(528 days)
Sysmex CS-2500
No
The description focuses on electrochemical sensors, reagents, and standard analytical methods for measuring coagulation time. There is no mention of AI/ML algorithms for data processing, interpretation, or decision support.
No
This device is an in vitro diagnostic (IVD) device used for quantitative measurement of the extrinsic coagulation pathway, specifically prothrombin time, to monitor patients on anticoagulant therapy. It provides diagnostic information rather than directly treating or preventing disease.
Yes
The "Intended Use / Indications for Use" states that the device is for "in vitro quantitative measurement of the extrinsic coagulation pathway" and that "Measurements of prothrombin time are used to aid in the monitoring of patients receiving anticoagulant therapy." The "Device Description" also clearly calls the i-STAT 1 analyzer an "in vitro diagnostic analytical device." These phrases directly indicate its use in diagnosing or monitoring medical conditions.
No
The device description clearly states that the i-STAT 1 System consists of both the i-STAT 1 analyzer (a handheld hardware device) and the i-STAT cartridges (which contain electrochemical sensors and reagents). The software runs on the analyzer to process the data from the cartridge, but the system is not software-only.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states the device is for "in vitro quantitative measurement" of the extrinsic coagulation pathway in "non-anticoagulated whole blood". This clearly indicates testing is performed on biological samples outside of the body.
- Device Description: The "Device Description" refers to the i-STAT 1 analyzer as a "handheld, in vitro diagnostic analytical device".
- Testing Process: The description of the cartridge and how it interacts with the sample (mixing with reagents, electrochemical sensors) confirms that the analysis is performed on the blood sample itself, which is characteristic of in vitro testing.
- Quality Controls: The mention of internal and external quality controls, as well as liquid quality controls, is standard practice for IVD devices to ensure accuracy and reliability of the test results.
- Regulatory Context: The document mentions "regulatory compliance requirements" and "prescription use only," which are common characteristics of regulated IVD devices.
- Performance Studies: The detailed performance studies (precision, linearity, interference, method comparison) are typical evaluations required for IVD devices to demonstrate their analytical performance.
All of these points strongly support the classification of this device as an In Vitro Diagnostic.
N/A
Intended Use / Indications for Use
The i-STAT PTP45 cartridge is intended for use in the in vitro quantitative measurement of the extrinsic coagulation pathway when activated by thromboplastin in non-anticoagulated whole blood (venous or capillary), using the i-STAT 1 System. Measurements of prothrombin time are used to aid in the monitoring of patients receiving anticoagulant therapy with coumarin derivatives. The i-STAT PT246 Prothrombin Time test result is reported in seconds and as an International Normalized Ratio (INR). The test is intended for point of care use and is for prescription use only.
Product codes
GJS
Device Description
The i-STAT 1 System consists of the i-STAT 1 analyzer and the i-STAT cartridges. Other components of the i-STAT 1 System are the Electronic Simulator, the i-STAT 1 Downloader/Recharger and the i-STAT Printer. The i-STAT 1 analyzer is a handheld, in vitro diagnostic analytical device designed to run only i-STAT test cartridges. The system is designed for use by trained medical professionals at the patient point of care or in the clinical laboratory and is for prescription use only.
The i-STAT PTPlus cartridge is a coagulation cartridge for determining the time required for complete activation of the extrinsic coagulation cascade. The cartridge contains electrochemical sensors and test reagents that must be mixed with the sample. The reagents include the reactive ingredient to activate the coagulation cascade as well as electrochemical markers that generate a sensor signal when the cascade is fully activated.
The analysis time of the i-STAT PT2405 cartridge is up to 300 seconds (5 minutes). The sample volume required for the i-STAT PT2105 cartridge is approximately 20 ul of whole blood (venous or capillary) without added anticoagulant. The i-STAT PTplus cartridge is a single-use disposable unit that is self-contained. The test reagents and sample fluids do not contact the instrument or user. All the test steps and fluid movements occur within the cartridge.
The i-STAT 1 System has an internal quality control (internal simulator) and an external quality control (Electronic Simulator). The internal and external simulators are used to check the instrument signal-reading function. In addition to the quality controls within the i-STAT 1 System, liquid quality controls are available as an optional quality control methodology to meet the regulatory compliance requirements applicable to the facility where they are to be used.
The liquid quality controls are the i-STAT PT2008 Control Levels 1 and 2 and can be used for the quality control of the i-STAT PT2005 cartridge. The coagulation controls consist of lyophilized citrated human plasma and calcium chloride fluid for reconstitution.
i-STAT PT2145 Control Level 1 has been formulated to produce a normal prothrombin time. Level 2 has been formulated to produce an extended prothrombin time.
Each level of control is packaged as a box of 5 vials containing 1 mL of lyophilized citrated human plasma and 5 vials of 1.5 mL of calcium chloride diluent.
The i-STAT PT2"45 controls are intended for use with the i-STAT PTP"46 cartridge on the i-STAT System, and values assigned to these controls may not be commutable with other commercial methods.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
trained medical professionals at the patient point of care or in the clinical laboratory
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Analytical Performance:
- Precision/Reproducibility:
- Precision 20 days (Liquid Controls): Evaluated using 3 lots of i-STAT PT cartridges and 3 fluid levels (i-STAT PT Controls Levels 1 and 2, and an internal fluid Level 3). Performed over 20 days by 2 operators running 2 test events per day at one site, based on CLSI document EP05-A3. Results shown in Table 2 (seconds) and Table 3 (INR).
