Hydrozid (also known as R134A or 1,1,1,2-tetrafluoroethane or HFC-134a or fluorocarbon 134a) is to be used for the treatment of verruca (warts) including plantar warts, sebortheic keratosis, actinic keratosis, achrochordon (skin tags), molluscum contagiosum, age spots, dermatofibroma, small keloids, granuloma annulare, porokeratosis plantaris, angiomas, keratoacanthoma, chondrodermatitis, epithelial nevus, leukoplakia, granuloma pyogenicum, and pyogenic granuloma.

Device Description

Hydrozid® is a portable aerosol cryosurgery device intended for the treatment of benign and premalignant skin lesions using a cryogen to freeze cells up to necrosis (cell destruction). The main device component is the aerosol canister containing cryogen spray. The device is provided in a kit containing a canister, application templates and Instructions for Use. The device is used with non-sterile, singlepatient application templates which are disposed after use.

AI/ML Overview

The provided document is a 510(k) Premarket Notification for the medical device Hydrozid®, a portable aerosol cryosurgery device. The purpose of this document is to demonstrate "substantial equivalence" to a legally marketed predicate device, Cool Renewal®. Therefore, the "acceptance criteria" and "study that proves the device meets the acceptance criteria" are framed in the context of demonstrating substantial equivalence rather than a clinical trial with specific performance metrics for a novel device.

Here's an analysis based on your requested information:

1. Table of Acceptance Criteria and Reported Device Performance

Since this is a 510(k) submission focused on substantial equivalence, the "acceptance criteria" are not explicit performance thresholds in the typical sense for a new device's efficacy/accuracy. Instead, the acceptance criteria are met if the new device (Hydrozid®) demonstrates comparable performance to the predicate device (Cool Renewal®) in areas related to its mechanism of action and intended use, and does not raise new questions of safety and effectiveness.

Acceptance Criteria (Implied by Substantial Equivalence)	Reported Device Performance (Hydrozid®)
Cryogen Comparison: The cryogen used in Hydrozid® should achieve a thermal profile comparable to the predicate device's cryogen.	Bench Test 1: "A bench test was performed to analyze the thermal profile (surface temperature, duration of the surface temperature and iceball geometry and size) of the cryogen R134A and the predicate device cryogen. The bench test determined that Hydrozid® cryogen performed equivalently to the cryogen of the predicate device."
Cryogen Efficacy: The cryogen should be able to reach the minimum desired temperature for cell destruction and vascular stasis.	Bench Test 2: "A second temperature testing performed on Hydrozid® confirmed that the cryogen R134A could reach the minimum desired temperature for cell destruction and vascular stasis in both the minimum and maximum treatment time."
Overall Safety and Effectiveness: The device should not introduce new safety or effectiveness concerns compared to the predicate.	The submission asserts: "Testing and argumentation rationale were provided to support the equivalence of the Hydrozid® and shows that no new questions of safety and effectiveness have been introduced with this device. The safety and effectiveness of the Hydrozid® are adequately supported by the testing rationale, substantial equivalence information, materials information, and comparison of technical characteristics provided within this premarket notification." Additionally, the comparison table (Table 5.3-1) highlights that despite a difference in cryogen composition (Hydrozid® uses R134A, predicate uses R404A which contains R134A, Pentafluoroethane, and 1,1,1,-trifluoroethane), the performance data showed Hydrozid® achieves a thermal profile comparable to the predicate, thus raising "no new safety or efficacy concerns."

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

Sample Size: Not explicitly stated. The document refers to "bench tests" being performed. These are laboratory-based tests on the device's physical properties (thermal profile, temperature reach) rather than tests on biological samples or patients.
Data Provenance: The tests are "bench tests," so the data provenance is internal laboratory testing rather than data from human subjects or clinical settings (e.g., country of origin of data is not applicable in this context). The document states, "There was no clinical testing required to support the medical device."

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

Not applicable. The ground truth for this type of submission is typically based on established scientific principles of cryosurgery (e.g., temperatures required for cell necrosis) and comparison against the performance of a legally marketed predicate device. There is no mention of experts required to establish ground truth for the bench tests.

