CROSSEAL APPLICATION DEVICE

K030032 · Omrix Biopharmaceuticals, Inc. · FMI · Mar 21, 2003 · General Hospital

Device Facts

• Record ID: K030032
• Device Name: CROSSEAL APPLICATION DEVICE
• Applicant: Omrix Biopharmaceuticals, Inc.
• Product Code: FMI · General Hospital
• Decision Date: Mar 21, 2003
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 880.5570
• Device Class: Class 2
• Attributes: Therapeutic

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.

Device Story

Sterile, single-use, disposable two-syringe device for applying Crosseal Fibrin Sealant to liver surfaces. Inputs: two biological components transferred from vials via Mixject Dispensing Pins into syringes. Operation: syringe pistons are yoke-coupled to ensure equal delivery volumes; device uses dual-lumen catheter for dripping or tri-lumen catheter for spraying. Spraying requires external pressurized gas (compressed air, nitrogen, or CO2) via a pressure regulator accessory. Used in hospital settings by surgeons. Output: uniform mixture of fibrin sealant applied to surgical site. Benefits: provides optimal coverage of fibrin sealant on tissue to assist in surgical procedures.

Clinical Evidence

Supported by two U.S. pivotal Phase III clinical trials evaluating optimal gas pressure (34 psi) and spray distance (10-15 cm). Studies demonstrated efficacious delivery and optimal coverage of fibrin sealant on surgical tissue with no associated adverse events. Biocompatibility testing included skin irritation, sensitization, cytotoxicity, acute systemic toxicity, pyrogenicity, and hemocompatibility (hemolysis and clotting time) studies, all showing non-reactive results.

Technological Characteristics

Two-syringe system with yoke-coupled pistons. Materials: sterile, disposable plastic components. Connectivity: manual or gas-assisted (compressed air, nitrogen, CO2). Dimensions: 1.0 mL, 2.0 mL, and 5.0 mL syringe volumes. Sterilization: Ethylene Oxide (EtO). Delivery: dual-lumen (dripping) or tri-lumen (spraying) catheter. Includes Mixject Dispensing Pins for needle-free vial transfer.

Indications for Use

Indicated for simultaneous topical application of two-component Crosseal Fibrin Sealant onto liver surfaces during liver surgery. For use in patients undergoing liver surgery.

Regulatory Classification

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.

Predicate Devices

• Duploject™ (K973510)
• Mixject® Dispensing Pin with Detachable Vial Holder (K963283)
• Tissomat® and Spray Set (K981089)

Submission Summary (Full Text)

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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: [phone] Fax: [phone]

## Date Summary was Prepared:

# Contact Person:

Sue Bhadare CROfessionals LLC 6599 Commerce Court Suite 200, Warrenton VA 20187, USA Tel: [phone] Fax: [phone]

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:

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,

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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 simultaneous<br>delivery of the two solutions of<br>Crosseal™ Fibrin Sealant onto the<br>surface of the liver in patients<br>undergoing liver surgery. | Intended for use in the simultaneous<br>delivery of two non-homogeneous<br>fluids 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 holder<br>ensures delivery of equal amounts of<br>the contents of the syringes. | The slide bar on the syringe holder<br>ensures delivery of equal amounts of<br>the contents of the syringes. |
| Syringe Assembly | Syringes preassembled into syringe<br>holster. Syringe pistons yoke-coupled. | Syringes preassembled into syringe<br>holster. Syringe pistons yoke-coupled |
| Method of drawing<br>solutions into syringes | Mixject Dispensing Pin with<br>Detachable Vial Holder | Syringe needles |
| Catheter Tip | Tri-lumen tip configuration,<br>Malleable cannula | Bi-lumen tip configuration,<br>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 simultaneous<br>application by dripping or spraying of<br>the two components of Crosseal™<br>Fibrin Sealant onto wound surfaces. | Intended for use in the simultaneous<br>application by spraying of the two<br>components of Tisseel Fibrin Sealant<br>onto 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 gas<br>pressure | 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 [phone]. 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 [phone] or [phone] 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:

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.

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)

Or

Over-the-Counter Use _________________________________________________________________________________________________________________________________________________________

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