Predicate Devices

Reference Devices

AI/ML (Artificial Intelligence / Machine Learning)

No
The document describes a device that uses SEER Sonorheometry and pre-filled reagents to measure viscoelastic properties of blood. There is no mention of AI or ML in the device description, intended use, or performance studies. The analysis focuses on traditional analytical and comparison studies.

Therapeutic

No.
The device is an in vitro diagnostic (IVD) device used to evaluate coagulation and clot lysis, and does not directly provide therapy.

Diagnostic

Yes

The "Intended Use / Indications for Use" section explicitly states, "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..." and "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." These statements clearly define the device's role in diagnosing medical conditions by analyzing biological samples.

SaMD (Software as a Medical Device)

No

The device description clearly states that the QStat Cartridge is a single-use, disposable plastic cartridge that is used with the Quantra Hemostasis Analyzer. It contains pre-filled reagents and is in direct contact with blood. This indicates a physical, hardware component, not a software-only device.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

Intended Use/Indications for Use: The document explicitly states "The QStat Cartridge is intended for in vitro diagnostic use". It also describes its use in evaluating blood coagulation and clot lysis in patient samples to assess medical conditions (hypocoagulable conditions).
Device Description: The description details how the device interacts with a "venous whole blood sample" and analyzes its properties using reagents. This is a hallmark of an in vitro diagnostic device, which is used to examine specimens taken from the human body.
Performance Studies: The document describes clinical performance studies comparing the device's results with a predicate device using blood samples from patients. This type of testing is required for IVD devices to demonstrate their accuracy and reliability in a clinical setting.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / 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.

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 and hypercoagulable conditions in trauma and liver transplantation procedures.

Results obtained with the QStat Cartridge should not be the sole basis for patient diagnosis.

For prescription use only.

Product codes (comma separated list FDA assigned to the subject device)

OFR

Device Description

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 degrees Celsius, 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).

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Blood sample

Indicated Patient Age Range

18 years and older

Intended User / Care Setting

Trained professionals at the point-of-care and in clinical laboratories.

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Not Found

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

Precision/Reproducibility:

Single Site Precision: Evaluated QStat Control Level 1 (QSL1) and QStat Control Level 2 (QSL2) in duplicate over 20 testing days. Analysis showed within-laboratory precision (total) of 0.0% - 9.5% CV for QSL1 and 0.6% - 9.3% CV for QSL2 parameters. Repeatability was 0.0% - 8.6% CV for QSL1 and 0.6% - 8.5% CV for QSL2. A second single site precision study with fibrinolysis-positive controls (internal use) showed total %CV for CT, CS, and FCS below 5.8% and CSL total %CV of 7.1% (SD of 10.2%).
Multi-Site Reproducibility: Performed at three external clinical sites with a panel of three whole blood samples over five days, using two Quantra Analyzers per site and a single reagent lot. Samples included one native and two contrived (tPA spiked) samples. Total imprecision of CSL parameter was =18 years) undergoing liver transplant surgery or experiencing major trauma, and 5 normal subjects for contrived samples. Blood samples were collected at various times (pre-surgery, anhepatic, post-reperfusion for liver; ER, OR, ICU for trauma). Contrived samples (6.7%) were prepared by spiking blood from normal volunteers with fibrinogen and tPA. All samples run in parallel on Quantra QStat Cartridge and ROTEM delta.
- Correlation (QStat vs. ROTEM delta):
  - CT vs INTEM CT: Pearson 0.89 (0.87, 0.91), Spearman 0.86 (0.83, 0.88)
  - CS vs EXTEM A20: Pearson 0.92 (0.91, 0.93), Spearman 0.91 (0.90, 0.93)
  - FCS vs FIBTEM A20: Pearson 0.89 (0.87, 0.91), Spearman 0.87 (0.85, 0.89)
- Clinical Agreement Analysis (QStat CSL vs. ROTEM delta EXTEM ML): Overall agreement of patient sample assignments into lysis-positive and lysis-negative was 92.6%. Agreement within lysis-positive was 90.2% and lysis-negative was 93.2%. Met acceptance criteria. The QStat CSL parameter appeared more sensitive at identifying moderate fibrinolytic samples.

Reference Range Study:

Multi-center, prospective, observational study with 155 healthy volunteers (>=18 years) across four external sites. Established reference intervals for CT, CSL, CS, PCS, and FCS.

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Not directly provided as standalone metrics, but agreement percentages are given for the clinical comparison study:

Overall agreement (QStat CSL vs ROTEM delta EXTEM ML): 92.6% (or 0.93 (0.90, 0.95))
Agreement for lysis-positive category (Quantra/ROTEM): 0.90 (0.82, 0.95)
Agreement for lysis-negative category (Quantra/ROTEM): 0.93 (0.90, 0.95)

Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.

K083842, K101533

Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.

DEN180017

Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).

Not Found

Regulation Number and Section

§ 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.

Summary

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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.

1

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:

K213917

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

1. Regulation Section: 21 CFR 864.5430 - Coagulation System For The Measurement Of Whole Blood Viscoelastic Properties
1. Classification: Class II

3. Product Code: QFR - Coagulation System For The Measurement Of Whole Blood Viscoelastic Properties

1. 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
1. 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.

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.

