Four-test §6.3 rewrite — autoimmune and genodermatoses

Scope. This document contains replacement prose for the CEP and CER edits listed in the task-3b5 plan. It is an internal scratch-pad; no audit-visible document references this file. After reviewer-agent approval, each block below is copy-pasted or rebuilt in the target file at the line ranges identified in the plan's "Edit surface" table.

Discipline. Wording gate: "confirms / strengthens" ✓, "fills / closes" ✗. Autoimmune and genodermatoses are being moved from MDCG 2020-6 §6.5(e) (acceptable gap + passive surveillance) to MDCG 2020-6 §6.3 (sufficient clinical evidence via triangulation) + PMCF confirmation. The indication stays broad; the CLAIM for these two sub-categories is qualified by a warning (handled in narrowed-claim-language.md).

Quotable anchor. CEP line 1275 (Rank 11 row) already states: MRMC "do not constitute 'clinical data' under the strict MDR Article 2(48) definition". This sentence is the regulatory justification for why MRMC is deliberately NOT used as the Test 3 anchor for these two sub-categories, and is quoted verbatim in A1.

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A1 — CEP replacement for lines 1238–1239 (the core four-test analysis)

Current text (DELETE):

4. Gap 4 (benefit 7GH, sub-criterion a — indication coverage): Autoimmune diseases evidence coverage; declared acceptable per MDCG 2020-6 § 6.5(e); addressed through post-market data collection during real-world deployment.
5. Gap 5 (benefit 7GH, sub-criterion a — indication coverage): Genodermatoses evidence coverage; declared acceptable per MDCG 2020-6 § 6.5(e); addressed through passive surveillance through PMS/PMCF data collection.

Replacement text (INSERT at the same position):

4. Low-prevalence sub-indication categories — autoimmune dermatoses and genodermatoses (benefit 7GH, sub-criterion a — indication coverage). Pre-certification evidence for these two low-prevalence categories (~3 % autoimmune + ~1 % genodermatoses of real-world dermatological presentations) is triangulated under MDCG 2020-6 §6.3 and is judged sufficient on the four-test analysis below. These categories are not declared as §6.5(e) acceptable gaps.

