Using in vitro methods, the antimicrobial treatment on the ClearGuard HD Antimicrobial Barrier Cap has been shown to be effective at reducing microbial colonization in hemodialysis catheter hubs against the following microorganisms: Enterococcus faecium (VRE), Enterococus faecalis (VRE), Acinetobacter baumannii, Escherichia coli, Staphylococcus aureus (MRSA), Staphylococcus aureus, Staphylococcus epidermidis (MRSE), Pseudomonas aeruginosa, Candida albicans and Candida parapsilosis and has not been shown to be effective against Candida paratropicalis and Klebsiella pneumoniae.

Using post-market clinical surveillance data, use of the ClearGuard HD Antimicrobial Barrier Cap has been shown to reduce the incidence of central-line associated bloodstream infections (CLABSI) in hemodialysis patients. Note: CLABSI was defined as a positive blood culture (PBC) not related to an alternative source of infection per the National Healthcare Safety Network (NHSN) surveillance definition. Alternative sources were excluded if dialysis sites attributed the PBC to vascular access on the dialysis event form. The actual reduction in CLABSI rates may be less substantial as the evaluation for alternative PBC sources was not pre-specified, nor standardized between pafients and clinical sites, and supplemental data evaluating for alternative sources were not available for review.

The subject device is not intended to be used for the treatment of existing infections. The antimicrobial is only present within the hub of the catheter and does not migrate to distal portions of the catheter.

Device Description

The ClearGuard HD Antimicrobial Barrier Cap (hereinafter also referred to as the ClearGuard HD cap) is a single-use male luer lock cap that incorporates an antimicrobial treatment on its surfaces.

The ClearGuard HD cap consists of 1) a polypropylene polymer plug, which has a rod extending from the luer region that is coated with the antimicrobial agent chlorhexidine acetate (CHA) and 2) a nylon lock ring with threads that are also coated with CHA. When a ClearGuard HD cap is inserted into a liquid-filled catheter, CHA elutes from the rod into the catheter lock solution. This CHA solution is designed to kill microorganisms in the hemodialysis catheter hub, which results in a reduction in Central Line-Associated Bloodstream Infection (CLABSI) rates.

The catheter extension line pinch clamps are used to maintain the lock solution within the catheter lumens to minimize the risk of air embolism and maintain catheter patency. These clamps, which are closed when the catheter is not in use, mechanically confine the CHA and prevent diffusion of CHA toward the catheter tip and the patient's bloodstream.

AI/ML Overview

The ClearGuard HD Antimicrobial Barrier Cap is designed to reduce microbial colonization in hemodialysis catheter hubs and, based on clinical surveillance data, to reduce the incidence of Central-Line Associated Bloodstream Infections (CLABSI) in hemodialysis patients.

Here's an analysis of the provided information:

1. Table of acceptance criteria and the reported device performance

Acceptance Criteria / Performance Aspect	Reported Device Performance (ClearGuard HD)
Antimicrobial Effectiveness (In Vitro)	Shown to be effective at reducing microbial colonization in hemodialysis catheter hubs against: Enterococcus faecium (VRE), Enterococcus faecalis (VRE), Acinetobacter baumannii, Escherichia coli, Staphylococcus aureus (MRSA), Staphylococcus aureus, Staphylococcus epidermidis (MRSE), Pseudomonas aeruginosa, Candida albicans, and Candida parapsilosis. Not shown to be effective against Candida paratropicalis and Klebsiella pneumoniae. These results were consistent "initially, and after 3 years real time shelf life."
Biocompatibility	Non-hemolytic, non-cytotoxic, non-irritating, non-sensitizing, non-mutagenic, non-toxic, and non-pyrogenic under intended use conditions.
Device Integrity	Met requirements for liquid leakage, disassembly torque, plug, shield and pouch integrity, and for antimicrobial quantity, elution, and solubility.
PBC Rate Reduction (Clinical)	ClearGuard HD: 0.28 per 1,000 CVC-daysControl (Tego+Curos): 0.75 per 1,000 CVC-daysIncidence Rate Ratio (IRR): 0.37Reduction in PBC Rate: 63%P-value: 0.001 (statistically significant reduction)
CLABSI Rate Reduction (Clinical)	ClearGuard HD: 0.17 per 1,000 CVC-daysControl (Tego+Curos): 0.50 per 1,000 CVC-daysIncidence Rate Ratio (IRR): 0.34Reduction in CLABSI Rate: 66% (This was an exploratory ad-hoc analysis, not a pre-specified primary endpoint, and has limitations as noted in the document.)
Safety	No device-associated adverse events reported during the clinical study or a previous study via the FDA's medical device reporting (MDR) system.

