The C2 CryoBalloon™ Ablation System is intended to be used as a cryosurgical tool in the field of general surgery. specifically for endoscopic applications, to include ablation of Barrett's Esophagus with dysplasia and treatment and management of Gastric Antral Vascular Ectasia (GAVE).

Device Description

The subject device is a cryosurgical unit with a nitrous oxide cooled balloon that is compatible with commercially available endoscopes with a minimum working chamel inner diameter of 3.7 mm and maximum length of 105 cm. The subject device is a cryosurgical system comprised of four components including a Catheter (sterile, single use), Controller (non-sterile, reusable), Foot Pedal (non-sterile, reusable), and Cartridge (non-sterile, single use). The system also includes NitroClip as an accessory that is intended to reduce the nitrous oxide exposure in the room.

The subject device is used to ablate unwanted tissue by application of extreme cold. The balloon at the distal end of the Catheter comes in contact with tissue and is inflated with nitrous oxide. Tissue is visualized through the pre-inflated balloon, and the treatment site is selected by adjusting the endoscope and Controller. The nitrous oxide spray cools the balloon to ablate the unwanted tissue, and the nitrous oxide exhausts through the Controller.

AI/ML Overview

The provided document is a 510(k) Premarket Notification from the FDA for the C2 CryoBalloon Ablation System. It outlines the device's indications for use, technological characteristics, and performance data. However, it does not contain specific acceptance criteria with quantifiable metrics, nor does it detail a study explicitly designed to prove the device meets pre-defined acceptance criteria for an AI/CADe device.

The document describes clinical testing to support the device's safety and effectiveness for new indications (GAVE) and a new treatment dose for Barrett's Esophagus. This is different from the type of study typically performed to validate an AI/CADe system against specific performance metrics for diagnostic accuracy.

Therefore, I cannot fulfill all parts of your request as the provided text does not describe an AI/CADe system or a study proving its acceptance criteria in the manner you've requested. The device described, the C2 CryoBalloon Ablation System, is a cryosurgical tool and not an AI or CADe system.

However, I can extract and structure the information available regarding the performance studies that were conducted for this surgical device.

Based on the provided document, here's an analysis of the performance data for the C2 CryoBalloon Ablation System, interpreted in the context of what was evaluated, rather than specific AI/CADe acceptance criteria:

The performance data presented in the document pertains to the surgical effectiveness and safety of the C2 CryoBalloon Ablation System for its stated indications, not the diagnostic performance of an AI system.

Summary of Device Performance and Related Studies:

The document describes:

Bench Testing: To verify temperature profiling, spray radius, and spray uniformity of the 180 Standard catheter at different speeds (1.0 mm/s and 1.2 mm/s).
Clinical Testing:
- Gastric Antral Vascular Ectasia (GAVE): A multi-center retrospective study.
- 180° Catheter Treatment Dose (Barrett's Esophagus): Two studies, one dose-finding (1.0mm/s) and one multi-center (1.2mm/s).

As there are no specific "acceptance criteria" provided in a table format for an AI/CADe device, nor a study proving meeting those, I will present the key outcomes and performance metrics reported for the clinical studies.

Simulated Table of "Acceptance Criteria" and Reported Device Performance (based on clinical outcomes, not AI/CADe metrics):

