COAGUCHEK XS SYSTEM

K060978 · Roche Diagnostics · GJS · Aug 11, 2006 · Hematology

Device Facts

• Record ID: K060978
• Device Name: COAGUCHEK XS SYSTEM
• Applicant: Roche Diagnostics
• Product Code: GJS · Hematology
• Decision Date: Aug 11, 2006
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 864.7750
• Device Class: Class 2

Intended Use

The CoaguChek® XS System is intended for use by professional healthcare providers for quantitative prothrombin time testing for the monitoring of warfarin therapy. The CoaguChek® XS System uses fresh capillary or non-anticoagulated venous whole blood.

Device Story

CoaguChek XS is a 3rd generation point-of-care meter for prothrombin time (PT) testing; used by professional healthcare providers to monitor warfarin therapy. Input: fresh capillary or non-anticoagulated venous whole blood applied to CoaguChek XS PT test strips. Operation: electrochemical technology with amperometric detection of thrombin activity; integrated quality control uses electrochemical signals to verify test strip integrity. Output: PT/INR results displayed on meter. System includes meter and test-specific code chips (containing lot/expiration data). Benefits: provides rapid, reliable clotting time monitoring; improved performance over optical-based predecessors; integrated quality control ensures test reliability. Healthcare providers use results to adjust warfarin dosage.

Clinical Evidence

Clinical performance was evaluated in a 361-patient study across 3 sites. Comparison against a laboratory-based Dade Innovin thromboplastin method on a Sysmex analyzer showed acceptable bias. Regression analysis for venous (n=710, r=0.974) and capillary (n=700, r=0.971) samples demonstrated strong correlation with laboratory results. Precision testing met acceptance criteria (≤4.5% INR for venous, ≤7.5% INR for capillary). Interference testing confirmed no significant impact from heparin (up to 2 u/ml), Tinzaparin/Enozaparin (up to 2 IU anti-Xa/ml), bilirubin, lipemia, or hemolysis. Normal range testing (n=121) established a reference interval of 0.9–1.1 INR.

Technological Characteristics

Electrochemical system using amperometric detection of thrombin activity. Test strips contain human recombinant tissue factor (ISI 1.0). Features integrated bi-level on-board quality control (OBC) for strip integrity monitoring. Meter includes infrared communication for data transfer and memory for 100 results. Calibrated to WHO International Reference Preparations (rTF/95).

Indications for Use

Indicated for professional healthcare providers to perform quantitative prothrombin time (PT) testing for monitoring warfarin therapy in patients using fresh capillary or non-anticoagulated venous whole blood.

Regulatory Classification

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).

Predicate Devices

• Roche Diagnostics CoaguChek S System (K020831)

Submission Summary (Full Text)

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510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION
DECISION SUMMARY
ASSAY AND INSTRUMENT COMBINATION TEMPLATE

A. 510(k) Number:
K060978

B. Purpose for Submission:
Clearance of a new instrument and test strip

C. Measurand:
Prothrombin Time

D. Type of Test:
Electrochemical

E. Applicant:
Roche Diagnostics Corporation

F. Proprietary and Established Names:
CoaguChek® XS System

G. Regulatory Information:
1. Regulation section:
21 CFR 864.7750
2. Classification:
Class II
3. Product code:
GJS
4. Panel:

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81 Hematology

## H. Intended Use:

1. Intended use(s):

The CoaguChek® XS System is intended for use by professional healthcare providers for quantitative prothrombin time testing for the monitoring of warfarin therapy. The CoaguChek® XS System uses fresh capillary or non-anticoagulated venous whole blood.

2. Indication(s) for use:

3. Special conditions for use statement(s):

4. Special instrument requirements:

## I. Device Description:

The CoaguChek® XS System includes a meter and CoaguChek® XS PT test strips. The test strip contains a human recombinant tissue factor, and is calibrated to an ISI of 1.0.

The test strip incorporates quality control material that accesses strip integrity.

The CoaguChek® XS meter automatically stores up to 100 test results along with their dates and times in memory.

## J. Substantial Equivalence Information:

1. Predicate device name(s):

Roche Diagnostics CoaguChek S System

2. Predicate 510(k) number(s):

K020831

3. Comparison with predicate:

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| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Intended Use | Quantitative prothrombin time (PT) using fresh capillary or non-anticoagulated venous whole blood | same |
| Measuring Range | 0.8- 8.0 INR | Same |
| Sample Volume | 10 μl | same |
| Reagent | Human recombinant thromboplastin | same |
| Differences | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Technology | Electrochemical with amperometric detection of thrombin activity | Optical detection of thrombin activity |
| Quality Control | On-board integrated QC which detects test strip integrity | External liquid controls and electronic quality control |
| Test Strip Dosing | Top and side dosing | Top dosing only |
| Memory | 100 test results with time and date | 60 test results with time and date |

K. Standard/Guidance Document referenced (if applicable):

NCCLS/CLSI Document C28-A, “How to Define and Determine Reference Intervals”

L. Test Principle:

When a blood sample is applied to the test strip, thromboplastin activates the coagulation cascade which leads to the formation of thrombin. Thrombin cleaves the thrombin substrate creating an electrochemically active peptide, which generates an electrical signal. The signal is converted to an INR value and displayed by the CoaguChek XS System.

The on-board quality control is a bi-level control that accesses test strip integrity. The PT test and QC testing are performed simultaneously. The test system determines whether the quality control is within preset limits. If it is, the meter displays a short term “QC√”, and then the PT test result. If the QC is not within limits, the meter displays “error QC”, and no PT test result will be displayed.

