CLAVE Neutron is a normally closed, bidirectional connector intended for use as an accessory to an intravascular catheter placed in the vein or artery. The device may be used for the administration of blood and fluids to patients, including pediatrics and immunocompromised patients. The device may also be used with power injector procedures up to 10mL per second of contrast media and a maximum pressure of 350psi. The device incorporates a technology that will prevent fluid displacement resulting from the following: Connection of a luer; syringe plunger compression; patient vascular pressure changes, such as coughing or sneezing; and IV solution container run-dry. The CLAVE Neutron incorporates a pre-slit septum that does not reguire the use of needles and will therefore passively aid in the reduction of needlestick injuries.

Device Description

The CLAVE Neutron is a normally closed, bidirectional connector that incorporates a unique silicone valve within the fluid path. The unique valve prevents fluid displacement, both positive and negative at all times, including when the device is accessed.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the CLAVE® Neutron™ device based on the provided 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are generally demonstrated by the CLAVE Neutron's performance being "substantially equivalent" to predicate devices, or meeting specific physical and functional benchmarks. The table below integrates information from the "Technological Characteristics and Substantial Equivalence Table" and other sections of the summary.

Specification/Acceptance Criteria	CLAVE® Neutron™ Reported Performance
Functional Use	Needleless connector with anti-fluid displacement and power injectable. Substantially equivalent to predicate devices for normally closed, needleless connection and fluid delivery.
Patient Populations	Adults, Pediatrics and Immunocompromised patients. Supported by clinical studies (Bouza 2003, Maragakis 2006) on the identical CLAVE pre-slit septum design.
Residual Volume	0.14mL. Less than half of the A6 predicate (0.30mL).
Gravity Fluid Flow	100mL/minute. Equivalent to the CLAVE predicate.
Syringe Disconnect: Fluid Displacement	Integral valve prevents displacement, both positive and negative. Substantially equivalent to fluid displacement feature of predicate devices during luer disconnection.
Syringe Plunger Compression: Fluid Displacement	Integral valve prevents displacement, both positive and negative. The valve operates in the identical manner as for luer disconnection, so deemed not significantly different from predicate.
Patient Pressure: Fluid Displacement	Integral valve prevents displacement, both positive and negative. The valve operates in the identical manner as for luer disconnection, so deemed not significantly different from predicate.
Bag Run-Dry: Fluid Displacement	Integral valve prevents displacement, both positive and negative. The valve operates in the identical manner as for luer disconnection, so deemed not significantly different from predicate.
Multiple Activations	96 intermittent, 3 extended time. This matches predicate CLAVE and CLC2000.
Positive Leak Pressure	45psig. Deemed adequate to prevent positive pressure leakage from a patient's line and therefore not significantly different from predicate devices (which had 60psig).
Negative Leak Pressure	-8.5psig. Matches predicate CLAVE and CLC2000.
Luer Retention	ISO 594-1 (5.4). Matches predicate CLAVE and CLC2000.
Component Assembly	>20lbf-in. (Predicates had >51bf-in or >15lbf-in, showing this is a strong assembly).
Chemical Compatibility	Lipids, Alcohol. Matches predicate CLAVE and CLC2000.
Power Injectable	10ml/sec of contrast media and < 350psi. This allows for higher pressure than the A6 predicate (300psi) but the overall feature is substantially equivalent. Explicitly tested up to 10mL per second.
Sterilization Method	Gamma or E-beam. Matches all predicate devices.
Packaging	Peel pouch. Matches all predicate devices.
Materials	Polyester, Silicone, ABS or Polycarbonate, and Nylon. Compared to predicates, differences in materials are noted but comprehensive biocompatibility testing (included in submission) ensures safety. Materials tested to latest ISO 10993 standards.
Microbial Ingress	Demonstrates equivalent ability to prevent bacterial ingress compared to the CLAVE predicate. Will prevent bacterial ingress completely if used in accordance with directions.
Biocompatibility	Comprehensive testing included in submission, meeting latest ISO 10993 standards.
Reduction of Needlestick Injuries	Incorporates a pre-slit septum that does not require the use of needles, passively aiding in needlestick reduction.
Safety and Efficacy (Overall)	Results of testing demonstrate no new issues of Safety and Efficacy are raised compared to predicates. Substantially equivalent for intended use.

