R-TF-013-001 Risk management plan

Scope

This risk management plan describes the different risk management activities carried out throughout the entire product life cycle, the responsibilities and authorities of those involved, the criteria for risk acceptability, the activities for the verification of risk control measures, and the production and post-production information to be collected and reviewed for the medical device Legit.Health Plus (hereinafter, the device).

The risk management plan will be reviewed and updated at least annually or when required as new information becomes available.

This document is drafted according to the requirements established in the harmonized standard UNE-EN ISO 14971:2020. Medical devices - Application of risk management to medical devices.

Terms and definitions

• Accompanying documentation: This term refers to the materials that come with a medical device, providing critical information for users and those responsible for its installation, use, maintenance, decommissioning, and disposal. The focus of these materials is to ensure the safe use of the medical device.
• AFAP (As far as possible): A commitment to extend efforts to the greatest extent achievable to accomplish a particular goal or task.
• Benefit: The positive effects or desirable outcomes associated with the use of a medical device. This could pertain to improvements in an individual's health, enhancements in patient management, or positive impacts on public health.
• Harm: Any injury or damage that affects the health of people, or causes damage to property or the environment.
• Hazard: A potential source of harm or adverse effect.
• Hazardous situation: A scenario where people, property, or the environment are exposed to one or more hazards, creating a potential risk.
• Intended use/Intended purpose: The specific application or function of a product, process, or service as intended by the manufacturer, in accordance with the provided specifications, instructions, and information.
• Life cycle: The entire span of a medical device's existence, from its initial conception, through its design, manufacturing, use, and eventual decommissioning and disposal.
• Manufacturer: The individual or entity responsible for designing and/or producing a medical device, intending to make it available for use under their name, regardless of whether the medical device was manufactured by them directly or on their behalf by others.
• Medical device: A broad category that includes instruments, apparatuses, machines, appliances, implants, reagents for in vitro use, software, materials, and other related articles intended for human use for medical purposes. These purposes include but are not limited to:
  • Diagnosing, preventing, monitoring, treating, or alleviating disease
  • Diagnosing, monitoring, treating, alleviating, or compensating for an injury
  • Investigating, replacing, modifying, or supporting anatomy or physiological processes
  • Sustaining life
  • Controlling conception
  • Disinfecting medical devices
  • Providing information via in vitro examination of specimens from the human body The device achieves its primary intended action not by pharmacological, immunological, or metabolic means, but may be assisted by such means.
• Objective evidence: Verifiable data that supports the existence or truth of a claim or statement.
• Post-production: The phase in a medical device's life cycle that begins after the design and manufacturing processes are complete.
• Procedure: A specific way of performing an activity or process, typically documented and standardized.
• Process: A series of interrelated or interacting activities, utilizing inputs to produce a desired result.
• Reasonably foreseeable misuse: The use of a product or system in a way not intended by the manufacturer, but which can result from predictable human behavior.
• Record: A document that provides evidence of completed activities or achieved results.
• Residual risk: The level of risk that remains after all risk control measures have been applied.
• Risk: The combination of the likelihood of occurrence of harm and the severity of that harm.
• Risk analysis: The systematic application of available information to identify hazards and estimate risks.
• Risk assessment: The comprehensive process that includes both risk analysis and risk evaluation.
• Risk control: The process of making decisions and implementing measures to reduce risks to, or maintain them within, specified levels.
• Risk estimation: The process of assigning values to the probability of occurrence of harm and the severity of that harm.
• Risk evaluation: The process of comparing estimated risks against predefined criteria to determine their acceptability.
• Risk management: The systematic application of management policies, procedures, and practices to the tasks of risk analysis, evaluation, control, and monitoring.
• Risk management file: A compilation of records and other documents produced as a result of risk management activities.
• Safety: The state of being free from unacceptable levels of risk.
• Severity: The extent of the possible consequences that could result from a hazard.
• State of the art: The most advanced and developed stage of technical capability at a given time, incorporating the latest findings from science, technology, and experience across products, processes, and services.
• Top management: The individuals or group of people who have the highest level of authority and responsibility in directing and controlling a manufacturer.
• Use error: A situation where a user's action or lack of action while using a medical device results in an outcome different from that intended by the manufacturer or expected by the user.
• Verification: The process of providing objective evidence to confirm that specified requirements have been fulfilled.