- Precision (Whole Blood): Evaluated using venous and capillary specimens at non-therapeutic (INR 0.8 - 1.9), therapeutic (INR 2.0 - 4.5), and very high therapeutic (INR 4.6 - 8.0) ranges. Data from duplicate testing in capillary and venous method comparison studies were used. Analysis conducted using data collected across three (3) point of care sites. Results summarized for capillary whole blood in Table 4 (seconds) and Table 5 (INR) and for venous whole blood in Table 6 (seconds) and Table 7 (INR).
- Linearity/assay reportable range:
- Linearity: Not applicable.
- Reportable range: 0.8 – 8.0 INR and 8.1 – 80.8 seconds. Determined through a method comparison study using venous and capillary whole blood from subjects on and not on anticoagulant therapy (Table 8).
- Traceability: i-STAT prothrombin time values are traceable to the WHO international reference measurement procedures using an International Reference Preparation (IRP).
- Detection Limit (LoQ, LoB/LoD): Not applicable.
- Factor Sensitivity: Estimated for FII (39.5%), FV (42.0%), FVII (21.5%), FX (22.0%) using samples prepared by combining pooled normal plasma, red blood cells, and factor-deficient plasma.
- Analytical Specificity (Interference): Evaluated the effect of potentially interfering endogenous or exogenous substances (e.g., Acetaminophen, Acetylsalicylic Acid, Bilirubin, Chlorhexidine digluconate, Daptomycin, Enoxaparin, Oritavancin, etc.) based on CLSI EP07-A2, EP07-ED3, and EP37-ED1. Results are in Table 9; some substances showed interference (Chlorhexidine digluconate, Daptomycin, Oritavancin).
- Other sensitivity studies:
- Fibrinogen Sensitivity: Insensitive to fibrinogen across 63 – 702 mg/dL.
- Platelet Sensitivity: Insensitive to platelets in the range of 70,000 - 670,000/mm².
- Hematocrit Sensitivity: Insensitive to hematocrit in the range of 24 to 54% packed cell volume (PCV).
- Heparin Sensitivity: Insensitive to unfractionated heparin concentrations up to 1.0 IU/mL.
- Sensitivity for Lupus Anticoagulant: Sensitive to both low and high levels of lupus anticoagulant antibodies.
- Assay cut-off: Not applicable.
Comparison Studies:
- Method Comparison with predicate device (CoaguChek® XS Plus System (K071041)):
- Study Design: Venous and capillary whole blood specimens prospectively collected from subjects (on and not on coumarin derivatives) at 3 clinical sites. Duplicate testing on i-STAT 1 Analyzer, singlicate on predicate device. Based on CLSI EP09c.
- Analysis: Passing-Bablok regression analysis for first replicate of i-STAT result vs. singlicate predicate result.
- Results:
- Venous (N=191*): Correlation coefficient (R) = 0.98 (0.97 to 0.98), Slope = 0.736 (0.715 to 0.757), Intercept = 1.352 (0.708 to 1.920) for seconds (Table 10). For INR, R = 0.98 (0.97 to 0.98), Slope = 0.875 (0.857 to 0.906), Intercept = 0.113 (0.045 to 0.157) (Table 11).
- Capillary (N=153*): Correlation coefficient (R) = 0.97 (0.96 to 0.98), Slope = 0.743 (0.711 to 0.776), Intercept = 1.051 (0.309 to 1.892) for seconds (Table 10). For INR, R = 0.97 (0.96 to 0.98), Slope = 0.885 (0.846 to 0.923), Intercept = 0.104 (0.009 to 0.171) (Table 11).
- Method comparison with reference device (Sysmex CS-2500):
- Study Design: Venous and capillary whole blood specimens prospectively collected from subjects (on and not on coumarin derivatives) at 3 clinical sites. Duplicate testing on i-STAT 1 Analyzer. Citrated plasma from venous whole blood tested in duplicate on Sysmex CS-2500 using Dade Innovin reagent. Based on CLSI EP09c.
- Analysis: Passing-Bablok regression analysis for first replicate of i-STAT result vs. first replicate Sysmex result.
- Results:
- Venous (N=211*): Correlation coefficient (R) = 0.92 (0.90 to 0.94), Slope = 1.037 (0.994 to 1.082), Intercept = -0.591 (-1.500 to 0.151) for seconds (Table 12). For INR, R = 0.92 (0.90 to 0.94), Slope = 1.037 (1.000 to 1.078), Intercept = 0.004 (-0.079 to 0.075) (Table 13).
- Capillary (N=203*): Correlation coefficient (R) = 0.91 (0.88 to 0.93), Slope = 1.023 (0.979 to 1.070), Intercept = -0.189 (-1.052 to 0.641) for seconds (Table 12). For INR, R = 0.91 (0.89 to 0.93), Slope = 1.022 (0.984 to 1.061), Intercept = 0.047 (-0.029 to 0.127) (Table 13).
Expected Values/Reference range:
- Reference range: Established with venous and capillary samples from apparently healthy adult subjects. Testing performed with 3 cartridge lots on the i-STAT 1 System at 3 clinical sites. Determined according to CLSI Guideline EP28-A3c.
- Capillary (N=146): INR range 0.9 - 1.3 (Mean 1.1), Seconds range 9.0 - 13.8 (Mean 10.6) (Table 14).
- Venous (N=154): INR range 0.9 - 1.3 (Mean 1.1), Seconds range 9.2 - 13.0 (Mean 10.6) (Table 14).
