The Ultegra Rapid Platelet Function Assay (RPFA) is a semi-quantitative, whole blood platelet function assay used to measure glycoprotein (GP) IIb/IIIa receptor blockade in patients treated with abciximab. Ultegra RPFA 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 citrated 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 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/IIIa 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. The analyzer is designed to measure this change in optical signal due to agglutination.

AI/ML Overview

Here's an analysis of the provided text, focusing on the acceptance criteria and the study used to demonstrate the device meets those criteria:

1. Table of Acceptance Criteria and Reported Device Performance

The text does not explicitly state pre-defined acceptance criteria in terms of specific thresholds for slope, intercept, or correlation. Instead, it presents a comparative study against a predicate device and relies on the statistical measures derived from that comparison to demonstrate substantial equivalence. Therefore, the "acceptance criteria" are implied by the results of the comparison to the predicate.

Performance Metric	Implied Acceptance Criteria (via Predicate Comparison)	Reported Device Performance (Ultegra RPFA vs. CHRONO-LOG)
Correlation (r)	High correlation with predicate (CHRONO-LOG)	0.89
Slope (Regression)	Slope demonstrating a relationship to predicate	2.91
Intercept (Regression)	Intercept demonstrating a relationship to predicate	-48.58
Qualitative Overlap	Visual overlap in time course of platelet inhibition with predicate and RBA (Reference Method)	Figure 1 (Visually demonstrates overlap of RPFA, AGG, and RBA over time)

2. Sample Sizes and Data Provenance

Test Set Sample Size:
- Patients: 120 patients
- Samples: Patients had samples taken at three time points (Baseline, During infusion, Post infusion), implying 360 total samples (120 patients * 3 time points), though this is not explicitly stated as 360 unique measurements for correlation.
Data Provenance:
- Country of Origin: Not explicitly stated, but the submission is to the US FDA, and the company is based in San Diego, California, suggesting a US-centric study.
- Retrospective or Prospective: Prospective. The study was "designed to study GP IIb/IIIa receptor blockade in patients undergoing percutaneous coronary intervention and receiving abciximab." Samples were "obtained at four clinical sites" at specific, defined time points.

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

The concept of "experts establishing ground truth" as typically seen in image or data interpretation studies is not directly applicable here. The ground truth for the device's performance is established by comparison to:

Predicate Device: CHRONO-LOG Platelet Aggregometry. This is considered the established method.
Reference Method: Receptor Binding Assay (RBA). This is presented as another objective measure of GP IIb/IIIa receptor blockade.

Therefore, no human experts were involved in subjectively interpreting images or data to create a "ground truth" for the test set. The ground truth is derived from established laboratory methods.

4. Adjudication Method

Not applicable. As described above, the ground truth is established by objective laboratory measurements from a predicate device and a reference method, not through expert review that would require adjudication.

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

No, an MRMC comparative effectiveness study was not performed. This type of study primarily applies to scenarios where human readers interpret data (e.g., medical images) and AI provides assistance. The Ultegra RPFA is an automated analytical device, not a human-in-the-loop diagnostic aid.

6. Standalone Performance Study

Yes, a standalone performance study was done for the Ultegra RPFA in comparison to a predicate device and a reference method. The "Performance Characteristics" section details this study, comparing the Ultegra RPFA's results directly against:

CHRONO-LOG Platelet Aggregometry (predicate)
Receptor Binding Assay (RBA) (a different, objective measure of the same physiological effect)

The reported correlation (r=0.89) and the visual overlap in Figure 1 demonstrate the Ultegra RPFA's standalone performance in relation to these established methods.

7. Type of Ground Truth Used

The ground truth used was based on results from a predicate device (CHRONO-LOG Platelet Aggregometry) and an objective reference method (Receptor Binding Assay - RBA). These are considered direct laboratory measurements of platelet function and receptor blockade.

8. Sample Size for the Training Set

The document does not explicitly mention a separate "training set" or its size. This likely indicates that the device's algorithms were developed and optimized internally by Accumetrics, and the described clinical study served as a validation/test set to demonstrate performance rather than a training set for machine learning models. Clinical trials of this nature in medical device submissions often focus on validation against established methods.

