The Ultegra Rapid Platelet Function Assay - TRAP (RPFA -TRAP) is a semi-quantitative, whole blood platelet function assay used to measure glycoprotein (GP) IIb/Illa receptor blockade in patients treated with abciximab or eptifibatide. Ultegra RPFA-TRAP results should be interpreted in conjunction with other clinical and laboratory data available to the clinician.

Device Description

The Ultegra System is a turbidimetric based optical detection system which measures platelet induced aggregation as an increase in light transmittance. The system consists of a stand-alone analyzer and disposable test cartridge with reagents based on microbead agglutination technology. The quality control system includes an electronic control and two levels of liquid control. The analyzer controls assay sequencing, establishes the assay temperature, controls the reagent-sample mixing for the required duration, determines the degree of platelet function, displays the results and status information to the user, and performs self-diagnostics. The test cartridge contains a lyophilized preparation of human fibrinogen coated beads, thrombin receptor activating peptide (iso-TRAP), buffer, and preservative. The patient sample is whole blood, which is automatically dispensed from the blood collection tube into the test cartridge by the analyzer, with no blood handling required by the user.

The Ultegra RPFA Assay is based upon the ability of activated platelets to bind fibrinogen. Fibrinogen coated microparticles agglutinate in whole blood in proportion to the number of unblocked platelet GP Ilb/Illa receptors. The rate of microbead agglutination is more rapid and reproducible if platelets are activated. Therefore the reagent iso-TRAP is incorporated into the assay to induce platelet activation without fibrin formation. As activated platelets bind and agglutinate fibrinogen coated beads, there is an increase in light transmittance which is measured by the Ultegra Analyzer. Results are reported in Platelet Aggregation Units (PAU).

AI/ML Overview

The provided document is a 510(k) summary for the Accumetrics Ultegra® System Rapid Platelet Function Assay (RPFA), focusing on its substantial equivalence to a predicate device. It primarily describes the device, its intended use, and a comparative performance study. It does not explicitly state "acceptance criteria" as typical clinical trial endpoints with specific thresholds (e.g., sensitivity > X%, specificity > Y%). Instead, the study's goal was to demonstrate "substantial equivalence" to a predicate device based on correlation and visual overlap of inhibition curves.

Here's an attempt to extract and interpret the requested information based on the provided text, acknowledging that some specific criteria (like numerical acceptance thresholds) are not explicitly stated.

Acceptance Criteria and Device Performance Study for Accumetrics Ultegra® System RPFA

1. Table of Acceptance Criteria and Reported Device Performance

As explicit numerical acceptance criteria for a "new" device approval (e.g., target sensitivity, specificity) are not present in this 510(k) summary for a substantial equivalence claim, the acceptance was based on demonstrating correlation and similar performance to the predicate device.

Aspect of Performance	Acceptance Criteria (Implicit from Substantial Equivalence Claim)	Reported Device Performance (Ultegra RPFA-TRAP vs. CHRONO-LOG Platelet Aggregometer)
Correlation with Predicate Device (Abciximab treated patients)	Strong correlation (e.g., correlation coefficient approaching 1) and linear relationship with the predicate device.	Deming (orthogonal) Regression: - Slope: 2.91 - Intercept: -48.58 - Correlation (r): 0.89
Time Course of Platelet Inhibition (Abciximab treated patients)	Visual overlap and similar trends in platelet inhibition over time compared to the predicate device and an independent receptor blockade assay (RBA).	Figure 1 (description): Shows overlap in time course of platelet inhibition for RPFA, AGG (CHRONO-LOG), and RBA.
Time Course of Platelet Inhibition (Eptifibatide treated patients)	Visual overlap and similar trends in platelet inhibition over time compared to the predicate device and an independent PAC1 Flow Cytometric Assay.	Figure 2 (description): Shows overlap in time course of platelet inhibition for RPFA, Agg (CHRONO-LOG), and PAC1.
Claim of Substantial Equivalence	Performance characteristics demonstrate that the new device is "substantially equivalent" to the predicate device.	"The Ultegra RPFA-TRAP performance was compared with the performance of the CHRONO-LOG Platelet Aggregometry in multi-center clinical trials... The results of the multi-center clinical studies demonstrate that the performance of the Ultegra RPFA-TRAP is substantially equivalent to that of the predicate device, CHRONO-LOG platelet aggregometer."