M. Performance Characteristics (if/when applicable):

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1. Analytical performance:

a. Precision/Reproducibility:

Precision was evaluated by performing duplicate measurements of both capillary and venous blood. The acceptance criteria for venous blood was ≤ 4.5% INR and ≤ 7.5% INR for capillary samples. Testing was performed on two lots of test strips and demonstrated acceptable performance.

b. Linearity/assay reportable range:

c. Traceability, Stability, Expected values (controls, calibrators, or methods):

d. Detection limit:

e. Analytical specificity:

Testing demonstrated no interference with unfractionated heparin up to 2 u/ml from normal donors, and up to 0.8 u/mL for warfarin patients. Acceptance criteria was ≤10% difference when compared to the unspiked sample.

Tinzaparin and Enozaprin (LMWH’s) showed no interference up to 2 IU anti-Xa activity/ml for both normal donors and warfarin patients. Acceptance criteria was ≤10% difference when compared to the unspiked sample.

Testing was performed to demonstrate the interference of bilirubin, lipemia, and hemolysis. Results showed no interference from bilirubin up to 30 mg/dL, lipemia up to 500 mg/dL, and hemolysis up to 1000 mg/dL. Acceptance criteria was ≤10% difference when compared to the unspiked sample.

f. Assay cut-off:

2. Comparison studies:

a. Method comparison with predicate device:

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Study involving 361 patients (43% female, 57% male) at 3 sites. Clinical conditions include normal -not on warfarin (63), atrial fibrillation (175), valve replacement (36), stroke/TIS (28), DVT (16), other heart-related disorders (4), other clotting disorders (6), other (33). Two lots of test strips, on two meters were used. Results were compared to a Dade Innovin® thromboplastin (ISI =1.02) assayed on a Sysmex® analyzer. Bias plots were presented to demonstrate bias with a laboratory plasma method. Acceptance criteria was ≤0.5 INR difference to lab INR for INR’s in the range of 0.8 to 2.9, and ≤30% difference to lab INR for INR’s in the range of 2.0 to 4.5. Data demonstrated acceptable results for all sites.

Regression analysis was presented for the entire data set (venous y= 1.034x -0.02, Slope CI 1.017-1.053, Int CI -0.04-0.01, r=0.974, n=710; capillary y= 1.006x +0.032, Slope CI 0.990-1.023, Int CI -0.01-0.06, r=0.971, n=700) and each site across the reportable range. The regression analysis for the entire data set is included in the package insert.

b. Matrix comparison:

Regression analysis was presented to compared capillary versus venous results by site, and combined for two lot of test strips. Lot 1 (y = 0.97 x + 0.033; y =1.00 x + 0; y =0.97 x + 0.047/y =0.98 x + 0.023) and Lot 2 (y = 1.00 x + 0; y =1.00 x + 0; y =1.00 x + 0/y =1.00 x + 0) both meet the acceptance criterion (slope 0.95-1.05, intercept of ± 0.1).

3. Clinical studies:

a. Clinical Sensitivity:

b. Clinical specificity:

c. Other clinical supportive data (when a. and b. are not applicable):

4. Clinical cut-off:

5. Expected values/Reference range:

Normal range testing was conducted on 121 patients who were not on oral anticoagulant therapy. Both capillary and venous samples were collect from each patient. Samples

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were tested on two lots of CoaguChek XS PT strips. Results demonstrated a normal range of 0.9 to 1.1 INR with more than 95% of all results falling within that range.

## N. Instrument Name:

CoaguChek XS meter

## O. System Descriptions:

1. Modes of Operation:

Manual, closed system

2. Software:

The CoaguChek XS software controls the user interface, buttons used to navigate the user interface and to configure the device, storage of patient results, transfer of measurement results using serial infrared communication in an open mode, transfer of production and calibration results using serial infrared communication in a protected mode, reading and storage of specific information for strip LOT from code key, calculation of PT time based on data received from measurement cycle, and checks for failsafe in order to recognize malfunctions of the measurement electronics or malfunctions within the strip used for testing.

FDA has reviewed applicant’s Hazard Analysis and software development processes for this line of product types:

☑ Yes or ☐ No

3. Specimen Identification:

Date and time of testing is recorded by the CoaguChek XS meter

4. Specimen Sampling and Handling:

Whole blood is manually applied to the target area of the test strip either from the top or side of the strip.

5. Calibration:

The CoaguChek XS Test strips are calibrated to a master reagent lot which has in turn been calibrated to a WHO International Reference Preparations (rTF/95) using the manual tilt tube method.

6. Quality Control:

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The CoaguChek XS System incorporates a bi-level on-board quality control (OBC) within the CoaguChek XS test strip that monitors test strip integrity.

Level 1 OBC detects strip defects such as reagent defects, capillary compression and electrode defects. Level 2 OBC directly measures strip damage due to such things as exposure to increased humidity, light, and temperature.

The pre-determined OBC ranges are programmed into the lot specific code chip that is packaged with the matching test strip lot.

Acceptable data was presented validating the OBC.

## P. Other Supportive Instrument Performance Characteristics Data Not Covered In the "Performance Characteristics" Section above:

An instrument failsafe checklist was presented outlining the QC check made by the CoaguChek XS meter.

## Q. Proposed Labeling:

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

## R. Conclusion:

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

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