The VerifyNow Aspirin Assay is a qualitative assay to aid in the detection of platelet dysfunction due to aspirin ingestion in citrated whole blood for the point of care or laboratory setting.

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

Device Description

The VerifyNow 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 instrument and disposable assay device with reagents based on microbead agglutination technology. The quality control system includes an electronic quality control, an assay device internal control, and two levels of external, wet quality control controls. The instrument controls assay sequencing, establishes the assay temperature, controls the reagentsample 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 assay device contains a lyophilized preparation of human fibrinogen coated beads, platelet agonist, a peptide, bovine serum albumin, buffer, and stabilizer. The patient sample is citrated whole blood, which is automatically dispensed from the blood collection tube into the assay device by the instrument, with no blood handling required by the user. Fibrinogen-coated microparticles are used in the VerifyNow-Aspirin assay device to bind activated platelet GP IIb/Ila receptors. When the activated platelets are exposed to the fibrinogen-coated microparticles, aggregation occurs in proportion to the number of activated platelet receptors. To ensure consistent and uniform activation of the platelets, the agonist arachidonic acid is incorporated into the assay device. The VerifyNow-Aspirin Assay reports results in Aspirin Reaction Units (ARU).

AI/ML Overview

Acceptance Criteria and Device Performance Study for VerifyNow-Aspirin Assay

This document summarizes the acceptance criteria for the VerifyNow-Aspirin Assay and the study conducted to demonstrate the device meets these criteria, based on the provided 510(k) summary.

1. Table of Acceptance Criteria and Reported Device Performance

The provided document does not explicitly state pre-defined acceptance criteria in terms of specific performance thresholds for sensitivity and specificity. However, the reported performance results can be interpreted as the achievement for acceptance.

Performance Metric	Acceptance Criteria (Implied)	Reported Device Performance
Sensitivity	High (to detect aspirin effect)	91.4%
Specificity	High (to avoid false positives)	100%

Note: The acceptance criteria are "implied" because the document states "The VerifyNow-Aspirin Assay was evaluated against the presence and absence of aspirin ingestion. The concordance table below illustrates performance results." This suggests that the reported numbers were deemed acceptable by the FDA for substantial equivalence.

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

Sample Size for Test Set:
- Total subjects: 136
- Subjects tested before and after 325 mg aspirin ingestion: 71
- Subjects on chronic 81 mg/day aspirin therapy (single post-aspirin time point): 65
- Total number of individual test results in the concordance table: 245 (Aspirin Present) + 0 (Aspirin Present, Negative result) + 23 (Aspirin Absent, Positive result) + 141 (Aspirin Absent, Negative result) = 409 test results. These results are derived from the 136 subjects.
Data Provenance: The study was a "multi-center clinical trial." The country of origin is not explicitly stated, but given the FDA 510(k) submission, it is highly likely the data includes or originates from studies conducted in the United States. The data is prospective as subjects were recruited and tested specifically for the study.

3. Number of Experts and Qualifications for Ground Truth

The document does not specify the number of experts used or their qualifications to establish the ground truth for the test set.

4. Adjudication Method for the Test Set

The document does not specify an adjudication method (e.g., 2+1, 3+1, none) for the test set. The ground truth ("Aspirin State: Present / Absent") appears to be determined by documented aspirin ingestion or lack thereof.

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

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not explicitly described. The study evaluated the standalone performance of the VerifyNow-Aspirin Assay against the patient's aspirin status, not against human reader performance with or without AI assistance.

6. Standalone Performance Study

Yes, a standalone (i.e., algorithm only without human-in-the-loop performance) study was performed. The reported sensitivity and specificity values are for the VerifyNow-Aspirin Assay itself, with its specified cutoff of 550 ARU, in determining aspirin ingestion status.

7. Type of Ground Truth Used

The type of ground truth used was documented aspirin ingestion status. Subjects were classified as "Aspirin Present" if they had ingested aspirin (either 325mg before testing or chronic 81mg/day therapy) or "Aspirin Absent" if they had not ingested aspirin. This is a direct measure based on treatment, not expert consensus, pathology, or outcomes data in this context.

8. Sample Size for the Training Set

The document does not explicitly state a separate sample size for a training set. The clinical trial described appears to be the primary dataset for performance evaluation. It is possible that the cutoff of 550 ARU was determined from a portion of this data or prior developmental studies, but this is not detailed.

9. How Ground Truth for the Training Set Was Established

As a separate training set is not explicitly mentioned, the method for establishing ground truth for any potential internal training or development would likely be the same as for the test set: documented aspirin ingestion status of the subjects.

Summary

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Image /page/0/Picture/1 description: The image contains a sequence of alphanumeric characters that appear to be handwritten. The sequence starts with the letters 'K0', followed by the numbers '424', and ends with the number '33'. The characters are written in a dark ink, and the handwriting style is somewhat cursive.

