The Crosseal™ Application Device is intended for the simultaneous topical application of the two biological components of Crosseal™ Fibrin Sealant via dripping (no air pressure) or via spraying (with air pressure utilizing the pressure regulator unit) onto the surface of the liver in patients undergoing liver surgery.

Device Description

The Crosseal" Application Device is a sterile, single-use, disposable two-syringe device used for the application by dripping or spraying of the two biological components of Crosseal "Fibrin Sealant onto the surface of the liver in patients undergoing liver surgery. . The two syringes are connected to either a dual (nonspraying) or tri-lumen (spraying) catheter. The device also has two Mixject Dispensing Pins with Detachable Vial Holders, a device that has already been cleared by the FDA through Premarket Notification [510(k)]. The Mixject is used to attach the glass vials containing the biological components for transfer into the syringes without the use of needles. For spraying, the Application Device must be connected through an air tube with a sterile filter to a supply of pressurized gas (compressed air, nitrogen, CO2) via a pressure regulator, which is an accessory to the Application Device. For dripping, the Application Device can be used with or without pressurized gas. The device is ethylene oxide (EtO) sterilized.

AI/ML Overview

The provided text describes a 510(k) premarket notification for the Crosseal™ Application Device. This type of regulatory submission focuses on demonstrating substantial equivalence to a predicate device rather than presenting detailed clinical trial data with specific acceptance criteria in the same way a PMA or de novo submission might.

Therefore, the information available is limited and structured differently from what would typically be presented for a diagnostic AI device requiring a study proving adherence to specific acceptance criteria.

However, I can extract the relevant information based on the sections provided to best answer your request.

Acceptance Criteria and Reported Device Performance for Crosseal™ Application Device

The "acceptance criteria" for this device, in the context of a 510(k), are not explicit numerical targets for diagnostic performance (e.g., sensitivity, specificity). Instead, the studies performed aimed to demonstrate that the device functions as intended and is safe for its indicated use, specifically concerning the application of fibrin sealant. The primary performance criteria revolve around the optimal application parameters for the sealant.

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criterion (Implicit)	Reported Device Performance
Optimal Spray Application: Uniformity of mixing and consistency of spray spread.	Performance testing studies determined an optimal gas pressure range and optimal spray distance to achieve uniformity of mixing and consistency of spray spread. The optimal gas pressure was 34 psi, and the optimal spray distance was 10-15 cm.
Safety - Biocompatibility: No skin irritation.	A Primary Skin Irritation Evaluation found the test article extract did not produce skin irritation.
Safety - Biocompatibility: No sensitization.	A Guinea Pig Maximization test found the test article extract did not produce sensitization.
Safety - Biocompatibility: Non-cytotoxic.	A Cytotoxicity Test (MEM Elution Test) found the test article to be non-cytotoxic.
Safety - Biocompatibility: No acute systemic toxicity.	An Acute Systemic Toxicity Test found no reaction in mice observed over 72 hours.
Safety - Biocompatibility: Non-pyrogenic.	A Pyrogenicity Test (Limulus Test) found the test article to be non-pyrogenic.
Safety - Biocompatibility: Non-hemolytic and no effect on clotting time.	In vitro hemolysis study (modified ASTM - Direct Contact Method) and determination of clotting time (Lee-White Method) revealed the test article was non-hemolytic and did not biologically affect clotting time.
Clinical Efficacy: Efficacious method for optimal coverage of fibrin sealant.	Two U.S. pivotal Phase III clinical trials evaluated the optimal gas pressure (34psi) and optimal spray distance (10-15 cm). The studies demonstrated this is an efficacious method of providing optimal coverage of fibrin sealant onto the surgical tissue surface. No adverse events were associated with the system.

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

Sample Size: The document does not explicitly state the sample size for the performance testing studies (e.g., how many sprays were tested or how many in vitro tests were performed). For the clinical trials, the number of patients is not specified, only that "Two U.S. pivotal Phase III clinical trials" were conducted.
Data Provenance:
- Performance Testing: Not explicitly stated, but implies laboratory testing.
- Clinical Trials: "Two U.S. pivotal Phase III clinical trials." This indicates retrospective or prospective (likely prospective for Phase III) clinical data from the United States.

