(420 days)
VerifyNow P2Y12 Assay, K051231
No
The summary describes a turbidimetric-based optical detection system and its components, focusing on chemical reactions and physical measurements. There is no mention of AI, ML, or related concepts in the device description, intended use, or performance studies.
No
This device is for in vitro diagnostic use, meaning it's used to test samples taken from the body, not to treat a patient directly. It measures a level of platelet receptor blockade, which is a diagnostic measurement, not a therapeutic action.
Yes
The "Intended Use / Indications for Use" section explicitly states that the device is "For in vitro diagnostic use," indicating its purpose is for diagnosis.
No
The device description explicitly states that the VerifyNow System consists of an instrument, a disposable test device, and quality control materials, indicating it is a hardware-based system with software components, not a software-only device.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Explicit Statement: The "Intended Use / Indications for Use" section clearly states: "For in vitro diagnostic use."
- Nature of the Test: The device is a "whole blood test used in the laboratory or point of care setting to measure the level of platelet P2Y12 receptor blockade." This involves analyzing a biological sample (whole blood) outside of the body to provide information about a patient's physiological state (platelet function). This is the core definition of an in vitro diagnostic test.
- Professional Use: The indication "For professional use only" further supports its use in a clinical or laboratory setting for diagnostic purposes.
N/A
Intended Use / Indications for Use
The VerifyNow PRUTest is a whole blood test used in the laboratory or point of care setting to measure the level of platelet P2Y12 receptor blockade. For in vitro diagnostic use. For professional use only.
Product codes
JOZ
Device Description
The VerifyNow System is a turbidimetric-based optical detection system that measures plateletinduced aggregation. The system consists of an instrument, a disposable test device and quality control materials. Quality control measures include an instrument based electronic quality control (EOC). two levels of wet quality controls (WOC), internal quality controls, and shipping controls. The instrument controls all assay sequencing, temperature, reagent-sample mixing and performs self-diagnostics. The degree of platelet function is determined and the result is displayed.
The VerifyNow PRUTest device contains three lyophilized reagent pellets in separate reaction chambers within the test device: 1) ADP pellet consisting of a preparation of Fibrinogen and BSA coated beads, adenosine-5-diphosphate (ADP), prostaglandin E1 (PGE1), dye, buffer, and a preservative; 2) TRAP pellet (Internal Control) consisting of a preparation of iso-TRAP (Thrombin Receptor Activating Peptide), Fibrinogen and BSA coated beads, buffer, dye, and a preservative; and 3) No-Agonist Pellet (NAP) consisting of a preparation of BSA coated beads, dye, buffer, and a preservative.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Laboratory or point of care setting / Not Found
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Method Comparison
Study Type: Method Comparison Study
Sample Size: 119 samples
Key Results: The PRU results from both the VerifyNow P2Y12 (predicate device) and VerifyNow PRUTest (subject device) demonstrate comparable performance, with a slope not statistically significantly different from 1.0 and an intercept not statistically significantly different from 0, and a correlation (r) greater than 0.9.
CLSI Precision Studies
Study Type: Complex precision for the VerifyNow PRUTest using Wet Quality Controls (WOC) and intermediate precision using whole blood samples from healthy donors and ACS patients.
Sample Size: WQC Level 2 tested over 20 nonconsecutive days (240 samples each for between-lot and between-instrument). Whole blood samples from nine donors (~30-120 reps per donor) were tested.
Key Results:
WQC Level 1 results: All results fell within the acceptable range of
§ 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).
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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
October 30, 2015
ACCUMETRICS, INC. FRANK LADUCA CHIEF SCIENTIFIC OFFICER 3985 SORRENTO VALLEY BLVD. SUITE B SAN DIEGO. CA92121
Re: K141427
Trade/Device Name: VerifyNow PRUTest Regulation Number: 21 CFR 684.5700 Regulation Name: Automated platelet aggregation system Regulatory Class: Class II Product Code: JOZ Dated: July 23, 2015 Received: July 24, 2015
Dear Dr. LaDuca:
This letter corrects our substantially equivalent letter of July 24, 2015.
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.
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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.
If vou desire specific advice for your device on our labeling regulation (21 CFR Part Parts 801 and 809), please contact the Division of Industry and Consumer Education 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 Industry and Consumer Education 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,
Leonthena R. Carrington -S
Leonthena R. Carrington, MS. MBA, MT (ASCP) Director 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) K141427
Device Name VerifyNow PRUTest
Indications for Use (Describe)
The VerifyNow PRUTest is a whole blood test used in the laboratory or point of care setting to measure the level of platelet P2Y12 receptor blockade. For in vitro diagnostic use. For professional use only.
| 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
This 510(k) summary is submitted in accordance with 21 CFR §807.92.
| Owner: | Accumetrics, Inc.