Product characterization

	Information
Device name	Legit.Health Plus (hereinafter, the device)
Model and type	NA
Version	1.0.0.0
Basic UDI-DI	8437025550LegitCADx6X
Certificate number (if available)	MDR 792790
EMDN code(s)	Z12040192 (General medicine diagnosis and monitoring instruments - Medical device software)
GMDN code	65975
Class	Class IIb
Classification rule	Rule 11
Novel product (True/False)	FALSE
Novel related clinical procedure (True/False)	FALSE
SRN	ES-MF-000025345

Intended use or purpose

Intended use

The device is a computational software-only medical device intended to support health care providers in the assessment of skin structures, enhancing efficiency and accuracy of care delivery, by providing:

• quantification of intensity, count, extent of visible clinical signs
• interpretative distribution representation of possible International Classification of Diseases (ICD) classes.

Quantification of intensity, count and extent of visible clinical signs

The device provides quantifiable data on the intensity, count and extent of clinical signs such as erythema, desquamation, and induration, among others; including, but not limited to:

• erythema,
• desquamation,
• induration,
• crusting,
• dryness,
• oedema,
• oozing,
• excoriation,
• swelling,
• lichenification,
• exudation,
• depth,
• edges,
• undermining,
• pustulation,
• hair loss,
• type of necrotic tissue,
• amount of necrotic tissue,
• type of exudate,
• peripheral tissue edema,
• peripheral tissue induration,
• granulation tissue,
• epithelialization,
• nodule count,
• papule count,
• pustule count,
• cyst count,
• comedone count,
• abscess count,
• draining tunnel count,
• lesion count

Image-based recognition of visible ICD classes

The device is intended to provide an interpretative distribution representation of possible International Classification of Diseases (ICD) classes that might be represented in the pixels content of the image.

Device description

The device is computational software-only medical device leveraging computer vision algorithms to process images of the epidermis, the dermis and its appendages, among other skin structures. Its principal function is to provide a wide range of clinical data from the analyzed images to assist healthcare practitioners in their clinical evaluations and allow healthcare provider organisations to gather data and improve their workflows.

The generated data is intended to aid healthcare practitioners and organizations in their clinical decision-making process, thus enhancing the efficiency and accuracy of care delivery.

The device should never be used to confirm a clinical diagnosis. On the contrary, its result is one element of the overall clinical assessment. Indeed, the device is designed to be used when a healthcare practitioner chooses to obtain additional information to consider a decision.

Intended medical indication

The device is indicated for use on images of visible skin structure abnormalities to support the assessment of all diseases of the skin incorporating conditions affecting the epidermis, its appendages (hair, hair follicle, sebaceous glands, apocrine sweat gland apparatus, eccrine sweat gland apparatus and nails) and associated mucous membranes (conjunctival, oral and genital), the dermis, the cutaneous vasculature and the subcutaneous tissue (subcutis).

Intended patient population

The device is intended for use on images of skin from patients presenting visible skin structure abnormalities, across all age groups, skin types, and demographics.

Intended user

The medical device is intended for use by healthcare providers to aid in the assessment of skin structures.

User qualification and competencies

In this section we specificy the specific qualifications and competencies needed for users of the device, to properly use the device, provided that they already belong to their professional category. In other words, when describing the qualifications of HCPs, it is assumed that healthcare professionals (HCPs) already have the qualifications and competencies native to their profession.

Healthcare professionals

No official qualifications are needes, but it is advisable if HCPs have some competencies:

• Knowledge on how to take images with smartphones.

IT professionals

IT professionals are responsible for the integration of the medical device into the healthcare organisation's system.

