R-TF-015-010 Annex E ISO 14155

ISO 14155:2020 Compliance Requirements

This section documents compliance with ISO 14155:2020 requirements for clinical investigations of medical devices. The table below provides a comprehensive checklist of documentation required under ISO 14155 and indicates which documents have been provided or prepared for this clinical investigation.

Document Title	Purpose	Included	Justification if not provided
Investigator's Brochure	Provides clinical and non-clinical data on the investigational device relevant to its study in human subjects.	TRUE	The Investigator's Brochure function is served by three technical-file records made available to all participating readers during onboarding: (i) the Instructions For Use (IFU v1.1.0.0), which summarises the device's clinical indications, intended user groups, principles of operation and performance characteristics; (ii) the Risk Management Record (R-TF-013-002), which summarises the residual-risk position and foreseeable adverse events associated with the device; and (iii) the preclinical-performance summary held within the technical file. All three are held by the manufacturer within the QMS and are available for audit on request.
Clinical Investigation Plan (CIP)	Describes the rationale, objectives, design, methodology, monitoring, and conduct of the clinical investigation.	TRUE	Recorded under R-TF-015-004 for this investigation.
Subject Information Sheet and Informed Consent Form (ICF)	Ensures that potential study subjects are adequately informed about the investigation and provide voluntary consent.	FALSE	The requirement for a Subject Information Sheet and Informed Consent Form (ICF) is waived due to the non-interventional nature of the research and the use of anonymised data. The investigation reviews fully anonymised dermatological images sourced from public atlases; no patient recruitment, patient contact, or clinical intervention took place. Healthcare professionals participating as readers received oral and written information about the investigation and signed a participation agreement. Under the Spanish framework and GDPR, no patient consent is required for the use of anonymised, non-identifiable images from public sources.
Ethics Committee Approval	Official approval from the ethics committee to conduct the clinical investigation.	FALSE	Ethics Committee approval is not applicable to this investigation. The investigation does not meet the definition of a clinical investigation of a medical device under MDR Article 2(45) because no patients are recruited, no patient-identifiable data is processed and no clinical intervention is performed on any patient; the research consists in the review and annotation of fully anonymised dermatological images sourced from public dermatological atlases by healthcare-professional readers acting in their professional capacity. Under the Spanish framework (Ley 14/2007, de 3 de julio, de Investigación Biomédica; Real Decreto 957/2020, de 3 de noviembre; Ley Orgánica 3/2018, de 5 de diciembre; and Regulation (EU) 2016/679 GDPR) the use of anonymised, non-identifiable images from public sources does not trigger the biomedical-research ethics-review requirement. The sponsor's documented Non-Applicability Determination, together with the signatory names, dates and the applicable Spanish legal instruments, is reproduced in the Ethics Committee Non-Applicability Determination section below.
Regulatory Authority Authorization	Authorization or notification from relevant regulatory bodies to proceed with the clinical investigation.	FALSE	This simulated-use multi-reader multi-case investigation does not require authorisation from or notification to a regulatory authority as a clinical investigation of a medical device. The determinative basis is MDR Article 2(45): the investigation does not meet the definition of a clinical investigation because no patients are recruited or contacted, no therapeutic or diagnostic intervention is performed on any patient, and the research uses only retrospective, fully anonymised images sourced from public dermatology atlases. Accordingly, MDR Article 62 (authorisation of clinical investigations) does not apply. The Spanish framework (Ley 14/2007, de 3 de julio, de Investigación Biomédica; Real Decreto 957/2020, de 3 de noviembre; Ley Orgánica 3/2018, de 5 de diciembre, on data protection; Regulation (EU) 2016/679) and ISO 14155:2020 §4.5 align with this exemption.
Case Report Forms (CRFs)	Documents designed to record all protocol-required information to be reported to the sponsor on each trial subject.	TRUE	CRF v1.0 was implemented through a secure web-based system designed for the standardised three-stage progressive-disclosure annotation of the investigation's 149 images; its data dictionary is maintained by the sponsor and is held in the technical file. Data generated through reader annotations were systematically captured (with timestamps and platform access logs providing source-data-verification traceability) and are available for export in a de-identified tabular format. Full traceability from source data to exported records is maintained in accordance with Good Clinical Practice (GCP) and applicable regulatory requirements; see also the CIP Data Management section.
Monitoring Plan	Describes the strategy, methods, responsibilities, and requirements for monitoring the clinical investigation.	TRUE	Detailed in the CIP.
Subject Recruitment Materials	Materials used to recruit subjects, ensuring they are ethically and appropriately informed.	FALSE	This investigation is exempt from the requirement to provide Subject Recruitment Materials because it involves the prospective observational review and annotation of fully anonymised dermatological images. No active patient recruitment, advertisement, or solicitation of potential subjects was conducted; there is no general subject-recruitment campaign. Healthcare professionals acting as readers were directly invited to participate by the Principal Investigator and by the manufacturer through the Principal Investigator's professional network. The invitation pathway, the participation-agreement template provided at onboarding, and the written study-information materials made available to readers are retained by the manufacturer within the QMS and are available for audit on request. Readers received oral and written information about the investigation and signed a participation agreement; no financial compensation was offered. This approach is in alignment with ISO 14155:2020 and relevant regulatory guidelines for observational investigations.
