For in vitro diagnostic use with the CARESIDE Analyzer to measure activated partial thromboplastin time from citrated whole blood or citrated plasma as an aid in the diagnosis of patients with clotting disorders and to monitor patients receiving heparin anticoagulation therapy.

Device Description

CARESIDE APTT cartridges are used with the CARESIDE Analyzer to measure activated partial thromboplastin time from citrated whole blood or plasma as the applied sample. The CARESIDE APTT cartridge, a single use disposable in vitro diagnostic test cartridge, aids in specimen separation and delivers a measured volume of plasma to a cartridge cuvette to initiate the measurement of an activated partial thromboplastin time. The patented cartridge contains all reagents necessary to measure an activated partial thromboplastin time.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the CARESIDE APTT device, based on the provided text:

Acceptance Criteria and Device Performance

Acceptance Criteria (Predicate Device Performance)	Reported CARESIDE APTT Device Performance
Reportable Range: 14 to 106 sec	Reportable Range: 20 to 140 sec
Precision: Total CV, 25 sec, less than 5%	Precision: Total CV, 29 sec, 4.1%
Accuracy: Not explicitly stated as a separate criterion, but likely implicitly expected to be comparable to the predicate device.	Accuracy via Method Comparison: CARESIDE = 0.96 (Actin on Electra 900C) + 3.16 sec, r = 0.94
- (Interference information not provided for predicate)	Interference: No significant interference observed at tested concentration of interferent (Bilirubin 10 mg/dL, Hemoglobin 250 mg/dL, Triglyceride 390 mg/dL)

Note on Acceptance Criteria: The document primarily focuses on demonstrating substantial equivalence to a predicate device (Dade Actin on Electra 900C). Therefore, the "acceptance criteria" are generally derived from the established performance characteristics of that predicate device. The CARESIDE APTT aims to meet or improve upon these characteristics.

Study Information

Due to the nature of the provided 510(k) summary for an in vitro diagnostic device (APTT test), the study information is structured differently than for a typical AI/software device. Many of the requested categories (e.g., expert ground truth, MRMC, training set details) are not directly applicable or are not explicitly detailed in this type of submission.

Here's an attempt to answer the questions based on the available text:

Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective):
- Sample Size: Not explicitly stated for the "test set" in terms of number of patient samples. The "Accuracy via Method Comparison" likely involved a set of samples compared against the predicate device, but the exact number isn't provided.
- Data Provenance: Not specified. It's common for such studies to be conducted by the manufacturer or their contract research organizations, but the location or whether it was retrospective/prospective is not mentioned.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience):
- This is an in vitro diagnostic device for measuring Activated Partial Thromboplastin Time (APTT). The "ground truth" for APTT measurements is typically established by laboratory testing using a reference method or predicate device, not by human experts adjudicating images or clinical cases. The predicate device (Dade Actin on Electra 900C) serves as the de-facto "ground truth" for comparison in the method comparison study. Therefore, this question is not directly applicable in the context of this device.
Adjudication method (e.g. 2+1, 3+1, none) for the test set:
- Not applicable. As this is an in vitro diagnostic device, "adjudication" in the sense of clinical expert consensus for interpreting results is not typically part of the regulatory submission for establishing performance. Performance is determined by quantitative comparison to a reference method.
If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
- No. This is an in vitro diagnostic device, not an AI-powered diagnostic imaging tool for human interpretation. Therefore, an MRMC study is not relevant or performed for this type of device.
If a standalone (i.e. algorithm only without human-in-the loop performance) was done:
- Yes, the performance data presented (accuracy, precision, interference) would be considered standalone performance of the device itself (CARESIDE APTT + CARESIDE Analyzer) measuring the APTT parameter. While a human initiates the test and interprets the final numerical result, the "performance" data refers to the accuracy and reliability of the device's measurement process.
The type of ground truth used (expert consensus, pathology, outcomes data, etc):
- The "ground truth" for evaluating the CARESIDE APTT device's performance is the measurement obtained from the legally marketed predicate device, Dade Actin on the Electra 900C. The study aims to show that the CARESIDE APTT measurements correlate highly and are substantially equivalent to those from the predicate.
The sample size for the training set:
- This document describes a premarket notification for an in vitro diagnostic assay, not a machine learning or AI algorithm in the contemporary sense that would involve explicit training data in the way an AI model is trained. Therefore, a "training set" as defined for AI is not applicable or mentioned. Device development involves calibration and validation, but not typically a "training set" for an algorithm in this context.
How the ground truth for the training set was established:
- Not applicable, as a "training set" for an AI algorithm is not implied by the provided text. The device is a diagnostic instrument and reagent system.

Summary

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CARESIDE, Inc. Page 10

FEB 0 8 2002

K014028

CARESIDE APTT Premarket Notification December 4, 2001

510(K) SUMMARY: CARESIDE APTT TIME SAFETY IV. AND EFFECTIVENESS

I. Applicant Information

A. Applicant Name
B. Applicant/Manufacturer Address
C. Telephone Number
Contact Person D.
E. FAX Number
P. e-Mail Address
Date 510(k) Summary prepared G.

