The AggreGuide A-100 AA Assay is a qualitative system to aid in the detection of platelet dysfunction due to aspirin ingestion by those 18 years of age or older in 3.2% citrated venous whole blood using the AggreGuide A-100 instrument. For professional use. This test 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 antiplatelet agents. The test results should be interpreted in conjunction with other clinical and laboratory data available to the clinician.

Device Description

The AggreGuide A-100 is a laser light scattering system that detects the level of platelet aggregation induced by arachidonic acid agonist in whole blood in motion. The system consists of an instrument and a disposable assay cartridge with pre-loaded freeze dried agonist. A whole blood sample is added to a disposable cartridge that is preloaded with freeze dried arachidonic acid agonist (AA) in a reaction chamber for an individual test. The amount of platelet aggregation is measured by detecting the laser light scattering caused by platelet aggregates. Aspirin is known to inhibit the level of platelet aggregation, or activity, when blood is mixed with arachidonic acid.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study details for the AggreGuide A-100, based on the provided 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance

The provided document primarily focuses on demonstrating substantial equivalence to a predicate device, rather than explicit pre-defined quantitative acceptance criteria for all performance aspects. However, it presents clinical performance results for sensitivity and specificity. Based on the clinical testing section, the implicit acceptance criteria are that the device demonstrates a clinically acceptable level of sensitivity and specificity for detecting aspirin-induced platelet dysfunction.

Acceptance Criteria (Implicit)	Reported Device Performance
Sensitivity	83% (115/138)
Sensitivity Lower 95% CI	76%
Sensitivity Upper 95% CI	89%
Specificity (True Negative Rate)	90% (151/167)
Specificity Lower 95% CI	85%
Specificity Upper 95% CI	94%
False Positive Rate	10% (16/167)
False Negative Rate	17% (23/138)

(Note: The document directly states "Sensitivity" in a table, and then provides a table titled "Pre 325mg Aspirin" that effectively describes the true negative rate (specificity) and false positive rate. The "Post 325mg Aspirin" table provides the true positive rate (sensitivity) and false negative rate. I've used these to construct the performance table.)

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

Test Set Sample Size:
- Total screened: 169 healthy subjects.
- For aspirin-induced dysfunction detection: 138 subjects were given aspirin and tested.
- For baseline (aspirin absent) assessment: 167 subjects (after 2 exclusions).
Data Provenance: The document does not explicitly state the country of origin. It indicates it was a clinical testing conducted for the purpose of this submission. The nature of the study (administering aspirin to healthy subjects) suggests a prospective study.

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

The document does not specify the use of experts or their qualifications for establishing ground truth in the clinical study. It describes a "qualitative system to aid in the detection of platelet dysfunction due to aspirin ingestion." The ground truth appears to be established by:
* Aspirin Administration: Whether a subject was given 325 mg of aspirin (to induce platelet dysfunction).
* Clinical Observation/Reference Method (Implied): The study design implies that "aspirin ingestion" itself serves as the ground truth for platelet dysfunction, and the device's ability to detect this is assessed. There's no mention of a separate "gold standard" laboratory test or expert consensus.

4. Adjudication Method for the Test Set

The document does not describe any adjudication method (e.g., 2+1, 3+1). The performance data is presented as direct results from the AggreGuide A-100, compared against the known condition of aspirin ingestion or absence.

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

A Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not performed as described in this summary. The study assessed the standalone performance of the AggreGuide A-100, not its effectiveness in assisting human readers.

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

Yes, a standalone performance study was done. The clinical testing section directly evaluates the AggreGuide A-100 system's ability to detect platelet dysfunction due to aspirin ingestion. The device produces a "Platelet Activity Index (PAI)," and the study assesses how well this PAI correlates with the presence or absence of prescribed aspirin. There is no mention of a human in the loop interpreting the device's output and then making a diagnosis.

7. The Type of Ground Truth Used

The ground truth used was primarily based on aspirin administration.