2. Sample size used for the test set and the data provenance

Test Set Sample Size: For the clinical study, 1,671 subjects participated in the primary and exploratory analyses, accruing approximately 183,000 CVC-days in the primary analysis.
- ClearGuard HD Arm: 826 subjects
- Control Arm (Tego® Connector with Curos™ Disinfecting Cap): 845 subjects
Data Provenance: The clinical study was a prospective, cluster-randomized, multi-arm, unblinded clinical study conducted at 40 dialysis facilities throughout the United States only.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

The document does not explicitly state the number or qualifications of experts used to establish the ground truth for the clinical study's test set. However, it notes that:

"As is standard policy at the participating facilities, blood culture results were reported into the electronic health record in automated fashion and to the National Healthcare Safety Network (NHSN) Dialysis Event (DE) Form, from which they were abstracted for analysis."
CLABSI was defined per the National Healthcare Safety Network (NHSN) surveillance definition.
"All cultures were processed by a single clinical laboratory."

This suggests that the ground truth for PBCs and CLABSIs was established through standard clinical laboratory procedures and adherence to NHSN surveillance definitions, rather than through a panel of independent experts reviewing cases.

4. Adjudication method for the test set

The document does not describe a formal adjudication method (e.g., 2+1, 3+1) for the clinical study's test set. The determination of Positive Blood Cultures (PBCs) and CLABSIs appears to be based on laboratory results and the NHSN surveillance definition, with physicians at the dialysis sites making preliminary attributions of the PBC source on the Dialysis Event form.

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

A Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. The device is an antimicrobial barrier cap, not an AI software intended for human interpretation improvement. The clinical study directly compared the effectiveness of two devices (ClearGuard HD vs. Tego+Curos) in reducing infection rates.

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

This question is not applicable as the ClearGuard HD Antimicrobial Barrier Cap is a physical medical device, not an algorithm or AI system.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

For antimicrobial effectiveness (in vitro tests): The ground truth was based on microbiological assays, specifically measuring reduction in microbial colonization.
For biocompatibility: Ground truth was established through standardized biological evaluation tests (e.g., cytotoxicity, irritation, sensitization, toxicity, pyrogenicity).
For clinical efficacy (PBC and CLABSI rates): The ground truth was based on outcomes data (positive blood cultures and CLABSI events) derived from patient medical records, laboratory results, and reported according to the National Healthcare Safety Network (NHSN) surveillance definition. Physicians at varying clinical sites attributed the PBC to a vascular access on the dialysis event form if no alternative source was identified. It is important to note the caveat regarding CLABSI: "The actual reduction in CLABSI rates may be less substantial as the evaluation for alternative PBC sources was not pre-specified, nor standardized between patients and clinical sites, and supplemental data evaluating for alternative sources were not available for review."

8. The sample size for the training set

This question is not applicable. The ClearGuard HD Antimicrobial Barrier Cap 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

This question is not applicable for the reasons stated above.

Summary

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May 25, 2018

Pursuit Vascular, Inc. Laurie E. Lynch, Ph.D. Director of Quality/Regulatory/Clinical 6901 East Fish Lake Road, Suite 166 Maple Grove, MN 55369

Re: K180111

Trade/Device Name: ClearGuard® HD Antimicrobial Barrier Cap Regulation Number: 21 CFR§ 876.5540 Regulation Name: Blood Access Device and Accessories Regulatory Class: II Product Code: PEH Dated: April 27, 2018 Received: April 30, 2018

Dear Laurie E. Lynch:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. 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.

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.

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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 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.

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.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Charles Viviano -S

For Benjamin R. Fisher, Ph.D. Director Division of Reproductive, Gastro-Renal, and Urological Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K180111

Device Name ClearGuard HD Antimicrobial Barrier Cap

Indications for Use (Describe)

ClearGuard HD Antimicrobial Barrier Cap is indicated for use with hemodialysis catheter hubs.