Performance Metric (Analogous to Acceptance Criteria)	Reported Device Performance (for CryoBalloon Ablation System)
I. GAVE Treatment
Technical success rate	100%
Device malfunctions	0
Serious adverse events (SAEs)	0
Efficacy at 6 months (transfusion independence)	71%
Endoscopic success at 6 months (GAVE eradication)	88%
Mean CryoBalloon ablation treatments	2.4
Blood hemoglobin increase (CryoBalloon vs APC/RFA)	4.6 g/dl (vs 2.55 g/dl with APC/RFA)
Monthly PRBC transfusions decrease (CryoBalloon vs APC/RFA)	0.77 units (vs 1.45 units with APC/RFA)
II. Barrett's Esophagus Treatment (1.0mm/s dose)
Median BE regression (8-10 weeks, single treatment)	90% (95% CI 70%-90%)
Technical success (per protocol)	96%
Stricture requiring dilation	1/23 (4%), resolved with two dilations
Severe bleeding, perforation, other SAEs	0
Adverse events (total)	5 (3 moderate strictures not requiring dilation, 1 dark stools, 1 chest pain)
III. Barrett's Esophagus Treatment (1.2mm/s dose)
Average BE surface regression (3-month follow-up)	95%
Serious adverse events (SAEs)	1 (post-procedure bleeding due to double-dosed anticoagulation, resolved)
Strictures requiring dilation	0
Mild adverse events	2 (no treatments required)
IV. Bench Testing (for 180 Standard catheter)
Temperature profiling data verification	Passed all acceptance criteria
Spray radius and uniformity verification	Confirmed for 1.0 and 1.2 mm/s speeds
Temperature distribution consistency & accuracy	Demonstrated consistently and accurately

Breakdown of Information as per Request (adapted to the available data for a surgical device):

A table of acceptance criteria and the reported device performance:
- See the simulated table above. The "acceptance criteria" are inferred from the outcomes measured and deemed acceptable by the manufacturer and FDA for substantial equivalence. These are not AI/CADe specific accuracy metrics.
Sample sizes used for the test set and the data provenance:
- GAVE Study:
  - Sample Size: 28 subjects (retrospective study).
  - Data Provenance: Not explicitly stated, but compared to a published study of 33 GAVE patients from "three tertiary referral centers in the United States." This suggests the retrospective data for the C2 CryoBalloon system were likely from similar clinical settings, though the specific country of origin is not given. It was a retrospective study.
- BE Study (1.0mm/s dose):
  - Sample Size: 25 patients.
  - Data Provenance: Not explicitly stated regarding country, but described as a "dose-finding phase."
- BE Study (1.2mm/s dose):
  - Sample Size: 25 patients.
  - Data Provenance: Described as a "multicenter study." Not explicitly stated regarding country.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Not applicable in the context of this surgical device. The "ground truth" for GAVE or BE treatment success/eradication would be based on endoscopic findings, histological analysis, and clinical outcomes (e.g., hemoglobin levels, transfusion independence) as determined by treating physicians, not expert readers establishing a consensus for image interpretation. No specific number of experts or their qualifications for "ground truth establishment" are mentioned.
Adjudication method (e.g. 2+1, 3+1, none) for the test set:
- Not applicable as this is not an image-based diagnostic AI/CADe study requiring adjudication of interpretations. Clinical outcomes were measured directly.
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:
- No MRMC study was done, as this is not an AI/CADe device. The comparisons are between the C2 CryoBalloon system and "other modalities" (e.g., APC, RFA) for GAVE treatment, or different doses/catheters for BE treatment.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Not applicable; this is a human-operated surgical device, not a standalone algorithm.
The type of ground truth used (expert concensus, pathology, outcomes data, etc):
- The "ground truth" for these clinical studies relied on:
  - Clinical Outcomes Data: Mean number of packed red blood cells (PRBC) transfused, transfusion independence, blood hemoglobin levels for GAVE.
  - Endoscopic Findings: GAVE eradication, BE surface regression.
  - Adverse Events: Occurrence and severity of complications like strictures, bleeding.
  - These are direct clinical and procedural outcomes, not interpretations of diagnostic images.
The sample size for the training set:
- Not applicable. This is a medical device, not a machine learning model that undergoes "training." The described studies are clinical evaluation studies, akin to validation/test sets for demonstrating safety and efficacy.
How the ground truth for the training set was established:
- Not applicable, as no machine learning training set is involved.

Conclusion based on the provided document:

The provided document refers to the FDA's 510(k) clearance for the C2 CryoBalloon Ablation System, a surgical device. The performance data presented focuses on the safety and effectiveness of the surgical intervention for specific indications (Barrett's Esophagus with dysplasia and Gastric Antral Vascular Ectasia). It outlines clinical study results (retrospective and multi-center studies) and bench testing results. The information requested regarding AI/CADe acceptance criteria, MRMC studies, AI training/test sets, and expert consensus/adjudication for diagnostic ground truth is not applicable to this type of device and the studies described.

