Predicate Devices

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The summary describes a mechanical system for temperature regulation using catheters and a console, with no mention of AI or ML algorithms for control, analysis, or prediction.

Therapeutic

Yes.
The device is indicated for fever reduction, achieving/maintaining normothermia, and inducing/maintaining/reversing hypothermia, all of which are direct interventions for medical conditions.

Diagnostic

No.

The device is intended for therapeutic purposes (temperature regulation), not for diagnosing conditions.

SaMD (Software as a Medical Device)

No

The device description clearly details physical components including catheters, a Start-Up Kit (SUK), and a console (CoolGard 3000 or Thermogard XP). It describes the physical connection and circulation of fluid through these hardware components for heat exchange. This is not a software-only device.

IVD (In Vitro Diagnostic)

Based on the provided information, this device is not an IVD (In Vitro Diagnostic).

Here's why:

Intended Use: The intended use clearly describes a system used for thermal regulation within the patient's body by circulating fluid through a catheter placed in the central venous circulation. This is a therapeutic intervention, not a diagnostic test performed on samples taken from the body.
Device Description: The device description details a system of catheters, a start-up kit, and a console that work together to control patient temperature. It involves the physical manipulation of temperature within the patient's bloodstream.
Lack of Diagnostic Activity: There is no mention of analyzing biological samples (blood, urine, tissue, etc.) or providing information about a patient's disease state or condition based on such analysis. The device's function is purely related to temperature management.

IVD devices are specifically designed to perform tests on samples taken from the human body to provide information for the diagnosis, monitoring, or treatment of diseases or conditions. This device does not fit that description.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

The Cool Line Catheter Model CL-2295A when used with the ZOLL Thermal Regulation System is indicated for use in fever reduction, as an adjunct to antipyretic therapy, in adult patients with cerebral infarction and intracerebral hemorrhage who require access to the central venous circulation and who are intubated and sedated.

The ZOLL ICY Intravascular Heat Exchange Catheter Model IC-3893-A, connected to the ZOLL CoolGard 3000/ Thermogard XP Thermal Regulation System, is indicated for use:

In cardiac surgery adult patients to achieve and/or maintain normothermia during surgery and recovery/intensive care, and
To induce, maintain and reverse mild hypothermia in neurosurgery adult patients in surgery and recovery/intensive care.

The ZOLL Quattro Catheter Model IC-4593, connected to a ZOLL Thermal Regulation System, is indicated for use:

In cardiac surgery adult patients to achieve and/or maintain normothermia during surgery and recovery/intensive care, and
To induce, maintain and reverse mild hypothermia in neurosurgery adult patients in surgery and recovery/intensive care.

The Start-Up Kit (SUK) is intended to control patient core temperature using heat exchange fluid in conjunction with CoolGard 3000 or Thermogard XP system and ZOLL Heat Exchange Catheters, but does not have a specific independent indications for use.

Product codes

NCX

Device Description

The ZOLL Intravascular Heat Exchange Catheters (Cool Line, ICY, and Quattro - ZOLL Catheters) are sterile, single use heparin coated flexible catheters designed for placement in the femoral, jugular, or subclavian veins. The Cool Line Catheter contains two heat exchange balloons, the ICY Catheter contains three heat exchange balloons, and the Quattro Catheter contains four heat exchange balloons.

The ZOLL Catheters are connected to a single use, disposable Start-Up Kit (SUK) and the CoolGard 3000® or Thermogard XP® Console. The catheters connect to the console coolant well via tubing integral to the SUK. The catheter is connected to the SUK by connecting the male outflow Luer of the SUK to the female inflow Luer of the catheter and the female inflow Luer of the SUK to the male outflow Luer of the catheter. Both SUK Luers, in turn, are connected via tubing to a heat exchange coil through which saline circulates. The coil is placed in a coolant well located in the console. The controlled temperature saline is circulated through the closed-loop circuit of the SUK and catheter using the console pump, after which the saline is then returned within the SUK to the console heater and chiller coolant well via the catheter's outflow lumen.

The Catheters. SUK and the CoolGard 3000 or Thermogard XP Console are supplied separately. The ZOLL Intravascular Heat Exchange System is also designed for use with an off-the-shelf temperature probe, which is supplied separately and not manufactured by ZOLL.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Central venous circulation (femoral, jugular, or subclavian veins)

Indicated Patient Age Range

Adult patients

Intended User / Care Setting

Not Found

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Not Found

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

Nonclinical testing was performed, including Packaging validation (SUK only), Bench Performance, Biocompatibility, and Usability Testing.

Bench Performance - Packaging Validation (SUK):

Test Name: Visual Inspection
Test Method Summary: Visual inspection to inspect shipping boxes and trays for damage.
Results: All shipping boxes and trays were undamaged.
Test Name: SUK Package Seal Visual Integrity
Test Method Summary: Visual inspection to inspect the package seal in the area where the syringe bag is attached.
Results: All package seals and tray seals were undamaged.
Test Name: Syringe Pouch Seal Visual Integrity & Adhesion to Tyvek
Test Method Summary: Visual inspection of the affected area to inspect the package seal area of the syringe bag and film and Tyvek portion of the pouch.
Results: All syringe pouch seals and the film and Tyvek portion of the pouches were undamaged.
Test Name: SUK Package Seal Peel Test
Test Method Summary: Peel testing of the affected area to ensure that seal peel data is not less than specified acceptance criteria.
Results: All SUK package seals were undamaged.

