The intended use of the Sysmex® CA-1500 is as a fully automated, computerized blood plasma coagulation analyzer for in vitro diagnostic use in clinical laboratories.

The instrument uses citrated human plasma to perform the following parameters and calculated parameters:

Clotting Analysis Parameters

Prothrombin Time (PT) .
Activated Partial Thromboplastin Time (APTT) .
Fibrinogen (Clauss) .

Chromogenic Analysis Parameters

Antithrombin III .
Calculated Parameters
. PT Ratio
PT INR
PT % ●
Extrinsic Factors (II, V, VII, X) ● Intrinsic Factors (VIII, IX, XI, XII) .
Derived Fibrinogen ●
Factor Assays % Activity .

Device Description

The CA-1500 is substantially equivalent in intended use and technological characteristics to the Sysmex® Automated Coagulation Analyzer CA-6000, Sysmex Corporation, Kobe, Japan, which was cleared by FDA under Document Control Nos. K964139 and K992321; or the Behring Coagulation Timer (BCT), Dade Behring, Marburg, Germany which was cleared by FDA under Document Control No. K955278.

AI/ML Overview

Here's an analysis of the provided text regarding the Sysmex® Automated Coagulation Analyzer CA-1500, focusing on acceptance criteria and the supporting study:

The provided document is a 510(k) Summary of Safety and Effectiveness Information for the Sysmex® Automated Coagulation Analyzer CA-1500, submitted to the FDA in 1999. It focuses on demonstrating substantial equivalence to predicate devices, primarily through method comparison and precision studies.

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria in terms of specific thresholds (e.g., "r > 0.95"). Instead, it reports the performance metrics achieved in comparison and precision studies, implying these demonstrate "similarity" or acceptable performance when compared to predicate devices. The key performance indicators used are the Coefficient of Correlation (r) for method comparison and various Coefficient of Variation (%CV) for precision.

Below is a table summarizing the reported device performance from the provided study, which serves as the de-facto demonstration of meeting acceptance for substantial equivalence:

Test	Performance Metric (Method Comparison)	Reported Value (Method Comparison)	Predicate Device	Performance Metric (Precision - Total %CV)	Reported Range (Precision - Total %CV)
Prothrombin Time (Innovin®, Seconds)	Coefficient of Correlation (r)	0.999	CA-6000	Total %CV	0.6 - 1.4
Prothrombin Time (Innovin®, INR)	Coefficient of Correlation (r)	0.999	CA-6000	Total %CV	0.6 - 1.4
Prothrombin Time (Thromborel® S, Seconds)	Coefficient of Correlation (r)	0.998	BCT	Total %CV	2.1 - 3.0
Prothrombin Time (Thromborel® S, %)	Coefficient of Correlation (r)	0.996	BCT	Total %CV	3.6 - 4.2
Derived Fibrinogen	Coefficient of Correlation (r)	0.945	BCT	Total %CV	4.7 - 2.6
Activated Partial Thromboplastin Time	Coefficient of Correlation (r)	0.995	CA-6000	Total %CV	2.4 - 2.0
Fibrinogen (Clauss)	Coefficient of Correlation (r)	0.985	CA-6000	Total %CV	3.2 - 9.2
Factor VII	Coefficient of Correlation (r)	0.997	CA-6000	Total %CV	2.7 - 3.0
Factor VIII	Coefficient of Correlation (r)	0.990	CA-6000	Total %CV	3.6 - 4.6
Antithrombin III	Coefficient of Correlation (r)	0.998	BCT	Total %CV	4.8 - 8.1

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

The "test set" in this context refers to the samples used in the clinical correlation (method comparison) studies and precision studies.

Clinical Correlation (Method Comparison) Studies:
- Sample sizes ranged from 66 to 165 samples, depending on the specific test.
- Data Provenance: The specimens were evaluated from "apparently healthy individuals and from patients with different pathological conditions." The country of origin is not explicitly stated, but Dade Behring Inc. is based in Miami, FL, and Sysmex Corporation in Kobe, Japan. Given the submission is to the FDA, it is most likely that at least some, if not all, of the clinical correlation studies were performed using data from the US, or globally applicable data following international standards. The studies appear to be prospective in the sense that they were conducted for the purpose of this submission (as clinical correlation studies comparing the new device to predicates).
Precision Studies:
- For all precision studies, the sample size (N) was 40. Note: For precision, N refers to the number of replicates or measurements taken, not necessarily unique patient samples.
- Data Provenance: The study utilized "Control Level" samples, specifically "CPN" (Control Plasma Normal) and either "Path. Pool" (Pathological Pool) or "CPP" (Control Plasma Pathological). These are likely commercially prepared quality control materials or pooled patient samples designed for assay validation. The provenance (country, retrospective/prospective) for these specific control materials is not detailed.

