For intraosseous access anytime in which vascular access is difficult to obtain in emergent, urgent, or medically necessary cases for up to 24 hours. Insertion sites: ADULTS (≥22 years old): proximal humerus, proximal tibia, distal tibia PEDIATRICS (≤21 years old): proximal humerus, proximal tibia, distal tibia, distal femur Use of the device may be extended for up to 48 hours when alternate intravenous access is not available or reliably established. Insertion sites: ADULTS (≥22 years): proximal humerus, proximal tibia, distal tibia PEDIATRICS (≥12 years through 21 years old): proximal humerus, proximal tibia, distal tibia, distal femur

Device Description

The EZ-IO System previously cleared with K14117 is designed to allow the user to insert a needle set consisting of a stylet and catheter through the cortex of the bone to a desired depth within the bone marrow to facilitate intraosseous infusion of desired fluids and medications for vascular access. All system materials are biocompatible. Needle sets are single-use and composed of 304 stainless steel with polycarbonate hubs and available in 15 mm (for patients 3-39 kg); 25 mm (for patients 3 kg or over) and 45 mm (for patients 40 kg or over) lengths. Black lines on the needle set serve as depth markers. The reusable cordless driver/drill is powered by lithium batteries with a battery-power indicator light. An extension tubing set accessory, the EZ-Connect, is included with every needle set. The EZ-Connect contains a needleless connector system and Luer lock adapter. An optional dressing, the EZ-Stabilizer, is an accessory to the EZ-IO Vascular Access System. It is designed as a securement device with an adhesive backing that is placed over an EZ-IO Needle to keep the needle securely anchored to the patient; and is recommended in the Instructions for use (IFU).

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study that proves the device meets them, based on the provided text:

Acceptance Criteria and Device Performance

The core change addressed by this submission is the expansion of the "EZ-IO Intraosseous Vascular Access System" indications for use from up to 24 hours to up to 48 hours. Therefore, the primary acceptance criteria revolve around demonstrating the safety and effectiveness of the device for this extended dwell time.

Acceptance Criteria (Implicit)	Reported Device Performance
Biocompatibility for Prolonged Contact (up to 48 hours)	Materials of construction evaluated according to ISO 10993-1 for prolonged contact duration (>24 hours to ≤ 30 days) for all relevant components (EZ-IO Needle Set, EZ-Connect extension tubing set, EZ-Stabilizer dressing). Results indicated the materials are biocompatible for this duration.
Maintenance of Physical Performance for Extended Use	Performance requirements for physical parameters (tensile strength, torsion strength, bend strength, leak, burst pressure) are not time-dependent and the materials are unchanged. The performance data from the predicate device (K141117) for 24-hour use is considered applicable for 48-hour use without additional testing.
Safety of Intraosseous Catheter Retention for 48 Hours	Primary endpoint of the clinical study was the absence of serious complications from IO catheter retention over a 48-hour period. No serious Adverse Events (AEs) or complications were reported for any subjects randomized into the study during a 30-day follow-up. The study concluded that IO access can be maintained for 48 hours without significant risk of serious adverse events.
Manageability of Pain during 48-hour Dwell and Infusion	The clinical study demonstrated that pain associated with catheter dwell and infusion can be well-managed.
Maintenance of Patency for 48 Hours	The clinical study noted that a slow infusion of 30 mL/hour maintained patency for 48 hours.
Identification and Mitigation of Risks for Extended Use	Identified limitations of the study (comparison to actual use, literature limitations) led to restricted Indications for Use (only when alternate IV access is unavailable/unreliable, and only in patients ≥12 years old for the extended duration). "CAUTION" statements were added to the Instructions for Use regarding increased risk for patients with comorbidities, increased risk with longer dwell times, and the importance of frequent monitoring.

Study Details

Sample size used for the test set and the data provenance:
- Sample Size (Test Set): 121 evaluable subjects.
  - 79 healthy volunteers
  - 39 with diabetes only
  - 3 with diabetes and renal insufficiency
- Data Provenance: US single-site, prospective clinical IDE trial.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Not explicitly stated. The study involved clinical trial procedures and observations, including physical examinations and x-rays, but the specific number or qualifications of "experts" establish ground truth in the sense of a diagnostic consensus is not detailed. The "ground truth" here is the clinical outcome (complications, pain, patency) observed in the subjects under the study protocol.
Adjudication method for the test set:
- Not explicitly stated in detail for all events. However, adverse events were assessed for relatedness to the device, implying a review process. The primary endpoint was the "absence of serious complications," suggesting a clear definition of what constitutes a serious complication and its determination by the study team.
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. This is not an AI/imaging device. It is a medical device for vascular access.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- N/A. This is not an AI/algorithm device.
The type of ground truth used:
- Clinical outcomes data: The ground truth was based on the presence or absence of serious complications, pain reports, patency, and other observed adverse events during the 48-hour indwelling period and subsequent 30-day follow-up of human subjects. This also included objective measures like IO aspirate cultures and x-rays.
The sample size for the training set:
- N/A. This is a medical device approval, not an AI model requiring a training set. The "development" of the device was based on prior predicate devices and engineering principles, with the clinical study serving as a validation of the extended use.
How the ground truth for the training set was established:
- N/A. As above, no training set in the AI sense was used.

