The AggreGuide A-100 ADP Assay is used with the AggreGuide A-100 instrument in non-CLIA waived physician's office or clinical laboratory for the detection of platelet dysfunction in patients age 22 or older receiving P2Y 12 antiplatelet drugs, prasugrel and ticagrelor, using 3.2% sodium citrated whole blood. The AggreGuide A-100 ADP Assay is a semi-quantitative assay. The level of platelet aggregation is determined by the platelet activity index (PAI) where values < 4.7 PAI suggest that platelet dysfunction is due to the presence of P2Y 12 antiplatelet drugs, prasugrel and ticagrelor. The test results should be interpreted in conjunction with all laboratory data available to the clinician.

Device Description

The AggreGuide A-100 ADP Assay is an individual use, disposable assay cartridge for use with the AggreGuide A-100 instrument. The cartridge contains preloaded freeze dried agonist. The level of platelet aggregation induced by the adenosine diphosphate (ADP) agonist in a sample of whole blood is detected within the cartridge. The amount of platelet aggregation is measured by detecting and quantifying the laser light scattering caused by platelet aggregates. P2Y12 inhibitor drugs e.g. clopidogrel, and ticagrelor are known to inhibit the level of platelet aggregation, causing platelet dysfunction.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study proving the device meets them, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

Metric	Acceptance Criteria	Reported Device Performance (AggreGuide A-100 ADP Assay)
Sensitivity
Prasugrel (Post-Loading, 24 hours)	≥ 0.80	1.000 (95% CI: 0.918 – 1.000)
Prasugrel (Post-Maintenance, 7 days)	≥ 0.80	0.907 (95% CI: 0.784 - 0.963)
Ticagrelor (Post-Loading, 3-6 hours)	≥ 0.80	0.906 (95% CI: 0.825 – 0.952)
Ticagrelor (Post-Maintenance, 7 days)	≥ 0.80	0.839 (95% CI: 0.770 - 0.890)
Specificity	Not explicitly stated as a numerical acceptance criterion, but "0.907" is given as an overall specificity value for the device.	0.907

Note: The document only explicitly states numerical acceptance criteria for sensitivity. Specificity is provided as a reported value, implying it met an internal or expected threshold, though the exact numerical acceptance criterion for specificity isn't listed.

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

The sample sizes for the sensitivity analysis (test set) are:

Prasugrel: 43 patients for both Post-Loading (24 hours) and Post-Maintenance (7 days).
Ticagrelor: 85 patients for Post-Loading (3-6 hours) and 143 patients for Post-Maintenance (7 days).

The document does not explicitly state the country of origin of the data or whether the study was retrospective or prospective. However, the study is described as "clinical testing" and evaluated against a "clinical truth data set comprising off-therapy (baseline) versus on-therapy with P2Y12 inhibitor medications. On-therapy clinical truth utilized high potency P2Y12 medications at a time of full-effect," which suggests a prospective clinical study design.

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

The document does not specify the number of experts used to establish the ground truth or their qualifications. It simply refers to a "clinical truth data set."

4. Adjudication Method for the Test Set

The document does not describe any adjudication method used for establishing the ground truth of the test set.

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

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not conducted. The study evaluated the standalone performance of the AggreGuide A-100 ADP Assay and compared its performance (sensitivity values) against another device (VerifyNow) on the same clinical truth data set, but not in the context of human reader improvement with and without AI assistance.

6. Standalone Performance (Algorithm Only Without Human-in-the-Loop Performance)

Yes, a standalone performance study was done. The reported sensitivity and specificity values are for the AggreGuide A-100 ADP Assay as a diagnostic device, without human intervention in the interpretation of the primary PAI result. The document says, "The level of platelet aggregation is determined by the platelet activity index (PAI) where values < 4.7 PAI suggest that platelet dysfunction..." This indicates the algorithm provides the direct output, which is then used for interpretation.

7. Type of Ground Truth Used

The ground truth used was clinical truth data. Specifically, it was established by comparing "off-therapy (baseline) versus on-therapy with P2Y12 inhibitor medications." The "on-therapy clinical truth utilized high potency P2Y12 medications at a time of full-effect." This implies a reference standard based on the known physiological state of the patient (presence or absence of platelet dysfunction due to specific P2Y12 inhibitors).

8. Sample Size for the Training Set

The document does not provide information regarding the sample size for the training set. It focuses solely on the performance testing carried out.

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

Since the document does not provide information on a training set, it also does not describe how the ground truth for any training set would have been established. The provided data relates to clinical performance testing, implying a pre-defined or externally validated cut-off point. It states, "Cut Off Point is confirmed by ROC Decision Threshold / J-statistic (Youden) analysis of the clinical truth data set," suggesting the cut-off was determined using the available clinical truth data, rather than being established pre-emptively on a separate training set.

Summary

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Image /page/0/Picture/0 description: The image contains two logos. The logo on the left is the Department of Health & Human Services - USA logo. The logo on the right is the FDA U.S. Food & Drug Administration logo. The FDA logo is in blue.

