(270 days)
The CORA PlateletMapping System is intended for in vitro diagnostic use to provide qualitative assessment of platelet function. The CORA System records the kinetic changes in a sample of heparinized whole blood as the sample clots.
The CORA System PlateletMapping Assay Cartridge provides four channels of dried-in-place reagents, HKH (Kaolin with Heparinase), Activator F, AA and ADP (one reagent in each channel). In combination, MA parameter results from these four reagents are used to calculate the parameters platelet % Inhibition and % Aggregation for AA and ADP.
Results from the CORA analysis should not be the sole basis for a patient diagnosis, but should be evaluated together with the patient's medical history, the clinical picture and, if necessary, further hemostasis tests.
The CORA System with CORA PlateletMapping Assay Cartridge is indicated for use with adult patients where an evaluation of their blood hemostasis properties is desired. Hemostasis evaluation with the CORA PlateletMapping System is used to assess clinical conditions in cardiovascular surgery and cardiology procedures to assess hemorrhage or thrombosis conditions.
The CORA PlateletMappingSystem consists of a four-channel diagnostic analyzer with integrated computer module, system reagents (ActF, AA, ADP and HKH) and microfluidic test cartridge. Reagents are dried-in-place within the cartridges during manufacturing.
To perform a test, a disposable CORA PlateletMapping Assay Cartridge is inserted into the analyzer. Blood is added to an entry port on the cartridge and drawn into the cartridge under analyzer control. The amount of the sample drawn into the cartridge is automatically determined by the volume of the blood chambers in the cartridge. Once in the disposable, the sample is metered into as many as four separate analysis channels, depending upon the assay being performed. Reconstitution of reagents dried within the cartridge is accomplished by moving the sample back and forth through reagent chambers, under the control of microfluidic valves and bellows within the cartridge. After each sample has been mixed with reagent, it is delivered to a test cell where it is monitored for changes due to coagulation. Excess sample material is moved under microfluidic control into an enclosed waste chamber within the cartridge.
The CORA technology is based on a disposable containing up to four independent measurement cells. Each cell consists of a short vertically-oriented injection molded tube (ring) with a diameter of 2.5mm and a length of 4.5mm. Detection of clotting in the CORA System is performed optically. Under control of the analyzer, approximately 20uL of prepared sample is delivered to the tube, where a meniscus naturally forms at each end of the tube. The tube is positioned so that the lower meniscus partially blocks light traveling from a collimated source toward a photodiode.
During testing, a piezoelectric actuator drives the measurement cell(s) through a motion profile composed of summed sinusoids at different frequencies. The profile has a maximum amplitude of under 10um and contains frequencies from 10-500Hz. Some, but not all, of the measurement cell motion will induce motion in the sample meniscus, which will be detected by the photodiode. The resulting motion of the meniscus is monitored optically and analyzed by the analyzer to calculate the resonant frequency and modulus of elasticity (stiffness) of the sample. By performing a Fast Fourier Transform (FFT) on meniscus motion data, it is possible to determine the frequencies of input motion that caused the greatest deflection of the sample (these are called the resonant frequencies).
Resonance is the tendency of a material or structure to oscillate with greater amplitude at some frequencies than others. The exact frequencies at which resonance occurs will depend on the stiffness and mass of the sample. Stiffness, in turn, is a function of a material's modulus of elasticity and the boundary conditions to which the material is exposed, such as the geometry and materials of a test cell. By holding these boundary conditions and sample mass constant from run to run, the CORA System allows direct comparison of elasticity between samples.
In a typical test, blood that has been delivered to the measurement cell will not clot for several minutes. During this time the sample has no inherent stiffness except that provided by surface tension, and since this remains constant the measured resonant frequencies will not change. Once clotting begins, however, the elastic modulus and thus the resonant frequencies increase rapidly. In tests where clotting does not occur, the resonant frequency of the sample will not change. During coagulation, however, a clot will bind to the test tube (ring) and the resonant frequency will rise with increasing firmness of the clot. The CORA Analyzer collects meniscus motion data, tracks changing resonant frequencies and analyzes the frequency data to provide parameters describing the clot. Results are presented in a format identical to the TEG 5000.
The CORA System with PlateletMapping Assay is intended for in vitro diagnostic use to provide a qualitative assessment of platelet function. The system records kinetic changes in heparinized whole blood samples as they clot, calculating % Inhibition and % Aggregation for AA and ADP parameters.
