The Exceed is a microneedling device and accessories is intended for the treatment of wrinkles in Fitzpatrick skintypes I, II and/or III in the following facial areas: glabellar frown lines, periorbital lines and cheek folds in adults aged 22 years or older.

Device Description

The Exceed micro needling device is intended to create many, very tiny, microscopic punctures in the epidermal and dermal layers of the skin using sterile stainless-steel nicro needling device consists of 7 component parts; Control Unit, Sterile single use Safety needle cartridge, Handpiece holder, Handpiece cover, Footswitch, Power supply
The control unit switches the device on and off and contains the power source (5.5-12 V, DC (150mA)). The control unit adjusts the frequency of the needle strom 100-150Hz using a digital display and a kevpad. The control unit receives power via a coaxial connector from a standard 100-240V, 50-60Hz, 1.2A wall socket transformer with an output of 15V. The handpiece contains a motor that moves the needles and a needle protrusion dial that allows the user to control the depth of the needle protrusion. The handpiece contains a scale that allows for the needle protrusion depth to be adjusted by the operator. The scale has a tolerance of +/-0.15 mm. The standard safety needle cartridge is a 6-stainless steel micro needle plate of 1.5 mm length. The safety needle cartridge is screwed into the handpiece. The safety needle cartridge is sterile and for single use only. This standard safety needle cartridge is used for microneedling only. The length of needles is 1.5 mm. In combination with the handpiece needle protrusion can be adjusted between 0.0 mm (min) and 1.5 mm (max).

AI/ML Overview

This document is a 510(k) summary for the Exceed Microneedling device, demonstrating its substantial equivalence to a predicate device. It includes information on the device's intended use, technological characteristics, and results from non-clinical and clinical performance testing. However, it does not explicitly define acceptance criteria as a standalone table with numerical thresholds for performance metrics. Instead, the "acceptance criteria" are implied by the clinical study's objective: to assess effectiveness by demonstrating a "clinically meaningful result" (defined as a >1 grade improvement on the Lemperle scale) in specific facial areas, and to assess safety by monitoring adverse events.

Here's an attempt to structure the information based on your request, inferring "acceptance criteria" from the study's stated goals and results:

1. Table of Acceptance Criteria and Reported Device Performance

Performance Metric (Inferred Acceptance Criteria)	Reported Device Performance (Results)	Conclusion
Effectiveness: Clinically meaningful improvement in wrinkles (defined as ≥1 grade improvement on Lemperle scale) in specific facial areas.	Glabella Frown Lines: 41/48 (85.4%) subjects showed ≥1 grade improvement. Mean change >1 grade. (Statistically significant)	Met for Glabella Frown Lines
	Periorbital Lines: 42/48 (87.5%) subjects showed ≥1 grade improvement. Mean change >1 grade. (Statistically significant)	Met for Periorbital Lines
	Cheek Folds: 43/48 (89.6%) subjects showed ≥1 grade improvement. Mean change >1 grade. (Statistically significant)	Met for Cheek Folds
	Horizontal Forehead Lines, Nasolabial Folds, Upper Lip Lines: Did not demonstrate a clinically meaningful improvement at day 150.	Not met for these areas (but not part of the primary treated areas stated)
Safety: Device is not associated with an unacceptable rate of severe adverse events and expected post-treatment responses are temporary and manageable.	Adverse Events: 13/48 (27%) subjects reported adverse events. 9 (18.75% of total subjects) were device-related and mild (8 Herpes Simplex Labialis (HSL) outbreaks, 1 dry skin). No severe adverse events reported. HSL outbreaks in predisposed individuals were managed with prophylactic antiviral therapy, with no further outbreaks. Erythema: 100% subjects experienced erythema immediately after treatment, physician-graded as minor (70%) or moderate (30%). Resolved largely by Day 8 (81% reported no erythema). Pain: 100% experienced some pain. Mean pain score 5.2 (0-10 scale) during treatment, decreasing to ~0.1 by Day 8. Discomfort: 100% experienced some discomfort. Mean discomfort score 1.3 (0-10 scale) during treatment, decreasing by Day 8. Skin Peeling: 100% experienced peeling from Day 3, peaking at Day 4 (3.4 on 0-10 scale), still reported in 65% by Day 8.	Met – AE rates managed, all reported AE were mild, and expected side effects were transient.