510(k) Summary

Accumetrics VerifyNow-Aspirin Assay (Formerly Ultegra RPFA-ASA)

Accumetrics 3985 Sorrento Vallev Blvd. San Diego, CA 92121

September 3, 2004

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

Device Names:

Trade Name:	VerifyNow-Aspirin Assay
Common Name:	VerifyNow-Aspirin Assay
Comprised of:	VerifyNow-Aspirin Assay Devices
	VerifyNow Wet Quality Controls, Levels 1 and 2
	VerifyNow Instrument

Classification Name: System, Automated Platelet Aggregation

The Accumetrics VerifyNow System and VerifyNow-Aspirin 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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blood handling required by the user. Fibrinogen-coated microparticles are used in the VerifyNow-Aspirin assay device to bind activated platelet GP IIb/Ila receptors. When the activated platelets are exposed to the fibrinogen-coated microparticles, aggregation occurs in proportion to the number of activated platelet receptors. To ensure consistent and uniform activation of the platelets, the agonist arachidonic acid is incorporated into the assay device. The VerifyNow-Aspirin Assay reports results in Aspirin Reaction Units (ARU).

Intended Use:

The VerifyNow-Aspirin Assay is a qualitative assay to aid in the detection of platelet dysfunction due to aspirin inqestion 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 VerifyNow-Aspirin Assay does not raise issues of safety or effectiveness since the aggregometer labeling includes platelet aggregation data for samples post-aspirin ingestion.

Technological Characteristics:

The VerifyNow-Aspirin Assay is similar to the CHRONO-LOG Optical Aggregometer in that it employs an optical measurement method. Whereas the CHRONO-LOG Whole Blood Aggregometer measures impedance, it has been found to be substantially equivalent to the optical detection version of the aggregometer. The VerifyNow-Aspirin Assay is similar to the CHRONO-LOG Whole Blood Aggregometer in that it uses citrated, whole blood samples and measures platelet aggreaation. The platelet agonist for the VerifyNow-Aspirin Assay is arachidonic acid, which is also an agonist used with the optical and whole blood aggregometers. The VerifyNow-Aspirin Assay adds the use of fibrinogen-coated microparticles, which are not used in the CHRONO-LOG aggregometry methods. This difference raises no new issues of safety or effectiveness, as shown by the performance characteristics of the two devices.

Performance Characteristics:

The VerifyNow-Aspirin Assay performance was evaluated in a multi-center clinical trial on venous whole blood samples from subjects with a history of vascular disease or existence of at least two of eight risk factors for developing vascular disease.

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Two aspirin ingestion schemes were studied. Seventy-one of the study's 136 subjects were tested before and after ingestion of 325 mg of aspirin. The remaining 65 subjects were on chronic aspirin therapy of 81 mg per day and were tested at a single post-aspirin time point. Samples were tested with the VerifyNow-Aspirin Assay and results were compared to the patient's aspirin status. VerifyNow-Aspirin Assay results were reported as positive or negative, based on a designated cutoff of 550 ARU. The VerifyNow-Aspirin Assay was evaluated against the presence and absence of aspirin ingestion. The concordance table below illustrates performance results.

Test Result	Aspirin State
	Present	Absent
Positive(<550 ARU)	245	0
Negative(≥ 550 ARU)	23	141

Aspirin Present: Sensitivity = 91.4% Specificity = 100%

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 pre-aspirin and post-aspirin. The reference range for pre-aspirin samples is 620-672 ARU (2.5 to 97.5 percentile).

Image /page/2/Figure/4 description: This image is a frequency distribution chart titled "Pre- and Post- Aspirin". The x-axis is labeled ARU and ranges from 200 to 700. The y-axis is labeled Frequency and ranges from 0 to 140. The chart compares the frequency of pre-aspirin and post-aspirin at different ARU levels.

Please see package insert for additional information.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

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Public Health Service

OCT 6 - 2004

od and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Barbara Stevens Regulatory and Clinical Affairs Accumetrics, Inc. 3985 Sorrento Valley Blvd San Diego, CA 92121

K042423 Re:

Trade/Device Name: VerifyNow™- Aspirin Assay (Modification to Ultegra® RPFA-ASA Assay) Regulation Number: 21 CFR 864.5700 Regulation Name: Automated platelet aggregation system Regulatory Class: Class II Product Code: JOZ Dated: September 3, 2004 Received: September 7, 2004

Dear Ms. Stevens:

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 Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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 Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin marketing your device as described in your Section 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.

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Page 2

If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 594-3084. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act 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,

Robert L. Becker Jr.

Robert L. Becker, Jr., M.D., Ph.D. Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known): K042423

VerifyNow™-Aspirin Assay (Modification to Ultegra® RPFA-ASA Assay) Device Name:

Indications For Use:

The VerifyNow Aspirin Assay is a qualitative assay to aid in the detection of platelet dysfunction due to aspirin ingestion in citrated whole blood for the point of care or laboratory setting.

X Prescription Use (Part 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use (21 CFR 801 Subpart C)

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Aurghim Bautista

1 Page 1 of

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K042423

0009

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).