FDA Software as a Medical Device (SaMD) Guide

The rapid integration of technology into healthcare has opened the doors to groundbreaking innovations, with Software as a Medical Device (SaMD) at the forefront. SaMD stands apart from traditional hardware-based medical devices, offering software-driven capabilities that diagnose, treat, or monitor medical conditions independently of dedicated hardware.

In this blog, we’ll explore every aspect of SaMD, from its technical underpinnings to its regulatory landscape, development lifecycle, and the transformative impact it’s having on the medical industry. Whether you're a developer, healthcare provider, or investor, understanding SaMD is critical in today’s technology-driven healthcare landscape.

What Defines Software as a Medical Device (SaMD)?

The International Medical Device Regulators Forum (IMDRF) defines Software as a Medical Device (SaMD) as "software intended to be used for one or more medical purposes that perform these purposes without being part of a hardware medical device."

SaMD is any standalone software used for medical purposes that does not require dedicated medical hardware to operate. Its flexibility and wide application range set it apart from embedded software typically tied to hardware devices. 

The IMDRF’s "Software as a Medical Device": Framework for Risk Categorization and Key Considerations also adds the following to the SaMD definition:

• SaMD includes in-vitro diagnostic (IVD) medical devices.
• SaMD is capable of running on general purpose (non-medical purpose) computing platforms. 
• “without being part of” means software not necessary for a hardware medical device to achieve its intended medical purpose. 
• Software does not meet the definition of SaMD if its intended purpose is to drive a hardware medical device. 
• SaMD may be used in combination (e.g., as a module) with other products including medical devices. 
• SaMD may be interfaced with other medical devices, including hardware medical devices and other SaMD software, as well as general purpose software. 
• Mobile apps that meet the definition above are considered SaMD.

Characteristics of SaMD

1. Intended Medical Purpose: SaMD is designed to serve a specific medical function, such as diagnosis, monitoring, or therapy support.
2. Independence from Hardware: Unlike embedded software, SaMD operates on general-purpose hardware like computers, smartphones, or cloud servers.
3. High Data Dependency: SaMD often relies on real-time data collection, processing, and interpretation to provide actionable medical insights.

What Products Classify as SaMD?

Software as a Medical Device (SaMD) refers to software designed to perform one or more medical functions without being part of a physical medical device. Below, we outline what products classify as SaMD, helping you understand this important category in the healthcare and regulatory landscape.

Examples of SaMD Products

Here are common examples of products that classify as SaMD:

1. Diagnostic Software
   
   • Applications that analyze medical images (e.g., X-rays, CT scans) to detect abnormalities.
   • Software used for pathology or lab results interpretation.
2. Monitoring Software
   
   • Mobile apps that monitor heart conditions using data from wearable devices.
   • Cloud-based platforms that track glucose levels for diabetic patients.
3. Therapeutic Software
   
   • Programs that guide physical therapy exercises based on patient-specific data.
   • Cognitive behavioral therapy (CBT) apps for mental health conditions like anxiety or depression.
4. Disease Risk Prediction Tools
   
   • Software that assesses genetic data to predict the likelihood of developing a particular disease.
   • Applications that evaluate lifestyle factors and provide preventive health recommendations.
5. Clinical Decision Support Systems (CDSS)
   
   • Software that helps healthcare providers make decisions by offering diagnostic or treatment recommendations.
6. Software for Remote Patient Management
   
   • Tools that enable remote monitoring and management of chronic conditions, such as hypertension or asthma.

What Does NOT Classify as SaMD?

Not all medical-related software qualifies as SaMD. Here are some examples of what does not classify as SaMD:

• Software that controls a hardware medical device (e.g., software embedded in a CT scanner).
• General-purpose wellness apps without diagnostic or treatment functions.
• Electronic health records (EHR) or software used solely for administrative purposes.