Summary

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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

July 24, 2024

PENTAX of America, Inc. Gurvinder Singh Nanda Senior Director, Regulatory and Quality 3 Paragon Drive Montvale, New Jersey 07645

Re: K240457

Trade/Device Name: C2 CryoBalloon Ablation System (C2 CryoBalloon Ablation System) Regulation Number: 21 CFR 878.4350 Regulation Name: Cryosurgical Unit And Accessories Regulatory Class: Class II Product Code: GEH Dated: June 21, 2024 Received: June 21, 2024

Dear Gurvinder Singh Nanda:

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 (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 available at https://www.accessdata.fda.gov/scripts/cdrb/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.

Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

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Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review. the OS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.70) and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

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 801); medical device reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 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 Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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,

Long H. Chen -Si Digitally signed by Long H.Chen -S
Date: 2024.07.24 08:20 Date: 2024.07.24 08:36:02 -04'00'

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 Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K240457

Device Name C2 CryoBalloon Ablation System

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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510(k) Summary

I. SUBMITTER

PENTAX of America 3 Paragon Drive Montvale, NJ 07645 Phone: 650-722-4189

Contact Name: Gurvinder Singh Nanda, PhD. Date Prepared: June 19, 2024

II. DEVICE

Name of Device: C2 CryoBalloon™ Ablation System Common or Usual Name: Cryosurgical Unit and Accessories Classification Name: Cryosurgical Unit and Accessories Regulatory Class: 21 CFR §878.4350 Product Code: GEH

III. PREDICATE DEVICE

C2 CryoBalloon™ Ablation System, K212814

IV. REFERENCE DEVICE

BARRX Medical HALO® System, K093008

V. DEVICE DESCRIPTION

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VI. INDICATIONS FOR USE

The C2 CryoBalloon™ Ablation System is intended to be used as a cryosurgical tool in the field of general surgery, specifically for endoscopic applications, to include ablation of Barrett's Esophagus with dysplasia and treatment and management of Gastric Antral Vascular Ectasia (GAVE).

VII. COMPARISON OF TECHNOLOGICAL CHARACTERISTICS WITH THE PREDICATE DEVICE

Cryoablation is the fundamental technological principle for both the subject C2 CryoBalloon Ablation System and the predicate C2 CryoBalloon Ablation System (K212824). There have been no significant changes to the technological characteristics of the C2 CryoBalloon Ablation System since of the predicate device. The subject and the legally marketed predicate device C2 CryoBalloon Ablation System have the same design, materials, energy source, and principles of operation.

The subject and the predicate devices are based on the following same technological elements:

· Inserted through an endoscope to access the treatment site
· Application of cryogen to ablate (freeze) the unwanted tissue
· Use of a compliant balloon to position the treatment diffuser and to contain and exhaust the cryogen
· User-controlled (trigger/foot pedal) to release cryogen
Software activated Controller

The only difference is the indication of use of the subject device now includes treatment and management of Gastric Antral Vascular Ectasia (GAVE).

The inclusion in the labeling of a lower dose to treat patients with short segment Barrett's Esophagus (BE) using the subject C2 CryoBalloon 180 catheter is within the device's current intended use and indications for use. The change of the catheter's RFID value of Maximum Treatment Speed from 1.0mm/s to 1.2mm/s for the lower dose falls under existing design verification. The addition of this lower treatment rate is also supported by bench and clinical data demonstrating its safety and effectiveness.

Two caution statements have been removed from the Instructions for Use. These modifications are supported by bench and / or clinical data regarding the safety and effectiveness of its use, which do not raise different questions of safety and effectiveness.

VIII.PREFORMANCE DATA

Bench Testing A.

Bench testing was performed to verify the results of the temperature profiling data of the 180 Standard catheter at 1.0 mm/s and 1.2 mm/s speeds. The tests passed all acceptance criteria. Testing results verified

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the spray radius and spray uniformity of the Standard 180 Catheter, confirming that the 180 Catheter can be used at speeds of 1.0 and 1.2mm/s.

