The Multiplate 5.0 aggregometer is intended for in vitro use to measure platelet aggregation in response to Arachidonic acid or ADP in citrated whole blood samples for the qualitative assessment of platelet function.

The ADPtest reagent is a lyophilized preparation of adenosine-5-diphosphate for in vitro diagnostic use to measure platelet aggregation for the qualitative assessment of platelet function. For professional laboratory use only.

The ASPItest reagent is a lyophilized preparation of arachidonic acid (AA) for in vitro diagnostic use to measure platelet aggregation for the qualitative assessment of platelet function. For professional laboratory use only.

For use as an assayed quality control verification of the resistance measure of impedance aggregometry.

Device Description

The Multiplate® 5.0 measures platelet function in whole blood samples using electrical impedance. The Multiplate technology employs multiple electrodes in a disposable test cell. Four electrodes form two independent sensor units allowing for two measurements on the same sample. Five independent channels of the instrument allow for testing of multiple reagents or samples simultaneously.

The instrument provides a five channel aggregometer and an integrated computer system with associated software and is connected to a computer screen, keyboard, mouse, and an electronic pipette. The software is used for data collection and is not used for diagnosis or treatment.

Currently, two test reagents (ADP and Arachidonic acid) are available that activate platelets through specific platelet membrane receptor/signal transduction pathways in order to measure platelet function or alterations in function.

AI/ML Overview

The Multiplate 5.0 device measures platelet aggregation in whole blood samples. This device report focuses on its performance compared to a predicate device (Chrono-log Model 700) and its ability to assess platelet function.

Here's a breakdown of the acceptance criteria and study details:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria in terms of numerical thresholds for agreement, sensitivity, or specificity. Instead, the "Performance" section reports the observed agreement and diagnostic accuracy against the predicate device and physician panel review, respectively. Therefore, the reported performance metrics can be considered the de facto "acceptance criteria" against which the device passed for substantial equivalence demonstration.

Performance Metric	Reagent: Arachidonic acid	Reagent: ADP
Agreement with Predicate Device
Positive Percent Agreement (PPA)	100% [96%, 100% CI]	93% [81%, 97% CI]
Negative Percent Agreement (NPA)	65% [54%, 75% CI]	54% [45%, 62% CI]
Diagnostic Accuracy vs. Clinical History
Sensitivity (ASPItest vs. Physician Panel)	93% [85%, 97% CI]	Not Applicable
Specificity (ASPItest vs. Physician Panel)	67% [44%, 84% CI]	Not Applicable
Sensitivity (ADPtest vs. Physician Panel)	Not Applicable	59% [46%, 70% CI]
Specificity (ADPtest vs. Physician Panel)	Not Applicable	80% [63%, 90% CI]

2. Sample Size and Data Provenance for the Test Set

Sample size for agreement study (Test Set 1): 171 patients.
Sample size for sensitivity/specificity study (Test Set 2): 91 patients.
Data Provenance: The document states "Multi-center studies were run," implying prospective data collection across multiple sites. There is no explicit mention of the country of origin of the data, but the submitting company is based in Germany. The data is implicitly prospective, as it was collected to compare the Multiplate 5.0 to the predicate device and against clinical status.

3. Number of Experts and Qualifications for Ground Truth (Test Set)

Number of experts: The document mentions a "physician panel" for establishing Platelet Function Status for the sensitivity/specificity study. The exact number of physicians on this panel is not specified.
Qualifications of experts: Not specified beyond being a "physician panel." Their specific specialty (e.g., hematologist, critical care physician) or years of experience are not provided.

4. Adjudication Method (Test Set)

For the agreement study with the predicate device, there was no independent adjudication method described. The comparison was direct measurement of the Multiplate 5.0 against the Chrono-log Model 700.
For the sensitivity/specificity study, the "Platelet Function Status of each sample was based upon a physician panel's review of each patient's clinical history." This implies a form of consensus or collective decision-making by the panel, but the specific adjudication method (e.g., unanimous, majority vote, 2+1) is not detailed.

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

No, an MRMC comparative effectiveness study that assesses human readers' improvement with vs. without AI assistance was not conducted. This device is an automated platelet aggregation system, not an AI diagnostic tool that assists human interpretation of images or data. The studies involved a direct comparison between devices or device output against clinical ground truth.

6. Standalone Performance Study (Algorithm Only)

Yes, a standalone study was performed. The reported performance metrics (agreement, sensitivity, specificity) reflect the performance of the Multiplate 5.0 device (the "algorithm only," as it's an automated system) without human interpretation or intervention in the measurement process itself. The software for data collection is explicitly stated as "not used for diagnosis or treatment," reinforcing that the device itself generates the results.

7. Type of Ground Truth Used

For agreement studies: The ground truth was the results obtained from the predicate device (Chrono-log Model 700).
For sensitivity and specificity studies: The ground truth was the "Platelet Function Status" based on a physician panel's review of each patient's clinical history. This can be categorized as expert consensus / clinical diagnosis.

8. Sample Size for the Training Set

The document does not specify a sample size for a training set. Given that this is a 510(k) submission for a device measuring electrical impedance (a well-established physical principle) rather than an AI/machine learning algorithm that requires extensive training, it's highly probable that there wasn't a "training set" in the modern machine learning sense. The device's operational parameters would likely be derived from engineering principles and validation, rather than data-driven training.

9. How Ground Truth for the Training Set Was Established

As no "training set" is mentioned or implied for a machine learning context, the concept of establishing ground truth for a training set does not apply in this document. The device operates based on physical principles and pre-defined reagents, with performance validated against clinical samples and a predicate device.

