Hydrozid Precise contains 1.1.1.2-tetrafluoroethane (also known as R134A, HFC-134a, HFA-134a or fluorocarbon 134a) and is to be used for the treatment of vertuca (warts), including plantar warts, seborrheic keratosis, acrochordon (skin tags), molluscum contagiosum, age spots (lentigo), dermatofibroma, small keloids, granuloma annulare, porokeratosis plantaris, angiomas, keratoacanthoma, chondrodermatits, epithelial nevus, leukoplakia, granuloma pyogenicum, and pyogenic granuloma.

Device Description

Hydrozid Precise™ is a portable aerosol cryosurgery device intended for the treatment of benign and premalignant skin lesions using a cryogen to freeze cells to induce 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, single-patient application templates which are disposed after use.

AI/ML Overview

The provided text describes a 510(k) premarket notification for the Hydrozid Precise™ device. The submission aims to establish substantial equivalence to a predicate device, Hydrozid®. The document focuses on demonstrating that the new device is as safe and effective as the predicate, rather than providing detailed acceptance criteria and a study to prove a predetermined performance outcome. The study described is a bench test comparing the thermal profile of the new device to the predicate device.

Here's an analysis of the available information:

1. A table of acceptance criteria and the reported device performance

The document does not explicitly state acceptance criteria in terms of numerical thresholds for a specific clinical performance metric (e.g., sensitivity, specificity, accuracy) for Hydrozid Precise™. Instead, the "acceptance criterion" in this context is demonstrating substantial equivalence to the predicate device Hydrozid® in terms of its thermal profile (surface temperature, duration of surface temperature, and ice-ball formation).

Acceptance Criteria (Implied for Substantial Equivalence)	Reported Device Performance (Hydrozid Precise™)
Capable of reaching the minimum desired temperature for cell destruction and vascular stasis in both minimum and maximum treatment time, equivalent to the predicate device.	Confirmed that the cryogen R134a was capable of reaching the minimum desired temperature for cell destruction and vascular stasis in both the minimum and maximum treatment time. Performed equivalently to the predicate device Hydrozid®.
Thermal profile (surface temperature, duration of surface temperature, and ice-ball) is equivalent to the predicate device.	The bench test determined that Hydrozid Precise™ performed equivalently to the predicate device Hydrozid® in terms of its thermal profile.

2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

The document mentions a "bench test" to analyze the thermal profile. For this type of test, "sample size" typically refers to the number of devices or test conditions evaluated. However, the specific sample size used for the bench test is not provided. The data provenance (country of origin, retrospective/prospective) is also not specified, though it is likely a prospective bench study conducted by the manufacturer, BIBAWO Medical A/S, based in Denmark.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

This information is not applicable as the described study is a non-clinical bench test analyzing the thermal profile of the device, not a study involving human subjects or expert assessment of clinical outcomes. Therefore, no experts were used to establish ground truth in this context.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

This information is not applicable as the described study is a non-clinical bench test. Adjudication methods are relevant for studies involving human interpretation or clinical outcomes where discrepancies need to be resolved.

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

A multi-reader, multi-case (MRMC) comparative effectiveness study was not done. This type of study is typically conducted for diagnostic or AI-powered devices involving human interpretation, which is not the case for this cryosurgical unit.

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

This refers to the performance of an algorithm without human intervention. The Hydrozid Precise™ is a medical device (cryosurgical unit), not an artificial intelligence (AI) algorithm. Therefore, a standalone algorithm performance study was not done. The "standalone" performance here would refer to the device's physical function in the bench test.

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

For the non-clinical bench test, the "ground truth" would be the measured physical properties (surface temperature, duration of surface temperature, and ice-ball characteristics) of the cryogen (R134a) under controlled experimental conditions, often established using calibrated measurement equipment. These measurements are then compared to the established performance of the predicate device.

8. The sample size for the training set

This information is not applicable. Cryosurgical devices are not typically "trained" in the way AI algorithms are. No training set was used.

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

This information is not applicable as there was no training set.

Summary

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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 FDA name and title on the right. The symbol on the left is a stylized representation of a human figure, while the text on the right reads "FDA U.S. FOOD & DRUG ADMINISTRATION" in blue letters.