3985 Sorrento Valley Blvd.
San Diego, CA 92121 USA
Contact: Frank M. LaDuca, PhD; Chief Scientific Officer
Telephone: (858) 263-2450
Fax: (858) 875-0603 |
|----------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Prepared: | 22 July 2015 |
| Trade name: | Accumetrics, Inc. VerifyNow PRUTest ™ |
| Common name: | Platelet reactivity test |
| Classification name: | Automated platelet aggregation system
(21 CFR §864.5700; Product Code: JOZ) |
| Predicate device: | VerifyNow P2Y12 Assay, Accumetrics, Inc., K051231 |
Device description:
The VerifyNow System is a turbidimetric-based optical detection system that measures plateletinduced aggregation. The system consists of an instrument, a disposable test device and quality control materials. Quality control measures include an instrument based electronic quality control (EOC). two levels of wet quality controls (WOC), internal quality controls, and shipping controls. The instrument controls all assay sequencing, temperature, reagent-sample mixing and performs self-diagnostics. The degree of platelet function is determined and the result is displayed.
The VerifyNow PRUTest device contains three lyophilized reagent pellets in separate reaction chambers within the test device: 1) ADP pellet consisting of a preparation of Fibrinogen and BSA coated beads, adenosine-5-diphosphate (ADP), prostaglandin E1 (PGE1), dye, buffer, and a preservative; 2) TRAP pellet (Internal Control) consisting of a preparation of iso-TRAP (Thrombin Receptor Activating Peptide), Fibrinogen and BSA coated beads, buffer, dye, and a preservative; and 3) No-Agonist Pellet (NAP) consisting of a preparation of BSA coated beads, dye, buffer, and a preservative.
Test principle:
The patient sample is citrate-anticoagulated whole blood, which is automatically dispensed from the blood collection tube into the test device by the instrument, with no blood handling required by the user. Fibrinogen-coated microparticles are used in the VerifyNow PRUTest device to bind activated platelet GP IIb/IIIa receptors. ADP is incorporated into the assay to activate platelets. and the reagent is formulated to specifically measure P2Y12-mediated platelet aggregation.
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When the activated platelets are exposed to the fibrinogen-coated microparticles, aggregation occurs in proportion to the number of activated platelet receptors. The VerifyNow PRUTest reports results in P2Y12 Reaction Units (PRU).
Intended use:
The VerifyNow PRUTest is a whole blood test used in the laboratory or point of care setting to measure the level of platelet P2Y12 receptor blockade. For in vitro diagnostic use. For professional use only.
Indications for use:
Same as the intended use.
Summary of the technological characteristics of the VerifyNow PRUTest (subject device) compared to VerifyNow P2Y12 Assay (predicate device):
The technological characteristics of the Accumetrics Inc. VerifyNow PRUTest are compared with the VerifyNow P2Y12 Assay (K051231) in the table below. This comparison demonstrates the substantial equivalence of this device to the predicate device. The devices are similar in intended use, principle of operation and specimen type. Both devices have similar analytical performance. The modifications from the predicate device are:
Reagents:
- ADP pellet: The reagent pellet was reformulated to contain 80% Fibrinogen/20% BSA coated beads from the previous 100% Fibrinogen coated beads.
- TRAP pellet: This reagent was moved from channel 4 to channel 3. The formulation . was unchanged. This channel is used as an internal assay control.
- NAP pellet: The No-Agonist pellet was introduced to channel 4. The purpose of this ● channel is to prevent a software error and provide no further input into the algorithm for generating the PRU result.
Controls (WQC):
- Level 1 (B-Carbon Sol Filler): This control was reformulated to contain BSA instead of ● Fish Skin Gelatin.
- . Level 2: The GPRP peptide conjugate length was modified from 2 x 10° MW AD to 500 MW AD.
Test Device/Instrumentation:
- . The humidity sensor was removed from the test device.
- Port cover added to instrument. ●
- The instrument reports results for the ADP pellet measurement in PRU units.
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| Item | Accumetrics, Inc.
VerifyNow PRUTest
(Subject Device) | Accumetrics, Inc.
VerifyNow P2Y12 Assay (K051231)
(Predicate Device) |
|---------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | Similarities | |
| Principle of
Operation | Fibrinogen bead / platelet aggregation
with optical detection. | Same. |
| Specimen Type | Citrate-anticoagulated whole blood. | Same. |
| Testing Site | Point of care or laboratory. | Same. |
| Assay Results | P2Y12 Reaction Units (PRU). | Same. |
| Controls | Pre-packaged, two-level Wet Quality
Controls (WQC); Internal control in
each assay device. | Same. |
| Test Procedure | 1. Add cartridge to instrument.