4. Adjudication Method for the Test Set

Not applicable. This was not a study involving human interpretation of data where adjudication would be necessary. The "tests" were bench tests measuring physical parameters.

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

Not applicable. This is not an AI/imaging device. It's a cryosurgical unit. No MRMC study was conducted.

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

Not applicable. This is not an algorithm-based device. No standalone performance was evaluated in this context.

7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)

The ground truth for the bench tests appears to be based on:

Established scientific understanding of cryosurgery, specifically the minimum temperatures required for cell destruction and vascular stasis.
The thermal profile and performance of the legally marketed predicate device (Cool Renewal®).

8. The Sample Size for the Training Set

Not applicable. This is not an algorithm, so there is no "training set."

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

Not applicable, as there is no training set.

Summary

{0}------------------------------------------------

Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: a symbol on the left and the text "FDA U.S. FOOD & DRUG ADMINISTRATION" on the right. The symbol on the left is a stylized image of a human figure, and the text on the right is in blue. The text is arranged in three lines, with "FDA" on the first line, "U.S. FOOD & DRUG" on the second line, and "ADMINISTRATION" on the third line.

July 7, 2021

MediLink A/S Cristina Teixeira Director for Regulatory Affairs & Quality Assurance Gammelmosevej 176A Kgs. Lyngby. 2800 Denmark

Re: K201740

Trade/Device Name: Hydrozid Regulation Number: 21 CFR 878.4350 Regulation Name: Cryosurgical Unit And Accessories Regulatory Class: Class II Product Code: GEH Dated: June 8, 2021 Received: June 9, 2021

Dear Cristina Teixeira:

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

{1}------------------------------------------------

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/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) 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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). 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 (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Long Chen, Ph.D. Assistant Director DHT4A: Division of General Surgery Devices OHT4: Office of Surgical and Infection Control Devices Office of Product Evaluation and Ouality Center for Devices and Radiological Health

Enclosure

{2}------------------------------------------------

Indications for Use

510(k) Number (if known) K201740

Device Name Hydrozid

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)
☑ Prescription Use (Part 21 CFR 801 Subpart D)
☐ Over-The-Counter Use (21 CFR 801 Subpart C)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

{3}------------------------------------------------

Traditional 510(k) Summary- Hydrozid®

In accordance with 21 CFR Part 807, Section 807.92, this information serves as a 510(k) summary for Hydrozid®.

Date Prepared: July 6, 2021

Submitted by: MediLink A/S Klintehøj Vænge 6

DK-3460 Birkerød Denmark +45 30 66 65 02

Contact Person: Cristina Teixeira

Director of Regulatory Affairs & Quality Assurance ct@medilink.dk

Proprietary Name: Hydrozid®

Common Name: Portable aerosol cryosurgery device Classification Name: Unit, Cryosurgical, Accessories Classification Regulation: 21 CFR 878.4350 Device: Class II Device Product Code: GEH Device Panel: General & Plastic Surgery Predicate Device: Cool Renewal® (K161296)

Description of the Device 1.

{4}------------------------------------------------

The mechanism of action for both Hydrozid® and the predicate device, Cool Renewal®, is based on the principles of cryosurgery (also referred as cryotherapy). Cryosurgery was first described in the 1800s and has since evolved into a wellestablished therapy within dermatology and other healthcare fields. Cryosurgery is performed using a cryogen to freeze the target tissue temperature to below the level that correlates with cell destruction also known as necrosis. The mechanism of action in cryosurgery are divided into 3 phases: (1) heat transfer, (2) cell death, and (3) inflammation. When the cryogen evaporates, it absorbs heat from its surroundings (heat transfer phase) causing cell destruction (cell death phase) due to:

. Direct effects of freezing on the cells
Vascular stasis which develops after thawing.

During cryosurgery, both extracellular and intracellular ice formation occur, with fast freezing in the center of the lesion, and slow freezing on the outside border. The loss of blood supply to the treated area eradicates the likelihood of survival of the cells in the frozen tissue (inflammation phase).

