Solex 7 Intravascular Heat Exchange Catheter, ZOLL Start-Up Kit

K153226 · Zoll Circulation, Inc. · NCX · Mar 24, 2016 · Cardiovascular

Device Facts

• Record ID: K153226
• Device Name: Solex 7 Intravascular Heat Exchange Catheter, ZOLL Start-Up Kit
• Applicant: Zoll Circulation, Inc.
• Product Code: NCX · Cardiovascular
• Decision Date: Mar 24, 2016
• Decision: SESU
• Submission Type: Traditional
• Regulation: 21 CFR 870.5900
• Device Class: Class 2
• Attributes: Therapeutic

Intended Use

The Solex 7™ Intravascular Heat Exchange Catheter connected to the CoolGard 3000®/Thermal Regulation System is indicated for use: · In cardiac surgery patients to achieve and or maintain normothermia during surgery and recovery/intensive care. (Maximum use period = 4 days) · To induce, maintain and reverse mild hypothermia in neurosurgery and recovery/intensive care. (Maximum use period = 4 days) · In fever reduction, as an adjunct to other antipyretic therapy, in adult patients with cerebral infarcerebral hemorrhage who require access to the central venous circulation and who are intubated and sedated. (Maximum use period = 7 days)

Device Story

Solex 7 Intravascular Heat Exchange Catheter is a 9.3F flexible, heparin-coated polyurethane catheter with a distal serpentine PET balloon. Used with CoolGard 3000 or Thermogard XP console and Start-Up Kit (SUK). Operates by circulating sterile saline in a closed-loop circuit through the balloon to exchange heat with blood in the superior vena cava; saline does not enter patient. Catheter includes infusion lumens for standard clinical use. Used in OR/ICU by clinicians. Output is patient core temperature regulation. Benefits include precise temperature management for cardiac/neurosurgical patients and fever reduction in specific adult populations. Modifications include custom Luer connectors and extended 7-day indwell time for fever reduction indication.

Clinical Evidence

No clinical data. Substantial equivalence demonstrated via bench performance testing (7-day indwell, tensile, burst/leak, flow, heat exchange power), packaging validation, biocompatibility (ISO 10993), and human factors/usability testing.

Technological Characteristics

9.3F polyurethane catheter; serpentine PET heat exchange balloon; SurModics Applause heparin coating. Closed-loop saline heat exchange. 5 lumens (2 heat exchange, 3 infusion). Custom Luer connectors. Sterilization: EO (catheter), Gamma (SUK). Standards: ISO 10555-1, ISO 594-1/2, USP <788>.

Indications for Use

Indicated for cardiac surgery patients (normothermia), neurosurgery patients (mild hypothermia), and adult patients with cerebral infarction or intracerebral hemorrhage requiring central venous access and sedation/intubation (fever reduction). Contraindicated for fever reduction in patients with subarachnoid hemorrhage or primary traumatic brain injury.

Regulatory Classification

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.

Predicate Devices

• Solex Intravascular Heat Exchange Catheter Kit (K141139)
• Cool Line Intravascular Heat Exchange Catheter Kit (K101987, K150046)
• Start-Up Kit Model CG-500D and Model CG-500D EX (K014241, K150046)

Reference Devices

• Quattro Intravascular Heat Exchange Catheter (K150046)

Submission Summary (Full Text)

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Image /page/0/Picture/1 description: The image shows the seal of the Department of Health & Human Services (HHS) of the United States. The seal features the department's name arranged in a circular pattern around a stylized emblem. The emblem consists of a stylized caduceus, a symbol often associated with medicine and healthcare, with three intertwined snakes and a staff.

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

March 24, 2016

ZOLL Circulation, Inc. Mr. Sam Nanavati Vice President, Quality & Regulatory Affairs 2000 Ringwood Avenue San Jose, California 95131

Re: K153226

Trade/Device Name: Solex 7™ Intravascular Heat Exchange Catheter and Start-Up Kit Regulation Number: 21 CFR 870.5900 Regulation Name: Thermal Regulating System Regulatory Class: Class II Product Code: NCX Dated: February 23, 2016 Received: February 25, 2016

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 this device 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 (IFU) statement:

#### 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. A randomized controlled trial of endovascular cooling in patients with fever associated with subarachnoid hemorrhage

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and primary traumatic brain injury showed increased mortality as compared to patients receiving standard of care.

