Published on May 5, 2021
The World Health Organization (WHO) reports that there are around 1.5 million medical devices globally, across more than 10,000 types. They range from simple medical equipment like stethoscopes to highly complex, expensive devices like MRI machines.
Over the last 40 years, the amount of software used both in and around medical devices has dramatically increased. The last 20 years in particular have seen an acceleration in this trend, thanks to the emergence of the “internet of things” (IoT) and its corresponding parts — smartphones, wireless connectivity, cheaper and better sensors, cloud computing, big data and AI — which are transforming how work gets done across almost every industry.
As these leading-edge technologies continue to cause a seismic shift in how healthcare is administered and delivered, software has become an increasingly prevalent and crucial component of highly sophisticated medical devices.
Medical device software comes in 4 primary subclasses:
- Software as a medical device (SaMD), which is standalone software that serves as a medical product in and of itself;
- Software in a medical device (SiMD). This is software that’s part of a medical product, such as implanted software in medical equipment;
- Software as an accessory to a medical device;
- General purpose software that is not a medical product by itself.
No matter its type, software is a game-changer in healthcare and is causing disruption to almost every aspect of the sector, including therapeutics, genomics, drug discovery & development, bioinformatics, robotics, point-of-care (POC) diagnostics, and even 3D printing.
SaMD has seen particularly fast growth in recent years. Because there is no hardware involved (or commercial hardware that is constantly evolving), there are fewer constraints to using fast feedback loops for improvement. One way to look at SaMD’s growth has been to monitor the rising use of Artificial Intelligence and Machine Learning (AI/ML) in medical devices. A 2020 article in Nature’s npj Digital Medicine identified 64 FDA-approved medical devices and algorithms that utilized AI/ML, and a 2021 article in The Lancet Digital Health identified 222 AI/ML medical devices approved in the USA and 240 devices in Europe.
SaMD brings new opportunities and new challenges for both device companies and for regulators, and is an area where new regulatory paradigms are being piloted to better enable innovation while ensuring patient safety and clinical effectiveness.
In this introductory article, we explore Software as a Medical Device. We cover its meaning, its benefits, who stands to benefit the most from using it (and why), and more.
Let’s get started.
What is Software as a Medical Device (SaMD)?
According to the FDA, SaMD is a class of software that is designed to carry out one or more medical functions. This includes software or mobile apps intended to treat, diagnose, cure, mitigate, or prevent disease or other conditions.
SaMD’s defining feature is that it performs these medical functions, without a need for actual hardware. It is typically used alongside non-medical computing platforms, which may be connected to virtual networks, traditional medical devices or other general-use hardware.
It’s important to remember that SaMD is not software that supports the functioning of medical device hardware (that’s SiMD). To determine if your software qualifies as SaMD, ask yourself these two questions:
- Question 1: Is my software a medical device? In other words, is there a medical benefit to its use, and is there patient risk if it malfunctions or is used incorrectly?
- Question 2: Can my software work independently from another device? While SaMD software can take data from another device, if your software supports the of a medical device, and that medical device does not work without your software, then your software is considered SiMD, not SaMD.
Let’s take, for example, a mobile app that acts as a remote control for a device. This is not SaMD. Because it serves as an accessory to the medical device, and is considered part of the medical device, it qualifies as SiMD instead.
Other examples to differentiate between SaMD and SiMD are:
- Software that helps radiologists and clinicians find and diagnose a cardiovascular condition by analyzing MRI scans is SaMD. However, the piece of software that turns the MRI magnets is SiMD. Similarly, the software that animates an X-ray control panel is SiMD.
- A mobile application that takes input from a blood glucose meter and patient food log to provide insulin dosage recommendations for diabetes is SaMD.
- A dedicated piece of software that monitors a mole for a given period of time to assess the risk of melanoma is SaMD.
- Software that analyzes a patient’s medical history and diagnostics data to determine the correct drug is SaMD.
- However, the software which gathers, retrieves or organizes the actual medical data is not SaMD or SiMD. For example, an Electronic Health Record (EHR) system is neither SaMD and nor SiMD. (The FDA’s approach to the classification and regulation of EHR software – is a topic for a different white paper or blog post.)