Conclusion: The studies demonstrate substantial equivalence to the predicate device.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Key metrics reported are:
Precision/Reproducibility: SD (Standard Deviation), %CV (Coefficient of Variation) for within-run, between-run, between-day, and within-laboratory.
Method Comparison: Correlation coefficient (R), Slope, Intercept.
Factor Sensitivity: Percent (%) factor activity for FII, FV, FVII, FX.
Analytical Specificity: "Interference (Yes/No)" and "Interference Result" for various substances.
Predicate Device(s)
Reference Device(s)
Sysmex CS-2500
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
§ 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).
0
Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, with the letters "FDA" in a blue square. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
July 14, 2023
Abbott Laboratories Melissa Tristani Senior Regulatory Affairs Specialist 400 College Road East Princeton, New Jersey 08540
Re: K220282
Trade/Device Name: i-STAT PTplus Cartridge with the i-STAT I System Regulation Number: 21 CFR 864.7750 Regulation Name: Prothrombin Time Test Regulatory Class: Class II Product Code: GJS Dated: January 31, 2022 Received: February 1, 2022
Dear Melissa Tristani:
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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
Please note that if you modify your IVD in the future to exceed any of the limitations to the exemption found in 21 CFR 864.9(c), your device will require a new 510(k) prior to marketing this device in the United States and will not be exempt from the premarket notification requirements so long as it exceeds the limitations to the exemption found in 21 CFR 864.9.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of
1
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 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Takeesha Taylor-bell -S
Takeesha Taylor-Bell Deputy Director Division of Immunology and Hematology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
2
Abbott Point of Care / Traditional 510(k) /
i-STAT PTplus cartridge with the i-STAT 1 System
| DEPARTMENT OF HEALTH AND HUMAN SERVICES | Form Approved: OMB No. 0910-0120 |
|---|---|
| Food and Drug Administration | Expiration Date: 06/30/2023 |
Indications for Use
See PRA Statement below.510(k) Number (if known)
Device Name
i-STAT PTPlus cartridge with the i-STAT 1 System
Indications for Use (Describe)
The i-STAT PTP45 cartridge is intended for use in the in vitro quantitative measurement of the extrinsic coagulation pathway when activated by thromboplastin in non-anticoagulated whole blood (venous or capillary), using the i-STAT 1 System. Measurements of prothrombin time are used to aid in the monitoring of patients receiving anticoagulant therapy with coumarin derivatives. The i-STAT PT246 Prothrombin Time test result is reported in seconds and as an International Normalized Ratio (INR). The test is intended for point of care use and is for prescription use only.
| Type of Use (Select one or both, as applicable) | |
|---|---|
| Prescription Use (Part 21 CFR 801 Subpart D) | Over-The-Counter Use (21 CFR 801 Subpart C) |
CONTINUE ON A SEPARATE PAGE IF NEEDED.
This section applies only to requirements of the Paperwork Reduction Act of 1995.
DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW!
The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:
Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."
Page 1 of 1
3
510(k) Summary
The information in this 510(k) summary is being submitted in accordance with the requirements of 21 CFR 807.92.
| Submitter Information | |
|---|---|
| Owner | Abbott Point of Care Inc. |
| 400 College Road East | |
| Princeton, NJ 08540 | |
| Contact | Primary: Melissa Tristani |
| Senior Regulatory Affairs Specialist | |
| Phone: 613-688-5949 |
Secondary contact person for all
communications: Maria L Figueroa
Associate Director Regulatory Affairs
Phone: 609-454-9271 |
| Date Prepared | January 28, 2022 |
2. Device Information
| Proprietary Name | i-STAT PTplus cartridge with the i-STAT 1 System |
|---|---|
| Common Name | Prothrombin time, PT, analyzer, handheld |
| Product
code | Device Classification
name | Regulation
Number | Class | Panel |
|-----------------|-------------------------------|----------------------|-------|------------|
| GJS | Test, Time, Prothrombin | 864.7750 | II | Hematology |
4
3. Predicate Device
Proprietary Name CoaguChek® XS Plus System
510(k) Number K071041
| Product
code | Device Classification
name | Regulation
Number | Class | Panel |
|-----------------|-------------------------------|----------------------|-------|------------|
| GJS | Test, Time, Prothrombin | 864.7750 | II | Hematology |
Device Description 4.
The i-STAT 1 System consists of the i-STAT 1 analyzer and the i-STAT cartridges. Other components of the i-STAT 1 System are the Electronic Simulator, the i-STAT 1 Downloader/Recharger and the i-STAT Printer. The i-STAT 1 analyzer is a handheld, in vitro diagnostic analytical device designed to run only i-STAT test cartridges. The system is designed for use by trained medical professionals at the patient point of care or in the clinical laboratory and is for prescription use only.
The i-STAT PTPlus cartridge is a coagulation cartridge for determining the time required for complete activation of the extrinsic coagulation cascade. The cartridge contains electrochemical sensors and test reagents that must be mixed with the sample. The reagents include the reactive ingredient to activate the coagulation cascade as well as electrochemical markers that generate a sensor signal when the cascade is fully activated.
The analysis time of the i-STAT PT2405 cartridge is up to 300 seconds (5 minutes). The sample volume required for the i-STAT PT2105 cartridge is approximately 20 ul of whole blood (venous or capillary) without added anticoagulant. The i-STAT PTplus cartridge is a single-use disposable unit that is self-contained. The test reagents and sample fluids do not contact the instrument or user. All the test steps and fluid movements occur within the cartridge.
