(349 days)
The QStat® Cartridge is a multi-channel cartridge that provides semi-quantitative indications of the coagulation and clot lysis state of a 3.2% citrated venous whole blood sample using the Quantra® Hemostasis Analyzer. The QStat Cartridge includes tests to assess coagulation via the intrinsic pathways and includes a test with tranexamic acid to evaluate clot lysis characteristics.
The QStat Cartridge is intended for in vitro diagnostic use by trained professionals at the point-of-care and in clinical laboratories to evaluate the viscoelastic properties of whole blood by means of the following functional parameters: Clot Time (CT), Clot Stiffness (CS), Fibrinogen Contribution to Clot Stiffness (FCS), Platelet Contribution to Clot Stiffness (PCS), and Clot Stability to Lysis (CSL).
The QStat Cartridge is indicated for the evaluation of blood coagulation and clot lysis in patients age 18 years and older to assess possible hypocoagulable conditions in trauma and liver transplantation procedures.
Results obtained with the OStat Cartridge should not be the sole basis for patient diagnosis.
For prescription use only.
The QStat Cartridge is a single-use, multi-channel (n=4) disposable plastic cartridge used with the Quantra Hemostasis Analyzer to assess a patient's coagulation and clot lysis (possible hypocoagulable and hypercoagulable conditions) in a hospital setting (point of care or laboratory) during trauma and liver transplantation procedures. The QStat Cartridge consists of four independent channels that can be tested simultaneously with Sonic Estimation of Elasticity via Resonance (SEER) Sonorheometry.
Each QStat Cartridge is pre-filled with reagents individually sealed in an airtight pouch. After a QStat Cartridge is removed from its primary packaging, it is inserted into the instrument dock. A venous whole blood sample, collected in a 3.2% sodium citrate anticoagulant blood collection tube (minimum volume 2.7 mL), is attached directly to the cartridge and the test is initiated using the touch screen interface on the Quantra Hemostasis Analyzer. The cartridge is the only component of the Quantra system that is in direct contact with blood. The fluidic system within the instrument draws the sample into the cartridge where it is warmed to 37℃, aliquoted, introduced and mixed with the lyophilized reagents, and analyzed. When the test is complete, the cartridge is released from the dock to be disposed of in an appropriate biosafety sharps container.
Each channel of the cartridge contains prefilled lyophilized reagents in the form of beads that enable differential testing without the need for any reagent preparation or pipetting before testing. The assay provides the following information for each patient sample: Clot Time (CT), Clot Stiffness (CS), Fibrinogen Contribution to Clot Stiffness (FCS), Platelet Contribution to Clot Stiffness (PCS) and Clot Stability to Lysis (CSL).
Here's an analysis of the provided text, extracting the requested information about acceptance criteria and the study proving device performance for the QStat® Cartridge:
Acceptance Criteria and Device Performance for QStat® Cartridge
1. Table of Acceptance Criteria and Reported Device Performance
| Parameter / Study Type | Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Precision/Reproducibility | ||
| Single Site Precision (QSL1) | Within-laboratory precision (total) CV% for CT, CS, FCS parameters ≤ 9.5% | CT: 3.5% CV, CS: 5.6% CV, FCS: 9.5% CV |
| Single Site Precision (QSL2) | Within-laboratory precision (total) CV% for CT, CS, FCS parameters ≤ 9.3% | CT: 6.1% CV, CS: 9.3% CV, FCS: 9.0% CV |
| Single Site Precision (Fibrinolysis-positive controls) | Total %CV for CT, CS, FCS below 5.8%. Total %CV for CSL below 7.1% OR total SD for CSL below 10.2% | CT, CS, FCS: ≤ 5.8% CV CSL: 7.1% CV and 10.2% SD |
| Multi-Site Reproducibility (CSL, Normal Sample) | Total imprecision of CSL parameter < 7% CV | 1.39% CV |
| Multi-Site Reproducibility (CSL, tPA spiked to CSL threshold) | Total imprecision of CSL parameter < 7% CV | 6.44% CV |
| Whole Blood Repeatability (CT, CS, FCS, PCS) | Total %CV below 15% | All sample types: < 15% CV |
| Whole Blood Repeatability (CSL) | Total %CV below 15% OR SD below 12% | All sample types: < 15% CV or < 12% SD (some exceptions with higher CV but still met SD criteria, e.g., 60 U/mL tPA: 26.1% CV but 11.8 SD was likely acceptable based on "OR" criteria) |
| Method Comparison with Predicate Device (ROTEM delta) | ||
| CT vs INTEM CT Correlation | Pearson correlation coefficient (95% CI) | 0.89 (0.87, 0.91) |
| CS vs EXTEM A20 Correlation | Pearson correlation coefficient (95% CI) | 0.92 (0.91, 0.93) |
| FCS vs FIBTEM A20 Correlation | Pearson correlation coefficient (95% CI) | 0.89 (0.87, 0.91) |
| CSL vs EXTEM ML Clinical Agreement (Overall) | Overall agreement ≥ 90% | 0.93 (0.90, 0.95), or 92.6% |
| CSL vs EXTEM ML Clinical Agreement (Lysis-Positive Subcategory) | Agreement ≥ 80% | 0.90 (0.82, 0.95), or 90.2% |
| CSL vs EXTEM ML Clinical Agreement (Lysis-Negative Subcategory) | Agreement ≥ 90% | 0.93 (0.90, 0.95), or 93.2% |
| Interference Study | Substances show no significant interference | Highest concentrations tested without significant interference are listed in the table (e.g., Lipid: 1335 mg/dL, Hemoglobin: 0.2 g/dL, etc.) |
| Short Draw / Discard Tube | No effect on results / no incomplete filling | Use of discard tube may affect results. Short draw (less than 80% fill) may affect results or cause incomplete filling. |
| Reader Study (Interpretation of Results) | >95% of questions pertaining to each display answered correctly | >95% correctly answered for all five QStat parameters |
2. Sample Size Used for the Test Set and Data Provenance
- Clinical Performance Study (Method Comparison):
- Sample Size: 289 adult subjects.
- Data Provenance: Multi-center prospective observational study conducted at thirteen clinical sites in the US.
- Sample Types: Involved blood samples from subjects undergoing liver transplant surgery, experiencing major trauma, and 5 normal subjects from whom contrived samples were prepared (6.7% of total samples were contrived by spiking blood from normal volunteers).
- Precision/Reproducibility Studies:
- Single Site: QSL1 (N=80), QSL2 (N=80) for each parameter.
- Multi-Site: 60 data points per parameter per sample type (unspiked, tPA spiked to CSL threshold, tPA spiked below CSL threshold) across all sites.
- Whole Blood Repeatability: Varied per study, but generally involved multiple native and contrived samples (total of 16 sample types) and 12 results obtained from each sample type for variance analysis.
- Data Provenance: Internal HemoSonics studies and external clinical sites within the US.
- Interference Study: "A total of n=13 native and contrived whole blood samples were evaluated for sample stability". Specific sample sizes for each interferent in screening and dose-response studies are not explicitly stated but are described as "n" or "multiple levels", "one or two levels", etc. The study utilized normal whole blood and hypocoagulable whole blood.
- Reference Range Study:
- Sample Size: 155 healthy men and women volunteers (≥18 years of age).
- Data Provenance: Multi-center, prospective, observational study across four (4) external sites in the United States.
- Reader Study:
- Sample Size: 10 readers.
- Data Provenance: Conducted with potential users who regularly assess blood coagulation status in critical care settings.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of those Experts
The document does not explicitly state the number of experts used to establish a ground truth in the traditional sense (e.g., for image labeling). Instead, the "ground truth" or reference for comparison in the method comparison study was the results from the predicate device, ROTEM Delta Thromboelastometry System, which is itself a commercially available and cleared device for similar measurements.