   1. Test 1 — Narrow and bounded scope. The two categories account for approximately 4 % of real-world dermatological presentations combined (autoimmune ~3 %, genodermatoses ~1 %). The remaining ~96 % carry the core benefit-risk determination independently.
   2. Test 2 — Core benefit-risk independence. The three declared clinical benefits (7GH Diagnostic Accuracy, 5RB Objective Severity Assessment, 3KX Care-Pathway Optimisation) are independently evidenced on the remaining ~96 % of presentations by the pre-market confirmatory clinical investigations (MC_EVCDAO_2019, COVIDX_EVCDAO_2022, DAO_Derivación_O_2022, DAO_Derivación_PH_2022, IDEI_2023, AIHS4_2025) and by the legacy-predecessor real-world evidence corpus (R-TF-015-012; legacy passive PMS Report R-TF-007-003).
   3. Test 3 — Adequate residual evidence for the two categories (two independently-scoring anchors).
      • Pillar 1 Valid Clinical Association. A dedicated structured literature review (22 load-bearing anchors scoring CRIT1–7 ≥ 15/21; 4 supporting-context anchors) appended to R-TF-015-011 State of the Art as a per-sub-category section establishes that image-based clinical recognition is an accepted clinical standard for the named conditions: discoid lupus erythematosus, lichen planus (cutaneous and nail; oral lichen planus retains a residual coverage note, see paragraph below), dermatomyositis, pemphigus vulgaris, bullous pemphigoid, mucous membrane pemphigoid, morphea, cutaneous vasculitis (autoimmune); ichthyoses, neurofibromatosis type 1 and type 2, tuberous sclerosis complex, epidermolysis bullosa (genodermatoses).
      • Pillar 2 Technical Performance. A per-epidemiological-group sub-analysis of the v27.5.1 ICD classifier on the held-out V&V test set (n = 36,321 images; 346 ICD-11 categories), published in R-TF-028-006 AI Release Report §Per-Epidemiological-Group Performance, reports AUC 0.948 (95 % CI 0.941 – 0.954, N = 2,040 images across 38 autoimmune classes) and AUC 0.905 (95 % CI 0.886 – 0.924, N = 391 images across 31 genodermatoses classes). Both AUCs exceed the pre-specified ≥ 0.80 acceptance criterion inherited from the binary-indicator threshold in R-TF-028-002 AI Development Plan and both sit within the range of the six binary-indicator AUCs on the same test set (0.863 – 0.959).
      • MRMC is deliberately not invoked as the Test 3 anchor for these categories. The MDCG 2020-6 Appendix III appraisal set out elsewhere in this Plan (§Clinical Evidence, MDCG 2020-6 Appendix III appraisal — Rank 11) records that simulated-use multi-reader multi-case (MRMC) reader studies "do not constitute 'clinical data' under the strict MDR Article 2(48) definition". Pillar 1 literature + Pillar 2 analytical performance are the two independently-scoring Test 3 anchors; MRMC evidence for these sub-categories, where applicable, is Pillar 3 §4.4 supporting evidence only and is not load-bearing.
      • Scope boundary with adjacent coverage gaps. The MAN_2025 MRMC supporting investigation (Pillar 3 §4.4 at Rank 11; Fitzpatrick V–VI phototype representativeness) and the legacy-device real-world-evidence study R-TF-015-012 (Pillar 3 at Rank 8 primary with a supplementary case at Rank 4 for the quantitative endpoints) address different sub-indication and coverage considerations and are therefore not invoked as Test 3 anchors for autoimmune dermatoses or genodermatoses. Both studies remain part of the broader evidence envelope that carries the three declared benefits for the remaining ~96 % of presentations (Test 2 above) and are cited in the relevant sections of this Plan and of R-TF-015-003.
   4. Test 4 — PMCF confirms and strengthens. Post-certification confirmation is pre-specified in the R-TF-007-002 PMCF Plan under Activities D.1 (autoimmune, prospective surveillance with interim analyses at defined case counts; primary safety-floor acceptance criterion Top-3 ≥ 60 % on the in-scope cohort together with a non-inferiority secondary criterion against the V&V-demonstrated Top-3; safety and surveillance triggers) and D.2 (genodermatoses, passive surveillance with safety and coverage triggers, with an early Pillar 3-equivalent performance readout from the legacy-predecessor post-market report corpus at the first PMS Update Report). The PMCF Plan additionally commits to analysing the autoimmune-dermatoses and genodermatoses slices of the ≈ 250,000 legacy-predecessor post-market report corpus in the first PMS Update Report R-TF-007-003, consistent with MDCG 2020-6 §6.3 under which PMCF confirms and strengthens an adequately-evidenced pre-certification base and is not invoked to fill or close pre-market evidence gaps.

   Why the absence of pre-certification Pillar 3 evidence is regulatorily acceptable for these two sub-indications. Pillar 1 and Pillar 2 are two different kinds of test and neither substitutes for Pillar 3. The acceptability of the §6.3 sufficient-evidence determination for these sub-categories in the absence of pre-certification Pillar 3 evidence rests on three cumulative elements: (a) the device's output for these sub-categories is supporting-information-only — the CLAIM is qualified by the Device Output Warning (see R-TF-015-003 §Consolidated limitations of the device and the IFU Device Output Warnings) to the effect that the device provides a probability ranking within its broader ICD-11 output distribution, to be interpreted in the HCP's differential-diagnosis workup; (b) final-diagnosis responsibility for these sub-categories rests wholly with the healthcare professional and is confirmed by histopathological, serological or genetic testing outside the device's loop, consistent with the current standard of care for autoimmune dermatoses and genodermatoses; (c) Pillar 3 real-world clinical performance is pre-specified for post-certification confirmation in PMCF Activities D.1 and D.2, and the pre-certification determination does not depend on pre-certification Pillar 3 data because of (a) and (b). This narrowed-CLAIM-plus-HCP-responsibility-plus-PMCF-confirmation construction is the defensible §6.3 pathway for low-prevalence sub-indications whose definitive diagnosis relies on non-imaging modalities.

   The remaining residual Pillar 1 coverage item is oral lichen planus: the abstract-only anchor identified in the supplementary literature search was excluded because the full text was not publicly available for appraisal at the load-bearing threshold. This residual coverage item is routed to PMCF Activity D.1 for post-market confirmation and is recorded in the State of the Art appendix (R-TF-015-011 §Autoimmune and genodermatoses).