While it won’t be replacing doctors anytime soon, SaMD nevertheless represents an increasingly critical tool to better treat patients. By helping with aspects of care that can be automated using the latest technology, SaMD can help accelerate the discovery, management, and treatment of a variety of medical conditions.
SaMD’s defining characteristics include:
- Improved health outcomes powered by data: As we’ll see shortly, SaMD can amplify the effectiveness of medical devices and existing treatment plans, as it enables easy and fast collection of high-quality data — which leads to better health outcomes.
- Faster production and feedback to drive faster innovation: SaMD enhances and builds on existing medical device functionality through software solutions that are faster, and often cheaper, to update than hardware. It also utilizes the latest technologies to integrate and share health data across various platforms, including the cloud, connected medical devices, smartphones, and more.
Because SaMD can collect large amounts of data quickly, it can also easily solicit user feedback through its availability on, for example, mobile devices. For companies using or developing SaMD, this fast feedback loop can enable quicker product iterations, shorten time to market, and drive faster innovation.
SaMD in Action
But what can Software as a Medical Device actually do?
Before we dive deeper, it’s important to remember that SaMD is a category of software, not an actual “thing.” When we speak of SaMD, we’re referring to the group of medical device software products that meet SaMD functionality requirements.
SaMD products “piggyback” on top of other connected technologies, while leveraging their benefits.
These technologies can include smaller, cheaper, more sophisticated sensors; connectivity such as LTE, Wi-Fi, and Bluetooth that make it easier, faster, and more reliable to access the internet or call someone; increasingly powerful mobile devices such as smartphones and tablets which act as a supercomputer in the palm of one’s hand; and cloud services that enable distributed processing and data storage without the need for physical storage space at one’s home or business.
The more data you can collect — from devices, from sensors, from smartphones, from user feedback or activity, from external conditions (including weather, pollution data, and information on events from other people based on their location, such as asthma attacks) — the more this data can be applied towards sophisticated algorithms that help deliver better care.
What’s more, SaMD not only collects critical data, it can get that data anywhere, combine it with other data, analyze it, and then use that data, either automatically, or by presenting it to users to take action.
This data mobility enables SaMD to deliver more precise treatment options, especially when combined with cutting-edge technologies like AI and powerful big data tools, to glean unique clinical insights.
State-of-the-art SaMD platforms can enhance the delivery and administration of care, reduce costs, and improve health outcomes.
This includes applications across:
1) Screening and diagnosis: By leveraging complex algorithms, software programs can accurately predict the risk of chronic disease and aid in treatment decisions.
SaMD can help deliver personalized treatment plans, as well as reduce the time from diagnosis to treatment for patients with more complex diseases.
Lung cancer, for example, is extremely hard to detect, and most lung cancers are at an advanced stage when they are discovered. SaMD devices can use smart algorithms capable of detecting anomalies that would otherwise go unnoticed such as blood vessel problems or pleural disorders, thus increasing the survival rates among these patients.
Provider/ clinician benefit:
By tapping into insights from SaMD, clinicians can gain a more holistic picture of a patient’s medical condition, history and real-time status, allowing them to make better, more precise diagnosis and treatment recommendations.
Similar to an MRI scanner, Genetesis’ biomagnetic imaging device, can evaluate the electromagnetic activity in the body at a deeper level. Its SaMD leverages the power of machine learning to extract a plethora of features from collected data. This allows radiologists to discover anomalies missed by other diagnostics tools like an electrocardiogram.
2) Monitoring and alerting: SaMD systems can be designed to use wearable sensors to collect multiple vital signs which can then be tracked using software. The software monitors and uses this data to enable targeted recommendations & alerts for both patients and clinicians.
SaMD can help patients better monitor their condition by identifying triggers and providing real-time recommendations on everything from drug dosages to physical activity to environmental conditions. It can also help improve overall patient adherence to treatment, and as a result, clinical outcomes.
Provider/ clinician benefit:
SaMD systems allow for ambulatory patient monitoring. They can collect and process data from wearable sensors
and detect subtle deviations that might flag important health issues. Using this information, physicians can refine their treatment decisions.
Propeller Health, a digital therapeutics company, works to treat respiratory disorders such as asthma and chronic obstructive pulmonary (COPD) using hardware and software-enabled by Bluetooth technology.