2. Sample Size Used for the Test Set and Data Provenance

Sample Size (Clinical Study/Test Set): 48 subjects were recruited for the study and 48 subjects completed the study.
Data Provenance: The document does not explicitly state the country of origin for the clinical study data in "human-readable" form. However, the submitter's address is listed as "Gustav-Krone-Str. 3, 14167 Berlin, Germany," implying the study could have been conducted in Germany or overseen by the German entity. The study was conducted at a "single center." The study appears to be prospective as it involves recruitment of subjects, a treatment protocol, and follow-up assessments over time.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

Number of Experts: Three (3) physicians.
Qualifications of Experts: They are described as "physicians" who independently analyzed randomized digital images using the Lemperle (2001) grading scale. No further specific qualifications like years of experience or specialization are provided in this summary.

4. Adjudication Method for the Test Set

Adjudication Method: The digital images were randomized and "analyzed independently by 3 physicians." The document does not specify an adjudication method like 2+1 or 3+1 if there were discrepancies in grading. It reports the results as aggregate percentages (e.g., "Subjects graded as having a ≥1 grade improvement"). It seems the consensus of the three reviewers was used, or the average/majority was taken, but the exact arbitration process is not detailed.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, and its effect size of how much human readers improve with AI vs without AI assistance

No, an MRMC comparative effectiveness study involving AI assistance for human readers was not done. This study evaluates the effectiveness and safety of a microneedling device itself, not an AI system. The "multi-reader" aspect refers to the three independent physicians assessing patient outcomes after treatment with the device, not assessing AI performance or AI-assisted human performance.

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

Not applicable. This document describes a medical device (microneedling device), not an algorithm or AI. Therefore, no standalone algorithm performance was evaluated.

7. The Type of Ground Truth Used

Type of Ground Truth: The ground truth for effectiveness was established by expert consensus (independent grading by 3 physicians using the validated Lemperle (2001) grading scale based on digital images). For safety, the ground truth was based on physician-reported adverse events and patient-reported outcomes (erythema, pain, discomfort, skin peeling).

8. The Sample Size for the Training Set

Not applicable. This device is hardware for a procedure, not an AI model that requires a training set. The clinical study described served as a validation/test set for the device's performance in humans.

9. How the Ground Truth for the Training Set Was Established

Not applicable. As stated above, this is not an AI device requiring a training set.

Summary

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September 7, 2018

MT. DERM GmbH % Susan D'Arcy Director Ismart Marketing Svcs 129 Green Lanes, Wylde Green Birmingham, B735LT Gb

Re: K180778

Trade/Device Name: Exceed Microneedling Device Regulation Number: 21 CFR 878.4430 Regulation Name: Microneedling device for aesthetic use Regulatory Class: Class II Product Code: QAI Dated: July 26, 2018 Received: August 6, 2018

Dear Susan D'Arcy:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part

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801); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.htm); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

David Krause -S

for Binita S. Ashar, M.D., M.B.A., F.A.C.S. Director Division of Surgical Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K180778

Device Name Exceed Microneedling device

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)

X | Prescription Use (Part 21 CFR 801 Subpart D)

| | Over-The-Counter Use (21 CFR 801 Subpart C)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

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510k Summary

This 510(k) Summary is submitted in accordance with 21 CFR Part 807, Section 807.92(c).

Date Prepared: March 21st, 2018

Date Amended: September 6th 2018

Submitter's Name: MT.DERM GmbH

Submitter's Address: Gustav-Krone-Str. 3, 14167 Berlin, Germany Submitter's telephone number: +49 30 845 885 171 Contact person: Andreas Pachten, DIRECTOR QM and Regulatory Affairs

Device Trade Name: Exceed Microneedling device

1. Device Classification Information:

RegulationNumber	DeviceClassificationname	DeviceClass	ProductCode	Generic description	ClassificationPanel	Type
21 CFR878.4430	Microneedlingdevice foraesthetic use	Class 2	QAI	A microneedling device for aesthetic use is a device using one or more needles to mechanically puncture and injure skin tissue for aesthetic use. This classification does not include devices intended for transdermal delivery of topical products such as cosmetics, drugs, or biologics.	General & PlasticSurgery	Traditional510 (k)

Device Description 2.