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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Date Prepared: 21-May-2018

Submitter's Name / Contact Person

Manufacturer	Contact Person
Pursuit Vascular, Inc.	Laurie Lynch, PhD
6901 E. Fish Lake Road, Suite 166	Director of Quality/Regulatory/Clinical
Maple Grove, MN 55369	Phone: (952) 221-2468
	Fax: (763) 592-8202
	Email: llynch@pursuitvascular.com
General Information
Trade Name	ClearGuard® HD Antimicrobial Barrier Cap
Common / Usual Name	Hemodialysis Catheter Luer End Cap
Regulation Name	21 CFR 876.5540; Blood Access Device and Accessories
Product Code	PEH; Hemodialysis Catheter Luer End Cap
Device Class	II
Predicate Devices	K131060 ClearGuard HD End Cap

Device Description

The ClearGuard HD Antimicrobial Barrier Cap (hereinafter also referred to as the ClearGuard HD cap) is a single-use male luer lock cap that incorporates an antimicrobial treatment on its surfaces.

Intended Use / Indications for Use

ClearGuard HD Antimicrobial Barrier Cap is indicated for use with hemodialysis catheter hubs.

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Staphylococcus aureus, Staphylococcus epidermidis (MRSE), Pseudomonas aeruginosa, Candida albicans and Candida parapsilosis and has not been shown to be effective against Candida paratropicalis and Klebsiella pneumoniae.

Using post-market clinical surveillance data, use of the ClearGuard HD Antimicrobial Barrier Cap has been shown to reduce the incidence of central-line associated bloodstream infections (CLABSI) in hemodialysis patients with catheters. Note: CLABSI was defined as a positive blood culture (PBC) not related to an alternative source of infection per the National Healthcare Safety Network (NHSN) surveillance definition. Alternative sources were excluded if dialysis sites attributed the PBC to vascular access on the dialysis event form. The actual reduction in CLABSI rates may be less substantial as the evaluation for alternative PBC sources was not prespecified, nor standardized between patients and clinical sites, and supplemental data evaluating for alternative sources were not available for review.

Substantial Equivalence Comparison

The predicate device is the Pursuit Vascular, Inc. ClearGuard HD End Cap, K131060.

In regard to the technological characteristics, the predicate and subject devices are both antimicrobial coated hemodialysis catheter caps manufactured by the same company, Pursuit Vascular, Inc. See comparison of the subject and predicate device in Table 1 below.

