The Ultegra® Rapid Platelet Function Assay-ASA (RPFA-ASA) is a qualitative test to aid in the detection of platelet dysfunction due to aspirin (ASA) ingestion in citrated whole blood for the point of care or laboratory setting.

Not for use in patients with underlying congenital platelet abnormalities, patients with non-ASA induced acquired platelet abnormalities or in patients receiving non-ASA anti-platelet agents (may be used in patients treated with selective COX-2 inhibitors, e.g., celecoxib (Celebrex®) and rofecoxib (Vioxx®)).

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, platelet agonist, 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. Fibrinogen-coated microparticles are used in the Ultegra RPFA-ASA cartridge to bind to available platelet receptors. When the activated platelets are exposed to the fibringgen-coated microparticles, agglutination occurs in proportion to the number of available platelet receptors. To ensure consistent and uniform activation of the platelets, cationic propyl gallate (c-PG) is incorporated into the assay cartridge to induce platelet activation without fibrin formation. The Ultegra Analyzer is designed to measure this agglutination as an increase in light transmittance. Utregra RPFA-ASA Assay results are reported as Aspirin Reaction Units (ARU).

AI/ML Overview

Acceptance Criteria and Device Performance Study for Accumetrics Ultegra® System Rapid Platelet Function Assay -ASA (RPFA-ASA)

1. Table of Acceptance Criteria and Reported Device Performance

Metric	Acceptance Criteria (Implied)	Reported Device Performance
Sensitivity	Sufficient for qualitative detection of aspirin-induced platelet dysfunction	92.1% (86.4% to 96.0%)
Specificity	Sufficient for qualitative detection of aspirin-induced platelet dysfunction	85.3% (78.4% to 90.7%)

Note: The document does not explicitly state numerical acceptance criteria for sensitivity and specificity. The implied criteria are that the device performance should be acceptable for its intended use as a qualitative test to aid in the detection of platelet dysfunction due to aspirin ingestion.

2. Sample Size and Data Provenance

Test Set Sample Size:
- "ASA Present" group (Post-ASA): 143 samples
- "ASA Absent" group (Pre-ASA): 140 samples
- Total Patients: 148 patients (each patient provided samples at two time points: pre-ASA and post-ASA).
Data Provenance:
- Country of Origin: Not specified in the provided document, but the study was a multi-center clinical trial.
- Retrospective or Prospective: Prospective. Samples were obtained from subjects before and after aspirin ingestion as part of the trial design.

3. Number of Experts Used to Establish Ground Truth & Qualifications

Not applicable. The ground truth for this study was established based on documented aspirin ingestion status, not expert interpretation of results.

4. Adjudication Method for the Test Set

Not applicable. The ground truth was based on the aspirin ingestion status of the patients. The device results (ARU < 550 for positive, ARU ≥ 550 for negative) were compared directly against this ground truth. There was no mention of human adjudication of device results itself.

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

No, an MRMC comparative effectiveness study was not done. This device is a standalone diagnostic assay designed to measure platelet function, not to assist human readers in interpreting images or other data that typically require MRMC studies.

6. Standalone Performance Study

Yes, a standalone performance study was done. The performance metrics (sensitivity and specificity) represent the algorithm's (device's) ability to correctly classify samples based on the designated cutoff of 550 ARU without human intervention in the interpretation of the ARU value.

7. Type of Ground Truth Used

The ground truth used was aspirin ingestion status. Patients were classified as "ASA Present" if they had ingested 325 mg of aspirin 2 to 30 hours prior to sample collection, and "ASA Absent" if samples were collected prior to aspirin ingestion.

8. Sample Size for the Training Set

The document does not explicitly state the sample size for a dedicated "training set". The performance characteristics were evaluated in a "multi-center clinical trial" where subjects provided samples before and after aspirin ingestion. It is possible that the cutoff of 550 ARU was determined based on an initial analysis of these or similar data, but the breakdown into distinct training and test sets is not provided in detail. The presented concordance table and metrics appear to be from the evaluation of the final device performance.

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

As with the test set, the ground truth for any potential "training set" (or for the determination of the 550 ARU cutoff) would have been established based on the aspirin ingestion status of the subjects. This involves knowing whether a patient had ingested aspirin (e.g., a 325 mg dose) and the timing relative to sample collection.

Summary

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K012701

JUN 1 2 2002

510(k) Summary

Accumetrics Ultegra® System Rapid Platelet Function Assay -ASA (RPFA-ASA)

Accumetrics 3985 Sorrento Valley Blvd. San Diego, CA 92121

June 6, 2002

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

Device Names:

Trade Name:

Ultegra System Analyzer, Ultegra System Rapid Platelet Function Assay-ASA (RPFA-ASA) Test Cartridges, RPFA Level One QC.and RPFA Level Two QC

Common Name:

Ultegra Analyzer, Ultegra RPFA-ASA Test Cartridges, RPFA Level One QC and RPFA Level Two QC

Classification Name: System, Automated Platelet Aggregation

The Accumetrics Ultegra System Analyzer and RPFA-ASA Assay have been found to be substantially equivalent to previously cleared, automated platelet aggregation devices, specifically to CHRONO-LOG Corporation's Whole Blood Aggregometer (K830749).