May 30, 2023

BIBAWO Medical A/S Sandra Larsen Manager of Regulatory Affairs and Ouality Assurance Klintehøj Vænge 6 Birkerød, 3460 Denmark

Re: K221897

Trade/Device Name: Hydrozid Precise Regulation Number: 21 CFR 878.4350 Regulation Name: Cryosurgical Unit And Accessories Regulatory Class: Class II Product Code: GEH Dated: April 24, 2023 Received: April 27, 2023

Dear Sandra Larsen:

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

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requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 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 (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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (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,

Digitally signed Mark by Mark Trumbore Trumbore -s Date: 2023.05.30 -5 09:42:22 -04'00' Mark Trumbore, 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

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Indications for Use

510(k) Number (if known) K221897

Device Name Hydrozid Precise

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)

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Image /page/3/Picture/1 description: The image shows the logo for BIBAWO Medical. The word "BIBAWO" is in large, bold, blue letters. Below it, in smaller blue letters, is the word "Medical."

510(k) Summary - Hydrozid Precise™

In accordance with 21 CFR Part 807, Section 807.92, this information serves as a 510(k) summary for Hydrozid Precise™ (K221897).

Date Prepared: May 24th, 2023 Submitted by: BIBAWO Medical A/S Klintehøj Vænge 6 3460 Birkerød Denmark

Contact Person:

Sandra Larsen Manager of Requlatory Affairs & Quality Assurance Sandra.larsen@bibawo-medical.com +45 81 40 18 43

Proprietary Name: Hydrozid Precise™ Common Name: Portable aerosol cryosurgery device Classification Name: Unit, Cryosurgical, Accessories Classification Requlation: 21 CFR 878.4350 Device: Class II Device Product Code: GEH Device Panel: General & Plastic Surgery Predicate Device: Hydrozid® (K201740) manufactured by BIBAWO Medical A/S is the predicate device.

5.1. Description of the Device

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non-sterile, single-patient application templates which are disposed after use.

The mechanism of action for both Hydrozid Precise™ and the predicate device, Hydrozid®, 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 5.2.

Hydrozid Precise™ contains 1,1,2-tetrafluoroethane (also known as R134a, HFC-134a, HFA-134a or fluorocarbon 134a) and is to be used for the treatment of verruca (warts), including plantar warts, seborrheic keratosis, actinic keratosis, acrochordon (skin tags), molluscum contagiosum, age spots (lentigo), dermatofibroma, small keloids, granuloma annulare, porokeratosis plantaris, angiomas, keratoacanthoma, chondrodermatitis, epithelial nevus, leukoplakia, granuloma pyogenicum, and pyogenic granuloma.

5.3. Substantial Equivalence Discussion

The Hydrozid Precise™ intended use, intended users, indications and clinical application as well as the overall technical characteristics are equivalent to the predicate device. The below table (table 5.3-1) compares the Hydrozid Precise™ to the predicate device with respect to intended use, technological characteristics and principles of operation.

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Image /page/5/Picture/1 description: The image shows the logo for BIBAWO Medical. The word "BIBAWO" is in large, bold, blue letters. Below "BIBAWO" is the word "Medical" in smaller, blue letters. The logo is simple and clean, with a focus on the company name.

Device TradeName	Hydrozid Precise™Subject Device	Hydrozid®Predicate Device	SignificantDifferences
Manufacturer	BIBAWO Medical A/S	BIBAWO Medical A/S	Same
Common Name	Portable aerosolcryosurgery device	Portable aerosolcryosurgery device	Same
Classificationname	Unit, Cryosurgical,Accessories	Unit, Cryosurgical,Accessories	Same
Regulationnumber	21 CFR 878.4350	21 CFR 878.4350	Same
Class	II	II	Same
Device ProductCode	GEH	GEH	Same
Device Panel	General & PlasticSurgery.	General & PlasticSurgery.	Same
Sterile	No	No	Same
Indicationsfor Use	Hydrozid Precise™contains 1,1,1,2-tetrafluoroethane (alsoknown as R134a, HFC-134a, HFA-134a orfluorocarbon 134a) andis to be used for thetreatment of verruca(warts) including plantarwarts, seborrheickeratosis, actinickeratosis,acrochordon (skin tags),molluscum contagiosum,age spots (lentigo),	Hydrozid® (also known asR134A or 1,1,1,2-tetrafluoroethane or HFC-134a or HFA-134a orfluorocarbon 134a) is to beused for the treatment ofverruca (warts) includingplantar warts, seborrheickeratosis, actinickeratosis, achrochordon(skin tags), molluscumcontagiosum, age spots,dermatofibroma, smallkeloids,	Same
	dermatofibroma, smallkeloids, granulomaannulare, porokeratosisplantaris, angiomas,keratoacanthoma,chondrodermatitis,epithelial nevus,leukoplakia, granulomapyogenicum, andpyogenic granuloma.	granuloma annulare,porokeratosis plantaris,angiomas,keratoacanthoma,chondrodermatitis,epithelial nevus,leukoplakia, granulomapyogenicum, andpyogenic granuloma.
Intended Users	For professionaluse only.	For professional useonly	Same
Mechanismof Action	Cryosurgery: freeze thetarget tissuetemperature to belowthe level that correlateswith cell destruction(necrosis). When thecryogen evaporates, itabsorbs heat from itssurroundings causingcell destruction due to:• Direct effects offreezing on the cells• Vascular stasiswhich develops afterthawing.	Cryosurgery: freeze thetarget tissue temperatureto below the level thatcorrelates with celldestruction (necrosis).When the cryogenevaporates, it absorbsheat from itssurroundings causingcell destruction due to:• Direct effects offreezing on the cells• Vascular stasiswhich develops afterthawing.	Same