	Subject Device	Predicate Device
510(k) Number	K180111	K131060
Classification	Class II; PEH; 21 CFR 876.5540; Bloodaccess device and accessories	Class II; PEH; 21 CFR 876.5540; Bloodaccess device and accessories
Indications forUse	ClearGuard HD Antimicrobial BarrierCap is indicated for use withhemodialysis catheter hubs.Using in vitro methods, the antimicrobialtreatment on the ClearGuard HDAntimicrobial Barrier Cap has beenshown to be effective at reducingmicrobial colonization in hemodialysiscatheter hubs against the followingmicroorganisms: Enterococcus faecium(VRE), Enterococcus faecalis (VRE),Acinetobacter baumannii, Escherichiacoli, Staphylococcus aureus (MRSA),Staphylococcus aureus, Staphylococcus	ClearGuard HD is indicated for use as anend cap for use with hemodialysiscatheter hubs.The antimicrobial treatment on theClearGuard HD end cap has been shownto be effective at reducing microbialcolonization in hemodialysis catheterhubs against the followingmicroorganisms: Enterococcus faecium(VRE), Enterococcus faecalis (VRE),Acinetobacter baumannii, Escherichiacoli, Staphylococcus aureus (MRSA),Staphylococcus aureus, Staphylococcusepidermidis (MRSE), Pseudomonas
	Subject Device	Predicate Device
	aeruginosa, Candida albicans andCandida parapsilosis and has not beenshown to be effective against Candidaparatropicalis and Klebsiellapneumoniae.Using post-market clinical surveillancedata, use of the ClearGuard HDAntimicrobial Barrier Cap has beenshown to reduce the rate of central line-associated bloodstream infections(CLABSI) in hemodialysis patients withcatheters. Note: CLABSI was defined asa positive blood culture (PBC) not relatedto an alternative source of infection perthe National Healthcare Safety Network(NHSN) surveillance definition.Alternative sources were excluded ifdialysis sites attributed the PBC tovascular access on the dialysis eventform. The actual reduction in CLABSIrates may be less substantial as theevaluation for alternative PBC sourceswas not pre-specified, nor standardizedbetween patients and clinical sites, andsupplemental data evaluating foralternative sources were not available forreview.The subject device is not intended to beused for the treatment of existinginfections. The antimicrobial is onlypresent within the hub of the catheter anddoes not migrate to distal portions of thecatheter.	Candida parapsilosis and has not beenshown to be effective against Candidaparatropicalis and Klebsiellapneumoniae.The antimicrobial effectiveness wasevaluated using in vitro methods, andcorrelation between in vitro antibacterialactivity and any clinical effectiveness hasnot been tested. The subject device is notintended to be used for the treatment ofexisting infections. The antimicrobial isonly effective within the hub of thecatheter, and does not migrate to distalportions of the catheter.
Materials/Design
Maximumamount ofchlorhexidineon the device	2.53 mg	2.43 mg
Maximumamount ofchlorhexidinethat ispotentiallyreleased to thepatient	0.6 mg	0.6 mg
Lock Ring	Nylon with red or blue dye	Nylon with red or blue dye
	Subject Device	Predicate Device
Plug	• Polypropylene with new white colorant• Specify minimum and maximumsurface roughness• Fins to prevent lock ring from rotating	• Polyester with white colorant• Specify maximum luer surfaceroughness• No fins, lock ring freely rotates
Shield	• Polypropylene with white colorant	• Polyester with white colorant
Packaging, Sterilization, Shelf Life
Packaging	Foil pouch	Foil pouch
Sterilization	Gamma, SAL 10-6	Gamma, SAL 10-6
Device shelflife	3 years	11 months

Table 1. Comparison of Subject and Predicate Devices

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Summary of Non-Clinical Testing

The ClearGuard HD Antimicrobial Barrier Caps have been found to be safe and effective for their intended use. Finished sterile ClearGuard HD Antimicrobial Barrier Caps have been subjected to biocompatibility testing and found to be non-hemolytic, non-cytotoxic, nonirritating, non-sensitizing, non-mutagenic, non-toxic and non-pyrogenic under intended use conditions. The ClearGuard Antimicrobial Barrier Caps have also met their requirements for liquid leakage, disassembly torque, plug, shield and pouch integrity, and for antimicrobial quantity, effectiveness, elution and solubility, initially, and after 3 years real time shelf life.

Biocompatibility testing was conducted in compliance with ISO 10993-1:2009/TC1 2010 Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process. Package integrity was conducted in compliance with ASTM D3078-02(2013) Standard Test Method for Determination of Leaks in Flexible Packaging by Bubble Emission.

Clinical Trial Results

A 13-month, prospective, cluster-randomized, multi-arm, unblinded clinical study with a control was conducted at 40 dialysis facilities throughout the United States only. Facilities were pairmatched and randomly assigned to treatment or control group. The treatment group received the ClearGuard HD Antimicrobial Barrier Cap and the control group received the Tego® Connector with the Curos™ Disinfecting Cap. The primary study endpoint was PBC rate. There were no other primary study endpoints but an ad hoc exploratory analysis of CLABSI was also conducted. 1,671 subjects participated in the study during the primary and exploratory analyses, accruing approximately 183,000 CVC-days in the primary analysis.1 The subject enrollment is shown in Table 2 and the subject demographics are shown in Table 3.

Stage	Investigation DeviceArm(ClearGuard HD)	Control DeviceArm(Tego+Curos)	Total inBoth Arms
Subjects enrolled	951	960	1911

Table 2. Subject Enrollment During the Intervention Period

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Stage	Investigation DeviceArm(ClearGuard HD)	Control DeviceArm(Tego+Curos)	Total inBoth Arms
Subjects excluded for historyof heparin allergy	9	0	9
Subjects receiving treatment	942	960	1902
Subjects excluded due totreatment ≤21 days	116	115	231
Subjects in primary andexploratory analyses	826	845	1671