March 29, 2019

Aggredyne, Inc. Philip Speros, COO 10530 Rockley Road. Suite 150 Houston, Texas 77099

Re: K181777

Trade/Device Name: AggreGuide A-100 ADP Regulation Number: 21 CFR 864.5700 Regulation Name: Automated platelet aggregation system Regulatory Class: Class II Product Code: JOZ Dated: June 29, 2018 Received: July 3, 2018

Dear Philip Speros:

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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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 Part

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801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.htm); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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 comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice

(https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Leonthena R. Carrington -S

Lea Carrington 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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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

Indications for Use

510(k) Number (if known)

K181777

Device Name

AggreGuide A-100 ADP Assay

Indications for Use (Describe)

The AggreGuide A-100 ADP Assay is used with the AggreGuide A-100 instrument in non-CLIA waived physician's office or clinical laboratory for the detection of platelet dysfunction in patients age 22 or older receiving P2Y 12 antiplatelet drugs, prasugrel and ticagrelor, using 3.2% sodium citrated whole blood. The AggreGuide A-100 ADP Assay is a semi-quantitative assay. The level of platelet aggregation is determined by the platelet activity index (PAI) where values < 4.7 PAI suggest that platelet dysf unction is due to the presence of P2Y 12 antiplatelet drugs, prasugrel and ticagrelor. The test results should be interpreted in conjunction with all laboratory data available to the clinician.

Type of Use (Select one or both, as applicable)

Prescription Use (Part 21 CFR 801 Subpart D)

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

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510(k) Summary—K181777 5.0

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 ADP Assay.

Name:	Aggredyne, Inc.
Address:	10530 Rockley RoadSuite 150Houston, Texas 77099
Telephone:	713-636-5996
Contact:	Phil Speros
E-Mail:	psperos@aggredyne.com

Company making the submission: 1.
1. Device Name:

Trade/ProprietaryName:	AggreGuide A-100 ADP Assay
Common/UsualName:	ADP platelet function test
Classification Name:	System automated plateletaggregation
Regulation Number:	864.5700
Product Code:	JOZ
Class	II

1. Predicate Devices:
  The predicate is:

VerifyNow-P2Y12 Assay [K141427]

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4. Description of Device:

5. Intended Use Statement:

The AggreGuide A-100 ADP Assay is used with the AggreGuide A-100 instrument in non-CLIA waived physician's office or clinical laboratory for the detection of platelet dysfunction in patients age 22 or older receiving P2Y12 antiplatelet drugs, prasugrel and ticagrelor, using 3.2% sodium citrated whole blood. The AggreGuide A-100 ADP Assay is a semi-quantitative assay. The level of platelet aggregation is determined by the platelet activity index (PAI) where values < 4.7 PAI suggest that platelet dysfunction is due to the presence of P2Y12 antiplatelet drugs, prasugrel and ticagrelor. The test results should be interpreted in conjunction with all other clinical and laboratory data available to the clinician.

1. Summary of the technological characteristics of the device compared to predicate device:
  The AggreGuide A-100 ADP Assay and VerifyNow PRUTest, each measure platelet aggregation in response to ADP. In the presence of ADP, platelets may be activated and aggregate. In both the AggreGuide A-100 and the VerifyNow the ADP reagent is freeze dried and pre-loaded into disposable, single use cartridges. The AggreGuide A-100 ADP Assay detects platelet aggregates in whole blood as they pass by the optical window by detecting and quantifying 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 P2Y12 Reactive Units (PRU). Conversely, if the platelets are inhibited by P2Y12 inhibitor drugs, they are not activated by ADP to form aggregates. Therefore, few, if any, aggregates form and the AggreGuide reports a low PAI, and, similarly, the VerifyNow® reports a low PRU. The AggreGuide's PAI, like the VerifyNow's PRU, is a function of the level of platelet aggregate formation in whole blood.

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7. Performance Testing:

Non-clinical testing: Precision, shelf life of the ADP reagent, sample stability, shipping stability, interfering substances, limit of blank (LOB), and lot-to-lot variability tests were carried out. These studies showed that the AggreGuide A-100 ADP Assay raised no safety concerns when used according to the Instructions for Use.

Clinical Testing:

Specificity of the AggreGuide A-100 ADP Assay is 0.907.

Sensitivity of the AggreGuide A-100 ADP Assay as evaluated against a clinical truth data set comprising off -therapy (baseline) versus on-therapy with P2Y12 inhibitor medications. On-therapy clinical truth utilized high potency P2Y12 medications at a time of full- effect. Sensitivity values are shown in this table:

Sensitivity
High Potency P2Y12 Inhibitors at Peak Effect
Stratified by Dose Status
with Exact Confidence Intervals
StudyAnti-PlateletDrug	N	TimingData point name(time from dose)	PAI (A-100)(95% CI Limits)	PRU (VerifyNow)(95% CI Limits)	Pre-SpecifiedSENSITIVITYAcceptanceCriteria
Prasugrel	43	Post-Loading(24 hours)	1.000(0.918 – 1.000)	0.977(0.877 – 0.996)	≥ 0.80
	43	Post-Maintenance(7 days)	0.907(0.784 - 0.963)	0.977(0.877 – 0.996)	≥ 0.80
Ticagrelor	85	Post-Loading(3 - 6 hours)	0.906(0.825 – 0.952)	1.000(0.957-1.000)	≥ 0.80
	143	Post-Maintenance(7 days)	0.839(0.770 - 0.890)	0.986(0.951 - 0.998)	≥ 0.80

Cut Off Point is confirmed by ROC Decision Threshold / J-statistic (Youden) analysis of the clinical truth data set.

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

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1. The AggreGuide A-100 ADP Assay is a prescription device per 21 CFR Subpart D.
1. Conclusion:

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

Aggredyne, Inc.

Philip C. Speros Chief Operating Officer

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).