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

The document mentions "a variety of functional tests including microbial ingress and performance criteria" and "simulated use environment testing" as part of the "CLAVE Neutron Design Verification Report." However, specific sample sizes for these tests (e.g., number of devices tested for each functional criterion) are not provided in this summary.

Data Provenance: The document states that the CLAVE Neutron Design Verification Report is proprietary and included in the submission. The information provided about the CLAVE and its use in pediatric/immunocompromised patients comes from two published clinical studies:
- Bouza (2003): Randomized clinical trial. Patient population: immunocompromised, intensive care patients. Location: Department of Cardiovascular Surgery, Hospital General University of Madrid, Madrid, Spain. Outcome: reduced catheter hub and tip bacterial colonization.
- Maragakis (2006): Clinical study. Patient population: pediatric ICU and pediatric oncology service patients. Location: John's Hopkins Hospital in Baltimore, Maryland. Outcome: observed catheter-related bloodstream infection rates.

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

For the CLAVE Neutron's design verification tests: This information is not provided in the summary. These are laboratory-based functional and performance tests, not clinical studies requiring expert ground truth setting in the same way an imaging AI might.
For the clinical studies referenced (Bouza 2003, Maragakis 2006): These studies evaluated clinical outcomes (bacterial colonization, bloodstream infection rates). The "ground truth" would be established by clinical diagnostic methods relevant to those outcomes, performed by healthcare professionals at the respective hospitals. The qualifications of these professionals are not explicitly detailed in this summary, beyond the fact they were conducted at medical institutions.

4. Adjudication Method for the Test Set

For the CLAVE Neutron's design verification tests: Adjudication methods are not described in the summary. These are typically objective measurements against engineering specifications.
For the clinical studies referenced: Standard clinical trial methodologies would have been used for data collection and outcome assessment in the Bouza (2003) and Maragakis (2006) studies. Specific adjudication methods for outcomes are not detailed in this summary.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, If So, What Was the Effect Size of How Much Human Readers Improve with AI vs Without AI Assistance

No MRMC comparative effectiveness study was mentioned or performed for the CLAVE Neutron. This device is a physical medical device (needleless connector), not an AI algorithm assisting human readers. The summary explicitly states: "There is no clinical data included in this submission." The referenced clinical studies (Bouza 2003, Maragakis 2006) are about the clinical performance of the predicate CLAVE connector, not about AI assistance.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Not applicable. The CLAVE Neutron is a physical medical device, not an algorithm.

7. The Type of Ground Truth Used

For the CLAVE Neutron's design verification tests: The "ground truth" is defined by the predetermined performance criteria and product specifications outlined in the submission (e.g., specific mL/minute flow rates, psig leak pressures, lbf-in component assembly strength).
For the referenced predicate CLAVE clinical studies (Bouza 2003, Maragakis 2006):
- Bouza (2003): Clinical outcomes data (catheter hub and tip bacterial colonization).
- Maragakis (2006): Clinical outcomes data (catheter-related bloodstream infection rates).

8. The Sample Size for the Training Set

Not applicable. The CLAVE Neutron is a physical medical device and does not involve a "training set" in the context of machine learning or AI.

9. How the Ground Truth for the Training Set Was Established

Not applicable. As the device is not an AI algorithm, there is no training set or corresponding ground truth establishment in that sense. The device's design and manufacturing rely on engineering principles, materials science, and functional testing to meet specified performance standards.

Summary

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510(K) Summary

K100434

ICU MEDICAL INC.

4455 Atherton Drive Salt Lake City, Utah (801) 264 - 1332, Phone (801) 264 - 1755, Fax Tracy S. Best, Sr. Regulatory Affairs Specialist Preparation Date: 06/23/2010

Summary of Safety and Effectiveness for the:

CLAVE® Neutron™ Trade Name: Needleless Connector, Closed Access Common Name: Classification Name: 21 CFR 880.5440, Class II Device, 80FPA & 80LHI, Accessory

Legally Marketed Predicate Devices for Substantial Equivalence:

*K970855 - CLAVE® Connector - ICU Medical Inc. * K021692 - CLC2000 Catheter Patency Device - ICU Medical, Inc. * K083723 - A6 Luer Access Device - B. Braun Medical, Inc.