For the Reader Study, the "ground truth" was the correct interpretation of the QStat results displays as determined by the device's design and intended use, rather than an expert panel judging unknown cases.
4. Adjudication Method for the Test Set
Not applicable in the typical sense of expert adjudication of a test set, as the comparison was primarily against a predicate device (ROTEM delta) or against pre-defined control values and reference ranges.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
No MRMC comparative effectiveness study was performed or described in the provided text for comparing AI assistance to human readers. The Reader Study mentioned (Section P.1) was a usability study to assess interpretation of the device's results displays by potential users, not a comparative effectiveness study of AI impact on reader performance.
6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done
Yes, the primary performance studies listed under "Analytical Performance" (Precision/Reproducibility, Linearity, Stability, Detection Limit, Analytical Specificity) and "Comparison Studies" (Method Comparison with predicate device, Reference Range) all represent standalone performance of the QStat® Cartridge and Quantra Hemostasis Analyzer system without human intervention in the result generation process itself. The system provides semi-quantitative measurements directly.
7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)
- Method Comparison Study: The predicate device (ROTEM delta) served as the comparative "truth" for evaluating linearity and clinical agreement of the QStat parameters. This is a common approach for establishing substantial equivalence for new diagnostic devices.
- Precision/Reproducibility Studies: Pre-defined control materials (QSL1, QSL2) and contrived samples (spiked with tPA, fibrinogen, DOACs) with expected values/characteristics served as the reference.
- Interference Studies: Pre-determined concentrations of known interferents and their expected effects/non-effects.
- Reference Range Study: Healthy volunteers (n=155) were used to establish normal reference intervals.
8. The Sample Size for the Training Set
The document does not provide details of a specific "training set" size. As this is a diagnostic device that measures viscoelastic properties rather than an AI/ML algorithm that predicts outcomes, the concept of a separate "training set" for model development, distinct from analytical and clinical validation data, is not directly applicable or explicitly detailed in this 510(k) summary. The data presented primarily relates to the analytical and clinical validation of the device.
9. How the Ground Truth for the Training Set was Established
As explained under point 8, the document does not discuss a specific "training set" in the context of an AI/ML model. The QStat Cartridge uses "Sonic Estimation of Elasticity via Resonance (SEER) Sonorheometry" to quantify shear modulus, which is a physics-based measurement, not a machine learning prediction. Therefore, the establishment of "ground truth for the training set" is not relevant for this type of device according to the provided text.
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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health and Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
November 29, 2022
HemoSonics, LLC Garrett Sparks Regulatory Affairs 400 Preston Avenue, Suite 250 Charlottesville, Virginia 22903
Re: K213917
Trade/Device Name: OStat® Cartridge Regulation Number: 21 CFR 864.5430 Regulation Name: Coagulation system for the measurement of whole blood viscoelastic properties in perioperative patients Regulatory Class: Class II Product Code: OFR Dated: December 15, 2021 Received: December 15, 2021
Dear Garrett Sparks :
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.
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.
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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 lectronic 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 mediation-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.
Min W
Min Wu Branch Chief Division of Immunology and Hematology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Ouality Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known)
Device Name QStat® Cartridge
Indications for Use (Describe)
The QStat® Cartridge is a multi-channel cartridge that provides semi-quantitative indications of the coagulation and clot lysis state of a 3.2% citrated venous whole blood sample using the Quantra® Hemostasis Analyzer. The QStat Cartridge includes tests to assess coagulation via the intrinsic pathways and includes a test with tranexamic acid to evaluate clot lysis characteristics.
The QStat Cartridge is intended for in vitro diagnostic use by trained professionals at the point-of-care and in clinical laboratories to evaluate the viscoelastic properties of whole blood by means of the following functional parameters: Clot Time (CT), Clot Stiffness (CS), Fibrinogen Contribution to Clot Stiffness (FCS), Platelet Contribution to Clot Stiffness (PCS), and Clot Stability to Lysis (CSL).
The QStat Cartridge is indicated for the evaluation of blood coagulation and clot lysis in patients age 18 years and older to assess possible hypocoagulable conditions in trauma and liver transplantation procedures.
Results obtained with the OStat Cartridge should not be the sole basis for patient diagnosis.
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) |
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Image /page/3/Picture/0 description: The image shows the logo for Hemosonics QStat Cartridge. The logo features a red blood drop with sound waves emanating from it on the left. To the right of the blood drop is the word "HEMOSONICS" in black, and below that is "QStat® Cartridge".
SECTION 5: 510(K) SUMMARY
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Image /page/4/Picture/1 description: The image shows the logo for Hemosonics QStat Cartridge. The logo features a stylized red blood drop with sound waves emanating from it. Next to the blood drop is the text "HEMOSONICS" in a sans-serif font. Below that is the text "QStat® Cartridge".
510(k) SUMMARY
A. 510(k) NUMBER:
B. PURPOSE OF SUBMISSION
Clearance of a new assay
C. MEASURAND
Clot Time (CT), Clot Stiffness (CS), Fibrinogen Contribution to Clot Stiffness (FCS), Platelet Contribution to Clot Stiffness (PCS), and Clot Stability to Lysis (CSL)
D. TYPE OF TEST
Sonic Estimation of Elasticity via Resonance (SEER) Sonorheometry to measure the shear modulus of whole blood during coagulation and clot lysis, semi-quantitative
E. APPLICANT
HemoSonics, LLC
F. PROPRIETARY AND ESTABLISHED NAMES
QStat® Cartridge
G. REGULATORY INFORMATION
-
- Regulation Section: 21 CFR 864.5430 - Coagulation System For The Measurement Of Whole Blood Viscoelastic Properties
-
- Classification: Class II
3. Product Code: QFR - Coagulation System For The Measurement Of Whole Blood Viscoelastic Properties
-
- Panel: Hematology (81)
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Image /page/5/Picture/0 description: The image shows the logo for Hemosonics. The logo features a red blood drop with sound waves emanating from it. Below the logo is the text "QStat® Cartridge".
H. INTENDED USE
-
l. Intended use(s):
See Indications for use below -
- Indications for use:
The QStat® Cartridge is a multi-channel cartridge that provides semi-quantitative indications of the coagulation and clot lysis state of a 3.2% citrated venous whole blood sample using the Quantra Hemostasis Analyzer. The QStat Cartridge includes tests to assess coagulation via the intrinsic and extrinsic pathways and includes a test with tranexamic acid to evaluate clot lysis characteristics.
- Indications for use:
The OStat Cartridge is intended for in vitro diagnostic use by trained professionals at the point-of-care and in clinical laboratories to evaluate the viscoelastic properties of whole blood by means of the following functional parameters: Clot Time (CT), Clot Stiffness (CS), Fibrinogen Contribution to Clot Stiffness (FCS), Platelet Contribution to Clot Stiffness (PCS), and Clot Stability to Lysis (CSL).
The QStat Cartridge is indicated for the evaluation of blood coagulation and clot lysis in patients age 18 years and older to assess possible hypocoagulable and hypercoagulable conditions in trauma and liver transplantation procedures.
Results obtained with the OStat Cartridge should not be the sole basis for patient diagnosis.
For prescription use only.
-
- Special conditions for use statement(s):
For prescription use only.
- Special conditions for use statement(s):
-
- Special instrument requirements:
Quantra Hemostasis Analyzer
- Special instrument requirements:
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Image /page/6/Picture/0 description: The image shows the logo for Hemosonics QStat Cartridge. The logo features a red blood drop with sound waves emanating from it, followed by the text "HEMOSONICS" in black. Below that is the text "QStat® Cartridge" in a smaller font, also in black.
DEVICE DESCRIPTION I.
