K Number

Device Name

Manufacturer

I-STAT CORPORATION

Date Cleared

2006-07-21

(210 days)

Product Code

Regulation Number

Type

Panel

Reference & Predicate Devices

N/A

Predicate For

N/A

Intended Use

The i-STAT BNP test is an in vitro diagnostic test for the quantitative measurement of B-Type Natriuretic Peptide (BNP) in whole blood or plasma samples using EDTA as the anticoagulant. BNP measurements can be used as an aid in the diagnosis and assessment of the severity of congestive heart failure.

The cartridge is to be used with the i-STAT 1 Analyzer bearing the (Immuno) symbol, but not with the i-STAT Portable Clinical Analyzer or the Philips Medical Systems (formerly Agilent Technologies) Blood Analysis Module (BAM). As part of the i-STAT System, the BNP test is to be used by trained health care professionals in accordance with a facility's policies and procedures.

The i-STAT BNP Controls are assayed liquid plasma used to verify the integrity of newly received i-STAT BNP cartridges.

The i-STAT BNP Calibration Verification Controls are assayed liquid plasma used to verify the calibration of i-STAT BNP cartridges throughout the reportable range.

Device Description

The i-STAT BNP test is contained in a single-use test cartridge. In use, the user scans a bar code and then places approximately 17 uL of whole blood or plasma in the cartridge. After the cartridge is closed, it is inserted into the thermally controlled i-STAT 1 Analyzer, and all analytical steps are performed automatically. Patient and use information may be entered into the analyzer via a keypad during the automated analysis cycle.

As the analyzer performs several quality checks and controls the temperature of the sensors via resistive heating to the underside of the sensor chips, the substrate/wash fluid is released into a conduit within the cartridge and a metered volume of the sample over the sensor chips. The enzyme-linked antibody conjugate dissolves into the sample incubates for a controlled time. The sample is then pushed into a waste chamber and the substrate/wash solution is brought over the sensors. The alkaline phosphatase captured on the BNP sensor cleaves the substrate present in the substrate/wash fluid, giving rise to an amperometric signal that is measured.

The i-STAT BNP Controls are supplied in three levels packaged as six vials of one level per box with each vial containing 1 mL of control material. The three levels are in frozen liquid form, require no reconstitution or dilution, and are each comprised of a different level of BNP, a chemical synthetic peptide, prepared in human EDTA plasma and preserved with sodium azide. The first level of BNP is set at a typical diagnostic cutoff level while the second and third are set at higher levels spanning the range of the test. The BNP value will be provided in the value assignment sheet for each level.

The i-STAT BNP Calibration Verification Control Set is packaged as a tri-level set comprised of two vials of each of three levels per box. The three levels in the BNP Calibration Verification Control Set are exactly the same materials as those used in the Level 1, Level 2, and Level 3 control products. The only difference between this product and the i-STAT BNP Controls is the number of vials and the number of levels that are packaged together.

AI/ML Overview

The provided 510(k) summary focuses on the i-STAT BNP Test and its associated controls, asserting its substantial equivalence to a predicate device, the Biosite Triage BNP test. This document describes an immunoassay, not an AI-powered device, so several of the requested categories (e.g., number of experts, adjudication method, MRMC study, training set) are not applicable. I will provide information for the relevant categories based on the provided text.

1. Table of Acceptance Criteria and Reported Device Performance

For an immunoassay like the i-STAT BNP test, "acceptance criteria" are typically demonstrated through various performance characteristics compared to a predicate device or established analytical standards. The study demonstrates the clinical performance through a method comparison study, establishing correlation with a reference method.