The control unit switches the device on and off and contains the power source (5.5-12 V, DC (150mA)). The control unit adjusts the frequency of the needle strom 100-150Hz using a digital display and a kevpad. The control unit receives power via a coaxial connector from a standard 100-240V, 50-60Hz, 1.2A wall socket transformer with an output of 15V. The handpiece contains a motor that moves the needles and a needle protrusion dial that allows the user to control the depth of the needle protrusion. The handpiece contains a scale that allows for the needle protrusion depth to be adjusted by the operator. The scale has a tolerance of £0.15 mm. The standard safety needle cartridge is a 6-stainless steel micro needle plate of 1.5 mm length. The safety needle cartridge is screwed into the handpiece. The safety needle cartridge is sterile and for single use only. This standard

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safety needle cartridge is used for microneedling only. The length of needles is 1.5 mm. In combination with the handpiece needle protrusion can be adjusted between 0.0 mm (min) and 1.5 mm (max).

3. Indications/Intended Use

The Exceed is a microneedling device and accessories is intended for the treatment of wrinkles in Fitzpatrick skin types I, II and/or III in the following facial areas: glabellar frown lines, periorbital lines and cheek folds in adults aged 22 years or older.

Caution: Federal law restricts this device to sale by or on the order of a physician.

4. Predicate Device

DEN160029 SkinPen Precision System

SkinPen Precision System DEN160029 is a microneedling device and accessories intended to be used as a treatment to improve the appearance of facial acne scars in adults aged 22 years or older.

The Exceed Micro needling device is predicated against the SkinPen Precision System because both devices are microneedling devices containing one or more needles to mechanically puncture and injure the skin tissue for aesthetic use.

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MT.DERM

K180778

5. Technological Characteristics

Property	Exceed Microneedling device	DEN160029SkinPen Precision System	Significant differences
Device Manufacturer	MT.DERM GmbHGustav-Krone-Str. 3,14167 Berlin, Germany	Bellus Medical, LLC, 4505Excel Parkway, Suite 100,Addison, TX 75001	Not applicable
Device Trade Name	Exceed Microneedling device	SkinPen Precision System	Not applicable
510(K) Number	K180778	DEN160029	Not applicable
Device Classification name	Microneedling device foraesthetic use	Microneedling device foraesthetic use	Identical
Device Product Code	QAI	QAI	Identical
Device Classification	Class II	Class II	Identical
Regulation number	21 CFR 878.4430	21 CFR 878.4430	Identical
Use	Prescriptive	Prescriptive	Identical
Intended Location of Use	Face	Face	Identical
Property	Exceed Microneedlingdevice	DEN160029SkinPen PrecisionSystem	Significant differences
Intended use andIndications	The Exceed is amicroneedling device andaccessories is intended forthe treatment of wrinkles inFitzpatrick skin types I, IIand/or III in the followingfacial areas: glabellar frownlines, periorbital lines andcheek folds in adults aged 22years or older.	SkinPen® Precision System isa microneedling device andaccessories intended to be usedas a treatment to improve theappearance of facial acne scarsin adults aged 22 years orolder.	Dissimilar – Clinical performancedata provided demonstrates that theExceed Microneedling device is safeand effective in the treatment offacial wrinkles in Fitzpatrick skintypes I, II and/or III and raises nonew issues in terms of safety andeffectiveness.
Geometry	6 needles, squaredarrangement	14 needles, radial arrangement	Dissimilar. Clinical and non-clinicalperformance testing demonstratesthat the Exceed microneedlingdevice does not pose any undue oradditional risks and is effective.
Needle protrusionsetting	0 - 1.9 mm	0 - 2.5 mm	Dissimilar. Clinical and non-clinicalperformance testing demonstratesthat the Exceed microneedlingdevice does not pose any undue oradditional risks and is effective.
Needle protrusionsetting	0 - 1.9 mm	0 - <2.7 mm1	Dissimilar. Clinical and non-clinicalperformance testing demonstratesthat the Exceed Microneedlingdevice does not pose any undue oradditional risks and is effective.
Max Needle lengthused in clinical study	1.5mm	1.5mm	Substantially equivalent
Maximum needlepenetration(maximum needlelength)	1.5mm	2.5 mm	Dissimilar. Clinical and non-clinicalperformance testing demonstratesthat the Exceed Microneedlingdevice does not pose any undue oradditional risks and is effective.
Property	Exceed Microneedlingdevice	DEN160029SkinPen PrecisionSystem	Significant differences
Frequency	100-150 Hz (±10%)	6300RPM to 7700 RPM¹(105 - 128.3 Hz)	Dissimilar. Clinical and non-clinicalperformance testing demonstratesthat the Exceed Microneedlingdevice does not pose any undue oradditional risks and is effective.
Treatment protocol	4 treatments spaced 4 weeksapart	3 treatments spaced 4 weeksapart	Dissimilar - Clinical performancedata provided demonstrates that theExceed Microneedling device is safeand effective in the treatment offacial wrinkles. and raises no newissues in terms of safety andeffectiveness.