The QStat Cartridge is a single-use, multi-channel (n=4) disposable plastic cartridge used with the Quantra Hemostasis Analyzer to assess a patient's coagulation and clot lysis (possible hypocoagulable and hypercoagulable conditions) in a hospital setting (point of care or laboratory) during trauma and liver transplantation procedures. The QStat Cartridge consists of four independent channels that can be tested simultaneously with Sonic Estimation of Elasticity via Resonance (SEER) Sonorheometry.
Each QStat Cartridge is pre-filled with reagents individually sealed in an airtight pouch. After a QStat Cartridge is removed from its primary packaging, it is inserted into the instrument dock. A venous whole blood sample, collected in a 3.2% sodium citrate anticoagulant blood collection tube (minimum volume 2.7 mL), is attached directly to the cartridge and the test is initiated using the touch screen interface on the Quantra Hemostasis Analyzer. The cartridge is the only component of the Quantra system that is in direct contact with blood. The fluidic system within the instrument draws the sample into the cartridge where it is warmed to 37℃, aliquoted, introduced and mixed with the lyophilized reagents, and analyzed. When the test is complete, the cartridge is released from the dock to be disposed of in an appropriate biosafety sharps container.
Each channel of the cartridge contains prefilled lyophilized reagents in the form of beads that enable differential testing without the need for any reagent preparation or pipetting before testing. The assay provides the following information for each patient sample: Clot Time (CT), Clot Stiffness (CS), Fibrinogen Contribution to Clot Stiffness (FCS), Platelet Contribution to Clot Stiffness (PCS) and Clot Stability to Lysis (CSL). The following table summarizes the lyophilized reagents contained in the QStat Cartridge and the test function for each cartridge channel and the output parameter.
| Channel | Reagents | QStat Cartridge Output Parameter(units of measure) |
|---|---|---|
| Measured Parameters | ||
| 1 | Kaolin, calcium, buffers and stabilizers | Clot Time (CT)(seconds) |
| 2 | Thromboplastin, tranexamic acid (TXA),polybrene, calcium, buffers, and stabilizers | No direct output (see calculated parameters) |
| 3 | Thromboplastin, polybrene, calcium, buffers,and stabilizers | Clot Stiffness (CS)(hectoPascals) |
| 4 | Thromboplastin, polybrene, abciximab,calcium, buffers, and stabilizers | Fibrinogen Contribution to Clot Stiffness(FCS) (hectoPascals) |
| Calculated Parameters | ||
| 2 & 3 | See above | Clot Stability to Lysis (CSL) (percent) |
| 3 & 4 | See above | Platelet Contribution to Clot Stiffness (PCS)(hectoPascals) |
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The analyzer displays the test results (n=5) in three different views: dial display screen, stiffness curves data, and trend screen. The dial display screen is the primary viewing screen and has a dial for each of the six output parameters. Each dial shows the reference range, assay measurement range, parameter abbreviation, and the numerical result for the corresponding parameter. The stiffness curves are a graphical display of shear modulus measurements over time that enable the user to view the development of clot stiffness over time. The trends screen displays results from a patient for up to six time points.
There are two levels of external QStat Controls (QSL1 and QSL2) that are supplied separately (required but not provided materials) for testing on the Quantra System when changing cartridge lots, changing control lots, or after significant changes are made to the Quantra instrument (e.g., software update).
The Quantra Cleaning Cartridge is an accessory for the Quantra Hemostasis Analyzer and is intended to be used for simple, periodic cleaning.
J. SUBSTANTIAL EQUIVALENCE INFORMATION
-
- Predicated Device Name:
ROTEM Delta Thromboelastometry System
- Predicated Device Name:
-
- Comparison with Predicate:
| QStat Cartridge(Proposed Device) | ROTEM Delta Thromboelastometry SystemK083842 and K101533(Predicates) | |
|---|---|---|
| Intended Use | The QStat Cartridge is a multi-channelcartridge that provides semi-quantitative indications of thecoagulation and clot lysis state of a3.2% citrated venous whole bloodsample using the Quantra HemostasisAnalyzer. The QStat Cartridge includestests to assess coagulation via theintrinsic and extrinsic pathways andincludes a test with tranexamic acid toevaluate clot lysis characteristics.The QStat Cartridge is intended for invitro diagnostic use by trainedprofessionals at the point-of-care and inclinical laboratories to evaluate theviscoelastic properties of whole bloodby means of the following functional | K083842The ROTEM® delta Thromboelastometry System isdesigned for in vitro diagnostic use by professionalsin a laboratory environment. The ROTEM® delta isintended to provide a qualitative and quantitativeindication of the coagulation state of a blood sample.For this purpose, the ROTEM® delta records theclot firmness changes in a sample of citrated wholeblood as the sample clots, retracts and lyses in realtime. The analyzer output consists of a qualitativegraphical representation (mirrored coagulation curve- clot firmness over time) and several definednumerical parameters describing the curvequantitatively.The in-TEM® assay is a semi-quantitative in vitrodiagnostic assay used to monitor the coagulationprocess via the intrinsic pathway in citrated whole |
| QStat Cartridge(Proposed Device) | ROTEM Delta Thromboelastometry SystemK083842 and K101533(Predicates) | |
| parameters: Clot Time (CT), ClotStiffness (CS), Fibrinogen Contributionto Clot Stiffness (FCS), PlateletContribution to Clot Stiffness (PCS),and Clot Stability to Lysis (CSL).The QStat Cartridge is indicated for theevaluation of blood coagulation and clotlysis in patients age 18 years and olderto assess possible hypocoagulable andhypercoagulable conditions in traumaand liver transplantation procedures.Results obtained with the QStatCartridge should not be the sole basisfor patient diagnosis.For prescription use only. | blood specimens. Clotting characteristics aredescribed by the functional parameters ClottingTime (CT), Speed of Clot formation (CFT and alphaangle), Clot Firmness (A20/MCF) and Clot Lysis(LOT, ML, LI(x)). The assay is intended forprofessional use in the clinical laboratory onthe ROTEM® delta Instrument.The hep-TEM® assay is a semi-quantitative in vitrodiagnostic assay used to monitor the coagulationprocess via the intrinsic pathway in the presence ofheparin, in citrated whole blood specimens. Clottingcharacteristics are described by thefunctional parameters Clotting Time (CT), Speed ofClot formation (CFT and alpha angle),Clot Firmness (A20/MCF) and Clot Lysis (LOT,ML, LI(x)). The assay is intended for professionaluse in the clinical laboratory on the ROTEM® deltaInstrument.The NATEM® assay is a semi-quantitative in vitrodiagnostic assay used to monitor the coagulationprocess contact activated by the surface of themeasurement cell, in citrated whole bloodspecimens. Clotting characteristics are described bythe functional parameters Clotting Time (CT), Speedof Clot formation (CFT and alpha angle),Clot Firmness (A20/MCF) and Clot Lysis (LOT,ML, LI(x)). The assay is intended for professionaluse in the clinical laboratory on the ROTEM® deltaInstrument.The star-TEM® reagent is intended for use asrecalcification reagent in the NATEM and in-TEMon the ROTEM® delta ThromboelastometrySystem.K101533The EXTEM® assay is a semi-quantitative in vitrodiagnostic assay used to monitor the coagulationprocess via the extrinsic pathway in citrated wholeblood specimens on the ROTEM® deltaThromboelastometry System. Clottingcharacteristics are described by the functionalparameters Clotting Time (CT), Speed of Clotformation (CFT and alpha angle), Clot Firmness | |
| QStat Cartridge(Proposed Device) | ROTEM Delta Thromboelastometry SystemK083842 and K101533(Predicates) | |