Device Description:

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activation without fibrin formation. The Ultegra Analyzer is designed to measure this agglutination as an increase in light transmittance. Utregra RPFA-ASA Assay results are reported as Aspirin Reaction Units (ARU).

Intended Use:

The Ultegra Rapid Platelet Function Assay-ASA (RPFA-ASA) is a qualitative test to aid in the detection of platelet dysfunction due to aspirin (ASA) ingestion in citrated whole blood for the point of care or laboratory setting.

This intended use 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-ASA Assay does not raise issues of safety or effectiveness since the CHRONO-LOG aggregometer contains data in its labeling regarding results after aspirin ingestion.

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-ASA differ from the CHRONO-LOG. Fibringen coated microbeads are used in the Ultegra RPFA-ASA Assay, but not the CHRONO-LOG aggregometer. The Ultegra RPFA-ASA Assay uses the agonist cationic propyl gallate, whereas the CHRONO-LOG uses several different agonists. The Ultegra RPFA-ASA Assay 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-ASA performance was evaluated in a multi-center clinical trial on venous whole blood samples from subjects with history of vascular disease or existence of at least two of eight risk factors for developing vascular disease.

The multi-center clinical trial was designed to study results from patients before and after aspirin ingestion (325 mg). Samples were obtained at four clinical sites from 148 patients at two time points: 1) Pre-ASA, prior to aspirin ingestion and 2) Post-ASA, 2 to 30 hours after ingestion of aspirin. Samples were tested in duplicate with the Ultegra RPFA-ASA Assay and compared to the patient's aspirin status. RPFA-ASA results were based on a designated cutoff of 550 ARU (extent of platelet aggregation measured).

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Testing was performed on patients newly introduced to aspirin. Ultegra RPFA-ASA was evaluated against the presence and absence of aspirin ingestion. The concordance table below illustrates performance results.

TEST RESULT	ASA STATE
	PRESENT (n=143)	ABSENT (n=140)
POSITIVE(<550 ARU)	129	21
NEGATIVE(≥ 550 ARU)	11	122

ASA Present:

Sensitivity = 92.1% (86.4% to 96.0%) Specificity = 85.3% (78.4% to 90.7%)

A reference range of expected values was identified from all patients enrolled in the clinical study. Results are illustrated in a non-parametric frequency distribution below. Values are distributed as no aspirin ingestion (pre-ASA) and 2 to 30 hours after ingestion of 325 mg aspirin (post-ASA). The reference range for pre-ASA samples is 399-780 ARU (based on a 2.5 to 97.5 percentile).

Image /page/2/Figure/5 description: The image is a bar graph titled "RPFA-ASA Frequency Distribution Pre- and Post-ASA". The x-axis is labeled "RPFA-ASA ARU" and ranges from 300 to "More" in increments of 50. The y-axis is labeled "Frequency" and ranges from 0 to 40 in increments of 5. The graph compares the frequency distribution of "Pre-ASA" and "Post-ASA" values, with a "Threshold" indicated at approximately 550 ARU.

Please see package insert for additional information.

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Image /page/3/Picture/0 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a circular design with the department's name encircling an emblem. The emblem consists of a stylized representation of three human profiles facing right, stacked on top of each other. The text is arranged around the circle's perimeter, with "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" clearly visible.

DEPARTMENT OF HEALTH & HUMAN SERVICES

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

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

Re: K012701

Trade/Device Name: Ultegra® System Rapid Platelet Function Assay - ASA (RPFA-ASA) Regulation Number: 21 CFR § 864.5700 Regulation Name: System, Automated Platelet Aggregation Regulatory Class: II Product Code: JOZ Dated: March 13, 2002 Received: March 14, 2002

JUN 1 2 2002

Dear Ms. Moe:

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 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 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 Part 801); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control 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 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 Sutman

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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Page_1_of_1

510(k) Number (if known): K012701 ____________________________________________________________________________________________________________________________________________

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

Indications For Use:

、、

The Ultegra® Rapid Platelet Function Assay-ASA (RPFA-ASA) is a whole blood assay ` used to measure platelet response to aspirin.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

(Optional Format 3-10-98)

Touraine-Routier.

(Division Sign-C Clinical La

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510(k) Number (if known): < 012701

Ultegra Rapid Platelet Function Assay-ASA_(RP) Device Name:

Indications For Use:

Not for use in patients with underlying congenital platelet abnormalities, patients with non-ASA induced acquired platelet abnormalities or in patients receiving non-ASA anti-plateler agents (may be used in patients treated with selective COX-2 inhibitors, e.g., celecoxib (Clelebrex) and rofecoxib (Vioxx®)).

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Josephine Bauter.

Division of Clinical Laboratory De

510(k) Number K.012701

(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).