Predicate Devices

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The description focuses on the physical and optical measurement of blood clotting properties and the calculation of standard hemostasis parameters (R, MA, LY30) based on resonant frequency analysis. There is no mention of AI or ML algorithms being used for data analysis, interpretation, or prediction.

Therapeutic

No.

Explanation: This device is explicitly described as an "in vitro diagnostic use" system intended to evaluate blood hemostasis properties, not to treat a condition. It provides semi-quantitative results to aid in diagnosis or assessment of clinical conditions, but does not provide therapy.

Diagnostic

Yes

The "Intended Use / Indications for Use" section explicitly states, "The TEG 6s Hemostasis System is intended for in vitro diagnostic use." Additionally, the "Device Description" states it is "intended for in vitro diagnostic use to provide semi-quantitative indications of a blood sample's ability to form and maintain a clot." These statements clearly indicate its purpose as a diagnostic device.

SaMD (Software as a Medical Device)

No

The device description clearly outlines a system consisting of both a hardware analyzer (TEG 6s Hemostasis Analyzer) and disposable assay cartridges. The analysis involves physical processes like vibrating measurement cells, detecting meniscus motion optically, and analyzing resonant frequencies, which are all hardware-dependent functions.

IVD (In Vitro Diagnostic)

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

Here's why:

Intended Use: The "Intended Use / Indications for Use" section explicitly states: "The TEG 6s Hemostasis System is intended for in vitro diagnostic use with adult patients where an evaluation of their blood hemostasis properties is desired."
Sample Type: The device analyzes "3.2% citrated whole blood," which is a biological sample taken from the human body.
Purpose: The system is used to "evaluate their blood hemostasis properties," "assess clinical conditions," and "aid in determining if a clotting dysfunction or coagulopathy is present." These are all diagnostic purposes.
Results: The system provides "semi-quantitative results" and "numerical values for parameters R, MA, and LY30," which are used in the diagnostic process.
Professional Use: The device is indicated for "professional use only," which is typical for IVDs used in a clinical setting.
Device Description: The description further clarifies that the system is "intended for in vitro diagnostic use to provide semi-quantitative indications of a blood sample's ability to form and maintain a clot."

All of these points align with the definition of an In Vitro Diagnostic device, which is a medical device intended to be used in vitro for the examination of specimens derived from the human body solely or principally for the purpose of providing information concerning a physiological or pathological state, or concerning a congenital abnormality, or to monitor therapeutic measures.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

The TEG 6s Hemostasis System consists of the TEG 6s Hemostasis Analyzer and the Citrated: K, KH, RTH, FFH assay cartridge. The TEG 6s Hemostasis System is intended for in vitro diagnostic use with adult patients where an evaluation of their blood hemostasis properties is desired. The TEG 6s Hemostasis System records the kinetic changes in a sample of 3.2% citrated whole blood as the sample clots and provides semi-quantitative results. The TEG 6s Hemostasis System can be used in the laboratory or at the point-of-care.

The Citrated: K, KH, RTH, FFH assay cartridge is intended to be used in patients where heparin/heparinoids may be present and who are at an increased risk of coagulopathy. Hemostasis evaluations are indicated to assess clinical conditions in cardiovascular surgery, cardiovascular procedures (e.g. minimally invasive valve replacement or repairs) and liver transplantation to assess hemorrhage or thrombosis conditions before, during and following the procedure.

The Citrated: K, KH, RTH, FFH assay cartridge contains four independent assays (CK, CKH, CRTH and CFFH) and the system output consists of a table of numerical values for parameters R, MA, and LY30.

The CK assay monitors the hemostasis process via the intrinsic pathway in 3.2% citrated whole blood specimens on the TEG 6s Hemostasis System. Clotting characteristics are described by the functional parameters R (clotting time) and MA (maximum clot strength).

The CKH assay monitors the effects of heparin in 3.2% citrated whole blood specimens on the TEG 6s Hemostasis System. CKH is used in conjunction with CK, and heparin influence is determined by comparing Clotting Times (R) between the two tests. LY30 describes fibrinolysis 30 minutes after reaching maximum clot strength.

The CRTH assay monitors the hemostasis process after stimulation of both the intrinsic and extrinsic pathways in 3.2% citrated whole blood specimens on the TEG 6s Hemostasis System, neutralizing the effect of heparin in the sample. Clotting characteristics are described by the functional parameter MA (maximum clot strength with contributions of both platelets and fibrin).

The CFFH assay monitors hemostasis of 3.2% citrated whole blood specimens in the TEG 6s Hemostasis System after blocking platelet contributions to clot strength, neutralizing the effect of heparin in the sample. Clotting characteristics are described by the functional parameter MA (fibrinogen contribution to maximum clot strength).

Results from the TEG 6s analysis should not be the sole basis for a patient diagnosis, but should be evaluated together with the patient's medical history, the clinical picture and, if necessary, further hemostasis tests.

For professional use only.