Indications for Use Statement 2.

Hydrozid® (also known as R134A or 1,1,1,2-tetrafluoroethane or HFC-134a or HFA-134a or fluorocarbon 134a) is to be used for the treatment of verruca (warts) including plantar warts, seborrheic keratosis, actinic keratosis, achrochordon (skin tags), molluscum contagiosum, age spots, dermatofibroma, small keloids, granuloma annulare, porokeratosis plantaris, angjomas, keratoacanthoma, chondrodermatitis, epithelial nevus, leukoplakia, granuloma pyogenicum, and pyogenic granuloma.

3. Substantial Equivalence Discussion

The Hydrozid® intended use, indications and clinical application as well as the overall technical characteristics are substantially equivalent to the predicate device. The below table (table 5.3-1) compares the Hydrozid® to the predicate device with respect to intended use, technological characteristics and principles of operation. Differences between Hydrozid® and the predicate device are related to minor material and design elements.

{5}------------------------------------------------

Table 5.3-1: Substantial Equivalence Summary

Device Trade Name	Hydrozid®	Cool Renewal®	Significant Differences
Manufacturer	MediLink A/S	Cool Renewal LCC	N/A
Common Name	Portable aerosol cryosurgery device	Portable aerosol cryosurgery device	Same
Classification name	Unit, Cryosurgical, Accessories	Unit, Cryosurgical, Accessories	Same
Regulation number	21 CFR 878.4350	21 CFR 878.4350	Same
Class	II	II	Same
Device Product Code	GEH	GEH	Same
Device Panel	General & Plastic Surgery.	General & Plastic Surgery.	Same
Sterile	No	No	Same
Indications for Use	Hydrozid® (also known as R134A or 1,1,1,2-tetrafluoroethane or HFC-134a or HFA-134a or fluorocarbon 134a) is to be used for the treatment of verruca (warts) including plantar warts, seborrheic keratosis, actinic keratosis, achrochordon (skin	1,1,1,2-tetrafluoroethane, Pentafluoroethane, and 1,1,1-trifluoroethane is to be used for the treatment of verruca (warts) including plantar warts, seborrheic keratosis, actinic keratosis, achrochordon (skin tags), molluscum contagiosum, age spots,	Same
	tags), molluscumcontagiosum, agespots,dermatofibroma,small keloids,granulomaannulare,porokeratosisplantaris, angiomas,keratoacanthoma,chondrodermatitis,epithelial nevus,leukoplakia,granulomapyogenicum, andpyogenicgranuloma.	dermatofibroma,small keloids,granuloma annulare,porokeratosisplantaris, angiomas,keratoacanthoma,chondrodermatitis,epithelial nevus,leukoplakia,granulomapyogenicum, andpyogenicgranuloma.
Intended Users	For professional use only.	For professional use only	Same
Mechanism of Action	Cryosurgery: freeze the target tissue temperature to below the level that correlates with cell destruction (necrosis). When the cryogen evaporates, it absorbs heat from its surroundings causing cell	Cryosurgery: freeze the target tissue temperature to below the level that correlates with cell destruction (necrosis). When the cryogen evaporates, it absorbs heat from its surroundings causing cell destruction due to:	Same
	Direct effects of freezing on the cells Vascular stasis which develops after thawing. The mechanism of action in cryosurgery are divided into 3 phases: (1) heat transfer, (2) Cell death, and (3) inflammation.	Direct effects of freezing on the cells Vascular stasis which develops after thawing. The mechanism of action in cryosurgery are divided into 3 phases: (1) heat transfer, (2) Cell death, and (3) inflammation.
Cryogen	R134A: 1,1,1,2-tetrafluoroethane (CAS 354-33-6).	R404A: 1,1,1,2-tetrafluoroethane (CAS 354-33-6);Pentafluoroethane (CAS 420-46-2);1,1,1,- trifluoroethane (CAS 811-97-2)	Similar.Hydrozid® contains only 1 cryogen which is also part of the Cool Renewal® mixture. The cryogen is already used in the predicate device as well as well-established in other medical application (e.g., asthma inhalers and
			skinapplications).Furthermore,performancedata showHydrozid®achieves athermal profilecomparable tothe predicatedevice. Hence,no new safetyor efficacyconcerns areraised.
Freezing time	Transient use; < 1 minute.Specific freeze timedetermined by thetype, size andlocation of thelesion being treated	Transient use; <1minute.Specific freeze timedetermined by thetype, size andlocation of the lesionbeing treated	Same.
Applicator	ApplicationTemplates	Foam TippedApplicatorPlastic IsolationFunnelFoam Tipped SkinTag Tweezer	Similar.Both devicesare suppliedwithaccessoriesthat allow theapplication for
			directly into the
			patient's skin.