Performance Characteristic	Acceptance Criteria (Implicit for Substantial Equivalence)	Reported Device Performance (i-STAT BNP Test)
Method Comparison (vs. Abbott ARCHITECT)	Acceptable correlation (e.g., high correlation coefficient, slope near 1, intercept near 0)	N: 433 samples (312 where [BNP] < 400 pg/mL) Mean (reference): 482.1 (51.9 for low BNP) Range (reference): 5.0 - 4797.7 (5.0 - 400.0 for low BNP) Slope: 0.971 (1.13 for low BNP) Intercept: -14.4 (-7.3 for low BNP) Correlation (r): 0.972 (0.964 for low BNP) Sy.x: 198.0 (25.7 for low BNP)
Hematocrit Insensitivity	Insensitive to hematocrit levels within a specified range	Insensitive to hematocrit levels from 0 to 60 %PCV
Interference (Peptides)	Not significantly influenced by related peptides	Not significantly influenced by NT-pro-BNP, ANP or CNP at 1000 pg/mL or 20,000 pg/mL
Interference (Medications)	No significant interference effects from common medications	No significant interference effects from common medications (particularly cardiovascular drugs)
Lower Limit of Detection (LLD)	Comparable to predicate device or clinically acceptable	15 pg/mL (Predicate: 5.0 pg/mL for Triage BNP)
Imprecision (Controls)	Acceptable %CV for specified control levels	Level 1 Control: 11.1% CV at 126 pg/mL Level 2 Control: 8.1% CV at 1551 pg/mL Level 3 Control: 9.8% CV at 3337 pg/mL

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

Sample Size: 433 patient samples were used for the method comparison study. A subset of 312 samples had BNP concentrations less than 400 pg/mL.
Data Provenance: The study was conducted "in-house" and used EDTA-anticoagulated samples. The country of origin is not specified, but the submission is to the U.S. FDA by an i-STAT Corporation based in East Windsor, NJ. The data is retrospective in the sense that existing patient samples were analyzed on both systems.

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

This is not applicable as this is an immunoassay, not a device requiring expert interpretation of images or other data. The "ground truth" for the method comparison study is the measurement obtained from the comparative method (Abbott ARCHITECT).

4. Adjudication Method for the Test Set

This is not applicable as this is an immunoassay. The comparison is between two quantitative measurement devices.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

This is not applicable as this is an immunoassay device, not one involving human readers interpreting outputs.

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

This is a standalone diagnostic test. The performance reported is that of the i-STAT BNP test system (cartridge and analyzer) itself. There is no "human-in-the-loop" performance in the sense of a human interpreting an algorithm's output. The human operator performs standard lab technician tasks like sample loading.

7. The Type of Ground Truth Used

The ground truth for the method comparison study was the quantitative measurement of BNP obtained from the Abbott ARCHITECT system. This refers to a laboratory-based, established clinical diagnostic method.

8. The Sample Size for the Training Set

This is not applicable. For an immunoassay, there isn't a "training set" in the machine learning sense. The device is developed and validated based on chemical and biological principles. The "in-house studies" mentioned for imprecision and interference would involve experimental runs, not a training set for an algorithm.

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

This is not applicable for the reasons stated in point 8.

Summary

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K053597

510(k) Summary

This summary of the 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1900 and CFR 807.92.

The assigned 510(k) number is:

Summary prepared on: December 9, 2005

Submitted by:

i-STAT Corporation 104 Windsor Center Drive E. Windsor, NJ 08520 Phone: 609-443-9300 FAX: 609-443-9310

Contact:

Sue Kent - Manager, Clinical Affairs i-STAT Corporation 104 Windsor Center Drive East Windsor, NJ 08520 Phone: 609-469-0250 Fax: 609-443-9310 Email: sue.kent@i-stat.com

Establishment Registration Number: 2245578

ldentification of Device:

Test:

Device Name: i-STAT® BNP Test Proprietary/Trade Name: i-STAT® BNP Test Common Name: BNP, B-Type Natriuretic Peptide Device Classification: II Regulation Number: CFR§ 862.1117 Panel: B-Type Natriuretic Peptide Test System Product Code: NBC

Controls/calibration verification controls:

Device Name: i-STAT® BNP Control Level 1 i-STAT® BNP Control Level 2 i-STAT® BNP Control Level 3 i-STAT® BNP Calibration Verification Control Set Proprietary/Trade Name: i-STAT® BNP Control Level 1 i-STAT® BNP Control Level 2 i-STAT® BNP Control Level 3 i-STAT® BNP Calibration Verification Control Set Common Name: BNP controls, BNP calibration verification controls Device Classification: I Regulation Number: 21 CFR§ 862.1660 Panel: Single (Specified) Analyte Controls (Assayed and Unassayed)

Product Code: JJX

Identification of the Predicate Device: Test:

Device Name: BNP test for use on the Biosite Triage® Meter.

Controls/calibration verification controls:

Device Name: Triage® BNP Calibration Verification Controls

JUL 2 1 2006

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Intended Use of the Device: Test:

The i-STAT BNP test is an in vitro diagnostic test for the quantitative measurement of B-twpe natriurelic peptide (BNP) in whole blood or plasma samples using EDTA as the anticoagulant. BNP measurements can be used as an aid in the diagnosis and assessment of the severity of congestive heart failure.