Please note that the above labeling limitations are 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.

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 [phone] or [phone] 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 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.

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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 [phone] or [phone] or at its Internet address

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

Sincerely yours,

# William H. Maisel - S

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

Enclosure

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### Indications for Use

#### 510(k) Number (if known) K153226

Device Name

Solex 7TM Intravascular Heat Exchange Catheter and Start-Up Kit

Indications for Use (Describe)

The Solex 7™ Intravascular Heat Exchange Catheter connected to the CoolGard 3000®/Thermal Regulation System is indicated for use:

· In cardiac surgery patients to achieve and or maintain normothermia during surgery and recovery/intensive care. (Maximum use period = 4 days)

· To induce, maintain and reverse mild hypothermia in neurosurgery and recovery/intensive care. (Maximum use period = 4 days)

· In fever reduction, as an adjunct to other antipyretic therapy, in adult patients with cerebral infarcerebral hemorrhage who require access to the central venous circulation and who are intubated and sedated. (Maximum use period = 7 days)

#### 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. A randomized controlled trial of endovascular cooling in patients with fever associated with subarachnoid hemorrhage and primary traumatic brain injury showed increased mortality as compared to patients receiving standard of care.

| Type of Use (Select one or both, as applicable) | |
|-------------------------------------------------|--|
|-------------------------------------------------|--|

X Prescription Use (Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR 801 Subpart C)

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## PREMARKET NOTIFICATION 510(K) SUMMARY K153226

| Date Prepared: | March 9, 2016 |
|-----------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Submitter: | ZOLL Circulation, Inc. |
| Address: | 2000 Ringwood Avenue<br>San Jose, CA 95131 |
| Phone: | 408-419-2950 |
| Fax: | 408-541-1030 |
| Contact Person: | Sam Nanavati, VP, Quality and Regulatory Affairs |
| Trade Name/Proprietary<br>Name: | Solex 7™ Intravascular Heat Exchange Catheter and<br>Start-Up Kit |
| Common Name: | Central Venous Catheter (short term) and Thermal Regulating<br>System |
| Classification/Name: | Class II; System, Hypothermia, Intravenous, Cooling |
| Regulation: | 21 CFR 870.5900, Thermal Regulating System |
| Product Code: | NCX |
| Legally marketed devices to<br>which substantial<br>equivalence is claimed: | Solex Intravascular Heat Exchange Catheter Kit, 510(k) K141139<br>Cool Line Intravascular Heat Exchange Catheter Kit, 510(k)<br>K101987 and K150046<br>Start-Up Kit Model CG-500D and Model CG-500D EX, 510(k)<br>K014241 and K150046 |

### I. Device Description:

The Solex 7 Intravascular Heat Exchange Catheter (Solex 7 Catheter) is a sterile, single use 9.3F flexible catheter designed for placement in the Superior Vena Cava from an insertion site in the Jugular and Subclavian Veins. The Solex 7 Catheter is connected to a single use, disposable CoolGard 3000 or Thermogard XP® Start-Up Kit (SUK) and the CoolGard 30000 or Thermogard XP® Console, all of which comprise the ZOLL Intravascular Heat Exchange The Start-Up Kit (SUK) and the CoolGard 3000 or Thermogard XP Console are System. supplied separately. The ZOLL Heat Exchange System is also designed for use with an off-theshelf temperature probe. The Solex 7 Catheter is comprised of a polyurethane shaft and a serpentine shaped PET balloon at the distal end. The blood contact surfaces of the catheter incorporate a hydrophilic heparin coating.

The catheter has five lumens, two of which when connected to the Start-Up Kit, are used to circulate sterile saline in a closed loop circuit for heat exchange with the blood in the central venous system. Warmed or chilled saline is pumped through the heat exchange lumens, inflating the diameter of the serpentine balloon that interfaces with the patient's blood to warm or cool circulating blood. The inflow/outflow lumens form a closed-loop system through which the warmed or chilled saline circulates. The warmed or chilled saline is not infused into the patient.

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Additional lumens of the Solex 7 Catheter consist of a 0.032" guidewire compatible lumen that can also be used as a primary infusion lumen, and two additional infusion lumens within the catheter shaft.