(Note to drafter: because this item is no longer a §6.5(e) acceptable gap, it should be removed from the "acceptable gap" enumeration format of the original numbered list at CEP §Post-Market Clinical Follow-up. Recommended implementation: keep numbering at the CEP level — this becomes a re-styled item 4 titled "Low-prevalence sub-indication categories" with an embedded four-test block. Former Gap 5 is absorbed into the single reframed item.)

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A1b — CEP line 1232–1233 introductory-paragraph update

Current text:

As detailed in R-TF-007-002 Post-Market Clinical Follow-up (PMCF) Plan, the program includes ten specific clinical activities (proactive data collection and targeted clinical studies) designed to confirm the long-term safety, performance, and clinical benefits of the device throughout its expected lifetime. These activities address five evidence gaps identified during the clinical evaluation:

Replacement text:

As detailed in R-TF-007-002 Post-Market Clinical Follow-up (PMCF) Plan, the program includes ten specific clinical activities (proactive data collection and targeted clinical studies) designed to confirm the long-term safety, performance, and clinical benefits of the device throughout its expected lifetime. These activities address three pre-certification evidence gaps identified during the clinical evaluation (Gaps 1, 2 and 3 below). Item 4 below is separately a §6.3 sufficient-evidence determination for two low-prevalence sub-indication categories (autoimmune dermatoses and genodermatoses); Activities D.1 and D.2 confirm and strengthen that determination in real-world deployment and are not invoked to fill a pre-certification evidence gap.

(Note: former Gap 5 is absorbed into item 4. Item 4 is the combined "Low-prevalence sub-indication categories" paragraph from A1. Items 1–3 remain as written in the source — Gaps 1, 2 and 3 — with their existing phrasing.)

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A2 — CEP replacement for line 1255 activity-summary row

Current row (DELETE):

| D / E / F (Gaps 4 & 5 + representativeness) | Gap 4 (autoimmune), Gap 5 (genodermatoses), §3.4 phototype representativeness | Passive / proactive surveillance of autoimmune and genodermatoses ICD-11 subsets; phototype-stratified real-world performance tracking (including Fitzpatrick V-VI post-MAN_2025 transition to real-world deployment) | Driven by real-world case accrual in deployed sites | Declared acceptable-gap thresholds per R-TF-007-002 (§6.5(e) MDCG 2020-6) | Rolling quarterly readouts; trigger-based review | CEP / CER update; claim-scope review if accrual persistently below threshold |

Replacement rows (INSERT two rows in place of the single row):

| D.1 / D.2 (autoimmune + genodermatoses) | Low-prevalence sub-indication categories (§6.3 triangulated pre-certification evidence; PMCF confirms and strengthens) | Prospective surveillance (D.1, autoimmune) and passive surveillance (D.2, genodermatoses) of the autoimmune and genodermatoses ICD-11 subsets, with retrospective analysis of the device output for each identified case; D.2 additionally draws an early Pillar 3-equivalent performance readout from the legacy-predecessor post-market report corpus in the first PMS Update Report (R-TF-007-003) | D.1: target 50 confirmed autoimmune cases within 36 months post-certification; D.2: governed by surveillance and coverage triggers plus the early legacy-corpus readout (no prospective enrolment target) | D.1 primary safety-floor: Top-3 ≥ 60 %; D.1 non-inferiority secondary: Top-3 not more than 15 pp below the V&V-demonstrated Top-3 of 0.820 (i.e., ≥ 0.67); D.2 primary safety: zero confirmed genodermatosis cases where the device output was identified by the treating HCP as contributing to patient harm; D.2 positive performance-confirmation: per-case Top-5 concordance reporting plus the early legacy-corpus Pillar 3-equivalent readout | D.1: first interim at 12 months post-certification (or at 15 cases, whichever comes first); final at 36 months or 50 cases. D.2: rolling, annual PMCF Evaluation Report integration; early legacy-corpus readout at approximately 6 months post-certification in R-TF-007-003 | Unscheduled CER update; protocol-driven re-review of the §6.3 sufficient-evidence determination if any primary, non-inferiority, safety or surveillance trigger breaches. No claim-scope review required (Pillar 1 + Pillar 2 anchors carry the pre-certification determination independently of the D-series readouts) | | E / F (Fitzpatrick V–VI + paediatric) | §3.4 phototype representativeness; paediatric representativeness (§6.5(e) acceptable gaps declared in the CER §Representativeness of the Study Populations and §Pediatric population) | Phototype-stratified real-world performance tracking (including Fitzpatrick V–VI post-MAN_2025 transition to real-world deployment); age-stratified paediatric performance tracking (0–2, 2–12, 12–18 years) within the C-series activities | Driven by real-world case accrual in deployed sites | Declared acceptable-gap thresholds per R-TF-007-002 (§6.5(e) MDCG 2020-6) | Rolling quarterly readouts; trigger-based review | CEP / CER update; claim-scope review if accrual persistently below threshold |