The company’s small sensors easily attach to a patient’s inhaler to track triggers and symptoms. The inhaler, which is wired with a Bluetooth transmitter, “talks” to the patient’s smartphone and can send personalized feedback, updates and data to both patients and physicians. Doctors can view this data and see, not only how frequently the patient suffers attacks, but also tease apart the environmental factors that caused the distress.
3) Chronic condition and disease management: SaMD allows both patients and clinicians to track and interpret health data, and adjust treatment plans to be more effective.
Connected care systems promote greater patient ownership of treatment decisions. Thanks to SaMD, patients can monitor their health activity or status in real time and seek medical help if needed.
Provider/ clinician benefit:
SaMD tools assist physicians in designing personalized treatment plans for patients with chronic diseases based on data collected by the software, such as blood glucose or cardiac enzyme levels.
Eli Lilly’s Go Dose is a diabetes management mobile app for users of Humalog, an insulin developed by the company. It can be used in the home and in a clinical environment to “aid in the review, analysis, and evaluation of historical blood glucose test values to support type 2 diabetes mellitus management.” Among its features, it provides dosage recommendations for meals based on a patient’s blood glucose levels, to help patients and physicians better manage their disease.
4) Digital therapeutics
SaMD also plays a vital role in the treatment or mitigation of critical illnesses thanks to its ability to generate — and feed — highly-relevant clinical data into “other medical devices, medicinal products, general purpose actuators or other means of providing therapy to a human body.”
SaMD is often used as an aid in the treatment of chronic conditions or diseases. Take sleep apnea, for instance. According to the IMDRF, SaMD can “use the microphone of a smart device to detect interrupted breathing during sleep and sounds a tone to rouse the sleeper” to prevent potentially serious effects.
Provider/ clinician benefit:
SaMD can also enable clinicians to provide cutting-edge treatment to patients with complex diseases such as cancer. For example, SaMD can act as an aid in a radiation treatment planning system by gathering data from a patient and “providing specific parameters that are tailored for a particular tumor and patient” to clinicians using a radiation medical device as part of treatment.
Pear Therapeutics develops software-based therapies for patients suffering from severe psychiatric and neurologic conditions.
Rather than swallowing a pill or taking an injection, patients with substance disorders are treated with software. The company’s lead product, reSET, delivers cognitive behavioral therapy to help patients abstain from using alcohol or drugs during treatment.
What’s more, reSET comes with a dashboard, where clinicians can look at their patients’ substance use, cravings, triggers, or drug screen results to provide more effective treatment options.
SaMD: An Evolution in Regulatory Oversight
The increasing importance of software, the increasing complexity of systems, and the increasing speed of innovation are not unique to SaMD — it is part of a larger trend: more software, more connectivity, more interdependence, and more data are shaping many medical device areas.
Nearly a decade ago, the Food & Drug Administration (FDA) recognized that their old paradigm of evaluating medical products wouldn’t suffice in a market of increasingly fast-paced innovation. Since then, they’ve been working to create a regulatory framework for medical devices and medical device software that prioritizes both patient safety and healthcare innovation.
We’ll explore the FDA’s initiatives in greater detail in an upcoming article. For now, important steps taken by the FDA include:
- 2011’s Case for Quality program, where the FDA began working with healthcare stakeholders to “identify device manufacturers that consistently produced high-quality devices ” in order to promote device manufacturing best practices.
- 2017’s Software Precertification Program, which expands on the Case for Quality program and applies it to medical device software, including SaMD, while emphasizing patient safety and innovation.
- The Digital Health Innovation Action Plan(2017), which aims to improve the federal agency’s digital health review process to provide timely access to safe and effective medical technologies.
- The alignment of U.S. medical device regulations from FDA 21 CFR Part 820 to ISO 13485:2016, a standard recognized by much of the rest of the world in the medical device market, and which emphasizes the FDA’s focus on risk management (2018).
- 2018’s reorganization of the FDA’s pre-market and post-market review process to address total product life cycle (TPLC) and “help facilitate information sharing to allow for more informed decisions, ensure process and policy consistency, and provide more straightforward and streamlined interactions.”
The FDA Software Precertification Program: A closer look
Due to the tremendous potential of software (and in particular, SaMD) to increase both the quality and effectiveness of care, as well as the growth of general computing platforms and connectivity, the FDA developed its Software Precertification Program.