Table 3. Subject Demographics During the Intervention Period

Characteristic	All	TreatmentGroup	ControlGroup	P-Value
No. of Facilities	40	20	20
No. of CVC Subjects	1671	826	845
Age, y	62.8 ± 14.9	63.7 ± 14.4	62.0 ± 15.3	0.02
Gender (% Male)	856 (51)	421 (51)	435 (51)	0.8
Race
Caucasian	778 (47)	414 (50)	364 (43)
African American	621 (37)	267 (32)	354 (42)	<0.001
Hispanic	171 (10)	83 (10)	88 (10)
Other	98 (6)	60 (7)	38 (5)
Missing	3 (0)	2 (0)	1 (0)
Diabetes	998 (60)	477 (58)	521 (62)	0.1
Dialysis vintage, y	1.7 ± 3.2	1.6 ± 3.3	1.8 ± 3.2	0.2

Note: Values for categorical variables are given as number (percentage); values for continuous variables, as mean ± standard deviation.

As is standard policy at the participating facilities, blood culture results were reported into the electronic health record in automated fashion and to the National Healthcare Safety Network (NHSN) Dialysis Event (DE) Form, from which they were abstracted for analysis.

The pre-specified primary study endpoint was PBC rate. This study demonstrated that use of the ClearGuard HD Antimicrobial Barrier Caps resulted in a statistically significant reduction in the rate of PBCs compared to the use of Tego connector plus Curos cap in hemodialysis patients with catheters. See Table 4 below.

Table 4. Randomized Clinical Study Results Primary Analysis: PBC rates of ClearGuard HD vs. Tego+Curos on a Per-Event Basis

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Variable	Result
PBC Rate, ClearGuard HD	0.28 per 1,000 CVC-days
PBC Rate, Tego+Curos	0.75 per 1,000 CVC-days
Incidence Rate Ratio (IRR)	0.37
Reduction in PBC Rate	63%
P value	0.001

The exploratory ad-hoc CLABSI analysis was conducted to explore the possible reduction of a more clinically meaningful outcome than PBC rates. However, this analysis was not prespecified in the protocol and may have limitations (see Note below).

For a PBC to be classified as a CLABSI in this study per the NHSN surveillance definition, it must have been a Laboratory-Confirmed Bloodstream Infection (LCBI)2 as follows: LCB11) a recognized pathogen (an organism not included on the NHSN common commensal list) identified from one or more blood specimens obtained by blood culture microbiologic testing and the organism(s) identified in the blood must not be related to an infection at another site (as indicated by the "vascular access" box being checked as the suspected source of the PBC on the Dialysis Event (DE) form), OR an LCBI2) the same NHSN common commensal identified by blood culture microbiologic testing from two or more blood specimens drawn on the same day, the organism(s) identified in blood must not be related to an infection at another site (as indicated by the "vascular access" box being checked as the suspected source of the PBC on the DE form), and the subject had at least one of the following symptoms: fever, chills, or hypotension (as indicated on the DE form). Also, the CLABSI analysis was conducted on a per-subject basis (i.e., censored the patient after the first CLABSI event to prevent potentially double counting the same infection). All cultures were processed by a single clinical laboratory. Note: CLABSI was defined as a positive blood culture (PBC) not related to an alternative source of infection per the National Healthcare Safety Network (NHSN) surveillance definition. Alternative sources were excluded if dialysis sites attributed the PBC to vascular access on the dialysis event form. The actual reduction in CLABSI rates may be less substantial as the evaluation for alternative PBC sources was not pre-specified, nor standardized between patients and clinical sites, and supplemental data evaluating for alternative sources were not available for review.

The CLABSI analysis demonstrated that using ClearGuard HD Antimicrobial Barrier Caps resulted in a reduction in the rate of CLABSIs compared to the control (Table 5).