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MT.DERM

K180778

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1 Data obtained from marketing material

6. Substantial Equivalency and Comparison of Technological Similarities & Differences

Key Similarities. 6.1.

i. The device classification (generic description) and basic technologies are equivalent in that both devices are micro needling devices containing >1 needle that mechanically punctures and injures the skin for aesthetic use.
Both devices are intended for prescriptive use. ii.
iii. The depth of penetration of the needles in clinical studies were equivalent 1.5mm

6.2. Differences.

iv. Although the devices share the basic generic description and technologies they do differ in several areas.
- Intended use and indication a.
- b. Geometry and needle count
- Needle protrusion setting c.
- Maximum needle length d.
- e. Maximum needle penetration
- Frequency f.
- Treatment protocol g.

These differences have been addressed by the manufacturer through the applicable safety standards (General controls and mitigation measures) and through clinical and non-clinical performance testing (Special controls).

7. Non-clinical performance testing

To demonstrate safety and effectiveness and support substantial equivalence the Exceed Microneedling device has undergone non-clinical performance testing in line with recognized standards in terms of general requirements, biocompatibility, electrical safety and software.

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In combination with the general controls of the FD&C Act, the microneedling device for aesthetic use is subject to the following special controls:

The technical specifications and needle characteristics are identified, including needle length, geometry, 1. maximum penetration depth, and puncture rate.
1. Non-clinical performance data demonstrates that the device performs as intended under anticipated conditions of use.

The following performance characteristics are tested:

i. Accuracy of needle penetration depth and puncture rate in pig skin with high-speed camera measurement;
ii. Safety features built into the device to protect against cross-contamination, including fluid ingress protection due to a safety membrane: and
iii. Identification of the maximum safe needle penetration depth for the device in pig skin with high-speed camera measurement.
1. Performance data demonstrates the sterility of the patient-contacting components of the device according to ISO 11135-1:2007, ISO/TS 11135-2:2008 and ISO 11737-1:2006.
1. Performance data supports the shelf life of the device by demonstrating continued sterility, package integrity, and device functionality over the intended shelf life according to ISO 11607-1:2006+A1:2014 and ISO11607-2:2006+A1:2014.
1. Performance data demonstrates the electrical safety and electromagnetic compatibility (EMC) of all electrical components of the device according to ISO 60601-1:2012 and ISO 60601-1-2:2014 (ed 4.0).
1. Software verification, validation, and hazard analysis werre performed for all software components of the device according to ISO 62304:2006 (ed 1.0).
1. The patient-contacting components of the device were demonstrated to be biocompatible including evaluation of cytotoxicity, irritation, and sensitization, acute systemic toxicity and material-mediated pyrogenicity per the FDA guidance document "Use of International Standard ISO 10993-1, "Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process.
1. A cleaning validation was performed for reusable components of the device. (Reprocessing Medical Devices in Health Care Settings: Validation Methods and Labeling.)
1. Labeling included the following:
- i. Information on how to operate the device and its components and the typical course of treatment;
- ii. A summary of the device technical parameters, including needle length, needle geometry, maximum penetration depth, and puncture rate;
- iii. Validated methods and instructions for reprocessing of any reusable components;
- iv. Disposal instructions; and
- Shelf life. v.
1. Patient labeling included:
- 1. Information on how the device operates and the typical course of treatment;
- ii. The probable risks and benefits associated with use of the device; and
- iii. Post-operative care instructions.

8. Clinical performance testing

A clinical study was conducted to support the safety and effectiveness of the Exceed Micro needling device for the treatment of facial wrinkles.