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

JPA

Device Description

The TEG® 6s Hemostasis System (TEG® hemostasis analyzer and TEG® 6s assay cartridges) is intended for in vitro diagnostic use to provide semi-quantitative indications of a blood sample's ability to form and maintain a clot. The TEG® 6s Hemostasis System records the kinetic changes in a sample of whole blood as the sample clots, retracts and/or lyses. The system output consists of a table of numerical values and graphs resulting from the hemostasis process over time. This information can be used by clinicians to aid in determining if a clotting dysfunction or coagulopathy is present.

To perform a test, a disposable TEG® 6s assay cartridge is inserted into the TEG® 6s hemostasis analyzer. The instrument reads the bar code on the cartridge and identifies the type of cartridge for operator confirmation. Blood (collected in a 3.2% sodium citrate tube) or Quality Control (QC) material is added to the entry port on the cartridge and drawn into the cartridge under the TEG® 6s hemostasis analyzer control. The amount of the sample drawn into the cartridge is determined by the pre-set volume of the blood chambers in the cartridge. Once in the cartridge, the sample is metered into as many as 4 separate analysis channels, depending upon the assays being performed. Reconstitution of reagents dried within the cartridge is accomplished by moving the sample back and forth through reagent chambers, under the control of microfluidic valves and bellows (pumps) within the cartridge. After each sample has been mixed with reagent, it is delivered to a test cell where it is monitored for viscoelastic changes due to coagulation. Excess sample material is moved under microfluidic control into an enclosed waste chamber within the cartridge.

The TEG® 6s technology is based on a disposable cartridge containing up to 4 independent measurement cells. Each cell consists of a short vertically-oriented injection molded tube (ring). Detection of clotting in the TEG® 6s Hemostasis System is performed optically. A piezoelectric actuator vibrates the measurement cell(s) through a motion profile composed of summed sinusoids at different frequencies. The movement of the measurement cells will induce motion in the sample meniscus, which will be detected by a photodiode. The resulting motion of the meniscus is monitored optically and analyzed by the instrument to calculate the resonant frequency and modulus of elasticity (stiffness) of the sample. By performing a Fast Fourier Transform (FFT) on meniscus motion data, the resonant frequencies can be determined. The analyzer monitors the harmonic motion of a hanging drop of blood in response to external vibration. As the sample transitions from a liquid state to a gel-like state during clotting, the modulus of elasticity (stiffness) and therefore resonant frequency increase. The TEG® 6s hemostasis analyzer measures these variations in resonant frequency during clotting and lysis.

Resonance is the tendency of a material or structure to oscillate with greater amplitude at some frequencies than others. The exact frequencies at which resonance occurs will depend on the stiffness and mass of the sample. Stiffness, in turn, is a function of a material's modulus of elasticity and the boundary conditions to which the material is exposed, such as the geometry and materials of a test cell. By holding these boundary conditions and sample mass constant from sample to sample, the TEG® 6s Hemostasis System allows direct comparison of elasticity between samples. The output measurements are displayed in a table and on a graphical tracing that reflects the hemostasis profile of the clot formation.

In a typical test, blood that has been delivered to the measurement cell will not clot for several minutes. During this time the sample has no inherent stiffness except that provided by surface tension, and since this remains constant the measured resonant frequencies will not change.

Once clotting begins, however, the elastic modulus and thus the resonant frequencies increase rapidly. During fibrinolysis, the process is reversed, with elastic modulus and resonant frequencies decreasing. In tests where clotting does not occur, the resonant frequency of the sample will not change. During coagulation, however, a clot will bind to the ring contained in the cartridge and the resonant frequency will rise with increasing firmness of the clot. The TEG® 6s hemostasis analyzer collects meniscus motion data, tracks changing resonant frequencies and analyzes the frequency data to provide semi-quantitative parameters describing the clot.

The TEG® 6s Hemostasis System monitors the interaction of platelets within the fibrin mesh of the clot during clot formation and lysis, all in a whole-blood setting. The TEG® 6s Hemostasis System uses thromboelastography to provide continuous measurement of clot elasticity.

Method Comparison testing has been performed, yielding data from 8 clinical sites. These data include the applicable parameters for the tests in the Citrated: K, KH, RTH, FFH assay cartridge.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Not Found

Indicated Patient Age Range

adult patients

Intended User / Care Setting

professional use only / laboratory or at the point-of-care

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

A Method Comparison study was conducted with patient samples collected at eight clinical trial sites, following CLSI EP09-A3 guidelines. The subjects enrolled were patients undergoing liver transplantation, cardiovascular surgery, or cardiology procedures. Blood samples were drawn before, during, and after the procedures and were analyzed using TEG® 6s analyzers with the Citrated: K, KH, RTH, FFH (Global Hemostasis - HN) cartridge, as well as the TEG 6s with the associated Cartridge (Citrated Multichannel Cartridge) and Clauss Fibrinogen as the comparators.
The linearity and correlation analysis were assessed for each assay parameter.
N of samples:
CK - R: 617
CK - MA: 539
CKH - R: 829
CKH - LY30: 828
CRTH - MA: 870
CFFH - MA: 883 (against Clauss Fibrinogen comparator)