Bench Performance - Start-Up Kit Performance Testing:

Test Name: SUK Flow Test
Test Method Summary: To verify that air flows through the SUK system.
Results: Air flowed through all SUK systems.
Test Name: SUK High Pressure Leak Test
Test Method Summary: To verify no leaks below specified acceptance criteria.
Results: No leaks were noted below the specified pressure.
Test Name: Modified SUK Indwell Life Test
Test Method Summary: To verify that Custom Luers and SUK Tubing are able to function normally at specified temperatures for the labeled indwell period.
Results: All custom Luers and SUK tubing were able to function normally for 7 days at the specified temperature.
Test Name: SUK Tubing to Luer Tensile
Test Method Summary: To verify that SUK Tubing and Custom Luers conform to EN ISO 10555-1:2013 and minimum specified acceptance criteria.
Results: The tensile strength of all inflow and outflow tubes to Luers met the requirements of ISO 10555-1:2013.

Bench Performance - Catheter Performance Testing:

Test Name: Visual Inspection
Test Method Summary: Visual inspection to inspect for Luers, caps, and extension tubes for correct colors.
Results: All Luer colors met the requirements of associated drawings.
Test Name: Dimensional Measurement of Extension Tube Lengths
Test Method Summary: Verify dimensions of extension tube lengths.
Results: All extension tubes met specific dimensional specifications.
Test Name: Guidewire Passage
Test Method Summary: Verify ability to frontload, backload, and remove J-tip 0.032" guidewire from catheter.
Results: The J-tip 0.032" guidewire was able to be frontloaded, backloaded, and removed from all catheters.
Test Name: Ink Stability
Test Method Summary: Verify that pad printed ink does not smudge or come off when tested in accordance with specified acceptance criteria.
Results: The pad printed ink on all infusion Luers remained legible after rubbing with alcohol.
Test Name: Alcohol Resistance
Test Method Summary: Verify that Luers do not craze or crack when tested in accordance with specified acceptance criteria.
Results: No Luers showed evidence of crazing or cracking after being soaked in alcohol.
Test Name: Balloon Deflation Using Deflation Syringe (20 mL Slip-Fit)
Test Method Summary: Verify that catheter balloons collapse upon aspiration at specified temperature using supplied slip-fit syringe.
Results: All catheter balloons collapsed upon aspiration using the supplied slip fit syringe.
Test Name: Balloons Leakage Upon Aspiration Using the Supplied Deflation (20 mL Slip-Fit) Syringe
Test Method Summary: To verify that catheter balloons conform to EN ISO 10555-1:2013 (must not show air leakage during aspiration).
Results: No air leakage was noted from the catheter balloons during aspiration using the supplied slip fit syringe.
Test Name: Heat Exchange Power
Test Method Summary: To verify that the modified catheters meet specified acceptance criteria.
Results: All catheters met the heat transfer performance requirement.
Test Name: Ultimate Burst/Leak (All Luers) - Embolic Failure
Test Method Summary: To verify that catheter Luers conform to EN ISO 10555-1:2013 (must meet minimum static pressure at specified temperature without embolic failure).
Results: All catheters were able to withstand 100-110 psi static pressure at 37°C without embolic failure.
Test Name: Catheter Inflow/Outflow Custom Luers connected to SUK Inflow/Outflow Pressure Test
Test Method Summary: To verify that catheter inflow/outflow Luers and extensions withstand minimum static pressure for specified period of time.
Results: All Luers and extension tubes were able to withstand a minimum static pressure while connected to an SUK for a specified period of time.
Test Name: Modified Catheter Indwell Life
Test Method Summary: To verify that catheter Luers and extensions are able to function normally for the labeled indwell period.
Results: All Luers and extension tubes were able to function normally for seven days.
Test Name: Extension Tubing to Luer Tensile.
Test Method Summary: To verify that extension tubing to Luer joints conform to EN ISO 10555-1:2013 (must meet minimum strength)
Results: All catheter joints demonstrated minimum tensile strength in accordance with the requirements of EN ISO 10555-1:2013

Bench Performance - Luer Performance Testing:

Test Name: Critical Dimensions Inspection
Test Method Summary: Critical dimensions must meet the dimensional tolerances for the Critical dimensions, of the respective drawing
Results: All samples met the dimensional tolerances for the critical dimensions.
Test Name: Gauging
Test Method Summary: Tested using test method similar to test specified in ISO594-1&2 (§4.1)
Results: All samples met the requirements of the test method used.
Test Name: Water/Liquid Leakage
Test Method Summary: Tested using test method similar to test specified in ISO594-1&2 (§4.2.1)
Results: All samples met the requirements of the test method used.
Test Name: Air Leakage
Test Method Summary: Tested using test method similar to test specified in ISO594-2 (§4.2.2)
Results: All samples met the requirements of the test method used.
Test Name: Separation Force
Test Method Summary: Tested using test method similar to that specified in ISO594-2 (§4.3)
Results: All samples met the requirements of the test method used.
Test Name: Unscrewing Torque
Test Method Summary: Tested using test method similar to that specified in ISO594-2 (§4.4)
Results: All samples met the requirements of the test method used.
Test Name: Ease of Assembly
Test Method Summary: Tested using test method similar to that specified in ISO594-2 (§4.5 b)
Results: All samples met the requirements of the test method used.
Test Name: Resistance to Overriding
Test Method Summary: Tested using test method similar to that specified in ISO594-2 (§4.6)
Results: All samples met the requirements of the test method used.
Test Name: Stress Cracking
Test Method Summary: Tested using test method similar to that specified in ISO594-2 (§4.7)
Results: All samples met the requirements of the test method used.

