The device is indicated for use for applying ink to the skin to identify the margins for radiation therapy. The device is intended to be used in clinical settings by Radiotherapy professionals.

Device Description

The Comfort Marker 2.0 is an application system for placing reference marks on or in patient's skin to facilitate set-up for radiation therapy treatment. The device includes the following components:

1. Battery powered control unit with pen
1. Main powered docking station with adapter and
1. Safety needle (single use, sterile)

Mode of operation: To achieve the intended use, the device uses a safety needle (shown in figure 2). This actuation is achieved by a longitudinal movement of the driving rod inside the pen. The driving mechanism comprises electromagnetic coils, switched on and off by the controller for generating magnetic fields. Hereby, the distance moved by the driving rod can be controlled precisely by controlling the amount of applied energy. The driving device comprises a guiding mechanism arranged for allowing only movement of the driving rod along the longitudinal direction. The actual distance travel is measured with a measuring coil and used to control the desired depth setting. The system contains a mechanical end stop in the safety needle to ensure that the needle will not protrude more than 1 mm. The docking station is used to recharge the control unit.

AI/ML Overview

The provided text describes the "Comfort Marker 2.0," a device for applying ink to the skin to identify margins for radiation therapy. It details the device's technical aspects, regulatory information, and summary of non-clinical/bench studies and a limited clinical study.

However, the Acceptance Criteria and the study proving the device meets those criteria are primarily focused on the physical and functional aspects of the device itself (e.g., needle penetration, material compatibility, sterility, electrical safety, software validation, and the durability/visibility of the marks), rather than a diagnostic AI system with associated performance metrics like sensitivity, specificity, or reader improvement.

Thus, the requested table and MRMC study details are not directly applicable in the typical sense for a diagnostic AI system using image analysis. The "study that proves the device meets the acceptance criteria" refers to the various bench tests and the limited human volunteer study that validate the device's physical performance, safety, and the persistence of the applied marks.

Nonetheless, I will extract the closest equivalents to "acceptance criteria" and "device performance" from the provided text and present them as requested, acknowledging the difference in context from an AI diagnostic device.

Acceptance Criteria and Reported Device Performance

Given that this is a physical device for marking, the "acceptance criteria" are derived from the performance tests and regulatory requirements for safety and functionality. The "reported device performance" refers to the results of these tests as stated in the document.

Table 1: Acceptance Criteria (as inferred from tests) and Reported Device Performance

Acceptance Criteria (Inferred from Study Purpose/Requirements)	Reported Device Performance
Sterility
SAL (Sterility Assurance Level) of needle cartridge	At least 10^-6 for needle cartridge (Validated per ANSVAAMI/ISO 11135:2014)
Sterilant Residuals	Under acceptable limits for EO and ECH
Packaging Integrity over Shelf-Life	Met acceptance criteria for seal strength and dye penetration tests after accelerated aging equivalent to one year (Evaluated per ISO 11607-1:2019)
Electrical Safety & EMC
Compliance with IEC 60601-1 (Basic Safety)	Passed all relevant portions of testing
Compliance with IEC 60601-1-2 (EMC)	Passed all relevant portions of testing
Compliance with IEC 60601-1-6 (Usability)	Passed all relevant portions of testing
Software
Verification & Validation (V&V)	Met pass/fail criteria at unit, integration, and system level. Hazard analysis performed and addressed.
Performance Testing (Bench)
Puncture Rate at each depth setting	Demonstrated operation at intended puncture rate on skin substitute (specifics not detailed)
Needle Puncture Depth	Evaluated depth of penetration into skin substitute at each depth setting (specifics not detailed)
Needle Sharpness	Tested based on required force for piercing standardized film (specifics not detailed)
Needle Arrangement	Demonstrated proper circular pattern after assembly (specifics not detailed)
Needle Protrusion	Ensured needle does not protrude more than 1 mm from tip housing (Confirmed by mechanical end stop in safety needle).
Needle Dimension (diameter, straightness)	Ensured within specifications (specifics not detailed)
Tip-to-Tip Alignment	Evaluated alignment of each needle tip within the assembly (specifics not detailed)
Glue Strength	Evaluated strength of bond between needles and carrier (specifics not detailed)
Squeeze Test (Needle carrier in housing)	Demonstrated carrier stays within protective housing when squeezed by hand (specifics not detailed)
Drop Test (Needle housing shielding)	Demonstrated adequate shielding of needle tips when dropped (specifics not detailed)
Colorant Migration (Fluid ingress protection)	Demonstrated adequate protection against fluid ingress into the handpiece.
Clinical Performance (Human Volunteer Study)
Ability to place well-defined reference points	Yes, well-defined reference points placed using Accu-Tatt® at all three depth settings (0.25, 0.45, and 0.75 mm).
Absence of Colorant Migration	Did not show any migration on the skin.
Visibility and Duration of Marks	All reference points from Accu-Tatt® were clearly visible during week 8 ("until" "a period in which radiotherapy treatment is provided"). Marks at 0.25 mm (lowest depth) faded at week 12 in most participants, but no impact on clinical treatment was observed.
Compatibility with indicated colorant	Confirmed with Accu-Tatt® usage.
Reproducible delivery of colorant	Implied by successful placement of well-defined points across volunteers and settings.