No specific official qualifications are needed, but it is advisable that IT professionals using the device have the following competencies:

• Basic knowledge of FHIR
• Understanding of the output of the device.

Use environment

The device is intended to be used in the setting of healthcare organisations and their IT departments, which commonly are situated inside hospitals or other clinical facilities.

The device is intended to be integrated into the healthcare organisation's system by IT professionals.

Operating principle

The device is computational medical tool leveraging computer vision algorithms to process images of the epidermis, the dermis and its appendages, among other skin structures.

Body structures

The device is intended to use on the epidermis, its appendages (hair, hair follicle, sebaceous glands, apocrine sweat gland apparatus, eccrine sweat gland apparatus and nails) and associated mucous membranes (conjunctival, oral and genital), the dermis, the cutaneous vasculature and the subcutaneous tissue (subcutis).

In fact, the device is intended to use on visible skin structures. As such, it can only quantify clinical signs that are visible, and distribute the probabilities across ICD classes that are visible.

Technical features

Features

API REST

Our device is accessed as an API that follows the REST protocol.

This protocol totally separates the user interface from the server and the data storage. Thanks to this, REST API always adapts to the type of syntax or platforms that the user may use, which gives considerable freedom and autonomy to the user. With a REST API, the user can use either PHP, Java, Python or Node.js servers. The only thing is that it is indispensable that the responses to the requests should always take place in the language used for the information exchange: JSON.

OpenAPI Specification

Our medical device includes an OpenAPI Specification.

OpenAPI Specification (formerly known as Swagger Specification) is an API description format for REST APIs. An OpenAPI file allows you to describe a entire API, including:

• Available endpoints and operations on each endpoint (GET, POST)
• Operation parameters Input and output for each operation
• Authentication methods
• Contact information, license, terms of use and other information.

This means that our API itself has embeded specifications that help the user undertand the type of values that are transmitted by the API.

HL7 FHIR

FHIR is a standard for health care data exchange, published by HL7®. FHIR is suitable for use in a wide variety of contexts: mobile phone apps, cloud communications, EHR-based data sharing, server communication in large institutional healthcare providers, and much more.

FHIR solves many challenges of data interoperability by defining a simple framework for sharing data between systems.

Accessories

Primary accesories

What are 'Primary accesories'?

Primary accesories are the components that interact directly with the device. These can be known by the manufacturer. They are also required to interact with the device.

The device is used through an API (Application Programming Interface). This means that the interface is coded, and used programatically, without a user interface.

In other words: the device is used server-to-server, by computer programs. Thus, no accesory is user directly in interaction with the device.

Secondary accesories

What are 'Secondary accesories'?

Secondary accesories are the components that may interact indirectly with the device. These are developed and mantained independently by the user, and the manufacturer has no visibility as to their identity or operating principles. They are also optional and not required to interact with the device.

The device may also be used indirectly through applications, such as the care provider's Electronic Health Records (EHR). The EHR is the software system that stores patients' data: medical and family history, laboratory and other test results, prescribed medications history, and more. This is developed and mantained independently of us, and may be used to indirectly interact with the device.

The patients and healthcare providers may use image capture devices to take photos of skin structures. In this regards, the minimim requirement is a 12 MP camera.

Performance attributes of the device

The relevant performance attributes are:

Metric	Value
Weight	33 kilobytes
Average response time	1400 miliseconds
Maximum requests per second	no limit
Service availability time slot	The service is available at all times
Service availability rate during its working slot (in % per month)	100%
Maximum application recovery time in the event of a failure (RTO/AIMD)	6 hours
Maximum data loss in the event of a fault (none, current transaction, day, week, etc.) (RPO/PDMA)	None
Maximum response time to a transaction	10 seconds
Backup device (software, hardware)	Software (AWS S3)
Backup frequency	12 hours
Backup modality	Incremental
Recomended dimensions of images sent	10,000px2

Product life cycles phases

The life cycle phases of the device are:

• Realization process
  • Design and development
  • Transfer to production
• Post-production phase
  • Installation and maintenance
  • Use
  • Decommissioning and disposal

Similar devices and science state

• FotoFinder, manufactured by FotoFinder Systems GmbH, that is a German company The product allows image recognition for skin cancer diagnosis, aesthetic medicine, psoriasis, alopecia and clinical trials.
• SkinVision, manufactured by Skinvision B.V,that is a Dutch company. SkinVision is an app for iOS and Android that allows you to assess and track skin spots to detect changes over time and differentiate between different types of skin cancer. It works by asking users to take a photo of worrisome spots on their skin using their mobile camera. It offers a risk assessment: low, low with symptoms or high.
• DermEngine, from MetaOptima Technology Inc, a Canadian company that provides digital health solutions and mobile technologies. The company develops solutions that enable physicians with technologies for early diagnosis and treatment of skin conditions such as cancer.
• Triage, manufactured by Triage Technologies Inc. It is an application capable of screening and triaging over 500 skin injuries through cell phone photos.

The state of the art is periodically analysed in the Clinical Evaluation Report (T-015-003 Clinical evaluation report (CER)) and updated according to the Post-Market Surveillance plan (R-TF-007-001 PMS plan), which is evaluated in the Periodic Safety updated report (R-TF-007-003 PSUR).

Assignment of responsibilities and authorities

This chapter of the risk management plan aims to identify the personnel or functions with responsibility for the execution of specific activities related to risk management.

Responsibilities and authorities

Design and development phase

Personnel

In this phase, the people involved are:

• JD-003 Design and Development Manager
• JD-005 Technical Manager & Person Responsible for Regulatory Compliance (PRRC)
• JD-004 Quality manager & Person Responsible for Regulatory Compliance (PRRC)

Activities

In this phase, the activities that must be carried out are:

• Identification and initial assessment of hazards.
• Implementation of risk control measures.
• Verification of control measures.
• Drafting of the initial risk management report.

Transfer to production phase

Personnel

In this phase, the people involved are:

• JD-003 Design and Development Manager
• JD-005 Technical Manager & Person Responsible for Regulatory Compliance (PRRC)
• JD-004 Quality manager & Person Responsible for Regulatory Compliance (PRRC)

Activities

In this phase, the activities that must be carried out are:

• Review of the applicability and correct implementation of all the risk control measures.
• Any unforeseen risks or any modified risk control measures will be documented in the risk management record.

Installation and maintenance phase

Personnel

In this phase, the people involved are:

• JD-003 Design and Development Manager
• JD-005 Technical Manager & Person Responsible for Regulatory Compliance (PRRC)
• JD-004 Quality manager & Person Responsible for Regulatory Compliance (PRRC)

Activities

In this phase, the activities that must be carried out are:

• Analysis of hazards and risk control measures in relation to installation, maintenance, service and support processes and practices.
• Analysis of hazards and risk control measures in relation to distribution.
• Any anomalous trends in security features will be analyzed to determine if corrective or preventive actions should be implemented.
• The impact of corrective or preventive measures to maintain or increase the safety of the product will be analyzed by incorporating it into the risk management asset.

Use phase

Personnel

In this phase, the people involved are:

• JD-001 General Manager
• JD-003 Design and Development Manager
• JD-005 Technical Manager & Person Responsible for Regulatory Compliance (PRRC)
• JD-004 Quality manager & Person Responsible for Regulatory Compliance (PRRC)

Activities

In this phase, the activities that must be carried out are:

• Any customer claim that results in changes/corrections to the product will be analyzed to determine its impact on the initial hazards assessment.
• Market feedback information will be monitored to determine if corrective/preventive actions should be implemented.

Disposal phase

Personnel

In this phase, the people involved are:

• JD-005 Technical Manager & Person Responsible for Regulatory Compliance (PRRC)
• JD-004 Quality manager & Person Responsible for Regulatory Compliance (PRRC)

Activities

In this phase, the activities that must be carried out are:

• The useful life will be determined by the Quality Manager.
• Report of the product will be retained to confirm its correct functionality even at the end of the designated service life.
• Risk management plan will be closed.