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

Non-Clinical Performance Testing

Reference Ranges: Established according to CLSI EP28-A3c using citrated whole blood from normal donors (representative of normal population distributions - age, gender, race) with no known coagulopathies and not taking any drugs that would potentially affect patient hemostasis. Non-parametric method for analysis was used.
- CK: N=157 for R, N=151 for MA. Ranges: R (4.6-9.1 min), MA (52-69 mm).
- CKH: N=155 for R, N=148 for LY30. Ranges: R (4.3-8.3 min), LY30 (0-3.2%).
- CRTH: N=162 for MA. Range: MA (53-69 mm).
- CFFH: N=162 for MA. Range: MA (15-34 mm).
Analytical Precision (Repeatability and Reproducibility):
- Cartridge Reagent QC Precision: Multi-site reproducibility and single-site repeatability studies performed with Cartridge Reagent QC Level 1 and Level 2 materials in accordance with CLSI-EP05 A3 guideline, and a within lab lot to lot precision study. Results demonstrate achievement of repeatability, within laboratory, reproducibility, and total precision requirements for all reported parameters.
  - Cartridge Reagent QC Level 1 (N=316 for R, MA; N=196 for LY30): All parameters passed. Total %CVs range from 3.3% (CK-MA) to 12.3% (CKH-R).
  - Cartridge Reagent QC Level 2 (N=316 for R, MA, LY30; N=313 for CK-MA): All parameters passed. Total %CVs range from 0.7% (CKH-Ly30) to 10.1% (CK-R, CKH-R).
- Whole Blood Repeatability: Two studies conducted with normal donor whole blood (N=24) and contrived (hypo-coagulable, hyper-coagulable, hyper-fibrinolytic) whole blood samples (N=23-24). Testing conducted at one location, with two operators, and three cartridge lots. Results indicate satisfactory precision, with all parameters passing.
Interference: Tested according to CLSI EP07-A3 using normal, contrived hyperfibrinolytic, and contrived hypocoagulable specimens. Various interfering factors (Discard Tube, Hemolysis, Short Draw, Dilution, Dabigatran, Rivaroxaban, Aspirin, Ticagrelor, Alcohol, Lipemia, TXA, EACA, Mycophenolic Acid, Tacrolimus, Prednisone, Rifaximin, Lactulose) were evaluated. Highest concentrations with no interference were identified for each parameter.
CK Sensitivity and Specificity: Two studies performed using blood samples from four normal donors and fifteen contrived donors (hypocoagulable, hypercoagulable, hyperfibrinolytic) spiked with heparin (0, 0.1, 0.15, 0.2 IU/ml).
- Normal donors: 95% specificity (0 IU/mL heparin), 95% sensitivity for 0.1 IU/mL, 100% for 0.15 IU/mL, 95% for 0.2 IU/mL.
- Contrived samples: 100% specificity without heparin and 100% sensitivity for detection of heparin at 0.2 IU/ml across all contrived conditions (hypo-coagulable, hyper-coagulable, hyper-fibrinolytic).
Assay Measuring Range (AMR): Established for MA (CRTH and CFFH) and LY30 (CKH). Existing AMR values for CK-R, CK-MA, and CKH-R from the predicate device are retained.
- CRTH-MA: Lower AMR 20 (2.8% CV), Upper AMR 78 (0.9% CV).
- CFFH-MA: Lower AMR 6 (8.7% CV), Upper AMR 61 (1.4% CV).
- CKH-LY30: Lower AMR 0 (0% CV), Upper AMR 30 (5.1% CV).
Heparin Neutralization Requirement Verification: Tests performed using Unfractionated Heparin (UFH) and Low Molecular Weight Heparin (LMWH) spiked and un-spiked samples. 200 cartridges tested across four donors, 10 replicates. Study acceptance criteria were met, verifying neutralization effectiveness for up to 5.0 IU/mL UFH and 0.013 mg/mL LMWH.

Clinical Performance Testing

Clinical Performance - Method Comparison:
- Study conducted with patient samples (N of Samples: CK-R=617, CK-MA=539, CKH-R=829, CKH-LY30=828, CRTH-MA=870, CFFH-MA=883) at eight clinical trial sites.
- Comparison of Citrated: K, KH, RTH, FFH assay cartridge with predicate device (K150041) for Type 1 and 2 parameters (CK-R, CK-MA, CKH-R, CKH-LY30, CRTH-MA) and with Clauss Fibrinogen for Type 3 (CFFH-MA).
- Key Results:
  - For Type 1 and Type 2 parameters, predicted bias estimates at the lower and upper limits of the normal reference range (NRR) were within acceptable bias limits, with entire confidence intervals contained within these limits, demonstrating excellent agreement.
  - Linear regression slope estimates for Type 1 and 2 parameters were close to 1.0 (range 1.00-1.11, e.g., CK-R slope 1.08, CK-MA slope 1.05, CKH-R slope 1.01, CKH-LY30 slope 1.00, CRTH-MA slope 1.11), with 95% CIs containing 1.0.
  - Pearson correlation coefficients for Type 1 and 2 parameters were greater than 0.82 (e.g., CK-R 0.90, CK-MA 0.95, CKH-R 0.82, CKH-LY30 0.99, CRTH-MA 0.97).
  - For Type 3 parameter (CFFH-MA vs. Clauss fibrinogen), Spearman correlation coefficient was 0.79 (95% CI: 0.757; 0.814).
  - Secondary within-device comparison confirmed excellent reproducibility.
  - Repeatability (Replicate 2 vs. Replicate 1) showed Pearson linear correlation coefficients above 0.88 for all parameters.
  - High number of contributing samples (over 90%) for CRTH-MA and CFFH-MA, suggests reduced incidence of heparin-induced data quality issues.