Controls:

The i-STAT BNP Controls are assayed liquid plasma used to verify the integrity of newly received i-STAT BNP cartridges.

Calibration verification controls:

The i-STAT BNP Calibration Verification Controls are assayed liguid plasma used to verify the calibration of i-STAT BNP cartridges throughout the reportable range.

Description of the Device:

Test:

The i-STAT BNP test is contained in a single-use test cartridge. In use, the user scans a bar code and then places approximately 17 u of whole blood or plasma in the cartridge. After the cartridge is closed, it is inserted into the thermally controlled i-STAT 1 Analyzer, and all analytical steps are performed automatically. Patient and use information may be entered into the analyzer via a keypad during the automated analysis cycle.

Controls:

Calibration verification controls:

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Comparison to Technological Features of the Predicate Device:

The following is a comparison of technological features of the i-STAT and Biosite Triage BNP test methods:

Characteristic	Triage BNP	I-STAT BNP
Assay methodology	Two-site ELISA	Two-site ELISA
Capture site	Heterogeneous	Heterogeneous
Capture antibodies	Monoclonal	Monoclonal
Enzyme label antibody	Monoclonal	Monoclonal
Enzyme label	Fluorescent dye	Alkaline phosphatase
Analysis sequence	Simultaneous capture/label	Simultaneous capture/label
Analysis time	15 minutes	10 minutes
Sample type	Whole blood or plasma	Whole blood or plasma
Enzyme detection	Fluorescent	Electrochemical

The similarities and differences between the i-STAT controls products and the Biosite Triage BNP control products can be seen in the table below:

Characteristics	Triage BNP CalibrationVerification Controls(predicate device)	i-STAT BNP ControlLevel 1, 2, & 3 andi-STAT BNP CalibrationVerification Control Set(new device)
Similarities
Matrix	Human Plasma	Human Plasma
Form	Frozen liquid	Frozen liquid
Analytes	BNP (assayed)	BNP (assayed)
Number of Levels	Three	Three
Differences
Opened Vial Claim	Tested same day as thaw	4 hours when stored at 2 to 8°C
Vial	Plastic vial with screw top lid	10 mL plastic vial with dropper-top
Fill volume	0.5 ml	1 ml
Storage (unopened)	≤ -20°Cuntil expiration date	≤ -18°Cuntil expiration date

Summary of Performance in Support of Substantial Equivalence:

Test:

Studies established that the i-STAT BNP test is insensitive to hematocrit levels from 0 to 60 . %PCV.
. The i-STAT BNP assay is not significantly influenced by the presence of NT-pro-BNP, ANP or CNP at 1000 pg/mL or 20,000 pg/mL.
Studies established that there are no significant interference effects on the i-STAT BNP test . from common medications, particularly those commonly prescribed to patients with cardiovascular conditions.
. Studies established that the lower limit of detection (LLD) for the i-STAT method is 15 pg/mL versus 5.0 pg/mL for the Triage BNP test.
. The imprecision of the i-STAT BNP test using plasma controls was established using in-house studies. The Level 1 Control %CV was 11.1% at 126 pg/mL; the Level 2 Control %CV was 8.1% at 1551 pg/mL, and the Level 3 Control %CV was 9.8% at 3337 pg/mL. This includes within-lot, lot-to-lot, vial-to-vial, analyzer-to-analyzer, and operator-to-operator components of the imprecision.

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Studies conducted in-house compared the results of the i-STAT BNP test to those of the BNP test on the Abbott ARCHITECT. EDTA-anticoagulated samples were analyzed on both systems. The methods were compared using Deming regression analysis. The results are summarized in the table below:

Statistic	Definition	i-STAT vs. Abbott ARCHITECT
		all samples	samples where$[BNP]$ <400 pg/mL
N	The number of patientsamples included inthe data set	433	312
Mean	The average of thecomparative methodresult over thesample population	482.1	51.9
Range	The range ofcomparative methodresults obtained overthe sample population	5.0 - 4797.7	5.0 - 400.0
Sxx	The pooled estimateof the within-samplestandard deviation ofthe comparativemethod over thesample population	38.1	7.2
Syy	The pooled estimateof the within-samplestandard deviation ofthe test method overthe sample population	97.6	11.5
Slope	The Deming slope ofthe correlation	0.971	1.13
Intercept	The Deming interceptof the correlation	-14.4	-7.3
Correlation	The correlationcoefficient determinedfrom regression	0.972	0.964
Sy.x	The standard error ofthe estimate of theregression of theregression of y (testmethod) on x(comparative method)calculated using theregular regressionslope	198.0	25.7