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A3 — CEP line 979 mermaid node (optional; split D/E/F node)

Current node:

Replacement nodes:

(Apply downstream edges consistently: every edge previously attached to DEF is now attached to the relevant node; P4 --> P5 stays unchanged.)

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A4 + B7 — CEP line 405 and CER line 2868 subspecialty-coverage row strengthening

Current row (both files — identical cell):

| Autoimmune and genodermatoses | Per-epidemiological-group ICD V&V (autoimmune AUC 0.948; genodermatoses AUC 0.905, both above the ≥ 0.80 success criterion) | R-TF-028-006 §Per-Epidemiological-Group Performance |

Replacement row:

| Autoimmune and genodermatoses | Structured literature review of image-based clinical recognition (22 load-bearing anchors CRIT1–7 ≥ 15/21) supporting the Pillar 1 Valid Clinical Association, and per-epidemiological-group ICD V&V measured on the device's stand-alone analytical output without a clinician in the loop (autoimmune AUC 0.948 with 95 % CI 0.941 – 0.954; genodermatoses AUC 0.905 with 95 % CI 0.886 – 0.924; both above the ≥ 0.80 acceptance criterion) supporting Pillar 2 Technical Performance | R-TF-015-011 State of the Art §Autoimmune and genodermatoses; R-TF-028-006 AI Release Report §Per-Epidemiological-Group Performance |

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B1 — CER replacement for line 195

Current text:

Two low-prevalence categories, autoimmune diseases (~3%) and genodermatoses (~1%), are declared as acceptable evidence gaps with justification per MDCG 2020-6 § 6.5(e). These are addressed through targeted PMCF activities documented in R-TF-007-002 Post-Market Clinical Follow-up (PMCF) Plan (see "Need for more clinical evidence" and "Necessary measures" in this CER).

Replacement text:

Two low-prevalence sub-indication categories, autoimmune dermatoses (~3 %) and genodermatoses (~1 %), are supported by triangulated pre-certification evidence judged sufficient per MDCG 2020-6 §6.3 on the four-test analysis set out in section Representativeness of the Study Populations — Pillar 1 Valid Clinical Association (22 load-bearing literature anchors, R-TF-015-011 §Autoimmune and genodermatoses) and Pillar 2 Technical Performance measured on the device's stand-alone analytical output without a clinician in the loop (per-epidemiological-group V&V in R-TF-028-006: autoimmune AUC 0.948, genodermatoses AUC 0.905; both above the pre-specified ≥ 0.80 acceptance criterion). Post-certification confirmation is pre-specified in R-TF-007-002 Post-Market Clinical Follow-up (PMCF) Plan Activities D.1 (autoimmune) and D.2 (genodermatoses) — described in sections Need for more clinical evidence and Necessary measures. These two categories are therefore not declared as §6.5(e) acceptable gaps.

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B2 — CER replacement for line 593 (consolidated-limitations item 5)

Current text:

5. Out-of-scope conditions: autoimmune dermatoses and genodermatoses are acceptable evidence gaps per MDCG 2020-6 § 6.5(e) and are addressed by passive surveillance in PMCF rather than by pre-market clinical evidence (see section Declared acceptable evidence gaps).

Replacement text:

5. Low-prevalence sub-indication categories: autoimmune dermatoses (~3 %) and genodermatoses (~1 %) are within the intended use and are supported by triangulated pre-certification evidence under MDCG 2020-6 §6.3 — Pillar 1 literature anchors in R-TF-015-011 and Pillar 2 per-epidemiological-group V&V in R-TF-028-006. PMCF Activities D.1 and D.2 confirm and strengthen the pre-certification base in real-world deployment (see section Representativeness of the Study Populations and R-TF-007-002 Activities D.1/D.2). For these two sub-categories specifically, the device's output is to be interpreted as supporting information within the healthcare professional's differential-diagnosis workup and not as a standalone diagnostic determination (see section Device outputs and the IFU Precautions).