Differences between SaMD and SiMD

In the realm of medical software, Software as a Medical Device (SaMD) and Software in a Medical Device (SiMD) are two distinct classifications. While both play critical roles in healthcare, they differ in purpose, functionality, and regulatory requirements. Understanding the differences between SaMD and SiMD is essential for developers, regulators, and healthcare providers navigating the evolving medical technology landscape.

Software as a Medical Device (SaMD) refers to standalone software designed to perform medical functions independently of any physical medical device. It operates on general-purpose platforms such as smartphones, computers, or in the cloud. On the other hand, Software in a Medical Device (SiMD) is software that is embedded within and operates as an integral part of a physical medical device. It cannot function independently and is designed to work specifically with the hardware it controls or supports.

The chart below illustrates the difference between SaMD and SiMD: 

Applications of SaMD in Healthcare

SaMD is reshaping the healthcare landscape, addressing unmet clinical needs across various domains.

SaMD Diagnostic Support

SaMD uses advanced algorithms to analyze medical data, such as imaging or test results, enabling faster and more accurate diagnoses. For example:

• Radiology: AI-powered imaging software detects abnormalities in X-rays, MRIs, or CT scans.
• Genomics: SaMD helps identify genetic markers for hereditary conditions or personalized medicine.

SaMD Monitoring and Management

Patients with chronic conditions benefit significantly from SaMD applications that provide continuous monitoring. Examples include:

• Diabetes Management: Apps track blood glucose levels, recommend insulin doses, and notify caregivers of irregularities.
• Cardiac Monitoring: Wearable devices with SaMD functionality monitor heart rhythms and detect arrhythmias.

SaMD Treatment Planning and Support

Clinicians rely on SaMD for personalized treatment recommendations. Examples include:

• Cancer Treatment: Software creates tailored chemotherapy plans based on a patient’s specific tumor profile.
• Mental Health: Apps offer cognitive behavioral therapy (CBT) techniques and monitor mental health progress.

Core Technologies Driving SaMD

Several advanced technologies underpin SaMD, enabling its transformative impact.

1. SaMD and Artificial Intelligence and Machine Learning (AI/ML)

AI and ML are integral to SaMD, allowing software to learn from data and improve its performance over time. Examples include:

• Image Recognition: AI algorithms identify patterns in medical images, aiding in early detection of diseases like cancer.
• Predictive Analytics: ML models forecast disease progression or treatment outcomes based on historical data.

2. SaMD Cloud Computing

Cloud platforms enable SaMD to process vast amounts of data securely and efficiently. Benefits include:

• Scalability: Rapidly increase computing resources as data demands grow.
• Collaboration: Share data seamlessly across healthcare providers for coordinated care.

3. SaMD and Internet of Medical Things (IoMT)

IoMT devices, such as wearable monitors and connected medical equipment, provide the data streams that SaMD requires for real-time functionality.

4. SaMD and Data Analytics

SaMD relies on advanced data analytics techniques to extract actionable insights from raw medical data. Key capabilities include:

• Trend Analysis: Monitoring patient data trends over time.
• Risk Prediction: Identifying patients at high risk of adverse events.

Regulatory Framework for SaMD

The International Medical Device Regulators Forum (IMDRF) has provided a globally recognized definition and framework for SaMD. Key principles include:

• Risk-Based Classification: SaMD is classified based on its intended use and the severity of potential harm if it malfunctions.
• Lifecycle Management: Continuous monitoring and updates are required to ensure patient safety.

U.S. FDA Guidelines regarding SaMD 

The U.S. Food and Drug Administration (FDA) provides comprehensive guidelines for the regulation and oversight of Software as a Medical Device (SaMD). These guidelines are rooted in global standards, such as those set by the International Medical Device Regulators Forum (IMDRF), and are tailored to the unique challenges and opportunities presented by SaMD.

