The i-STAT lactate test is useful for (1) the diagnosis and treatment of lactic acidosis in conjunction with measurements of blood actifbase status, (2) monitoring tissue hypoxia and strenuous physical exertion, and (3) diagnosis of hyperlactatemia.

Device Description

The i-STAT lactate test is contained in a single use cartridge. In use, two to three drops of blood are placed in the cartridge as described below. The cartridge is inserted into the thermally controlled i-STAT Model 200 Portable Clinical Analyzer and all analytical steps are performed automatically. Patient and user information may be entered into the analyzer via a keypad during the automated analysis cycle. The i-STAT System is an in vitro analytical system comprising a network of one or more portable clinical analyzers designed to be used at the point of patient care. The analyzers employ single-use test cartridges containing biosensor chips to perform diagnostic tests on whole blood. The system further comprises an infrared communications link from the analyzers to auxiliary information management devices such as printers, personal computers, laboratory information systems and hospital information systems. The i-STAT analyzers, as part of the i-STAT System, are intended for use by health-care professionals for the in vitro analysis of arterial, venous or capillary whole blood at the point of patient care. Tests with the i-STAT System are carried out in test cartridge. It houses the sensor array, aqueous calibrator, fluid channels, and a waste reservoir). Electrochemical sensors on biosensor chips are housed in cartridges in a variety of sensor test configurations appropriate to clinical needs. Test panels are identified by name and color code on the cartridge label. In addition, test panel configurations are encoded into the cartridge in a mechanical feature in the cartridge housing. An array of electrical pins in the analyzer recognizes the mechanical feature and automatically identifies the cartridge test panel type. In use, whole blood is introduced into the sample well of the cartridge at the sample port. After closure, the cartridge is inserted into the cartridge door of the analyzer. Insertion of the cartridge initiates a precisely controlled and monitored sequence of steps performed by the instrument without user intervention. These steps are: - Electrical contact is made between the analyzer electronic input circuits and the . The analyzer identifies the type of cartridge being used and the tests cartridge. contained in the cartridge. - Calibrator is positioned over the sensors. Each lactate test is calibrated with calibrator . fluid that contains a pre-determined amount of lactic acid. - Calibration measurements are made as the sensors generate signals mathematically . related to analytic concentrations. In the i-STAT lactate test the concentration of lactate is directly related to the appearance of hydrogen peroxide (measured by amperometrically) generated by lactic acid oxidase acting on lactic acid in the calibrator fluid or in the blood sample. - . Blood sample washes out the calibrator with the aid of an air bubble between the two. - . Blood sample is positioned over the sensors. - . Calculations of sample concentrations are performed and displayed. The displayed results are also stored in the analyzer memory and can be transmitted by infrared communication link to commercially available computers or printers. The lactate test cartridge is assembled from plastic components that provide the conduits for fluid handling and house the sensor chips. In the cartridge containing the test for lactate, the sensors comprise a patterned metallic layer, supported on a silicon/silicon dioxide substrate, coated with a thin membrane containing lactic acid oxidase.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study details for the i-STAT Lactate test, based on the provided 510(k) summary:

Acceptance Criteria and Device Performance for i-STAT Lactate Test

1. Table of Acceptance Criteria and Reported Device Performance

The provided document describes a predicate device comparison study rather than explicitly stating acceptance criteria in advance. However, the "conclusions" section confirms that the device meets established standards by being substantially equivalent to the predicate. The performance comparisons provided serve as the basis for this determination.

Acceptance Criterion (Inferred from Predicate Equivalence)	Reported i-STAT Lactate Performance
Linearity Range	0.3 to 20 mmol/L
Imprecision (Normal Range)	0.81 ± 0.03 mmol/L [3.3% c.v.]
Imprecision (Abnormal Range)	6.35 ± 0.08 mmol/L [1.2% c.v.]
Correlation to Predicate Device (Blood)	Slope: 0.993, Intercept: 0.036, r: 0.998 (N=46)
Correlation to Standard Lab Instrument (Plasma)	Slope: 1.118, Intercept: -0.052, r: 0.998 (N=47)
Medical Allowable Error	Within standards accepted by the medical community (based on CAP Surveys)

2. Sample Size and Data Provenance for Test Set

Sample Size (Test Set):
- Clinical Comparison - Blood: 46 patient samples
- Clinical Comparison - Plasma: 47 patient samples
Data Provenance: The document does not explicitly state the country of origin or whether the data was retrospective or prospective. It refers to "patient samples" and "sites" (Site 1 for blood comparison, Site 2 for plasma comparison), implying clinical data rather than simulated. Without further detail, it's difficult to categorize definitively.

3. Number of Experts and Qualifications for Ground Truth

The document does not mention the use of experts to establish ground truth for the clinical comparison. The "ground truth" was established by comparison to existing, cleared analytical devices (the predicate device and a standard laboratory instrument).

4. Adjudication Method for Test Set

No adjudication method is described. The comparison is directly between the i-STAT device and the reference devices.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No MRMC comparative effectiveness study was performed. This device is an in vitro diagnostic (IVD) for measuring a analyte; therefore, human reader improvement with AI assistance is not applicable.