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

This type of information is not applicable to this device submission. The "ground truth" here is objective performance (e.g., pressure, distance, biocompatibility results) and clinical outcomes (efficacy of sealant application, absence of adverse events). There is no mention of experts assessing image data or making diagnostic judgments.

4. Adjudication Method for the Test Set

Not applicable. This device is not a diagnostic device requiring adjudication of expert opinions for a test set.

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 device is an application device for a sealant, not an AI-powered diagnostic tool, and therefore, an MRMC study is not relevant to its evaluation.

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

Not applicable. This is not an algorithm or AI system.

7. The Type of Ground Truth Used

For Spray Application Performance: Physical measurements of spray uniformity and consistency, potentially visual inspection, and likely quantitative analysis of sealant distribution in laboratory settings.
For Biocompatibility: Standardized laboratory assays (e.g., primary skin irritation, guinea pig maximization, cytotoxicity, acute systemic toxicity, pyrogenicity, hemolysis, clotting time) with specific endpoint criteria.
For Clinical Efficacy: Clinical observations within the Phase III trials, likely involving assessment of sealant coverage and related surgical outcomes, and monitoring for adverse events.

8. The Sample Size for the Training Set

Not applicable. This is not an AI-based device, 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, this information is not relevant.

Summary

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K030032

510(k) SUMMARY

Submitter:

OMRIX biopharmaceuticals, Ltd. MDA blood bank, Sheba Hospital, Ramat-Gan POB 888, Kiryat Ono 55000 ISRAEL Tel: +972 3 531 6531 Fax: +972 3 535 0265

Date Summary was Prepared:

Contact Person:

Sue Bhadare CROfessionals LLC 6599 Commerce Court Suite 200, Warrenton VA 20187, USA Tel: (540) 428 2828 Fax: (540) 428 2834

March 2003

Name of Device:

Crosseal™ Application Device

Identification of Predicate Devices:

Duploject™ Baxter Healthcare Corporation, Hyland Immuno K973510

Mixject® Dispensing Pin with Detachable Vial Holder Medimop Medical Projects, Ltd. (Israel) K963283

Tissomat® and Spray Set Baxter Healthcare Corporation, Hyland Immuno K981089

Description of Device:

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OMRIX biopharmaceuticals, Inc. Crosseal™Application Device Premarket Notification

nitrogen, CO2) via a pressure regulator, which is an accessory to the Application Device. For dripping, the Application Device can be used with or without pressurized gas. The device is ethylene oxide (EtO) sterilized. Intended Use:

The Crosseal" Application Device is intended for the simultaneous topical application of the two biological components of Crosseal Fibrin Sealant via dripping (no air pressure) or via spraying (utilizing the pressure regulator unit) onto the surface of the liver in patients undergoing liver surgery.

Similar Technical Characteristics between Crosseal Application Device and Duploject®

Characteristic	Crosseal™ Application Device	Duploject®
Indications	Intended for use in the simultaneousdelivery of the two solutions ofCrosseal™ Fibrin Sealant onto thesurface of the liver in patientsundergoing liver surgery.	Intended for use in the simultaneousdelivery of two non-homogeneousfluids or solutions onto a surgical site.
Syringe Volume	1.0 mL, 2.0 mL, and 5.0 mL	0.5/1.0 mL, 2.0 mL, and 5.0 mL
Delivery Accuracy	The slide bar on the syringe holderensures delivery of equal amounts ofthe contents of the syringes.	The slide bar on the syringe holderensures delivery of equal amounts ofthe contents of the syringes.
Syringe Assembly	Syringes preassembled into syringeholster. Syringe pistons yoke-coupled.	Syringes preassembled into syringeholster. Syringe pistons yoke-coupled
Method of drawingsolutions into syringes	Mixject Dispensing Pin withDetachable Vial Holder	Syringe needles
Catheter Tip	Tri-lumen tip configuration,Malleable cannula	Bi-lumen tip configuration,malleable cannula
Use	Single-use, disposable for hospital use	Single-use, disposable for hospital use
Sterilization	EtO	EtO

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Similar Technical Characteristics between Crosseal™ Application Device and Tissomat® and Spray Set