Here's an analysis of the acceptance criteria and the study performance for the CORA System with PlateletMapping Assay:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria for the clinical performance. Instead, it presents the device's sensitivity and specificity and compares them to the predicate device, the TEG 5000 Platelet Mapping Assay.
| Metric | CORA System Performance | Predicate Device (TEG 5000) Performance |
|---|---|---|
| ADP | ||
| Sensitivity | 74.5% (95% CI: 64.7-82.8%) | 94.9% (95% CI: 88.5-98.3%) |
| Specificity | 82.9% (95% CI: 77.7-87.4%) | 39.0% (95% CI: 29.7-49.1%) |
| AA | ||
| Sensitivity | 84.0% (95% CI: 77.8-89.0%) | 88.4% (95% CI: 82.8-92.7%) |
| Specificity | 86.5% (95% CI: 80.4-91.2%) | 50.0% (95% CI: 29.1-70.9%) |
For analytical precision, the reported data indicates the variability (SD and %CV) across various factors (reagent lot, operator, analyzer, day, and repeatability) for MA parameters in HKH, and indicates that the percent positive and negative agreement for AA and ADP % aggregation inhibition at low and high level is 100%. However, no specific acceptance criteria for precision are provided.
2. Sample Size Used for the Test Set and Data Provenance
-
Reference Range Determination (Clinical Performance):
- Sample Size: Up to 55 normal volunteer subjects were taken at each of the three clinical sites, totaling approximately 150 samples.
- Data Provenance: Prospective, collected from normal volunteer subjects by three clinical sites representing demographic populations of the three areas regarding age, race, and gender.
-
Method Comparison (Clinical Performance):
- Sample Size: Not explicitly stated, but the study was conducted on "patient samples" from "surgical patients and normal donors (for CORA)." The sensitivity and specificity percentages are derived from these samples.
- Data Provenance: The patients were undergoing heart surgery or PCI procedures, with blood samples drawn pre- and post-surgery and in the ICU. This indicates a prospective collection within a clinical setting. The study was conducted at three clinical sites.
-
Analytical Precision (Non-Clinical Performance):
- Sample Size: For HKH, blood draws from 3 donors (Hypo, Normal, Hyper). For AA and ADP Percent Aggregation and Inhibition, blood draws from 2 donors (Normal, Abnormal). Each testing scenario involved 5 non-consecutive days, 2 operators, 3 reagent lots, 12 analyzers, and 2 replicates. This results in n=120 for each MA parameter level (Hypo, Hyper, Normal) for HKH.
- Data Provenance: The testing was performed in Coramed's laboratory, suggesting internally generated data.
-
Interference (Non-Clinical Performance):
- Sample Size: Not explicitly stated.
- Data Provenance: Performed in Coramed's laboratory.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not specify the use of experts to establish a "ground truth" in the traditional sense (e.g., radiologists interpreting images).
- For the Reference Ranges, the ground truth is established by selecting "normal volunteer subjects" and then deriving the range from their results. This is based on a statistical approach to define normalcy within the tested population.
- For the Method Comparison, the ground truth for determining disease status (e.g., platelet dysfunction) is implicitly established through clinical diagnosis of "surgical patients or PCI procedures" who are known to have conditions where blood hemostasis properties evaluation is desired. However, the exact method of confirming ground truth for individual results to calculate sensitivity and specificity (e.g., by another gold standard method, pathology, or expert clinical diagnosis) is not detailed. The comparison is made against the TEG 5000 as a predicate, which usually implies that the predicate serves as a reference, but a true independent ground truth for classification is not explicitly defined in the provided text.
4. Adjudication Method (for the test set)
No adjudication method involving experts is mentioned for clinical performance results. The sensitivity and specificity would be derived by comparing the CORA device's output against the "true" clinical status of the patients, or the predicate device's output, but the process of determining that "true" status is not elaborated in terms of an adjudication panel.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and the Effect Size of How Much Human Readers Improve with AI vs Without AI Assistance
This is an in vitro diagnostic device for assessing platelet function, not an imaging device typically involving human readers interpreting results. Therefore, an MRMC comparative effectiveness study involving human readers and AI assistance is not applicable and was not performed or described in this document.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done
Yes, the studies presented appear to be standalone performance assessments of the CORA System. The "system" is an automated analyzer that generates quantitative results (MA, % Aggregation, % Inhibition). Its performance (precision, reference ranges, sensitivity, specificity) is evaluated directly, without explicitly describing a human-in-the-loop interaction in the context of the performance data. While the "results from the CORA analysis should not be the sole basis for a patient diagnosis, but should be evaluated together with the patient's medical history, the clinical picture and, if necessary, further hemostasis tests," this statement refers to the clinical application rather than the performance study design.