	The mechanism of	The mechanism of action
	action in cryosurgery	in cryosurgery are divided
	are divided into 3	into 3 phases:
	phases:	(1) heat transfer,
	(1) heat transfer,	(2) Cell death, and
	(2) Cell death, and	(3) inflammation.
	(3) inflammation.
	R134a: 1,1,1,2-	R134a: 1,1,1,2-	Same
Cryogen	tetrafluoroethane	tetrafluoroethane
	(CAS 354-33-6).	(CAS 354-33-6).
Freezing time	Transient use; < 1 minute.Specific freeze timedetermined by the type,size and location of thelesion being treated	Transient use; < 1 minute.Specific freeze timedetermined by the type,size and location of thelesion being treated	Same
Treatmentdistance	Approximately 1 cm (0.4in) from the lesion.	2 to 3 cm (0.79 to 1.18 in)from the lesion.	Similar
Accessories	Application Templates	Application Templates	Same
TechnicalcharacteristicsDevice	Portable cryosurgerydevice to be applied directlyon the indication.	Portable cryosurgerydevice to be applied directlyon the indication.	Same
TechnicalcharacteristicsSpray head design	Spray head has a sprayoutlet that is 0.1 mm.	Spray head has a sprayoutlet that is 0.25 mm.	Similar
Technical	Consist of a spray head	Consist of a spray head	Similar
characteristics	witha fixed tip/tube	with a somewhat flexible
Spray head design		tip/tube
TechnicalcharacteristicsSpray head design	Color: black	Color: white	Similar

Table 5.3-1: Substantial Equivalence Summary

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Image /page/6/Picture/1 description: The image shows the logo for BIBAWO Medical. The text "BIBAWO" is in large, bold, blue letters. Below that, the word "Medical" is in smaller, blue letters. The logo is simple and professional.

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Image /page/7/Picture/1 description: The image shows the logo for BIBAWO Medical. The word "BIBAWO" is in large, bold, blue letters on the top line. Below that, the word "Medical" is in smaller, bold, blue letters. The logo is simple and clean, with a focus on the company name.

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Image /page/8/Picture/1 description: The image shows the logo for BIBAWO Medical. The text "BIBAWO" is in large, bold, blue letters. Below that, the word "Medical" is in smaller, bold, blue letters. The logo is simple and professional.

Testing and arqumentation rationale were provided to support the equivalence of the Hydrozid Precise™ and shows that no new questions of safety and effectiveness have been introduced with this device. The safety and effectiveness of the Hydrozid Precise™ 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 5.4.

As part of demonstrating safety and effectiveness of Hydrozid Precise™, 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 ice-ball) of the cryogen R134a.

The bench test determined that Hydrozid Precise™ performed equivalently to the predicate device Hydrozid®.

The temperature testing performed on Hydrozid Precise™ confirmed that the cryogen R134a was capable of reaching the minimum desired temperature for cell destruction and vascular stasis in both the minimum and maximum treatment time.

Statement of Substantial Equivalence 5.5.

By definition, a device is substantially equivalent when the device has the same intended use and the same technological characteristics as the previously cleared predicate device. Hydrozid Precise™ does not raise new questions regarding safety and effectiveness as compared to the predicate device.

5.6. Conclusion

The Hydrozid Precise™ device is determined, based on comparison test to the predicate device, to be substantially equivalent to the predicate device, Hydrozid®.

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.