| Thromboelastometry System to monitor the clotfirmness of a citrated whole blood specimen afterblocking platelet contribution to the clot firmness.The fibTEM® is always used in conjunction withexTEM®. Clotting characteristics are described bythe functional parameter Clot Firmness (A20/MCF).The APTEM® assay is a semi-quantitative in vitrodiagnostic assay on the ROTEM® deltaThromboelastometry System to monitor the clotfirmness of a citrated whole blood specimen afterblocking hyperfibrinolysis by aprotinin. The ap-TEM® is always used in conjunction with ex-TEM®. Clotting characteristics are described bythe functional parameters Clotting Time (CT), Speedof Clot formation (CFT and alpha angle), ClotFirmness (A20/MCF) and Clot Lysis (LOT, ML,LI(x)). CFT and alpha (Speed of Clot Formation) arecomplementary parameters and should be usedin conjunction with the main parameters ClottingTime (CT) and Clot Firmness (A20/MCF). | ||
| Similarities | ||
| Classification | II | Same |
| Indications forUse | Trauma and liver transplantation | Trauma, organ transplantation, cardiovascularsurgery, and cardiology procedures |
| TechnologicalPurpose | Measuring "clot stiffness" during clotformation | Measuring "clot firmness" during clot formation |
| MeasuringChannels | 4 | Same |
| Sample Type | 3.2% sodium citrated whole blood | Same |
| Results Display | Graphical (curves) and numericaldisplay of patient results | Same |
| Measurands | Clot time (CT) | Same |
| Measurands | Clot Stiffness (CS) | Same. Reported as EXTEM A20 (clot firmness) |
| Measurands | Fibrinogen Contribution to ClotStiffness (FCS) | Same Reported as FIBTEM A20 |
| Reagents | Thromboplastin (extrinsic pathway) | Same |
| Differences | ||
| Instrument | Quantra Hemostasis Analyzer | ROTEM delta instrument |
| Sample Volume | 3.0 mL citrated whole bloodsample (2.7 mL whole blood + citrate) | 300 µL citrated whole blood sample perassay (INTEM, EXTEM, FIBTEM, APTEM) |
| SamplePreparation | Automated | Manual |
| QStat Cartridge(Proposed Device) | ROTEM Delta Thromboelastometry SystemK083842 and K101533(Predicates) | |
| SignalGeneration | Ultrasonic pulses directed into astationary well | Oscillating pin in stationary cup |
| Assay Output | Platelet Contribution to ClotStiffness (PCS) | Output not directly provided but can be calculatedoffline from comparison of EXTEM and FIBTEM |
| Clot Stability to Lysis (CSL) | ||
| Reagents | Kaolin (intrinsic pathway activator) | Ellagic acid (intrinsic pathway activator) |
| Abciximab (platelet inhibitor) | Cytochalasin D (platelet inhibitor) | |
| Tranexamic acid (fibrinolysisinhibitor) | Aprotinin (fibrinolysis inhibitor) |
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Image /page/8/Picture/1 description: The image shows the logo for Hemosonics QStat Cartridge. The logo features a red blood drop with sound waves emanating from it on the left. To the right of the blood drop is the word "HEMOSONICS" in black, and below that is "QStat® Cartridge" also in black.
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Image /page/9/Picture/1 description: The image contains the logo for Hemosonics QStat Cartridge. The logo features a red blood drop with sound waves emanating from it, followed by the word "HEMOSONICS" in black text. Below that, the words "QStat" and "Cartridge" are written in black text, with a registered trademark symbol next to "QStat".
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K. STANDARDS/GUIDANCE DOCUMENTS REFERENCED
- CLSI EP05-A3, Evaluation of Precision of Quantitative Measurement Procedures; ● Approved Guideline - Third Edition
- CLSI EP07-A2: Interference Testing in Clinical Chemistry; Approved Guideline Second Edition
- CLSI EP25-A. Evaluation of Stability of In Vitro Diagnostic Reagents: Approved ● Guideline
- CLSI EP28-A3c: Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory; Approved Guideline - Third Edition
L. TEST PRINCIPLE
SEER Sonorheometry uses ultrasound pulses to quantify the shear modulus (i.e., stiffness) of a blood sample during the process of coagulation and clot lysis. A focused ultrasound pulse is transmitted into the blood sample to generate a shear wave, causing the sample to resonate once the clot begins to form. Multiple parameters measured from the four channels of the cartridge provide information about the functional role of the coagulation factors, fibrinogen, platelets, and clot lysis factors in the sample.
Clot Time (CT) Test
This test uses kaolin to provide contact surface activation of coagulation via the intrinsic pathway. Kaolin is an aluminum silicate mineral with a negatively charged surface. Calcium acetate is included to recalcify the blood sample used for testing. Prolongation of the intrinsic pathway clot time is likely due to deficiencies in intrinsic pathway coagulation factors, presence of anticoagulants, or inhibitors that affect the intrinsic pathway.
Clot Stiffness (CS) Test
This test uses thromboplastin (tissue factor) to activate the extrinsic pathway of coagulation. The test includes polybrene, a reagent that neutralizes heparin. Calcium acetate is included to recalcify the blood sample used for testing. This test allows an evaluation of the total clot stiffness from the combined contributions from both platelets and fibrinogen.
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Image /page/11/Picture/0 description: The image shows the logo for Hemosonics QStat Cartridge. The logo features a red blood drop with sound waves emanating from it on the left. To the right of the blood drop is the word "HEMOSONICS" in black, and below that is "QStat® Cartridge" also in black.
Fibrinogen Contribution to Clot Stiffness (FCS) Test
This test uses thromboplastin (tissue factor) to activate the extrinsic pathway of coagulation, in combination with a reagent that inhibits platelet aggregation and contraction (Abciximab). Abciximab is the Fab fragment of a monoclonal antibody that binds on the platelet surface receptor GPIIb/IIIa. Polybrene is included to neutralize heparin in addition to calcium acetate to recalcify the blood sample used for testing. This test allows an evaluation of the contribution of functional fibrinogen to clot stiffness without the effect of heparin anticoagulation. In addition, when used in combination with the Clot Stiffness (CS) Test, the contribution of platelets to the clot stiffness can be determined.
Two additional functional parameters are calculated:
Platelet Contribution to Clot Stiffness (PCS)
The Platelet Contribution to Clot Stiffness (PCS) is a functional parameter that is calculated as the difference between the overall Clot Stiffness (CS) and the Fibrinogen Contribution to Clot Stiffness (FCS), reported in hectoPascals (hPa).
Clot Stability to Lysis (CSL)
The Clot Stability to Lysis (CSL) is a functional parameter defined as the normalized difference of the clot stiffness change after maximum clot stiffness in the absence of tranexamic acid and the corresponding clot stiffness change in the presence of tranexamic acid. The CSL parameter may indicate the reduction of clot stiffness that is likely due to the influence of fibrinolysis. The CSL parameter is reported in %.
M. PERFORMANCE CHARACTERISTICS
-
- Analytical Performance
a. Precision/Reproducibility
- i. Single Site Precision
The single site precision study included testing of the QStat Control Level 1 (QSL1) and QStat Control Level 2 (QSL2) in duplicate with 2 runs per day over 20 testing days. All sample testing was conducted using one Quantra instrument and reagent lot for cartridge and controls. Analysis of the Single Site Precision Study data for the OStat cartridge demonstrated withinlaboratory precision (total) of 0.0% - 9.5% CV for QSL1 and 0.6% - 9.3% CV for OSL2 parameters. The repeatability for the OStat cartridge on the Quantra showed a replicate precision of 0.0% - 8.6% CV for QSL1 and 0.6% - 8.5% CV for QSL2 parameters. The results are summarized below.
