PT-S TEST STRIPS FOR THE COAGUCHEK SYSTEM, MODEL# 2032422 by ROCHE DIAGNOSTICS CORP.

The CoaguChek System is intended for quantitative Prothrombin Time (PT) testing for monitoring of warfarin therapy, using fresh capillary or non-anticoagulated venous whole blood by professional healthcare providers.

Device Description

The PT•S test strip is intended for quantitative prothrombin time (PT) testing for monitoring of warfarin therapy, using fresh capillary or non-anticoagulated venous whole blood with the CoaguChek System by professional health care providers. Blood coagulation is one of the body's protective responses. Blood clots (thrombi) form as a direct response to vessel injury, preventing excessive loss of blood. Certain disease conditions require oral anticoagulants, sometimes known as blood thinners. Warfarin, sometimes known as Coumadin®, is a commonly used anticoagulant. Patients on warfarin must be carefully monitored to ensure the anticoagulant level is maintained in the therapeutic range. One method for monitoring the anticoagulant level is by using the one-stage Prothrombin Time (PT) Test. The PT•S test strip uses a modified version of this method. The PT•S test strip, used as directed with the CoaguChek monitor, will accurately measure blood PT values. After placing a drop of fresh whole blood on the test strip, the blood is drawn into the reaction chamber and mixed with reagents that cause coagulation to begin. In the test strip, tiny iron particles are mixed with the sample. Alternating magnetic fields cause the iron particles to move within the sample. The endpoint is reached when the blood clot stops the iron particles from moving. The PT result is then displayed by the monitor.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the PT•S Test Strips and Controls for the CoaguChek System, based on the provided 510(k) summary:

Acceptance Criteria and Device Performance

The acceptance criteria are not explicitly stated as distinct pass/fail thresholds in the provided document. Instead, the submission demonstrates equivalence to the predicate device by comparing performance characteristics. For this reason, the "Acceptance Criteria" column below reflects the performance observed for the predicate device (ITC ProTime Microcoagulation System), which the PT•S system aims to be substantially equivalent to, and the "Reported Device Performance" shows the results for the PT•S system.

Acceptance Criteria (Predicate Device Performance)	Reported Device Performance (PT•S Test Strips)
Precision with Controls	Level 1 (Mean INR 1.3 Controls):
Standard ProTime Cuvette:	Lot to Lot SD: 0.02 (%CV: 1.72)
Level I: within day 0.9 (SD 0.06)	Monitor to monitor SD: 0.01 (%CV: 0.95)
day to day 1.0 (SD 0.08)	Strip to strip SD: 0.04 (%CV: 3.32)
Level III: within day 3.2 (SD 0.19)	Total SD: 0.05 (%CV: 3.86)
day to day 3.2 (SD 0.12)	Level 2 (Mean INR 3.4 Controls):
ProTime 3 Cuvette:	Lot to Lot SD: 0.05 (%CV: 1.33)
Level I: within day 0.9 (SD 0.07)	Monitor to monitor SD: 0.08 (%CV: 2.22)
day to day 0.9 (SD 0.12)	Strip to strip SD: 0.13 (%CV: 3.79)
Level III: within day 4.0 (SD 0.19)	Total SD: 0.16 (%CV: 4.59)
day to day 4.2 (SD 0.22)
Accuracy (Regression vs. Lab Plasma)	Venous Samples:
Standard ProTime Cuvette (Fingerstick): y=0.94x + 0.38 (r=0.95)	Regression Equation: y = 1.065x - 0.12 (Slope CI: 1.041, 1.090; Intercept CI: -0.19, -0.06; Correlation: 0.961)
Standard ProTime Cuvette (Venous): y=0.91x + 0.44 (r=0.94)	Capillary Samples:
ProTime 3 Cuvette (Fingerstick): y=1.05x + 0.07 (r=0.95)	Regression Equation: y = 1.089x - 0.17 (Slope CI: 1.058, 1.119; Intercept CI: -0.25, -0.09; Correlation: 0.958)
ProTime 3 Cuvette (Venous): y=0.97x + 0.19 (r=0.95)
Normal Range	99% of venous and capillary INRs ranged from 0.8 to 1.1 for 122 normal, healthy, warfarin-free individuals.
Reportable Range	0.8 - 8.0 INR
Hematocrit Range	32-52% (no significant effect)
Heparin Levels	Unaffected up to 2.0 U/mL heparin and insensitive to low molecular weight heparins up to 1 IU anti-factor Xa activity/mL (for PT•S, predicate stated "may be affected")

Study Details

This submission describes standalone performance of the device, not a comparative effectiveness study with human readers.