#### II. Indications for Use:

The intended use/indications for use of the modified Solex Catheter (Solex 7 Catheter) is as follows:

The Solex 7™ Intravascular Heat Exchange Catheter connected to the CoolGard 3000 /Thermogard XP® Thermal Regulation System is indicated for use:

- In cardiac surgery patients to achieve and or maintain normothermia during surgery and . recovery/intensive care. (Maximum use period = 4 days)
- To induce, maintain and reverse mild hypothermia in neurosurgery patients in surgery and recovery/intensive care. (Maximum use period = 4 days)
- In fever reduction, as an adjunct to other 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. (Maximum use period = 7 days)

#### 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. A randomized controlled trial of endovascular cooling in patients with subarachnoid hemorrhage and primary traumatic brain injury showed increased mortality as compared to patients receiving standard of care.

### III. Summary of Technological Characteristics of the Proposed Device Compared to the Predicate Device:

#### The Solex 7 Catheter

The modified Solex Catheter (Solex 7 Catheter) is substantially equivalent to the 510(k) cleared Solex Catheter (K141139) and the ZOLL Cool Line Catheter (K101987) with regard to intended use / indications for use, technological characteristics, and principles of operation. With the exception of the Custom Luers, the modified Solex Catheter (Solex 7 Catheter) is identical to the cleared Solex Catheter with respect to design and materials. Table 1 provides a comparison of the similarities and differences between the modified Solex Catheter (Solex 7 Catheter), the cleared Solex Catheter, and the cleared ZOLL Cool Line Catheter (comparisons are relative to the subject device).

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| Table 1. Comparison of Solex 7 Catheter with Custom Luers to Predicates | | |
|-------------------------------------------------------------------------|--|--|
|-------------------------------------------------------------------------|--|--|

| | ZOLL Intravascular Heat Exchange Catheters | | | |
|--------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------|
| Feature | SUBJECT DEVICE<br>Solex 7 Intravascular<br>Heat Exchange Catheter | PRIMARY PREDICATE<br>DEVICE<br>Cool Line Intravascular<br>Heat Exchange Catheter | REFERENCE<br>PREDICATE<br>DEVICE<br>Solex Intravascular<br>Heat Exchange<br>Catheter | REFERENCE<br>PREDICATE DEVICE<br>Quattro Intravascular<br>Heat Exchange<br>Catheter |
| 510(k)<br>Number | K153226 | K101987 and K150046 | K141139 | K150046 |
| Class | II | Same | Same | Same |
| Classification/<br>Regulation<br>Name | System, Hypothermia,<br>Intravenous.<br>Cooling/Thermal<br>Regulating System | Same | Same | Same |
| Regulation<br>Number | 21 CFR 870.5900 | Same | Same | Same |
| Product Code | NCX | Same | Same | Same |
| Heparin<br>Coating | SurModics Applause<br>Heparin Coating | Same | Same | Same |
| Luer Designs | Inflow and Outflow Luers:<br>ZOLL Custom Luers*<br>Infusion Luers: Standard<br>Luers<br>Vent Caps: ZOLL Custom<br>Vent Caps | Same | Inflow and Outflow<br>Luers: Standard Luers<br>Infusion Luers: Same<br>Vent Caps: Standard<br>Vent Caps | Same as Subject Device |
| Catheter<br>working<br>length (tip to<br>manifold) | 26cm | 22 cm | Same as Subject<br>Device | 48 cm |
| Shaft<br>diameter | 9.3 Fr | Same | Same | Same |
| Number of<br>lumens | 5 lumens:<br>2 infusion | Same | Same | Same |
| Feature | ZOLL Intravascular Heat Exchange Catheters | | | |
| | SUBJECT DEVICE<br>Solex 7 Intravascular<br>Heat Exchange Catheter | PRIMARY PREDICATE<br>DEVICE<br>Cool Line Intravascular<br>Heat Exchange Catheter | REFERENCE<br>PREDICATE<br>DEVICE<br>Solex Intravascular<br>Heat Exchange<br>Catheter | REFERENCE<br>PREDICATE DEVICE<br>Quattro Intravascular<br>Heat Exchange<br>Catheter |
| Guidewire<br>Compatibility | 1 guidewire (also infusion)<br>1 inflow<br>1 outflow<br>0.032" | Same | Same | Same |
| Flow Rate (by<br>lumen) | Distal - 1900 mL/hr<br>Medial - 1300 mL/hr<br>Proximal - 1300 mL/hr | Distal - 2100 mL/hr<br>Medial - 1200 mL/hr<br>Proximal - 1400 mL/hr | Distal - Same as<br>Subject Device<br>Medial - Same as<br>Subject Device<br>Proximal - Same as<br>Subject Device | Distal - 1300 mL/hr<br>Medial - 800 mL/hr<br>Proximal - 1100 mL/hr |
| Heat<br>exchange<br>balloons | 1 (serpentine) | 2 (straight/coaxial) | Same as Subject<br>Device | 4 (straight/coaxial) |
| Inflated<br>Balloon OD<br>(Cross-<br>sectional Area) | Balloon OD: N/A<br>Cross-sectional Area:<br>54mm2 | Balloon OD: 5mm<br>Cross-sectional area: N/A | Same as Subject<br>Device | Balloon OD: 8mm<br>Cross-sectional area:<br>N/A |
| Cross<br>Sectional<br>Area (approx.<br>inflated outer<br>diameter) | 54mm2 (12.2 mm OD) | 20mm2 (5 mm) | Same as Subject<br>Device | 50mm2 (8 mm) |
| Insertion Site | Jugular and<br>Subclavian Veins | Femoral, Jugular, Subclavian<br>Veins | Jugular Vein | Femoral |
| Max. Use<br>Period | 7 days | 7 days | 2 days | 4 days |
| | ZOLL Intravascular Heat Exchange Catheters | | | |
| Feature | SUBJECT DEVICE<br>Solex 7 Intravascular<br>Heat Exchange Catheter | PRIMARY PREDICATE<br>DEVICE<br>Cool Line Intravascular<br>Heat Exchange Catheter | REFERENCE<br>PREDICATE<br>DEVICE<br>Solex Intravascular<br>Heat Exchange<br>Catheter | REFERENCE<br>PREDICATE DEVICE<br>Quattro Intravascular<br>Heat Exchange<br>Catheter |
| Materials | Shaft: Polyurethane<br>Heat Exchange Balloon:<br>PET | Shaft: Same<br>2 Heat Exchange Balloons:<br>Polyurethane | Shaft: Same<br>Heat Exchange<br>Balloon:<br>Same as Subject<br>Device | Shaft: Same<br>Heat Exchange<br>Balloons: Same as<br>Subject Device |
| Sterilization<br>method and<br>SAL | EO, SAL 10-6 | Same | Same | Same |