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Image /page/12/Picture/1 description: The image shows the logo for Hemosonics QStat Cartridge. The logo features a red blood drop with sound waves emanating from it on the left. To the right of the blood drop is the word "HEMOSONICS" in bold, black letters. Below that is the text "QStat® Cartridge".
| QSL1 (N=80) | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Parameter | Mean | Repeatability(Replicate) | Between-Day | Between- Run | Total | ||||
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | ||
| CT (sec) | 158.6 | 4.3 | 2.7 | 1.5 | 1.1 | 3.2 | 2.0 | 5.6 | 3.5 |
| CSL (%) | 100 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 |
| CS (hPa) | 14.09 | 0.74 | 5.3 | 0.24 | 1.7 | 0.14 | 1.0 | 0.79 | 5.6 |
| FCS (hPa) | 14.69 | 1.26 | 8.6 | 0.38 | 2.6 | 0.47 | 3.2 | 1.4 | 9.5 |
| PCS (hPa)* | < 0.2 | NA | NA | NA | NA | NA | NA | NA | NA |
| QSL2 (N=80) | |||||||||
| Parameter | Mean | Repeatability(Replicate) | Between-Day | Between- Run | Total | ||||
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | ||
| CT (sec) | 269.9 | 16.0 | 5.9 | 4.2 | 1.6 | 0.0 | 0.0 | 16.6 | 6.1 |
| CSL (%) | 99.9 | 0.6 | 0.6 | 0.0 | 0.0 | 0.0 | 0.0 | 0.6 | 0.6 |
| CS (hPa) | 4.62 | 0.39 | 8.5 | 0.17 | 3.8 | 0.0 | 0.0 | 0.43 | 9.3 |
| FCS (hPa) | 4.69 | 0.37 | 7.9 | 0.15 | 3.3 | 0.12 | 2.7 | 0.42 | 9.0 |
| PCS (hPa)* | < 0.2 | NA | NA | NA | NA | NA | NA | NA | NA |
*OStat Control materials do not contain platelets
A second single site precision study was also performed with two levels of fibrinolysis-positive control materials (developed only for internal use at HemoSonics) prepared to simulate two different levels of fibrinolysis over the reportable range of the CSL parameter. Results from this study demonstrated total %CV for CT, CS, and FCS below 5.8% across the two controls. For the CSL parameter, both the total %CV and total standard deviation (SD) were evaluated, with results demonstrating %CV of 7.1% and SD of 10.2% for the controls.
- ii. Multi-Site Reproducibility
A multi-site repeatability and reproducibility study performed at three external clinical sites that were selected to represent different intended user locations. Testing was conducted with a panel of three whole blood samples over five days with two Quantra Analyzers per site and a single reagent lot. Samples were created daily including one native sample and two contrived samples to evaluate different levels of fibrinolysis at and below the CSL threshold (spiked with tissue-type plasminogen activator (tPA)). The results across all sites per sample type are summarized in the table below. Total imprecision of CSL parameter was < 7% CV for normal and low tPA concentration (at CSL threshold).
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Image /page/13/Picture/1 description: The image contains the logo for Hemosonics QStat Cartridge. The logo features a red blood drop with sound waves emanating from it, followed by the text "HEMOSONICS" in a bold, sans-serif font. Below this, the text "QStat® Cartridge" is displayed, with the registered trademark symbol next to "QStat".
| All Sites - Sample 1 (unspiked) | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Parameter | N | Mean | Repeatability (Replicate) | Between-Day | Between-Analyzer | Within-Site | Between-Site | Total | |||||||
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | ||||
| CT | 60 | 148.7 | 5.52 | 3.71 | 3.39 | 2.28 | 0 | 0 | 1.45 | 0.97 | 2.42 | 1.63 | 7.06 | 4.75 | |
| CSL | 60 | 98.38 | 1.33 | 1.35 | 0.24 | 0.24 | 0 | 0 | 0 | 0 | 0.2 | 0.2 | 1.37 | 1.39 | |
| CS | 60 | 21.33 | 0.96 | 4.49 | 0.49 | 2.3 | 0.63 | 2.95 | 0 | 0 | 0.68 | 3.2 | 1.42 | 6.66 | |
| PCS | 60 | 19.48 | 0.94 | 4.8 | 0.39 | 1.99 | 0.64 | 3.3 | 0 | 0 | 0.76 | 3.92 | 1.42 | 7.3 | |
| FCS | 60 | 1.85 | 0.1 | 5.47 | 0.11 | 5.94 | 0 | 0 | 0 | 0 | 0.08 | 4.29 | 0.17 | 9.14 | |
| All Sites - Sample 2 (tPA spiked to CSL threshold) | |||||||||||||||
| Parameter | N | Mean | Repeatability (Replicate) | Between-Day | Between-Analyzer | Within-Site | Between-Site | Total | |||||||
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | ||||
| CT | 60 | 129.62 | 8.43 | 6.5 | 3.74 | 2.89 | 0 | 0 | 0 | 0 | 0 | 0 | 9.22 | 2.89 | |
| CSL | 60 | 85.07 | 3.58 | 4.21 | 2.84 | 3.34 | 0 | 0 | 1.06 | 1.25 | 2.82 | 3.31 | 5.47 | 6.44 | |
| CS | 60 | 13.95 | 0.69 | 4.93 | 0.24 | 1.71 | 0.36 | 2.58 | 0.32 | 2.33 | 0.29 | 2.11 | 0.92 | 6.61 | |
| PCS | 60 | 12.75 | 0.68 | 5.36 | 0.23 | 1.83 | 0.36 | 2.81 | 0.32 | 2.5 | 0.36 | 2.81 | 0.94 | 7.35 | |
| FCS | 60 | 1.2 | 0.07 | 6.14 | 0 | 0 | 0 | 0 | 0 | 0 | 0.08 | 6.78 | 0.11 | 9.15 | |
| All Sites - Sample 3 (tPA spiked to below CSL threshold) | |||||||||||||||
| Parameter | N | Mean | Repeatability (Replicate) | Between-Day | Between-Analyzer | Within-Site | Between-Site | Total | |||||||
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | ||||
| CT | 60 | 132.8 | 6.9 | 5.22 | 1.25 | 0.94 | 0 | 0 | 3.49 | 2.63 | 0 | 0 | 7.86 | 5.92 | |
| CSL | 60 | 21.97 | 8.8 | 40.07 | 2.64 | 12.01 | 0 | 0 | 1.73 | 7.88 | 0 | 0 | 9.35 | 42.56 | |
| CS | 60 | 24.38 | 1.36 | 5.56 | 0.17 | 0.7 | 0.7 | 2.87 | 0 | 0 | 0.7 | 2.86 | 1.69 | 6.92 | |
| PCS | 60 | 22.25 | 1.34 | 6.03 | 0.22 | 0.97 | 0.73 | 3.27 | 0.74 | 3.35 | 0 | 0 | 1.71 | 7.69 | |
| FCS | 60 | 2.13 | 0.21 | 9.91 | 0 | 0 | 0.02 | 0.88 | 0 | 0 | 0.05 | 2.29 | 0.22 | 10.21 |
iii. Whole blood repeatability
The precision of the QStat Cartridge on the Quantra was evaluated using whole blood samples across multiple instruments, operators, and cartridge lots. Four separate studies were conducted that included testing a total 16 native and contrived sample types including the following: normal (unspiked), fibrinolytic (CSL values between 18.7% and 99.3%), and hypocoagulable samples.
Study #1 evaluated the single source of variance between paired cartridges and instruments. Testing included a panel of seven samples (normal, fibrinolytic and hypocoagulable) tested in duplicate on three reagent lots with three instruments and multiple operators within a single day.
Study #2 evaluated the single source of variance between paired operators and instruments. Testing included a panel of four contrived fibrinolytic samples ranging from hyperfibrinolysis to normal fibrinolysis. Samples were tested in duplicate with two lots per instrument (n=3) and 3 operators within a single dav.