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

Sensitivity:
Normal: 95% (0.1 IU/mL), 100% (0.15 IU/mL), 95% (0.2 IU/mL)
Contrived Hypo-coagulable: 100% (0.1 IU/mL), 100% (0.15 IU/mL), 100% (0.2 IU/mL)
Contrived Hyper-coagulable: 100% (0.1 IU/mL), 100% (0.15 IU/mL), 100% (0.2 IU/mL)
Contrived Hyper-fibrinolytic: 95% (0.1 IU/mL), 100% (0.15 IU/mL), 100% (0.2 IU/mL)

Specificity:
Normal: 95% (0 IU/mL)
Contrived Hypo-coagulable: 100% (0 IU/mL)
Contrived Hyper-coagulable: 100% (0 IU/mL)
Contrived Hyper-fibrinolytic: 100% (0 IU/mL)

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.

K150041

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.

Not Found

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

§ 864.5425 Multipurpose system for in vitro coagulation studies.

(a)
Identification. A multipurpose system for in vitro coagulation studies is a device consisting of one automated or semiautomated instrument and its associated reagents and controls. The system is used to perform a series of coagulation studies and coagulation factor assays.(b)
Classification. Class II (special controls). A control intended for use with a multipurpose system for in vitro coagulation studies is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 864.9.

Summary

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Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA logo on the right. The FDA logo is in blue and includes the letters "FDA" followed by the words "U.S. Food & Drug Administration".

March 29, 2024

Haemonetics Corporation Julie Bergeman Senior Regulatory Affairs Specialist 125 Summer St Boston, Massachusetts 02110

Re: K232018

Trade/Device Name: Citrated: K, KH, RTH, FFH Regulation Number: 21 CFR 864.5425 Regulation Name: Multipurpose System For In Vitro Coagulation Studies Regulatory Class: Class II Product Code: JPA Dated: July 6, 2023 Received: July 7, 2023

Dear Julie Bergeman:

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 (the 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 available 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.

Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device"

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(https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30. Design controls; 21 CFR 820.90. Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review. the OS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

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 Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-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 Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). For questions regarding of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medicaldevices/medical-device-safety/medical-device-reporting-mdr-how-report-medical-device-problems.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely.

Min Wu -S

Min Wu, Ph.D. Branch Chief Division of Immunology and Hematology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K232018

Device Name Citrated: K. KH, RTH, FFH

Indications for Use (Describe)

The TEG 6s Hemostasis System consists of the TEG 6s Hemostasis Analyzer and the Citrated: K, KH, RTH, FFH assay cartridge. The TEG 6s Hemostasis System is intended for in vitro diagnostic use with adult patients where an evaluation of their blood hemostasis properties is desired. The TEG 6s Hemostasis System records the kinetic changes in a sample of 3.2% citrated whole blood as the sample clots and provides semi-quantitative results. The TEG 6s Hemostasis System can be used in the laboratory or at the point-of-care.

The Citrated: K, KH, RTH, FFH assay cartridge is intended to be used in patients where heparinheparinoids may be present and who are at an increased risk of coagulopathy. Hemostasis evaluations are indicated to assess clinical conditions in cardiovascular surgery, cardiovascular procedures (e.g. minimally invasive valve replacement or repairs) and liver transplantation to assess hemorrhage or thrombosis conditions before, during and following the procedure.

The Citrated: K, KH, RTH, FFH assay cartains four independent assays (CK, CKH, CRTH and CFFH) and the system output consists of a table of numerical values for parameters R, MA, and LY30.

The CK assay monitors the hemostasis process via the intrinsic pathway in 3.2% citrated whole blood specimens on the TEG 6s Hemostasis System. Clotting characteristics are described by the functional parameters R (clotting time) and MA (maximum clot strength).

The CKH assay monitors the effects of heparin in 3.2% citrated whole blood specimens on the TEG 6s Hemostasis System. CKH is used in conjunction with CK, and heparin influence is determined by comparing Clotting Times (R) between the two tests. LY30 describes fibrinolysis 30 minutes after reaching maximum clot strength.

The CRTH assay monitors the hemostasis process after stimulation of both the intrinsic pathways in 3.2% citrated whole blood specimens on the TEG 6s Hemostasis System, neutralizing the effect of heparin in the sample. Clotting characteristics are described by the functional parameter MA (maximum clot strength with contributions of both platelets and fibrin).

The CFFH assay monitors hemostasis of 3.2% citrated whole blood specimens in the TEG 6s Hemostasis System after blocking platelet contributions to clot strength, neutralizing the effect of heparin in the sample. Clotting characteristics are described by the functional parameter MA (fibrinogen contribution to maximum clot strength).

