AggreGuide A-100 ADP

K181777 · Aggredyne, Inc. · JOZ · Mar 29, 2019 · Hematology

Device Facts

• Record ID: K181777
• Device Name: AggreGuide A-100 ADP
• Applicant: Aggredyne, Inc.
• Product Code: JOZ · Hematology
• Decision Date: Mar 29, 2019
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 864.5700
• Device Class: Class 2

Intended Use

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.

Device Story

Disposable assay cartridge used with AggreGuide A-100 instrument; detects platelet dysfunction in patients on P2Y12 inhibitors. Cartridge contains preloaded freeze-dried ADP agonist. Whole blood sample introduced to cartridge; ADP induces platelet aggregation. Device quantifies aggregates via laser light scattering as they pass an optical window. Output is Platelet Activity Index (PAI); values < 4.7 PAI indicate platelet dysfunction due to drug presence. Used in physician offices or clinical labs by trained personnel. Clinicians interpret PAI alongside other laboratory data to assess patient response to antiplatelet therapy.

Clinical Evidence

Clinical study evaluated sensitivity against a truth data set of off-therapy vs. on-therapy patients. Sensitivity for prasugrel (post-loading) was 1.000 (95% CI: 0.918–1.000) and (post-maintenance) 0.907 (95% CI: 0.784–0.963). Sensitivity for ticagrelor (post-loading) was 0.906 (95% CI: 0.825–0.952) and (post-maintenance) 0.839 (95% CI: 0.770–0.890). Specificity was 0.907. Cut-off point determined via ROC/Youden analysis.

Technological Characteristics

Disposable, single-use assay cartridge; freeze-dried ADP agonist; laser light scattering detection principle; whole blood sample input; semi-quantitative output (PAI).

Indications for Use

Indicated for patients age 22 or older receiving P2Y12 antiplatelet drugs (prasugrel and ticagrelor) to detect platelet dysfunction using 3.2% sodium citrated whole blood.

Regulatory Classification

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.

Predicate Devices

• VerifyNow-P2Y12 Assay (K141427)

Submission Summary (Full Text)

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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 ([e-mail]) or phone [phone] 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.

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 Road<br>Suite 150<br>Houston, Texas 77099 |
| Telephone: | 713-636-5996 |
| Contact: | Phil Speros |
| E-Mail: | [e-mail] |

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

| Trade/Proprietary<br>Name: | AggreGuide A-100 ADP Assay |
|----------------------------|------------------------------------------|
| Common/Usual<br>Name: | ADP platelet function test |
| Classification Name: | System automated platelet<br>aggregation |
| Regulation Number: | 864.5700 |
| Product Code: | JOZ |
| Class | II |

- 3. Predicate Devices:
The predicate is:

VerifyNow-P2Y12 Assay [K141427]

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# 4. Description of Device:

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.

## 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.

- 6. 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 | | | | | |
| Study<br>Anti-<br>Platelet<br>Drug | N | Timing<br>Data point name<br>(time from dose) | PAI (A-100)<br>(95% CI Limits) | PRU (VerifyNow)<br>(95% CI Limits) | Pre-Specified<br>SENSITIVITY<br>Acceptance<br>Criteria |
| Prasugrel | 43 | Post-Loading<br>(24 hours) | 1.000<br>(0.918 – 1.000) | 0.977<br>(0.877 – 0.996) | ≥ 0.80 |
| | 43 | Post-Maintenance<br>(7 days) | 0.907<br>(0.784 - 0.963) | 0.977<br>(0.877 – 0.996) | ≥ 0.80 |
| Ticagrelor | 85 | Post-Loading<br>(3 - 6 hours) | 0.906<br>(0.825 – 0.952) | 1.000<br>(0.957-1.000) | ≥ 0.80 |
| | 143 | Post-Maintenance<br>(7 days) | 0.839<br>(0.770 - 0.890) | 0.986<br>(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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- 8. The AggreGuide A-100 ADP Assay is a prescription device per 21 CFR Subpart D.
- 9. 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