K Number
K020831
Date Cleared
2002-10-24

(224 days)

Product Code
Regulation Number
864.7750
Reference & Predicate Devices
Predicate For
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview
Intended Use

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 S System by professional health care providers.

Device Description

The PT•S test strip, used as directed with the CoaguChek S 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 details for the PT•S Test Strips and Controls for the CoaguChek S System, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The provided text compares the PT•S Test Strips and Controls for the CoaguChek S System to a predicate device, the ProTime Microcoagulation System (K010599). While explicit "acceptance criteria" for the PT•S device are not listed as pass/fail thresholds, the document presents performance characteristics of the PT•S system. For the purpose of this response, I will consider the reported performance of the PT•S system as meeting its intended design requirements, as the device received 510(k) clearance implying substantial equivalence.

Acceptance Criteria (Performance Claim)Reported Device Performance (PT•S Test Strips)
Normal RangeWhen performed on 122 normal, healthy, warfarin-free individuals (venous and capillary samples), 99% of venous and capillary INRs ranged from 0.8 to 1.1.
Reportable RangeHas a PT reportable range of 0.8 - 6.0 INR.
Factor SensitivityInternal studies utilizing four replicates of each Factor Level (II, V, VII, and X) showed sensitivity. Samples were assayed on CoaguChek S and Ortho Recombiplastin on the MLA 900 Analyzer. Results are shown as graphs in the test strip insert. (Specific quantitative results not provided in this summary).
Hematocrit RangeHematocrit ranges between 32-52% do not significantly affect test results.
Heparin LevelsResults are unaffected by heparin concentrations up to 2.0 U/mL. Insensitive to low molecular weight heparins up to 1 IU anti-factor Xa activity/mL.
Precision with Controls (Level 1)Mean INR 1.2. Total SD: 0.06, Total %CV: 4.57 (combining lot-to-lot, monitor-to-monitor, strip-to-strip variability).
Precision with Controls (Level 2)Mean INR 3.0. Total SD: 0.17, Total %CV: 5.76 (combining lot-to-lot, monitor-to-monitor, strip-to-strip variability).
Precision with BloodWhole blood precision for venous samples determined from sample duplicates at three external sites. Whole blood capillary data collected from sample duplicates at two external sites. (Bland Altman plots in insert, specific numerical results not provided in this summary).
Accuracy (Venous Samples vs. Lab Plasma)506 venous samples from 255 outpatients. Compared to MLA 900 analyzer with Ortho Recombiplastin. Regression: y = 1.049x - 0.08. Correlation = 0.975. Slope 95% CI: (1.028, 1.070), Intercept 95% CI: (-0.13, -0.03).
Accuracy (Capillary Samples vs. Lab Plasma)294 capillary samples from 147 outpatients. Compared to MLA 900 analyzer with Ortho Recombiplastin. Regression: y = 1.048x - 0.10. Correlation = 0.969. Slope 95% CI: (1.017, 1.079), Intercept 95% CI: (-0.17, -0.02).

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

  • Normal Range Study: 122 individuals.
  • Accuracy Study (Venous): 506 venous samples from 255 outpatients.
  • Accuracy Study (Capillary): 294 capillary samples from 147 outpatients.
  • Precision with Blood: Not explicitly stated as a count, but involved sample duplicates at "three external sites" for venous and "two external sites" for capillary.
  • Data Provenance: The accuracy studies mention "outpatients at three external sites" and "outpatients at two external sites," implying a prospective collection of patient samples within a clinical setting. The country of origin is not specified but is implicitly the location of these "external sites."

3. Number of Experts Used to Establish Ground Truth and Qualifications

Not applicable. This device is a quantitative diagnostic test for Prothrombin Time (PT), where the "ground truth" is a laboratory reference method, not subjective expert interpretation of an image or signal.

4. Adjudication Method for the Test Set

Not applicable. For this type of quantitative diagnostic device, adjudication by experts for ground truth is not typically performed. The gold standard (MLA 900 analyzer with Ortho Recombiplastin) provides the comparative "ground truth."