Sample Size Used for the Test Set and Data Provenance:
- Normal Range: 122 normal, healthy, warfarin-free individuals. Sample types: Venous and capillary. Data provenance: Not explicitly stated, but likely prospective to gather data specifically for this device's normal range. Country of origin not specified, but usually presumed US for FDA submissions unless otherwise stated.
- Precision with Controls: Two levels of liquid controls, three test strip lots, nine CoaguChek monitors. The number of replicates for each control level, monitor, and lot is detailed in the table. This is an internal study.
- Accuracy (Venous Samples): 610 venous samples collected from 309 outpatients. Data provenance: Prospective observational study at four external sites. Country of origin not specified.
- Accuracy (Capillary Samples): 448 capillary samples collected from 226 outpatients. Data provenance: Prospective observational study at three external sites. Country of origin not specified.
- Factor Sensitivity: Internal studies utilizing four replicates of each Factor Level (II, V, VII and X).
- Hematocrit Range: Internal studies, details on sample size not provided in the summary.
- Heparin Levels: Internal studies, details on sample size not provided in the summary.
Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications:
- For the accuracy studies, the ground truth was established by laboratory plasma samples measured on an MLA 900 Analyzer using Ortho Recombiplastin. This is an automated laboratory instrument using a standardized reagent, implying no human expert "ground truth" per se. The device's performance is compared against this established laboratory method.
Adjudication Method for the Test Set:
- Not applicable as the ground truth was an automated laboratory reference method, not human expert interpretation requiring adjudication.
Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
- No. This is a medical device for measuring Prothrombin Time (PT) and INR, not an imaging or interpretive AI system that would typically involve human readers.
Standalone Performance:
- Yes, the studies presented are for the standalone performance (algorithm only, though "algorithm" here refers to the device's measurement mechanism) of the PT•S test strips used with the CoaguChek monitor, without a human-in-the-loop component for result interpretation. Healthcare providers use the device, but the measurement itself is automated.
Type of Ground Truth Used:
- Laboratory-based reference method: For accuracy, the PT•S system's results were compared to INR values obtained from venous plasma samples measured on an MLA 900 Analyzer using Ortho Recombiplastin. This is considered the gold standard or reference method for Prothrombin Time testing.
- For the normal range determination, individuals were classified as "normal, healthy, warfarin-free," which represents a clinical ground truth for typical INR values.
Sample Size for the Training Set:
- The document does not explicitly mention a "training set" in the context of device development or algorithm training. This device appears to be based on a physical-chemical reaction and an electromechanical detection system, rather than a machine learning algorithm requiring a distinct training phase. Therefore, the concept of a "training set" as understood in AI/ML is not directly applicable here. The internal studies and method development would involve extensive testing and refinement, but not in the sense of an ML training set.
How the Ground Truth for the Training Set Was Established:
- As noted above, a distinct "training set" and corresponding ground truth establishment process, as typically seen in AI/ML, is not described or implied for this type of device. The development and internal validation would have relied on established laboratory standards and comparisons to known PT values from various sources.

Summary

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K021190

510(k) Summary	OCT 25 2002
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Introduction	According to the requirements of 21 CFR 807.92, the following information provides sufficient detail to understand the basis for a determination of substantial equivalence.
1) Submitter name, address, contact	Roche Diagnostics Corporation 9115 Hague Rd. P.O. Box 50457 Indianapolis, IN 46250-0457 Contact Person: Jennifer Tribbett Date Prepared: October 21, 2002
2) Device name	Proprietary name: PT•S Test Strips and Controls for the CoaguChek System Common name: Prothrombin time test Classification name: Prothrombin time test
3) Predicate device	We claim substantial equivalence to International Technidyne Corporation's (ITC) ProTime Microcoagulation System- ProTime 3 Cuvette (K010599)