6. Standalone (Algorithm Only) Performance

Yes, a standalone performance was done. The study evaluates the i-STAT Lactate test (the algorithm/device) directly against established methods without human interpretation of results influencing the primary analytical performance.

7. Type of Ground Truth Used

The ground truth for the clinical test set was established by comparison to existing, cleared analytical devices:

Predicate Device: Stat Profile® Plus Ultra/Lactic acid test (for whole blood comparison).
Standard Laboratory Instrument: (unspecified, but used for plasma comparison).

8. Sample Size for Training Set

The document does not explicitly mention a "training set" in the context of machine learning or AI. The i-STAT Lactate test is an IVD device based on biosensor technology. Its performance is characterized through:

Non-clinical studies: Calibration verification solutions (5 concentrations) and aqueous controls (N=120 for normal range, N=120 for abnormal range) were used to establish linearity and imprecision.
Clinical studies: Blood and plasma samples from patients were used for comparison.

There is no mention of a "training set" in the sense of data used to train a predictive model.

9. How Ground Truth for Training Set was Established

As there is no explicit mention of a "training set" in the context of AI/ML, this question is not directly applicable. For the non-clinical studies (linearity, imprecision), the ground truth was established by using known concentrations of lactic acid in calibration verification solutions and aqueous controls.

Summary

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K982071
1

i-STAT Corporation

JUN 2 9 1998

510(k) SUMMARY

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

1982071

The assigned 510(k) number is:

Summary Prepared on:

Submitted by:

i-STAT Corporation 303 A College Road East Princeton, New Jersey 08550 Phone: 609-243-9300 Fax: 609-243-9311

Contact:

Paul VanDerWerf, Ph.D., Vice President Regulatory Affairs and Quality Assurance

Establishment Registration Number: 2245578

Identification of the Device:

Device Name:	Lactic Acid
Proprietary/Trade Name:	i-STAT® Lactate test
Common Name:	Lactic Acid, Lactate
Classification Name:	Lactic acid test system.
Device Classification:	I
Regulation Number:	21 CFR § 862.1450
Panel:	Clinical Chemistry and Clinical Toxicology
Product Code:	KHP

Identification of the Predicate Device:

Device Name:

Stat Profile® Plus Ultra/Lactic acid test.

Intended use of the Device:

The Lactate test, as part of the i-STAT System, is intended for the in vitro measurement of the concentration of (lactate) lactic acid in fresh, arterial, venous or capillary whole blood. Blood samples may be untreated or treated with lithium heparin.

Description of the Device:

® i-STAT is a registered trademark of i-STAT Corporation, Princeton, NJ.

® Stat Profile is a registered trademark of Nova Biomedical, Waltham, MA.

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The i-STAT System is an in vitro analytical system comprising a network of one or more portable clinical analyzers designed to be used at the point of patient care. The analyzers employ single-use test cartridges containing biosensor chips to perform diagnostic tests on whole blood. The system further comprises an infrared communications link from the analyzers to auxiliary information management devices such as printers, personal computers, laboratory information systems and hospital information systems.

The i-STAT analyzers, as part of the i-STAT System, are intended for use by health-care professionals for the in vitro analysis of arterial, venous or capillary whole blood at the point of patient care.

Tests with the i-STAT System are carried out in test cartridge. It houses the sensor array, aqueous calibrator, fluid channels, and a waste reservoir). Electrochemical sensors on biosensor chips are housed in cartridges in a variety of sensor test configurations appropriate to clinical needs.

Test panels are identified by name and color code on the cartridge label. In addition, test panel configurations are encoded into the cartridge in a mechanical feature in the cartridge housing. An array of electrical pins in the analyzer recognizes the mechanical feature and automatically identifies the cartridge test panel type.

In use, whole blood is introduced into the sample well of the cartridge at the sample port. After closure, the cartridge is inserted into the cartridge door of the analyzer. Insertion of the cartridge initiates a precisely controlled and monitored sequence of steps performed by the instrument without user intervention. These steps are:

Electrical contact is made between the analyzer electronic input circuits and the . The analyzer identifies the type of cartridge being used and the tests cartridge. contained in the cartridge.
Calibrator is positioned over the sensors. Each lactate test is calibrated with calibrator . fluid that contains a pre-determined amount of lactic acid.
Calibration measurements are made as the sensors generate signals mathematically . related to analytic concentrations. In the i-STAT lactate test the concentration of lactate is directly related to the appearance of hydrogen peroxide (measured by amperometrically) generated by lactic acid oxidase acting on lactic acid in the calibrator fluid or in the blood sample.
. Blood sample washes out the calibrator with the aid of an air bubble between the two.
. Blood sample is positioned over the sensors.
. Calculations of sample concentrations are performed and displayed.

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The displayed results are also stored in the analyzer memory and can be transmitted by infrared communication link to commercially available computers or printers.

The lactate test cartridge is assembled from plastic components that provide the conduits for fluid handling and house the sensor chips. In the cartridge containing the test for lactate, the sensors comprise a patterned metallic layer, supported on a silicon/silicon dioxide substrate, coated with a thin membrane containing lactic acid oxidase.