Biocompatibility:

Test Category: Cytotoxicity
Test Method Summary: MEM Elution Test
Results: The reactivity grade of all test article extract samples was "0”.
Test Category: Sensitization
Test Method Summary: ISO 10993 Part 10 Guinea Pig Maximization Sensitization Test (GLP)
Results: The test article extracts did not cause sensitization reactions under the conditions of the assay.
Test Category: Irritation
Test Method Summary: ISO/USP Intracutaneous Reactivity Irritation Test in Rabbits (GLP)
Results: The data indicated that the test article extracts did not cause a skin irritation reaction.
Test Category: Acute Systemic Toxicity
Test Method Summary: ISO/USP Medical Device Acute Systemic Toxicity Test in Mice (GLP)
Results: Based on the clinical observations and body weight evaluations, the test article (device) extracts did not show significantly greater biological reaction than the control article extracts.
Test Category: Material Mediated Pyrogen
Test Method Summary: ISO/USP Materials Mediated Pyrogen Test in Rabbits (GLP)
Results: None of the animals in the study showed abnormal clinical signs prior to dose administration or during the observation period and no animals showed a temperature increase of 0.5°C or greater during the study period.
Test Category: Hemocompatibility
Test Method Summary: ASTM Hemolysis (Extract Method) Test (GLP)
Results: The difference between the hemolytic indexes of the test article and the negative control equals 0.00 percent. This places the test article in the non-hemolytic range. All test method acceptance criteria were met.
Test Category: Hemocompatibility
Test Method Summary: Complement Activation Test (GLP)
Results: C3a: The P value was >0.050 when the test article was compared to the predicate at the 30, 60, and 90 minute time points; the test article and predicate are statistically similar at these time points. The P value was >=0.050 when the test article was compared to the negative control at the 30, 60, and 90 minute time points; the test article and predicate are statistically similar at these time points. SC5b-9: The P value was >0.050 when the test article was compared to the predicate at the 30, 60, and 90 minute time points; the test article and predicate are statistically similar at these time points. The P value was ≥0.050 when the test article was compared to the negative control at the 30 and 60 minute time points; the test article and negative control are statistically similar at these time points. The P value was ≤0.050 when the test article was compared to the negative control at the 90 minute time point; the test article is statistically lower than the negative control at this time point.

Usability/Human Factors - Formative Testing:

Summary: Human factors formative testing was performed to determine if users trained according to the IFU can properly perform tasks related to identifying infusion lumens, connecting Luers to the SUK, identifying saline IN and OUT Luers, identifying appropriate lumens for pharmacological infusate, and disconnecting and evacuating saline from the catheter. Four scenarios were presented, and all participants correctly executed each scenario with no failures. This indicates that the device design, training content and the IFU adequately mitigate the risk of misconnections.

Usability/Human Factors - Summative Testing:

Summary: Human factors summative testing was performed to evaluate if users trained according to the ZOLL Custom Luer Training Program and IFU can properly perform tasks related to matching new catheter and SUK with custom Luers, placing a 20 cc syringe on the saline hook, connecting IN and OUT Luers on the catheter to the SUK, selecting an infusion lumen, using a 20 cc syringe for aspiration after temperature management, and aspirating saline prior to catheter removal. All 5 scenarios were presented. The acceptance criteria were met with 100% of the users passing the critical tests (9-13). All of the non-critical items (1-8 and 14-15) were passed with at least 12 participants passing (80%). This testing confirms that the custom Luer design, training, and IFU facilitate appropriate catheter and SUK connections.

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Not Found

Predicate Device(s)

K101987, K014241

Reference Device(s)

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information

Not Found

Regulation Number and Section

§ 870.5900 Thermal regulating system.

(a)
Identification. A thermal regulating system is an external system consisting of a device that is placed in contact with the patient and a temperature controller for the device. The system is used to regulate patient temperature.(b)
Classification. Class II (performance standards).

Summary

0

Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized caduceus symbol, which is a staff with two snakes coiled around it, and the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged in a circular pattern around the symbol. The caduceus is depicted in a dark color, and the text is in a smaller font size.

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

October 30, 2015

ZOLL Circulation, Inc. Mr. Sam Nanavati V.P., Quality Assurance and Regulatory Affairs 2000 Ringwood Avenue San Jose, California 95131

Re: K150046

Trade/Device Name: Cool Line Intravascular Heat Exchange Catheter, ICY Intravascular Heat Exchange Catheter, Quattro Intravascular Heat Exchange Catheter, Start-Up Kit (SUK) Regulation Number: 21 CFR 870.5900 Regulation Name: Thermal Regulating System Regulatory Class: Class II Product Code: NCX Dated: September 30, 2015

Received: October 2, 2015

Dear Mr. Sam Nanavati:

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 and the limitations described below. 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.

The Office of Device Evaluation has determined that there is a reasonable likelihood that the Cool Line Intravascular Heat Exchange Catheter will be used for an intended use not identified in the proposed labeling and that such use could cause harm. Therefore, in accordance with Section 513(i)(1)(E) of the Act, the following limitation must appear in the Warnings section of the device's labeling as a box warning immediately following the indications for use statement:

The safety of this device has not been demonstrated for fever reduction in patients presenting with subarachnoid hemorrhage or primary traumatic brain injury. The safety and effectiveness of this device was examined in a randomized controlled trial of 296 patients. The mortality results reported in this trial, for the four patient cohorts enrolled,

1

are presented in the table below (CI - cerebral infarction, ICH - intracerebral hemorrhage, PTBI - primary traumatic brain injury, SAH - subarachnoid hemorrhage).

	Cool Line			Control
	n	N	%	n	N	%	p*
CI	3	16	18.8	3	14	21.4	0.74
ICH	8	33	24.2	7	27	25.9	1.00
PTBI	10	44	22.7	4	38	10.5	0.24
SAH	13	61	21.3	7	63	11.1	0.15

Mortality by Diagnosis (ITT analysis)
---------------------------------------	--	--	--	--

*Fischer's exact test

For more details on the clinical trial results please refer to Physician's Manual - "Normothermia for the Neuro-critically Ill stroke patient" PN 8700-0634-01.

