Bringing an aesthetic or skin-contact medical device such as wound dressing to market requires rigorous safety evaluation. Regulators such as the U.S. FDA and the EU MDR require that manufacturers demonstrate their product does not cause irritation, sensitization, or allergic reactions under real-world use.
Two clinical studies are typically required:
- HRIPT (Human Repeat Insult Patch Test) to evaluates delayed irritation and sensitization.
- SPT (Skin Prick Test) to evaluates immediate hypersensitivity (allergy).
Together, these studies form a comprehensive safety profile.
What is HRIPT (Human Repeat Insult Patch Test)?
The Human Repeat Insult Patch Test (HRIPT) is the gold standard clinical method used to evaluate whether a product causes delayed irritation or sensitization after repeated exposure. Unlike a single application test, HRIPT is specifically designed to mimic real-life use scenarios, where patients are exposed to a wound dressing, patch, or aesthetic device multiple times over weeks or months.
Study Design & Phases
An HRIPT (Human Repeat Insult Patch Test) typically follows a three-phase design:
Induction Phase (Repeated Application)
- The investigational product (e.g., wound dressing, patch, topical device) is applied under occlusion to the same site on the back or arm of healthy volunteers.
- Applications are repeated several times per week for 3–4 weeks.
- The goal is to "prime" the immune system if the product has sensitization potential.
Rest Phase (Recovery Period)
- A break period of 10–14 days allows any short-term irritation to subside.
- If the immune system has been sensitized during induction, it will remain "primed" to react when re-exposed.
Challenge Phase (Re-exposure)
- The product is reapplied to a new site (often on the opposite arm or a different patch location).
- After the 72 hours grading/assessment, investigators assess whether an allergic-type response occurs upon re-exposure, which would indicate sensitization.
Scoring System: Berger/Bowman Scale
Skin reactions are graded using the Berger/Bowman scale (0–4):
- 0: No visible reaction
- 1: Barely perceptible erythema (mild redness)
- 2: Moderate erythema, possible edema
- 3: Strong erythema with papules/vesicles
- 4: Severe reaction with spreading dermatitis
This objective system ensures consistency across investigators and helps differentiate normal irritation from clinically relevant sensitization.
Specific FDA-accepted adaptation of the Berger/Bowman Scoring Scale where grades 0–7 are used, but scores are collapsed (0 or 1 or 2 or 3) for analysis.
Berger/Bowman Scoring Scale (Expanded Grades 0–7, Collapsed into 0–3 Scores)
| Grade | Score | Definition |
|---|---|---|
| 0 | 0 | No evidence of irritation |
| 1 | 1 | Minimal erythema; barely perceptible |
| 2 | 2 | Definite erythema, readily visible; OR minimal edema; OR minimal papular response |
| 3 | 3 | Erythema and papules |
| 4 | 3 | Definite edema |
| 5 | 3 | Erythema, edema, and papules |
| 6 | 3 | Vesicular eruption |
| 7 | 3 | Strong reaction spreading beyond test site |
When to Use Which?
- Medical device irritation/biocompatibility: FDA and ISO often accept 0–4 Berger/Bowman.
- Cosmetics, topical drugs, detailed HRIPT: Regulators may prefer 0–7 scale for sensitivity.
Meet Our HRIPT & SPT Experts
Dr. Nikhil Khadabadi
Chief Medical Officer Orthopedics & Spine
Dr. Nikhil brings extensive clinical expertise in dermatological safety assessments and aesthetic device evaluations. His deep understanding of skin irritation mechanisms and regulatory pathways ensures rigorous HRIPT and SPT protocol design.
Prof. Luc Teot
Advisory Board Wound-Care
Prof. Luc Teot is a world-renowned wound care specialist with decades of experience in clinical investigations. His leadership ensures that HRIPT and SPT studies meet the highest standards of scientific rigor and regulatory acceptance.
Study Design & Methodology
An SPT follows a simple but highly controlled procedure:
Skin Preparation
- The volar surface of the forearm or the upper back is cleaned.