7. The Type of Ground Truth Used
- Reference Ranges: The ground truth is effectively derived from the measurements of a healthy reference population (normal volunteer subjects) to establish what is considered "normal."
- Method Comparison: The ground truth for calculating sensitivity and specificity is implicitly clinical diagnosis of patients undergoing cardiovascular procedures, where blood hemostasis evaluation is desired. However, the specific gold standard or method used to classify each patient's 'true' platelet function status (e.g., by another established assay, pathology, or expert clinical assessment) against which the CORA results are benchmarked is not explicitly defined. The comparison also heavily relies on the predicate device (TEG 5000), suggesting that the predicate might serve as a de facto reference for classification if an independent gold standard was not available or used. It states "studies were conducted... on patient samples following CLSI EP09-A3 Guideline," which typically involves comparison to a reference method.
8. The Sample Size for the Training Set
The document does not explicitly describe a "training set" in the context of an AI/machine learning model. The CORA System is an automated diagnostic device based on physical measurement techniques (e.g., resonance, optical detection), not typically an AI system that requires a training set. The descriptions of "precision testing" and "reference ranges" are for analytical and clinical validation, not algorithm training.
9. How the Ground Truth for the Training Set Was Established
Since no "training set" for an AI/machine learning model is described, the question of how its ground truth was established is not applicable.
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Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is a stylized image of three human profiles facing to the right, stacked on top of each other.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
January 3, 2015
Coramed Technologies, LLC c/o Mr. Norman Brunner Director of RA/OA 6225 W. Howard Street Niles IL 60714
Re: K140893
Trade/Device Name: CORA (Coagulation Resonance Analysis) System with Platelet Mapping Assay Regulation Number: 21 CFR 864.5700 Regulation Name: Automated platelet aggregation system Regulatory Class: II Product Code: JOZ Dated: December 2, 2014 Received: December 3, 2014
Dear Mr. Brunner:
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. 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.
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 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 Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the
{1}------------------------------------------------
electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. 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
http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Leonthena R. Carrington -A
Mary S. Pastel, ScD for Deputy Director for Radiological Health Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K140893
Device Name CORA PlateletMapping Hemostasis System
Indications for Use (Describe)
The CORA PlateletMapping System consists of the CORA analyzer and the CORA PlateletMapping Assay Cartridge. The CORA Platelet Mapping System is intended for in vitro diagnostic use to provide qualitative assessment of platelet function. The CORA System records the kinetic changes in a sample of heparinized whole blood as the sample clots.
The CORA System PlateletMapping Assay Cartridge provides four channels of dried-in-place reagents, HKH (Kaolin with Heparinase), Activator F. AA and ADP (one reagent in each channel). In combination, MA parameter results from these four reagents are used to calculate the parameters platelet % Inhibition and % Aggregation for AA and ADP.
Results from the CORA analysis should not be the sole basis for a patient diagnosis, but should be evaluated together with the patient's medical history, the clinical picture and, if necessary, further hemostasis tests.
The CORA System with CORA PlateletMapping Assay Cartridge is indicated for use with adult patients where an evaluation of their blood hemostasis properties is desired. Hemostasis evaluation with the CORA PlateletMapping System is used to assess clinical conditions in cardiology procedures to assess hemorrhage on thrombosis conditions.
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) |
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Coramed Technologies, LLC 6225 W. Howard Street, Niles, Illinois 60714 847-647-8800 | 847-510-0502 FAX
CORA MED
CORA® System PlateletMapping Assay 510(k) Summary
APPLICANT INFORMATION
Name of Manufacturer: Coramed Technologies, LLC
Manufacturer Street Address: 6225 W. Howard St.