Comparison of the Technological Features to the Predicate Device:

The following technological differences between the i-STAT lactate and the Nova test are noteworthy.

1. The Nova lactate has to be calibrated daily with a two-point calibration. The i-STAT lactate is automatically calibrated during each sample analysis cycle.
1. The Nova analyzer is a much larger multi-channel analyzer while the i-STAT system is a handheld device.
1. The Nova lactate sensor is a multiple-use analytical system and is therefore prone to contamination and carry-over while the i-STAT sensor is single use and free of such interferences.

Summary of Non-Clinical Test Performance in Support of Substantial Equivalence:

Studies using calibration verification solutions at five concentrations of lactic acid, has established that the i-STAT Lactate test is linear over the claimed reportable range of 0.3 to 20 mmol/L. The reportable range of the Nova Stat Profile Plus Ultra lactate test is also 0.3 to 20 mmol/L.

Imprecision of the i-STAT Lactate test was established over 20 days using duplicate aqueous controls. In the normal range the average (N=120) was 0.81 ± 0.03 mmol/L [3.3% c.v.]. In the abnormal range (N=120) was 6.35 ± 0.08 mmol/L [1.2% c.v.]. Within run precision (using control materials) for the Stat Profile Plus Ultra (N = 18-25) is reported to be 0.8 ± 0.05 mmol/L (6.1% c.v) in the normal range and 7.6 ± 0.19 mmol/L (c.v 2.5%) in the abnormal range.

Summary of Clinical Test Performance in Support of Substantial Equivalence:

Studies compared the i-STAT Lactate test (y) was to the predicate device (x) using blood (site 1) and to a standard laboratory instrument (x) using plasma (site 2). The methods were compared using Deming regression analysis. The results summarized in the table below indicate that the i-STAT test performance is similar to the predicate device.

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Statistic	Definition	Blood	Plasma
		Pred Device	Lab Device
N pairs	The number of patient samples	46	47
Mean	The average of the comparative method	5.92	3.25
Sx	The standard deviation of comparative method results	3.485	2.091
Syx	Standard error of the estimate of the regression of y on x	0.154	0.146
Slope	Deming linear regression slope	0.993	1.118
Intercept	Deming linear regression intercept	0.036	-0.052
Range	Range of comparative method results	0.9-13.2	0.81-13.2
r	Correlation coefficient	0.998	0.998
Sxx	Pooled imprecision of x duplicates	0.125	0.027
Syy	Pooled imprecision of y duplicates	0.106	0.054

Conclusions:

Based on the non-clinical data, the new i-STAT lactate test is usable over the range of 0.3 to 20 mmol/L. Studies using controls indicate adequate precision at normal and medical decision levels. Clinical data indicates acceptable correlation to plasma and whole blood instruments. Based on data from CAP Surveys, the medically allowable error associated with the new test is within the standards accepted by the medical community. Thus, the safety and effectiveness of the new i-STAT Lactate test is established as substantially equivalent to that of a predicate device previously cleared for distribution and sale.

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Image /page/4/Picture/3 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle-like symbol with three curved lines representing wings or feathers. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular fashion around the symbol.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JUN 29 1998

Paul VanDerWerf, Ph.D. . Vice President, Regulatory Affairs and Quality Assurance i-STAT Corporation 303 College Road East Princeton, New Jersey 08540

Re : K982071 i-STAT®¹ Lactate Test Regulatory Class: I Product Code: КНР Dated: June 10, 1998 Received: June 12, 1998

Dear Dr. VanDerWerf:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to 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). 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 (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Requlations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory In addition, FDA may publish further announcements action. concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.

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Page 2

This letter will allow you to begin marketing your device as This lecter will arrow you co reget notification. The FDA described in your 510(x) premaince of your device to a legally marketed predicate device results in a classification for your marketed predicate device robated in oproceed to the market.
device and thus, permits your device to proceed to the ling device and thus, permice your device for your device on our labeling If you desire Specific advise Lodditionally 809.10 for in regulation (21 crk rares), please contact the Office of Vitro diagnoscic deviceb/, productionally, for questions on Compliance at (301) 354 4500. the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to
the regulation entitled, "Misbranding by reference for may information on your responsibilities under the Act may be Information on your responsible of Small Manufacturers Assistance obcathed from the Driver (800) 638-2041 or (301) 443-6597 or at its internet address "dsmo@fdadr.cdrh.fda.gov".

Sincerely yours,

Steven Autman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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III INDICATIONS FOR USE

510(k) Number (if known):

Device Name: Lactic Acid test.

(Please do not write below this limecontinue on another page if needed.)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use V

Over-The-Counter-Use

(Per 21 CFR 801.109)

(Optional Format 1-2-96)

Carol C. Benson / Alfred Monty

Division of Clinical Laboratory Devices 510(k) Number

Page l of I

Regulation Number and Section

§ 862.1450 Lactic acid test system.

(a)
Identification. A lactic acid test system is a device intended to measure lactic acid in whole blood and plasma. Lactic acid measurements that evaluate the acid-base status are used in the diagnosis and treatment of lactic acidosis (abnormally high acidity of the blood).(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 862.9.