Study #3 included testing with 12 instruments in parallel to eliminate variability introduced by contriving samples using multiple aliquots of tPA. Testing included a panel of three contrived fibrinolytic samples across the
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Image /page/14/Picture/1 description: The image shows the logo for Hemosonics QStat Cartridge. The logo features a red blood drop with sound waves emanating from it. The text "HEMOSONICS" is written in a bold, sans-serif font to the right of the blood drop. Below that, the text "QStat® Cartridge" is written in a smaller font.
CSL reportable range. All samples were tested in duplicate using three lots across six different instruments per operator (n=2).
Study #4 included testing with 12 instruments run in parallel to eliminate variability introduced by sample stability limitations of DOAC-based hypocoagulable samples. Testing included a panel of two hypocoagulable samples in duplicate per lot per operator with two cartridge lots by three operators with four different instruments per operator within a single day.
Variance analysis was performed using 12 results obtained from each sample type across the three studies. The results demonstrated total %CV below 15% for CT, CS, FCS, and PCS across all sample types. For the CSL parameter, both the total %CV and total standard deviation (SD) were evaluated. The CSL %CV results were below 15% or SD below 12% across the various sample types and are summarized in the table below.
| CSL Variance Analysis for Whole Blood Repeatability Testing | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Sample ID | Study | N | Mean | Between-Replicate | Between-Operator | Between-(Instrument/Cartridge Lot) | Interaction Operator (Instrument/Cartridge Lot) | Total | |||||
| SD | CV% | SD | CV% | SD | CV% | SD | CV% | SD | CV% | ||||
| Normal | 1 | 12 | 99.3 | 1.0 | 1.0 | 0.5 | 0.5 | 0.0 | 0.0 | 0.0 | 0.0 | 1.2 | 1.2 |
| Normal | 1 | 12 | 98.8 | 1.4 | 1.4 | 0.0 | 0.0 | 0.0 | 0.0 | 0.8 | 0.8 | 1.6 | 1.6 |
| 42.5 U/mL tPA | 1 | 12 | 92.2 | 2.3 | 2.5 | 2.7 | 2.9 | 1.3 | 1.4 | 0.0 | 0.0 | 3.7 | 4.1 |
| 42 U/mL tPA | 1 | 12 | 73.8 | 7.9 | 10.7 | 0.0 | 0.0 | 3.3 | 4.5 | 0.0 | 0.0 | 8.6 | 11.6 |
| 60 U/mL tPA | 1 | 12 | 45.4 | 10.5 | 23.1 | 0.0 | 0.0 | 0.0 | 0.0 | 5.5 | 12.0 | 11.8 | 26.1 |
| Apixaban5 mg bidaily | 1 | 12 | 97.8 | 2.5 | 2.5 | 0.0 | 0.0 | 0.0 | 0.0 | 4.4 | 4.5 | 5.1 | 5.2 |
| Rivaroxaban80 ng/mL | 1 | 12 | 98.8 | 2.2 | 2.2 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 2.2 | 2.2 |
| 35 U/mL tPA | 2 | 12 | 95.8 | 2.2 | 2.3 | 1.5 | 1.6 | 0.0 | 0.0 | 1.2 | 1.2 | 2.9 | 3.1 |
| 22.5 U/mL tPA | 2 | 12 | 75.6 | 7.5 | 10.0 | 3.2 | 4.2 | 2.4 | 3.2 | 0.0 | 0.0 | 8.5 | 11.3 |
| 40 U/mL tPA | 2 | 12 | 75.8 | 5.7 | 7.5 | 0.0 | 0.0 | 0.0 | 0.0 | 8.9 | 11.7 | 10.5 | 13.9 |
| 50 U/mL tPA | 2 | 12 | 51.1 | 8.0 | 15.6 | 0.0 | 0.0 | 0.0 | 0.0 | 4.2 | 8.3 | 9.0 | 17.7 |
| 30 U/mL tPA | 3 | 12 | 80.3 | 5.4 | 6.8 | 0.0 | 0.0 | 0.0 | 0.0 | 4.3 | 5.3 | 6.9 | 8.6 |
| 60 U/mL tPA | 3 | 12 | 65.3 | 8.7 | 13.3 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 8.7 | 13.3 |
| 80 U/mL tPA | 3 | 12 | 18.7 | 5.5 | 29.7 | 3.6 | 19.4 | 6.5 | 34.9 | 0.0 | 0.0 | 9.3 | 49.7 |
| Rivaroxaban20 mg daily | 4 | 12 | 99.3 | 1.0 | 1.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 1.0 | 1.0 |
| Dabigatran300 ng/mL | 4 | 12 | 98.3 | 1.7 | 1.8 | 0.0 | 0.0 | 0.0 | 0.0 | 1.5 | 1.5 | 2.3 | 2.3 |
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-
b. Linearitv
Not Applicable. -
Traceability, Stability, Expected values (controls, calibrators, or methods): C.
Shelf-Life Reagent Stability
Unopened QStat Cartridge pouches may be stored up to 17 months after the date of manufacture at 2-28°C.
In-Use Reagent Stability
Recommend testing within 15 minutes after removing QStat Cartridge from its primary package pouch.
Specimen Stability
A total of n=13 native and contrived whole blood samples were evaluated for sample stability including normal whole blood as well as fibrinolytic and hypocoagulable whole blood samples. Fresh blood kept at room temperature should be analyzed within 2 hours after collection.
Controls
The OSL1 and OSL2 are single use vials containing a lyophilized mixture of porcine and caprine pooled animal plasma (3.2% sodium citrate), fixed red blood cells of human origin, buffers, additives, and preservatives (no platelets). QSL1 and QSL2 are reconstituted by the end user with the provided diluent and loaded onto the QStat by the same method as patient samples. The plastic diluent vial is shipped with an extender that serves to guide the vial into the cartridge's evacuated sample tube attachment, after reconstitution.
-
d. Detection limit:
Not Applicable. -
e. Analytical specificity:
The Interference Study evaluated the effect of potential interfering substances with normal whole blood and hypocoagulable whole blood. Interference was evaluated with unspiked ("Control") and at one or more spiked levels ("Test"). Screening studies were performed at one or two levels with the number of replicates at each level generally selected to provide a 95% confidence interval (2-sided), per CLSI EP07-A2 guidelines. Dose-response studies were also performed.
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Image /page/16/Picture/1 description: The image shows the logo for Hemosonics QStat Cartridge. The logo features a red blood drop with sound waves emanating from it, followed by the text "HEMOSONICS" in black. Below that is the text "QStat® Cartridge" in a smaller font, also in black.
The following endogenous interferences were evaluated with a screening study: lipid. hemolysis, and hemoglobin. In addition. lupus anticoagulant, hemodilution. and hematocrit were evaluated as potential endogenous interferents with a doseresponse study to determine the relationship between the test levels and their effects on the QStat Cartridge results.
