Response

We acknowledge BSI's observation that the PMS Plan did not make compliance with MDR Chapter VII and Annex III 1(a) and 1(b) sufficiently traceable at section level.

The underlying procedures and controls were already established in the quality management system. However, the previous version of R-TF-007-001 Post-Market Surveillance (PMS) Plan did not direct the reviewer to the exact section headings within those procedures where the requirements are implemented, and it did not consolidate the specific indicators and threshold values used for benefit-risk reassessment in one dedicated section. As a result, the traceability was not sufficiently explicit for review from the PMS Plan alone.

R-TF-007-001 has now been revised to address this point. No new procedures were created. Instead, the PMS Plan was updated so that each relevant requirement is now linked to the exact SOP or plan section where it is implemented, and the key indicators, thresholds and regulatory mappings are now presented directly in the PMS Plan. Red-lined documentation is provided.

Summary of the update

The revised PMS Plan now:

• provides section-heading level traceability for the Annex III 1(a) and 1(b) requirements;
• consolidates the indicators and threshold values used for continuous benefit-risk reassessment;
• includes a dedicated § Trend analysis section setting out the observation period, statistical trigger and escalation path;
• provides explicit regulatory traceability for Articles 83, 86, 87, 88 and Annex XIV.

1. Enhanced Annex III 1(a) and 1(b) traceability table

The Annex III traceability table has been revised so that each requirement now points to the exact section heading in the relevant procedure or plan where that requirement is implemented. This addresses the core issue raised by BSI, namely that the previous version identified the applicable procedures but did not make the traceability sufficiently precise.

• Annex III 1(a) — Collection and utilization of available information on serious incidents and FSCAs (including PSURs), non-serious incidents and undesirable side-effects, trend reporting, specialist/technical literature, databases and registers, feedback and complaints from users, distributors and importers, and publicly available information about similar devices: R-TF-007-001 Post-Market Surveillance (PMS) Plan, § Data collection activities (consolidated mapping of all six information sources); GP-004 Vigilance system, § Receipt of notification of an incident; § Field Safety Corrective Action (FSCA); § Trend report; GP-014 Feedback and complaints, § Information coming from customers; § Customer complaint management; GP-007 Post-market surveillance, § Active monitoring of the information received.
• Proactive and systematic data collection (Annex III 1(b)): GP-007 Post-market surveillance, § Post-market surveillance system; § Active monitoring of the information received
• Methods to assess collected data: GP-020 Data analysis, § Data analysis procedure
• Indicators and threshold values for benefit-risk reassessment: R-TF-007-001 Post-Market Surveillance (PMS) Plan, § Indicators and threshold values for benefit-risk reassessment; § Trend analysis; R-TF-007-002 Post-Market Clinical Follow-up (PMCF) Plan, § Specific PMCF Methods
• Methods to investigate complaints (Article 87): GP-014 Feedback and complaints, § Information coming from customers; § Customer complaint management; § Customer complaint investigation and evaluation
• Trend report methods (Article 88): GP-004 Vigilance system, § Trend report; GP-020 Data analysis, § Data analysis procedure; R-TF-007-001 PMS Plan, § Trend analysis
• Communication with competent authorities, notified bodies and users: GP-004 Vigilance system, § Notification to Regulatory Authorities; § Field Safety Corrective Action (FSCA); § Criteria to notify an incident to the national competent authorities
• Procedures for Articles 83, 84 and 86: GP-007 Post-market surveillance, § Post-market surveillance (PMS) plan; § Periodic Safety Update Report (PSUR)
• Corrective actions: GP-006 Non-conformities, Corrective and preventive actions, § Reception of Non-conformity; § Corrective and Preventive Actions (CAPA); § Verification of the efficacy of CAPAs
• Device tracing: GP-016 Traceability and identification, § Traceability; § Product serial number and UDI assignment; SP-004-001 Product withdrawal, § Procedure

2. Specific indicators and threshold values for benefit-risk reassessment

A dedicated section, "Indicators and threshold values for benefit-risk reassessment," has been added to R-TF-007-001. This section brings together, in one place, the specific thresholds that were previously dispersed across the PMS and PMCF documentation:

• Trend detection threshold: A 25% increase over historic or foreseeable data triggers a formal investigation, as defined in GP-020 Data analysis, § Data analysis procedure. Trends are recorded as either a T-020-001 Trend report or a T-006-001 Non-conformity report, with escalation into root cause analysis and corrective actions where applicable.
• Clinical performance thresholds (PMCF): AUC > 0.8; Top-5 >= 70%; Top-3 >= 55%; Top-1 >= 40%, as defined in R-TF-007-002 PMCF Plan, § Specific PMCF Methods, Activity C.1: Image-based diagnosis non-interventional performance analysis, under Acceptance Criteria. Sustained performance below any of these criteria triggers benefit-risk reassessment.
• Severity assessment agreement: Measured using the Interobserver Correlation Coefficient (ICC) per R-TF-007-002 PMCF Plan, Activities B.1–B.4.
• Quality indicators: Established in T-002-002 Quality objectives and T-002-003 Quality indicators, reviewed quarterly and compared against expected values at each annual management review.
• Benefit-risk reassessment triggers: Defined criteria for initiating a reassessment, including threshold exceedance, performance below PMCF thresholds, identification of new risks, statistically significant increase in incident frequency or severity, and contradictory clinical evidence.

3. Trend analysis methodology: observation period, statistical method and escalation path (Article 88)

To make the Article 88 methodology directly visible, R-TF-007-001 now contains a dedicated § Trend analysis heading. This section was expanded so that the reviewer can see, in one place, the observation period, the statistical trigger and the escalation route that apply when a trend is detected:

• Observation period: The primary observation period is annual, aligned with the PSUR cycle. Quality indicators are reviewed quarterly to enable early detection. Multi-year comparisons are performed at each annual management review.
• Statistical methods and threshold for statistically significant increase: Statistical and comparison techniques are applied in accordance with GP-020 Data analysis, § Data analysis procedure. The threshold used to trigger formal investigation is a 25% increase over historic or foreseeable data.
• Escalation and reporting: Non-conformity reports and CAPA initiation per GP-006; trend reports submitted to the NCA using MEDDEV 2.12-1 rev.8 Annex VII form per GP-004 Vigilance system, § Trend report.

4. Article 87 sub-clause level traceability

A new section, Article 87: Reporting of serious incidents and field safety corrective actions, has been added under § Detailed regulatory traceability in R-TF-007-001. This section makes explicit which SOP heading addresses each of the sub-clauses raised by BSI, as now set out in the PMS Plan:

• Article 87(1): Criteria for determining whether an incident is reportable as a serious incident: GP-004 Vigilance system, § Criteria to notify an incident to the national competent authorities.
• Article 87(2): Reporting timelines of 15, 10 and 2 calendar days: GP-004 Vigilance system, § Timelines for initial communication of incidents.
• Article 87(7): Content requirements for the manufacturer's report: GP-004 Vigilance system, § Notification to Regulatory Authorities.
• Article 87(8): Follow-up reporting where the investigation exceeds the initial reporting period: GP-004 Vigilance system, § Incidents occurred in Spain (follow-up report submission to the NCA when the investigation exceeds the period established in the initial report).
• Article 87(9): Final report detailing investigation results and actions taken: GP-004 Vigilance system, § Notification to Regulatory Authorities.
• Article 87(11): Field safety corrective actions and field safety notices: GP-004 Vigilance system, § Field Safety Corrective Action (FSCA); § Field Safety Notice (FSN).