"Aspirin 325 mg Present" was the ground truth for aspirin-induced platelet dysfunction.
"Aspirin 325 mg Absent" was the ground truth for normal platelet function (or at least, not aspirin-induced dysfunction).

This is a form of clinical condition or intervention as ground truth, rather than pathology, expert consensus, or outcomes data in the traditional sense for diagnostic assays.

8. The Sample Size for the Training Set

The document does not mention a separate training set or its sample size. The description of performance testing focuses solely on the clinical validation study described. For a device like this (an in-vitro diagnostic instrument), "training" might refer to internal development and calibration, but a distinct "training set" for statistical model development and validation as seen in AI/ML products is not discussed.

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

Since a separate training set is not explicitly mentioned as distinct from the reported clinical testing, the method of establishing its ground truth is not provided.

Summary

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K122162 DEC 2 0 2013
510(k) (Traditional) Submission

Section 5, 510(k) Summary

510(k) Summary December 18, 2013

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR Part 807.92 for the Aggredyne, Inc., AggreGuide A-100.

Company making the submission: 1.

Name:	Aggredyne, Inc.
Address:	10530 Rockley RoadSuite 150Houston, Texas 77099
Telephone:Toll FreeFax:	713-636-5996866-800-1955281-317-1874
Contact:	Edward R. Teitel, MD, JD, MBA
E-Mail:	eteitel@aggredyne.com

1. Device Name:

Trade/ProprietaryName:	AggreGuide A-100 andAggreGuide A-100 AA Assay
Common/UsualName:	Aggregometer
Classification Name:	System automated plateletaggregation
Regulation Number:	864.5700
Product Code:	JOZ

1. Predicate Devices:
  The predicate is the Accumetrics VerifyNow-Aspirin Assay [K042423].
1. Description of Device:
  The AggreGuide A-100 is a laser light scattering system that detects the level of platelet aggregation induced by arachidonic acid agonist in whole blood in motion. The system consists of an instrument and a disposable assay cartridge with pre-loaded freeze dried agonist. A whole blood sample is Page 1 of 4

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added to a disposable cartridge that is preloaded with freeze dried arachidonic acid agonist (AA) in a reaction chamber for an individual test. The amount of platelet aggregation is measured by detecting the laser light scattering caused by platelet aggregates. Aspirin is known to inhibit the level of platelet aggregation, or activity, when blood is mixed with arachidonic acid.

1. Intended Use Statement:
  The AggreGuide A-100 AA Assay is a qualitative system to aid in the detection of platelet dysfunction due to aspirin ingestion by those 18 years of age or older in 3.2% citrated venous whole blood using the AggreGuide A-100 instrument. For professional use. This test 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 antiplatelet agents. The test results should be interpreted in conjunction with other clinical and laboratory data available to the clinician.
1. Summary of the technological characteristics of the device compared to predicate device:
  The AgareGuide A-100 and Accumetrics VerifyNow® agaregometers both measure platelet aggregation in response to arachidonic acid (AA). In the presence of AA, platelets may be activated and aggregate. These aggregates occur when activated platelets in motion come into contact with other activated platelets. In both the AggreGuide A-100 and the VerifyNow® the AA is freeze dried and pre-loaded into disposable, single use cartridges. The AgareGuide detects the aggreaates in whole blood as they pass by the optical window by light scattering. The VerifyNow® detects platelet aggregation at its optical window by measuring light transmittance. With the AggreGuide, the more active the platelets, the more aggregates are formed and the higher the Platelet Activity Index (PAI). With the VerifyNow®, the more active the platelets, the more light transmittance and the higher the Aspirin Reactive Units (ARU). Conversely, if the platelets are inhibited by aspirin, they are not activated by AA to form aggregates. Therefore, few, if any, aggregates form and the AggreGuide shows a low PAI, and, similarly, the VerifyNow® shows a low ARU. The AggreGuide's PAI, like the

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VerifyNow's® ARU is a function of the number of aggregates that form in the blood.