Table 5. Randomized Clinical Study Results Exploratory Analysis: CLABSI Rates of
ClearGuard HD vs. Tego+Curos on a Per-Subject Basis

Variable	Result
CLABSI Rate, ClearGuard HD	0.17 per 1,000 CVC-days
CLABSI Rate, Tego+Curos	0.50 per 1,000 CVC-days
Incidence Rate Ratio (IRR)	0.34
Reduction in CLABSI Rate	66%

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There was no formal safety endpoint associated with this clinical study. There were no deviceassociated adverse events reported via the FDA's medical device reporting (MDR) during this study or in a previous study.4

Conclusions

Results of design verification and validation testing demonstrate that 1) the ClearGuard HD Antimicrobial Barrier Cap is safe for its intended use as an end cap for hemodialysis catheters and 2) the chlorhexidine antimicrobial agent effectively reduces the number of microorganisms in hemodialysis catheter hubs following three years of real time ambient aging. The risk assessment results, together with the results of design verification and validation testing presented in this submission, confirm that the ClearGuard HD Antimicrobial Barrier Cap raised no new questions of safety or effectiveness compared to the predicate device. The ClearGuard HD Antimicrobial Barrier Cap has, therefore, been shown to be substantially equivalent to a legally marketed device for the purpose of 510(k) clearance. The post-market clinical study demonstrated a reduction in the rate of CLABSIs with use of the device, thus supporting the expanded indications for use.

1 Brunelli, SM MD, MSCE, Van Wyck, DB MD, Njord, L PhD, Killion, DP MBA, Lynch, LE, PhD and Ziebol, RJ BS. Cluster-Randomized Trial of Devices to Prevent Catheter-Related Bloodstream Infection. J Am Soc Nephrol: 29:1336-1343, 2018.

ର Centers for Disease Control and Prevention (CDC): National Healthcare Safety Network (NHSN) Patient Safety Component Manual, January 2018. Bloodstream Infection Event. Chapter 4 Device-associated Module: Central Line-Associated Bloodstream Infection and Non-central Line Associated Bloodstream Infection). https://www.cdc.gov/nhsn/pdfs/pscmanual/pcsmanual current.pdf. Accessed Apr 23, 2018.

ന https://www.cdc.gov/nhsn/forms/57.502_DIAL_BLANK.pdf. Accessed Apr 23, 2018.

ব Hymes JL, Mooney A, Van Zandt C, Lynch L, Ziebol R, Killion D: Dialysis catheter-related bloodstream infections: a cluster-randomized trial of the ClearGuard HD antimicrobial barrier cap. Am J Kidney Dis 69(2): 220-227, 2017.

Regulation Number and Section

§ 876.5540 Blood access device and accessories.