2. Attach blood collection tube.
No other operator intervention. | Same. |
| Calibration | Factory. | Same. |
| Time to result | 3 minutes. | Same. |
| Analytical Claims | Hematocrit range = 33-52% | Same. |
| | Modifications | |
| Intended Use | The Accumetrics, Inc. VerifyNow
PRUTest is a whole blood test used in
the laboratory or point of care setting
to measure the level of platelet P2Y12
receptor blockade. For in vitro
diagnostic use. For professional use
only. | The VerifyNow P2Y12 Assay is a
whole blood assay used in the
laboratory or point of care setting to
measure the level of platelet P2Y 12
receptor blockade. |
| Reagents | ADP Pellet contains 80%
Fibrinogen/20% BSA coated beads | ADP Pellet contains 100% Fibrinogen
coated beads |
| | TRAP Pellet found in channel 3. | TRAP Pellet found in channel 4. |
| | NAP Pellet introduced into channel 4. | No NAP Pellet |
| | Level 1 (B-Carbon Sol Filler) contains
BSA | Level 1 (F-Carbon Filler) contains Fish
Skin Gelatin |
| | Level 2 GPRP Peptide Conjugate
length truncated to 500,000 kDa | Level 2 GPRP |
| Test Device | No humidity sensor | Contains humidity sensor |
| Analytical Claims | Stability = 9 months (ongoing real-
time study in process) | Stability = 18 months |
Table A. Comparison of Predicate to Subject Device
Reference range:
A reference range study (Healthy Donor PRU Reference Range) was conducted to measure platelet function in a healthy donor population using VerifyNow PRUTest. A total of 152 evaluable healthy donors were recruited and their blood samples tested with the VerifyNow PRUTest. The data were evaluated as recommended in EP28-A3c "Defining, Establishing and
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Verifying Reference Intervals in the Clinical Laboratory; Approved Guideline – Third Edition. " The reference range determined from this study, expressed as the central 95% Confidence Interval of the mean, is 182-335 PRU. The data are summarized in the table below.
Table B. Reference Range
| N | Mean | SD | 95% confidence interval (CI) | |
|---|---|---|---|---|
| Lower limit (95% CI) | Upper limit (95% CI) | |||
| 152 | 266 | 42 | 182 (116–197) | 335 (324–354) |
Expected PRUTest values:
Treatment-naïve patients in the intended use population
Whole blood samples from 84 patients with acute coronary syndrome (ACS) that were not receiving a P2Y12 receptor inhibiting drug were tested with VerifyNow PRUTest. The data were evaluated as recommended in EP28-A3c "Defining, Establishing and Verifying Reference Intervals in the Clinical Laboratory: Approved Guideline – Third Edition." The range of values expressed as the central 95% Confidence Interval of the mean is 180-376 PRU. The data are summarized in the table below.
Table C. Expected PRU values in treatment-naïve patients
| N | Mean
(PRU) | SD
(PRU) | 95% confidence interval (CI) | |
|----|---------------|-------------|---------------------------------------|---------------------------------------|
| 84 | 274 | 48 | Lower limit (95% CI)
180 (160–200) | Upper limit (95% CI)
376 (358–395) |
ACS patients receiving treatment with clopidogrel
Whole blood samples from 71 patients with ACS receiving dual treatment with aspirin and clopidogrel were tested with VerifyNow PRUTest. The data were evaluated as recommended in EP28-A3c "Defining, Establishing and Verifying Reference Intervals in the Clinical Laboratory: Approved Guideline - Third Edition. " The range of values expressed as the central 95% Confidence Interval of the mean is 6-300 PRU. The data are shown in the table below.
Table D. Expected PRU values in patients receiving clopidogrel treatment
| N | Mean
(PRU) | SD
(PRU) | 95% confidence interval (CI) | |
|----|---------------|-------------|------------------------------|---------------|
| 71 | 156 | 73 | 6 (0-34) | 300 (269-329) |
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Performance studies
Method Comparison
A method comparison study (VerifyNow P2Y12 and PRUTest Method Comparison Study) was performed using the VerifyNow P2Y12 Assay System (predicate device) and the VerifyNow PRUTest System (subject device). A total of three investigational intended use sites were used to gather data for this investigation. The VerifyNow test analysis was performed at each site by intended users who were trained by the manufacturer. Test device and instrument configurations are described below.