- Small drops of test solutions (the investigational product or its extracts) are placed on the skin.
Prick Application
- A sterile lancet is used to lightly prick the skin through each drop without drawing blood.
- This introduces trace amounts of the test substance into the epidermis.
Observation Period
- The site is observed after 15–20 minutes.
- Immediate skin reactions (redness, wheals, flare-ups) indicate IgE-mediated hypersensitivity.
Controls
- A positive control (histamine) ensures the skin reacts as expected.
- A negative control (saline) ensures there is no false background response.
Scoring System
SPT results are typically scored based on wheal (swelling) and flare (redness) diameter, compared to the histamine positive control:
| Score | Definition |
|---|---|
| 0 | No reaction |
| +/- | Erythema < 3 mm, no wheal |
| 1+ | Wheal 3–5 mm |
| 2+ | Wheal 5–7 mm |
| 3+ | Wheal 7–9 mm |
| 4+ | Wheal ≥ 9 mm or with pseudopodia (irregular borders) |
This standardized scoring system ensures quantifiable, reproducible data on immediate allergic responses.
Why SPT Matters for FDA
Immediate Risk Detection:
Identifies rapid IgE-mediated allergic reactions, which can cause hives, swelling, or in rare cases, anaphylaxis.
Complement to HRIPT:
While HRIPT assesses delayed-type hypersensitivity (Type IV), SPT specifically detects immediate-type hypersensitivity (Type I). Both are needed for a full immunological safety profile.
Patient Safety:
Early detection of immediate allergy risk prevents serious adverse events in real-world use.
Regulatory Requirement:
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FDA recommends SPT alongside HRIPT for aesthetic devices, dressings, adhesives, and other long-term skin-contact products.
Typical Study Parameters
- Subjects: ~20 healthy adults
- Duration: ~1–2 weeks (including screening and reporting)
- Endpoints: Incidence and severity of immediate wheal/flare reactions, relative to controls
- Output: Confirmation that the product does not cause clinically relevant immediate allergic responses
Skin Type Diversity required by FDA and Notified body
When evaluating the safety of aesthetic devices, skin type diversity is importan to know that the appearance and detectability of irritation or allergy differ significantly across skin tones and can impact study outcomes.
The Fitzpatrick Skin Type Classification
The Fitzpatrick scale is the international standard used to classify skin types based on pigmentation and response to U
| Type | Description |
|---|---|
| Type I | Very fair skin, always burns, never tans |
| Type II | Fair skin, usually burns, tans minimally |
| Type III | Light to olive skin, sometimes burns, tans gradually |
| Type IV | Moderate brown skin, rarely burns, tans easily |
| Type V | Dark brown skin, very rarely burns, tans profusely |
| Type VI | Deeply pigmented dark brown to black skin, never burns |
This classification is directly relevant to HRIPT and SPT studies because erythema (redness) ,the earliest visible sign of irritation or allergy is easier to detect in lighter skin (I–III) and often masked in darker skin (IV–VI).
FDA's Concern
The FDA requires that studies conducted in regions with predominantly darker skin types (IV–VI) may miss early signs of erythema that could correspond to a Berger/Bowman score of 1 or 2. These early reactions, although mild, are clinically relevant because they may:
- Signal an influx of inflammatory cells
- Lead to delayed wound healing
- Increase risk of scarring or granuloma formation
- Conceal early infection signals beneath the device
Thus, FDA recommends at least 10% of participants represent Fitzpatrick skin types I–III to ensure sensitivity in detecting early-stage reactions.
Practical Implications for Clinical Trials
Recruitment Planning
- Studies must deliberately recruit lighter skin types (I–III), especially in countries where the population skews toward IV–VI.
- Recruitment campaigns may need to target specific geographic regions or populations to ensure representation.
Investigator Training
Clinicians must be trained to recognize erythema across different skin types, including subtler signs such as texture changes, edema, or heat in darker tones.