Signed Agreements	Contracts between the sponsor, investigators, and institutions detailing roles and responsibilities.	TRUE	Accessible upon formal request addressed to the sponsor.
Delegation of Duties Log	Documents identifying the study-related duties and responsibilities assigned to each team member.	TRUE	Detailed in the CIP.
Training Records	Evidence of training provided to the investigation team on the CIP, investigational device, and GCP principles.	TRUE	Training materials were provided to all participating readers as part of the onboarding flow, covering the investigation's design, the correct use of the device output in Stages 1 to 3, data entry procedures on the platform, and the essentials of ISO 14155 and Good Clinical Practice. Platform access logs and onboarding completion records substitute for paper attendance logs. Training materials are retained as part of the study's essential documents and can be provided for audit or inspection upon request.
Investigational Device Accountability Records	Tracks the receipt, use, and disposition of the investigational device to ensure traceability.	FALSE	Given the software-only nature of the investigational device, the research team was granted controlled access to the manufacturer's annotation platform through individualised login credentials (username and password). Platform access logs provide full traceability of all annotation activities. The corresponding communications confirming access provision can be provided for audit on request.
Subject Identification Code List	Confidential list linking subjects' codes to their identities, maintained by the investigator.	FALSE	This prospective observational investigation did not involve patient recruitment or the use of identifiable patient images. The research used fully anonymised dermatological images sourced from public atlases. Healthcare professionals participating as expert readers are identified in the CIR by anonymised codes (R-01, R-02, …); the corresponding code-to-identity master list, together with reader CVs, certification evidence and signed participation agreements, is maintained by the Principal Investigator under restricted access and is available for audit on request.
Screening and Enrollment Logs	Documents tracking the screening and enrollment status of potential and actual study subjects.	FALSE	This prospective observational investigation did not require formal screening and enrolment logs for patient subjects. Instead of recruiting patients, the research invited healthcare professionals to participate in the annotation of dermatological images. Healthcare professionals were directly invited and completed an onboarding flow that captured a professional-profile form, CV and certification or training evidence, conflict-of-interest declaration, signed participation agreement and data-protection acknowledgement. Enrolment and screen-failure decisions are documented in the CIR §CIP Compliance and Deviations and in the reader-qualification records retained under the Principal Investigator's custody.
Investigational Device Dossier (IDD)	Comprehensive technical and clinical data on the investigational device, including design, manufacturing, and performance information.	TRUE	The Investigational Device Dossier is provided by the complete technical file held by the manufacturer (R-TF-012 series, covering design, manufacturing, preclinical performance and risk-management summary); it is available for audit on request. Investigators were oriented to the device via the IFU (see Investigator's Brochure row above) and the onboarding materials retained for this investigation.
Insurance Statement	Proof of insurance coverage for participants in case of study-related injuries.	FALSE	Insurance coverage was not required for this prospective observational investigation. The research involved only the review and annotation of anonymised dermatological images on a secure web-based platform. No procedures, interventions, or direct patient contact occurred that would create risk of injury to any participant. Healthcare professionals participated voluntarily with informed understanding of the investigation's observational and non-interventional nature through participation agreements. Therefore, liability insurance specific to study-related injuries was not applicable.
Financial Disclosure Records	Documentation of any financial interests of investigators that could affect the study's integrity.	TRUE	Financial disclosure forms were collected from all investigators and readers involved in the clinical investigation. These forms document any potential financial interests, conflicts of interest, or relationships that could affect the investigation's integrity or objectivity. The disclosures are maintained as essential study documents and are available upon formal request.
Audit Certificates	Reports from independent audits assessing compliance with the CIP and GCP.	FALSE	An external independent audit was not deemed necessary for this investigation. Internal monitoring was conducted by the sponsor's Quality function — organisationally independent from the sponsor's regulatory-and-quality-document authoring and scientific-analysis functions — and covered platform-access audit trails, source-data-verification sampling and documentation review. Monitor qualifications and the sponsor / monitor / investigator independence arrangement are documented in the Monitoring Plan referenced in the CIP and retained in the QMS. Given the non-interventional design, limited duration, focused team and internal monitoring arrangement in place, an external audit certificate was not required under ISO 14155:2020 §9.2. All monitoring records are maintained as part of the study's essential documents and are available for audit on request.
Final Clinical Investigation Report	A comprehensive report summarizing the clinical investigation's methodology and results.	TRUE	Recorded under R-TF-015-006 for this investigation.