2. Sample size used for the test set and the data provenance

Test Set (Clinical Study): "(b) (4) healthy human volunteers" participated in the study. The specific number is redacted, but indicated as a count of men and women (e.g., "10 (4) men and " women").
Data Provenance: The study was conducted in a radiotherapy preparation room. The country of origin is not explicitly stated for the data itself, but the sponsor is from the Netherlands ("Medical Precision B.V. Zwolle Netherlands") and the ink used was Accu-Tatt® "in the United States of America". The study seems to be prospective, as it involved actively recruiting and following up with volunteers over 12 weeks.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

Ground Truth Establishment (Clinical Study): The document states: "The procedure was performed in a radiotherapy preparation room by a radiotherapy technician." and "The reference points were marked according to the Comfort Marker 2.0 instructions for use."
Expert Qualifications: The assessment of mark visibility, migration, and clearance was likely done by the "radiotherapy professional" mentioned in the description of expected use and assessment. Their specific qualifications (e.g., years of experience, independent adjudication) are not detailed in the provided text. No formal expert panel for ground truth generation (as for an AI diagnostic device) is described.

4. Adjudication method for the test set

Adjudication Method: Not applicable in the context of this device's clinical study. The study involved placement, observation, and documentation of the marks. There is no mention of multiple readers or an adjudication process for subjective interpretation of results, as there would be for a diagnostic imaging study.

5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

MRMC Study: No, an MRMC comparative effectiveness study was not done. This is a physical marking device, not an AI diagnostic system. There is no AI component assisting human readers for interpretation, hence no "effect size of how much human readers improve with AI vs without AI assistance" can be calculated or is relevant to this submission.

6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done

Standalone Performance: Not applicable directly as this is not an AI algorithm. The closest equivalent would be the bench testing, which evaluates the device's mechanical and electrical performance characteristics in a "standalone" fashion (without human interaction beyond operating the device). For instance, puncture rate, penetration depth, electrical safety, and software functionality tests are "algorithm only" in the sense that they assess the device's inherent functional capabilities.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

Type of Ground Truth (Clinical Study): The ground truth for the clinical study was qualitative observation and documentation of physical attributes:
- Visibility: "well defined reference points," "clearly visible."
- Migration: "did not show any migration."
- Duration: "faded away at week 12," "no impact on clinical treatment was observed" (outcomes related to the mark's utility rather than direct patient outcomes).
- The assessment was based on direct observation by a "radiotherapy technician" and potentially other "radiotherapy professionals." It's best described as clinical observation/assessment by trained personnel rather than a formal expert consensus or pathology.

8. The sample size for the training set

Training Set Sample Size: Not applicable. This is a physical device, not a machine learning model. Therefore, no "training set" in the context of AI model development exists.

9. How the ground truth for the training set was established

Ground Truth for Training Set Establishment: Not applicable, as there is no AI training set.

Summary

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DE NOVO CLASSIFICATION REQUEST FOR COMFORT MARKER 2.0.

REGULATORY INFORMATION

FDA identifies this generic type of device as:

Radiation therapy marking device. A radiation therapy marking device is a powered device that transdermally delivers a permanent or temporary colorant to the skin for the purpose of placing marks to guide radiation therapy. This classification does not include devices with reusable or reprocessed needles or devices intended for diagnostic, therapeutic, or aesthetic use or to deliver other products for these uses.

NEW REGULATION NUMBER: 21 CFR 892.5785

CLASSIFICATION: Class II

PRODUCT CODE: QRN

BACKGROUND

DEVICE NAME: Comfort Marker 2.0.