1. Definition and Scope
   
   • The FDA defines SaMD as software intended to be used for one or more medical purposes, operating independently of a physical medical device. This includes mobile apps, cloud-based platforms, and other standalone software systems with medical applications.
2. Risk-Based Classification
   
   • The FDA references the IMDRF’s possible risk categorization framework as one method for identifying risk categories of SaMD based on how the output of a SaMD is used for healthcare decisions in different healthcare situations. 
   • The framework categorizes SaMD based on its intended use and the level of risk associated with its function. The framework has four categories (I, II, III, and IV) based on the levels of impact on the patient or public health. Level I is SaMD with the lowest impact on the patient or public health and Level IV is the highest impact.
3. Premarket Submissions
   
   • The FDA requires premarket submissions for SaMD products with higher risk categories, including 510(k) clearance, De Novo classification, or premarket approval (PMA), depending on the software's intended use and risk profile.
4. Quality Management Systems (QMS)
   
   • Developers of SaMD must follow QMS principles, ensuring the software is designed, developed, and maintained under rigorous quality controls.
   • Compliance with FDA's 21 CFR Part 820 (Quality System Regulation) or ISO 13485:2016 is typically required.
5. Cybersecurity and Data Privacy
   
   • SaMD products must incorporate robust cybersecurity measures to protect patient data and system functionality.
   • The FDA emphasizes the need for secure software design, vulnerability assessments, and post-market monitoring of potential threats.
6. Post-Market Surveillance
   
   • The FDA requires SaMD developers to implement systems for ongoing monitoring of software performance, adverse events, and user feedback after product deployment.
   • Developers are expected to provide software updates and patches to address identified risks and maintain regulatory compliance.
7. Guidance for Mobile Medical Apps
   
   • The FDA has specific guidelines for mobile medical applications that qualify as SaMD, distinguishing them from general wellness apps and ensuring appropriate regulation.

Notable FDA Guidance Documents for SaMD

• "Software as a Medical Device (SaMD): Clinical Evaluation"
  
  • Provides recommendations on how to assess the clinical performance of SaMD.
• "Content of Premarket Submissions for Software Contained in Medical Devices"
  
  • Offers detailed instructions for the information required in premarket submissions for SaMD.
• "Postmarket Management of Cybersecurity in Medical Devices"
  
  • Focuses on cybersecurity measures and post-market considerations for medical software, including SaMD.

European Union MDR and SaMD

The European Union Medical Device Regulation (EU MDR) governs the classification, development, and regulation of Software as a Medical Device (SaMD) in the EU. As a comprehensive regulatory framework, the EU MDR emphasizes patient safety, transparency, and quality assurance for all medical devices, including standalone software.

Key Points of EU MDR Regarding SaMD

1. Definition of SaMD Under EU MDR
   
   • SaMD is classified as software with a medical purpose that operates independently of hardware medical devices. This includes diagnostic, monitoring, and therapeutic software running on general-purpose devices like computers, tablets, or smartphones.
2. Classification Based on Risk
   
   • SaMD is classified under the MDR using a risk-based approach, aligning with the potential impact on patient health and safety.
   • The classification follows the MDR’s Annex VIII rules:
     
     • Class I: Low-risk software, such as apps for general health tracking.
     • Class IIa: Medium-risk software that supports decision-making for non-critical conditions.
     • Class IIb: Higher-risk software, such as diagnostic tools with potential to influence significant treatment decisions.
     • Class III: High-risk software used in critical or life-threatening situations, such as applications for surgical planning or cancer treatment.
3. Conformity Assessment
   
   • SaMD developers must conduct a conformity assessment to ensure compliance with the MDR’s essential safety and performance requirements.
   • For Class IIa, IIb, and III SaMD, this process typically involves a Notified Body, which reviews the technical documentation and certifies compliance.
4. Clinical Evaluation Requirements
   
   • SaMD under MDR must undergo a clinical evaluation to demonstrate its safety, performance, and efficacy.
   • This includes a detailed analysis of clinical data, usability testing, and validation studies.
5. General Safety and Performance Requirements (GSPR)
   
