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Software as a medical device (SaMD) has gained the attention of medical device regulatory bodies as the prospects of standalone software for use in diagnositic and therapeutic settings have increased. However, to date, figures related to SaMD have not been made available by regulators, which limits the understanding of how prevalent these devices are and what actions should be taken to regulate them.
The aim of this study is to empirically evaluate the market approvals and clearances related to SaMD and identify adverse incidents related to these devices.
Using databases managed by the US medical device regulator, the US Food and Drug Administration (FDA), we identified the counts of SaMD registered with the FDA since 2016 through the use of product codes, mapped the path SaMD takes toward classification, and recorded adverse events.
SaMD does not seem to be registered at a rate dissimilar to that of other medical devices; thus, adverse events for SaMD only comprise a small portion of the total reported number.
Although SaMD has been identified in the literature as an area of development, our analysis suggests that this growth has been modest. These devices are overwhelmingly classified as moderate to high risk, and they take a very particular path to that classification. The digital revolution in health care is less pronounced when evidence related to SaMD is considered. In general, the addition of SaMD to the medical device market seems to mimic that of other medical devices.
Appropriate application of new digital technologies for health care is dependent on ever-evolving ethical and regulatory frameworks [
In 2011, the FDA undertook a study to predict trends for medical devices for the next 10 years. The study involved technical managers from the FDA and 15 non-FDA participants with a range of backgrounds, including clinical, policy making, and technological [
Although it may be possible to use an arbitrary device within a clinical setting or to address a medical issue, not all such devices may be categorized as “medical devices” for the purposes of regulation. Section 201(h) of the Food, Drug, and Cosmetic Act [
any instrument, apparatus, implement, machine, appliance, implant, reagent for in vitro use, software, material or other similar or related article, intended by the manufacturer to be used alone or in combination, for human beings, for one or more [. . . ] specified medical purpose(s) . . .
The “specified medical purposes” covers a wide range of activities, including (1) the diagnosis, prevention, monitoring, treatment, or alleviation of disease or injury; (2) the investigation, replacement, modification, or support of the anatomy or of a physiological process; (3) supporting or sustaining life; (4) the control of conception; or (5) providing information by means of in vitro examination of specimens derived from the human body.
A registered medical device receives a classification according to the risk it poses to the individual. The device’s intended use and purpose provide an indication of the risk level and, thus, the classification. The FDA describes three risk levels that set the types of controls and assessments that need to be considered before the device can be placed on the market [
A generalization of the US Food and Drug Administration risk classifications for medical devices.
Class | Risk level | Controls |
Class I | Low to moderate | General controls |
Class II | Moderate to high | General controls and special controls |
Class III | High | General controls, special controls, premarket clearance |
The classification of a device also plays a role in determining its pathway to final approval as a medical device. Class I devices are exempt from premarket submission. All devices are subject to general controls, which include notification, basic safety measures, and registration requirements. Special controls are those that consist of more stringent risk management processes, such as mandatory reporting of adverse events. Class III devices also require these measures, as well as a premarket approval (PMA) application, due to their high-risk nature (eg, supporting or sustaining human life) or novelty. A PMA involves more rigorous testing of the product before it can be released to market.
The FDA uses a system of product codes to facilitate the classification of medical devices. A product code is a three-letter combination that designates the technological type of a device and its class. The Center for Devices and Radiological Health provides the names and attributes of each product code. The classification codes allow for rapid identification of the device type and the types of regulation that would apply, with the aim of making the path to market more efficient and rapid. The 510(k) is a submission made to the FDA to demonstrate that the device to be marketed is equivalent in safety and effectiveness to a legally marketed device, which is not subject to premarket approval.
A simplified model of the FDA classification pathways for new medical devices. The 510(k) is a submission made to the FDA to demonstrate that the device to be marketed is equivalent in safety and effectiveness to a legally marketed device, which is not subject to premarket approval. FDA: US Food and Drug Administration.
In 2013, there was regulatory recognition that standalone software may constitute a medical device, given the proliferation of developed systems. The software was previously classified according to an affiliated hardware device before the explicit inclusion of software in the regulations [
In this work, we used the Global Unique Device Identification Database (GUDID), which is maintained by the FDA and made freely available to the public [
To identify SaMD, we used the Global Medical Device Nomenclature (GMDN) terms [
We analyzed the data between February 2014 and August 2020, comprising 2,628,409 devices. A total of 32 product codes contain the term “software” in their name for these years. Devices that are software but were not assigned one of the relevant codes previously mentioned were not considered in this analysis. In this work, we used a Sankey diagram to explore and visualize the pathway to market approval. The diagram shows the transitions and relations within the data, allowing for a more immediate understanding of the relationship of the variables within the data.