The program helps address the following:
- How to apply the faster, more iterative design method used in software development towards SaMD;
- How to capture health data both inside and outside a hospital setting to enable problems to be addressed quicker;
- How to improve product performance on a much faster timescale;
- The creation of an agile regulatory model that supports the faster innovation rate of software-based products, while still ensuring high standards of safety and efficacy.
The Precertification Program, which is meant to serve as a test for eventual large scale adoption, has several important benefits, including:
- The expansion of the FDA’s Digital Health Unit;
- Greater clarity on the scope of oversight and approach to digital technology;
- The development of a more efficient, risk-based regulatory framework for overseeing digital health technologies;
- More post-market collection of real-world data;
- Enables faster patient access to technologies.
The Precertification (Pre-Cert) Pilot Program
In 2017, the FDA selected nine companies to participate in its Pre-Cert Pilot Program.
The chosen companies include some of the biggest players in tech (Apple, Google, Samsung and FitBit); traditional large, multiline medical device firms (Johnson & Johnson); digital therapeutic companies (Pear Therapeutics), and not-for-profit startups such as Tidepool, which develops free software for the diabetes community, among others.
The FDA bases the criteria for their pre-cert approval on five excellence principles, which are essential for success not only in the medical space, but beyond. Because the same dynamics apply for Software in a Medical Device (SiMD) as they do for SaMD, companies in healthcare and related industries should generally be familiar with the pre-cert standards, as this working model provides a good roadmap for competing in the market.
What the Industry is Saying
The FDA’s move to regulate medical software has been enthusiastically received by digital health software developers and providers, and the pre-cert working model was a hot topic at the recent Digital Health & Medtech showcase in San Francisco.
Dave Amor, Vice President of Quality and Regulatory Affairs at Pear Therapeutics voiced support for the collaborative nature of the agency’s pre-cert pilot program.
While the panelists commended the FDA for its collaborative regulatory approach, they also pointed out stumbling blocks that the regulatory framework might face.
Perhaps the most apparent challenge, according to the panelists, is the potential gap between the FDA employees actually doing the reviews of SaMD requests and the long-term strategy of the agency. It was suggested that employees undergo rigorous training and education to ensure smooth implementation of the regulations.
Bottom line: The FDA recognizes the need to adapt to a changing technological landscape. Through its Software Precertification Program, the shift towards a TPLC focus and more, the FDA has begun laying the groundwork to promote faster innovation, without losing its stringent focus on patient safety.
The Fundamental Challenges of SaMD
As described earlier, two of SaMD’s defining characters are 1) its ability to improve health outcomes using data; and 2) using fast feedback loops to drive faster product iteration and ultimately, faster innovation.
While this will undoubtedly move the industry forward, it underlies the fundamental challenge many builders of SaMD face: How do you integrate modern product development methodology that is designed for a fast-changing, ever-evolving “internet of everything” world with patient safety, clinical efficacy and regulatory compliance?
Companies that can do this successfully will reap the rewards; those that cannot will be left behind.
Developers of SaMD should be asking themselves how they can get faster, cheaper feedback loops while also ensuring patient safety and product innovation.
This is challenging but doable.
We’ll explore best practices that can be applied to SaMD in greater detail in upcoming articles and eBook.
Rigorous agile development methodologies with integrated verification, test automation, better real-world data collection, lean UX and human factors, agile risk management, and documentation automation are all techniques that can be integrated as part of a total product lifecycle (TPLC) approach.
There are other areas in the early stages of being addressed that will enable faster feedback, including:
- Risk-based software segregation to determine where you can iterate freely and where you need Institutional Review Board (IRB) oversight;
- Continuous IRBs for faster feedback on higher risk areas;
- Faster, more frequent formative human factors, both during development and in-market, coupled with real-world performance analytics;
- Faster, cheaper, and more effective clinical validation.
The good news, as we have seen, is that the FDA is open to these things, and even encouraging them. The Pre-cert Program, the Case for Quality and an increased focus on total product lifecycle all demonstrate this.
Remember, for the FDA, the fundamental challenge they face is how to ensure patient safety and clinical effectiveness WHILE enabling faster innovation.