   • SaMD products must comply with the GSPR outlined in Annex I of the MDR. This includes:
     
     • Data accuracy, reliability, and precision.
     • Risk management throughout the product lifecycle.
     • Cybersecurity and protection against unauthorized access.
6. Post-Market Surveillance and Vigilance
   
   • Under the MDR, SaMD manufacturers are required to implement post-market surveillance (PMS) systems.
   • Developers must continuously monitor software performance, address adverse events, and provide updates to ensure ongoing compliance and safety.
   • Serious incidents must be reported to the appropriate regulatory authority within strict timeframes.
7. Unique Device Identification (UDI)
   
   • SaMD products must include a Unique Device Identification (UDI) to ensure traceability and facilitate market surveillance.
8. Key Changes from the Previous MDD
   
   • The EU MDR introduced stricter requirements for software compared to the previous Medical Device Directive (MDD), including broader definitions and enhanced emphasis on clinical evaluation and risk management.

ISO Standards and SaMD

Software as a Medical Device (SaMD) operates in a highly regulated environment where compliance with international standards is critical to ensure safety, quality, and reliability. The International Organization for Standardization (ISO) provides a framework of standards that guide the design, development, and maintenance of SaMD products. These standards are essential for global regulatory approval and market access.

Key ISO Standards Relevant to SaMD

1. ISO 13485:2016 – Quality Management Systems for Medical Devices
   
   • ISO 13485 is the cornerstone standard for quality management in medical devices, including SaMD.
   • It outlines requirements for establishing a Quality Management System (QMS) to ensure the consistent design, development, and delivery of safe and effective SaMD.
   • Key elements include:
     
     • Risk management integration.
     • Documentation of processes and procedures.
     • Continuous improvement mechanisms.
2. ISO 14971:2019 – Application of Risk Management to Medical Devices
   
   • This standard provides a framework for risk management in medical devices, including SaMD.
   • It focuses on identifying, analyzing, and mitigating risks throughout the SaMD lifecycle.
   • Developers must document how risks are assessed and controlled to ensure patient safety.
3. ISO 62304:2006/Amd 1:2015 – Medical Device Software Lifecycle Processes
   
   • ISO 62304 specifies requirements for the entire lifecycle of SaMD, from development and testing to maintenance and updates.
   • It emphasizes software safety classification based on risk, with specific guidelines for each classification level.
   • Key stages include:
     
     • Software development planning.
     • Verification and validation processes.
     • Post-market surveillance for updates and patches.
4. ISO/IEC 27001 – Information Security Management
   
   • As SaMD often processes sensitive patient data, ISO 27001 is crucial for implementing robust cybersecurity and data protection measures.
   • It ensures confidentiality, integrity, and availability of data, reducing the risk of breaches and unauthorized access.
5. ISO 62366-1:2015 – Application of Usability Engineering to Medical Devices
   
   • This standard addresses usability engineering for medical devices, ensuring SaMD is intuitive and reduces user error.
   • It focuses on designing user interfaces that meet clinical needs and support safe operation.
6. ISO/TR 80002-1:2009 – Risk Management for Medical Device Software
   
   • A supplementary standard to ISO 14971, it provides specific guidance on applying risk management principles to software development.
   • It helps SaMD developers identify software-specific risks, such as coding errors or cybersecurity vulnerabilities.

Why ISO Standards Are Essential for SaMD

Global Regulatory Compliance

• Many regulatory bodies, including the FDA and EU MDR, require compliance with ISO standards as part of their approval processes.
• Adhering to ISO standards facilitates market access in multiple regions.

Ensuring Safety and Quality

• ISO standards establish best practices for managing risks, ensuring usability, and maintaining high-quality products throughout the SaMD lifecycle.