City, State, Zip: Niles, IL 60714
Phone Number: (847) 647-8800
FAX Number: (847) 510-0502
Contact person for all communications: Norman E. Brunner
Email for contact person: nbrunner@coramedtech.com
Date that Summary was prepared: January 2, 2015
DEVICE INFORMATION
Trade name (proprietary name): CORA® (Coagulation Resonance Analysis) System and the following assays and reagents
- PlateletMapping® Assay Reagents (heparinized blood) 트
- HKH (Kaolin with Heparinase), Kaolin + Heparinase ●
- ActF (ActivatorF) ●
- ADP (adenosine-5'-diphosphate) ●
- AA (Arachidonic Acid) ●
Common name (usual name): Whole Blood Hemostasis System
Classification Name: 21CFR 864.5700 Automated Platelet Aggregation System
PREDICATE DEVICE
- Thrombelastograph® (TEG® PlateletMapping Assay), K041502, Product Code JOZ (System, O Automated Platelet Aggregation), Haemoscope Corporation
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DESCRIPTION OF THE DEVICE
System Description
The CORA PlateletMappingSystem consists of a four-channel diagnostic analyzer with integrated computer module, system reagents (ActF, AA, ADP and HKH) and microfluidic test cartridge. See below for a description of system reagents. Reagents are dried-in-place within the cartridges during manufacturing.
To perform a test, a disposable CORA PlateletMapping Assay Cartridge is inserted into the analyzer. Blood is added to an entry port on the cartridge and drawn into the cartridge under analyzer control. The amount of the sample drawn into the cartridge is automatically determined by the volume of the blood chambers in the cartridge. Once in the disposable, the sample is metered into as many as four separate analysis channels, depending upon the assay being performed. Reconstitution of reagents dried within the cartridge is accomplished by moving the sample back and forth through reagent chambers, under the control of microfluidic valves and bellows within the cartridge. After each sample has been mixed with reagent, it is delivered to a test cell where it is monitored for changes due to coagulation. Excess sample material is moved under microfluidic control into an enclosed waste chamber within the cartridge.
The CORA Measurement Technique
The CORA technology is based on a disposable containing up to four independent measurement cells. Each cell consists of a short vertically-oriented injection molded tube (ring) with a diameter of 2.5mm and a length of 4.5mm. Detection of clotting in the CORA System is performed optically. Under control of the analyzer, approximately 20uL of prepared sample is delivered to the tube, where a meniscus naturally forms at each end of the tube. The tube is positioned so that the lower meniscus partially blocks light traveling from a collimated source toward a photodiode.
During testing, a piezoelectric actuator drives the measurement cell(s) through a motion profile composed of summed sinusoids at different frequencies. The profile has a maximum amplitude of under 10um and contains frequencies from 10-500Hz. Some, but not all, of the measurement cell motion will induce motion in the sample meniscus, which will be detected by the photodiode. The resulting motion of the meniscus is monitored optically and analyzed by the analyzer to calculate the resonant frequency and modulus of elasticity (stiffness) of the sample. By performing a Fast Fourier Transform (FFT) on meniscus motion data, it is possible to determine the frequencies of input motion that caused the greatest deflection of the sample (these are called the resonant frequencies).
Resonance is the tendency of a material or structure to oscillate with greater amplitude at some frequencies than others. The exact frequencies at which resonance occurs will depend on the stiffness and mass of the sample. Stiffness, in turn, is a function of a material's modulus of elasticity and the boundary conditions to which the material is exposed, such as the geometry and materials of a test cell. By holding these boundary conditions and sample mass constant from run to run, the CORA System allows direct comparison of elasticity between samples.
In a typical test, blood that has been delivered to the measurement cell will not clot for several minutes. During this time the sample has no inherent stiffness except that provided by surface tension, and since this remains constant the measured resonant frequencies will not change. Once clotting begins, however, the elastic modulus and thus the resonant frequencies increase rapidly. In tests where clotting does not occur, the resonant frequency of the sample will not change. During coagulation, however, a clot will bind to the test tube (ring) and the resonant frequency will rise with increasing firmness of the clot. The CORA Analyzer collects meniscus motion data, tracks changing resonant frequencies and analyzes the frequency data to provide parameters describing the clot. Results are presented in a format identical to the TEG 5000.
