The i-STAT Celite Activated Clotting Time (ACT) test cartridge is an in vitro diagnostic test used to monitor moderate- and high-level hevarin therapy through analysis of arterial and venous whole blood samples. The cartridge is to be used with the i-STAT System 200 model analyzer.

As part of the i-STAT System, the Celite ACT test cartridge is to be used by trained and certified health care professionals in accordance with a facility's policies and procedures.

The i-STAT Celite ACT test is useful for monitoring patients receiving heparin for treatment of pulmonary embolism or venous thrombosis, and for monitoring anticoagulation therapy in patients undergoing medical procedures such as catheterization, cardiac surgery, surgery, organ transplant and dialysis.

Device Description

The i-STAT Celite ACT test is contained in a single test cartridge. In use, approximately 40 microliters of fresh whole blood are placed in the cartridge as described below. The cartridge is inserted into the thermally controlled i-STAT Model 200 Portable Clinical Analytical steps are performed automatically. Patient and user information may be entered into the analyzer via a keypad during the automated analysis cycle.

In the i-STAT ACT test the endpoint is indicated by the appearance of an electroactive marker generated by the thrombin-mediated conversion of a synthetic substrate included in the reagent. Detection of the marker indicates generation of thrombin and therefore complete activation of the coagulation cascade. The reported result is calculated from the time and rate of the substrate conversion and is given in seconds. The reported result correlates to the result of a traditional ACT in which the endpoint is indicated by physical clot formation.

The ACT cartridge is assembled from plastic components that provide the conduits for fluid handling and house the sensor chips. The coagulation test is identified to the user through the name and color code on the cartridge label and by the analyzer through features integral to the cartridge.

In the ACT cartridge the sensor comprises a gold film patterned on a silicon/silicon dioxide substrate.

During the test the blood sample is mixed with reagents which are coated on the cartridge cover in a segment of the sensor channel. The reagent layer includes an activating agent, a thrombin substrate, and inert matrix components. These reagents allow activation of the coagulation cascade and detection of clot formation.

Whole blood is introduced into the sample well of the cartridge at the sample port and the cartridge is closed and inserted into the analyzer. Insertion of the cartridge initiates a controlled and monitored sequence of steps in the instrument. These are:

Electrical contact is made between the analyzer electronic input circuits and the cartridge. The analyzer identifies the type of cartridge being used and the tests contained in the cartridge.
The dry chips and sensor channel are heated to 37C.
The blood is then moved forward. Feedback from the fluid position sensor is used to allow controlled oscillation of the blood segment resulting in dissolution of the reagent layer.
Following mixing, a count up time is displayed.
During the course of testing, the position of the blood segment is actively controlled to maintain the length of the blood containing the reagent coincident with the endpoint detector.
Calculation of sample clot time is performed and displayed.

AI/ML Overview

The provided 510(k) summary describes the i-STAT Celite ACT test and its comparison to a predicate device, the Hemochron Systems Activated Clotting Time. The document focuses on demonstrating substantial equivalence, not on pre-defined acceptance criteria in the way AI/ML devices typically present them. However, we can extract performance metrics and the study design to infer the criteria being met.

Here's an analysis based on the provided text, structured to align with your request for acceptance criteria and study details:

Acceptance Criteria and Device Performance

The acceptance criteria here are implicitly derived from demonstrating substantial equivalence to the predicate device, the Hemochron Systems Activated Clotting Time. The study's goal was to show that the i-STAT Celite ACT test performs comparably to the predicate device in various clinical settings.