Please note that the above labeling limitation is required by Section 513(i)(1)(E) of the Act. Therefore, a new 510(k) is required before these limitations are modified in any way or removed from the device's labeling. This limitation does not apply to the ICY and Quattro Intravascular Heat Exchange Catheters.

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

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 801); medical device reporting (reporting of medical devicerelated adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part

2

807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Jonette R. Foy -S

William H. Maisel, MD, MPH Director (Acting) Office of Device Evaluation Deputy Center Director for Science Center for Devices and Radiological Health

Enclosure

3

Indications for Use

510(k) Number (if known) K150046

Device Name

Cool Line Intravascular Heat Exchange Catheter, ICY Intravascular Heat Exchange Catheter, Quattro Intravascular Heat Exchange Catheter, Start-Up Kit (SUK)

Indications for Use (Describe)

The Cool Line Catheter Model CL-2295A when used with the ZOLL Thermal Regulation System is indicated for use in fever reduction, as an adjunct to antipyretic therapy, in adult patients with cerebral infarction and intracerebral hemorrhage who require access to the central venous circulation and who are intubated and sedated.

WARNING - Fever Reduction

The safety of this device has not been demonstrated for fever reduction with subarachnoid hemorrhage or primary traumatic brain injury. The safety and effectiveness of this device was examined in a randomized controlled trial of 296 patients. The mortality results reported in this trial, for the four patient cohorts enrolled, are presented in the table below (CI - cerebral infarction, ICH - intracerebral hemorrhage, PTBI - primary traumatic brain injury, SAH subarachnoid hemorrhage).

| Mortality by Diagnosis (ITT analysis)

.
--------------------------------------------

	Cool Line
	n	N	%	n	N	%	p*
CI	3	16	18.8	3	14	21.4	0.74
ICH	8	33	24.2	7	27	25.9	1.00
PTBI	10	44	22.7	র্ব	38	10.5	0.24
SAH	13	61	21.3	7	63	11.1	0.15

*Fischer's exact test

For more details on the clinical trial results planial is Manual - "Normothermia for the Neuro-critically III stoke patient" PN 8700-0634-01.

4

The ZOLL ICY Intravascular Heat Exchange Catheter Model IC-3893-A, connected to the ZOLL CoolCard 3000/ Thermogard XP Thermal Regulation System, is indicated for use:

· In cardiac surgery adult patients to achieve and/or maintain normothermia during surgery and recovery/intensive care, and
· To induce, maintain and reverse mild hypothermia in neurosurgery adult patients in surgery and recovery/intensive care.

The ZOLL Quattro Catheter Model IC-4593, connected to a ZOLL Thermal Regulation System, is indicated for use:

· In cardiac surgery adult patients to achieve and/or maintain normothermia during surgery and recovery/intensive care, and
· To induce, maintain and reverse mild hypothermia in neurosurgery adult patients in surgery and recovery/intensive care.

The Start-Up Kit (SUK) is intended to control patient core temperature using heat exchange fluid in conjunction with CoolGard 3000 or Thermogard XP system and ZOLL Heat Exchange Catheters, but does not have a specific independent indications for use.

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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5

PREMARKET NOTIFICATION 510(K) SUMMARY

Date Prepared:	September 25, 2015
Submitter:	ZOLL Circulation, Inc.
Address:	2000 Ringwood Avenue
San Jose, CA 95131
Phone:	408-419-2950
Fax:	408-541-1030
Contact Person:	Sam Nanavati, VP, Quality and Regulatory Affairs
Trade Name/Proprietary
Name:	Cool Line® Intravascular Heat Exchange Catheter
ICY® Intravascular Heat Exchange Catheter
Quattro™ Intravascular Heat Exchange Catheter
Start-Up Kit (SUK)
Common Name:	Central Venous Catheter (short term) and Thermal Regulating
System
Classification/Name:	Class II; System, Hypothermia, Intravenous, Cooling
Regulation:	21 CFR 870.5900, Thermal Regulating System
Product Code:	NCX
Legally marketed devices to
which substantial
equivalence is claimed:	Cool Line Catheter Kit Model CL-2295A (K101987); ICY
Catheter Kit Model IC-3893A (K101987); Quattro Catheter Kit
Model IC-4593 (K101987); Start-Up Kit Model CG-500D and
Model CG-500D EX (K014241)

I. Device Description

The ZOLL Intravascular Heat Exchange Catheters (Cool Line, ICY, and Quattro - ZOLL Catheters) are sterile, single use heparin coated flexible catheters designed for placement in the femoral, jugular, or subclavian veins. The Cool Line Catheter contains two heat exchange balloons, the ICY Catheter contains three heat exchange balloons, and the Quattro Catheter contains four heat exchange balloons.

The ZOLL Catheters are connected to a single use, disposable Start-Up Kit (SUK) and the CoolGard 3000® or Thermogard XP® Console. The catheters connect to the console coolant well via tubing integral to the SUK. The catheter is connected to the SUK by connecting the male outflow Luer of the SUK to the female inflow Luer of the catheter and the female inflow Luer of the SUK to the male outflow Luer of the catheter. Both SUK Luers, in turn, are connected via tubing to a heat exchange coil through which saline circulates. The coil is placed in a coolant well located in the console. The controlled temperature saline is circulated through the closed-loop circuit of the SUK and catheter using the console pump, after which the saline is then returned within the SUK to the console heater and chiller coolant well via the catheter's outflow lumen.