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

This type of submission (510(k) for an automated coagulation analyzer) does not involve human expert interpretation of images or clinical findings to establish a "ground truth" in the way medical imaging AI devices do.

Instead, the "ground truth" for the test set is established by the predicate devices (Sysmex® Automated Coagulation Analyzer CA-6000 and Behring Coagulation Timer (BCT)), which are legally marketed and accepted devices for performing these coagulation tests. The new device's results are compared to the predicate device's results.

Therefore, there were no human experts establishing ground truth in the typical sense for this device. The 'gold standard' is the measurement provided by the established predicate device and associated reference methods/standards for coagulation assays.

4. Adjudication Method for the Test Set

As explained above, there isn't an "adjudication method" involving human experts in the context of this device. The comparison is between the quantitative results of the proposed device and the predicate device. If discrepancies were observed, standard laboratory procedures for investigating outliers or re-running samples would be employed, but not a panel of experts adjudicating a "truth."

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. MRMC studies are typically used for diagnostic imaging devices where human readers interpret medical images, and the AI's impact on their performance (e.g., accuracy, efficiency) is measured. This submission is for an automated laboratory analyzer, which produces quantitative results directly, not interpretations by human readers in the same way.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, the provided studies are for standalone performance. The Sysmex® Automated Coagulation Analyzer CA-1500 is an in vitro diagnostic (IVD) device designed to perform coagulation tests automatically. The method comparison and precision studies directly evaluate the performance of this analyzer (the "algorithm/device only") without human intervention during the measurement process, beyond loading samples and reagents. The results presented (correlation coefficients, %CV) represent the inherent analytical performance of the device itself.

7. The Type of Ground Truth Used

The "ground truth" for the method comparison studies was established by the measurements obtained from the legally marketed predicate devices (Sysmex® CA-6000 and Behring Coagulation Timer (BCT)). For precision studies, the ground truth refers to the expected or consensus values for the control materials used. This is a form of reference method/predicate device comparison rather than pathology, expert consensus, or outcomes data in the traditional sense.

8. The Sample Size for the Training Set

The document does not mention a "training set" in the context of machine learning or AI models, as this is a traditional IVD device. The device's operation is based on established electrochemical/optical principles and pre-programmed algorithms for signal processing and calculation, not on a machine learning model that requires a distinct training phase with labeled data.

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

As there is no mention of a "training set" for an AI model, this question is not applicable to the provided document. The device's operational parameters and algorithms would have been developed and validated internally by the manufacturer through engineering design, laboratory testing, and adherence to performance specifications, rather than through an AI training paradigm.

Summary

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DEC - 7 1999

K993299

510(k) Summary of Safety and Effectiveness Information Sysmex ® Automated Coagulation Analyzer CA-1500 September 30, 1999

Dade Behring Inc. 1851 Delaware Parkway Miami, FL 33125 Contact Person: Radames Riesgo at 305.636.7727 or by facsimile at 305.637.6887.

Trade or Proprietary Name: Sysmex® Automated Coagulation Analyzer CA-1500

Common or Usual Name:	Automated Coagulation Instruments
Classification Name:	Coagulation instrument (21 CFR §864.5400)
Registration Number:
	Manufacturing SiteSysmex CorporationKobe, Japan	9613959
	ImporterSysmex Corporation of AmericaOne Wildlife WayLong Grove, IL 60047-9596	1422681
	DistributorDade Behring Inc.Glasgow SiteP.O. Box 6101Newark, DE 19714-6101	2517506

As demonstrated by clinical correlation studies, the performance claims of the proposed device are similar to the predicate devices. During those studies, specimens were evaluated from apparently healthy individuals and from patients with different pathological conditions which are expected to affect the results for a particular assay. The following summary shows the results of the comparison studies between the proposed and the predicate devices.