Summary

{0}------------------------------------------------

Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, with the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG" in blue, and then the word "ADMINISTRATION" in a smaller font below.

November 9, 2018

Arrow International, Inc. (Subsidiary of Teleflex, Inc.) Frank Pelc Sr. Regulatory Affairs Specialist 2400 Bernville Road Reading, Pennsylvania 19605

Re: K180395

Trade/Device Name: EZ-IO Intraosseous Vascular Access System Regulation Number: 21 CFR 880.5570 Regulation Name: Hypodermic Single Lumen Needle Regulatory Class: Class II Product Code: FMI Dated: October 9, 2018 Received: October 10, 2018

Dear Frank Pelc:

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 mav, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be avare that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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. You must comply with all the Act's

{1}------------------------------------------------

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) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.html; good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; 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 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.

Alan M.
Stevens -S

for Tina Kiang, Ph.D. Acting Director Division of Anesthesiology, General Hospital, Respiratory, Infection Control, and Dental Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

{2}------------------------------------------------

Indications for Use

510(k) Number (if known) K180395

Device Name

EZ-IO Intraosseous Vascular Access System

Indications for Use (Describe)

For intraosseous access anytime in which vascular access is difficult to obtain in emergent, urgent, or medically necessary cases for up to 24 hours. Insertion sites:

ADULTS (>22 years old): proximal humerus, proximal tibia, distal tibia

PEDIATRICS (≤21 years old): proximal humerus, proximal tibia, distal tibia, distal femur

Use of the device may be extended for up to 48 hours when alternate intravenous access is not available or reliably established. Insertion sites:

ADULTS (>22 years): proximal humerus, proximal tibia, distal tibia

PEDIATRICS (≥12 years through 21 years old): proximal tibia, distal tibia, distal tibia, distal femur

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)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

{3}------------------------------------------------

Image /page/3/Picture/0 description: The image shows the logo for Arrow International. The word "ARROW" is in large, white, sans-serif font, with the "A" and "W" having extended serifs. Below "ARROW" is the word "INTERNATIONAL" in a smaller, white, sans-serif font. The background is a solid blue color.

K180395 510(k) SUMMARY

EZ-IO Intraosseous Vascular Access System

1. Submitter Information

Name:	Arrow International, Inc. (subsidiary of Teleflex Inc.)
Address:	2400 Bernville RoadReading, PA 19605-9607
Telephone Number:	(610) 378-0131
Contact Person:	Frank Pelc
Telephone Number:	(610) 478-3107
Fax Number:	(610) 478-3179
Email:	frank.pelc@teleflex.com

Date Prepared: November 9, 2018

2. Device Name

Device Trade Name:	EZ-IO Intraosseous Vascular Access System
Common Name:	Intraosseous Infusion System
Classification Name:	Needle, Hypodermic, Single Lumen
	(Class II, FMI, 21 CFR 880. 5570)

3. Predicate Device

EZ-IO Intraosseous Infusion System (K141117)

4. Device Description

{4}------------------------------------------------

to keep the needle securely anchored to the patient; and is recommended in the Instructions for use (IFU).

The following is a summary of the device operation: Clinicians locate anatomical landmarks and clean the insertion site. Using the cordless driver with needle set attached, the needle set is pressed through the soft tissue to the outer cortex of the bone. Depth markers on the catheter must be visible prior to powering the driver to ensure adequate needle length for proper placement within the medullary space. Clinicians then squeeze the driver trigger and apply moderate, steady pressure. The trigger is released when a sudden "give" or "pop" is felt, which indicates entry into the medullary space; the needle set will not always be inserted to the hub. After insertion of the needle set, the driver unit is detached from the needle set, leaving the stylet and catheter firmly seated in the bone. The stylet is then separated and removed from the catheter by turning the stylet hub counterclockwise leaving the catheter with a standard Luer lock hub securely seated in the bone. The catheter Luer lock permits attachment of the provided EZ-Connect, standard syringes or other IV tubing for administration of medications and fluids.

5. Indications for Use

Use of the device may be extended for up to 48 hours when alternate intravenous access is not available or reliably established. Insertion sites: ADULTS (≥22 years): proximal humerus, proximal tibia, distal tibia PEDIATRICS (≥12 years through 21 years old): proximal humerus, proximal tibia, distal tibia, distal femur

6. Technological Characteristics and Substantial Equivalence

The proposed device is identical to the predicate device described in K141117 in design, materials of construction, functional performance, principles of operation, manufacturing, packaging, sterilization, and shelf life. They are also identical in target population and environment of use.