The Catheters. SUK and the CoolGard 3000 or Thermogard XP Console are supplied separately. The ZOLL Intravascular Heat Exchange System is also designed for use with an off-the-shelf temperature probe, which is supplied separately and not manufactured by ZOLL.

6

II. Indications for Use

The intended use / indications for use of the modified Cool Line, ICY, and Quattro Catheters are identical to the intended use / indications for use of the predicate Cool Line, ICY, and Quattro Catheters [cleared by FDA on October 12, 2010 under 510(k) K101987], which is as follows:

Cool Line Intravascular Heat Exchange Catheter

The Cool Line Catheter Model CL-2295A when used with the ZOLL Thermal Regulation System is indicated for use in fever reduction, as an adjunct to antipyretic therapy, in adult patients with cerebral infarction and intracerebral hemorrhage who require access to the central venous circulation and who are intubated and sedated.

Warning - Fever Reduction

The safety of this device has not been demonstrated for fever reduction in patients presenting with subarachnoid hemorrhage or primary traumatic brain injury. The safety and effectiveness of this device was examined in a randomized controlled trial of 296 patients. The mortality results reported in this trial, for the four patient cohorts enrolled, are presented in the table below (CI - cerebral infarction, ICH - intracerebral hemorrhage, PTBI - primary traumatic brain injury, SAH - subarachnoid hemorrhage).

Cool Line				Control
	n	N	%	n	N	%	p*
CI	3	16	18.8	3	14	21.4	0.74
ICH	8	33	24.2	7	27	25.9	1.00
PTBI	10	44	22.7	4	38	10.5	0.24
SAH	13	61	21.3	7	63	11.1	0.15

Mortality by Diagnosis (ITT analysis)

*Fischer's exact test

For more details on the clinical trial results please refer to Physician's Manual - "Normothermia for the Neuro-critically III stroke patient" PN 8700-0634-01.

ICY Intravascular Heat Exchange Catheter

The ZOLL ICY Intravascular Heat Exchange Catheter Model IC-3893-A, connected to the ZOLL CoolGard 3000/Thermogard XP Thermal Regulation System, is indicated for use:

. In cardiac surgery adult patients to achieve and/or maintain normothermia during surgery and recovery/intensive care, and
. To induce, maintain and reverse mild hypothermia in neurosurgery adult patients in surgery and recovery/intensive care.

Quattro Intravascular Heat Exchange Catheter

The ZOLL Quattro Catheter Model IC-4593, connected to a ZOLL Thermal Regulation System, is indicated for use:

. In cardiac surgery adult patients to achieve and/or maintain normothermia during surgery and recovery/intensive care, and
. To induce, maintain and reverse mild hypothermia in neurosurgery adult patients in surgery and recovery/intensive care.

7

The SUK is intended to control patient core temperature using heat exchange fluid in conjunction with CoolGard 3000 or Thermogard XP system and ZOLL Heat Exchange Catheters, but does not have a specific independent indications for use.

III. Technological Characteristics of the Device Compared to the Predicate Device

The modified SUK and the modified Cool Line. ICY, and Quattro Intravascular Heat Exchange Catheters are substantially equivalent to the 510(k) cleared Cool line, ICY and Quattro Catheters (SUK: K072234; Catheters: K101987), with regard to intended use / indications for use, technological characteristics, and principles of operation. Table 2 provide a comparison of the similarities and differences in technological characteristics between the modified SUK and Cool Line, ICY, and Quattro Catheters, to the cleared SUK and Cool Line, ICY, and Quattro Catheters.

| Characteristic | PREDICATE DEVICES
ZOLL Cool Line, ICY and Quattro
Catheters with ZOLL Standard Luers | SUBJECT DEVICES
ZOLL Cool Line, ICY and Quattro
Catheters with ZOLL Custom Luers
(modified) |
|-------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| 510(k) Number | K101987 | K150046 |
| Class | II | Same |
| Classification/
Regulation Name | System, Hypothermia, Intravenous,
Cooling/Thermal Regulating System | Same |
| Regulation
Number | 21 CFR 870.5900 | Same |
| Product Code | NCX | Same |
| Insertion Site | Cool Line – femoral vein, jugular vein,
subclavian vein
ICY – femoral vein
Quattro – femoral vein | Same |
| Heparin Coating | SurModics Applause Heparin Coating | Same |
| Luer Designs | Inflow and Outflow Luers: ZOLL Standard Luers
Infusion Luers: ZOLL Standard Luers
Vent Caps: ZOLL Standard Vent Caps | Inflow and Outflow Luers: ZOLL Custom
Luers
Infusion Luers: ZOLL Standard Luers
Vent Caps: ZOLL Custom Vent Caps |
| Luer Materials | Base material is polyurethane (for all luers
except for vent caps)

Inflow and outflow Luers: Polyurethane:
Tecoplast
OP-770-321 Teal Green

Distal infusion Luer: Polyurethane:
Tecoplast
OP-770-477 Brown

Medial infusion Luer: Polyurethane:
Tecoplast | Same

Inflow and outflow Luers: Polyurethane:
Tecoplast
OP-770-164 Orange

Distal infusion Luer: Same as predicate
(except pad printing has changed from black
ink to white ink)

Table 1. Comparison of Proposed Modified Catheters with Predicates

8

9

** The Indication for Use for the Cool Line Catheter also includes the following black box warning:

Warning - Fever Reduction

The safety of this device has not been demonstrated for fever reduction with subarachnoid hemorrhage or primary traumatic brain injury. The safety and effectiveness of this device was examined in a randomized controlled trial of 296 patients. The mortality results reported in this trial, for the four patient cohorts enrolled, are presented in the table below (CI cerebral infarction, ICH - intracerebral hemorrhage, PTBI - primary traumatic brain injury, SAH - subarachnoid hemorrhage).