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done

No, an MRMC comparative effectiveness study was not done. This type of study is relevant for medical devices that assist human readers in interpreting clinical data (e.g., radiologists reading images). The PT•S System is a standalone diagnostic test performed by professional healthcare providers, not an AI assistance tool for human interpretation.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) was done

Yes, the performance characteristics provided are for the standalone performance of the PT•S Test Strips used with the CoaguChek S monitor. The results reported (e.g., accuracy, precision, reportable range) reflect the device's inherent measurement capabilities without direct human interpretive input being part of the primary measurement. The healthcare provider acts as the operator, not as an interpreter whose performance is being assisted.

7. The Type of Ground Truth Used

The ground truth for the accuracy studies was established by comparing the PT•S System measurements to laboratory plasma PT methods performed on an MLA 900 analyzer using Ortho Recombiplastin. This is a well-established and recognized reference method for Prothrombin Time testing in a clinical laboratory setting.

8. The Sample Size for the Training Set

The document does not explicitly state the sample size for a "training set." This type of diagnostic device development often involves internal development and validation, but the term "training set" is more commonly associated with machine learning algorithms. The reported "internal studies" for precision and factor sensitivity likely represent a portion of the development and validation work.

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

Given that "training set" is not explicitly mentioned and the device is a chemical-mechanical diagnostic system rather than an AI algorithm requiring iterative training data, information on how a "training set ground truth" was established is not provided. The development process would have involved calibrating the device and reagents against known standards and reference methods, similar to the "ground truth" used for the performance evaluation, but this isn't framed as a distinct "training set" in the context of machine learning.

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510(k) Summary
IntroductionAccording 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, contactRoche Diagnostics Corporation9115 Hague Rd.P.O. Box 50457Indianapolis, IN 46250-0457
Contact Person: Jennifer Tribbett
Date Prepared: October 22, 2002
2) Device nameProprietary name: PT•S Test Strips and Controls for the CoaguChek S System
Common name: Prothrombin time test
Classification name: Prothrombin time test
3) Predicate deviceWe claim substantial equivalence to International Technidyne Corporation's (ITC) ProTime Microcoagulation System- ProTime 3 Cuvette (K010599)
Continued on next page

OCT 2 4 2002

.

1020831/

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510(k) Summary Continued

The PT•S test strip is intended for quantitative prothrombin time (PT) testing 4) Device for monitoring of warfarin therapy, using fresh capillary or non-Description anticoagulated venous whole blood with the CoaguChek S 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 Cournadin®, 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 S 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.

  • For quantitative prothrombin time (PT) testing for monitoring of warfarin 5) Intended use therapy, using fresh capillary or non-anticoagulated venous whole blood by professional health care providers.
    The Roche Diagnostics PT.S test strip and controls for the CoaguChek S 6) Comparison to predicate System are substantially equivalent to other products in commercial device distribution intended for similar use. Most notably, the PT.S test strip and substantially equivalent to International Technidyne controls are Corporation's (ITC) ProTime Microcoagulation System- ProTime 3 Cuvette (K010599).

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510(k) Summary Continued

Similarities topredicatedeviceThe PT-S test strip and controls are similar to the ITC ProTime System in thefollowing items:
-------------------------------------------------------------------------------------------------------------------------------------------
TopicProTime Microcoagulation System(K010599)As Indicated in the ProTime Device InsertPT•S Test Strips For Use WithCoaguChek S System
Intended UseFor 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 PrincipleMeasures the PT using fibrin clotformation and detection.Same
ReagentsSensitive recombinant thromboplastinwith an ISI of approximately 1.0.Same
ClaimProTime Microcoagulation System(K010599)As Indicated in the ProTime Device InsertPT•S Test Strips For Use WithCoaguChek S System
Normal RangeNot Indicated in the ProTime Insert.When the PT•S test was performedusing the CoaguChek S monitor on122 normal, healthy, warfarin-freeindividuals using venous andcapillary samples, 99% of the venousand capillary INRs ranged from 0.8to 1.1.
Reportable RangeINR 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 numerical resultup to 9.9 INR.The CoaguChek S System has a PTreportable range of 0.8 - 6.0 INR.
Factor SensitivityProTime 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 eachFactor Level (II, V, VII and X).Samples were assayed on theCoaguChek S and OrthoRecombiplastin on the MLA 900Analyzer. Results are shown asgraphs in the test strip insert.
Hematocrit RangeHematocrit levels between 20% and 60% donot significantly affect test results.Hematocrit ranges between 32-52%do not significantly affect test results.
Heparin LevelsResults 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.