Controls/calibration verification controls:

The within-level vial-to-vial imprecision for all three levels of the i-STAT BNP controls was . found to range from 0.8% to 5.8% testing three lots of each control level.
. Studies demonstrated that all three levels meet the claim of 4 hours' stability after the product has been thawed.

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Conclusions:

Test:

Based on the data, the i-STAT BNP test is insensitive to hematocrit level from 0 – 60 %PCV, is not significantly influenced by the presence of related peptides, shows no significant interference effects to common drugs, and has a comparable lower limit of detection (LLD) as the Biosite Triage BNP. Studies using plasma controls indicate adequate imprecision for low, mid-range, and high results. Clinical data indicates acceptable correlation to the predicate device.

Controls/calibration verification controls:

The i-STAT BNP Controls Level 1, Level 2, and Level 3, and the i-STAT BNP Calibration Verification Control Set are substantially equivalent to the previously cleared Triage® BNP Calibration Verification Controls as indicated by the data.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/5/Picture/1 description: The image shows the logo for the U.S. Department of Health and Human Services (HHS). The logo features a stylized caduceus, a symbol often associated with medicine and healthcare, with three parallel lines forming a stylized human figure. The caduceus is encircled by the words "U.S. DEPARTMENT OF HEALTH & HUMAN SERVICES" in a circular arrangement.

Re:

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Paul VanDerWerf, Ph.D. Director, Regulatory Affairs i-STAT Corporation 104 Windsor Center Drive East Windsor, NJ 08520

JUL 2 1 2006

K053597 Trade/Device Name: i-STAT BNP test i-STAT BNP Control Level 1 i-STAT BNP Control Level 2 i-STAT BNP Control Level 3 i-STAT BNP Calibration Verification Control Set Regulation Number: 21 CFR8862.1117 Regulation Name: B-type natriuretic peptide test system Regulatory Class: Class II Product Code: NBC, JJX Dated: June 14, 2006 Received: June 15, 2006

Dear Dr. VanDerWerf

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.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR). Parts 800 to 895. 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 Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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Page 2 -

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

If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240) 276-0484. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). 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) 443-6597 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely vours.

Alberto G

Alberto Gutierrez, Ph.D. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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3 a. Indications for use

510(k) Number (if known):

K05 3597

Device Name: i-STAT BNP test

Prescription Use
(Part 21 CFR 801 Subpart D)
o

AND/OR

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

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

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Carol C. Benson
Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safet

K053597

Page 1 of

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b. Indications for use ಳು 510(k) Number (if known):

Device Names: i-STAT BNP Control Level 1 i-STAT BNP Control Level 2 i-STAT BNP Control Level 3

The i-STAT BNP Controls are assayed liquid plasma used to verify the integrity of newly received i-STAT BNP cartridges.

AND/OR Over-The-Counter Use Prescription Use (21 CFR 801 Subpart C) (Part 21 CFR 801 Subpart D) 0 (PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Carl Benson

Vision Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safe

K053597

Page 2 of 2

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3 c. Indications for use

510(k) Number (if known):

Device Name: i-STAT BNP Calibration Verification Control Set

The i-STAT BNP Calibration Verification Controls are assayed liquid plasma used to verify the calibration of i-STAT BNP cartridges throughout the reportable range.

(Prescription Use (Part 21 CFR 801 Subpart D)

AND/OR

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

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

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Carol C. Benson
Vision Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

K053597

Page 3 of 3

Regulation Number and Section

§ 862.1117 B-type natriuretic peptide test system.

(a)
Identification. The B-type natriuretic peptide (BNP) test system is an in vitro diagnostic device intended to measure BNP in whole blood and plasma. Measurements of BNP are used as an aid in the diagnosis of patients with congestive heart failure.(b)
Classification. Class II (special controls). The special control is “Class II Special Control Guidance Document for B-Type Natriuretic Peptide Premarket Notifications; Final Guidance for Industry and FDA Reviewers.”