The i-STAT 1 System has an internal quality control (internal simulator) and an external quality control (Electronic Simulator). The internal and external simulators are used to check the instrument signal-reading function. In addition to the quality controls within the i-STAT 1 System, liquid quality controls are available as an optional quality control methodology to meet the regulatory compliance requirements applicable to the facility where they are to be used.
The liquid quality controls are the i-STAT PT2008 Control Levels 1 and 2 and can be used for the quality control of the i-STAT PT2005 cartridge. The coagulation controls
5
consist of lyophilized citrated human plasma and calcium chloride fluid for reconstitution.
i-STAT PT2145 Control Level 1 has been formulated to produce a normal prothrombin time. Level 2 has been formulated to produce an extended prothrombin time.
Each level of control is packaged as a box of 5 vials containing 1 mL of lyophilized citrated human plasma and 5 vials of 1.5 mL of calcium chloride diluent.
The i-STAT PT2"45 controls are intended for use with the i-STAT PTP"46 cartridge on the i-STAT System, and values assigned to these controls may not be commutable with other commercial methods.
5. Intended Use Statement
The i-STAT PTplus cartridge is intended for use in the in vitro quantitative measurement of the clot time of the extrinsic coagulation pathway when activated by thromboplastin in non-anticoagulated whole blood (venous or capillary), using the i-STAT 1 System. Measurements of prothrombin time are used to aid in the monitoring of patients receiving anticoagulant therapy with coumarin derivatives. The i-STAT PT20145 Prothrombin Time test result is reported in seconds and as an International Normalized Ratio (INR). The test is intended for point of care use and is for prescription use only.
| Table 1: Summary Comparison | ||
|---|---|---|
| Feature or | ||
| Characteristic | Candidate: | |
| i-STAT PTplus cartridge with the i-STAT | ||
| 1 System | Predicate: | |
| CoaguChek® XS Plus System | ||
| (K071041) | ||
| Intended Use | The i-STAT PTplus cartridge is intended for use | |
| in the in vitro quantitative measurement of the | ||
| clot time of the extrinsic coagulation pathway | ||
| when activated by thromboplastin in non- | ||
| anticoagulated whole blood (venous or | ||
| capillary), using the i-STAT 1 System. | ||
| Measurements of prothrombin time are used | ||
| to aid in the monitoring of patients receiving | ||
| anticoagulant therapy with coumarin | ||
| derivatives. The i-STAT PTplus Prothrombin | ||
| Time test result is reported in seconds and as | ||
| an International Normalized Ratio (INR). The | ||
| test is intended for point of care use and is for | ||
| prescription use only. | Intended for use by professional | |
| healthcare providers for | ||
| quantitative prothrombin time | ||
| testing for the monitoring of | ||
| warfarin therapy. The system uses | ||
| fresh capillary or non- | ||
| anticoagulated venous whole | ||
| blood. | ||
| Reportable | ||
| Range | 0.8-8.0 INR | |
| 8.1-80.8 seconds | 0.8-8.0 INR | |
| Sample Type | Fresh whole blood from venous or capillary | |
| samples | Same |
Summary Comparison of Technological Characteristics 6.
6
| Table 1: Summary Comparison | ||
|---|---|---|
| Feature or | ||
| Characteristic | Candidate: | |
| i-STAT PTplus cartridge with the i-STAT | ||
| 1 System | Predicate: | |
| CoaguChek® XS Plus System | ||
| (K071041) | ||
| Sample Volume | Approximately 20 µL | Minimum of 10 µL |
| Sample | ||
| Preparation | Ready to Use. No sample preparation required. | Same |
| Traceability | Traceable to the WHO international reference method. | Same |
| Reagent | Human recombinant thromboplastin. | Same |
| Electronic | ||
| Quality | ||
| Controls | On-board quality control built into the analyzer and external Electronic Simulator. | On-board quality control which uses electrochemical signal to detect test strip integrity. |
| Liquid Quality | ||
| Controls | Two levels of liquid controls | Same |
| Principle of | ||
| Measurement | Electrochemical technology with amperometric (electric current) detection of thrombin activity | Same |
| Analyzer Type | Handheld | Same |
Performance Characteristics 7.
A. Analytical Performance
a. Precision/Reproducibility:
- Precision 20 days (Liquid Controls) i.
The precision of the prothrombin time test in the i-STAT PT2465 cartridge was evaluated using three (3) lots of i-STAT PT2"16 cartridges and three (3) fluid levels. The fluids included the i-STAT PT2145 Controls (Levels 1 and 2) as well as an internal fluid level (Level 3). The study was performed based on CLSI document EP05-A3: Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline-Third Edition. Each cartridge and fluid level was tested over 20 days by two operators running two test events per day at one site. The results of the 20-day precision study are shown in Table 2 (seconds) and Table 3 (INR).