Photographic Documentation
Standardized digital imaging is critical, since erythema may be under-detected visually in darker skin. EDC platforms like MILO allow investigators to capture and centralize high-resolution photos for expert review.
Regulatory Justification
- Medical device manufacturers should document Fitzpatrick classification of each subject in their protocol and final report.
- If lighter skin types (I–III) are underrepresented, additional testing may be required.
Why This Matters for Aesthetic Devices: Unlike systemic drugs, aesthetic devices and dressings
Why This Matters for Aesthetic Devices: Unlike systemic drugs, aesthetic devices and dressings are applied directly to the skin, making dermatological safety across diverse populations a priority. Because these products are used in global markets, regulators expect assurance that all skin types are adequately protected. In short: inclusivity in skin type representation is not just good practice ,it's a regulatory expectation.
HRIPT + SPT Execution Timeline (Gantt Chart)
Here's a typical 6–7 month execution timeline for an FDA-aligned HRIPT and SPT program:
How Eclevar MedTech Helps Medical device manufacturers Succeed
At Eclevar MedTech, we offer a full-service CRO solution tailored for FDA and EU MDR expectations in aesthetic devices. Our differentiator lies in combining clinical operations, patient recruitment, regulatory expertise, and MILO technology into one streamlined process.
Wound care and aesthetics manufacturers testify to the services and technology that Eclevar provides:
1️⃣ Patient Recruitment strategy for Fitzpatrick I–III Representation
- Targeted Campaigns: Use of social media advertising, referral incentives to ensure sufficient Fitzpatrick I–III recruitment (≥10%), often underrepresented in global studies.
- We often recruit backup sites from different regions to ensure that the recruitment plan is not compromised if the primary sites fail to meet their patient enrollment commitments
Hospital Partnerships for Aesthetics trials: Access to patients through trusted centers such as:
- Hôpital Henri-Mondor (AP-HP)
- Hôpital Rothschild
- CHU Montpellier
2️⃣ MILO: AI-Powered Data Capture for Dermatology
- Photographic Data Capture: Standardized wound/skin photographs uploaded directly into MILO, linked to subject IDs.
- Integrated Scoring: Investigators record Berger/Bowman irritation grades directly into the EDC.
- Automated QC: Real-time checks detect missing or inconsistent entries.
- Audit-Ready Compliance: Full traceability, 21 CFR Part 11 compliant, designed for FDA and EU MDR audits.
3️⃣ Data Management & Biostatistics Excellence
ECLEVAR has a world-class data management and biostatistics department with extensive expertise in both EMEA and FDA requirements:
- ECLEVAR MEDTECH Data Management team will draft the Data Management Plan (DMP) and eCRF Guidelines during study start-up and send the DMP to Serigenmed for review. The DMP and eCRF Guidelines may be revised as needed throughout the study as processes change and adapt to the reality of the study.
- ECLEVAR HEALTHTECH's Data Management team will develop unique study-specific eCRFs in the MILO EDC system that closely mirror the CRFs. This budget estimate includes programming of skip logic, edit checks, and user acceptance testing of the system
- ECLEVAR HEALTHTECH's Data Management team will program tablets at the sites before site
- ECLEVAR MEDTECH 's Data Management team will prepare reports based on the data, including but not limited to enrollment, demographic summaries, adverse events, protocol
- HEALTHTECH's Data Management team will perform a final database lock and work closely with the CRAs to ensure all queries have been closed, data has been source data verified deviations, and data trends activation.
4️⃣ Internal Clinical Review & Oversight
ECLEVAR has in house word class clinical review with experience within notified bodies,
- Medical Oversight: In-house clinical reviewers evaluate adverse events (erythema, dermatitis, granuloma, hypersensitivity).
- Materiovigilance: Real-time SAE and device dysfunction reporting.
- Project Coordination: Dedicated clinical project managers oversee timelines, budget, and stakeholder communication.
- KOL Engagement: Coordination with dermatology experts to ensure scientific robustness and regulatory alignment.
Ready to Launch Your HRIPT & SPT Studies?
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