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*The ZOLL Custom Luers on the ZOLL Cool Line, ICY, and Quattro Catheters were cleared via K150046 on October 30, 2015

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### The Modified Start-Up Kit with Custom Luers

The modified Start-Up Kit (SUK) with Custom Luers is substantially equivalent to the 510(k) cleared SUK (K014241) with regard to intended use, technological characteristics, and principles of operation. Table 2 provides a comparison of the similarities and differences between the modified SUK and the predicate SUK.

| Characteristic | SUBJECT DEVICE<br>ZOLL Start-up Kit with ZOLL Custom<br>Luers | PREDICATE DEVICE<br>ZOLL Start-up Kit with ZOLL Standard<br>Luers |
|-----------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------|
| | (modified)<br>K150046 | |
| 510(k) Number | TBD | K014241 |
| Intended Use | To control patient core temperature using<br>heat exchange fluid in conjunction with the<br>CoolGard 3000 or Thermogard XP system<br>and ZOLL Heat Exchange Catheters | Same |
| Class | II | Same |
| Classification/<br>Regulation Name | System, Hypothermia, Intravenous,<br>Cooling/Thermal Regulating System | Same |
| Regulation<br>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<br>of the catheters, and allow saline to circulate<br>through the catheter/SUK fluid path | Same |
| Supplied 20 ml<br>Sterile Deflation<br>(Slip-Fit) Syringe | Syringe, compatible with new Custom Luer<br>locks, provided with SUK for removal of<br>saline from catheter heat exchange balloon<br>prior to catheter removal | Syringe not provided with SUK |
| Sterilization | Provided sterile (Gamma sterilization) | Same |

Table 2. Comparison of Modified Start-up Kit with Custom Luers to Predicate

### IV. Summary of the Nonclinical Tests Performed:

Nonclinical testing was performed to ensure that the modified Solex Catheter (Solex 7 Catheter) and modified SUK meet their design performance specifications and that the product is substantially equivalent to the predicate devices (Catheters: K141139, K101987; SUK: K014241). Nonclinical testing performed includes: Bench Performance. Packaging Validation (SUK only), Biocompatibility, and Usability Testing. The nonclinical test results demonstrate that the modified devices continue to meet product design specifications.