Results from the TEG 6s analysis should not be the sole basis for a patient diagnosis, but should be evaluated together with the patient's medical history, the clinical picture and, if necessary, further hemostasis tests.

For professional 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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510(k) Summary

| Submitter: | Haemonetics Corporation
125 Summer Street
Boston MA 02110 United States |
|----------------|-----------------------------------------------------------------------------------------------------|
| Contact: | Julie Bergeman
Senior Regulatory Affairs Specialist
262-693-8368
jbergeman@haemonetics.com |
| Date Prepared: | March 26, 2024 |

1. Device Information

Device Trade Name:	Citrated: K, KH, RTH, FFH
Common Name:	Whole Blood Hemostasis System
Classification Name:	System, Multipurpose For In Vitro Coagulation Studies
Regulatory Class:	2
Regulation Number:	21 CFR 864.5425
Product Code:	JPA

2. Legally Marketed Predicate Device

Predicate #	Predicate Trade Name	Product Code
K150041	TEG 6s with the Citrated Multichannel Cartridge	JPA

3. Device Description Summary

TEG® 6s System Description

The TEG® 6s Hemostasis System (TEG® hemostasis analyzer and TEG® 6s assay cartridges) is intended for in vitro diagnostic use to provide semi-quantitative indications of a blood sample's ability to form and maintain a clot. The TEG® 6s Hemostasis System records the kinetic changes in a sample of whole blood as the sample clots, retracts and/or lyses. The system output consists of a table of numerical values and graphs resulting from the hemostasis process over time. This information can be used by clinicians to aid in determining if a clotting dysfunction or coagulopathy is present.

5

To perform a test, a disposable TEG® 6s assay cartridge is inserted into the TEG® 6s hemostasis analyzer. The instrument reads the bar code on the cartridge and identifies the type of cartridge for operator confirmation. Blood (collected in a 3.2% sodium citrate tube) or Quality Control (QC) material is added to the entry port on the cartridge and drawn into the cartridge under the TEG® 6s hemostasis analyzer control. The amount of the sample drawn into the cartridge is determined by the pre-set volume of the blood chambers in the cartridge. Once in the cartridge, the sample is metered into as many as 4 separate analysis channels, depending upon the assays being performed. Reconstitution of reagents dried within the cartridge is accomplished by moving the sample back and forth through reagent chambers, under the control of microfluidic valves and bellows (pumps) within the cartridge. After each sample has been mixed with reagent, it is delivered to a test cell where it is monitored for viscoelastic changes due to coagulation. Excess sample material is moved under microfluidic control into an enclosed waste chamber within the cartridge.

TEG® 6s Measurement Technique

The TEG® 6s technology is based on a disposable cartridge containing up to 4 independent measurement cells. Each cell consists of a short vertically-oriented injection molded tube (ring). Detection of clotting in the TEG® 6s Hemostasis System is performed optically. A piezoelectric actuator vibrates the measurement cell(s) through a motion profile composed of summed sinusoids at different frequencies. The movement of the measurement cells will induce motion in the sample meniscus, which will be detected by a photodiode. The resulting motion of the meniscus is monitored optically and analyzed by the instrument to calculate the resonant frequency and modulus of elasticity (stiffness) of the sample. By performing a Fast Fourier Transform (FFT) on meniscus motion data, the resonant frequencies can be determined. The analyzer monitors the harmonic motion of a hanging drop of blood in response to external vibration. As the sample transitions from a liquid state to a gel-like state during clotting, the modulus of elasticity (stiffness) and therefore resonant frequency increase. The TEG® 6s hemostasis analyzer measures these variations in resonant frequency during clotting and lysis.

Resonance is the tendency of a material or structure to oscillate with greater amplitude at some frequencies than others. The exact frequencies at which resonance occurs will depend on the stiffness and mass of the sample. Stiffness, in turn, is a function of a material's modulus of elasticity and the boundary conditions to which the material is exposed, such as the geometry and materials of a test cell. By holding these boundary conditions and sample mass constant from sample to sample, the TEG® 6s Hemostasis System allows direct comparison of

6

HAEMONET

elasticity between samples. The output measurements are displayed in a table and on a graphical tracing that reflects the hemostasis profile of the clot formation.

In a typical test, blood that has been delivered to the measurement cell will not clot for several minutes. During this time the sample has no inherent stiffness except that provided by surface tension, and since this remains constant the measured resonant frequencies will not change.

Once clotting begins, however, the elastic modulus and thus the resonant frequencies increase rapidly. During fibrinolysis, the process is reversed, with elastic modulus and resonant frequencies decreasing. In tests where clotting does not occur, the resonant frequency of the sample will not change. During coagulation, however, a clot will bind to the ring contained in the cartridge and the resonant frequency will rise with increasing firmness of the clot. The TEG® 6s hemostasis analyzer collects meniscus motion data, tracks changing resonant frequencies and analyzes the frequency data to provide semi-quantitative parameters describing the clot.