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B3 — CER replacement for line 2359

Current text:

7. Autoimmune skin disease AI evidence (Gap 4): No published clinical skin image AI studies specifically validated on autoimmune skin conditions identified in the primary corpus.

Replacement text:

7. Autoimmune skin disease image-based clinical-recognition evidence: The primary corpus did not identify published AI-validation studies specifically focused on autoimmune skin conditions. A dedicated structured literature review was therefore executed in April 2026 and produced 22 load-bearing anchors (CRIT1–7 ≥ 15/21) supporting the Pillar 1 Valid Clinical Association for image-based recognition of the in-scope autoimmune and genodermatosis conditions. The review is appended to R-TF-015-011 as section Autoimmune and genodermatoses. Oral lichen planus retains a residual coverage item (the abstract-only anchor identified in the supplementary search was excluded because the full text was not publicly available for appraisal at the load-bearing threshold) and is routed to PMCF Activity D.1 for post-market confirmation.

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B4 — CER replacement for the D.1 and D.2 rows at lines 2710–2711

Current rows:

| D.1 | Autoimmune skin conditions (Gap 4) | Prospective surveillance, 50 cases | Top-3 accuracy ≥ 60% in confirmed autoimmune cases | More than 20% of confirmed autoimmune cases with the correct category ranked below Top-5 at annual review | | D.2 | Genodermatoses (Gap 5) | Passive surveillance, no active recruitment | Per-case clinical review; Top-5 ranking documented for each identified case | More than 3 cases in any 12-month period had all genodermatosis categories ranked below Top-5 |

Replacement rows:

| D.1 | Autoimmune dermatoses (§6.3 PMCF confirmation of triangulated pre-certification evidence) | Prospective surveillance, 50-case target justified on a systematic-misclassification-detectability rationale, 12-month and 36-month interims | Primary safety-floor: Top-3 ≥ 60 % on the 50-case cohort. Non-inferiority secondary: Top-3 post-certification not more than 15 pp below the V&V-demonstrated Top-3 of 0.820 (i.e., ≥ 0.67). Safety: zero confirmed cases where the device output was identified by the treating HCP as contributing to a clinically significant delay in diagnosis. HCP user-concordance (supporting): routine device-aided differential-diagnosis workup recorded per protocol. | > 20 % of confirmed autoimmune cases with the correct category ranked below Top-5 at any annual review, OR a breach of the non-inferiority secondary criterion, OR a breach of the primary safety-floor — triggers unscheduled CER update and protocol-driven re-review of the §6.3 sufficient-evidence determination | | D.2 | Genodermatoses (§6.3 PMCF confirmation of triangulated pre-certification evidence) | Passive surveillance, no active recruitment; surveillance and coverage triggers; early Pillar 3-equivalent performance readout from the legacy-predecessor post-market report corpus at the first PMS Update Report (R-TF-007-003) | Safety (primary): zero confirmed genodermatosis cases where the device output was identified by the treating HCP as contributing to patient harm. Per-case Top-5 concordance reporting (positive performance-confirmation) for every identified case. Early Pillar 3-equivalent performance readout on the legacy corpus slice at approximately 6 months post-certification. | > 3 confirmed genodermatosis cases in any 12-month period with all genodermatosis categories ranked below Top-5 — triggers unscheduled clinical-evaluation review. Coverage trigger: at 30 cumulative cases, a formal diagnostic-accuracy analysis is conducted and fed back into the §6.3 sufficient-evidence determination. |

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B5 — CER replacement for the §6.5(e) bundle at line 2741

Current text:

• §6.5(e) acceptable evidence gaps (autoimmune diseases, genodermatoses, Fitzpatrick V–VI) — declared per MDCG 2020-6 §6.5(e); addressed by PMCF Activities D.1, D.2, E.1 in R-TF-007-002; unscheduled CER update triggered if Fitzpatrick-stratified Top-N accuracy breaches threshold.