Ethics Committee Non-Applicability Determination

This clinical investigation is a simulated-use multi-reader multi-case (MRMC) study performed entirely on retrospective, fully anonymised dermatological images obtained from public dermatology atlases and other freely available public sources. The investigation does not involve the recruitment of patients, direct contact with patients, or the collection or processing of patient-identifiable data; no therapeutic or diagnostic intervention is performed on any patient as a consequence of the study. Healthcare professionals acting as readers participate in their professional capacity as expert evaluators of device performance; they are not enrolled as research subjects within the meaning of biomedical-research law.

Accordingly, the sponsor has determined, and documents herein, that this investigation does not fall within the material scope of:

• Ley 14/2007, de 3 de julio, de Investigación Biomédica, which governs biomedical research involving human subjects, human biological samples and personal health data in Spain.
• Real Decreto 957/2020, de 3 de noviembre, por el que se regulan los estudios observacionales con medicamentos de uso humano and, by analogy for medical-device performance studies, the Spanish framework transposing the requirements of Regulation (EU) 2017/745 Article 62 and Annex XV for clinical investigations of medical devices involving human subjects.

The sponsor further confirms that the study is conducted in accordance with the ethical principles of the Declaration of Helsinki to the extent applicable to retrospective studies of anonymised material; complies with Regulation (EU) 2016/679 (GDPR) and with Ley Orgánica 3/2018, de 5 de diciembre, de Protección de Datos Personales y garantía de los derechos digitales for the handling of any personal data collected from reader-participants; and is registered in the public trial registries identified in the corresponding Clinical Investigation Plan and Clinical Investigation Report.

This determination of non-applicability is signed off by the sponsor and retained in the technical file. Where a participating site or competent authority requires a formal ethics-committee opinion or waiver for local conduct, such opinion is obtained and attached separately; otherwise this determination applies.

Signature meaning

The signatures for the approval process of this document can be found in the verified commits at the repository for the QMS. As a reference, the team members who are expected to participate in this document and their roles in the approval process, as defined in Annex I Responsibility Matrix of the GP-001, are:

• Author: Team members involved
• Reviewer: JD-018 Clinical Research Coordinator
• Approver: JD-022 Medical Manager