The TEG® 6s Hemostasis System monitors the interaction of platelets within the fibrin mesh of the clot during clot formation and lysis, all in a whole-blood setting. The TEG® 6s Hemostasis System uses thromboelastography to provide continuous measurement of clot elasticity.

Method Comparison testing has been performed, yielding data from 8 clinical sites. These data include the applicable parameters for the tests in the Citrated: K, KH, RTH, FFH assay cartridge. Table 1 provides the definitions that apply to calculated parameters in the TEG® 6s Hemostasis System.

| TEG® 6s
Parameter | Definition | Parameter Relation to
Hemostasis |
|----------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------|
| | R | R is the time from the start of the test until initial
fibrin formation. This represents the enzymatic
portion of coagulation. |
| MA | MA, or Maximum Amplitude, represents the
maximum firmness of the clot during the test. | Normal / reduced / increased
clot elasticity/strength |
| LY30 | LY30 is a measurement of the rate of fibrinolysis
30 minutes after MA is reached. The LY30
measurement is based on the reduction of the
tracing area that occurs between the time that M
A is measured until 30 minutes after the MA is | Normal / reduced clot
stability; clot dissolution |

Table 1. TEG® 6s parameter definitions

7

defined.
----------

Citrated Assays Citrated Kaolin (CK) assay

The CK assay is a semi-quantitative in vitro diagnostic assay for monitoring the hemostasis process via the intrinsic pathway in 3.2% citrated whole blood specimens on the TEG® 6s Hemostasis System. The CK assay consists of Kaolin which is used in the assay for activation of coagulation. It is combined with calcium chloride to neutralize the sodium citrate used to anticoagulate the blood sample.

The clotting characteristics of the CK generated hemostasis profile are described by the functional parameters Clotting Time (R) and Maximum Clot strength (MA). Since it may take an hour or more for a non-activated whole blood sample to reach maximum amplitude MA, Kaolin is essential to reduce run time and variability associated with running non-activated whole blood samples.

Citrated Kaolin with Heparinase (CKH) assay

The CKH assay is a semi-quantitative in vitro diagnostic assay for monitoring the hemostasis process via the intrinsic pathway in 3.2% citrated whole blood specimens on the TEG® 6s Hemostasis System. CKH is used in conjunction with CK, and heparin influence is determined by comparing Clotting Times (R) between the two tests. LY30 describes fibrinolysis 30 minutes after reaching maximum clot strength. The Kaolin with heparinase assay neutralizes the anticoagulant property of heparin. Calcium Chloride (CaCl2) is included to neutralize any sodium citrate in the blood.

The CKH assay monitors the effects of heparin, a commonly used anticoagulant in surgical procedures. Even very low concentrations of heparin, fractions of IU/mL of blood, can noticeably increase the R time and can even completely anticoagulate the blood, making it difficult if not impossible to monitor developing coagulopathies that are masked by high levels of therapeutic heparin.

Citrated RapidTEGTM with Heparinase (CRTH) assay

The CRTH assay is a semi-quantitative in vitro diagnostic assay that monitors the hemostasis process after stimulation of both the intrinsic and extrinsic pathways in 3.2% citrated whole blood specimens on the TEG® 6s Hemostasis System, neutralizing the effect of heparin in the sample. Clotting characteristics are described by the functional parameter: MA (maximum clot strength with contributions of both platelets and fibrin). The CRTH assay produces an

8

HAEMONET

accelerated clotting time which allows for an earlier MA result compared to the CK assay. Therefore, in the TEG® Hemostasis System, the CRTH assay is simultaneously run along with the CK and CKH assays to provide a fast way to reach a stable value for MA (CRTH) while still measuring the time- dependent parameters (CK).

As described in the CK assay, Kaolin is used for activation of coagulation and is combined with Calcium Chloride to neutralize sodium citrate in the blood sample. The addition of Tissue Factor is used for coagulation activation that would be classically described as extrinsic. The addition of heparinase in the assay cartridge neutralizes the effects of heparin in the sample. The CRTH hemostasis profile resulting from Kaolin and Tissue Factor activation provides a measure of the strength of the clot and the breakdown of the clot, or fibrinolysis.

Citrated Functional Fibrinogen with Heparinase (CFFH) assay

The CFFH assay is a semi-quantitative in vitro diagnostic assay for monitoring the hemostasis process after blocking platelet contributions to clot strength in 3.2 % citrated whole blood specimens, neutralizing the effect of heparin in the sample. The CFFH assay consists of Tissue Factor and abciximab. It is combined with Calcium Chloride to neutralize sodium citrate in the blood sample. The addition of heparinase in the assay cartridge neutralizes the effects of heparin in the sample. Tissue Factor is used for coagulation activation that would be classically described as extrinsic, with platelet aggregation inhibited by abciximab (a GPIIb/IIIa inhibitor), excluding its contribution to clot strength, and thereby measuring fibrinogen contribution to clot strength.

The Clotting characteristics are described by the functional parameter: MA (fibrinogen contribution to maximum clot strength) and measures the part of clot strength that is contributed by fibrinogen in the blood sample.