Replacement text (two bullets — split the bundle):

• Low-prevalence sub-indication categories (autoimmune dermatoses, genodermatoses) — not declared as §6.5(e) gaps. Pre-certification evidence is triangulated under MDCG 2020-6 §6.3 (Pillar 1 literature review in R-TF-015-011 §Autoimmune and genodermatoses; Pillar 2 per-epidemiological-group V&V in R-TF-028-006 §Per-Epidemiological-Group Performance). PMCF Activities D.1 and D.2 in R-TF-007-002 confirm and strengthen in real-world deployment; the D-series acceptance criteria and triggers are documented above.
• §6.5(e) acceptable evidence gaps (Fitzpatrick V–VI phototype representativeness, paediatric representativeness) — declared per MDCG 2020-6 §6.5(e) in sections Representativeness of the Study Populations and Pediatric population; addressed by PMCF Activities E.1 (Fitzpatrick) and F.1 (paediatric) in R-TF-007-002; unscheduled CER update triggered if Fitzpatrick-stratified or age-stratified Top-N accuracy breaches the per-band threshold.

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B6 — NEW CER sub-paragraph inside §Representativeness of the Study Populations (insert after line 1867)

Insertion point. Immediately after the existing _Note on pediatric coverage_ paragraph (line 1867), before the ##### Methodological approach to data integration and pooling subheading (line 1869).

New content:

Note on low-prevalence sub-indication categories (autoimmune dermatoses and genodermatoses). Two low-prevalence sub-indication categories — autoimmune dermatoses (~3 % of real-world dermatological presentations) and genodermatoses (~1 %) — are under-represented in the pivotal real-patient investigations because of low population prevalence and because the clinical diagnostic pathway for these conditions relies on serological, histopathological and genetic testing that is not directly reproduced in an image-based study. These two categories remain within the intended use. Pre-certification evidence is triangulated under MDCG 2020-6 §6.3 on the four-test analysis set out below, and is confirmed post-certification by PMCF Activities D.1 (autoimmune) and D.2 (genodermatoses) in R-TF-007-002.

1. Narrow and bounded scope. The two sub-indication categories account for approximately 4 % of real-world presentations combined; the remaining ~96 % carry the core benefit-risk determination independently.
2. Core benefit-risk independence. The three declared benefits (7GH Diagnostic Accuracy, 5RB Objective Severity Assessment, 3KX Care-Pathway Optimisation) are independently evidenced on the remaining ~96 % of presentations by the pre-market confirmatory clinical investigations and by the legacy-predecessor real-world evidence corpus, and do not depend on the two sub-indication categories.
3. Adequate residual evidence (two independently-scoring anchors). (a) Pillar 1 Valid Clinical Association — a dedicated structured literature review (22 load-bearing CRIT1–7 ≥ 15/21 anchors) appended to R-TF-015-011 State of the Art §Autoimmune and genodermatoses establishes that image-based clinical recognition is an accepted standard for the named conditions (DLE, lichen planus, dermatomyositis, pemphigus vulgaris, bullous pemphigoid, mucous membrane pemphigoid, morphea, cutaneous vasculitis for autoimmune; ichthyoses, NF1/NF2, tuberous sclerosis complex, epidermolysis bullosa for genodermatoses). Oral lichen planus retains a residual coverage item routed to PMCF Activity D.1. (b) Pillar 2 Technical Performance — R-TF-028-006 AI Release Report §Per-Epidemiological-Group Performance reports, measured on the device's stand-alone analytical output without a clinician in the loop, AUC 0.948 (95 % CI 0.941 – 0.954, N = 2,040, 38 classes) for autoimmune dermatoses and AUC 0.905 (95 % CI 0.886 – 0.924, N = 391, 31 classes) for genodermatoses, both above the pre-specified ≥ 0.80 acceptance criterion inherited from R-TF-028-002 AI Development Plan. The ≥ 0.80 threshold is retained across the per-epidemiological-group sub-analysis because both measure types (binary indicators and per-epidemiological-group ICD discrimination) quantify the same device property — the probability that the correct class is scored higher than any incorrect class — and because MDCG 2020-1 §4.4 Pillar 2 does not require a different numerical threshold for multi-class versus binary analytical measures. The MDCG 2020-6 Appendix III evidence-hierarchy appraisal, set out in R-TF-015-001, records that simulated-use MRMC reader studies "do not constitute 'clinical data' under the strict MDR Article 2(48) definition" and that Rank 11 supporting evidence from such studies cannot, on its own, carry a pre-certification sufficient-evidence determination on a named sub-indication; Pillar 1 Valid Clinical Association and Pillar 2 Technical Performance are therefore the two independently-scoring Test 3 anchors for these sub-indication categories and MRMC evidence, where applicable, is Pillar 3 §4.4 supporting evidence only. (c) Why the absence of pre-certification Pillar 3 evidence is regulatorily acceptable for these two sub-indications — three cumulative elements: the device's CLAIM for these sub-categories is qualified by the Device Output Warning as supporting information within the HCP's differential-diagnosis workup (see section Consolidated limitations of the device and the IFU Device Output Warnings); final-diagnosis responsibility rests wholly with the healthcare professional and is confirmed by histopathological, serological or genetic testing outside the device's loop, consistent with the current standard of care for autoimmune dermatoses and genodermatoses; and Pillar 3 real-world clinical performance is pre-specified for post-certification confirmation in PMCF Activities D.1 and D.2. (d) Scope boundary with adjacent coverage gaps — MAN_2025 (Pillar 3 §4.4 at Rank 11; Fitzpatrick V–VI phototype representativeness) and the legacy-device real-world-evidence study R-TF-015-012 (Pillar 3 at Rank 8 primary with a supplementary case at Rank 4 for the quantitative endpoints) address different sub-indication and coverage considerations and are therefore not invoked as Test 3 anchors for autoimmune dermatoses or genodermatoses; both remain part of the broader evidence envelope that carries the three declared benefits for the remaining ~96 % of presentations.
4. PMCF confirmation (confirms and strengthens; does not fill or close). Activity D.1 (prospective surveillance of autoimmune dermatoses, 50-case target justified on a systematic-misclassification-detectability rationale, 12-month and 36-month interim analyses, Top-3 ≥ 60 % primary safety-floor acceptance criterion together with a non-inferiority secondary criterion against the V&V-demonstrated Top-3, safety and surveillance triggers) and Activity D.2 (passive surveillance of genodermatoses with safety and coverage triggers, plus an early Pillar 3-equivalent performance readout on the legacy-predecessor post-market report corpus scheduled into the first PMS Update Report) in R-TF-007-002 confirm and strengthen the pre-certification base in routine clinical deployment. The PMCF Plan additionally commits to analysing the autoimmune-dermatoses and genodermatoses slices of the ≈ 250,000 legacy-predecessor post-market report corpus in the first PMS Update Report (R-TF-007-003), consistent with MDCG 2020-6 §6.3 under which PMCF confirms and strengthens an adequately-evidenced pre-certification base and is not invoked to fill or close pre-certification evidence gaps.