The only change is the labeled indications to allow for up to 48 hour use when alternate intravenous access is not available or reliably established.

The table below provides a comparison of the proposed and predicate devices.

{5}------------------------------------------------

	Proposed DeviceEZ-IO Intraosseous VascularAccess System(Expansion of indication forup to 48 Hour Use)	Predicate Device - K141117EZ-IO Intraosseous Infusion System
Indications for Use	For intraosseous access anytime inwhich vascular access is difficult toobtain in emergent, urgent, or medicallynecessary cases for up to 24 hours.Insertion sites:ADULTS (≥22 years old): proximalhumerus, proximal tibia, distal tibiaPEDIATRICS (≤21 years old): proximalhumerus, proximal tibia, distal tibia,distal femurUse of the device may be extended forup to 48 hours when alternateintravenous access is not available orreliably established. Insertion sites:ADULTS (≥22 years): proximal humerus,proximal tibia, distal tibiaPEDIATRICS (≥12 years through 21 yearsold): proximal humerus, proximal tibia,distal tibia, distal femur	The EZ-IO Intraosseous InfusionSystem provides intraosseous accessin the proximal tibia, distal tibia andhumeral head (proximal humerus) ofadult and pediatric patients, and thedistal femur in pediatric patientswhen intravenous access is difficultor impossible to obtain in emergent,urgent, or medically necessary casesfor up to 24 hours.
Contraindications	• Fracture in target bone.• Previous, significant orthopedicprocedure at the site, prostheticlimb or joint.• IO access (or attempted IOaccess) in targeted bone withinpast 48 hours.• Infection at the area of insertion.• Excessive tissue (severe obesity)and/or absence of adequateanatomical landmarks.	• Fracture in target bone• Previous significant orthopedicprocedure at the site (IO accessin past 48 hours, prosthetic limbor joint)• Infection at area of insertion• Excessive tissue and/or absenceof adequate anatomicallandmarks.
Target Population	SAME: Adult and pediatric patientswho are in need of vascular access.	Adult and pediatric patients who arein need of vascular access.
Where Used	SAME: Pre-hospital, In hospital, Acutecare	Pre-hospital, In hospital, Acute care
Anatomical Sites Used	SAME:Proximal Tibia	Proximal Tibia
	Proposed Device	Predicate Device - K141117
	EZ-IO Intraosseous VascularAccess System	EZ-IO Intraosseous Infusion System
	(Expansion of indication forup to 48 Hour Use)
	Humeral Head (proximalhumerus)	Humeral Head (proximalhumerus)
	Distal Tibia	Distal Tibia
	Distal Femur in pediatricpopulation	Distal Femur in pediatricpopulation
Needle/Cannula Design	SAME:Sterile, single use	Sterile, single use
	Hubs: polycarbonate and color additive	Hubs: polycarbonate and color additive
	Stylet/catheter: Stainless Steel	Stylet/catheter: Stainless Steel
	Faceted tip	Faceted tip
	Standard Luer connection 15 mm; 25mm; 45 mm	Standard Luer connection 15 mm; 25mm; 45 mm
	15 gauge (0.071", 1.8 mm)	15 gauge (0.071", 1.8 mm)
	Needle Cover: Polypropylene	Needle Cover: Polypropylene
Needle Set Guidelines	SAME:Available Needle Sets:15 mm: 3-39 kg25 mm: 3 kg or over45 mm : 40 kg or over	Available Needle Sets:15 mm: 3-39 kg25 mm: 3 kg or over45 mm : 40 kg or over
Depth Control	SAME:Positioning marks at 5 cm and 10 cmapart to provide visual referencepoints	Positioning marks at 5 cm and 10 cmapart to provide visual referencepoints
	Tactile feedback for change ofpressure	Tactile feedback for change ofpressure
Sterile single usecomponents/accessories	SAME:EZ-IO Needle SetsEZ-Connect Extension SetEZ-IO Patient WristbandNeedleVISE 1-port Sharps BlockEZ-Stabilizer Dressing	EZ-IO Needle SetsEZ-Connect Extension SetEZ-IO Patient WristbandNeedleVISE 1-port Sharps BlockEZ-Stabilizer Dressing
Sterility of single usecomponents/accessories	SAME: Ethylene Oxide	Ethylene Oxide
Shelf life of single use	SAME: 4 Years	4 Years
	Proposed Device	Predicate Device - K141117
	EZ-IO Intraosseous VascularAccess System(Expansion of indication forup to 48 Hour Use)	EZ-IO Intraosseous Infusion System
components/accessories
Biocompatibility	Biocompatible materials used (per ISO10993-1 prolonged contact duration).	Biocompatible materials used (per ISO10993-1 limited contact duration).