Rationale for Substantial Equivalence:

The CLAVE Neutron is substantially equivalent to all three predicates by providing a normally closed, needleless connection and a route to deliver blood and fluids to a patient through a vascular access device. All three predicate devices and the proposed device are free of steel needle components and designed such that the use of a needle in the device would render them inoperable. This design feature passively aids in the prevention needles cannot be introduced into the system during use.

The anti-displacement feature of the CLAVE Neutron is substantially equivalent to both the CLC2000 and the A6 in that it prevents negative displacement.

The power injectable feature is substantially equivalent as the A6 Luer Access Device which allows the infusion of contrast media at 10mL per second at a maximum pressure of 300psi. The CLAVE Neutron allows infusion of contrast media of 10mL per second with a maximum pressure of 350psi.

Components of the CLAVE Neutron are made from materials that are substantially equivalent to the predicate devices. Comprehensive biocompatibility testing for the CLAVE Neutron is included in this Submission.

The CLAVE Neutron was sublected to a variety of functional tests including microbial ingress and performance criteria which prove it to be substantially equivalent to the predicate devices. Results of the testing demonstrate that there are no new issues of Safety and Efficacy that are raised with the introduction of the CLAVE Neutron.

Description of Submitted Device:

1. Connection or Disconnection of an Adaptable Luer Device. Fluid displacement occurs when a luer is inserted, or removed, from a connector by displacing a specific volume. This is also commonly known as positive or negative pressure when describing connectors.
1. Syringe Plunger Rebound. This occurs when a flush has been done using a standard syringe. Once the syringe is emptied, the clinician has the ability to compress the syringe plunger in an effort to infuse all available solutions which, once released by the clinician's hand, will rebound and cause negative fluid displacement.
1. Patient Vascular Pressure Changes. Routine events such as coughing, sneezing, crying and bearing down can cause a temporary increase in a patient's vascular pressure. This pressure can cause negative fluid displacement back through a standard needleless connector.

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1. IV Bag Run Dry. When an IV solution bag is allowed to empty, the normal gravity infusion pressure which is caused by the weight of the fluid hung at 36" head height diminishes to little or zero positive pressure. Normal patient vascular pressure may then overcome the fluid head height pressure and cause negative fluid displacement back through a standard needleless connector.

Intended Uses of the CLAVE® Neutron™:

CLAVE Neutron is a normally closed, bidirectional connector intended for use as an accessory to an intravascular catheter placed in the vein or artery. The device may be used for the administration of blood and fluids to patients, including pediatrics and immunocompromised patlents. The device may also be used with power injector procedures up to 10mL per second of contrast media and a maximum pressure of 350psi. The device incorporates a technology that will prevent fluid displacement resulting from the following: Connection of a luer; syringe plunger compression; patlent vascular pressure changes, such as coughing or sneezing; and IV solution container run-dry. The CLAVE Neutron incorporates a pre-slit septum that does not require the use of needles and will therefore passively aid in the reduction of needlestick injuries.

Safety and Performance:

The CLAVE Neutron is intended for use on a patient's vascular access device including pediatrics and immunocompromised patients. As discussed in the Executive Summary, the CLAVE Neutron incorporates proprietary design features from the CLAVE Needleless Connector. Specifically the preslit septum and the internal cannula of the predicate CLAVE which are used to transfer fluid to the patient's catheter, are identical in design. These two components are the functional components which prohibit bacterial transfer. Microbial Ingress testing as provided in this submission demonstrates that the CLAVE Neutron in comparison to the CLAVE was equivalent in its ability to prevent bacterial ingress. Said testing shows that the device will prevent bacterial in gress. completely if used in accordance with the directions for use. The prevention of bacterial ingress is specifically important for pediatrics and immunocompromised patients that would otherwise be at risk of infection.

In Bouza (2003), the CLAVE was found in a randomized clinical trial to independently reduce catheter hub and tip bacterial colonization. The patient population for the study was immunocompromised, intensive care patients at the Department of Cardiovascular Surgery, Hospital General University of Madrid, Madrid, Madrid, Spain. The identical CLAVE pre-slit septum component used in the study, is still used in the CLAVE today and also in the proposed CLAVE Neutron. This study demonstrates that the specific CLAVE split-septum design may safely be used In immunocompromised patient populations.