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| CORAParameter | Definition | Purpose |
|---|---|---|
| MA | MA, or Maximum Amplitude, represents themaximum firmness of the clot during the test. | Normal / reduced / increasedclot elasticity/strength |
| ADP% Aggregation | See below | Level of ADP platelet activityaggregation |
| ADP% Inhibition | See below | Level of ADP platelet activityinhibition |
| AA% Aggregation | See below | Level of AA platelet activityaggregation |
| AA% Inhibition | See below | Level of AA platelet activityinhibition |
The following definitions apply to calculated parameters in the CORA System:
PlateletMapping Assay and Reagents
The assay uses AA and ADP agonists to assess platelet aggregation or inhibition. Since thrombin (present in blood samples) is the primary and most potent activator of platelets, its activity must be inhibited with heparin so that the platelet inhibiting effects of ADP and AA can be measured. Thrombin also converts fibrinogen into fibrin to create the fibrin mesh necessary for any clot formation, and converts Factor XIII to Factor XIIIa for fibrin cross linking. Since thrombin has been rendered inactive by heparin, ActivatorF is used to replace thrombin's role in the conversion of fibrinogen to fibrin and Factor XIII to Factor XIIIa. Thus, with this cross-linked fibrin network as the foundation (represented by $MA_{ActF}$), additional clot strength due to platelet-fibrin bonding related to ADP ($MA_{ADP}$) and AA ($MA_{AA}$) platelet receptor activation can be measured. The HKH reagent, a combination of Kaolin and Heparinase, generates test data for the uninhibited MA ($MA_K$) resulting from thrombin activation of the blood sample, while the Heparinase neutralizes the effects of heparin.
For calculations of clot strength reduction, percent MA reduction is
$$100 - \left[ \left{ \frac{MA_P - MA_{Act}r}{MA_K - MA_{Act}r} \right} * 100 \right], \quad (Equation \ l).$$
where $MA_P$ can be either $MA_{ADP}$ or $MA_{AA}$. AA Aggregation and Inhibition, and ADP Aggregation and Inhibition are parameters derived from the CORA MA parameters for the ActF, AA, ADP and HKH reagents, as described above. Following are the equations used by the CORA System to derive these parameters:
| AA Percent Aggregation = | $\left[\left{\frac{MA_{AA}-MA_{ActF}}{MA_K-MA_{ActF}}\right}*100\right].$ | (maximum of 100%) | (Equation 2) |
|---|---|---|---|
| ADP Percent Aggregation = | $\left[\left{\frac{MA_{ADP}-MA_{ActF}}{MA_K-MA_{ActF}}\right}*100\right].$ | (maximum of 100%) | (Equation 3) |
| AA Percent Inhibition = | 100 – AA Percent Aggregation, | (minimum of 0%) | (Equation 4) |
| ADP Percent Inhibition = | 100 – ADP Percent Aggregation, | (minimum of 0%) | (Equation 5) |
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INTENDED USE AND INDICATIONS FOR USE
The CORA PlateletMapping System consists of the CORA analyzer and the CORA PlateletMapping Assay Cartridge. The CORA Platelet Mapping System is intended for in vitro diagnostic use to provide qualitative assessment of platelet function. The CORA System records the kinetic changes in a sample of heparinized whole blood as the sample clots.
The CORA System PlateletMapping Assay Cartridge provides four channels of dried-in-place reagents, HKH (Kaolin with Heparinase), Activator F, AA and ADP (one reagent in each channel). In combination, MA parameter results from these four reagents are used to calculate the parameters platelet % Inhibition and % Aggregation for AA and ADP.
Results from the CORA analysis should not be the sole basis for a patient diagnosis, but should be evaluated together with the patient's medical history, the clinical picture and, if necessary, further hemostasis tests.
The CORA System with CORA PlateletMapping Assay Cartridge is indicated for use with adult patients where an evaluation of their blood hemostasis properties is desired. Hemostasis evaluation with the CORA PlateletMapping System is used to assess clinical conditions in cardiovascular surgery and cardiology procedures to assess hemorrhage or thrombosis conditions.