The objective of the study was to assess the effectiveness of the Exceed micro needling device in reducing the signs of skin aging as measured by the improvement in wrinkles, after 4 standardized treatment sessions and to assess the safety of the device as measured by the number of adverse events.

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The study was conducted at a single center. Subjects were treated 4 times, 30 days apart (Day 0, 30, 60 and 90) with final assessment 60 days after the last treatment at 150 days.

Treatments were conducted by medically trained healthcare professionals.

The face was cleansed and a numbing cream containing a local anesthetic was applied to the skin for 30 minutes. After 30 minutes the numbing cream was removed from the patient's face and a small quantity of hydrogel was applied prior to the treatment to protect the skin against abrasion and friction during the procedure. The operator was instructed to start at the lowest needle depth setting and gradually increase the depth until pin point bleeding was observed with a maximum needle depth of 1.5 mm. Following the treatment, the skin was cleansed with warm water and sterile gauze. A physical sunblock (SPF≥ 40) was applied to the skin.

Demographics:

Forty-eight subjects were recruited for the study and 48 subjects completed the study. The average age of the subjects was 51.1 years (age range 39-67). Predominantly the population was female (1/48 (2%) subjects were male). The study included subjects with Fitzpatrick skin types I to III and V. None of the subjects were smokers (table i). No subjects with Fitzpatrick skin type IV or VI were included in the study.

No subject dropped out during the treatment phase of the study or during the follow-up. All subjects who were enrolled into the study and completed all treatment visits were included in the assessment and analysis.

Analysis	Age		M:F	Smoke	Fitzpatrick Skin type
	Mean	Range			I	II	III	V
N = 48	55.1	39 - 67	1:47	0	3	36	8	1

Table i - Demographic characteristics

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Measurement of effectiveness

At each visit digital photographs (VISIA) were taken of the subject's face and the principal investigator assessed facial photodamage (including wrinkles) using a validated scale (Lemperle (2001)*. At the end of the study the digital images of the subject's face were randomized and analyzed independently by 3 physicians using the same grading scale (Lemperle (2001). The Lemperle grading scale divides the face into 9 regions and scores each facial area for the signs of aging using a photonumeric scale (0-5) reference pictures where 0 indicates no wrinkles at rest and 5 being deep wrinkles at rest.

"Lemperle G, Holmes RE, Lemperle SS. A Classification of Facial Wrinkles. Plastic and reconstructive surgery. 2001 Nov 1;108(6):1735-50

Measurement of safety

Immediately after each micro needling procedure the principal investigator was asked to grade the amount of visible erythema in the treatment area. Grading was carried out using a 5-point grading scale;

None: No erythema or redness. Skin is normal color.
Minor: very faint erythema or redness. Skin has a slight redness to it.
. Mild: blotchy, visible redness that does not cover the entire face. Skin has a noticeable inconsistent redness to it.
. Moderate: dull red color to the skin. Skin has a very definite redness to it.
. Severe: Bright or dark red color to the skin. Skin is severely red.

Subjects also graded their erythema immediately after each micro needling procedure and in addition graded pain and discomfort experienced during the treatment procedure. A descriptive grading scale was used for subjects to evaluate their erythema with the addition of photography depicting grades of erythema in different phototypes.

This photonumeric scale was also used for subjects to record their erythema at home.

Pain and discomfort were recorded using an 11-point visual analogue scale (0-10) where 0 was equivalent to "ho pain" or "no discomfort" to 10, "most intense pain ever" and "most discomfort ever". This grading structure was also used to record changes to pain and discomfort from the evening of the treatment to Day 8 (7 days after the treatment). In addition, skin peeling was assessed by the patient from day 3 to day 8 using a visual analogue scale where 0 represented "no skin peeling or flakiness" to 10 "heavy skin peeling over the whole face." During all times any potential adverse events were recorded by the research staff.

Results - Safety - Physician reported outcomes

In 13 out of 48 subjects (27%) adverse events were reported during the study (table ii).

Nine (9) adverse events were related to the treatment. Eight (8) were herpes simplex labialis (HSL) outbreaks and 1 adverse event was dry skin. Of the 8 HSL outbreaks, 5 occurred in subjects with Fitzpatrick skin type 2, 2 occurred in skin type 3 and 1 occurred in skin type V. One subject (skin type 2) reported extremely dry skin which was selflimiting and not reported again by the subject.