### 1. 7-Day Indwell Testing

Bench Performance testing of the modified Solex Catheter (Solex 7 Catheter) was performed to support the proposed modification to the 7 day indwell time.

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

- . ISO 10555-1:2013 - Sterile, single-use intravascular catheters Part 1. General requirements

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- ISO 594-1:1986 Conical fittings with a 6% (Luer) taper for syringes, needles and . certain other medical equipment Part 1: General requirements
- ISO 594-2:1998 Conical fittings with a 6% (Luer) taper for syringes, needles and ● certain other medical equipment Part 2: Lock fittings

The modified Solex Catheter (Solex 7 Catheter) was functionally tested after being subjected to 7 days of simulated use conditions to verify that the catheter continues to perform as intended. Testing completed is shown in Table 3.

| Test Name | Test Method Summary | Results |
|----------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Visual Inspection | Visual inspection to ensure catheter<br>is smooth without major pits. | Catheter samples met the<br>acceptance criterion for smooth<br>appearance with no pits. |
| Catheter Indwell Life (7 days) | Verification that the catheter does<br>not leak saline from the heat<br>exchange path during simulated use<br>for seven days. | Catheter samples met the<br>acceptance criterion for normal<br>function for seven days without<br>leakage. |
| Dimensional Measurement | Measurement of catheter<br>dimensional aspects | Catheter samples met the<br>acceptance criteria for dimensional<br>requirements per the product<br>specification. |
| Toluidine Blue Staining | Dye staining of catheter and visual<br>inspection to ensure consistent<br>coverage of blue purple color and<br>that stained portion covers all depth<br>markers. | Catheter samples met the<br>acceptance criteria for consistent<br>blue purple color and stained<br>portion covered all depth markers. |
| Particulate Testing | Determination of catheter coating<br>integrity following simulated<br>indwell and flow rate conditions. | Solex 7 samples and Cool Line<br>samples tested demonstrated levels<br>of particulate below that required in<br>USP <788>. |
| Tensile Testing | Strength testing of various catheter<br>joints. Must conform to EN ISO<br>10555-1:2013. | Catheter joints met the acceptance<br>criteria for tensile strength<br>requirements of EN ISO 10555-<br>1:2013. |
| Burst/Leak Testing | Determination of catheter burst/leak<br>resistance. Must conform to EN<br>ISO 10555-1:2013. | Catheter samples met the<br>acceptance criteria to withstand a<br>minimum of 100 psi static pressure<br>at 37°C without embolic failure. |
| Flow Resistance Testing | Measurement of catheter back<br>pressure. | Catheter samples met the<br>acceptance criterion for a back<br>pressure of less than 7 psi at a flow<br>rate of 2000 ml/hr. |
| Flow Rate Testing | Measurement of catheter infusion<br>lumen flow rates. Must conform to<br>EN ISO 10555-1:2013. | Catheter samples met the<br>acceptance criteria for flow rate<br>requirements of EN ISO 10555-<br>1:2013 |
| Heat Exchange Testing | Determination of heat exchange<br>capability of catheter. | Catheter samples met the<br>acceptance criterion for a heat<br>exchange power of 125 Watts<br>minimum. |
| Flexural Fatigue/Tip Flex Testing | Determination of catheter tip<br>strength and flexure. | Catheter samples met the<br>acceptance criteria to withstand 100 |
| Test Name | Test Method Summary | Results |
| Infusion Lumen Aspiration Rate Testing | Determination of catheter blood sampling rate | cycles of tip flexure.<br>Catheter samples met the<br>acceptance criterion of a blood<br>sampling rate of 10cc in 15 seconds<br>or less. |
| Torsional Integrity Testing | Determination of catheter (tip to<br>manifold) ability to withstand<br>twisting. | Catheter samples met the<br>acceptance criterion to withstand<br>one complete twist without failure |
| In Vitro Thrombogenicity Testing | Measurement of thrombogenic<br>behavior of catheter following 7<br>day simulated use by radioactive<br>platelet quantification and visual<br>inspection. | Coated catheter samples showed<br>statistically significant decreases ( $p$<br>< 0.05) in thrombogenicity when<br>compared to normalized<br>thrombogenic behavior of uncoated<br>catheters. |

