety, product quality, clinical responsibility, cybersecurity responsibility and proactive culture. The FDA is currently considering two levels of precertification based on how a company meets the excellence principles and whether it has demonstrated a track record in delivering safe and effective software products.

Review determination

Developing a risk-based framework so that a pre-certified company can determine the pre-market review pathway for their products. Potentially pre-certified companies could market their lower-risk devices without FDA pre-market review, or only a streamlined pre-market review, based on the company’s pre-certification level and international medical device regulators forum (IMDRF) risk categorisation.

The FDA is planning to leverage the IMDRF framework to help determine the risk categorisation of an SaMD product, incorporating information about the medical purpose of the SaMD and the seriousness of the medical condition that the SaMD is intended to treat.

The FDA is also considering appropriate means to educate patients and providers about the pre-market review and post-market monitoring obligations for each SaMD risk category.

Streamlined review

This involves identifying the type of information that a pre-certified company would include in its pre-market submission for the FDA to review software products for safety and effectiveness before patients access them.

The FDA is exploring using an interactive streamlined review of a SaMD with information the agency has already gained from the process to pre-certify a company, and additional information the company would share about the SaMD’s product performance, clinical association between the SaMD output and a clinical condition, and safety measures.

Real-world performance

Identifying the type of information that a pre-certified company may have access to about how its software product is performing with patients to support the regulatory status of the product, and new and evolving product functions.

The FDA is considering how best to work with a company to collect and interpret real-world information about an SaMD, and evolve the product’s safety and effectiveness to address any emerging risks. The sources of real-world performance data may include information about a user’s experience, software performance data and clinical outcomes.

Source: FDA