In Maragakis' (2006), the CLAVE was clinically studied in pediatric and immunocompromised patient populations. In this study, pediatric ICU and pediatric oncology service patients at the John's Hopkins Hospital in Baltimore Maryland were observed for Cather Related Bloodstream Infection Rates. The identical CLAVE pre-slit septum component used in this study, is still used in the CAVE today and also in the proposed CLAVE Neutron. This study demonstrates that the CLAVE split-septum design may safely be wed in pediatric and immunocompromised patient populations.

The CLAVE Neutron has been tested in accordance with its product specifications which accommodate known functional requirements for Critical Care, Neonatal Care and Pediatrics.

The CLAVE Neutron is individually packaged and pre-sterilized in a peel type pouch. The device can be included as part of a kit or set - as the physician may prescribe. ICU Medical performs analysis and design verification testing based on predetermined criteria, which is documented in the Performance Specification contained in this submission. All testing meets themements on the la as defined for the device, including power infusion up to 1000 per second of contrast media. The design of the device allows it to accept a male luer as defined by ISO 594-1 and ISO 594-2 which is considered to be an industry standard.

ICU Medical has also performed testing that is recommended by the guidance document "Intravascular Administration Sets Premarket Notifications [510(k)/i and we have included that successful testing as part of this submission.

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Specification:	CLAVE®	CLC2000®	Braun A6	CLAVE® Neutron™
510(k) Approval	K970855	K021692	K083723	This submission
Functional use	Needleless connector	Needleless Connectorwith anti-reflux	Needleless connectorwith anti-fluiddisplacement andpower injectable	Needleless connectorwith anti-fluiddisplacement andpower injectable
Patient Populations*	Adults, Pediatrics andImmunocompromisedpatients	Adults	Adults	Adults, Pediatrics andImmunocompromisedpatients
Residual Volume	0.06mL	0.07mL	0.30mL	0.14mL
Gravity Fluid Flow	100mL/min	200mL/min	Unavailable for test	100mL/minute
Syringe Disconnect:Fluid Displacement	Negative Displacement	Positive Displacement	Positive Displacement	Integral valve preventsdisplacement, bothpositive and negative®
Syringe PlungerCompression: FluidDisplacement	N/A	N/A	N/A	Integral valve preventsdisplacement, bothpositive and negative
Patient Pressure: FluidDisplacement	N/A	N/A	N/A	Integral valve preventsdisplacement, bothpositive and negative
Bag Run-Dry:Fluid Displacement	N/A	N/A	N/A	Integral valve preventsdisplacement, bothpositive and negative
Multiple Activations	96 intermittent3 extended time	96 intermittent3 extended time	Unavailable for test	96 Intermittent3 extended time
Positive Leak Pressure	60psig	60psig	Unavailable for test	45psig **
Negative Leak Pressure	-8.5psig	-8.5psig	Unavailable for test	-8.5psig
Luer Retention	ISO 594-1 (5.4)	ISO 594-1 (5.4)	Unavailable for test	ISO 594-1 (5.4)
Component Assembly	>51bf-in	>15lbf-in	Unavailable for test	>20lbf-in
Chemical Compatibility	Lipids, Alcohol	Lipids, Alcohol	Unavailable for test	Lipids, Alcohol
Power injectable	N/A	N/A	10ml/sec of contrastmedia and < 300psl.	10ml/sec of contrastmedia and < 350psi.
Sterilization Method	Gamma or E-beam	Gamma or E-beam	Gamma or E-beam	Gamma or E-beam
Packaging	Peel pouch	Peel pouch	Peel pouch	Peel pouch
Materials	Polyester; Silicone; andABS or Polycarbonate	Polyester; Silicone;Stainless Steel;Polypropylene; andPolycarbonate	Polycarbonate; rubber;silicone	Polyester: Silicone: ABSor Polycarbonate; andNylon

Technological Characteristics and Substantial Equivalence Table:

*A single, integral valve in the CLAVE Neutron is used to prevent the four forms of fluid displacement. This fluid displacement feature is substantially equivalent to the fluid displacement feature of all three predicate devices during the disconnection of a luer. For the additional three fluid displacement features (Syringe Plunger Compression, Patient Pressure and Bag-Run Dry), the valve operates in the identical manner which renders these new features not significantly different from the predicate devices.

**45 psig is adequate to prevent positive pressure leakage from a patient's line and is therefore not significantly different from the predicate devices.