The key difference between the PT-S test strip and the ProTime Differences from predicate Microcoagulation System is the location of the Quality Controls. Both 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 PT.S test strip utilizes external liquid controls.

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510(k) Summary, Continued

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

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510(k) Summary, Continued

ClaimProTime Microcoagulation System (K010599)As Indicated in the ProTime Device InsertPT-S Test Strips For Use With CoaguChek S System
Precision with controlsPrecision testing was conducted with two levels of standard control plasma substrate preparations.Standard ProTime cuvette:N mean SD Level I within day 17 0.9 0.06 day to day 4/day 1.0 0.08 Level III within day 19 3.2 0.19 day to day 4/day 3.2 0.12 ProTime 3 cuvette: N mean SD Level I within day 18 0.9 0.07 day to day 4/day 0.9 0.12 Level III within day 20 4.0 0.19 day to day 4/day 4.2 0.22The monitor-to-monitor, lot-to-lot and strip-to-strip variability was assessed during internal studies which used two levels of liquid controls, with three test strip lots across nine CoaguChek S monitors. The following data was obtained:Level 1 Mean INR 1.2SD %CV Lot to Lot 0.03 2.49 Monitor to monitor 0.01 0.61 Strip to strip 0.05 3.79 Total 0.06 4.57 Level 2 Mean INR 3.0SD %CV Lot to Lot 0.07 2.35 Monitor to monitor 0.03 1.17 Strip to strip 0.15 5.13 Total 0.17 5.76
Precision with bloodNot Indicated in the ProTime Insert.Whole blood precision for venous samples was determined from sample duplicates at three external sites. Whole blood capillary data was collected from sample duplicates at two external sites.Bland Altman plots for both capillary and venous blood are provided in the test strip insert

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510(k) Summary, Continued

ClaimProTime Microcoagulation System(K010599)As Indicated in the ProTime Device InsertPT•S Test Strips For Use WithCoaguChek S System
AccuracyINR 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.Standard ProTime cuvette vs Lab (Plasma)506 venous samples were collectedfrom 255 outpatients at three 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:
Regression equation
Fingersticky=0.94x + 0.38
Venousy=0.91x + 0.44
ry = 1.049x - 0.08
0.95Slp Cl (1.028, 1.070)
0.94Int Cl (-0.13, -0.03)
nCorrelation = 0.975
229
232
ProTime 3 cuvette vs Lab (Plasma):294 capillary samples were collectedfrom 147 outpatients at two externalsites. Capillary blood samples wereassayed on the CoaguChek S 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:
Regression equation
Fingersticky=1.05x + 0.07
Venousy=0.97x + 0.19
ry = 1.048x - 0.10
0.95Slp Cl (1.017, 1.079)
0.95Int Cl (-0.17, -0.02)
nCorrelation = 0.969
229
219

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Image /page/6/Picture/1 description: The image shows the seal of the Department of Health & Human Services (HHS). The seal features an abstract image of an eagle with three lines representing its body and wings. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the eagle.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

SOT 2 4 2002

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

Re: K020831

Trade/Device Name: PT.S Test Strips and Controls for the CoaguChek™ S System Regulation Number: 21 CFR § 864.7750 Regulation Name: Prothrombin Time Test Regulatory Class: II Product Code: GJS, JPA Dated: July 22, 2002 Received: July 23, 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 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 mav 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 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 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): K020831

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

Indications for Use:

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

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Auchin Bautister

Divis n of Clinical Laboratory Device

510(k) Number K020831

Prescription Use
(Per 21 CFR 801.109)

OR

Over-The-Counter Use

(Optional Format 1-2-96)

4

§ 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).