Mortality by Diagnosis (ITT analysis)
	Cool Line			Control
	n	N	%	n	N	%	p*
CI	3	16	18.8	3	14	21.4	0.74
ICH	8	33	24.2	7	27	25.9	1.00
PTBI	10	44	22.7	4	38	10.5	0.24
SAH	13	61	21.3	7	63	11.1	0.15

*Fischer's exact test

For more details on the clinical trial results please refer to Physician's Manual - "Normothermia for the Neuro-critically III stroke patient" PN 8700-0634-01.

Table 2. Comparison of Proposed Modified Start-Up Kit with Predicates

| Characteristic | PREDICATE DEVICES
ZOLL Start-Up Kit with ZOLL
Standard Luers | SUBJECT DEVICES
ZOLL Start-Up Kit with ZOLL Custom
Luers
(modified) |
|------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------|
| 510(k) Number | K014241 | K150046 |
| Intended Use | To control patient core temperature using
heat exchange fluid in conjunction with
CoolGard 3000 or Thermogard XP
system and ZOLL Heat Exchange
Catheters | Same |
| Indications for Use | Start-Up Kit does not have a specific
independent indications for use | Same |
| Class | II | Same |
| Classification/
Regulation Name | System, Hypothermia, Intravenous,
Cooling/Thermal Regulating System | Same |
| Regulation Number | 21 CFR 870.5900 | Same |
| Product Code | NCX | Same |
| Patient Contact | Indirect patient contact | Same |
| Luer Function | Join the SUK to the InFlow/OutFlow
Lumens of the catheters, and allow saline
to circulate through the catheter/SUK
fluid path | Same |

10

| Characteristic | PREDICATE DEVICES
ZOLL Start-Up Kit with ZOLL
Standard Luers | SUBJECT DEVICES
ZOLL Start-Up Kit with ZOLL Custom
Luers
(modified) |
|-----------------------------------------------------------|--------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Supplied 20 ml
Sterile Deflation
(Slip-Fit) Syringe | Syringe not provided with SUK | Syringe, compatible with new custom Luer
locks, provided with SUK for optional
removal of saline from catheter heat exchange
balloons prior to catheter removal |
| Luer Materials:
SUK Female Luer
(InFlow) | PVC: Alpha Gary 2212-RHT/1-118
Clear | PVC:Alpha Gary 2212-RHT/1-118
UN2243 Orange |
| SUK Male Luer
(OutFlow) | Acrylic: 65117 | PVC:Alpha Gary 2212-RHT/1-118
UN2243 Orange |
| Sterilization | Provided sterile (Gamma sterilization) | Same |

IV. Summary of the Nonclinical Tests Performed

Nonclinical testing was performed to ensure that the modified SUK and the modified Cool Line, ICY, and Quattro Intravascular Heat Exchange Catheters meet their predetermined design and performance specifications and that the product is substantially equivalent to the predicate devices (SUK: K014241; Catheters: K101987).

The modified SUK and the modified Cool Line, ICY, and Quattro Intravascular Heat Exchange Catheters are identical to the 510(k) cleared SUK and 510(k) cleared Cool Line, ICY, and Quattro Intravascular Heat Exchange Catheters in terms of intended use/indications for use and principles of operation, and the modified devices have equivalent technological characteristics to the cleared devices. Nonclinical testing completed includes Packaging validation (SUK only), Bench Performance, Biocompatibility, and Usability Testing. The non-clinical test results demonstrate that the modified devices continue to meet product design specifications.

Bench Performance

Packaging Validation

Packaging performance testing of the modified SUK was performed to verify that following exposure to simulated shipping conditions, the addition of the sterile packaged 20 mL Deflation (Slip-Fit) syringe to the outside of the sterilized SUK packaging does not impact the integrity of the SUK sterile packaging. Packaging testing completed is shown in Table 3.

Test Name	Test Method Summary	Results
Visual Inspection	Visual inspection to inspect
shipping boxes and trays for
damage.	All shipping boxes and trays were
undamaged.
SUK Package Seal Visual Integrity	Visual inspection to inspect the
package seal in the area where the
syringe bag is attached.	All package seals and tray seals
were undamaged.
Syringe Pouch Seal Visual Integrity
& Adhesion to Tyvek	Visual inspection of the affected
area to inspect the package seal area	All syringe pouch seals and the film
and Tyvek portion of the pouches
were undamaged.

Table 3. Start-Up Kit Packaging Testing

11

Test Name	Test Method Summary	Results
	of the syringe bag and film and
Tyvek portion of the pouch.
SUK Package Seal Peel Test	Peel testing of the affected area to
ensure that seal peel data is not less
than specified acceptance criteria	All SUK package seals were
undamaged.

In addition, testing was performed (following exposure to simulated shipping conditions and packaging testing) to verify that product design specifications were met at T=0. Bench performance testing completed is shown in Table 4.

			Table 4. Start-Up Kit Performance Testing
--	--	--	-------------------------------------------	--

Test Name	Test Method Summary	Results
SUK Flow Test	To verify that air flows through the
SUK system.	Air flowed through all SUK
systems.
SUK High Pressure Leak Test	To verify no leaks below specified
acceptance criteria.	No leaks were noted below the
specified pressure.
Modified SUK Indwell Life Test	To verify that Custom Luers and
SUK Tubing are able to function
normally at specified temperatures
for the labeled indwell period.	All custom Luers and SUK tubing
were able to function normally for 7
days at the specified temperature.
SUK Tubing to Luer Tensile	To verify that SUK Tubing and
Custom Luers conform to EN ISO
10555-1:2013 and minimum
specified acceptance criteria.	The tensile strength of all inflow
and outflow tubes to Luers met the
requirements of ISO 10555-1:2013.

