Response

BSI Observation

The device description and intended purpose/indications remain unclear, specifically: the list of possible ICD categories relevant to the device; the specific indications including the comprehensive list of malignant/high-risk diseases; and the specific outputs of the device. BSI requested a clear and comprehensive device description, intended purpose, and indication demonstrating compliance with Annex II and Annex XIV 1(a), sub-bullets 2 and 3.

Response

We thank the reviewer for this observation. We acknowledge that the CER's device description, as previously submitted, relied on shared components that, while accurate, did not provide the level of standalone specificity required for independent clinical review. We have updated R-TF-015-003 Clinical Evaluation Report with explicit, self-contained content addressing each of the three points raised. The updated device description section is designed to satisfy the requirements of MEDDEV 2.7.1 Rev 4, Annex A3 and MDR Annex XIV 1(a), sub-bullets 2 and 3, without requiring cross-reference to other technical file documents.

1. ICD categories relevant to the device

The device covers 346 validated ICD-11 categories spanning diseases of the skin and related structures. These categories are drawn primarily from ICD-11 chapter 14 (Diseases of the skin), with additional categories from chapter 2 (Neoplasms) for malignant and pre-malignant conditions, and chapter 1 (Certain infectious or parasitic diseases) for cutaneous infections. The categories were derived from the device's training dataset through the mapping process documented in R-TF-028-004 Data Annotation Instructions — ICD-11 Mapping, which consolidates visually indistinguishable conditions into single "Visible ICD-11 category" targets to ensure clinically meaningful discrimination.

We have added a new subsection "Scope of ICD-11 categories" to the CER (R-TF-015-003) providing a structured summary of all 346 categories organised by epidemiological domain, based on the Global Burden of Skin Disease framework (Karimkhani et al. 2017):

• Infectious diseases (~57% of global burden): tinea variants (corporis, pedis, capitis, versicolor), herpes simplex, herpes zoster, bacterial cellulitis, impetigo, scabies, molluscum contagiosum, cutaneous leishmaniasis, verruca vulgaris, and others
• Other conditions (~19%): acne vulgaris, alopecia areata, vitiligo, urticaria, keloid, androgenetic alopecia, contact dermatitis (irritant), prurigo nodularis, and others
• Inflammatory diseases (~15%): psoriasis variants (vulgaris, guttate, pustular), eczema, atopic dermatitis, seborrhoeic dermatitis, lichen planus, rosacea, pityriasis rosea, granuloma annulare, and others
• Malignant and pre-malignant neoplasms (~5%): see full enumeration in point 2 below
• Autoimmune diseases (~3%): pemphigus variants, bullous pemphigoid, cutaneous lupus erythematosus, dermatomyositis, morphea
• Vascular conditions (~1%): vasculitis variants, venous ulcer, chronic arterial occlusive disease, livedoid vasculopathy
• Genodermatoses (~1%): ichthyosis, epidermolysis bullosa, Darier disease, neurofibromatosis

The complete list of 346 categories and their ICD-11 code mappings is maintained in R-TF-028-004.

2. Specific indications including malignant and high-risk conditions

The formal medical indication of the device is: all diseases of the skin and its appendages, encompassing conditions affecting the epidermis, its appendages and associated mucous membranes, the dermis, the cutaneous vasculature, and the subcutaneous tissue. In operational terms, the device is indicated for use on images of visible skin abnormalities presented by any patient for whom clinical assessment by a healthcare professional is appropriate. The device covers all 346 validated ICD-11 categories described above.