5. Articles 83 and 86 sub-clause level traceability

New sections for Articles 83 and 86 have also been added to R-TF-007-001, under § Detailed regulatory traceability:

Article 83:

• 83(1): Obligation to plan, establish, document, implement, maintain and update a PMS system proportionate to the risk class and integrated in the QMS: R-TF-007-001 and GP-007, § Post-market surveillance system.
• 83(2): PMS system suited to actively and systematically gather, record and analyse relevant data on quality, performance and safety throughout the device lifetime, and to draw necessary conclusions and determine, implement and monitor preventive and corrective actions: GP-007, § Post-market surveillance system; § Active monitoring of the information received; GP-020, § Data analysis procedure.
• 83(3): Use of PMS data to update benefit-risk determination, design and manufacturing information, IFU and labelling, clinical evaluation, and SSCP; to identify need for preventive, corrective or FSCA; to identify usability/performance/safety improvements; to contribute to PMS of other devices; and to detect and report trends per Article 88: R-TF-007-001, § Indicators and threshold values for benefit-risk reassessment; § Update risk management file; GP-015 Clinical evaluation; GP-006, § Corrective and Preventive Actions (CAPA); GP-004, § Trend report; PSUR (prepared per Article 86, annually for class IIb).
• 83(4): Implementation of preventive or corrective measures when identified, and informing competent authorities and notified body: GP-006, § Corrective and Preventive Actions (CAPA); GP-004, § Notification to Regulatory Authorities; § Field Safety Corrective Action (FSCA); SP-004-001 Product withdrawal, § Procedure.

Article 86:

• 86(1): PSUR content and preparation: GP-007, § Periodic Safety Update Report (PSUR); structure follows MDCG 2022-21.
• 86(2): Annual update for class IIb: confirmed in R-TF-007-001, § Planned PSUR.

6. Annex XIV traceability

A new section, Annex XIV: Clinical evaluation and post-market clinical follow-up, has been added to R-TF-007-001, under § Detailed regulatory traceability, covering both Part A and Part B:

Annex XIV Part A (Clinical evaluation):

• Clinical literature is reviewed annually as part of PMS activities, and results feed into the clinical evaluation per GP-015 Clinical evaluation.
• All relevant PMS and PMCF findings are systematically incorporated into the R-TF-015-003 Clinical Evaluation Report.
• PMS data is compared with previous clinical data per GP-020 Data analysis, § Data analysis procedure and GP-015 Clinical evaluation.

Annex XIV Part B (Post-market clinical follow-up):

• The PMCF plan (R-TF-007-002) has been developed in accordance with Annex XIV Part B. The PMCF evaluation report is prepared in accordance with Article 86 and Annex XIV Part B, Section 5.

7. Integration of the equivalent legacy device's post-market conclusions into the PMS Plan (MDCG 2020-6 §6.2.2)

R-TF-007-001 now routes the conclusions of the equivalent legacy device's post-market programme into the Plus post-market activities as structural, named inputs rather than decorative citations. Three subsections have been added and one existing subsection has been expanded so that the reviewer can see, in one place, how the four-plus-year legacy operational experience and the results of the cross-sectional observational PMS study shape the Plus PMS system.

• Benefit confirmation — continuity with legacy evidence (new subsection under § PMCF activities). Names the three MCID-positive co-primary endpoints of the legacy cross-sectional observational PMS study (B2 diagnostic-assessment change rate, C4 treatment decisions informed by severity, D4 referral-adequacy improvement) under Holm-Bonferroni family-wise α = 0.05, and commits the Plus PMCF activities (A.1, A.2, A.3 for 7GH and 3KX; B.1 – B.5 for 5RB; C.1, C.2.1 – C.2.3, D.1 and D.2 for indication coverage) to continued benefit-confirmation monitoring at least at the legacy cadence.

• Carried-forward safety-signal baselines from legacy post-market (new subsection under § Indicators and threshold values for benefit-risk reassessment). Sets pre-specified, denominator-bearing breach triggers for F1 (26.8% baseline on N = 56 → 30% trigger), F2 (30.4% → 40% trigger), F3 (mean 4.14 / 5 → 3.5 trigger) and F4 (7.1% → 10% trigger) directly against the legacy study's Section F results, so that deviation from the legacy-device safety pattern during Plus deployment triggers unscheduled CER and benefit-risk reassessment through the same escalation path used for trend reporting under Article 88.

• Surveillance cadence — calibrated against legacy-device operational experience (new subsection under § Legacy Device Data). Declares that the annual PSUR cycle with quarterly quality-indicator reviews is calibrated against the legacy operational record (approximately 250,000 diagnostic reports over four-plus years across 21 active client contracts with zero Article 87 serious incidents, zero Article 88 trend reports and zero FSCAs) rather than defaulted from a template. This makes the cadence rationale auditable against a concrete evidence basis.