The claim for these two sub-indication categories is qualified by an output-interpretation warning rendered in the Device Output Warnings section of the IFU, which states that for autoimmune dermatoses and genodermatoses the device provides a probability ranking within the broader ICD-11 output distribution that is to be interpreted as supporting information within the healthcare professional's differential-diagnosis workup; final diagnosis for these categories is an HCP determination based on clinical evaluation and histopathological, serological or genetic examination as per the current standard of care, and the device's probability ranking is supporting information only. The intended use and indication remain unchanged.

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Review notes for this file

• Audit-deliverable-reviewer concern: check that no references to task-3b5, task-3b7, bsi-non-conformities, or any engineering path (TS/JSON/Python/React/Docusaurus/npm/git) appear in the replacement prose. The prose cites only regulatory identifiers (R-TF-015-001, R-TF-015-003, R-TF-015-011, R-TF-028-006, R-TF-007-002, R-TF-007-003, MDCG clauses, MDR articles).
• BSI clinical-auditor concern: check that "confirms / strengthens" discipline holds across every sentence; check that §6.3 is cited correctly (sufficient evidence, not "acceptable gap"); check that Pillar 1 and Pillar 2 anchors are correctly attributed (VCA + analytical performance, not conflated with Pillar 3); check that the quote about MRMC not being Article 2(48) clinical data is not misrepresented.
• Celine clinical-consultant concern: check pillar mapping — Pillar 1 (VCA literature) + Pillar 2 (ICD analytical performance) are the Test 3 anchors; MRMC would be Pillar 3 §4.4 supporting only. Check Rank-vs-Pillar orthogonality: Rank 6 (literature) and Rank 12 (bench / analytical V&V) populate different ranks than the Pillar 3 ranks; neither the Rank-11 simulated-use MRMC nor a pre-certification Pillar 3 study is load-bearing on the Test 3 anchors here.