Results:
The PRU results from both the VerifyNow P2Y12 (predicate device) and VerifyNow PRUTest (subject device) demonstrate comparable performance, with a slope not statistically significantly different from 1.0 and an intercept not statistically significantly different from 0, and a correlation (r) greater than 0.9 as shown in the table below.
| Regression | Slope | Slope | Intercept | Correlation | ||
|---|---|---|---|---|---|---|
| Comparison | N | Method | (95% CI) | p-value | (95% CI) | Coefficient R |
| P2Y12 Rep 1 vs. | 119 | Ordinary | 1.01 | -0.77 | 0.98 | |
| PRUTest Rep 1 | Least Squares | (0.97—1.05) | 0.56 | (-8.00-6.50) | ||
| P2Y12 Avg. vs. | 119 | Ordinary | 1.04 | -4.57 | ||
| PRUTest Avg. | Deming | (1.00-1.07) | 0.07 | (-11.2-2.05) | 0.98 |
Table E. Method Comparison
CLSI Precision Studies
Complex precision for the VerifyNow PRUTest was assessed using Wet Quality Controls (WOC). Levels 1 and 2, and intermediate precision was assessed using whole blood samples from healthy donors and from ACS patients receiving clopidogrel with or without aspirin by testing three different lots of test devices and three instruments. Data were analyzed in accordance with Clinical Laboratory Standards Institute (CLSI) guidance EP05-A2, "Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline – Second Edition."
Testing over several days with samples from the same patient is expected to yield variable results between days because platelet reactivity in response to orally ingested medications known to vary based upon time between dosages, as well as the time between dosage and blood collection. A summary of the precision verification studies performed is shown in Table F.
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Table F. Description of precision studies
| Type | Description |
|---|---|
| Complex precision using WQC Levels 1 | |
| and 2 | Measured intermediate precision with WQC |
| Level 2 samples over multiple days. | |
| Complex precision between instruments | |
| using WQC Level 2 | Measured Level 2 WQC between-instrument |
| precision over multiple days using a single lot of | |
| PRUTest devices. | |
| Intermediate precision using whole blood | |
| samples from donors and ACS patients | Measured intermediate precision and instrument- |
| to-instrument precision with whole blood | |
| samples over multiple days using subjects on | |
| dual antiplatelet therapy, healthy subjects dosed | |
| in vivo with P2Y12 clopidogrel / P2Y12 | |
| inhibitor, and normal healthy donors | |
| Intermediate precision between | |
| instruments using whole blood samples | |
| from donors and ACS patients | Measured whole blood between-instrument |
| precision over multiple days using a single lot of | |
| PRUTest devices. |
Complex precision using WQC Levels 1 and 2:
WQC Level 1 and Level 2 samples were tested over 20 nonconsecutive days. WQC Level 1 is a negative control (blank) from which no aggregation is expected. All WQC Level 1 results fell within the acceptable range of ≤ 30 PRU and data are not shown. WQC Level 2 results are detailed below. Analysis of variance (ANOVA) was used to estimate the components of variance in accordance with CLSI guidance EP05-A2.
Table G. Reproducibility using WQC Level 2
Between-lot
| N | Mean
PRU | Within-run | | Between-run | | Between-day | | Between-lot | | Total | |
|-----|-------------|------------|-----|-------------|-----|-------------|-----|-------------|-----|-------|-----|
| | | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| 240 | 300.5 | 13.6 | 4.5 | 7.7 | 2.5 | 8.3 | 2.8 | 13.5 | 4.5 | 22.2 | 7.4 |
Between instrument
| N | Mean
PRU | Within-run | | Between-run | | Between-day | | Between-lot | | Total | |
|-----|-------------|------------|-----|-------------|-----|-------------|-----|-------------|-----|-------|-----|
| | | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| 240 | 302.7 | 22.6 | 7.5 | 0.0 | 0.0 | 8.5 | 2.8 | 0.0 | 0.0 | 24.2 | 8.0 |
Intermediate precision using whole blood samples
Whole blood samples from nine donors were drawn once or twice a day, run in duplicate, using three device lots on three instruments over a minimum of five non-consecutive days. Analysis of variance (ANOVA) was used to estimate the components of variance within individual donors in accordance with CLSI guidance EP05-A2. The results of these precision measurements are
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detailed in the following two tables. Table H evaluates precision across multiple PRUTest device lots using whole blood samples. Table I evaluates precision across multiple VerifyNow instruments using whole blood samples.
| ID | Rx1 | Days | Runs | Reps | Mean PRU | SD | Within-run
%CV | SD | Between-run
%CV | SD | Between-day
%CV | SD | Between-lot
%CV |
|----|-----|------|------|----------------------|----------|------|-------------------|------|--------------------|------|--------------------|------|--------------------|
| | | | | Acceptance criteria: | | |