II. Device Information

Device Name (Trade) A.
Device Name (Classification) B.
C. Device Classification

CARESIDE, Inc.

6100 Bristol Parkway Culver City, CA 90230 310-338-6767 Kenneth B. Asarch, Pharm.D., Ph.D. 310-670-6986 kasarch@careside.com December 4, 2001

CARESIDE APTT

APTT test system Hematology and Pathology Panel Activated partial thromboplastin time test system Regulation Number: 21 CFR 864.7925 Regulatory Class 2 Classification Number: 81GFO Subject to performance standard, but none published

D. Special controls and performance standards

III. Substantial Equivalence Claim

A. General equivalency claim

The ability to monitor clotting time tests in a variety of formats is widely recognized and has gained widespread acceptance.

Activated partial thromboplastin time in vitro diagnostic products are already on the U.S. market, including activated partial thromboplastin time products that utilize optical clot detection and reagents based upon rabbit brain phospholipids and a silicate activator, kaolin.

B. Specific equivalency claim

This CARESIDE APTT test is substantially equivalent in principle, intended use, and clinical performance to the currently marketed Actin® (also known as Dade Actin, manufactured by Dade Behring) reagent for the quantitative measurement of activated partial thromboplastin time on Medical Laboratory Automation's (MLA) Hemoliance Electra 900C (henceforth refered to as Electra 900C or MLA Electra 900C).

Name of Predicate Device: Dade Actin on the Electra 900C. Predicate Device 510K number: K884863 (MLA Electra 900C) K760318 (Dade Actin) Product Code: 81GF0

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IV. Device Description

a. Explanation of Device Function

Each CARESIDE APTT cartridge consists of a cuvette with dried rabbit brain phospholipid with kaolin mounted in a plastic cartridge with a hinged lid. The user introduces the citrated whole blood or plasma specimen into the cartridge sample well, closes the lid and inserts the cartridge into the CARESIDE Analyzer.

Once loaded, the CARESIDE Analyzer scans the cartridge barcode, brings the cartridge and the contained specimen to 37℃, and spins the cartridge to move the sample from the Sample Well into the cartridge channels and chambers. As the cartridge continues to spin. the blood cells are separated from the plasma and the cells accumulate in the Separation Well.

The APTT test is a two-step process. The first step of the APTT test involves reconstitution of the dried reagent in the cartridge cuvette by the sample and subsequent incubation. Forty microliters of citrated plasma remains in the metering passage after spinning is completed. Any excess sample flows into an Overflow Well. The metered volume of sample is dispensed into the cuvette by a plunger that displaces a flexible seal that covers the Sample Well while a second plunger seals the cartridge vent. As the flexible seal is displaced, air is pushed through the metering passage, forcing the sample out and into the cuvette. The sample reconstitutes the dried reagent in the cuvette. The sample and reagent within the cartridge is mixed and incubated for 3 minutes.

In the second step of the APTT, 80 microliters of a 15 mM calcium chloride pouch reagent is added to initiate the coagulation reactions. To accomplish the addition, a plunger breaks a foil pouch housed within the test cartridge and pushes the calcium chloride reagent into the cuvette. The calcium chloride is mixed with the sample and a phospholipid/activator. The cuvette is then positioned over an LED and the coagulation event is optically monitored. An onboard timer automatically measures the coagulation time.

b. Test Cartridge Architecture

Sample 1 Dried APTT Reagent -APTT Reagent/Plasma Calcium > Stable Clot Contact Activated Plasma -

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c. Test Summary

Phospholipids, a contact activator, and calcium are required to initiate clotting in an APTT test. The use of a contact activator, kaolin, which standardizes the activation of factor XII is an advancement (introduced over 30 years ago) over the original partial thromboplastin time test (PTT).

Under these conditions, the time required for the formation of a fibrin clot provides information regarding the presence and activity of coagulation factors. An activated partial thromboplastin time test is recommended to be sensitive to coagulation factor abnormalities and to factor inhibitors affecting coagulation factors VIII, IX, X, XI, XII, prekallikrein, and kininogen. CARESIDE APTT is sensitive to deficiencies in these factors.

Activated partial thromboplastin time tests are used as a screening test APTT is for the intrinsic and common coagulation pathways. commonly used to monitor heparin anticoagulant therapy.

Intrinsic Coagulation Pathway

[Abbreviations: Roman numerals refer to factors, subscript "a" refers to activated form, PK refers to prekallekrein, and HMWK refers to kininogen (high molecular weight kininogen)]

Image /page/2/Figure/8 description: This image shows a diagram of the intrinsic pathway of coagulation. Factor XII is converted to XIIa by PK and HMWK. XIIa then converts XI to XIa, which converts IX to IXa. IXa then converts VIII to its activated form.

Image /page/2/Figure/9 description: The image shows the text "VIIIa" in a bold, sans-serif font. The text is black against a white background. The Roman numeral VIII is followed by the lowercase letter 'a'.

$$\mathbf{x} \xrightarrow[]{\text{vulla}} \mathbf{Xa}$$

Xa, Va → Thrombin Prothrombin -

Thrombin → Fibrin → Cross linked Fibrin Fibrinogen

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V. Intended Use

Intended Use A.