We have added a new subsection "High-risk and malignant conditions" to the CER (R-TF-015-003) providing the comprehensive enumeration requested by BSI. Among the 346 ICD-11 categories in the probability distribution, the following are clinically classified as malignant neoplasms:

• Cutaneous melanoma (ICD-11: 2C30), including acral lentiginous melanoma (2C30.3) and amelanotic malignant melanoma (2E63.00)
• Basal cell carcinoma (2C32)
• Squamous cell carcinoma (2C31)
• Merkel cell carcinoma (2C34)
• Adnexal carcinoma (2C33)
• Cutaneous T-cell lymphoma (2B0Z), including mycosis fungoides (2B01) and pleomorphic T-cell lymphoma (2B0Y)
• Dermatofibrosarcoma protuberans (2B53.Y)
• Angiosarcoma (2B56.1)
• Metastatic malignant neoplasm involving skin (2E08)

In addition, the device covers pre-malignant conditions — actinic keratosis and Bowen disease — as well as high-risk non-malignant conditions requiring urgent clinical assessment, including Stevens-Johnson syndrome and toxic epidermal necrolysis (EB13), erythroderma, drug eruptions, bacterial cellulitis, and dissecting cellulitis.

Framing consistent with the device's output architecture: The device does not independently diagnose malignancy. It outputs a probability distribution across all 346 ICD-11 categories simultaneously; the malignant categories listed above are elements of this distribution. Clinical benefit 7GH, sub-criterion (c), specifically validates that the device's distributional output, when presented to healthcare professionals, improves their accuracy in assessing lesions suspicious for skin cancer (AUC criterion: ≥ 0.90; achieved: 0.97). The clinical decision and specialist referral remain with the healthcare professional at all times.

3. Specific outputs of the device

We have added a new subsection "Device outputs" to the CER (R-TF-015-003) providing a structured, unambiguous specification of all three output types. The device produces three categories of output for every image processed, regardless of the condition depicted:

Output 1 — ICD-11 probability distribution. For each image, the device outputs a normalised probability vector across all 346 validated ICD-11 categories. Each element represents the estimated probability that the image depicts a condition belonging to that ICD-11 category; the probabilities sum to 1.0. The device always outputs the full distribution across all 346 categories and does not produce a binary positive/negative result for any specific condition.

Output 2 — Clinical sign measurements. The device provides quantitative measurements for 37 clinical signs using three measurement methods:

• Intensity (continuous scale, 0–10): erythema, desquamation, induration, crusting, xerosis, swelling, oozing, excoriation, lichenification, exudation, wound depth, wound border, undermining, necrotic tissue, granulation tissue, epithelialization, maceration, slough or biofilm, hypopigmentation or depigmentation, hyperpigmentation, scar, and external material over the lesion
• Count (integer, with bounding boxes): nodule, papule, pustule, cyst, comedone, abscess, hive, draining tunnel, non-draining tunnel, inflammatory lesion, scab, spot, and blister
• Extent (cm² or percentage of affected area, with segmentation masks): hair loss, and exposed wound/bone and adjacent tissues

Output 3 — Explainability media. For count-based signs, the device outputs bounding boxes identifying the location of each detected structure. For extent-based signs, the device outputs segmentation masks delineating the affected area.

The device does not output a diagnosis, a binary positive/negative result, a treatment recommendation, a referral decision, or a prognosis. The device output is one element of the overall clinical assessment; the healthcare professional must consider the patient's medical history and other clinical findings before reaching a clinical decision.

Per MDCG 2020-1, Valid Clinical Association (VCA) has been established for both claimed output types. VCA for the ICD-11 probability distribution is demonstrated via systematic literature review (R-TF-015-011 State of the Art), establishing that the visual morphological features processed by the AI model are clinically associated with the ICD-11 dermatological categories in the distribution. VCA for the quantitative clinical sign severity measurements is established via the clinical validation of structured severity scoring scales (EASI, IHS4, DLQI, and others) documented in peer-reviewed literature and referenced in R-TF-015-011.

Documentation updated

1. R-TF-015-003 (Clinical Evaluation Report): Three new subsections added to the device description: "Device outputs" (specifying all three output types with full detail, including the complete list of 37 clinical signs and their measurement methods), "Scope of ICD-11 categories" (structured summary of all 346 categories organised by epidemiological domain with illustrative condition examples), and "High-risk and malignant conditions" (explicit enumeration of all malignant ICD-11 categories with ICD-11 codes, plus pre-malignant and high-risk conditions). The updated section explicitly states that VCA per MDCG 2020-1 has been established for both claimed outputs. Red-lined version provided.