Acceptance Criterion (Inferred from Predicate Equivalence)	Reported Device Performance (i-STAT Celite ACT vs. Hemochron ACT)
Linearity to Heparin Concentration: Device should respond linearly to heparin across its reportable range, similar to the predicate.	Responds linearly in the range of 50 to 1000 seconds. Average sensitivity across multiple donors is 77 seconds / U/ml heparin, "equivalent to the sensitivity of the Hemochron System Activated Celite Clotting Time test."
Within-Sample Reproducibility/Precision (whole blood): Imprecision should be comparable or better than the predicate device.	5.6% within-sample reproducibility across the reportable range. (Predicate: 8.8%)
Imprecision (plasma controls - Level 1): Imprecision should be acceptable for plasma controls.	221 ± 19 seconds (8.4% C.V.). (Predicate: 6.5% for whole blood controls)
Imprecision (plasma controls - Level 2): Imprecision should be acceptable for plasma controls.	456 ± 22 seconds (4.8% C.V.). (Predicate: 5.3% for whole blood controls)
Clinical Correlation (Cardiac Catheterization/Bypass Procedures) - Sample Size (N): Adequate number of samples for comparison.	Site 1: 118; Site 2: 74; Site 3: 101
Clinical Correlation (Cardiac Catheterization/Bypass Procedures) - Correlation Coefficient: High correlation between the two methods.	Site 1: 0.949; Site 2: 0.923; Site 3: 0.949
Clinical Correlation (Cardiac Catheterization/Bypass Procedures) - Slope: Slope close to 1.0.	Site 1: 1.00; Site 2: 0.951; Site 3: 0.902
Clinical Correlation (Cardiac Catheterization/Bypass Procedures) - Intercept: Intercept close to 0.	Site 1: 0; Site 2: 25; Site 3: 24
Clinical Correlation (Cardiac Catheterization/Bypass Procedures) - Relative Standard Error of the Estimate (Syx %): Acceptable error between methods.	Site 1: 15.9%; Site 2: 15.7%; Site 3: 12.6%
Clinical Comparison (Hemodialysis/ECMO) - Mean Bias: Acceptable average bias between the methods.	Site 1: -24; Site 2: -24
Insensitivity to Interfering Factors:	Not affected by hematocrit (20-70%), fibrinogen (100-500 mg/dL), or sample temperature (15-37°C).

Note: The document does not explicitly state numerical "acceptance criteria" but presents performance data to demonstrate "substantial equivalence" to the predicate device, which is the regulatory standard for 510(k) clearance. The favorable comparisons above (e.g., better precision, high correlation) implicitly meet these unstated criteria.

Study Details:

Sample sizes used for the test set and the data provenance:
- Cardiac Catheterization and Bypass Procedures:
  - Site 1: 118 patient samples
  - Site 2: 74 patient samples
  - Site 3: 101 patient samples
- Hemodialysis and Extra-corporeal Membrane Oxygenation:
  - Site 1: 52 patient samples
  - Site 2: 14 patient samples
- Data Provenance: The studies were conducted at "three external sites" and "two sites" for different patient populations. The samples were "fresh whole blood samples" from patients undergoing the described procedures. The data is prospective in the sense that samples were collected and tested on both devices concurrently. Location (country of origin) is not explicitly stated but implies clinical sites within the same regulatory jurisdiction as the submission (likely USA).
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Not applicable in the typical sense for an AI/ML device. For this in vitro diagnostic device, "ground truth" for the clinical studies was established by the predicate device (Hemochron® Systems Activated Clotting Time). The goal was to show correlation and agreement with an existing, legally marketed device, not to establish a new gold standard. Therefore, no "experts" for ground truth adjudication are described.
Adjudication method for the test set:
- Not applicable as the "ground truth" was the measurement from the predicate device. The identical sample was tested on both the i-STAT device and the predicate device. Statistical comparisons (least squares regression, average bias) were then performed.
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:
- Not applicable. This is an in vitro diagnostic device, not an AI/ML medical imaging device that requires human reader interpretation. The device provides a quantitative measurement (Activated Clotting Time).
If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Yes, implicitly. The performance data presented (linearity, precision, clinical correlation) represents the performance of the i-STAT device itself in generating an ACT result, compared to the predicate device. The i-STAT system automatically performs the analytical steps and calculates the result, so this is a standalone performance assessment in its context.
The type of ground truth used:
- For the clinical correlation studies, the "ground truth" was effectively the measurement obtained from the predicate device (Hemochron® Systems Activated Clotting Time). The internal studies for linearity and precision used established methods for determining heparin concentration and control material values.
The sample size for the training set:
- Not applicable. This device is not an AI/ML algorithm that requires a "training set" in the conventional sense. Its underlying principles are electrochemical detection and established chemical reactions, not machine learning from a dataset. The development likely involved internal validation and calibration using various samples, but this is not generally referred to as a "training set" for such a device.
How the ground truth for the training set was established:
- Not applicable, as there is no traditional "training set" for this type of medical device. The "ground truth" for method development would be based on established analytical standards, reference methods, and gravimetric/volumetric preparations for control materials.

Summary

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Image /page/0/Picture/1 description: The image shows the logo for i-STAT Corporation. The logo is in black and white and features the text "i-STAT" in a bold, sans-serif font. Below the text "i-STAT" is the word "CORPORATION" in a smaller, sans-serif font. There is a line above the text "i-STAT" and below the word "CORPORATION".