SUBMISSION NUMBER: DEN200041

DATE DE NOVO RECEIVED: June 22, 2020

SPONSOR INFORMATION:

Medical Precision B.V. Telfordstraat 9 - 30 NL 8013 RL. Zwolle Netherlands

INDICATIONS FOR USE

The Comfort Marker 2.0. is indicated as follows:

The device is indicated for use for applying ink to the skin to identify the margins for radiation therapy. The device is intended to be used in clinical settings by Radiotherapy professionals.

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LIMITATIONS

The sale, distribution, and use of the Comfort Marker 2.0 are restricted to prescription use in accordance with 21 CFR 801.109.

Colorant is not distributed with this device.

Do not use the device on damaged skin.

Do not use the device on skin with dermatitis.

The Safety Needle is sterile, single use and cannot be reprocessed.

Only use specified consumables.

Not intended for use in magnetic resonance imaging rooms.

PLEASE REFER TO THE LABELING FOR A COMPLETE LIST OF WARNINGS, PRECAUTIONS AND CONTRAINDICATIONS.

DEVICE DESCRIPTION

The Comfort Marker 2.0 is an application system for placing reference marks on or in patient's skin to facilitate set-up for radiation therapy treatment. The device includes the following components:

1. Battery powered control unit with pen
1. Main powered docking station with adapter and
1. Safety needle (single use, sterile)

Figure 1: Control unit, Pen (with safety needles) and docking station

Image /page/1/Picture/15 description: The image shows a control unit, pen, and docking station. The control unit is white and has a power button, as well as three colored buttons: green, pink, and blue. The pen is blue and is connected to the control unit by a black cord. The docking station is white and has a slot for the pen.

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Image /page/2/Figure/1 description: The image shows a safety needle assembly. The assembly includes a carrier with needles, a tip, and a spring. The image also includes a section view of the assembled needle, labeled SECTION A-A. The length of the assembly is labeled as (42,60).

Direction of use: Reference points / markers are placed transdermally to facilitate patient set-up for radiation therapy treatment. After disinfection of the skin area, placement of the Safety Needle on the pen, calibration of the system and applying the colorant, the user selects the shallow setting on the Control Unit and places the marker. If the user decides the marker point is not sufficiently visible, the medium setting on the control unit is selected.

SUMMARY OF NONCLINICAL/BENCH STUDIES

STERILITY

The safety needle is a sterile, single use component of the device system. The safety needle is sterilized using EO sterilization and sterilant residuals were quantified and under the acceptable limits for EO and ECH. The sterilization method was validated per ANSVAAMI/ISO 11135:2014: Sterilization of health-care products - Ethylene oxide -Requirements for the development, validation and routine control of a sterilization process for medical devices. The sterility assurance level (SAL) for the needle cartridge is at least 10 %.

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The requirements of the packaging system for the safety needle were evaluated in accordance with ISO 11607-1:2019 Requirements for materials, sterile barrier systems and packaging systems. The shelf-life of the needle cartridge was evaluated after accelerated aging equivalent to one year. The package integrity was evaluated using the seal strength test and the dye penetration test to demonstrate the performance of the sterile barrier system (SBS) over time. The test article met the acceptance criteria for each test.

ELECTRICAL SAFETY AND ELECTROMAGNETIC CAPABILITY (EMC)

The following Electrical Safety and EMC testing has been performed:

ANSI/AAMI ES60601- 1:2005+A2 (R2012) +A1: Medical Electrical Equipment -. Part 1: General Reauirements For Basic Safety And Essential Performance (IEC 60601-1:2005, MOD) (Consolidated Text) (Includes ANSI/AAMI ES60601-1:2005/(R)2012 And A1:2012, C1:2009/(R)2012 And A2:2010/(R)2012)
IEC 60601-1-2: 2014 (Edition 4): Medical electrical equipment Part 1-2 General . requirements for basic safety and essential performance – Electromagnetic compatibility
. IEC 60601-1-6: Collateral Standard: Usability

The Comfort Marker 2.0 passed all relevant portions of the testing.

SOFTWARE

The software is responsible for implementing and testing the required drivers, communication interface and the application software for both the Comfort Marker 2.0 control unit and pen. All of the elements of software information corresponding to moderate level of concern (LOC) devices as outlined in FDA's guidance document "Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices" (issued May 11, 2005) were provided. Adequate documentation describing the software development program was provided. Verification and validation (V&V) activities were described at the unit, integration, and system level and the results of these activities met the pass/fail criteria. In addition, a hazard analysis from both the patient's and user's standpoint was performed, hazards were addressed; and an appropriate validation process has been carried out.