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

Sample Size (Test Set):
- Abciximab treated patients: 120 patients
- Eptifibatide treated patients: Number not explicitly stated, but "samples were obtained... from patients treated with eptifibatide."
Data Provenance:
- Country of Origin: Not explicitly stated, but clinical trials were "multi-center," indicating multiple locations. Given the 510(k) submission to the FDA, it is highly likely the studies were conducted in the USA.
- Retrospective or Prospective: The description "Multi-center clinical trials were designed to study GP IIb/IIa receptor blockade in patients undergoing percutaneous coronary intervention and receiving abciximab or eptifibatide. Samples were obtained... at three time points: 1) Baseline... 2) During... and 2) Post..." strongly suggests a prospective collection of data during the course of patient treatment.

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

This study relies on a comparative approach against a predicate device (CHRONO-LOG Platelet Aggregometer) and other established assays (RBA, PAC1 Flow Cytometric Assay), rather than establishing "ground truth" through expert consensus on individual case interpretations. The performance of these comparator methods is the standard against which the Ultegra RPFA-TRAP is measured. Therefore, information on the number and qualifications of experts for establishing ground truth in the traditional sense is not applicable or provided.

4. Adjudication Method for the Test Set

Not applicable. The study compares the device's measurements against those of established laboratory methods, not against expert interpretation of images or clinical outcomes requiring adjudication.

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

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This study is for an in-vitro diagnostic device measuring a physiological parameter, not for an imaging device requiring human reader interpretation. The comparison is between the new device and existing laboratory tests for platelet function.

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

Yes, the performance study describes the standalone performance of the Ultegra RPFA-TRAP system "assay." The system performs the measurement and reports results (Platelet Aggregation Units) without human interpretation as part of its core function, akin to other laboratory assays. The "correlation" and "time course of inhibition" figures represent this standalone output compared to other standalone laboratory tests.

7. The Type of Ground Truth Used

The "ground truth" in this context is the measurement obtained by established comparator methods for platelet function inhibition. Specifically:

CHRONO-LOG Platelet Aggregometer: A predicate device commonly used for measuring platelet aggregation.
Receptor Blockade Assay (RBA): Measures the percentage of blocked GP IIb/IIIa receptors.
PAC1 Flow Cytometric Assay: Another method for assessing platelet inhibition.

These methods, rather than clinical outcomes or pathology, serve as the reference for validating the new device's measurements.

8. The Sample Size for the Training Set

The document does not explicitly mention a separate "training set" or its sample size. This is a 510(k) submission focused on clinical performance for demonstrating substantial equivalence. For algorithmic devices, training data is often distinct from validation data, but this document does not distinguish such sets for the Ultegra RPFA. The assay itself consists of reagents and an analyzer, implying a development and optimization process (which would involve internal testing/training) rather than an explicit "training set" for an AI algorithm.

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

Since an explicit "training set" is not detailed, the method for establishing its "ground truth" is also not provided. For an IVD device like this, the development process would involve optimizing reagent formulations and analyzer parameters to accurately measure platelet function, likely using reference methods and well-characterized samples during the development and internal validation phases. However, this is not described in the 510(k) summary as a dedicated "training set" process with ground truth establishment in the context of an AI/ML algorithm.

Summary

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Ko13596-S2

510(k) Summary

Accumetrics Ultegra® System Rapid Platelet Function Assay (RPFA)

Accumetrics 3985 Sorrento Valley Blvd. San Diego, CA 92121

October 26, 2001

For information regarding this 510(k) Summary, please contact Accumetrics, Rhonda Moe (858) 643-1600.

Device Names:

Trade Name:	Accumetrics Ultegra System Analyzer, Accumetrics UltegraSystem Rapid Platelet Function Assay (RPFA-TRAP) TestCartridges, AccumetricsUltegra System Level 1 QCUltegra System Level 2 QC
Common Name:	Accumetrics Ultegra System Analyzer, Accumetrics UltegraSystem Rapid Platelet Function Assay (RPFA-TRAP) TestCartridges, AccumetricsUltegra System Level 1 QCUltegra System Level 2 QC

Classification Name: System, Automated Platelet Aggregation

The Accumetrics Ultegra System Analyzer and Rapid Platelet Function Assay have been found to be substantially equivalent to CHRONO-LOG Corporation's Whole Blood Aggregometer (K830749) and CHRONO-PAR Reagent (K760198).