Characteristic	Crosseal™ Application Device	Tissomat® and Spray Set
Indications	Intended for use in the simultaneousapplication by dripping or spraying ofthe two components of Crosseal™Fibrin Sealant onto wound surfaces.	Intended for use in the simultaneousapplication by spraying of the twocomponents of Tisseel Fibrin Sealantonto wound surfaces.
Gas Supply	Compressed air, nitrogen, or CO2	Compressed air, nitrogen, or CO2
Spraying distance	10 to 15 cm	Minimum of 10 cm
Recommended gaspressure	2 to 3 bars (30 to 40 psi)	Maximum of 2 bars (28.5 psi)

Performance Information:

Use of the spray application technology is supported by performance testing studies that determined the optimal gas pressure range and the optimal distance that the spray catheter is required to be from the surgical tissue surface to obtain uniformity of mixing and consistency of spray spread. The optimal gas pressure (34psi) and optimal spray distance 10-15 cm was evaluated in two U.S. pivotal Phase III clinical trials. There were no adverse events associated with this system and the clinical studies demonstrated that this is an efficacious method of providing optimal coverage of fibrin sealant onto the surgical tissue surface.

Summary of Biocompatibility Tests:

A Primary Skin Irritation Evaluation was conducted using a test extract of the . device. Under the conditions of the test, the test article extract was found to not produce skin irritation.
A Guinea Pig Maximization was performed using a test extract of the device. . Under conditions of the test, the Test Article, extracted in normal saline, was found to not produce sensitization.
A Cytotoxicity Test (MEM Elution Test) was performed using a test extract of . the device. Under conditions of the test, the Test Article was found to be noncytotoxic.
An Acute Systemic Toxicity Test was conducted using a test extract of the ● device. Under conditions of the test, there was no reaction of the mice to the Test article when observed at intervals of a period of 72 hours following treatment.

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A Pyrogenicity Test (Limulus Test)-Materials Mediated, was performed using . a test extract of the device. Under conditions of the test, the Test Article was found to be non-pyrogenic.
Two studies were conducted to determine hemocompatibility: an in vitro . hemolysis study (modified ASTM - Direct Contact Method) and a determination of clotting time using the Lee-White Method. The studies revealed that the test article was non-hemolytic, and did not biologically effect the clotting time.

Conclusions:

The intended use, design, materials of fabrication and performance of the Crosseal" Application Device are substantially equivalent to both the Duploject and the Tissomat and Spray Set. Differences in spray parameters (spray distance, pressure) have been justified through both laboratory performance testing and human clinical trials. It is concluded that the Crosseal" Application Device is substantially equivalent to these legally marketed devices.

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Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" around the perimeter. Inside the circle is a stylized image of three human profiles facing right, with flowing lines above them that resemble a bird in flight.

Public Health Service

MAR 2 1 2003

Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

OMRIX Biopharmaceuticals, Incorporated Ms. Sue Bhadare Consultant CRO Fessionals, LLC 6599 Commerce Court, Suite 200 Warrenton, Virginia 20187

Re: K030032

Trade/Device Name: Crosseal Application Device Regulation Number: 880.5860 Regulation Name: Piston Syringe Regulatory Class: II Product Code: FMI Dated: January 3, 2003 Received: January 3, 2003

Dear Ms. Bhadare:

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. 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.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting vour 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.

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Page 2 - Ms. Bhadare

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): good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of Compliance at (301) 594-4618. Also, please note the regulation entitled. "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html

Sincerely vours.

Susan Runner, DDS, MA

Interim Director Division of Anesthesiology, General Hospital, Infection Control and Dental Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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4.0 INDICATIONS FOR USE

510(k) Number:

Device Name: Crosseal™ Application Device

Classification: Class II

Product Code: 80FMF, Piston Syringe

Indications for Use:

Concurrence of CDRH, Office of Device Evaluation (ODE)

Patricio Cucente

(Division Sign-Off) (Division Sign-Off)
Division of Anesthesiology, General Hospital, Division of Anesthesion Control, Dental Devices

510(k) Number: K030032

Prescription Use (Per 21 C.F.R. 801 109)

Over-the-Counter Use _________________________________________________________________________________________________________________________________________________________

4-1

Regulation Number and Section

§ 880.5570 Hypodermic single lumen needle.

(a)
Identification. A hypodermic single lumen needle is a device intended to inject fluids into, or withdraw fluids from, parts of the body below the surface of the skin. The device consists of a metal tube that is sharpened at one end and at the other end joined to a female connector (hub) designed to mate with a male connector (nozzle) of a piston syringe or an intravascular administration set.(b)
Classification. Class II (performance standards).