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4) DeviceDescription	The PT•S test strip is intended for quantitative prothrombin time (PT) testingfor monitoring of warfarin therapy, using fresh capillary or non-anticoagulated venous whole blood with the CoaguChek System byprofessional health care providers.
	Blood coagulation is one of the body's protective responses. Blood clots(thrombi) form as a direct response to vessel injury, preventing excessive lossof blood. Certain disease conditions require oral anticoagulants, sometimesknown as blood thinners. Warfarin, sometimes known as Coumadin®, is acommonly used anticoagulant. Patients on warfarin must be carefullymonitored to ensure the anticoagulant level is maintained in the therapeuticrange. One method for monitoring the anticoagulant level is by using theone-stage Prothrombin Time (PT) Test. The PT•S test strip uses a modifiedversion of this method.
	The PT•S test strip, used as directed with the CoaguChek monitor, willaccurately measure blood PT values. After placing a drop of fresh wholeblood on the test strip, the blood is drawn into the reaction chamber andmixed with reagents that cause coagulation to begin. In the test strip, tinyiron particles are mixed with the sample. Alternating magnetic fields causethe iron particles to move within the sample. The endpoint is reached whenthe blood clot stops the iron particles from moving. The PT result is thendisplayed by the monitor.
5) Intended use	For quantitative Prothrombin Time (PT) testing for monitoring of warfarintherapy, using fresh capillary or non-anticoagulated venous whole blood byprofessional health care providers.
6) Comparisonto predicatedevice	The Roche Diagnostics PT•S test strip and controls for the CoaguChekSystem are substantially equivalent to other products in commercialdistribution intended for similar use. Most notably, the PT•S test strip andcontrols are substantially equivalent to International TechnidyneCorporation's (ITC) ProTime Microcoagulation System- ProTime 3 Cuvette(K010599).
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Similarities topredicatedevice	The PT•S test strip and controls are similar to the ITC ProTime System in thefollowing items:
Topic	ProTime Microcoagulation System(K010599)As Indicated in the ProTime Device Insert	PT•S Test Strips For Use WithCoaguChek System
Intended Use	For the quantitative determination ofprothrombin time from fingerstick wholeblood or anticoagulant-free venous wholeblood. Intended for professional use inthe management of patients treated withoral anticoagulants.	For the quantitative prothrombintime (PT) testing for monitoring ofwarfarin therapy, using freshcapillary or non-anticoagulatedvenous whole blood by professionalhealth care providers.
Test Principle	Measures the PT using fibrin clotformation and detection.	Same
Reagents	Sensitive recombinant thromboplastinwith an ISI of approximately 1.0.	Same
Claim	ProTime Microcoagulation System(K010599)As Indicated in the ProTime Device Insert	PT•S Test Strips For Use WithCoaguChek System
Normal Range	Not Indicated in the ProTime Insert.	When the PT•S test was performedusing the CoaguChek monitor on 122normal, healthy, warfarin-freeindividuals using venous and capillarysamples, 99% of the venous andcapillary INRs ranged from 0.8 to 1.1.
Reportable Range	INR range of 0.8 to 7.0 with a calculated INRfrom 0.8 to 9.9. If INR >7.0, the numericalresult is marked with an "*". If INR >9.9 amessage indicating this is displayed.NOTE: The ProTime gives a numericalresult up to 9.9 INR.	The CoaguChek System has a PTreportable range of 0.8 - 8.0 INR.
Factor Sensitivity	ProTime is sensitive to deficiencies in vitaminK-dependent coagulation factors known toinfluence the PT test (ie. Factors II, VII and X)	Internal studies were performedutilizing four replicates of each FactorLevel (II, V, VII and X). Sampleswere assayed on the CoaguChek andOrtho Recombiplastin on the MLA900 Analyzer. Results are shown asgraphs in the test strip insert.
Hematocrit Range	Hematocrit levels between 20% and 60% donot significantly affect test results.	Hematocrit ranges between 32-52%do not significantly affect test results.
Heparin Levels	Results may be affected in patients receivingheparin or who have an abnormal response toheparin.	The results are unaffected by heparinconcentrations up to 2.0 U/mL. ThePT•S test strip is insensitive to lowmolecular weight heparins up to 1 IUanti-factor Xa activity/mL.

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Differences The key difference between the PT.S test strip and the ProTime Microcoagulation System is the location of the Quality Controls. Both from predicate device systems offer quality controls that satisfy the same function and requirements. However, the ProTime System utilizes quality controls which are built into the reagent cuvette, where the Roche Diagnostics PT.S test strip utilizes external liquid controls.

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Performance characteristics

The following chart shows a comparison of performance characteristics for the PT.S test strip and the ProTime Microcoagulation System.