Note: Thirteen (13) out of 48 subjects (27%) reported a predisposition to HSL at the beginning of the study. Of this predisposed population, an HSL outbreak was observed in 8 subjects were treated for their HSL using conventional antiviral thereafter were given prophylactic antiviral therapy prior to the micro needling procedure. There were no further reported outbreaks.

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	Severity of adverse event
Event	Mild		Moderate		Severe		Total
	Related to	Not-related to	Related	Non-	Related	Non-	Related
	the device	the device		related		related	+
	(R)	(NR)					Non-
							related
Herpes Labialis n=8	8 (100%)	0	0	0	0	0	8
Dry skin n=1	1(100%)	0	0	0	0	0	1
Cold/Flu n=2	0	2(100%)	0	0	0	0	2
Surgery n=2	0	2(100%)	0	0	0	0	2
Total	9	4	0	0	0	0	13

Table ii. Adverse event - summary of observations and rate

Following treatment, 48/48 (100%) of subjects experienced erythema. Physician grading of erythema immediately after the treatment was recorded as minor in 70% (34/48) of subjects. The remainder of subjects were graded as moderate by the physician.

Results - Safety - Patient reported outcomes

Subjects were also asked to grade their erythema immediately at the treatment. Nineteen out of 48 (40%) subjects graded their skin redness as moderate and 29/48 (60%) subjects as severe (table iii).

	Table iii. Erythema assessment by physician and subject immediately after treatment

Grading of erythemaimmediately aftertreatment	Grading
	Minor	Moderate	Severe
Physician	34/48 (70%)	14/48 (30%)	0
Subject	0	19/48 (40%)	29/48 (60%)

Subjects indicated that although the treatment appeared to be moderately painful it was not particularly uncomfortable (table iv).

Table iv. Pain and discomfort experienced during the treatment

Subject assessment of pain and discomfort during the treatment(average over 4 treatments)	Pain score¹(range)
Pain during treatment	5.2 (3.8 to 6.1)
Discomfort during treatment	1.3 (<1 - 2.1)

based on a scale 0-10 0 = No pain or discomfort. 10 = Worst pain or discomfort ever

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Erythema, pain, discomfort and skin peeling were recorded up to 8 days after treatment.

Erythema was experienced by 48 out of 48 subjects (100%) immediately after the treatment lasting 8 days. . Eight days after the treatment 39/48 (81%) subjects reported no ervthema. 9/48 (19%) subjects reported minor erythema and 1/48 (2%) subjects mild erythema.
Pain was experienced by 48 out of 48 subjects (100%) to some degree during the treatment lasting 8 days. By day 3, 37/48 (77%) of subjects still reported pain. By day 8, 2/48 (4%) still reported some pain.
Discomfort was experienced by 48 out of 48 subjects (100%) to some degree during the treatment lasting 8 ● days. Eight days after the treatment, discomfort was still reported by 9/48 (20%).
Skin peeling was experienced by 48 out of 48 subjects (100%) from day 3 lasting 8 days. The amount of ● skin peeling reached a maximum of 3.4 day 4 (on a scale of 0-10 where 0 = no peeling and 10= heavy skin peeling over the whole face). Skin peeling was still reported in 31/48 (65%) subjects by the evening of day 8. figure i).

Image /page/12/Figure/7 description: The image is a line graph that shows the average pain, discomfort, and peeling scores during treatment and on days 1, 2, 3, 4, 5, 6, and 8. The y-axis represents the scores, ranging from 0.0 to 10.0. The x-axis represents the time points. The average pain scores decrease from 5.2 during treatment to 0.1 on day 8, while the average discomfort scores increase from 1.3 during treatment to 2.5 on day 1 and then decrease to 0.1 on day 8. The average peeling scores remain at 0.0 until day 2, then increase to 3.4 on day 4, and then decrease to 1.7 on day 8.

Figure i. Subject assessment of pain, discomfort and peeling immediately after the treatment to day 8

Results - Effectiveness - Physician reported outcomes

A blinded assessment by three blinded evaluators were performed. In accordance with the original clinical study the physicians used the grading structures of Lemperle (2001) for wrinkles. Lemperle's grading scale divides the face into nine regions and scores each facial area using a numeric scale (0-5).