SUMMARY OF TECHNOLOGICAL CHARACTERISTICS COMPARING THE CORA SYSTEM TO THE TEG 5000 PREDICATE DEVICE
| Item | TEG® 5000 Platelet Mapping | CORA® System Platelet Mapping |
|---|---|---|
| Predicate | ||
| Analyzer | ||
| Technological Purpose | Monitoring the response of a clot tolow levels of applied strain | Monitoring the response of a clot tolow levels of applied strain |
| What is measured | Changes in clot elasticity over time | Changes in clot elasticity over time |
| Initial Warm Up Time | 5 min | 5 min |
| Time to Complete a Test | Varies with assay | Same as TEG 5000 |
| Assays and Reagents | ||
| Platelet Mapping Assay | ActF, AA, ADP and Kaolin withHeparinase | ActF, AA, ADP and HKH reagents,same materials as TEG 5000 |
| Item | TEG® 5000 Predicate | CORA® System |
| Analyzer | Thrombelastography analyzer, separate computer and software | Fully integrated Thrombelastography analyzer |
| Measuring Technique | Direct-contact measurement of shear elasticity of a coagulating sample | Non-contact measurement of shear elasticity of a coagulating sample |
| Measuring Channels | 2, each independent and interchangeable | 4, each independent and interchangeable |
| Signal Transducer | Electromechanical detection (rotary variable inductive transformer) of rotary motion of a pin suspended in the sample | Optical detection (silicon photodiode) of the motion of a free surface of the sample |
| Temperature Control | 20° to 40°C | 20° to 50°C |
| Sample Volume (per channel) | 360-380 μL | 63μL |
| Total Reaction Volume (single channel) | 360-380μL | 20μL |
| Mains Supply Voltage | 120V, 60Hz and 220V, 50Hz model available | 100-240V, 50-60Hz (international power supply) |
| Analyzer Input Voltage | 24 volts AC, 30 watts max | 12 volts DC, 60 watts max |
| Environment | Level and vibration free position, no solar radiationOperating temperature:10° to 35°CStorage Temperature:-30° to 50°C (analyzer only)Relative humidity 20 to 80% (non-condensing) | Stable and level surfaceOperating Temperature10° to 32°CStorage Temperature:-20° to 50°C (analyzer only)Relative humidity 20 to 80% (non-condensing) |
| Sample Preparation | Performed by the operator using pipettes to reconstitute reagents and mix reagents with the sample | Performed under analyzer control within the disposable cartridge |
| Pipetting | Manual accurate pipettes(10, 20, 50, 100, 340, 360, 500, 1000μL) | Unmetered transfer pipette or syringe; blood sample is added until it fills to a level above the line marked on the blood intake well of the cartridge |
| Consumables | Cups & Pins (acrylic plastic) | Carrier (acrylic plastic) with microfluidics laminate and test rings |
Table of Similarities
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Table of Differences
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SUMMARY OF NON-CLINICAL PERFORMANCE DATA
Analytical Precision
Testing was performed in Coramed's laboratory for precision, using CLSI EP5-A2 as guidance.
Three types of donor heparinized whole blood (CWB) samples were used in precision testing for the HKH reagent:
- Hypo (donors with naturally low coagulation levels, as indicated by MA parameter near the . lower limit of the reference range);
- Normal (donors with natural coagulation levels of MA parameters near the center of the . reference ranges):
- Hyper (donors with naturally high coagulation levels, as indicated by and MA parameter near the . upper limit of the reference range.
For ADP and AA Aggregation and Inhibition Precision testing, sample types to be used are:
- Normal (donors with little or no platelet inhibition levels well below cut-off values)
- Abnormal (donors with platelet inhibition levels above cut-off values)
Testing was performed with blood draws from three donors (one Hypo, one Normal, and one Hyper) for HKH and two donors (Normal and Abnormal) for AA and ADP Percent Aggregation and Inhibition, on each of five days (non-consecutive). Testing was performed by two operators using three reagent lots and twelve analyzers, two replicates. The structure of this precision test is shown below.
| Sample Type (Hypo, Normal or Hyper) | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Day 1 (Total of 5 days) | ||||||||||||
| Operator | Operator 1 | Operator 2 | ||||||||||
| Reagent lot | 1 | 2 | 3 | 1 | 2 | 3 | ||||||
| Analyzer | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 |
| Replicates | 1,2 | 1,2 | 1,2 | 1,2 | 1,2 | 1,2 | 1,2 | 1,2 | 1,2 | 1,2 | 1,2 | 1,2 |
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Structure of Precision Testing
Precision test estimates by test, parameter and donor sample test level are shown in the table on the following page.