Device Description:

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reagent iso-TRAP is incorporated into the assay to induce platelet activation without fibrin formation. As activated platelets bind and agglutinate fibrinogen coated beads, there is an increase in light transmittance which is measured by the Ultegra Analyzer. Results are reported in Platelet Aggregation Units (PAU).

Intended Use:

The Ultegra Rapid Platelet Function Assay (RPFA-TRAP) is a semi-quantitative, whole blood platelet function assay used to measure glycoprotein (GP) Ilb/Illa receptor blockade in patients treated with abciximab or eptifibatide. Ultegra RPFA-TRAP results should be interpreted in conjunction with other clinical and laboratory data available to the clinician.

This indication statement is more specific than the broader statement in the labeling for the CHRONO-LOG Whole Blood Aggregometer: "…measuring platelet aggregation in whole blood or platelet rich plasma." The narrower indication of the Ultegra RPFA does not raise issues of safety or effectiveness because the CHRONO-LOG aggregometer is commonly used to measure inhibition of platelet activity in patients treated with abciximab or eptifibatide.

Description of Device Modification:

Reagent formulations for the currently marketed RPFA Level 1 and Level 2 QC Controls have been modified to react more closely to the Ilb/IIIa binding site of activated platelets. The blue latex reagent in the Level 1 Control has been replaced with a carbon-sol reagent. Human thrombin in the Level 2 Control has been replaced with a GPRPc (glycine-proline-arginine-proline-cysteine) peptide conjugated to an amino dextran. The same level of performance has been maintained with no change to the function, storage conditions or intended use of the product.

Technological Characteristics:

The Ultegra Analyzer and the CHRONO-LOG aggregometer utilize optical detection as the measurement method for platelet aggregation/agglutination. Both systems are used to determine platelet function.

Certain characteristics of the Ultegra RPFA-TRAP differ from the CHRONO-LOG. Fibrinogen-coated microbeads are used in the Ultegra RPFA-TRAP, but not the CHRONO-LOG aggregometer. The Ultegra RPFA-TRAP uses the agonist iso-TRAP, whereas the CHRONO-LOG uses several different agonists. The Ultegra RPFA-TRAP includes two levels of liguid control and the CHRONO-LOG does not.

Differences raise no new issues of safety or effectiveness, as shown by the performance characteristics of the two devices.

Performance Characteristics:

The Ultegra RPFA-TRAP performance was compared with the performance of the CHRONO-LOG Platelet Aggregometry in multi-center clinical trials.

Multi-center clinical trials were designed to study GP IIb/IIa receptor blockade in patients undergoing percutaneous coronary intervention and receiving abciximab or eptifibatide. Samples were obtained at four clinical sites from 120 patients treated with abciximab and three clinical sites from patients treated with eptifibatide. Whole blood samples were collected at three time points: 1) Baseline, prior to abciximab or

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eptifibatide administration; 2) During (post bolus administration) to evaluate the effects of the abciximab or eptifibatide bolus; and 2) Post, 24 hours post procedure or at the time the ubtilities of Samples were tested with the Ultegra RPFA-TRAP assay and the CHRONO-LOG Platelet Aggregometer.

For the aggregometry method, platelet rich plasma was prepared from the blood sample and tested in the optical model of the aggregometer, using 20 µM ADP as the agonist.

Correlation of the two methods was evaluated for patients treated with abciximab using Deming (orthogonal) regression. The results are shown in Table 1.

RegressionMethod	Deming(orthogonal)
Slope	2.91
Intercept	-48.58
Correlation (r)	0.89

In addition to Ultegra RPFA-TRAP and platelet aggregometry, clinical trial patient samples treated with abciximab were tested with a receptor blockade assay (RBA), which measures the percentage of blocked GP IIb/IIIa receptors. Figure 1 shows the time course of platelet inhibition for the three methods, as individual points and mean +/standard error, respectively, and illustrates the overlap in the three assays.