Clinical evaluation

As we detail in the R-TF-015-001 Clinical Evaluation Plan_2023_001, the team performing the risk management activities is completed with two external Healthcare Professionals. They are responsible for reviewing the clinical evaluation, that includes the evaluation of the Risk Analysis and minimization and management of side effects and other risks and the acceptability of Benefit-Risk-Ratio and undesirable side-effects, among other clinical evaluation activities.

Qualification of the risk management team

The team performing the risk mangement is comprised by persons with knowledge and experience of not just risk management, but also with knowledge on the medical device, technologies involved and its use.

The responsibilities are defined at the corresponding T-005-001 Job description and the qualification for each of the components is registered in the T-005-002 Personnel card. Additionally, their CVs are documented as independent files and archived within each member personnel file within the human resources tool in use.

Andy Aguilar

• Job position: General Manager
• Education: Andy has a degree in business administration and business strategies from Tecnologico de Monterrey and has completed two internships: one in innovation and entrepreneurship at the University of Mississippi and another in business administration and marketing at the University of the Basque Country.
• Experience with the product/process/technology: Her professional experience includes more than 4 years in sales and more than 2 years as e-commerce manager in two international B2C companies. Her experience includes more than 3 years of working with the product throughout its life cycle, as she is one of the co-funders of the company and she has participated in the product manufacturing since the begining.
• Training in risk management and other applicable: Not required
• Valuation: QUALIFIED
• Date: 02/07/2023
• Approved by: Alfonso Medela (Technical Manager & Person Responsible for Regulatory Compliance (PRRC))

Taig Mac Carthy

• Job position: Design and Development Manager
• Education: with a specialization in Strategic Management and Innovation from Copenhagen Business School, he has a foundational understanding of business practices essential in product development. His knowledge in quality management systems is well-established, having completed ISO 13485, ISO 9001:2015, and ISO 27001 Lead Auditor certifications from Bureau Veritas Group. These certifications underscore his ability to maintain high-quality standards in device manufacturing. Additionally, his training in ICH Good Clinical Practice and as an Equal Opportunity Agent, alongside courses in Python, Data Science, and Graphic Design, provide a diverse skill set applicable to his current role. His academic journey also includes a degree from the University of the Basque Country.
• Experience with the product/process/technology: solid background in both the medical and entrepreneurial fields. He has contributed to four scientific publications in computer vision applied to medicine, showcasing his expertise in areas directly relevant to medical device development. His involvement from the inception of the company, given his position as co-founder, has afforded him comprehensive knowledge of the device's development journey. His six years as a front-end software developer and the founding of three companies demonstrate his technical skills and entrepreneurial mindset. Additionally, his authorship of two business management books indicates his grasp on business operations, all of which collectively support his capacity to lead in design and development.
• Training in risk management and other applicable: ISO 13485 and ISO 27001.
• Valuation: QUALIFIED
• Date: 02/07/2023
• Approved by: Alfonso Medela (Technical Manager & Person Responsible for Regulatory Compliance (PRRC))

Alfonso Medela

• Job position: Technical Manager & Person Responsible for Regulatory Compliance (PRRC)
• Education:He holds a degree in physics from the University of the Basque Country. In addition, he completed his training with a MSc. in Physics at the University of Groningen and a MSc. in Big Data and intelligence. University of Groningen and another Master in Big Data and Business Intelligence at the University of Deusto.
• Experience with the product/process/technology: expert in computer vision, machine learning and artificial intelligence with more than 5 years of experience in the development of projects with medical approaches. His experience includes his time at Tecnalia Research & Innovation where he worked as a data scientist focused on Deep Learning algorithms in the area of Computer Vision. He has written 7 papers on machine learning and image recognition, he also teaches workshops and courses on machine learning and deep learning. At the European level, he is one of the few experts on the few-shot learning methodology in the field of artificial intelligence.
• Training in risk management and other applicable: ISO 13485 and Medical Devices regulatory.
• Valuation: QUALIFIED
• Date:02/07/2023
• Approved by: Andy Aguilar (General Manager)