(a)
Identification. A blood access device and accessories is a device intended to provide access to a patient's blood for hemodialysis or other chronic uses. When used in hemodialysis, it is part of an artificial kidney system for the treatment of patients with renal failure or toxemic conditions and provides access to a patient's blood for hemodialysis. The device includes implanted blood access devices, nonimplanted blood access devices, and accessories for both the implanted and nonimplanted blood access devices.(1) The implanted blood access device is a prescription device and consists of various flexible or rigid tubes, such as catheters, or cannulae, which are surgically implanted in appropriate blood vessels, may come through the skin, and are intended to remain in the body for 30 days or more. This generic type of device includes various catheters, shunts, and connectors specifically designed to provide access to blood. Examples include single and double lumen catheters with cuff(s), fully subcutaneous port-catheter systems, and A-V shunt cannulae (with vessel tips). The implanted blood access device may also contain coatings or additives which may provide additional functionality to the device.
(2) The nonimplanted blood access device consists of various flexible or rigid tubes, such as catheters, cannulae or hollow needles, which are inserted into appropriate blood vessels or a vascular graft prosthesis (§§ 870.3450 and 870.3460), and are intended to remain in the body for less than 30 days. This generic type of device includes fistula needles, the single needle dialysis set (coaxial flow needle), and the single needle dialysis set (alternating flow needle).
(3) Accessories common to either type include the shunt adaptor, cannula clamp, shunt connector, shunt stabilizer, vessel dilator, disconnect forceps, shunt guard, crimp plier, tube plier, crimp ring, joint ring, fistula adaptor, and declotting tray (including contents).
(b)
Classification. (1) Class II (special controls) for the implanted blood access device. The special controls for this device are:(i) Components of the device that come into human contact must be demonstrated to be biocompatible. Material names and specific designation numbers must be provided.
(ii) Performance data must demonstrate that the device performs as intended under anticipated conditions of use. The following performance characteristics must be tested:
(A) Pressure versus flow rates for both arterial and venous lumens, from the minimum flow rate to the maximum flow rate in 100 milliliter per minute increments, must be established. The fluid and its viscosity used during testing must be stated.
(B) Recirculation rates for both forward and reverse flow configurations must be established, along with the protocol used to perform the assay, which must be provided.
(C) Priming volumes must be established.
(D) Tensile testing of joints and materials must be conducted. The minimum acceptance criteria must be adequate for its intended use.
(E) Air leakage testing and liquid leakage testing must be conducted.
(F) Testing of the repeated clamping of the extensions of the catheter that simulates use over the life of the device must be conducted, and retested for leakage.
(G) Mechanical hemolysis testing must be conducted for new or altered device designs that affect the blood flow pattern.
(H) Chemical tolerance of the device to repeated exposure to commonly used disinfection agents must be established.
(iii) Performance data must demonstrate the sterility of the device.
(iv) Performance data must support the shelf life of the device for continued sterility, package integrity, and functionality over the requested shelf life that must include tensile, repeated clamping, and leakage testing.
(v) Labeling of implanted blood access devices for hemodialysis must include the following:
(A) Labeling must provide arterial and venous pressure versus flow rates, either in tabular or graphical format. The fluid and its viscosity used during testing must be stated.
(B) Labeling must specify the forward and reverse recirculation rates.
(C) Labeling must provide the arterial and venous priming volumes.
(D) Labeling must specify an expiration date.
(E) Labeling must identify any disinfecting agents that cannot be used to clean any components of the device.
(F) Any contraindicated disinfecting agents due to material incompatibility must be identified by printing a warning on the catheter. Alternatively, contraindicated disinfecting agents must be identified by a label affixed to the patient's medical record and with written instructions provided directly to the patient.
(G) Labeling must include a patient implant card.
(H) The labeling must contain comprehensive instructions for the following:
(
1 ) Preparation and insertion of the device, including recommended site of insertion, method of insertion, and a reference on the proper location for tip placement;(
2 ) Proper care and maintenance of the device and device exit site;(
3 ) Removal of the device;(
4 ) Anticoagulation;(
5 ) Management of obstruction and thrombus formation; and(
6 ) Qualifications for clinical providers performing the insertion, maintenance, and removal of the devices.(vi) In addition to Special Controls in paragraphs (b)(1)(i) through (v) of this section, implanted blood access devices that include subcutaneous ports must include the following:
(A) Labeling must include the recommended type of needle for access as well as detailed instructions for care and maintenance of the port, subcutaneous pocket, and skin overlying the port.
(B) Performance testing must include results on repeated use of the ports that simulates use over the intended life of the device.
(C) Clinical performance testing must demonstrate safe and effective use and capture any adverse events observed during clinical use.
(vii) In addition to Special Controls in paragraphs (b)(1)(i) through (v) of this section, implanted blood access devices with coatings or additives must include the following:
(A) A description and material characterization of the coating or additive material, the purpose of the coating or additive, duration of effectiveness, and how and where the coating is applied.
(B) An identification in the labeling of any coatings or additives and a summary of the results of performance testing for any coating or material with special characteristics, such as decreased thrombus formation or antimicrobial properties.
(C) A Warning Statement in the labeling for potential allergic reactions including anaphylaxis if the coating or additive contains known allergens.
(D) Performance data must demonstrate efficacy of the coating or additive and the duration of effectiveness.
(viii) The following must be included for A-V shunt cannulae (with vessel tips):
(A) The device must comply with Special Controls in paragraphs (b)(1)(i) through (v) of this section with the exception of paragraphs (b)(1)(ii)(B), (b)(1)(ii)(C), (b)(1)(v)(B), and (b)(1)(v)(C), which do not apply.
(B) Labeling must include Warning Statements to address the potential for vascular access steal syndrome, arterial stenosis, arterial thrombosis, and hemorrhage including exsanguination given that the device accesses the arterial circulation.
(C) Clinical performance testing must demonstrate safe and effective use and capture any adverse events observed during clinical use.
(2) Class II (performance standards) for the nonimplanted blood access device.
(3) Class II (performance standards) for accessories for both the implanted and the nonimplanted blood access devices not listed in paragraph (b)(4) of this section.
(4) Class I for the cannula clamp, disconnect forceps, crimp plier, tube plier, crimp ring, and joint ring, accessories for both the implanted and nonimplanted blood access device. The devices subject to this paragraph (b)(4) are exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 876.9.