PERFORMANCE TESTING - BENCH

Bench testing was conducted to demonstrate that the Comfort Marker 2.0 performs as expected under the anticipated conditions of use. This testing included evaluation of key device parameters such as needle penetration depth, puncture rate, and the ability of the safety features of the device to mitigate the risk of cross-contamination. The following bench testing was conducted to demonstrate the device performance characteristics:

. Puncture Rate: The purpose of this test was to demonstrate that the device operates at the intended puncture rate at each depth setting when used on a skin substitute.

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Needle Puncture Depth: The purpose of this test was to evaluate the depth of needle . penetration into a skin substitute at each depth setting.
Needle Sharpness: The purpose of this test is to test the sharpness of the needle based ● on required force for piercing standardized film.
Needle Arrangement: The objective of this test is to demonstrate that the needles are ● properly arranged in a circular pattern after assembly.
. Needle Protrusion: The purpose of this test was to ensure that the needle does not protrude more than 1 mm from the tip housing.
Needle Dimension: The purpose of this test was to ensure that the needle diameter . and straightness are within specifications
Tip-to-Tip Alignment: The purpose of this test was to evaluate the alignment of each . needle tip within the needle assembly.
Glue Strength: The purpose of this test was to evaluate the strength of the bond ● between the needles and the needle carrier.
Squeeze Test: The purpose of this test was to demonstrate that the needle carrier stays within the protective housing when squeezed by hand during assembly.
Drop Test: The purpose of this test was to demonstrate that the needle housing adequately shields the needle tips when dropped.
. Colorant Migration: The purpose of this test was to demonstrate adequate protection against fluid ingress into the handpiece.

SUMMARY OF CLINICAL INFORMATION

A limited study to validate the durability of reference points placed with the Comfort Marker 2.0 for a duration of twelve weeks was conducted on healthy volunteers. The study focused on the following elements: technique to place the mark, colorant to be used with the Comfort Marker 2.0, whether the mark is visible to the radiation therapy professional, whether the colorant migrates impacting the matter that would affect clinical management and duration that the mark remains visible.

(b) (4)healthy human volunteers participated in the study, between the age group of "10 (4) men and " women). They did not have any underlying skin conditions. All volunteers were informed about the test procedure and provided with details of the test center. Before participating, all the volunteers signed the consent form.
The procedure was performed in a radiotherapy preparation room by a radiotherapy technician. The procedure used Accu-tatt® - ink in the United States of America and the Comfort Marker 2.0 device. The colorant was applied to the arms of two volunteers and to the thoracic area of four volunteers. Endpoints defined were visibility, migration, and clearance.

The reference points were marked according to the Comfort Marker 2.0 instructions for use. Each volunteer received reference points using Accu-Tatt® at all the depth settings (0.25, 0.45 and 0.75 mm). Documentation of the reference points were taken immediately and followed for 12 weeks. Each reference point was made only once.

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Results

a) The healthy volunteer study showed that Comfort Marker 2.0 can place well defined reference points using Accu-Tatt® at all three depth settings.
b) The reference points did not show any migration on the skin. All reference points from Accu-Tatt® were clearly visible during week" until " a period in which radiotherapy treatment is provided.
c) Generally, Accu-Tatt® when used at the lowest depth settings (0.25 mm) faded away at week 12 in most of the participants, however no impact on clinical treatment was observed.

Pediatric Extrapolation

In this De Novo request, existing clinical data were not leveraged to support the use of the device in a pediatric patient population.

LABELING

Labeling has been included which consists of a user manual, instructions for use, box labeling, and patient labeling. The user manual and instructions for use include a description of the device technical parameters, contraindications, warnings and precautions. These documents summarize the main steps for using the device as well as the necessary measures to properly dispose of any single use items and clean the reusable components of the device.

The instructions for use contain the following:

1. Only use specified consumables with the Comfort marker 2.0
- a. Safety Needle: Safety needle, Medical Precision B.V.
- b. Accu-tatt® ink
1. Warnings:
- a. Inadequate disinfection may lead to cross-contamination when used on multiple patients.
- b. During operation the needle is continuously exposed out of the Safety Needle. Be careful not to induce a needle stick incident.
1. Contraindications:
- a. Do not use on damaged skin.
- b. Do not use the Comfort Maker 2.0 on skin with dermatitis. Radiation therapy can cause radiation dermatitis. Due to superficial placement of the pigment, radiation dermatitis may alter the appearance or duration of the marker placed by the Medical Precision device. Radiation dermatitis may accelerate immune system dispersion or clearing of the tattoo pigment, resulting in loss of usable marker before the radiation mark is no longer needed.
- 1. Precautions
  - The reference points made with a shallow depths 0.25 mm may not be visible a. immediately after placing the reference point in certain situations. In such cases, use medium depth setting 0.45 mm on the same location.