| Table 2: 20 Day Precision Results (seconds) | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Cartridge | ||||||||||||
| Lot | Fluid | |||||||||||
| Level | N | Mean | Within-run | Between-run | Between-day | Within-laboratory | ||||||
| (sec) | SD | |||||||||||
| (sec) | %CV | SD | ||||||||||
| (sec) | %CV | SD | ||||||||||
| (sec) | %CV | SD (sec) | %CV | |||||||||
| A | L1 | 119 | 10.38 | 0.279 | 2.7 | 0.019 | 0.2 | 0.134 | 1.3 | 0.310 | 3.0 | |
| L2 | 116 | 24.51 | 0.881 | 3.6 | 0.227 | 0.9 | 0.075 | 0.3 | 0.912 | 3.7 | ||
| L3 | 104 | 53.95 | 3.488 | 6.5 | 0.986 | 1.8 | 0.709 | 1.3 | 3.693 | 6.8 |
7
| Table 2: 20 Day Precision Results (seconds) | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Cartridge | |||||||||||||
| Lot | Fluid | ||||||||||||
| Level | N | Mean | |||||||||||
| (sec) | Within-run | Between-run | Between-day | Within-laboratory | |||||||||
| SD | |||||||||||||
| (sec) | %CV | SD | |||||||||||
| (sec) | %CV | SD | |||||||||||
| (sec) | %CV | SD (sec) | %CV | ||||||||||
| B | L1 | 120 | 10.36 | 0.279 | 2.7 | 0.065 | 0.6 | 0.186 | 1.8 | 0.342 | 3.3 | ||
| L2 | 119 | 22.82 | 0.812 | 3.6 | 0.272 | 1.2 | 0.298 | 1.3 | 0.906 | 4.0 | |||
| L3 | 118 | 49.54 | 1.884 | 3.8 | 0.734 | 1.5 | 0.568 | 1.1 | 2.099 | 4.2 | |||
| C | L1 | 120 | 10.58 | 0.266 | 2.5 | 0.128 | 1.2 | 0.004 | 0.0 | 0.295 | 2.8 | ||
| L2 | 120 | 23.62 | 0.540 | 2.3 | 0.139 | 0.6 | 0.189 | 0.8 | 0.589 | 2.5 | |||
| L3 | 117 | 52.07 | 0.818 | 1.6 | 0.332 | 0.6 | 0.211 | 0.4 | 0.907 | 1.7 |
| Table 3: 20-day Precision Results (INR) | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Cartridge | ||||||||||||
| Lot | Fluid | |||||||||||
| Level | N | Mean | ||||||||||
| (INR) | Within-run | Between-run | Between-day | Within-laboratory | ||||||||
| SD | ||||||||||||
| (INR) | %CV | SD | ||||||||||
| (INR) | %CV | SD | ||||||||||
| (INR) | %CV | SD | ||||||||||
| (INR) | %CV | |||||||||||
| A | L1 | 119 | 1.03 | 0.028 | 2.7 | 0.002 | 0.2 | 0.013 | 1.3 | 0.031 | 3.0 | |
| L2 | 116 | 2.43 | 0.087 | 3.6 | 0.022 | 0.9 | 0.007 | 0.3 | 0.090 | 3.7 | ||
| L3 | 104 | 5.34 | 0.345 | 6.5 | 0.098 | 1.8 | 0.070 | 1.3 | 0.366 | 6.8 | ||
| B | L1 | 120 | 1.03 | 0.028 | 2.7 | 0.006 | 0.6 | 0.018 | 1.8 | 0.034 | 3.3 | |
| L2 | 119 | 2.26 | 0.080 | 3.6 | 0.027 | 1.2 | 0.029 | 1.3 | 0.090 | 4.0 | ||
| L3 | 118 | 4.91 | 0.186 | 3.8 | 0.073 | 1.5 | 0.056 | 1.1 | 0.208 | 4.2 | ||
| C | L1 | 120 | 1.05 | 0.026 | 2.5 | 0.013 | 1.2 | 0.000 | 0.0 | 0.029 | 2.8 | |
| L2 | 120 | 2.34 | 0.053 | 2.3 | 0.014 | 0.6 | 0.019 | 0.8 | 0.058 | 2.5 | ||
| L3 | 117 | 5.16 | 0.081 | 1.6 | 0.033 | 0.6 | 0.021 | 0.4 | 0.090 | 1.7 |
ii. Precision (Whole Blood)
Whole blood precision (repeatability) was evaluated using venous and capillary specimens at three (3) ranges: non-therapeutic (INR 0.8 - 1.9), therapeutic (INR 2.0 -4.5), and very high therapeutic (INR 4.6 - 8.0). The repeatability analysis was conducted using the data collected across three (3) point of care sites. Data from duplicate testing in both the capillary method comparison study and the venous method comparison study were used to evaluate whole blood precision. The whole blood precision results for all three (3) sites combined are summarized for capillary whole blood in Table 4 (seconds) and Table 5 (INR) and for venous whole blood are summarized in Table 6 (seconds) and Table 7 (INR).