1. Special conditions for use statement(s):
  For prescription use only.
1. Special instrument requirements:
  Quantra Hemostasis Analyzer

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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

1. Predicated Device Name:
  ROTEM Delta Thromboelastometry System
1. Predicate 510(k) Numbers:
  K083842 and K101533
1. Comparison with Predicate:

| | QStat Cartridge
(Proposed Device) | ROTEM Delta Thromboelastometry System
K083842 and K101533
(Predicates) |
|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended 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.
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 | K083842
The ROTEM® delta Thromboelastometry System is
designed for in vitro diagnostic use by professionals
in a laboratory environment. The ROTEM® delta is
intended to provide a qualitative and quantitative
indication of the coagulation state of a blood sample.
For this purpose, the ROTEM® delta records the
clot firmness changes in a sample of citrated whole
blood as the sample clots, retracts and lyses in real
time. The analyzer output consists of a qualitative
graphical representation (mirrored coagulation curve

clot firmness over time) and several defined
numerical parameters describing the curve
quantitatively.
The in-TEM® assay is a semi-quantitative in vitro
diagnostic assay used to monitor the coagulation
process via the intrinsic pathway in citrated whole |
| QStat Cartridge
(Proposed Device) | ROTEM Delta Thromboelastometry System
K083842 and K101533
(Predicates) | |
| 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 QStat
Cartridge should not be the sole basis
for patient diagnosis.

For prescription use only. | blood specimens. Clotting characteristics are
described by the functional parameters Clotting
Time (CT), Speed of Clot formation (CFT and alpha
angle), Clot Firmness (A20/MCF) and Clot Lysis
(LOT, ML, LI(x)). The assay is intended for
professional use in the clinical laboratory on
the ROTEM® delta Instrument.

The hep-TEM® assay is a semi-quantitative in vitro
diagnostic assay used to monitor the coagulation
process via the intrinsic pathway in the presence of
heparin, in citrated whole blood specimens. Clotting
characteristics are described by the
functional parameters Clotting Time (CT), Speed of
Clot formation (CFT and alpha angle),
Clot Firmness (A20/MCF) and Clot Lysis (LOT,
ML, LI(x)). The assay is intended for professional
use in the clinical laboratory on the ROTEM® delta
Instrument.

The NATEM® assay is a semi-quantitative in vitro
diagnostic assay used to monitor the coagulation
process contact activated by the surface of the
measurement cell, in citrated whole blood
specimens. Clotting characteristics are described by
the functional parameters Clotting Time (CT), Speed
of Clot formation (CFT and alpha angle),
Clot Firmness (A20/MCF) and Clot Lysis (LOT,
ML, LI(x)). The assay is intended for professional
use in the clinical laboratory on the ROTEM® delta
Instrument.

The star-TEM® reagent is intended for use as
recalcification reagent in the NATEM and in-TEM
on the ROTEM® delta Thromboelastometry
System.

K101533
The EXTEM® assay is a semi-quantitative in vitro
diagnostic assay used to monitor the coagulation
process via the extrinsic pathway in citrated whole
blood specimens on the ROTEM® delta
Thromboelastometry System. Clotting
characteristics are described by the functional
parameters Clotting Time (CT), Speed of Clot
formation (CFT and alpha angle), Clot Firmness
| |
| | QStat Cartridge
(Proposed Device) | ROTEM Delta Thromboelastometry System
K083842 and K101533
(Predicates) |
| | | Thromboelastometry System to monitor the clot
firmness of a citrated whole blood specimen after
blocking platelet contribution to the clot firmness.
The fibTEM® is always used in conjunction with
exTEM®. Clotting characteristics are described by
the functional parameter Clot Firmness (A20/MCF).
The APTEM® assay is a semi-quantitative in vitro
diagnostic assay on the ROTEM® delta
Thromboelastometry System to monitor the clot
firmness of a citrated whole blood specimen after
blocking hyperfibrinolysis by aprotinin. The ap-
TEM® is always used in conjunction with ex-
TEM®. Clotting characteristics are described by
the functional parameters Clotting Time (CT), Speed
of Clot formation (CFT and alpha angle), Clot
Firmness (A20/MCF) and Clot Lysis (LOT, ML,
LI(x)). CFT and alpha (Speed of Clot Formation) are
complementary parameters and should be used
in conjunction with the main parameters Clotting
Time (CT) and Clot Firmness (A20/MCF). |
| | Similarities | |
| Classification | II | Same |
| Indications for
Use | Trauma and liver transplantation | Trauma, organ transplantation, cardiovascular
surgery, and cardiology procedures |
| Technological
Purpose | Measuring "clot stiffness" during clot
formation | Measuring "clot firmness" during clot formation |
| Measuring
Channels | 4 | Same |
| Sample Type | 3.2% sodium citrated whole blood | Same |
| Results Display | Graphical (curves) and numerical
display of patient results | Same |
| Measurands | Clot time (CT) | Same |
| Measurands | Clot Stiffness (CS) | Same. Reported as EXTEM A20 (clot firmness) |
| Measurands | Fibrinogen Contribution to Clot
Stiffness (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 blood
sample (2.7 mL whole blood + citrate) | 300 µL citrated whole blood sample per
assay (INTEM, EXTEM, FIBTEM, APTEM) |
| Sample
Preparation | Automated | Manual |
| | QStat Cartridge
(Proposed Device) | ROTEM Delta Thromboelastometry System
K083842 and K101533
(Predicates) |
| Signal
Generation | Ultrasonic pulses directed into a
stationary well | Oscillating pin in stationary cup |
| Assay Output | Platelet Contribution to Clot
Stiffness (PCS) | Output not directly provided but can be calculated
offline 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 (fibrinolysis
inhibitor) | 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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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

1. 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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			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)*	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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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 Category
Quantra/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.
1. Clinical Studies:
  Not applicable.
1. Clinical Cut-Off:
  See reference range study below for CSL cutoff description.
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

1. Software:
  FDA has reviewed applicant's Hazard Analysis and software development processes for this line of product types:

Yes X or No _________

Specimen Identification: 3.
Bar code reader

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1. 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.
న్. Calibration:
User calibration is not required, based on the design of the instrument.
1. 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.

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.