The Proposed Organizational Elements to Demonstrate Excellence Principles and the Real-World Performance Analytics for Product Monitoring in the Working Model for Software Precertification are an excellent guide for developers to work against; ask yourself how you might address them.
It’s also important to remember that there is no “one size fits all” approach. Some approaches may be better suited to nimble startups, while others are better suited to global MedTech giants.
For larger companies, starting with pilot programs to implement best practices, as well as fast feedback loops throughout the product life cycle, may be the best approach. In some cases, this may involve changes to your quality management system (QMS). If you already have a loose coupling within your QMS (leaving methodology decisions at the product level), you are likely in a better shape to get started.
Why You Should Care
If you’re a company operating in a medical space that may cross over into areas regulated by the FDA, but are intentionally staying outside of regulated medical devices, you should pay careful attention.
While there are pros and cons to such a strategy, some of your competitors will pursue getting FDA clearance for their medical device.
They will be able to make medical claims that you cannot and use this to their advantage to market to the healthcare ecosystem in a way that you won’t be able to. They will also get reimbursement much more easily, and be highly valued by the market (including any potential acquirers).
As a result, many companies are taking a Minimum Viable Product (MVP) approach: trying to get over the FDA clearance threshold but with as minimal effort as possible.
Medical Device Companies with no SaMD
If you develop SiMD (software in a medical device), but not SaMD, all of the same pressures and dynamics of the internet of everything apply: more connectivity, more software, more change, more complex systems. Not just for you, but for the FDA as well.
The reason the Precertification Pilot Program is for SaMD only is to simply get it off the ground — not to limit its learnings and approach.
As you can see from the other related activities ( the transition to ISO 13485:2016, OPEQ, Case for Quality), the expectation is that these learnings and improvements, along with a different regulatory paradigm, will move through the system.
If you’re not building skills and processes around this, you will have a hard time adapting. Moreover, you may well end up with SaMD companion software to your devices, either developed by you or by someone else.
And companies that traditionally operate without software (say pharmaceutical companies, or “dumb” device makers of hip or shoulder implants), are not immune to the increase in value that software creates, either.
Why? Because as soon as you put a sensor on these devices, they become a “smart” device (for an example of this, see the FDA’s workshop on Orthopaedic Sensing, Measuring, and Advanced Reporting Technology (SMART) Devices .
If you’re a pharmaceutical company, the same pressures to demonstrate real-world performance, to improve adherence, and to have precision therapies will eventually affect you, just as they are currently affecting medical device companies.
That will eventually mean being judged and compensated based on real-world performance of your therapies, rather than on purely clinical trial outcomes. At the same time, there is the growing area of SaMD called digital therapeutics — digitally administered therapies that are FDA cleared — with outcomes in clinical trials that are as good as or better than drugs treating the same conditions.
Some of these digital therapeutics can also work in combination with drugs to provide even better outcomes than the individual drug or digital therapeutic; and because they are also designed to collect data while interacting with the patient, they will make it much easier and cost-effective to monitor performance and influence adherence.
The “internet of everything” will continue to expand and have a greater effect on all areas of society, including the medical device industry. While Software as a Medical Device is the niche where this is evolving fastest, the effect is accelerating across connected devices and starting to impact areas like pharma as well.
The FDA recognizes the great innovation potential of software, as well as the regulatory challenges, and through its various initiatives, is beginning to address this.
The future of software-based medical devices is exciting for not only patients and clinicians, but society at large. As we look ahead, some of the technology that brings the most value (in healthcare and other industries) will not necessarily be new devices, but the companion software that assembles critical data, analyzes it, and then shares it with relevant parties.
Both Software as a Medical Device (SaMD) and Software in a Medical Device (SiMD), are exactly this type of value-driving innovation.
And while not all companies will decide to develop SaMD, it’s in everyone’s best interest to understand its best practices in order to create better and safer products.
Ultimately, companies face a choice. They can ignore the effects of the “internet of everything” and get disrupted, acquire companies with who already have this expertise, or engage with and build this capacity internally by working with experts in the area.
Whatever your choice, the time to act is now.
Orthogonal integrates modern agile product development best practices with patient safety and regulatory compliance to build SaMD and connected medical device systems. If you need help building your next SaMD, or to learn more, contact us or call us at (312) 372-1058.