(992571

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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: July 25, 1999

Submitted by:

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

Contact: Paul VanDerWerf, PhD Vice President, Regulatory Affairs and Quality Assurance

Establishment Registration Number: 2234478

Identification of Device:

Device Name: Activated Clotting Time Test Proprietary/Trade Name: i-STAT® Celite® ACT Common Name: ACT Classification: Activated Clotting Time Tests Device Classification: II Regulation Number: CFR § 864.7140 Panel: Hematology Product Code: JBP

Identification of the Predicate Device:

Device Name: Hemochron® Systems Activated Clotting Time

Intended Use of the Device:

As part of the i-STAT System, the Celite ACT test cartridge is to be used by trained and certified health care professionals in accordance with a facility's policies and procedures.

Description of the Device:

104 Windsor Center Drive, East Windsor, NJ 08520 Tel: 609-43-9310 Web: http://www.i-STAT.com #

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reported result correlates to the result of a traditional ACT in which the endpoint is indicated by physical clot formation.

In the ACT cartridge the sensor comprises a gold film patterned on a silicon/silicon dioxide substrate.

Electrical contact is made between the analyzer electronic input circuits and the cartridge. The . analyzer identifies the type of cartridge being used and the tests contained in the cartridge.
The dry chips and sensor channel are heated to 37C. .
The blood is then moved forward. Feedback from the fluid position sensor is used to allow . controlled oscillation of the blood segment resulting in dissolution of the reagent layer.
. Following mixing, a count up time is displayed.
During the course of testing, the position of the blood segment is actively controlled to . maintain the length of the blood containing the reagent coincident with the endpoint detector.
. Calculation of sample clot time is performed and displayed.

Comparison to Technological Features of the Predicate Device:

The following technological differences between the i-STAT and the Hemochron Systems Activated Clotting Time tests are noteworthy.

Endpoint detection in both the Hemochron and i-STAT Systems relies upon detecting the action of . thrombin, the final enzyme activated in the coagulation cascade, on a substrate within the sample. In the case of the Hemochron, thrombin converts its natural substrate, fibrin which then crosslinks and causes localized or extended clotting throughout the sample. The instrument detects clot formation as the resulting impedance of the magnet's motion through the sample. In the i-STAT test the generated thrombin converts an added substrate to a species which can be detected electrochemically. The signal for the appearance of this marker is used to assign the endpoint time. Because the traditional ACT test is not highly sensitive to fibrinogen, however, this does not cause a method-to-method bias that is a function of the fibrinogen values greater than 100 mg/dl. Below 100 mg/dl the Hemochron result may be prolonged relative to that of the i-STAT.
. The volume of blood required for the Hemochron and i-STAT tests is significantly different. The Hemochron requires either 2.0 or 0.4 ml of blood depending on the tube type where the i-STAT test requires 0.040 ml. Although such a difference does not necessarily imply systematic differences in the results of test methods, in this case it is a contributor to a between method bias that is a function of the pre-analytical temperature of the blood. The relatively long time constant for sample heating in the Hemochron results in prolongation of results with hypothermic samples.

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

. Studies using ex-vivo heparinized whole blood samples establish that the i-STAT Celite ACT test responds linearly to the heparin concentration across its reportable range of 50 to 1000 seconds. The

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average sensitivity across multiple donors is 77 seconds / U/ml heparin. This is equivalent to the sensitivity of the Hemochron System Activated Celite Clotting Time test.

. From the heparin linearity experiments it can be seen that the within-sample reproducibility of the i-STAT test is 5.6% in samples spanning the reportable range. The Hemochron Celite ACT package insert indicates imprecision of 8.8% in whole blood samples
. The imprecision of the i-STAT test in plasma controls was established using in-house and user studies. Overall the Level 1 and Level 2 Controls read 221 ± 19 seconds (8.4% C.V.) and 456 ± 22 seconds (4.8% C.V.), respectively. This includes within-lot, lot-to-lot, vial-to-vial, analyzer-to-analyzer, and operator-to-operator components of the imprecision. The total imprecision in whole blood controls reported for the Hemochron Celite ACT is 6.5% and 5.3% for Level 1 and Level 2 Controls, respectively.

Summary of Clinical Test Performance in Support of Substantial Equivalence Claims: Studies conducted at three external sites compared the results of the i-STAT Celite ACT (y) to those of the predicate device (x) for samples from cardiac catheterization and bypass procedures. The identical sample was tested on each instrument. The methods were compared using least square regression analysis. The results are summarized in the table below.