{6}------------------------------------------------

{7}------------------------------------------------

{8}------------------------------------------------

{9}------------------------------------------------

Testing and argumentation rationale were provided to support the equivalence of the Hydrozid® and shows that no new questions of safety and effectiveness have been introduced with this device. The safety and effectiveness of the Hydrozid® are adequately supported by the testing rationale, substantial equivalence information, materials information, and comparison of technical characteristics provided within this premarket notification.

Non-Clinical Performance Data 4.

As part of demonstrating safety and effectiveness of Hydrozid®, and substantial equivalence to the predicate device, a bench test was performed to analyze the thermal profile (surface temperature, duration of the surface temperature and iceball geometry and size) of the cryogen R134A and the predicate device cryogen. The bench test determined that Hydrozid® cryogen performed equivalently to the cryogen of the predicate device.

A second temperature testing performed on Hydrozid® confirmed that the cryogen R134A could reach the minimum desired temperature for cell destruction and vascular stasis in both the minimum and maximum treatment time.

5. Clinical Performance Data

There was no clinical testing required to support the medical device as the indications for use are equivalent to those of the predicate devices. Portable aerosol cryosurgery devices have been on the market for decades and their clinical safety and efficacy has been established. The non-clinical testing detailed in this submission supports the substantial equivalence of the device.

6. Statement of Substantial Equivalence

By definition, a device is substantially equivalent when the device has the same intended use and the same technological characteristics as the previously cleared

{10}------------------------------------------------

predicate device. While there are minor differences between the Hydrozid® and its predicate device, such differences do not affect the principle of operation or mode of action of the Hydrozid®. Existing differences do not raise new questions regarding safety and effectiveness as compared to the predicate device.

It has been shown in these 510(k) submissions that the minor differences between the Hydrozid® and the predicate device do not raise any questions regarding its safety and effectiveness. The Hydrozid® device is determined to be substantially equivalent to the predicate device, Cool Renewal®.

Conclusion 7.

The Hydrozid® device, based on comparison test to the predicate, is substantially equivalent to the predicate device, Cool Renewal®.

Regulation Number and Section

§ 878.4350 Cryosurgical unit and accessories.

(a)
Identification —(1)Cryosurgical unit with a liquid nitrogen cooled cryoprobe and accessories. A cryosurgical unit with a liquid nitrogen cooled cryoprobe and accessories is a device intended to destroy tissue during surgical procedures by applying extreme cold.(2)
Cryosurgical unit with a nitrous oxide cooled cryoprobe and accessories. A cryosurgical unit with a nitrous oxide cooled cryoprobe and accessories is a device intended to destroy tissue during surgical procedures, including urological applications, by applying extreme cold.(3)
Cryosurgical unit with a carbon dioxide cooled cryoprobe or a carbon dioxide dry ice applicator and accessories. A cryosurgical unit with a carbon dioxide cooled cryoprobe or a carbon dioxide dry ice applicator and accessories is a device intended to destroy tissue during surgical procedures by applying extreme cold. The device is intended to treat disease conditions such as tumors, skin cancers, acne scars, or hemangiomas (benign tumors consisting of newly formed blood vessels) and various benign or malignant gynecological conditions affecting vulvar, vaginal, or cervical tissue. The device is not intended for urological applications.(b)
Classification. Class II.