• § Legacy Device Data (existing subsection, expanded). Now names the legacy umbrella PMS Plan (R-TF-007-005), the paired legacy umbrella PMS Report (R-TF-007-003) and the study-specific cross-sectional observational study Protocol (R-TF-015-012) and Report (Appendix D to R-TF-015-012) as the concrete legacy inputs under MDCG 2020-6 §6.2.2, and anchors the five integration points implemented in the subsections above and in R-TF-007-002 PMCF Plan.

Companion subsections have been added to R-TF-007-002 PMCF Plan to route each of the legacy study's three residual uncertainties (physician-reported outcomes, cross-sectional design, attribution uncertainty) to the PMCF activities that deliver confirmation, and to continue the legacy study's evidence-quality substantiation principle and 35.9% records-consulted threshold across the Plus PMCF activities. R-TF-015-003 Clinical Evaluation Report § PMS and PMCF feedback loop has been updated with a dedicated bullet that consolidates the five integration points. No new benefits or performance claims are introduced by this integration; it strengthens the benefit-risk argument by making the Plus post-market programme demonstrably informed by the equivalent legacy device's actual market experience.

Summary

All seven concerns raised in the observation are addressed by existing quality management procedures. No new SOPs were required. The corrective action taken was to revise R-TF-007-001 so that it now clearly shows where each requirement is implemented by means of section-heading level references, a dedicated section on indicators and threshold values, a dedicated § Trend analysis section, explicit regulatory traceability for Articles 83, 86, 87, 88 and Annex XIV, and integration of the equivalent legacy device's post-market conclusions into the Plus PMS and PMCF programmes under MDCG 2020-6 §6.2.2.

Accordingly, this response addresses the observation by correcting the traceability and clarity of the PMS Plan, rather than by introducing new process content.

Relevant commits

• 54a827183 (2026-03-08, Taig Mac Carthy): Updated R-TF-007-001 Post-Market Surveillance (PMS) Plan. Expanded "Analyse trends" section with observation period (annual/quarterly), statistical methods (25% threshold from GP-020), and escalation procedures. Added new "Indicators and threshold values for benefit-risk reassessment" section consolidating trend detection threshold, PMCF clinical performance thresholds (AUC, Top-N accuracy), severity assessment agreement (ICC), quality indicators, and benefit-risk reassessment triggers. Added new "Detailed regulatory traceability" section with sub-clause mappings for Articles 83(1–4), 86(1–2), 87(1,2,7,8,9,11), 88, and Annex XIV Parts A and B. Updated Annex III 1(b) traceability table to reference the new indicators section.
• e5d63dd8b (2026-04-17, Saray Ugidos Semán): Tightened Item 5 PMS traceability mappings so that every Annex III 1(b) requirement points to the exact SOP section heading. Renamed the "Analyse trends, decide on necessary measures and implement them" section in R-TF-007-001 to "Trend analysis". Aligned PMCF threshold notation in R-TF-007-001 with the authoritative wording in R-TF-007-002 PMCF Plan (AUC > 0.8; Top-5 >= 70%; Top-3 >= 55%; Top-1 >= 40%). Corrected Article 87 sub-clause mappings in the research-and-planning document to match the MDR text.
• 2d212c80c (2026-04-18, Taig Mac Carthy): Aligned the Annex III 1(a), Article 83(3) and Article 83(4) traceability with the verbatim text of MDR 2017/745 in both the response and R-TF-007-001: Annex III 1(a) now lists the six information sources the plan must address; Article 83(3) now describes the obligatory uses of PMS data; Article 83(4) now covers implementation of preventive or corrective measures and notification of competent authorities. Restored the "Relevant commits" section. Removed inline backtick formatting from the response so it copies cleanly into BSI's Word template. Strengthened the Article 87(8) mapping with a parenthetical on follow-up reporting. Fixed a truncated "§ Criteria to notify an incident" heading.