Statistic	Definition	Site 1	Site 2	Site 3
N	The number of patient samples used in thecomparison	118	74	101
Mean	The average of the comparative method resultover the sample population	272	396	371
Range	The range of comparative method resultsobtained over the sample population	887	1182	1079
Sx	The standard deviation of the comparativemethod results across the sample population	180	240	272
Slope	The least squares linear regression estimate ofthe slope	1.00	0.951	0.902
Intercept	The least squares linear regression estimate ofthe intercept	0	25	24
Correlation	The correlation coefficient calculated fromlinear regression	0.949	0.923	0.949
Syx	The standard error of the estimate of theregression of y on x	94	97	55
Syx %	The relative standard error of the estimate	15.9%	15.7%	12.6%
Sxx %	Relative within-sample imprecision of thecomparative method over the samplepopulation	9.1%	9.7%	6.7%
Syy %	Relative within-sample imprecision of the testmethod over the sample population	5.6%	4.4%	4.7%

A comparison of the i-STAT and comparative method was also performed at two sites using samples from patients undergoing hemodialysis and extra-corporeal membrane oxygenation. Because the limited range of the results precludes comparison using linear regression, the average bias of the methods was determined. The results are presented in the table below.

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Parameter	Definition	Site 1	Site 2
Number	Number of patient samples used in the comparison	52	14
Mean	The average of the comparative method result overthe sample population	189	213
Range	The range of comparative method results obtainedover the sample population	93-270	199-233
Mean bias	Average bias between the i-STAT and comparativemethod	-24	-24
$s_x$	Standard deviation of the comparative methodresults across the sample population	37	10
$s_{xx}$	Pooled imprecision of the x duplicates	16	10
$s_{yy}$	Pooled imprecision of the y duplicates	9	6
$s_{yx}$	The standard error of the estimate of the regressionof y on x	19	8

Limitations:

The i-STAT Celite ACT test is to be used with fresh venous or arterial whole blood samples. The presence of exogenously added heparin, citrate, oxalate, or EDTA will interfere with test results. Poor technique in sample collection may also compromise the results. Samples drawn from insufficiently flushed catheters or from traumatic venipunctures may be contaminated with interfering substances. Samples should be collected into plastic syringes or tubes. Collection into glass may prematurely activate coagulation resulting in accelerated clotting times.

The i-STAT ACT test uses Celite brand diatomaceous earth as the activator of the intrinsic pathway. The result may, therefore, be prolonged in the presence of aprotinin. The test is not recommended for use with patients receiving aprotinin.

Hemodilution, platelet dysfunction, factor deficiencies, and dysprothrombinemias may affect the results of this test.

The i-STAT ACT test is not affected by hematocrit in the range of 20 - 70%, fibrinogen concentration in the range from 100 - 500 mg/dL, or sample temperature from 15 - 37℃.

Conclusions:

Based on the non-clinical data the i-STAT Celite ACT test responds linearly to heparin concentration in the range from 50-1000 seconds, is insensitive to sample temperature, hematocrit, and fibrinogen. Studies using plasma controls and whole blood indicate adequate precision for normal and prolonged clot times. Clinical data indicates acceptable correlation to the predicate device.

i-STAT is a registered trademark of i-STAT Corporation, East Windsor, NJ. Celite is a registered trademark of Celite Corporation, Santa Barbara, CA. Hemochron is a registered trademark of International Technidyne Corporation, Edison, NJ.

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Image /page/4/Picture/1 description: The image shows the logo for the Department of Health & Human Services - USA. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" written around the perimeter. Inside the circle is an image of three stylized human profiles facing to the right, with a stylized bird-like shape above them.

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Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Paul VanDerWerf, Ph.D. Vice President, Regulatory Affairs and Quality Assurance i-STAT Corporation 104 Windsor Center Drive E. Windsor, New Jersey 08520

Re: K992571 Trade Name: i-STAT® Celite® ACT Regulatory Class: II Product Code: JBP Dated: December 21, 1999 Received: December 22, 1999

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 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). 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 Regulations, 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 action. In addition, FDA may publish further announcements 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 described in your 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 advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled. "Misbranding by reference to premarket notification" (21CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsma/dsmamain.html".

Sincerely yours,

Steven Butman

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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3 Indications for use

510(k) Number (if known): _ K99857)_

Device Name: Celite ACT test.

Peter E. Maklin
(Division Sign-Off)
Division of Clinical Laboratory Devices K992591

(Please do not write below this line-continue on another page if needed.)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use _____________________________________________________________________________________________________________________________________________________________

Over-The-Counter-Use__________________________________________________________________________________________________________________________________________________________

(Per 21 CFR 801.109)

(Optional Format 1-2-96)

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Regulation Number and Section

§ 864.7140 Activated whole blood clotting time tests.

(a)
Identification. An activated whole blood clotting time tests is a device, used to monitor heparin therapy for the treatment of venous thrombosis or pulmonary embolism by measuring the coagulation time of whole blood.(b)
Classification. Class II (performance standards).