{6}------------------------------------------------

{7}------------------------------------------------

{8}------------------------------------------------

7. Nonclinical Testing

Biocompatibility testing for prolonged (>24 hours to ≤ 30 days) contact duration was completed on the proposed device materials in accordance with the FDA Guidance "Use of International Standard ISO 10993-1, "Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process" (issue date June 16, 2016) as appropriate for the contact type for each component:

. EZ-IO Needle Set: External communicating device; blood path indirect and tissue/bone/dentin contact, prolonged duration.
. EZ-Connect extension tubing set: External communicating device; blood path, indirect contact; prolonged duration.
. EZ-Stabilizer dressing: Surface device, intact skin contact; prolonged duration.

Biocompatibility of the materials of construction were previously reviewed in K141117 for limited duration (≤24 hours). The materials have not changed for the proposed device, but the contact duration, for the purpose of biocompatibility testing is changed to prolonged (>24 hours to ≤30 days) contact to account for the 48 hour dwell time. Testing addressing the ISO 10993-1 requirements for prolonged contact was conducted.

The performance testing of the predicate K141117 remains applicable to the proposed device. Performance requirements for the EZ-IO components relate to physical parameters such as tensile strength, torsion strength, bend strength, leak and burst pressure. These performance tests are not dependent upon factors of time or number of occurrences of an action or event. The device materials are unchanged and there is no additional risk or change to the materials' physical properties when subjected to 48 hour use compared to 24 hour use. Therefore, the information supporting performance of the device for up to 24 hour use in the predicate K141117 also applies to the proposed device. No new performance testing is required.

8. Clinical Data

A US single-site, prospective clinical IDE trial was performed to study use of the EZ-IO Intraosseous Vascular Access System for up to 48 hours indwelling time; the primary study endpoint was the absence of serious complications resulting from intraosseous (IO) catheter retention over a 48-hour period.

The study participants were either healthy or health-compromised adult volunteers with mild to moderate renal disease (NHANES Stage 1 to 3) and/or controlled diabetes (HbA1C ≤8). There were 121 evaluable subjects enrolled in the study; 79 were in the healthy subset, 39 were in the diabetes only subset, and 3 in the diabetes with renal insufficiency subset. Placement site was randomized with 61 proximal tibia and 60 proximal humerus insertions. Subjects were infused with 0.9% sodium chloride at a rate

{9}------------------------------------------------

of 100 mL/hr for the initial eight hours then a rate of 30 ml/hr. Pain control during the study was managed with a slow infusion of preservative and epinephrine-free lidocaine before initial flush, and analgesics. An IO aspirate culture was obtained before catheter removal, followed by an x-ray of the site. After 30 days, subjects returned for examination and repeat x-ray.

Three subjects were discontinued from the 48-hour procedural portion of the study: one with pain and left arm swelling after 10 hours; and two adverse events (AE) between 30-32 hours, swelling secondary to extravasation; and leaking at the hub of the device and accidental dislodgement. Four subjects withdrew following IO needle insertion before 48 hours due to inability to control pain or pain and fever.

Study follow-up was performed at 30 days. There were no serious AEs or complications, or unexpected AEs reported for any of the subjects randomized into the study. AEs determined to be related and/or possibly related to the device included: pain, swelling; elevated white blood cell counts and neutrophils; skin demarcation/ scar; fever; local skin allergy; and vasovagal response during initial insertion.

Under the conditions of the study, IO access can be maintained for 48 hours without significant risk of serious adverse events. Pain associated with catheter dwell and infusion can be well-managed, and a slow infusion of 30 mL/hour maintains patency for 48 hours.

Based on limitations of the study as compared to the expected actual use of the device during the 24-48-hour period as well as the limitations of clinical literature regarding IO use for 24-48 hours, the Indications for Use statement restricts the use of the device beyond 24 hours (and only up to 48 hours) to when alternate intravenous access is not available or readily established and only in patients ≥12 years of age. In addition, specific "CAUTION" statements were added to the Instructions for Use to inform clinicians that patients with comorbidities may have an increased risk for complications, and that the risks may increase as the device remains in place a longer period of time. Other "CAUTION" statements state the importance of frequent monitoring of the intraosseous site and infusion.

9. Conclusions

The EZ-IO Intraosseous Vascular Access System is substantially equivalent to the predicate device.

Regulation Number and Section

§ 880.5570 Hypodermic single lumen needle.

(a)
Identification. A hypodermic single lumen needle is a device intended to inject fluids into, or withdraw fluids from, parts of the body below the surface of the skin. The device consists of a metal tube that is sharpened at one end and at the other end joined to a female connector (hub) designed to mate with a male connector (nozzle) of a piston syringe or an intravascular administration set.(b)
Classification. Class II (performance standards).