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The shallow depth setting 0.25 mm may tend to fade after week 8. Assess the b. reference points at each patient visit. If signs of fading or clearing are noted, it is recommended to repeat the placement of reference points on intact skin as per established standard of care.

RISKS TO HEALTH

The table below identifies the risks to health that may be associated with use of a radiation therapy marking device and the measures necessary to mitigate these risks.

Identified Risks to Health	Mitigation Measures
Adverse tissue reaction	Biocompatibility evaluation
Cross contamination and infection	Reprocessing validation
	Sterilization validation
	Non-clinical performance testing
	Shelf-life testing
	Labeling
Needle stick injury to provider	Non-clinical performance testing
	Labeling
Device and/or software failure leading to	Clinical performance testing
ineffective marking	Non-clinical performance testing
	Software validation, verification, and
	hazard analysis
	Labeling
Electrical shock or electromagnetic	Electromagnetic compatibility testing
interference with other devices	Electrical safety testing
	Labeling

Table 1. Identified Risks to Health and Mitigation Measures

SPECIAL CONTROLS

In combination with the general controls of the FD&C Act, the radiation therapy marking device is subject to the following special controls:

(1) Design verification and validation must include:
- Documentation of performance data from studies that demonstrate: (i)
  - (A) The indicated colorant is compatible with the device and its method of delivery:
  - (B) The device can reproducibly deliver the indicated colorant with the specifications described; and
  - (C) The length of time that compatible colorants remain visible on the skin following device application.
- (ii) Documentation of performance data from studies that demonstrate:
  - Accuracy and reproducibility of needle penetration depth; (A)

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Device protection from cross-contamination, including fluid ingress (B) protection:
Adequacy of the cleaning and disinfection instructions to ensure that the (C) reusable components of the device can be cleaned and disinfected; and
(D) The sterility of all patient-contacting components (e.g., safety needle).
Documentation of performance data from studies that demonstrate electrical (iii) safety and electromagnetic compatibility (EMC) of all electrical components of the device.
Documentation of performance data from studies that demonstrate continued (iv) sterility, package integrity, and device functionality over the intended shelf life.
(v) Documentation of software verification, validation, and hazard analysis.
The labeling required under 21 CFR 801.109(c) must include: (2)
- An explanation of the device and the mechanism of operation; (i)
- Validated methods and instructions for reprocessing of any reusable components; (ii)
- (iii) Disposal instructions: and
- A shelf life for all sterile components. (iv)

BENEFIT-RISK DETERMINATION

The probable benefits of the Comfort Marker 2.0 outweigh the probable risks of the device in light of the special controls proposed for this device in addition to the applicable general controls. The device may be used to apply marks using Accu-tatt® to the skin to assist with patient set-up for radiation therapy. In the data provided, the marks were visible and durable for a minimum period of 8 weeks. Risks associated with adverse tissue reaction are addressed with biocompatibility evaluation. Risks related to infection and cross-contamination are mitigated by reprocessing validation, sterilization, and labeling. Labeling and other special controls related to needle performance and colorant delivery will also help address risks associated with ineffective marking. Risks associated with interference with other devices are mitigated by special controls concerning electromagnetic compatibility and software validation, verification, and hazard analysis. The performance data provided, including those data required by the special controls, when combined with the device labeling suggest that the device will be safe and effective for its proposed indications for use.

Patient Perspectives

This submission did not include specific information on patient perspectives for this device.

BENEFIT/RISK CONCLUSION

In conclusion, given the available information above, for the following indication statement:

The device is indicated for use for applying ink to the skin to identify the margins for radiation therapy. The device is intended to be used in clinical settings by Radiotherapy professionals.

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The probable benefits outweigh the probable risks for the Comfort Marker 2.0. The device provides benefits, and the risks can be mitigated by the use of general controls and the identified special controls.

CONCLUSION

The De Novo request for the Comfort Marker 2.0 is granted and the device is classified as follows:

Product Code: QRN Device Type: Radiation therapy marking device Regulation Number: 21 CFR 892.5785 Class: II

Regulation Number and Section

N/A