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Claim	ProTime Microcoagulation System(K010599)As Indicated in the ProTime Device Insert			PT•S Test Strips For Use WithCoaguChek System
Precision withcontrols	Precision testing was conducted with two levels ofstandard control plasma substrate preparations.			The monitor-to-monitor, lot-to-lot andstrip-to-strip variability was assessedduring internal studies which used twolevels of liquid controls, with three teststrip lots across nine CoaguChekmonitors. The following data wasobtained:
		Standard ProTime cuvette:	N	mean	SD
	Level I	within day	17	0.9	0.06	Level 1
		day to day	4/day	1.0	0.08
	Level III	within day	19	3.2	0.19		Mean INR 1.3
		day to day	4/day	3.2	0.12		SD	%CV
		ProTime 3 cuvette:	N	mean	SD	Lot to LotMonitor to monitorStrip to stripTotal	0.020.010.040.05	1.720.953.323.86
	Level I	within day	18	0.9	0.07	Level 2
		day to day	4/day	0.9	0.12
						Mean INR 3.4
							SD	%CV
	Level III	within day	20	4.0	0.19	Lot to Lot	0.05	1.33
		day to day	4/day	4.2	0.22	Monitor to monitorStrip to stripTotal	0.080.130.16	2.223.794.59
Precision withblood	Not Indicated in the ProTime Insert.						Whole blood precision for venoussamples was determined from sampleduplicates at four external sites.Whole blood capillary data wascollected from sample duplicates atthree external sites.Bland Altman plots for both capillaryand venous blood are provided in thetest strip insert.

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Claim	ProTime Microcoagulation System(K010599)As Indicated in the ProTime Device Insert		PT•S Test Strips For Use WithCoaguChek System
Accuracy	INR results generated by the ProTime andProTime 3 cuvettes using venous and fingerstickwhole blood samples were compared to INRvalues obtained using standard Laboratory PlasmaPT Methods with samples collected in 3.2%sodium citrate tubes. The following accuracy datawere obtained.		610 venous samples were collectedfrom 309 outpatients at four externalsites. The INR of each sample wascompared to the INR of a venousplasma sample measured on an MLA900 Analyzer, using OrthoRecombiplastin. A scatterplot graph isprovided in the test strip insert. Theresults are as follows:$y = 1.065x - 0.12$Slp Cl (1.041, 1.090)Int Cl (-0.19, -0.06)Correlation = 0.961
	Standard ProTime cuvette vs Lab (Plasma):Regression equation	r	n
	FingerstickVenous	$y=0.94x + 0.38$$y=0.91x + 0.44$	0.950.94	229232
	ProTime 3 cuvette vs Lab (Plasma):Regression equation	448 capillary samples were collectedfrom 226 outpatients at three externalsites. Capillary blood samples wereassayed on the CoaguChek monitorwith the PT•S test strips and venousplasma samples were measured on anMLA 900 analyzer with OrthoRecombiplastin. A scatterplot graph isprovided in the test strip insert. Theresults are as follows:
	FingerstickVenous	$y=1.05x + 0.07$$y=0.97x + 0.19$	0.950.95	229219
			$y=1.089x - 0.17$Slp Cl (1.058, 1.119)Int Cl (-0.25, -0.09)Correlation = 0.958

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/6/Picture/1 description: The image shows a circular logo for the Department of Health and Human Services. The logo features a stylized image of an eagle with three lines representing its wings. The text "HUMAN SERVICES DEPARTMENT" is arranged around the top of the circle.

Food and Drug Administration
2098 Gaither Road
Rockville MD 20850

Ms. Jennifer Tribbett Regulatory Affairs Principal Roche Diagnostics Corporation 9115 Hague Road P.O. Box 50457 Indianapolis, Indiana 46250-0457

Re: K021190

Trade/Device Name: PT.S Test Strips and Controls for the CoaguChek System Regulation Number: 21 CFR § 864.7750 Regulation Name: Prothrombin Time Test Regulatory Class: II Product Code: GJS Dated: August 29, 2002 Received: August 30, 2002

Dear Ms. Tribbett:

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 reguirements for annual registration. Iisting 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 (OS) 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 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" (21CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers International and Consumer 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 Butman

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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22 119 510(k) Number (if known):

Device Name: PT.S Test Strips and Controls for the CoaguChek System

Indications for Use:

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

Concurrence of CDRH, Office of Device Evaluation (ODE)
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(Division Sign-Division of Clinical Laboratory Devices

510(k) Number K021190

Prescription Use
(Per 21 CFR 801.109)

Over-The-Counter Use

(Optional Format 1-2-96)

Regulation Number and Section

§ 864.7750 Prothrombin time test.

(a)
Identification. A prothrombin time test is a device used as a general screening procedure for the detection of possible clotting factor deficiencies in the extrinsic coagulation pathway, which involves the reaction between coagulation factors III and VII, and to monitor patients receiving coumarin therapy (the administration of one of the coumarin anticoagulants in the treatment of venous thrombosis or pulmonary embolism).(b)
Classification. Class II (performance standards).