Conclusion:

As demonstrated by the table above, there are equivalent features and functional uses between devices. Differences are in materials; maximum pressure; residual volume; and additional types of displacement that the CLAVE Neutron is able to accommodate. Materials are tested to the latest ISO 10993 standards; the unique design allows the additional pressure up to 350ps; residual volume is less than half of the A6 predicate due to an internal fluid path versus an external fluid path; and additional displacement types are due to the manner in which the valve operates on the CLAVE Neutron. These differences do not introduce any new safety or efficacy risks to the patient.

The operational characteristics are equivalent to luer needleless connection technology and intended use when compared to the three predicate devices. The proprietary technology in the CLAVE Neutron is unique to this type of product and is confidentially discussed further in this submission.

Materials, performance, operational features, environment of use, and connection methodology of the submitted device compared to the predicate devices show that they are substantially equivalent

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and that they are safe and effective for their intended use as demonstrated and supported in the performance testing according to the product specification, included in this submission.

Clinical and Non-Clinical Data:

There is no clinical data included in this submission.

I nere is no alliner solo nether CLAVE Neutron Design Verification Report in the submission as simulated use environment testing. The testing subjected the CLAVE Neutron to a series of simulated use environment cesang. The mig oblal ingress challenges to verify the safe and performance testing, alocentify alocating demonstrates that there are no differences between the eredicate and proposed device that raise any new issues of safety or effectiveness. This proprietary data is included in this submission.

² Bouza, E, Munoz, P, Lopez-Rodriguez, J, Jesus Perez, M, & Rincon, C, et. al, (2003). A Needleless closed system device (clave) protects from intravascular catheter tip and hub colonization: a prospective randomized study. Journal of Hospital Infection, 54, 279-287.

2 Maragakis, L, Bradley, K, Song, X, Beers, C, & Miller, M, et. al, (2006). Increased catheter-related bloodstream infection rates after the introduction of a new mechanical valve intravenous access port. Infection Control ond Hospital Epidemiology, 27, 67-70.

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Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle or bird-like symbol with three curved lines forming its body and wings. The logo is encircled by the text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" in a circular arrangement.

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

Mr. Tracy Best Senior Regulatory Affairs Specialist ICU Medical, Incorporated 4455 Atherton Drive Salt Lake City, Utah 84123

Re: K100434

Trade/Device Name: Clave® Neutron™ Regulation Number: 21 CFR 880.5970 Regulation Name: Percutaneous, Implanted, Long Term Intravascular Catheter Regulatory Class: II Product Code: FPA Dated: June 24, 2010 Received: June 25, 201

AUG 9 - 2010

Dear Mr. Best:

This letter corrects our substantially equivalent letter of July 7, 2010.

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 (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to 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.

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Page 2- Mr. Best

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 device-related 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 go to

http://www.fda.gov/AboutFDA/CentersOffices/CDRH/CDRHOffices/ucm115809.htm for the Center for Devices and Radiological Health's (CDRH's) Office of Compliance. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 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.

You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely vours.

Susan Panas
Anthony D. Watson, B.S.

ny D. Watson, B.S., M.S., M.B.A. Director Division of Anesthesiology, General Hospital, Infection Control and Dental Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known): K100434

Device Name: Clave® Neutron™

Indications for Use:

Prescription Use XX (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use (21 CFR 807 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Rill C. 8/5/10

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

510(k) Number: K100434

Regulation Number and Section

§ 880.5440 Intravascular administration set.

(a)
Identification. An intravascular administration set is a device used to administer fluids from a container to a patient's vascular system through a needle or catheter inserted into a vein. The device may include the needle or catheter, tubing, a flow regulator, a drip chamber, an infusion line filter, an I.V. set stopcock, fluid delivery tubing, connectors between parts of the set, a side tube with a cap to serve as an injection site, and a hollow spike to penetrate and connect the tubing to an I.V. bag or other infusion fluid container.(b)
Classification. Class II (special controls). The special control for pharmacy compounding systems within this classification is the FDA guidance document entitled “Class II Special Controls Guidance Document: Pharmacy Compounding Systems; Final Guidance for Industry and FDA Reviewers.” Pharmacy compounding systems classified within the intravascular administration set are exempt from the premarket notification procedures in subpart E of this part and subject to the limitations in § 880.9.