| Test | Parameter | Level | n | Mean | Reagent Lot | Operator¹ | Analyzer (withinOperator, ReagentLot) | Day(within Analyzer,Operator, ReagentLot) | Repeatability | Total² | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | |||||
| HKH | MA | Hypo | 120 | 59.6 | 0.35 | 0.6% | 0.22 | 0.4% | 0.00 | 0.0% | 0.96 | 1.6% | 0.39 | 0.6% | 1.12 | 1.9% |
| HKH | MA | Hyper | 120 | 67.6 | 0.11 | 0.2% | 0.07 | 0.1% | 0.00 | 0.0% | 0.56 | 0.8% | 0.46 | 0.7% | 0.74 | 1.1% |
| HKH | MA | Normal | 120 | 63.4 | 0.30 | 0.5% | 0.28 | 0.4% | 0.00 | 0.0% | 0.34 | 0.5% | 0.57 | 0.9% | 0.78 | 1.2% |
1 Operator includes operator and operator-by-reagent lot interaction
"Total includes reagent lot, operator, operator lot interaction, analyzer (within operator, reagent lot), day (within analyzer, operator, reagent lot) and repeatability
The percent positive and negative agreement for the AA and ADP % aggregation inhibition at low and high level plas 100%.
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Interference
Testing was performed in Coramed's laboratory for interference, using CLSI EP7-A2 as guidance.
For PlateletMapping Assays ActF, AA and ADP, potential interferents tested were Short Draw and Hemodilution. AA and ADP were also tested for interference with Hemolysis. For ActF, no interferents were found. For AA, Hemolysis and Short Draw (less than 2.5 mL in a 4 mL tube) were found to be interferents. For ADP, Short Draw (less than 2.5 mL in a 4 mL tube) and Hemodilution levels above 40% were found to be interferents. HKH potential interferents tested were Absence of a Discard Tube, Short Draw, Hemolysis, Hemodilution and epsilon aminocaprioc acid (EACA). Interferents were Hemolysis and Hemodilution levels above 40%.
SUMMARY OF CLINICAL PERFORMANCE DATA
Testing was performed at three clinical sites for Reference Ranges and Method Comparison.
Reference Ranges
Reference Ranges for the CORA PlateletMapping Assays were estimated using the CLSI C28-A3c Guideline on three reference sample groups. Blood samples from up to 55 normal volunteer subjects were taken at each of the three sites, for a total of approximately 150 samples (see below). Subjects were chosen representing demographic populations of the three areas, regarding age, race and gender. These reference ranges are shown below.
| Assay | Heparinized BloodParameter | N | Range |
|---|---|---|---|
| HKH | MA (mm) | 149 | 53 - 68 |
| ActF | MA (mm) | 152 | 2 - 19 |
| ADP | MA (mm) | 145 | 45 - 69 |
| AA | MA (mm) | 144 | 51 - 71 |
| ADP | % Aggregation | 145 | Abnormal < 83% |
| ADP | % Inhibition | 145 | Normal ≥ 83% |
| AA | % Aggregation | 144 | Abnormal < 89% |
| AA | % Inhibition | 144 | Normal ≥ 89% |
Method Comparison
Method Comparison studies were conducted at three clinical sites on patient samples following CLSI EP09-A3 Guideline. The subjects enrolled were patients undergoing heart surgery or PCI procedures. with blood samples drawn pre- and post-surgery and in the ICU. Summary statistics are presented below.
{11}------------------------------------------------
| Surgical Patients and Normal Donors (for CORA) | ||||
|---|---|---|---|---|
| All Sites | ADP | AA | ||
| Sensitivity | Specificity | Sensitivity | Specificity | |
| CORA | 74.5% | 82.9% | 84.0% | 86.5% |
| (95% CI) | 64.7% to 82.8% | 77.7% to 87.4% | 77.8% to 89.0% | 80.4% to 91.2% |
| TEG 5000 | 94.9% | 39.0% | 88.4% | 50.0% |
| (95% CI) | 88.5% to 98.3% | 29.7% to 49.1% | 82.8% to 92.7% | 29.1% to 70.9% |
CONCLUSIONS DRAWN FROM NON-CLINICAL AND CLINICAL TESTING
The data and information provided in this submission support a substantial equivalence determination for the CORA System with PlateletMapping Assay and the TEG 5000 Thromboelastograph Platelet Mapping Assay predicate device. Therefore, clearance of this 510(k) premarket notification for the CORA analyzer, with PlateletMapping Assay should be granted.
§ 864.5700 Automated platelet aggregation system.
(a)
Identification. An automated platelet aggregation system is a device used to determine changes in platelet shape and platelet aggregation following the addition of an aggregating reagent to a platelet-rich plasma.(b)
Classification. Class II (performance standards).