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510(k) Summary of Safety and Effectiveness Information Sysmex® Automated Coagulation Analyzer CA-1500 Page 2

Test	Predicate Device	Sample Number (n)	Coefficient of Correlation (r)	Regression Equation
Prothrombin Time(Innovin®, Seconds)	CA-6000	165	0.999	Y = 0.97X + 0.09
Prothrombin Time(Innovin®, INR)	CA-6000	165	0.999	Y = 0.99X + 0.01
Prothrombin Time(Thromborel® S, Seconds)	BCT	163	0.998	Y = 1.04X - 0.51
Prothrombin Time(Thromborel® S, %)	BCT	161	0.996	Y = 1.08X - 2.44
Derived Fibrinogen	BCT	149	0.945	Y = 1.17X - 0.54
Activated Partial Thromboplastin Time	CA-6000	128	0.995	Y = 1.00X + 0.15
Fibrinogen (Clauss)	CA-6000	115	0.985	Y = 0.96X + 0.41
Factor VII	CA-6000	122	0.997	Y = 1.04X - 1.67
Factor VIII	CA-6000	66	0.990	Y = 0.96X + 4.25
Antithrombin III	BCT	104	0.998	Y = 0.97X - 4.72

Summary of Method Comparison Studies Between CA-1500 and CA-6000 or BCT

Summary of Precision Studies Sysmex® Automated Coagulation Analyzer CA-1500

Sysmex® Automated Coagulation Analyzer CA-1500
Test	ControlLevel	N	Mean	WithinRun%CV	BetweenRun%CV	Total%CV
Prothrombin Time(Dade® Innovin®, Seconds)	CPNPath. Pool	40	11.523.3	0.41.2	0.50.9	0.61.4
Prothrombin Time(Dade® Innovin®, INR)	CPNPath. Pool	40	1.12.2	0.41.2	0.50.9	0.61.4
Prothrombin Time(Thromborel® S, Seconds)	CPNPath. Pool	40	11.828.4	0.60.6	2.03.0	2.13.0
Prothrombin Time(Thromborel® S, %)	CPNPath. Pool	40	95.023.4	0.90.8	3.44.1	3.64.2
Derived Fibrinogen(Dade® Innovin® on CA-1500)	CPNPath. Pool	40	1.85.0	3.72.4	3.21.2	4.72.6
Activated Partial ThromboplastinTime (Dade® Actin® FSL)	CPNPath. Pool	40	28.139.5	2.10.5	1.41.9	2.42.0
Fibrinogen (Clauss)(Dade® Thrombin Reagent)	CPNCPP	40	2.70.7	1.98.4	2.74.9	3.29.2
Factor VII(Dade® Innovin®)	CPNCPP	40	91.632.5	2.52.3	1.52.1	2.73.0
Factor VIII(Dade® Actin® FSL)	CPNCPP	40	89.126.0	1.61.8	3.34.3	3.64.6
Antithrombin III(Berichrom® Antithrombin III(A))	CPNCPP	40	97.432.3	1.32.7	4.67.6	4.88.1

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Image /page/2/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 lines representing its wings or feathers. The eagle is facing to the left. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" is arranged in a circular fashion around the eagle.

DEC - 7 1999

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Mr. Radames Riesgo Manager, Regulatory Affairs Biology Dade Behring. Inc. 1851 Delaware Parkway Miami, Florida 33125

K993299 Trade Name: Sysmex® Automated Coagulation Analyzer CA-1500 Regulatory Class: II Product Code: GKP Dated: September 30, 1999 Received: October 1, 1999

Dear Mr. Riesgo:

Re:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we 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). 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 (Premarket Approval), 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 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (OS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic OS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition. FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.

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Page 2

Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770) 488-7655.

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 predicate device results in a classification 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 (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification"(21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers 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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510(k) Number (if known): K9932999

Device Name: Sysmex® Automated Coagulation Analyzer CA-1500

Indications for Use:

The intended use of the Sysmex® CA-1500 is as a fully automated, computerized blood plasma coagulation analyzer for in vitro diagnostic use in clinical laboratories.

The instrument uses citrated human plasma to perform the following parameters and calculated parameters:

Clotting Analysis Parameters

Prothrombin Time (PT) .
Activated Partial Thromboplastin Time (APTT) .
Fibrinogen (Clauss) .

Chromogenic Analysis Parameters

Antithrombin III .
Calculated Parameters
. PT Ratio
PT INR
PT % ●
Extrinsic Factors (II, V, VII, X) ● Intrinsic Factors (VIII, IX, XI, XII) .
Derived Fibrinogen ●
Factor Assays % Activity .

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Peter E. Madini

Clinical Laboratory Device

Prescription Use (Per 21 CFR 801.109)

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

Regulation Number and Section

§ 864.5400 Coagulation instrument.

(a)
Identification. A coagulation instrument is an automated or semiautomated device used to determine the onset of clot formation for in vitro coagulation studies.(b)
Classification. Class II (special controls). A fibrometer or coagulation timer intended for use with a coagulation instrument is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 864.9.