Bench Performance

Bench Performance Testing was conducted on samples of the Cool Line Intravascular Heat Exchange Catheter (as a representative model for all three catheters subject to the same modifications) to verify that product design specifications were met at T=0. The Luers and Extension tubings are identical in all models. Testing completed is shown in Table 5.

Test Name	Test Method Summary	Results
Visual Inspection	Visual inspection to inspect for Luers, caps, and extension tubes for correct colors.	All Luer colors met the requirements of associated drawings.
Dimensional Measurement of Extension Tube Lengths	Verify dimensions of extension tube lengths.	All extension tubes met specific dimensional specifications.
Guidewire Passage	Verify ability to frontload, backload, and remove J-tip 0.032" guidewire from catheter.	The J-tip 0.032" guidewire was able to be frontloaded, backloaded, and removed from all catheters.
Ink Stability	Verify that pad printed ink does not smudge or come off when tested in accordance with specified acceptance criteria.	The pad printed ink on all infusion Luers remained legible after rubbing with alcohol.
Alcohol Resistance	Verify that Luers do not craze or crack when tested in accordance with specified acceptance criteria.	No Luers showed evidence of crazing or cracking after being soaked in alcohol.

Table 5. Catheter Performance Testing

12

Test Name	Test Method Summary	Results
Balloon Deflation Using Deflation
Syringe (20 mL Slip-Fit)	Verify that catheter balloons
collapse upon aspiration at
specified temperature using
supplied slip-fit syringe.	All catheter balloons collapsed
upon aspiration using the supplied
slip fit syringe.
Balloons Leakage Upon Aspiration
Using the Supplied Deflation (20
mL Slip-Fit) Syringe	To verify that catheter balloons
conform to EN ISO 10555-1:2013
(must not show air leakage during
aspiration).	No air leakage was noted from the
catheter balloons during aspiration
using the supplied slip fit syringe.
Heat Exchange Power	To verify that the modified
catheters meet specified acceptance
criteria.	All catheters met the heat transfer
performance requirement.
Ultimate Burst/Leak (All Luers) -
Embolic Failure	To verify that catheter Luers
conform to EN ISO 10555-1:2013
(must meet minimum static
pressure at specified temperature
without embolic failure).	All catheters were able to withstand
100-110 psi static pressure at 37°C
without embolic failure.
Catheter Inflow/Outflow Custom
Luers connected to SUK
Inflow/Outflow Pressure Test	To verify that catheter
inflow/outflow Luers and
extensions withstand minimum
static pressure for specified period
of time.	All Luers and extension tubes were
able to withstand a minimum static
pressure while connected to an
SUK for a specified period of time.
Modified Catheter Indwell Life	To verify that catheter Luers and
extensions are able to function
normally for the labeled indwell
period.	All Luers and extension tubes were
able to function normally for seven
days.
Extension Tubing to Luer Tensile.	To verify that extensiuon tubing to
Luer joints conform to EN ISO
10555-1:2013 (must meet minimum
strength)	All catheter joints demonstrated
minimum tensile strength in
accordance with the requirements
of EN ISO 10555-1:2013

Where applicable, testing was performed in accordance with the following standards:

. ISO 10555-1:2013 - Sterile, single-use intravascular catheters Part 1. General requirements
The results of design verification testing performed demonstrate that the modified SUK and the modified Cool Line, ICY, and Quattro Intravascular Heat Exchange Catheters meet their design performance specifications at T=0.

Additional testing was conducted as part of Testing to Luer Standards on the injection molded components used to manufacture the modified SUK and the modified Cool Line, ICY, and Quattro Intravascular Heat Exchange Catheters. Results of testing verify compliance to the following applicable standard:

ISO 594-1:1986 Conical fittings with a 6% (Luer) taper for syringes, needles and certain ● other medical equipment Part 1: General requirements
In addition, tests methods similar to those specified in the following standard were used to test the Custom Luers with Custom reference fittings:
ISO 594-2:1998 Conical fittings with a 6% (Luer) taper for syringes, needles and certain ● other medical equipment Part 2: Lock fittings

13

Testing completed is shown in Table 6.

Test Name	Test Method Summary	Results
Critical Dimensions Inspection	Critical dimensions must meet the dimensional tolerances for the Critical dimensions, of the respective drawing	All samples met the dimensional tolerances for the critical dimensions.
Gauging	Tested using test method similar to test specified in ISO594-1&2 (§4.1)	All samples met the requirements of the test method used.
Water/Liquid Leakage	Tested using test method similar to test specified in ISO594-1&2 (§4.2.1)	All samples met the requirements of the test method used.
Air Leakage	Tested using test method similar to test specified in ISO594-2 (§4.2.2)	All samples met the requirements of the test method used.
Separation Force	Tested using test method similar to that specified in ISO594-2 (§4.3)	All samples met the requirements of the test method used.
Unscrewing Torque	Tested using test method similar to that specified in ISO594-2 (§4.4)	All samples met the requirements of the test method used.
Ease of Assembly	Tested using test method similar to that specified in ISO594-2 (§4.5 b)	All samples met the requirements of the test method used.
Resistance to Overriding	Tested using test method similar to that specified in ISO594-2 (§4.6)	All samples met the requirements of the test method used.
Stress Cracking	Tested using test method similar to that specified in ISO594-2 (§4.7)	All samples met the requirements of the test method used.