The CARESIDE APTT cartridge is intended for in vitro diagnostic use in conjunction with CARESIDE Analyzer to quantitatively measure activated partial thromboplastin time in citrated whole blood or citrated plasma.

B. Indications for Use
For in vitro diagnostic use with the CARESIDE Analyzer to measure activated partial thromboplastin time from citrated whole blood or citrated plasma as an aid in the diagnosis of patients with clotting disorders and to monitor patients receiving heparin anticoagulation therapy.

Technological Characteristics VI.

Similarities A.

	CARESIDE APTT	Actin on Electra 900C
Intended Use	For in vitro diagnostic use toaid in the diagnosis of patientswith clotting disorders and tomonitor patients receivinganticoagulation therapy.	For in vitro diagnostic use todetermine the activated partialthromboplastin time and othercoagulation tests requiring anactivated partial thromboplastinreagent.
Measurementtype	Quantitative	Same
Method Principle	Optical clot detection basedupon rabbit brain phospholipidreagent with kaolin activator	Optical clot detectionbasedupon rabbit brain phospholipidreagent
Specimen dilution	Not required	Same
Materials	Rabbit brain phospholipid withkaolin + calcium chloride	Rabbit brain Cephaline(phospholipid) in ellagic acid +calcium chloride
DetectionPrinciple	Photometric detection of"knee" of transmission-timetrace; 570 nM	Same; 550 nM
Test time	Approx. 12 minutes: includeswarm-up (on-board), andincubation, and 3 minutes clotmonitoring time.	Warm-up, 3 minute incubation,plus clot monitoring time.
Sample Type	Citrated whole blood orCitrated plasma	Citrated plasma
Specimen volume	40 microliter test volume(300±50 microliter appliedwhole blood or plasma)	100 microliter volume (plasma)
Quality Control	External, multi-level controls	Same
Reporting Units	Sec	Same
Reaction Temp.	37°C	Same

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Differences B.

	CARESIDE APTT	Actin on Electra 900C
Direct bloodspecimen	Yes, whole blood	No, requires separation ofwhole blood prior to sampleapplication
Reportable range	20 to 140 sec	14 to 106 sec
Accuratepipetting	Not required	Required
Reagent pre-warming	Not required	Required

C. Comparative Performance Characteristics

	CARESIDE APTT	Actin on Electra 900C
Reportable range	20 to 140 sec	14 to 106 sec
Accuracy viaMethodcomparison	CARESIDE = 0.96 (Actin on Electra 900C ) + 3.16 sec,r = 0.94
Precision	Total CV, 29sec, 4.1%	Total CV, 25sec, less than 5%
Interference	No significant interferenceobserved at testedconcentration of interferent:Bilirubin 10 mg/dLHemoglobin 250 mg/dLTriglyceride 390 mg/dL	Not provided.

D. Conclusion

The nonclinical and clinical data provided demonstrate that the CARESIDE APTT product is as safe, effective, and performs as well as or better than the legally marketed predicate device.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/5/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 three stripes representing the department's mission to promote health, well-being, and human services. The eagle is encircled by the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA".

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

FEB 0 8 2002

Kenneth B. Asarch, Pharm.D., Ph.D. VP Quality Systems and Regulatory Affairs CARESIDE, Inc. 6100 Bristol Parkway Culver City, CA 90230

Re: K014028

Trade/Device Name: CARESIDE APTT Regulation Number: 21 CFR 864.7925 Regulation Name: Partial thromboplastin time tests Regulatory Class: Class II Product Code: GFO Dated: December 4, 2001 Received: December 6, 2001

Dear Dr. Asarch:

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.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such 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 801); 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 -

This letter will allow you to begin marketing your device as described in your 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed nothication. The I Dri Imanig of Sustion for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (2) CFFR Part 801 and 1 IT you desire specific acrise of november devices), please contact the Office of Compliance at additionally 007.10 for mi rice ar questions on the promotion and advertising of your device, (201) 594-4508. Additionally, 10. quice at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Information on your responsioner Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsma/dsmamain.html".

Sincerely yours,

Steven Sutman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory-Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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CARESIDE, Inc. Page 16

VI. INDICATIONS FOR USE

510(k) Number:

K014028

Device Name:

CARESIDE APTT

Indications for use:

For in vitro diagnostic use with the CARESIDE Analyzer to measure activated partial thromboplastin time from citrated whole blood or citrated plasma as an partial in the diagnosis of patients with clotting disorders and to monitor patients receiving heparin anticoagulation therapy.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

(Division DivisionVof Clinical La 510(k) Number

Prescription Use
(Per 21 CFR 801.109)

Over-The-Counter Use (Optional Format 1-2-96)

Regulation Number and Section

§ 864.7925 Partial thromboplastin time tests.

(a)
Identification. A partial thromboplastin time test is a device used for primary screening for coagulation abnormalities, for evaluation of the effect of therapy on procoagulant disorders, and as an assay for coagulation factor deficiencies of the intrinsic coagulation pathway.(b)
Classification. Class II (performance standards).