The study also evaluated the potential effects of the following exogenous interferences: tranexamic acid (TXA), epsilon-aminocaproic acid (EACA), clopidogrel (2-MeSAMP), and aspirin (salicylic acid, sodium salt) in screening studies. In addition, dabigatran (Pradaxa), rivaroxaban (Xarelto), protamine sulfate, mycophenolic acid (MPA), tacrolimus, prednisone, rifaximin, and lactulose were evaluated as potential exogenous interferents in dose-response studies performed at multiple levels. The effects of potential sample variable interferences such as the use of discard tube and short draw were also evaluated. The following table shows the highest concentration at which each substance showed no significant interference in whole blood samples collected in 3.2% sodium citrate anticoagulant collection tubes.
| Interferent | Concentration |
|---|---|
| Lipid | 1335 mg/dL |
| Hemolysis | Interfered at all levels tested (≥0.02 g/dL) |
| Hemoglobin | 0.2 g/dL |
| Lupus Anticoagulant | Interfered at all levels tested (≥20%) |
| Clopidogrel | 300 μM (highest level tested) |
| Aspirin | 4.34 mM (0.694 mg/mL) (highest level tested) |
| Protamine sulfate | 20 µg/mL |
| Mycophenolic Acid | 7 µg/mL |
| Tacrolimus | 144 ng/mL (highest level tested) |
| Prednisone | 99 ng/mL (highest level tested) |
| Rifaximin | 40.5 ng/mL (highest level tested) |
| Lactulose | 12 µg/mL (highest level tested) |
As expected and designed for, the following substances showed significant effects on QStat parameters. The anti-fibrinolytic agents TXA and EACA demonstrated an effect at concentrations greater than 1 ug/mL and 10 ug/mL respectively in fibrinolytic samples. The direct oral anticoagulants rivaroxaban and dabigatran demonstrated a dose response effect at concentrations greater than 25 ng/mL. Hemodilution demonstrated a dose response effect at dilutions greater than 10%. Increasing hematocrit levels in the range of 13 to 55% generated a decrease in most QStat results with effects starting at hematocrit changes of >2%.
Specimen collection tubes filled at less than 80% of the required/specified volume may affect results or cause incomplete filling of the QStat Cartridge. Use of a discard tube may affect QStat results.
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Image /page/17/Picture/1 description: The image shows the Hemosonics logo. The logo consists of a red blood drop with sound waves emanating from it, followed by the text "HEMOSONICS". Below the logo is the text "QStat® Cartridge", with the registered trademark symbol after the word "QStat".
2. Comparison Studies:
- a. Method Comparison with predicate device:
The clinical performance of the Quantra Hemostasis Analyzer with the QStat Cartridge with the predicate device, ROTEM delta, was evaluated in a multi-center prospective observational study involving subjects 18 years of age or older undergoing liver transplant surgery or experiencing major trauma requiring a full trauma team response. Two hundred eighty-nine adult subjects were eligible for this study across thirteen clinical sites in the US including five normal subjects from which contrived samples were prepared.
From subjects undergoing liver transplant, a minimum of three blood samples were collected at the following times for analysis on the QStat Cartridge and the ROTEM delta: before surgery, during the anhepatic phase, and post-reperfusion.
For trauma subjects, at least one blood sample was collected in the emergency room, the operating room, or the intensive care unit at the time of admission, during acute hemorrhage and transfusion of blood products, or 24 to 48 hours after arrival at the trauma unit to assess potential hypercoagulability. Trauma severity was assessed by injury scores in 71% of trauma subjects. For the majority of subjects (68%), the injury score was reflective of severe trauma. Contrived samples (6.7%) were prepared by spiking blood samples from normal volunteers with fibrinogen and tPA to broaden the range of measurements for CS, FCS and CSL. All blood samples were run in parallel on the Quantra QStat Cartridge and the ROTEM delta. Correlation and clinical agreement analyses were performed to compare measurements obtained with the QStat Cartridge to comparable measures obtained with the ROTEM delta. A linear regression analysis was performed to evaluate the correlation between the QStat parameters and comparable ROTEM delta parameters. For the primary analysis, samples from liver transplant and trauma subjects were combined with contrived samples.
| Slope Estimate(95% CI) | Intercept Estimate(95% CI) | Correlation Coefficients | ||
|---|---|---|---|---|
| Pearson(95% CI) | Spearman(95% CI) | |||
| CT vs INTEM CT | 0.37 (0.35, 0.39) | 75.51 (69.90, 81.11) | 0.89 (0.87, 0.91) | 0.86 (0.83, 0.88) |
| CS vs EXTEM A20 | 2.84 (2.74, 2.94) | -1.46 (-2.16, -0.78) | 0.92 (0.91, 0.93) | 0.91 (0.90, 0.93) |
| FCS vs FIBTEM A20 | 3.08 (2.95, 3.21) | -0.30 (-0.45, -0.15) | 0.89 (0.87, 0.91) | 0.87 (0.85, 0.89) |
A clinical agreement analysis was performed to evaluate the ability of the QStat CSL parameter to identify fibrinolytic samples relative to the ROTEM delta lysis parameter EXTEM ML. The overall agreement of patient sample assignments into lysis-positive and lysis-negative based on data for OStat CSL and ROTEM delta EXTEM ML was 92.6%. Agreement within the lysis-positive and lysis-negative subcategories was 90.2% and 93.2%, respectively. These results met the acceptance criteria for overall and subcategory agreements. The QStat CSL parameter appeared
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Image /page/18/Picture/1 description: The image contains the logo for Hemosonics. The logo consists of a red blood drop with sound waves emanating from it, followed by the text "HEMOSONICS". Below that is the text "QStat® Cartridge".
to be more sensitive at identifying moderate fibrinolytic samples than the ROTEM delta lysis parameter.
Clinical Agreement Analysis for Comparison of QStat and ROTEM delta Lysis Parameters
| ROTEM delta | ||||
|---|---|---|---|---|
| Yes* | No* | Total | ||
| QUANTRA | Yes** | 83 | 28 | 111 |
| QStat | No** | 9 | 381 | 390 |
| Total | 92 | 409 | 501 |
**Classification based on Quantra definition of lysis
- Classification based on ROTEM definitions of lysis
Summary Metrics for Clinical Agreement Analysis for Comparison of QStat and ROTEM delta Lysis Parameters
| Category | N in CategoryQuantra/ROTEM | Agreement(95% CI) |
|---|---|---|
| Yes | 83/92 | 0.90 (0.82, 0.95) |
| No | 381/409 | 0.93 (0.90, 0.95) |
| Overall | 464/501 | 0.93 (0.90, 0.95) |
-
b. Matrix Comparison
Not Applicable. -
- Clinical Studies:
Not applicable.
- Clinical Studies:
-
- Clinical Cut-Off:
See reference range study below for CSL cutoff description.
- Clinical Cut-Off:
-
ડ. Expected Values/Reference Range:
The reference range study was a multi-center, prospective, observational study aimed at establishing reference range intervals for a healthy population for the test parameters measured by the QStat Cartridge. The study population consisted of 155 healthy men and women volunteers (≥18 years of age) enrolled across four (4) external sites that are representative of the general population in the United States. The results are summarized in the table below.
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| Healthy Reference Range Intervals | |
|---|---|
| Output Parameter | Units | Reference Ranges |
|---|---|---|
| Clot Time (CT) | Seconds | 121–175 |
| Clot Stability to Lysis (CSL) | Percent | 92–100* |
| Clot Stiffness (CS) | hectoPascals | 14.0–35.4 |
| Platelet Contribution to Clot Stiffness (PCS) | hectoPascals | 12.8–32.3 |
| Fibrinogen Contribution to Clot Stiffness (FCS) | hectoPascals | 0.9–4.2 |
*The Clot Stability to Lysis (CSL) is a calculated parameter. CSL values of 92%-100% are demonstrated to be typical of "normal" patient samples. Samples with CSL values below 90% are indicative of reduction of clot stiffness that is likely due to the influence of fibrinolysis. The 90% threshold was calculated as the lower bound of the 95% confidence interval around the lower limit of the reference interval for CSL determined in healthy volunteers.
N. INSTRUMENT
Quantra Hemostasis Analyzer (DEN180017)
O. SYSTEM DESCRIPTIONS
Modes of Operation: 1.
Does the applicant's device contain the ability to transmit data to a computer. webserver, or mobile device?
Yes X
Does the applicant's device transmit data to a computer, webserver, or mobile device using wireless transmission?