Test method validation was performed for the C2 CryoBalloon Catheters that use the 180-degree diffuser. Temperature distribution tests were performed to verify temperature spray profiles for catheters, where the profile determines what percentage of the spray pattern reaches optimal temperatures for treatment. The results of the testing demonstrated that the temperature distribution can be produced consistently and accurately.

No animal data was used to support this 510(k) premarket notification.

B. Clinical Testing
1. Gastric Antral Vascular Ectasia (GAVE)

A multi-center retrospective study evaluated the C2 CryoBalloon system focal for the treatment and management of GAVE. 28 subjects were included based on endoscopic report findings and history of clinical evidence of GAVE. All patients in the study had been previously treated to manage their GAVE disease with argon plasma coagulation (APC), radiofrequency ablation (RFA), liquid nitrogen cryotherapy (LNC) or were treatment naïve. The primary outcome was the mean number of packed red blood cells (PRBC) transfused before treatment versus after CryoBalloon ablation (CBA). Outcomes were compared to a published study of 33 GAVE patients that were treated with APC or RFA from three tertiary referral centers in the United States.

With the CryoBalloon ablation system treatment, technical success was 100% with no device malfunctions and no serious adverse events. Efficacy at 6 months was 71% for transfusion independence. Endoscopic success at 6 months was 88% GAVE eradication with 2.4 mean CryoBalloon ablation treatments.

Literature review shows clinical success for CryoBalloon ablation treatment (62-83%) is comparable to other modalities (50-100%). Blood hemoglobin increased 4.6 g/dl with CryoBalloon ablation treatment versus 2.55 g/dl with APC/RFA. Monthly packed red blood cell transfusions decreased by 0.77 units with CryoBalloon ablation treatment versus 1.45 units with APC/RFA.

Overall, the study shows CryoBalloon ablation treatment is effective for long-term GAVE treatment, with 6-month outcomes similar or better than other modalities and supported by literature review.

1. 180° Catheter Treatment dose
  Two studies evaluated the safety and efficacy of the 180° CryoBalloon ablation catheter for treatment of Barrett's esophagus (BE) related. The first study enrolled 25 patients at a 1.0mm/s dose in a dose-finding phase to establish the effective dose that resulted in BE regression at 8-10 weeks of ≥60 %. The study's results demonstrated a median BE regression as evaluated of 90 % (95 % CI 70 %-90%) after a single 1.0mm/s treatment. Technical success was 96% per protocol. One patient (1/23; 4 %), developed a stricture that was resolved with two dilations. No severe bleeding, perforation, or other SAEs occurred. Five patients had adverse events. Three patients had moderate strictures not requiring dilation, one patient had dark

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colored stools (no melena), which resolved spontaneously, and one patient experienced heavy chest pain on the day of treatment and additional analgesics were prescribed.

The second study was a multicenter study treating 25 patients with short segment BE using a lower 180° CryoBalloon Ablation catheter dose of 1.2mm/s. Average BE surface regression was 95% at a 3-month follow-up visit. One serious adverse event (post-procedure bleeding from a patient with double-dosed anticoagulation therapy due to a pre-existing cardiac condition.) occurred which resolved. No strictures requiring dilation occurred. Two mild adverse events occurred post procedure in which no treatments were required.

In summary, both studies demonstrate the 180° CryoBalloon ablation system catheter is safe and effective for BE treatment using doses of 1.0mm/s and 1.2mm/s. Excellent technical success and BE regression were achieved with minimal adverse events. The data supports the lower dose labeling for short segment BE treatment.

IX. CONCLUSIONS

C2 CryoBalloon Ablation System meets all substantial equivalence criteria for use as a cryosurgical tool in the field of general surgery, specifically for endoscopic applications, to include ablation of Barrett's Esophagus with dysplasia and treatment and management of Gastric Antral Vascular Ectasia(GAVE) based on comparable use, technology, data, and minor differences not affecting safety/effectiveness.

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.