Table 3. Solex 7 Catheter Bench Performance Testing

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### 2. Solex Catheter and Modified SUK with Custom Luers

Nonclinical testing was performed to ensure that the Solex Catheter and modified SUK with Custom Luers meet their design and performance specifications and that the product is substantially equivalent to the predicate devices.

- a. Packaging Validation (SUK only)
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. | Shipping boxes and trays met the acceptance criteria with respect to visible damage. |
| SUK Package Seal Visual Integrity | Visual inspection to inspect the package seal in the area where the syringe bag is attached. | Package seals and trays met the acceptance criteria with respect to visible damage. |
| Syringe Pouch Seal Visual Integrity & Adhesion to Tyvek | Visual inspection of the affected area to inspect the package seal area of the syringe bag. | Syringe pouch seals and the film and Tyvek portion of the pouches met the acceptance criteria with respect to visible damage. |
| SUK Package Seal Peel Test | Peel testing of the affected area to ensure that seal peel data is not less than specified acceptance criteria | SUK package seals met the acceptance criterion for peel strength. |

### Table 3. Start-Up Kit Packaging Testing

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

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| Test Name | Test Method Summary | Results |
|--------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| SUK Flow Test | To verify that air flows through the<br>SUK system. | C SUK systems met the acceptance<br>criterion for air flow. |
| SUK High Pressure Leak Test | To verify no leaks below specified<br>acceptance criteria. | SUK systems met the acceptance<br>criterion for no leaks below the<br>specified pressure. |
| Modified SUK Indwell Life Test | To verify that Custom Luers and<br>SUK Tubing are able to function<br>normally at specified temperatures<br>for the labeled indwell period. | Custom Luers and SUK tubing met<br>the acceptance criterion for normal<br>function for 7 days at the specified<br>temperature. |
| SUK Tubing to Luer Tensile | To verify that SUK Tubing and<br>Custom Luers conform to EN ISO<br>10555-1:2013 and minimum<br>specified acceptance criteria. | The SUK tubing meet the<br>acceptance criterion for the tensile<br>strength of all inflow and outflow<br>tubes to Luers with respect to the<br>requirements of ISO 10555-1:2013. |

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

The packaging of the Solex catheter remains unchanged; therefore, re-validation of the catheter packaging was not warranted.

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

Table 5. Custom Luer Catheter Bench Performance Testing

| Test Name | Test Method Summary | Results |
|---------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------|
| Visual Inspection | Visual inspection to inspect for Luers, caps, and extension tubes for correct colors. | Luers colors met the acceptance criteria based on the requirements of associated drawings. |
| Dimensional Measurement of<br>Extension Tube Lengths | Verify dimensions of extension tube lengths. | Extension tubes met the acceptance criteria for specific dimensional specifications. |
| Guidewire Passage | Verify ability to frontload, backload, and remove J-tip 0.032" guidewire from catheter. | Catheters met the acceptance criterion for the J-tip 0.032" guidewire to be frontloaded, backloaded, and removed from the 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 met the acceptance criterion of remaining legible after rubbing with alcohol. |
| Alcohol Resistance | Verify that Luers do not craze or crack when tested in accordance with specified acceptance criteria. | Luers met the acceptance criterion of no evidence of crazing or cracking after being soaked in alcohol. |
| Balloon Deflation Using Deflation<br>Syringe (20 mL Slip-Fit) | Verify that balloons collapse upon aspiration at specified temperature using supplied slip-fit syringe. | Catheter balloons met the acceptance criterion of collapse upon aspiration using the supplied slip fit syringe. |
| Balloons Leakage Upon Aspiration | To verify that catheter balloons | Catheters met the acceptance |