Table 6. Luer Performance Testing

Based on the test results obtained, it can be concluded that all of the standard and custom catheter Luers, custom SUK Luers, and custom catheter vented caps are qualified for use in the assemblies used to manufacture the modified SUK and the modified Cool Line, ICY and Quattro Intravascular Heat Exchange Catheters.

Biocompatibility

To verify the biocompatibility of the modified Luers for the Cool Line, ICY, and Quattro Intravascular Heat Exchange Catheters. ZOLL conducted biocompatibility testing on the proximal (modified) portion of the catheter only. Similarly, to verify the biocompatibility of the modified SUK, ZOLL conducted biocompatibility testing on the SUK Custom Luers only. Biocompatibility testing was conducted in accordance with GLP regulations.

Because the Custom Molded Luer Set components located on the SUK and on the proximal end of the catheter only have indirect blood contact and prolonged exposure. ZOLL conducted testing based on the classification of an externally communicating device, blood path indirect for prolonged exposure (>24hrs and 0.050
when the test article was compared
to the predicate at the 30, 60, and
90 minute time points; the test
article and predicate are statistically
similar at these time points.

The P value was >=0.050 when the
test article was compared to the
negative control at the 30, 60, and
90 minute time points; the test
article and predicate are statistically
similar at these time points.

SC5b-9: The P value was >0.050
when the test article was compared
to the predicate at the 30, 60, and
90 minute time points; the test
article and predicate are statistically
similar at these time points. |

15

Test Category	Test Method Summary	Results
		The P value was ≥0.050 when the
test article was compared to the
negative control at the 30 and 60
minute time points; the test article
and negative control are statistically
similar at these time points. The P
value was ≤0.050 when the test
article was compared to the
negative control at the 90 minute
time point; the test article is
statistically lower than the negative
control at this time point.

The results of the testing demonstrate that the modified SUK and the modified Cool Line. ICY . and Quattro Intravascular Heat Exchange Catheters are biocompatible for their intended use and the modifications made to the subject devices do not adversely affect the established biocompatibility of the predicate devices.

Usability/Human Factors

Pursuant to the FDA guidance document titled "Draft Guidance for Industry and Food and Drug Administration Staff - Applying Human Factors and Usability Engineering to Optimize Medical Device Design" Human Factors testing was conducted as follows:

Summary of Formative Testing 1.

Human factors formative testing was performed to determine if users trained according to the IFU can properly perform the following:

Identify infusion lumens, (proximal, medial, and distal) ●
. Properly connect the IN and OUT Luers to the Start-Up Kit (SUK)
Identify the saline IN and OUT Luers ●
Identify any lumen that is appropriate for pharmacological infusate. ●
Disconnect the Saline IN and OUT track (SUK Luers) including evacuating the saline . from the catheter using a syringe.

User tasks were based on identifying and (or) making proper connections as documented in the Formative Human Factors Protocol for ZOLL Custom Luers. The test session ran over the course of two days.

Four scenarios were presented, and participants were evaluated based on 14 predefined success metrics. All participants correctly executed each scenario, with no failures. All participants who received representative level of training and had access to the IFU successfully completed all of the tasks. This indicates that the device design, training content and the IFU adequately mitigate the risk of misconnections. No device design, training or IFU modifications were indicated based on this formative test.

2. Summary of Summative Testing

16

Human factors summative testing was performed to evaluate if users trained according to the ZOLL Custom Luer Training Program and IFU can properly perform the following:

Match the new catheter and new Start-Up Kit (SUK) with custom Luers
Place 20 cc syringe on saline hook on TGXP (Thermogard XP) console ●
Connect the IN and OUT Luers on the catheter to its counterpart on the SUK .
. Select an infusion lumen for an IV infusion
. Use 20 cc syringe for aspiration of saline after a catheter is used as a CVC after temperature management therapy ends
Aspirate saline prior to catheter removal. .

A total of five scenarios were presented, and each participant had to correctly answer questions 9-13 to achieve a passing score. All other questions (1-8, 14-15) required a minimum of an 80% passing score. The acceptance criteria were met with 100% of the users passing the critical tests (9-13). All of the non-critical items (1-8 and 14-15) were passed with at least 12 participants passing (80%).

All participants who received training and followed the IFU successfully met the acceptance criteria. This testing confirms that the custom Luer design, training, and IFU facilitate appropriate catheter and SUK connections. No device design, training or IFU modifications were indicated based on the summative evaluation.

V. Summary of Clinical Tests Performed

Clinical evaluations were not performed for the modified SUK and the modified Cool Line, ICY, and Quattro Intravascular Heat Exchange Catheters because such evaluations were not necessary to demonstrate substantial equivalence of the modified devices to the predicate devices (SUK: K014241; Catheters: K101987).

VI. Substantial Equivalence

The modified SUK and the modified Cool Line. ICY, and Quattro Intravascular Heat Exchange Catheters have the same intended use / indications for use as the 510(k) cleared SUK (K014241) and the 510(k) cleared Cool Line, ICY, and Quattro Intravascular Heat Exchange Catheters; Catheters (K101987). The results of the packaging validation (SUK only), bench performance, biocompatibility, and usability testing demonstrate that the modifications do not affect the performance or function of the devices. The minor differences in the design between the modified and cleared devices, do not raise any new types of safety or effectiveness questions as confirmed by design verification testing. Therefore, the modified SUK and the modified Cool Line, ICY, and Quattro Intravascular Heat Exchange Catheters are substantially equivalent to the previously cleared predicate devices.

VII. Conclusions

ZOLL concludes that based on the results of the packaging validation, bench performance, biocompatibility and usability testing performed, the modified SUK and the modified Cool Line, ICY, and Quattro Intravascular Heat Exchange Catheters are substantially equivalent to the predicate devices.