4. Intended Use/Indications for Use

The TEG 6s Hemostasis System consists of the TEG 6s Hemostasis Analyzer and the Citrated: K, KH, RTH, FFH assay cartridge. The TEG 6s Hemostasis System is intended for in vitro diagnostic use with adult patients where an evaluation of their blood hemostasis properties is desired. The TEG 6s Hemostasis System records the kinetic changes in a sample of 3.2% citrated whole blood as the sample clots and provides semi-quantitative results. The TEG 6s Hemostasis System can be used in the laboratory or at the point-of-care.

9

The Citrated: K, KH, RTH, FFH assay cartridge is intended to be used in patients where heparin/heparinoids may be present and who are at an increased risk of coagulopathy. Hemostasis evaluations are indicated to assess clinical conditions in cardiovascular surgery, cardiovascular procedures (e.g. minimally invasive valve replacement or repairs) and liver transplantation to assess hemorrhage or thrombosis conditions before, during and following the procedure.

The Citrated: K, KH, RTH, FFH assay cartridge contains four independent assays (CK, CKH, CRTH and CFFH) and the system output consists of a table of numerical values for parameters R, MA, and LY30.

The CK assay monitors the hemostasis process via the intrinsic pathway in 3.2% citrated whole blood specimens on the TEG 6s Hemostasis System. Clotting characteristics are described by the functional parameters R (clotting time) and MA (maximum clot strength).

The CKH assay monitors the effects of heparin in 3.2% citrated whole blood specimens on the TEG 6s Hemostasis System. CKH is used in conjunction with CK, and heparin influence is determined by comparing Clotting Times (R) between the two tests. LY30 describes fibrinolysis 30 minutes after reaching maximum clot strength.

The CRTH assay monitors the hemostasis process after stimulation of both the intrinsic and extrinsic pathways in 3.2% citrated whole blood specimens on the TEG 6s Hemostasis System, neutralizing the effect of heparin in the sample. Clotting characteristics are described by the functional parameter MA (maximum clot strength with contributions of both platelets and fibrin).

The CFFH assay monitors hemostasis of 3.2% citrated whole blood specimens in the TEG 6s Hemostasis System after blocking platelet contributions to clot strength, neutralizing the effect of heparin in the sample. Clotting characteristics are described by the functional parameter MA (fibrinogen contribution to maximum clot strength).

Results from the TEG 6s analysis should not be the sole basis for a patient diagnosis, but should be evaluated together with the patient's medical history, the clinical picture and, if necessary, further hemostasis tests.

For professional use only.

10

5. Comparison Citrated: K, KH, RTH, FFH and predicate device

Indications for Use Comparison

The TEG® 6s Hemostasis System consists of the TEG® 6s hemostasis analyzer including analyzer software and assay cartridges. The assay cartridges predicate device is the K 150041 TEG 6s with the Citrated Multichannel Cartridge (07-601-US). The indications for use are of the same intent with the following inclusions:

1. Heparinase is included in the RT and FF channels of the new assay cartridge.
1. Use location is defined as laboratory and point-of-care for the new assay cartridge.
1. Patient types are defined for the new assay to include the same population as the predicate (cardiovascular surgery, cardiology procedures) with expansion to patients undergoing liver transplant.

Technology Comparison

Substantial equivalence is being demonstrated through a method comparison clinical study. No key design elements required changes for the cartridge including the reagent spotting technology, the microfluidic pathway, the shaker design, or the cartridge interface with the analyzer. The reagent channel order has been rearranged; however, that has been shown to not influence cartridge functionality. There is no change to the design of the cartridge and there is no change in the mechanics of how the cartridge is run on the TEG® 6s hemostasis analyzer. No additional product development of the TEG® 6s analyzer hardware and TEG® 6s software was required to add the Citrated: K. KH. RTH. FFH assay cartridge.

| Item | K150041 TEG 6s with the Citrated
Multichannel Cartridge (Predicate)
Analyzer | Citrated: K, KH, RTH, FFH |
|--------------------------|--------------------------------------------------------------------------------------------------------|---------------------------|
| Technological
Purpose | Monitoring the physical response of
a clot to low levels of applied strain
(resonance frequency) | Same |
| Measurement | Changes in physical clot elasticity
over time | Same |
| Matrix | 3.2% citrated whole blood | Same |
| Initial Warm Up
Time | 5 minutes | Same |

Table-2 Summary of Technological Characteristics for Substantial Equivalence: Similarities

11

| Item | K150041 TEG 6s with the Citrated
Multichannel Cartridge (Predicate) | Citrated: K, KH, RTH, FFH | |
|------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------|
| Analyzer-Hardware | Fully integrated
Thromboelastography analyzer | Same | |
| | Analyzer-Measuring
Technique | Non-contact optical measurement of
shear elasticity of a coagulating
sample | Same |
| Measurement Output | | Graphical tracings of resonant
frequency per reagent type; table of
parameters | Same |
| | Assay and Reagents | | |
| | Assays | CK, CKH, CRT, CFF | CK, CKH, CRTH, CFFH
Same with inclusion of heparinase
for the CRT and CFF channels |
| Assay Reagents | CK – kaolin and CaCl2
CKH – kaolin and CaCl2 with
heparinase
CRT – tissue factor, kaolin and
CaCl2
CFF – abciximab, tissue factor and
CaCl2 | Same with inclusion of heparinase
for the CRT and CFF channels | |
| Assay Parameters
Reported | CK: R, K, Angle, MA | CK: R, MA | |
| | CKH: R | CKH: R, LY30 | |
| | CRT: MA | CRTH: MA | |
| | CFF: MA, FLEV | CFFH: MA | |
| Quality Controls | Cartridge Reagent QC - Level 1
Cartridge Reagent QC - Level 2 | Same | |