Summary

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JUL 27 2012 K1035

Multiplate 5.0: 510(k) Summary Version: 1.0 / Date: 26.07.2012 Released by: Verum Diagnostica GmbH

Image /page/0/Picture/2 description: The image shows the Multiplate logo. The logo consists of a circular graphic on the left and the word "multiplate" on the right. The graphic is a black circle with white lines inside, resembling a fingerprint or a stylized mountain range. The word "multiplate" is written in a bold, sans-serif font, with a small circle containing a dot above and to the right of the "e".

Device:	Multiplate Analyzer 5.0
Prepared on:	November 29, 2010
Submitted by:	Verum Diagnostica GmbH, Reichenbachstrasse 27, 80469 Munich, Germany
Contact person:	Dr. Maximilian Zucker, +49 89 12 55 56-0
Device Names:	- Trade name: Multiplate 5.0- Common name: Whole Blood Analyzer- Classification name: Automated Platelet Aggregation System

The Multiplate 5.0 has been found to be substantially equivalent to the previously cleared Chronolog Model 700 Whole Blood Lumi-Aggregometer (K050265).

1. Device Description

2. Intended Use

3. Technical Description

The Multiplate uses the same scientific principles of detection as the predicate Chrono-log Model 700 with the exception that it does not include the capability of platelet function measurement based on luminescence or turbidimetric light transmission measurement.

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Both devices employ the same principle of measurement: electrical impedance, first cited in 1980 by Cardinal and Flower, (J Pharmacol Methods.1980;3:135-158). An electrical current passes through individual sets of electrodes. When the electrodes come into contact with a whole blood sample platelets bind to and cover the electrodes in a small monolayer. As the platelets become activated after exposure to a specific platelet agonist, the platelets strongly adhere to the electrodes and begin to aggregate. An increase in the number of platelets adhering to the electrodes increases the resistance (impedance) between the pair of electrodes.

Potential improvements of the Multiplate system are the introduction of dual sensor technology that records two measurements in each test cell based on two individual pairs of electrodes. The mean value is then reported. The final measurement is reported in Units (U) which represents the area under the curve that is generated by graphing the change in resistance.

4. Performance

...

Multi-center studies were run to compare the performance of the Multiplate 5.0 to the predicate device. Samples from 171 patients suspected of decreased platelet function were drawn and measured in duplicate.

The positive and negative percent agreements of the Multiplate to the Chrono-log were calculated. The results were considered positive if the test value was below the reference range for the specific device. The results were considered negative if they fell within the reference range for the specific device. Using this data, the positive percent agreements (PPA) and negative percent agreements (NPA) were calculated.

	Arachidonic acid		ADP
	PPA	NPA	PPA	NPA
Agreement	100%	65%	93%	54%
95% Confidence Interval	[96%, 100%]	[54%, 75%]	[81%, 97%]	[45%, 62%]

Sensitivity and Specificity were analysed by considering samples from 91 patients suspected of decreased platelet function which were drawn and measured in duplicate. Clinical sensitivity and specificity were calculated against Platelet Function Status. Platelet Function Status of each sample was based upon a physician panel's review of each patient's clinical history.

	Sensitivity	Specificity
ASPItest	93%	67%
95% CI	[85%, 97%]	[44%, 84%]
ADPtest	59%	80%
95% CI	[46%, 70%]	[63%, 90%]

5. Conclusion

The data and information provided in this submission demonstrate substantial equivalence and support clearance of the 510(k) premarket notification for the Multiplate 5.0 and associated reagents.

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Image /page/2/Picture/1 description: The image shows the logo for the Department of Health & Human Services (HHS). The logo consists of a circle with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an abstract symbol that resembles a stylized human figure or a bird in flight. The logo is black and white.

10903 New Hampshire Avenue Silver Spring, MD 20993

AUG = 7 2012

Verum Diagnostica GmbH c/o Maximilian Zucker, Ph.D. Reichenbachstrasse 27 80469 Munich Germany

Re: K103555

Trade/Device Name: Verum Multiplate 5.0 Regulation Number: 21 CFR 864.5700 Regulation Name: Automated Platelet Aggregation System Regulatory Class: Class II Product Code: JOZ Dated: June 19, 2012 Received: June 22, 2012

Dear Dr. Zucker:

This letter corrects our substantially equivalent letter of July 27, 2012.

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 (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 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 Part 801); 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 you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please go to

http://www.fda.gov/AboutFDA/CentersOffices/CDRH/CDRHOffices/ucm115809.htm for the Center for Devices and Radiological Health's (CDRH's) Office of Compliance. 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/Resourcesfor You/Industry/default.htm.

Sincerely yours,

Reena Philip

Maria M. Chan, 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):

K103555

Device Name: Multiplate 5.0 (Indications for Use of the ADPtest)

Indications For Use:

Prescription Use X (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)

Division Sign-Off

Office of In Vitro Diagnostic
Device Evaluation and Safety

510(k) K103555

Page 1 of

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Indications for Use

510(k) Number (if known): K103555

Device Name:

Multiplate 5.0 (Indications for Use of the ASPItest)

Indications For Use:

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)

Reena Philip

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

S10K K103555

Page 1 of

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Indications for Use

510(k) Number (if known):

Device Name: Multiplate 5.0 (Indications for Use of the Liquid Control Set)

K103555

Indications For Use:

For use as an assayed quality control verification of the resistance measure of impedance aggregometry.

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)

Division Sign-Off

510k)

Office of In Vitro Diagnostic Device Evaluation and Safety

K103555

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).