Image /page/2/Figure/5 description: The image is a bar graph that shows the mean and standard deviation of percent baseline GPIIb/IIIa receptors or aggregation as a function of time after Abciximab infusion. The x-axis shows the time after infusion, with three categories: baseline, during infusion, and post infusion. The y-axis shows the percent of baseline GPIIb/IIIa receptors or aggregation. The graph shows three different types of measurements: RBA, RPFA, and AGG.

Image /page/2/Figure/6 description: The image shows the text "Figure 1" in bold font. The text is black and is set against a white background. The text appears to be a title or label for a figure in a document.

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Clinical trial patient samples treated with eptifibatide were also evaluated. This study tested patient samples with the Ultegra RPFA-TRAP assay, platelet aggregometry and a PAC1 Flow Cytometric Assay. Figure 2 shows the time course of platelet inhibition for the three methods and illustrates the overlap in the three assays.

Image /page/3/Figure/1 description: This image is a bar graph that shows the percentage of baseline GPIIb/IIIa aggregation for PAC1, RPFA, and Agg during baseline, during infusion, and post infusion. At baseline, all three measurements are at 100%. During infusion, all three measurements are below 20%, and post infusion, all three measurements are between 20% and 40%.

Mean Percent Baseline GPIIb/IIIa Aggregation (all methods) as a function of Time after Eptifibatide Infusion

Image /page/3/Figure/3 description: The image contains the words "Figure 2" in bold font. The word "Figure" is on the first line, and the number "2" is on the second line. The text is black and the background is white.

The results of the multi-center clinical studies demonstrate that the performance of the Ultegra RPFA-TRAP is substantially equivalent to that of the predicate device, CHRONO-LOG platelet aggregometer.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized image of an eagle with three lines representing its wings and body.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

MAY 1 6 2002

Ms. Rhonda Moe Director, Regulatory and Clinical Affairs Accumetrics, Inc. 3985 Sorrento Valley Boulevard San Diego, CA 92121

K013596 Re:

K015590
Trade/Device Name: Ultegra® System Rapid Platelet Function Assay-TRAP (RPFA-TRAP) Regulation Number: 21 CFR 864.5700 Regulation Name: Whole Human Plasma or Serum Immunological Test System Regulatory Class: Class II Product Code: JOZ Dated: March 18, 2002 Received: March 19, 2002

Dear Ms. Moe:

We have reviewed your Section 510(k) premarket notification of intent to market the device we nave reviewed your becamed the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate for use suated in the May 28, 1976, the enactment date of the Medical Device Amendments, or to conniner of the ride) 2011-11-11 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 r ou may y arous 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 If your device is elaborined too arounds. 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 r that FDA has made a determination that your device complies with other requirements of the Act that I Dri has made a word regulations administered by other Federal agencies. You must or uny I vith all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); good manufacturing practice requirements as set Of R rate 007), hossystems (QS) regulation (21 CFR Part 820); and if applicable, the electronic rord in the quany by would provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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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 1 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 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/dsma/dsmamain.html".

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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INDICATIONS FOR USE STATEMENT

510(k) Number (if known): K Q 135 9 le _______________________________________________________________________________________________________________________________________

Device Name: Ultegra® System Rapid Platelet Function Assay-TRAP (RPFA -TRAP)

Indications For Use:

The Ultegra Rapid Platelet Function Assay - TRAP (RPFA -TRAP) is a semi-The Ollegra Flatolor Platelet function assay used to measure glycoprotein (GP) IIb/Illa receptor blockade in patients treated with abciximab or eptifibatide. (Or ) hbhma leooplor brookado "interpreted in conjunction with other clinical and laboratory data available to the clinician.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Sousan S. Altaie

(Division Sign-Off) Division of Clinical Laboratory Devices 510(k) Number_KAL 3596

(Optional Format 3-10-98)

Regulation Number and Section

§ 864.5700 Automated platelet aggregation system.

(a)
Identification. An automated platelet aggregation system is a device used to determine changes in platelet shape and platelet aggregation following the addition of an aggregating reagent to a platelet-rich plasma.(b)
Classification. Class II (performance standards).