María Diez

• Job position: Quality manager & Person Responsible for Regulatory Compliance (PRRC)
• Education: María studied Biology at the Complutense University of Madrid. In addition, she holds a PhD on Biochemistry and Molecular Biology by the same University.
• Experience with the product/process/technology: With more than 7 years on Quality and Regulatory experience, María started developing her abilities implementing a Quality Management system based on ISO 15189, CLIA and Spanish sanitary regulations (specific for medical laboratories), clinical studies and in vitro Software as medical device. On her last work experience she developed and integrated QMS combining the ISO 9001, ISO 13485, ISO 15189 and ISO 27001 regulations with the requirements established at the 2017/746 European in vitro medical device regulations, again for a Software as medical device.
• Training in risk management and other applicable: ISO 14971, ISO 13485, ISO 9001, ISO 27001, 2017/745 Medical Device Regulations.
• Valuation: QUALIFIED
• Date: 02/07/2023
• Approved by: Alfonso Medela (Technical Manager & Person Responsible for Regulatory Compliance (PRRC))

Risk management activities review

During each phase of the life cycle of the medical device, the personnel in charge of each activity will review the risk management activities. Moreover, a R-TF-013-003 Risk management report is carried out:

• Annually.
• When a new hazard is identified for which the corresponding control action must be implemented (occasionally).
• Or when a known hazard requires the redesign of control actions (occasionally).

In any case, a new version of the R-TF-013-002 Risk management record must be created, drafting the new hazards and/or the revaluation of the new conditions of known hazard.

Criteria for risk acceptability

The acceptability of the risk will be evaluated by means of a qualitative analysis of the casuistry of the ranges of probability and severity of every identified risk, always considering the current state of the art and the available information as existing technology and practice provided. The acceptance of a potential risk will be assessed according to the parameters defined in the general procedure GP-013 Risk management.

As explained in the GP-013, when the probability of occurrence of harm cannot be estimated, the probability will be assigned in terms of detectability.

Evaluation and criteria for individual benefit-risk acceptability and the overall residual risk

The method to evaluate the criteria for individual benefit-risk acceptability and the overall residual risk considers the clinical benefits provided by the performance of the intended use of the medical device, an it is defined GP-013 Risk management.

The results of the evaluation of the overall residual risk are documented in the R-TF-013-002 Risk Management Record.

Verification activities

Two different verifications activities required by the harmonized standard UNE-EN ISO 14971:2020 are carried out as defined GP-013 Risk management.

The evidence for verification of implementation and effectiveness of risk control measures are collected in the R-TF-013-002 Risk Management Record.

Collection and review of production and post-production information

We establish a system to actively collect and review information related to the device in the production and post-production phases and to review this information for relevance to safety.

These activities are described in the Procedures GP-006 Non-conformity. Corrective and preventive actions, GP-007 Post-market surveillance and GP-014 Feedback and complaints.

Associated documents

• JD-001 General Manager
• JD-003 Design and Development Manager
• JD-005 Technical Manager & Person Responsible for Regulatory Compliance (PRRC)
• JD-004 Quality manager & Person Responsible for Regulatory Compliance (PRRC)
• T-005-002 Personnel card
• R-TF-007-001 PMS plan
• R-TF-007-003 PSUR
• R-TF-013-002 Risk Management Record
• R-TF-013-003 Risk management report
• R-TF-015-003 Clinical evaluation report (CER)
• GP-004 Vigilance system
• GP-006 Non-conformity. Corrective and preventive actions
• GP-007 Post-market surveillance
• GP-014 Feedback and complaints

Record signature meaning

• Author: JD-004 María Diez
• Review: JD-003 Taig Mac Carthy
• Approval: JD-005 Mr. Alfonso Medela