1. Performance Testing:
  Non-clinical testing: Non-clinical testing was carried out on the AggreGuide A-100 instrument for electrical safety and electromagnetic interference, as well as software validation against multiple standards. Non-clinical studies were also carried out to assess simple and complex precision, shelf life of the AA reagent, interfering substances, limit of blank (LOB), inter-instrument variability, and lot-to-lot variability. These studies showed that the AggreGuide A-100 System raised no safety concerns when used for the Intended Use.

Clinical testing: One hundred sixty nine (n=169) healthy subjects were screened for study of the sensitivity of the AggreGuide A-100 in identifying platelet dysfunction due to aspirin ingestion. One hundred thirty eight (n=138) subjects were given an aspirin dose of 325 mg (1 adult non-coated fablet) and tested with the AggreGuide for aspirin induced platelet dysfunction within 2 -30 hours. The results shown in the tables below:

Site	Sensitivity	CI (95%)
All Sites	115/138 (83%)	76% - 89%

Aspirin 325 mg Absent		Total
≥4 PAI(Platelet dysfunction notdetected)	<4 PAI(Platelet dysfunctiondetected)
151	16	167*
True Negative:90% (151/167)95% CI: (85%; 94%)	False Positive:10% (16/167)95% CI: (6%; 15%)
*2 subjects were excluded due to inclusion/exclusion criteria

Table 1 - Sensitivity Results

Table 2 - Pre 325mg Aspirin

Aspirin 325 mg Present			Total
≥4 PAI	<4 PAI
(Platelet dysfunctionnot detected)	(Platelet dysfunctiondetected)	Missing PAI(due to non-return)
23	115	13	151*
False Negative:	True Positive:	Missing
17% (23/138)	83% (115/138)	9% (13/151)
95% CI: (11%; 24%)	95% CI: (76%; 89%)	95% CI: (5%; 14%)
*16 subjects with PAI <4 at baseline were not evaluated

Table 3 - Post 325mg Aspirin

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The combination of non-clinical and clinical performance test results shows that the instrument performs in a substantially equivalent manner to the predicate.

1. The AggreGuide A-100 and the AgggreGuide A-100 AA Assay are a prescription device per 21 CFR Subpart D.
1. Conclusion:

The AggreGuide A-100 and AggreGuide A-100 AA Assay are substantially equivalent to the predicate device based on intended use, technology and performance testing results.

Aggredyne, Inc.

Edward R. Teitel, MD, JD, MBA Chairman & CEO

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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 stylized eagle with its wings spread, and three human figures underneath. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular fashion around the eagle.

Public Health Service

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

December 20, 2013

AGGREDYNE, INC. C/O MR. J. HARVEY KNAUSS 11874 SOUTH EVELYN CIRCLE HOUSTON TX 77071

Re: K122162

Trade/Device Name: AggreGuide A-100 and AggreGuide A-100 AA Assay Regulation Number: 21 CFR 864.5700 Regulation Name: Automated platelet aggregation system Regulatory Class: II Product Code: JOZ Dated: December 18, 2013 Received: December 19, 2013

Dear Mr. Knauss:

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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to 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 Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); 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-Mr. J. Harvey Knauss

If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

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) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Maria M. Chan -S

Maria M. Chan, PhD Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known): K122162

Device Name: AggreGuide A-100 and AggreGuide A-100 AA Assay

Indications For Use:

The AggreGuide A-100 AA Assay is a qualitative system to aid in the detection of platelet dysfunction due to aspirin ingestion by those 18 years of age or older in 3.2% citrated venous whole blood using the AggreGuide A-100 instrument. For professional use. This test 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. The test results should be interpreted in conjunction with other clinical and laboratory data available to the clinician.

Prescription Use × (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use (21 CFR 807 Subpart C)

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

Concurrence of Center for Devices and Radiological Health (CDRH)

Leonthena R. Carrington -S

Page 1 of ____________________________________________________________________________________________________________________________________________________________________

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).