Assessments of labiomental crease, marionette lines and the preauricular area from the VISIA images were found to be technically difficult and were therefore excluded from the blinded assessment.

The following six areas were therefore assessed for wrinkles: horizontal forehead lines, glabella frown lines, periorbital lines, cheek folds, nasolabial folds and upper lip lines.

Of the six facial areas which were evaluated, three areas achieved a clinically meaningful result, while three areas did not show improvement. For glabella frown lines, periorbital lines and cheek folds the mean value of change was > 1 grade improvement in the grading scale (see Table v). This change was statistically significant. For horizontal

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forehead lines, nasolabial folds, and upper lip lines, the results did not demonstrate a clinically meaningful improvement at day 150.

	Glabella Frown Linesn (%)	Periorbital Linesn (%)	Cheek Foldsn (%)
Subjects graded ashaving a ≥1 gradeimprovement	41/48 (85.4%)	42/48 (87.5%)	43/48 (89.6%)
Subjects graded asunchanged(Change = 0)	7/48 (14.6%)	6/48 (12.5%)	5/48 (10.4%)
Subjects graded asworsened	0/48 (0%)	0/48 (0%)	0/48 (0%)

Table v Comparison of Grade on the Lemperle Scale at Baseline and Day 150 by Three Blinded Assessors (primary endpoint)

For glabella frown lines, periorbital lines and cheek folds an improvement of >1 grade was shown for 18/48 (37.5%), 20/48 (41.7%) and 17/48 (35.4%) subjects (see Table v).

9. Statement of Substantial Equivalence:

MT.DERM GmbH has demonstrated that the Exceed Microneedling device has the same generic classification (generic description) and basic technologies as the predicate device DEN160029. Both devices are micro needling devices containing >1 needle that mechanically punctures or injures the skin for aesthetic use. Both devices have used needle depths of up to 1.5mm in clinical investigations.

Where there are differences between the Exceed micro needling device and the predicate (DEN160029) MT.DERM GmbH has conducted substantial clinical and non-clinical performance testing applicable to those general and special controls deemed necessary by the agency for this product classification and has determined that the Exceed microneedling device raises no new questions relating to safety or effectiveness and therefore has demonstrated that the Exceed microneedling device is substantially equivalent to the referenced predicate DEN160029.

Regulation Number and Section

§ 878.4430 Microneedling device for aesthetic use.

(a)
Identification. A microneedling device for aesthetic use is a device using one or more needles to mechanically puncture and injure skin tissue for aesthetic use. This classification does not include devices intended for transdermal delivery of topical products such as cosmetics, drugs, or biologics.(b)
Classification. Class II (special controls). The special controls for this device are:(1) The technical specifications and needle characteristics must be identified, including needle length, geometry, maximum penetration depth, and puncture rate.
(2) Non-clinical performance data must demonstrate that the device performs as intended under anticipated conditions of use. The following performance characteristics must be tested:
(i) Accuracy of needle penetration depth and puncture rate;
(ii) Safety features built into the device to protect against cross-contamination, including fluid ingress protection; and
(iii) Identification of the maximum safe needle penetration depth for the device for the labeled indications for use.
(3) Performance data must demonstrate the sterility of the patient-contacting components of the device.
(4) Performance data must support the shelf life of the device by demonstrating continued sterility, package integrity, and device functionality over the intended shelf life.
(5) Performance data must demonstrate the electrical safety and electromagnetic compatibility (EMC) of all electrical components of the device.
(6) Software verification, validation, and hazard analysis must be performed for all software components of the device.
(7) The patient-contacting components of the device must be demonstrated to be biocompatible.
(8) Performance data must validate the cleaning and disinfection instructions for reusable components of the device.
(9) Labeling must include the following:
(i) Information on how to operate the device and its components and the typical course of treatment;
(ii) A summary of the device technical parameters, including needle length, needle geometry, maximum penetration depth, and puncture rate;
(iii) Validated methods and instructions for reprocessing of any reusable components;
(iv) Disposal instructions; and
(v) A shelf life.
(10) Patient labeling must be provided and must include:
(i) Information on how the device operates and the typical course of treatment;
(ii) The probable risks and benefits associated with use of the device; and
(iii) Postoperative care instructions.