| Site | Interval | N | Mean | Standard Deviation | %CV | |||
|---|---|---|---|---|---|---|---|---|
| Estimate | 95% CI | Estimate | 95% CI | Estimate | 95% CI | |||
| Non-therapeutic | 58* | 14.89 | 14.06 to 15.73 | 1.414 | 1.197 to 1.727 | 9.5 | 8.0 to 11.6 |
8
| Table 4: Capillary Whole Blood PT (seconds) Precision | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Site | Interval | N | Mean | Standard Deviation | %CV | ||||
| Estimate | 95% CI | Estimate | 95% CI | Estimate | 95% CI | ||||
| All | |||||||||
| Sites | Therapeutic | 119* | 28.51 | 27.73 to 29.30 | 1.495 | 1.327 to 1.713 | 5.2 | 4.7 to 6.0 | |
| Very High | |||||||||
| Therapeutic | 9 | 50.71 | 42.88 to 58.54 | 2.109 | 1.451 to 3.851 | 4.2 | 2.9 to 7.6 |
*Results with outliers included
| Table 5: Capillary Whole Blood PT INR Precision | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Site | Interval | N | Mean | Standard Deviation | %CV | ||||
| Estimate | 95% Cl | Estimate | 95% Cl | Estimate | 95% Cl | ||||
| All | |||||||||
| Sites | Non-therapeutic | 58* | 1.48 | 1.39 to 1.56 | 0.143 | 0.121 to 0.174 | 9.7 | 8.2 to 11.8 | |
| Therapeutic | 119* | 2.82 | 2.74 to 2.90 | 0.148 | 0.131 to 0.169 | 5.2 | 4.6 to 6.0 | ||
| Very High | |||||||||
| Therapeutic | 9 | 5.02 | 4.24 to 5.80 | 0.201 | 0.139 to 0.368 | 4.0 | 2.8 to 7.3 |
*Results with outliers included
| Table 6: Venous Whole Blood PT (seconds) Precision | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Site | Interval | N | Mean | Standard Deviation | %CV | ||||
| Estimate | 95% Cl | Estimate | 95% Cl | Estimate | 95% Cl | ||||
| All | |||||||||
| Sites | Non-therapeutic | 65* | 14.69 | 13.95 to 15.43 | 1.047 | 0.894 to 1.263 | 7.1 | 6.1 to 8.6 | |
| Therapeutic | 131 | 28.78 | 27.97 to 29.59 | 0.660 | 0.589 to 0.751 | 2.3 | 2.0 to 2.6 | ||
| Very High | |||||||||
| Therapeutic | 13* | 54.37 | 48.44 to 60.31 | 0.785 | 0.569 to 1.264 | 1.4 | 1.0 to 2.3 |
*Results with outliers included
| Table 7: Venous Whole Blood PT INR Precision | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Site | Interval | N | Mean | Standard Deviation | %CV | ||||
| Estimate | 95% CI | Estimate | 95% CI | Estimate | 95% CI | ||||
| All | |||||||||
| Sites | Non-therapeutic | 65* | 1.45 | 1.38 to 1.53 | 0.109 | 0.093 to 0.131 | 7.5 | 6.4 to 9.0 | |
| Therapeutic | 131 | 2.85 | 2.77 to 2.93 | 0.069 | 0.061 to 0.078 | 2.4 | 2.1 to 2.7 | ||
| Very High | |||||||||
| Therapeutic | 13* | 5.38 | 3.80 to 5.97 | 0.088 | 0.064 to 0.141 | 1.6 | 1.2 to 2.6 |
*Results with outliers included
b. Linearity/assay reportable range:
-
i. Linearity
Not applicable. -
ii. Reportable range
The reportable range of the prothrombin time test in the i-STAT PT2015 cartridge with the i-STAT 1 System was determined through a method comparison study by using venous and capillary whole blood specimens from subjects undergoing anticoagulant therapy with coumarin derivatives and from subjects who were not on anticoagulant therapy. The result of the reportable range is shown in
9
Table 8.
| Table 8: Reportable Range | ||
|---|---|---|
| Test / | ||
| Abbreviation | Units | ReportableRange |
| Prothrombin Time | ||
| (PTplus) | INR | 0.8 – 8.0 |
| seconds | 8.1 – 80.8 |
c. Traceability, Stability, Expected values (controls, calibrators, or methods):
i. Traceability
i-STAT prothrombin time values are traceable to the World Health Organization (WHO) international reference measurement procedures using an International Reference Preparation (IRP) recommended by the WHO.
d. Detection Limit
- i. Limit of Quantitation (LoQ) Not applicable
- ii. Limit of Blank and Detection (LoB/LoD) Not applicable.
- iii. Other
1) Factor Sensitivity
The factor sensitivity for factors FII, FV, FV, FVII and FX was determined using samples prepared by proportionately combining pooled normal plasma, red blood cells and factor-deficient plasma with various percent (%) factor activity ranging from 20%-100%. The factor sensitivity for the i-STAT PTPlus test was estimated to be FII - 39.5%; FV - 42.0%; FVII - 21.5%; FX - 22.0%.
e. Analytical Specificity
i. Interference
The interference performance of the prothrombin time test in the i-STAT PT2ulus cartridge with the i-STAT 1 System was evaluated in the presence of potentially interfering endogenous or exogenous substances based on CLSI EP07-A2: Interference Testing in Clinical Chemistry, 2nd Edition, CLSI EP07-ED3, and supplement document EP37-ED1. The effect of each substance at each prothrombin time level (normal and therapeutic) was evaluated by comparing the performance of a test sample spiked to a high concentration of the substance and a control sample spiked with an equal volume of solvent. For an identified interferent, a doseresponse was performed to determine the degree of interference as a function of the substance concentration. Table 9 contains the list of substances tested and the interference results.