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| Test Name | Test Method Summary | Results |
|-------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| @ 37°C Using the Supplied<br>Deflation (20 mL Slip-Fit) Syringe | conform to EN ISO 10555-1:2013<br>(must not show air leakage during<br>aspiration). | criterion for no air leakage from the<br>catheter balloons during aspiration<br>using the supplied slip fit syringe |
| Heat Exchange Power | To verify that the modified<br>catheters meet specified acceptance<br>criteria. | Catheters met the acceptance<br>criterion for heat transfer<br>performance. |
| Ultimate Burst/Leak (All Luers -<br>Custom and Infusion Luers) -<br>Embolic Failure | To verify that catheter Luers<br>conform to EN ISO 10555-1:2013<br>(must meet minimum static<br>pressure at specified temperature<br>without embolic failure). | Catheters met the acceptance<br>criterion to withstand 100-110 psi<br>static pressure at 37°C without<br>embolic failure. |
| Catheter Inflow/Outflow Custom<br>Luers connected to SUK Custom<br>Inflow/Outflow Pressure Test | To verify that catheter<br>inflow/outflow Luers and<br>extensions withstand minimum<br>static pressure for specified period<br>of time. | Luers and extension tubes met the<br>acceptance criterion to withstand a<br>minimum static pressure while<br>connected to an SUK for a specified<br>period of time. |
| Catheter with Modified Luers -<br>Indwell Life | To verify that catheters Luers and<br>extensions are able to function<br>normally for the labeled indwell<br>period. | Luers and extension tubes met the<br>acceptance criterion to be able to<br>function normally for seven days. |
| Extension Tubing to Luer Tensile. | To verify that extensiuon tubing to<br>Luer joints conform to EN ISO<br>10555-1:2013 (must meet minimum<br>strength). | Catheter joints met the acceptance<br>criteria for minimum tensile<br>strength in accordance with the<br>requirements of EN ISO 10555-<br>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 Catheter and SUK with Custom Luers meet their design performance specifications at T=0.

- c. Testing to Luer Standards
Additional testing was conducted as part of Testing to Luer Standards on the injection molded components used to manufacture the modified SUK and Catheter with Custom Luers. Results of testing verifies compliance to the following applicable standards:

- ISO 594-1:1986 - Conical fittings with a 6% (Luer) taper for syringes, needles and certain other medical equipment Part 1: General requirements
- . ISO 594-2:1998 - Conical fittings with a 6% (Luer) taper for syringes. needles and certain other medical equipment Part 2: Lock fittings

The testing completed are shown in Table 6.

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

Table 6. Luer Standards 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 Solex Catheter with Custom Luers.

#### d. Biocompatibility

The only material change for the Solex Catheter and SUK has been to the Custom Luers. To verify the biocompatibility of the new materials of the Custom Luers for the Solex Catheter, 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 Luer components located on the SUK and on the proximal end of the catheter 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 ≤30 days). Based on this classification, the following categories of biocompatibility tests were performed: Cytotoxicity, Sensitization, Irritation/Intracutaneous Reactivity, Acute Systemic Toxicity and Hemocompatibility.

The biocompatibility test results are shown in Table 7.

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### Table 7. Biocompatibility Testing

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The results of the testing demonstrate that the modified SUK and the modified Solex Catheter with Custom Luers 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.

### e. Usability/Human Factors

Pursuant to FDA's guidance document entitled, "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:

### 1. Summary of Formative Testing

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

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:

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- Match the new catheter and new Start-Up Kit (SUK) with Custom Luers
- Place 20 cc syringe on saline hook on Thermogard XP (TGXP) 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 necessary to evaluate the modifications incorporated in the Solex Catheter and SUK to demonstrate substantial equivalence to the predicate devices.

#### VI. Substantial Equivalence:

Based on the results of the Bench Performance, Packaging Validation (SUK only), Biocompatibility, and Usability testing, the modified Solex Catheter (Solex 7 Catheter) and modified SUK are substantially equivalent to the currently cleared Solex Catheter (K141139), Cool Line Catheter (K101987), and SUK (K014241) with respect to intended use/indication for use, technological characteristics, and principles of operation and 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 Solex Catheter (Solex 7 Catheter) and modified SUK are substantially equivalent to the previously cleared predicate devices.

#### VII. Conclusions:

ZOLL concludes that based on the results of the Bench Performance. Packaging Validation (SUK only). Biocompatibility, and Usability testing, that the modified Solex Catheter (Solex 7 Catheter) and modified SUK are substantially equivalent to the predicate devices.