Yes
-
- Software:
FDA has reviewed applicant's Hazard Analysis and software development processes for this line of product types:
- Software:
Yes X or No _________
- Specimen Identification: 3.
Bar code reader
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Image /page/20/Picture/1 description: The image shows the logo for Hemosonics QStat Cartridge. The logo features a red blood drop with sound waves emanating from it, followed by the text "HEMOSONICS" in black. Below that, the text "QStat® Cartridge" is displayed in a smaller font, also in black.
-
- Specimen Sampling and Handling:
The QStat Cartridge requires a fresh sample of 3 mL or more of citrated whole blood collected in an evacuated tube containing 3.2% sodium citrate. The blood collection tube must be filled to the minimum fill line. The entire blood sample will be used for analysis on the Quantra. Do not use a discard tube as the sample as it may affect results or cause incomplete filling of the cartridge.
- Specimen Sampling and Handling:
-
న్. Calibration:
User calibration is not required, based on the design of the instrument. -
- Quality Control:
The Ouantra Analyzer performs internal quality control checks of all system components at regular intervals and during each phase of a test run on a cartridge to verify that the instrument hardware and all subsystems are functioning properly. Two levels of external QStat Controls (Level 1 and Level 2) are available and supplied separately (with an accompanying package insert) for testing on the Quantra System. The controls are designed to be used as part of a laboratory quality control program and are manufactured with non-overlapping ranges for CT, CS, and FCS.
- Quality Control:
P. OTHER SUPPORTIVE INSTRUMENT PERFORMANCE CHARACTERISTICS DATA NOT COVERED IN THE "PERFORMANCE CHARACTERISTICS" SECTION
- Reader Study: 1.
A reader study was conducted to assess the ability of potential users of Quantra System with the QStat Cartridge to correctly interpret results displayed on the Quantra Dials Display and Curve screens. The QStat Reader Study was conducted with a total of 10 readers who regularly assess the blood coagulation status of patients in the critical care setting including the following: a) anesthesiologists, b) surgeons, and c) other trained medical professionals who may assess the blood coagulation status of patients. Participants viewed 12 QStat results display screens, each containing results for five QStat Cartridge parameters, and answered a total of 131 multiple-choice questions. For all five QStat parameters, >95% of the questions pertaining to each of the displays were answered correctly.
Q. PROPOSED LABELING
The labeling is sufficient and satisfies the requirements of 21 CFR 809.10.
R. CONCLUSION
The submitted information in this premarket notification supports a substantial equivalence decision.
§ 864.5430 Coagulation system for the measurement of whole blood viscoelastic properties in perioperative patients.
(a)
Identification. A coagulation system for the measurement of whole blood viscoelastic properties in perioperative patients is an in vitro diagnostic device used to evaluate blood coagulation, fibrinolysis, or both, in perioperative patients, as an aid in the assessment of coagulopathies when used in conjunction with clinical signs and symptoms and other clinical and laboratory findings.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Design verification and validation must include detailed documentation of, and results from, the following:
(i) A study assessing precision using protocols determined to be acceptable by FDA, to cover the measurement range for each reported parameter (test output). Testing must include native specimens with coagulation profiles representative of the intended use population. In order to cover the measuring range, testing may include a limited number of contrived specimens, not to exceed 10 to 20 percent, or as otherwise deemed appropriate by FDA. The contrived specimens must be prepared to resemble clinical specimens. This testing must evaluate repeatability and reproducibility and provide assessments of within-run, within-day, between-run, between-day, between-reagent lot, between-instrument, between-site, and between-operator precision, as applicable to the system;
(ii) Studies that demonstrate the performance of each parameter (test output) throughout the claimed measurement range, to include linearity studies or dose-response studies, as applicable to the parameter (test output);
(iii) Potential interferent study that includes evaluation of hemolyzed and lipemic samples as potential interferents; exogenous and endogenous interferents associated with each patient population intended for use with the device, and which might be expected to affect assay performance, must be evaluated; and potential interferents that are specific for, or related to, the technology or methodology of the device. Evaluation of all potential interferents must be performed using a protocol determined to be acceptable to the FDA (
e.g., an FDA-recognized standard) and include both normal and abnormal specimens covering coagulation profiles representative of the intended use population;(iv) A study that evaluates specimen stability under the intended conditions for specimen collection, handling, and storage, using samples that cover the coagulation profiles representative of the intended use population, and using protocols determined to be acceptable by FDA;
(v) A multisite clinical study, determined to be acceptable by FDA, demonstrating performance, relative to clinically relevant and clinically validated laboratory test(s) for each parameter (test output). Further, the study must meet all of the following criteria:
(A) The study must be performed in the intended use population and include representation from all patient populations for whom the device is intended to be used. Potential endogenous and exogenous interferents for each target patient population must be evaluated or known prior to the study;
(B) The study must be conducted at a minimum of three external sites representative of the intended use setting by the intended operators;
(C) Test samples must be collected at time intervals relevant to the device's use in the intended use population;
(D) Clinical specimens, which cover coagulation profiles representative of the intended use population, must be evaluated at each of the three clinical sites in the study;
(E) Analysis of the concordance of clinical interpretation of patient coagulation status made from individual test parameter (test output) results as compared to clinical interpretation of coagulation status from a clinically relevant laboratory test or tests (
e.g., a comparative viscoelastic device or standard laboratory tests) must be conducted; and(F) Expected (reference) values for each parameter (test output) must be demonstrated by testing a statistically appropriate number of samples from apparently healthy normal individuals;
(vi) For a device with a user interface that has information that needs to be interpreted by the user in correctly using the device to achieve the intended test results or a device that does not provide a final output that is a comprehensive interpretation of all parameter (test output) results, a study evaluating the ability of device users to correctly interpret results;
(vii) For any device indicated to guide blood product use, a clinical outcome study determined to be acceptable by FDA that specifically validates the device's indicated use in guiding blood product use; and
(viii) For any device indicated to guide use of medication, a clinical outcome study determined to be acceptable by FDA that specifically validates the device's indicated use in guiding use of medication.
(2) The labeling required under § 809.10(b) of this chapter must include the following:
(i) A summary of results from the study required by paragraph (b)(1)(i) of this section, including repeatability, reproducibility, and assessments of within-run, within-day, between-run, between-day, between-reagent lot, between-instrument, between-site, and between-operator precision, as applicable to the system.
(ii) The claimed measurement range of each parameter (test output), as supported by demonstrated performance of the parameter (test output) throughout the claimed measurement range, including studies required by paragraphs (b)(1)(i) through (iii) and (v) of this section, and, if applicable, paragraphs (b)(1)(vii) and (viii) of this section.
(iii) Identification of known interferents, including all endogenous, exogenous, technology-specific, and patient population-specific interferents, specific to each parameter (test output). The information must include the concentration(s) or level(s) at which interference was found to occur and the concentration range or levels at which interference was not found to occur.
(iv) Information regarding the multisite clinical study required by paragraph (b)(1)(v) of this section, including:
(A) Each patient population evaluated;
(B) Each intended use setting and the operators;
(C) A summary of the results, including the concordance analysis to clinically relevant laboratory test(s); and
(D) Demonstrated expected (reference) values for each parameter (test output).
(3) The labeling required under § 809.10 of this chapter must include the following:
(i) A limiting statement that the result(s) from the device is(are) not intended to be used as the sole basis for a patient diagnosis.
(ii) Unless appropriate clinical outcome studies are done in accordance with paragraph (b)(1)(vii) of this section that specifically validate an indication for the device's use in guiding blood product use, a limiting statement that the device has not been evaluated to guide blood product use.
(iii) Unless appropriate clinical outcome studies are done in accordance with paragraph (b)(1)(viii) of this section that specifically validate an indication for the device's use in guiding use of medication, a limiting statement that the device has not been evaluated to guide use of medication.