10
| Table 9: Potentially Interfering Substances and Test Concentration | ||||
|---|---|---|---|---|
| Substance | Test | |||
| Concentration | Test | |||
| Concentration | ||||
| (mg/dL) | Interference | |||
| (Yes/No) | Interference | |||
| Result | ||||
| Acetaminophen | 1324 µmol/L | $2.0x10^1$ | No | |
| Acetylsalicylic | ||||
| Acid | 3.62 mmol/L | $6.5x10^1$ | No | |
| Ascorbic Acid | 342 µmol/L | 6.0 | No | |
| Atorvastatin | 750 µg/L | $7.5x10^{-2}$ | No | |
| Unconjugated | ||||
| Bilirubin | 684 µmol/L | $4.0x10^1$ | No | |
| Conjugated | ||||
| Bilirubin | 475 µmol/L | $4.0x10^1$ | No | |
| Chlorhexidine | ||||
| digluconate | 0.1%* | $1.0x10^{-3}$ | Yes | Increased results |
| ≥ $9.58x10^{-4}$ % | ||||
| Daptomycin | 0.55 mg/mL | $5.5x10^1$ | Yes | Increased results |
| ≥ 0.22 mg/mL | ||||
| Enoxaparin | 2.0 IU/mL* | 2.0 | No | |
| Epsilon- | ||||
| aminocaproic | ||||
| acid | 0.39 mg/mL | $3.9x10^1$ | No | |
| Fondaparinux | 3.78 mg/L* | $3.8x10^{-1}$ | No | |
| Hemoglobin | 10 g/L | $1.0x10^3$ | No | |
| Ibuprofen | 2425 µmol/L | $5.0x10^1$ | No | |
| Oritavancin | 414 mg/L* | $4.1x10^1$ | Yes | Increased results |
| ≥ 104 mg/L | ||||
| Prasugrel | 265.5 ng/mL* | $2.7x10^{-2}$ | No | |
| Tranexamic | ||||
| Acid | 45 µg/mL* | $4.5x10^6$ | No | |
| Triglycerides | 37 mmol/L | $3.2x10^3$ | No | |
| Uric Acid | 1.4 mmol/L | $2.4x10^1$ | No |
- No CLSI EP07-A2, EP07-ED3, or EP37-ED1 recommended test concentration available.
ii. Other sensitivity studies
1) Fibrinogen Sensitivity
Fibrinogen sensitivity was evaluated across five (5) fibrinogen levels. The study demonstrated that the prothrombin time test in the i-STAT PTPlus cartridge with the i-STAT 1 System is insensitive to fibrinogen across a concentration range of 63 – 702 mg/dL. In addition, results from the clinical method comparison study (including subjects receiving coumarin therapy as well as subjects not receiving coumarin therapy) supports insensitivity to fibrinogen in the range of 63 – 702 mg/dL.
2) Platelet Sensitivity
11
Platelet sensitivity was evaluated at three (3) platelet levels (low, nominal, and high). The study demonstrated that the prothrombin time test in the i-STAT PTplus cartridge with the i-STAT 1 System is insensitive to platelets in the range of 70,000 - 670,000/mm². In addition, results from the clinical method comparison study (including subjects receiving coumarin therapy as well as subjects not receiving coumarin therapy) supports insensitivity to platelets in the range of 70,000 - 670,000/mm3.
3) Hematocrit Sensitivity
Hematocrit sensitivity was evaluated at three (3) hematocrit levels (low, nominal, and high). The study demonstrated that the prothrombin time test in the i-STAT PTplus cartridge with the i-STAT 1 System is insensitive to hematocrit in the range of 24 to 54% packed cell volume (PCV). In addition, results from the clinical method comparison study (including subjects receiving coumarin therapy as well as subjects not receiving coumarin therapy) supports insensitivity to hematocrit in the range of 24 to 54% PCV.
4) Heparin Sensitivitv
Sensitivity to unfractionated heparin was evaluated at two (2) heparin levels. The study demonstrated that the prothrombin time test in the i-STAT PT2/us cartridge with the i-STAT 1 System is insensitive to unfractionated heparin concentrations up to 1.0 IU/mL.
5) Sensitivity for Lupus Anticoagulant
Sensitivity to lupus anticoagulant antibodies (LA) was evaluated using two (2) levels (low and high) of positive LA and one (1) level of negative LA (control). The study demonstrated that the prothrombin time test in the i-STAT PT2/us cartridge with the i-STAT 1 System is sensitive to both low and high levels of lupus anticoagulant antibodies.
f. Assay cut-off
Not applicable.
B. Comparison Studies
a. Method Comparison with predicate device
Venous and capillary whole blood specimens were prospectively collected from subjects undergoing anticoagulant therapy with coumarin derivates and from subjects who were not on anticoagulant therapy at three (3) clinical sites. Both venous and capillary specimens were tested in duplicate on the i-STAT 1 Analyzer and were tested in singlicate on the Roche CoaguChek predicate device. The study design and analysis
12
method were based on recommendations from CLSI EP09c Measurement Procedure Comparison and Bias Estimation Using Patient Samples, 3rd ed. Passing-Bablok regression analysis was performed for the first replicate of the i-STAT prothrombin time result versus the singlicate result from the CoaguChek. The results of the method comparison of venous whole blood and capillary whole blood samples are presented in Table 10 (seconds) and Table 11 (INR).