Streamlining Development Processes

• Following ISO frameworks reduces development inefficiencies, enhances collaboration, and supports innovation while meeting compliance requirements.

Building Trust with Stakeholders

• ISO compliance demonstrates a commitment to safety, quality, and reliability, building trust with regulators, healthcare providers, and patients.

Integrating ISO Standards in SaMD Development

1. Quality Management System Implementation (ISO 13485)
   
   • Start with a robust QMS that incorporates all aspects of SaMD development, including design controls, risk management, and post-market surveillance.
2. Risk Assessment and Mitigation (ISO 14971)
   
   • Conduct a thorough risk analysis at every stage of development to identify potential hazards and implement appropriate controls.
3. Software Lifecycle Management (ISO 62304)
   
   • Follow a systematic approach for SaMD lifecycle processes, including requirements definition, design, testing, and maintenance.
4. Usability (ISO 62366)
   
   • Prioritize intuitive user interfaces for ease of use.
5. Security (ISO 27001)
   
   • Prioritize robust cybersecurity measures to enhance safety and mitigate vulnerabilities. 

Challenges in SaMD Development

Cybersecurity

Protecting sensitive patient data is a top priority. Challenges include:

• Data Breaches: Unauthorized access to patient records.
• Device Hacking: Malicious actors manipulating SaMD to produce incorrect results.

Regulatory Compliance

Navigating complex regulations across multiple jurisdictions requires significant expertise and resources.

Software Updates

Frequent updates, necessary for improving functionality, can disrupt regulatory compliance or introduce new risks.

The SaMD Development Lifecycle

Developing SaMD is a meticulous process involving multiple stages:

1. Requirements Analysis

• Define the software's intended use and medical purpose.
• Identify regulatory requirements and potential risks.

2. Design and Prototyping

• Create a user-centered design that addresses both clinician and patient needs.
• Build a functional prototype for initial testing.

3. Development

• Use agile methodologies to develop the software in iterative cycles.
• Ensure traceability of all changes to maintain compliance.

4. Verification and Validation

• Verification: Confirm the software meets design specifications.
• Validation: Ensure the software fulfills its intended medical purpose.

5. Clinical Evaluation

Conduct clinical trials to demonstrate the safety and effectiveness of the software in real-world scenarios.

6. Post-Market Surveillance

• Monitor the software for adverse events or performance issues.
• Release updates to address vulnerabilities or improve functionality.

Future Trends in SaMD

1. Personalized Medicine

SaMD will increasingly enable personalized treatment plans based on genetic, lifestyle, and medical data.

2. Real-Time Remote Care

With advancements in IoMT, SaMD will facilitate real-time monitoring and intervention, particularly for remote and underserved populations.

3. Adaptive AI

Regulatory frameworks are evolving to accommodate AI-based SaMD that continuously learns and improves in real-world environments.

While challenges such as regulatory compliance and cybersecurity remain, ongoing advancements in AI, cloud computing, and IoMT are paving the way for even more innovative applications. Developers, clinicians, and regulators must collaborate to unlock the full potential of SaMD while prioritizing patient safety and data privacy.

By understanding the intricacies of SaMD’s development lifecycle, regulatory frameworks, and technological drivers, stakeholders can navigate this rapidly evolving field with confidence. SaMD is not just a tool; it’s the future of digital health.

How Ketryx can Help Companies with their Software as a Medical Device

Ketryx accelerates the development of Software as a Medical Device (SaMD) by providing automated traceability, streamlined documentation, and seamless integration with existing tools like Jira and GitHub. AI-powered Ketryx Intelligence assists teams in maintaining compliance with standards like IEC 62304 by proactively suggesting updates to traceability and documentation. The platform’s approval system configurability and eQMS features ensure efficient workflows for quality management, CAPAs, and training. By synchronizing data across systems in real time, Ketryx eliminates silos, enabling faster iteration and smoother audits, empowering teams to deliver safer, compliant software more efficiently.