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

Since no separate "training set" with ground truth establishment is described, this question is not applicable based on the provided text. The development of the device likely involved internal verification and validation against known standards and laboratory results, but these details are not part of this 510(k) summary.

Summary

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0008

DEC 21 1999

510(k) Summary

Accumetrics Ultegra® System Rapid Platelet Function Assay (RPFA)

Accumetrics, Inc. 3985 Sorrento Valley Blvd. San Diego, CA 92121

December 13, 1999

For information regarding this 510(k) Summary, please contact Accumetrics, Inc., Frances E. Harrison, (619) 643-1600.

Device Names:

Trade Name: Accumetrics Ultegra System Analyzer, Accumetrics Ultegra System Rapid Platelet Function Assay (RPFA-TRAP) Test Cartridges, Accumetrics Ultegra System Level One QC, Accumetrics Ultegra System Level Two QC.
Accumetrics Ultegra System Analyzer, Accumetrics Ultegra Common Name: System Rapid Platelet Function Assay (RPFA-TRAP) Test Cartridges, Accumetrics Ultegra System Level One QC, Accumetrics Ultegra System Level Two 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:

The Ulteara RPFA is based upon the ability of activated platelets to bind fibrinogen. Fibrinogen coated microparticles agglutinate in whole blood in proportion to the number

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of unblocked platelet GP Ilb/IIIa 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. The analyzer is designed to measure this change in optical signal due to agglutination.

Intended Use:

The Ultegra Rapid Platelet Function Assay (RPFA) is a semi-quantitative, whole blood platelet function assay used to measure glycoprotein (GP) IIb/Illa receptor blockade in patients treated with abciximab. Ultegra RPFA 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.

Technological Characteristics:

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

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

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

Performance Characteristics:

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

The multi-center clinical trial was designed to study GP IIb/Illa receptor blockade in patients undergoing percutaneous coronary intervention and receiving abciximab. Samples were obtained at four clinical sites from 120 patients at three time points: 1) Baseline, prior to abciximab administration; 2) During, witin 1 hour following post bolus administration to evaluate the effects of the abciximab bolus; and 2) Post, 24 hours post procedure or at the time of discharge. Samples were tested with the Ultegra RPFA and the CHRONO-LOG Platelet Aggregometer.

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For the aggregometry method, platelet rich plasma was prepared from the blood sample ron the aggregometry mothed, plater nemator and 20 µM ADP as the agonist.

Correlation of the two methods was evaluated using (orthogonal) regression. The results are shown in Table 1.

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

Table 1.

In addition to Ultegra RPFA and platelet aggregometry, clinical trial patient samples in addition to Onegra NY FA and plateler aggregorial which measures the percentage of were tested with a receptors blocked by abciximab. 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/7 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 y-axis represents the percentage of baseline GPIIb/IIIa receptors or aggregation, ranging from 0 to 120. The x-axis represents the time after Abciximab infusion, with three categories: Baseline, During infusion, and Post infusion. There are three different types of data represented in the bar graph: RBA, RPFA, and AGG.

Figure 1.

The results of the multi-center clinical study demonstrate that the performance of the The results of the morther onlined butty the predicate device, CHRONO-LOG platelet aggregometer.

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Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with three stripes forming its body and wings. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" is arranged in a circular pattern around the eagle.

Public Health Service

DEC 2 1 1999

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Frances E. Harrison Senior Regulatory Affairs Specialist Accumetrics, Inc. 3985 Sorrento Valley Boulevard San Diego, California 92121

K992531 Re:

Trade Name: Ultegra® System Rapid Platelet Function Assay (RPFA) Regulatory Class: II Product Code: JOZ Dated: November 3, 1999 Received: November 4, 1999

Dear Ms. Harrison:

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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Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770) 488-7655.

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"(21 CFR 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 Putman

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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.. 33

S10(Is) Number (if Known): 99253

Device Name: Ultegra System Rapid Platelet Function Assay

Indications For Use:

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

	Xetu & Matin
(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number	K992531

Prescription Use(Per 21 CFR 801.109)	OR	Over-The-Counter Use
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(Optional Format 1-2-96)

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).