| Table 10: Method Comparison Results for i-STAT PTplus Cartridge with i-STAT 1 System vs. CoaguChek® XS System |
|---|
| (Seconds) |
| Matrix | N | i-STAT 1 PT (sec) Range | CoaguChek PT (sec) Range | Correlation coefficient (R) Estimate | 95% CI | Slope Estimate | 95% CI | Intercept Estimate | 95% CI |
|---|---|---|---|---|---|---|---|---|---|
| Venous | 191* | 8.5 – 67.9 | 10.8 – 84.6 | 0.98 | 0.97 to 0.98 | 0.736 | 0.715 to 0.757 | 1.352 | 0.708 to 1.920 |
| Capillary | 153* | 8.6 – 61.9 | 11.1 – 83.7 | 0.97 | 0.96 to 0.98 | 0.743 | 0.711 to 0.776 | 1.051 | 0.309 to 1.892 |
Results with outliers included
Table 11: Method Comparison Results for i-STAT PTP48 Cartridge with i-STAT 1 System vs. CoaguChek® XS System (INR)
| Matrix | N | i-STAT 1
INR Range | CoaguChek
INR Range | Correlation coefficient
(R) | | Slope | | Intercept | |
|-----------|------|-----------------------|------------------------|--------------------------------|--------------|----------|----------------|-----------|----------------|
| | | | | Estimate | 95% CI | Estimate | 95% CI | Estimate | 95% CI |
| Venous | 191* | 0.8 – 6.7 | 0.9 – 7.0 | 0.98 | 0.97 to 0.98 | 0.875 | 0.857 to 0.906 | 0.113 | 0.045 to 0.157 |
| Capillary | 153* | 0.8 – 6.1 | 0.8 – 7.0 | 0.97 | 0.96 to 0.98 | 0.885 | 0.846 to 0.923 | 0.104 | 0.009 to 0.171 |
*Results with outliers included
b. Method comparison with reference device
Venous and capillary whole blood specimens were prospectively collected from subjects undergoing anticoagulant therapy with coumarin derivates and from subjects who were not on anticoagulant therapy at three (3) clinical sites. Both venous and capillary specimens were tested in duplicate on the i-STAT 1 Analyzer and citrated plasma from the venous whole blood specimens was tested in duplicate on the Sysmex CS-2500 reference instrument using Dade Innovin reagent. The study design and analysis method were based on recommendations from CLSI EP09c Measurement Procedure Comparison and Bias Estimation Using Patient Samples, 3rd ed. Passing-Bablok regression analysis was performed for the first replicate of the i-STAT prothrombin time result versus the first replicate result from the Sysmex CS-2500. The results of the method comparison of venous whole blood and capillary whole blood samples is presented in Table 12 (seconds) and Table 13 (INR).
| Table 12: Method Comparison Results for i-STAT 1 System vs. Sysmex CS-2500 (seconds) | |||||
|---|---|---|---|---|---|
| Matrix | N | i-STAT 1
PT (sec)
Range | Sysmex
PT (sec)
Range | Correlation coefficient
(R)
Estimate | Correlation coefficient
(R)
95% CI | Slope
Estimate | Slope
95% CI | Intercept
Estimate | Intercept
95% CI |
|-----------|------|-------------------------------|-----------------------------|--------------------------------------------|------------------------------------------|-------------------|-----------------|-----------------------|---------------------|
| Venous | 211* | 8.5 – 80.5 | 9.7 – 83.1 | 0.92 | 0.90 to 0.94 | 1.037 | 0.994 to 1.082 | -0.591 | -1.500 to 0.151 |
| Capillary | 203* | 8.6 – 80.5 | 9.7 – 83.1 | 0.91 | 0.88 to 0.93 | 1.023 | 0.979 to 1.070 | -0.189 | -1.052 to 0.641 |
*Results with outliers included
13
| Table 13: Method Comparison Results for i-STAT PTplus Cartridge with i-STAT 1 System vs. Sysmex CS-2500 (INR) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Matrix | N | i-STAT 1 | ||||||||
| INR | ||||||||||
| Range | Sysmex | |||||||||
| INR | ||||||||||
| Range | Correlation coefficient | |||||||||
| (R)/ | ||||||||||
| Estimate | Correlation coefficient | |||||||||
| (R)/ | ||||||||||
| 95% CI | Slope | |||||||||
| Estimate | Slope | |||||||||
| 95% CI | Intercept | |||||||||
| Estimate | Intercept | |||||||||
| 95% CI | ||||||||||
| Venous | 211* | 0.8 – 8.0 | 0.9 – 8.1 | 0.92 | 0.90 to 0.94 | 1.037 | 1.000 to 1.078 | 0.004 | -0.079 to 0.075 | |
| Capillary | 203* | 0.8 – 8.0 | 0.9 – 8.1 | 0.91 | 0.89 to 0.93 | 1.022 | 0.984 to 1.061 | 0.047 | -0.029 to 0.127 |
*Results with outliers included
C. Expected Values/Reference range
a. Reference range
A reference interval study was conducted with venous and capillary samples from apparently healthy adult subjects. Venous specimens were tested in singlicate and after testing venous blood, a capillary specimen from the subject was collected via fingerstick. Testing was performed with three cartridges lots on the i-STAT 1 System at three (3) clinical sites. Reference intervals for INR and seconds in venous and capillary samples were determined according to the CLSI Guideline EP28-A3c Defining, Establishing, and Verifying, Reference Intervals in the Clinical Laboratory: Approved Guideline -Third Edition. The reference intervals established for each capillary and venous sample type are summarized in Table 14.
| Table 14: Reference Range for i-STAT PTPlus Cartridge with i-STAT 1 System | ||||
|---|---|---|---|---|
| Specimen Type | N | Unit | Mean | Range |
| Capillary | 146 | INR* | 1.1 | 0.9 - 1.3 |
| Seconds** | 10.6 | 9.0 - 13.8 | ||
| Venous | 154 | INR* | 1.1 | 0.9 - 1.3 |
| Seconds** | 10.6 | 9.2 - 13.0 |
*Pooled by sample type across all sites.
** Due to the rounding of parameters in the equation to convert INR to seconds, small differences in seconds can be observed.
8. Conclusion
The results of these studies demonstrate that performance of the prothrombin time test in the i-STAT PT2445 cartridge with the i-STAT 1 System are substantially equivalent to the predicate device.