Adverse events related to medical devices are recorded in the Manufacturer and User Facility Device Experience (MAUDE) database [
During the period from 2014 to 2020, 6193 devices were registered with “software” as a GMDN term. However, it is unclear from the GMDN whether the device is solely composed of software or merely incorporates it. To resolve this, we relied on product codes. Of the total devices registered with software product codes, 515 had only a single product code that was related to software. These devices were identified as SaMD.
Classification proportions for all the GUDID data for software (generally, as a subset by GMDN terms) and SaMD (defined as a subset by product codes).
Class type | Value, n (%) | |
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||
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Class I | 599,277 (22.8) |
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Class II | 1,968,678 (74.9) |
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Class III | 49,940 (1.9) |
|
||
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Class I | 793 (12.8) |
|
Class II | 5208 (84.1) |
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Class III | 155 (2.5) |
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Class I | 12 (2.3) |
|
Class II | 476 (92.4) |
|
Class III | 0 (0) |
aGUDID: Global Unique Device Identification Database.
bGMDN: Global Medical Device Nomenclature.
cSaMD: software as a medical device.
In
Index-generating electroencephalograph software (product code OLW [
The pathways to classification are shown in
The pathway to classification is shown for both SaMD and non-SaMD devices (
Registration of devices in the Global Unique Device Identification Database by yearly quarter. The vertical axis is on a logarithmic scale. GMDN: Global Medical Device Nomenclature; Q: quarter; SaMD: software as a medical device.
Frequency of software product codes set by the US Food and Drug Administration [
Pathways to classification for software as a medical device (n=515).
Submission type | Value, n (%) |
Premarket notification (510(k)) | 483 (93.8) |
Contact office of device evaluation | 22 (4.3) |
510(k) exempt | 5 (0.97) |
Paths to classification compared between SaMD (red) and non-SaMD (grey) devices. The data are shown in log scale to visualize the distinctions between the paths. The questions are given at the bottom of each column. SaMD: software as a medical device.
For the years from 2015 to 2019, there were 5.1 million reported adverse events in MAUDE for all devices (
Total adverse events for all medical devices reported in the Manufacturer and User Facility Device Experience database.
Adverse events for software as a medical device reported in the Manufacturer and User Facility Device Experience database.
This work represents a first empirical look at SaMD pathways to market and representation in adverse events based on publicly available data. These findings give a clearer understanding of the nature of SaMD within the regulatory environment. SaMD patterns for entry into market and in adverse events do not seem to deviate from those of medical devices in general. However, the number of new devices entering into the market and adverse events for both types of devices have been rising in the last few years. This rise, however, is rather modest, and it seems that regulations may be an (appropriate) barrier, as not all technologies developed are indeed safe or perform at a suitable level. The number of adverse incidents related to SaMD has also been rising, but at a faster rate than the number of devices. This could indicate that software enters the market earlier than it should, or it may simply identify a tendency toward better reporting of adverse events. This may also explain the higher percentage of adverse event reporting that was found for SaMD manufactures. However, the number of adverse events reported for SaMD is so small compared to the overall number of reported events that any interpretation needs to be carefully considered.
Almost all SaMD requires a 510(k) premarket notification, as demonstrated in Table 3. This indicates that the majority of SaMD is not an exempt product and that manufacturers often aim to enter the market by describing the similarity of their devices to other products that are already available. It has been suggested that although the 510(k) clearing process may offer expediency in bringing devices to market, this may impact the safety of the device. It remains a question for further investigation whether the 510(k) process has a negative impact on the safety of SaMD [
There is a noted anomalous spike in the third quarter of 2016 across the data. In that year, the United States passed the 21st Century Cures Act [
Several challenges still remain in developing SaMD. The modern software development pattern frequently uses a form of iterative cycles wherein problems (as well as needed features) are identified and developed within the cyclonic period. However, safety-critical software requires formal verification to determine that it performs as intended and that it can manage identified risks appropriately. Although there is strong evidence that formal verification methods more readily address regulatory compliance, the associated documentation, management, and training costs may not directly contribute to the delivery of customer value [
Overall, it seems that SaMD has not yet developed at a different rate from that of other medical devices. Although more research is needed to robustly explain the results reported here, this work does provide useful insight for considering the digital revolution in medicine and how it relates to the market reality.
US Food and Drug Administration
Global Medical Device Nomenclature
Global Unique Device Identification Database
International Medical Device Regulators Forum
Manufacturer and User Facility Device Experience
premarket approval
software as a medical device
None declared.