Table-3 Summary of Technological Characteristics for Substantial Equivalence: Differences and Clinical Value Comparisons

| Item | K150041 TEG 6s with the Citrated
Multichannel Cartridge (Predicate) | Citrated: K, KH, RTH, FFH |
|------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Use Location | N/A | The TEG® 6s Hemostasis System
with Citrated: K, KH, RTH, FFH
assay cartridge can be used in the
laboratory or at the point-of-care. |
| Patient Population
from Intended Use | Hemostasis evaluations are
commonly used to assess clinical
conditions in cardiovascular surgery
and cardiology procedures to assess
hemorrhage or thrombosis | The Citrated: K, KH, RTH, FFH
assay cartridge is intended to be
used in patients where
heparin/heparinoids may be present
and who are at an increased risk of
coagulopathy. Hemostasis |
| | conditions before, during and | evaluations are indicated to assess |
| | following the procedure. | clinical conditions in cardiovascular
surgery, cardiovascular procedures
(e.g. minimally invasive valve
replacement or repairs) and liver
transplantation to assess hemorrhage
or thrombosis conditions before,
during and following the procedure. |
| Clinical Value Comparisons | | |
| Clinical Value of
Citrated: Kaolin
(CK)
Parameter R (min) | Initiation phase of coagulation
triggered by enzymatic clotting
factors and culminating with the
initial fibrin formation. A prolonged
R value is indicative of slow clot
formation, due to coagulation factor
deficiencies or heparin. | Kaolin R is the time in minutes
elapsing between sample
activation and the point in time
where clotting provides enough
resistance to produce a 2 mm
amplitude reading on the TEG
analyzer tracing. The CK - R
parameter represents the initiation
phase of coagulation triggered by
enzymatic clotting factors and
culminating with the initial fibrin
formation. A prolonged R value is
indicative of slow clot formation,
and a shortened R value is
indicative of fast clot formation.
Clinical Value . A prolonged R value is
indicative of slow clot formation, due to
coagulation factor deficiencies, heparin,
or other anticoagulants. |
| Clinical Value of
Citrated: Kaolin
(CK)
Parameter MA (mm) | MA, or Maximum Amplitude,
represents the maximum firmness of
the clot during the test. The MA
provides information about the
contribution of platelets/fibrin to the
overall strength of the clot. | The maximal strength of the clot
when activated with kaolin. This
represents the combination of the
contribution of fibrinogen and
platelets to clot strength.
Clinical Value : The MA provides
information of platelets and fibrinogen
to the overall clot strength without
excluding the influence of heparin. A
decreased MA is indicative of low clot
strength, which could be due to
decreased platelet contribution or
decreased fibrinogen; whereas, an
increased MA is indicative of high clot
strength, which could be due to
increased platelet or fibrinogen
contribution. |
| Clinical Value of
Citrated: Kaolin with
Heparinase (CKH)
Parameter R (min)
Heparinase is
included in the
predicate and
subject device | Initiation phase of coagulation
triggered by enzymatic coagulation
factors and culminating with the
initial fibrin formation.
A prolonged R value is indicative of
slow clot formation, due to
coagulation factor deficiencies or
heparin. Inclusion of heparinase in
the blood chamber channel of the
cartridge provides ability to
compare R (min) without the effect
of heparin on the clot. | The reaction time between
initiation of the clot (via kaolin)
and the point where the tracing
reaches 2mm of amplitude, with
heparinase being used to
neutralize the effect of heparin.
Clinical Value: A prolonged R value is
indicative of slow clot formation, due to
coagulation factor deficiencies or non-
heparin anticoagulant. A shortening of
the CKH-R compared to the CK-R
indicates effect of heparin in the blood
sample. |
| Clinical Value of
Citrated: Kaolin with
Heparinase (CKH)
Parameter LY30 (%) | Parameter LY30 (%) is not reported
for the predicate device. | Clot lysis, in a sample with
heparinase to neutralize effects of
heparin, expressed as a percent
reduction in clot strength 30 minutes
after the MA is reached. Clinical
Value: LY30 provides information
about fibrinolytic activity. |
| Clinical Value of
Citrated: RapidTEG
with Heparinase
(CRTH) Parameter
MA (mm)
Heparinase is
included in the
subject device | RapidTEG™ MA is the point at
which clot strength reaches its
maximum and reflects the end result
of minimal platelet-fibrin interaction
via the GPIIb/IIIa receptors. Due to
faster coagulation activation, clot
strength is measured faster than
Citrated: Kaolin (K) activated
samples. Same results as CK
maximum amplitude (CK-MA).
The MA provides information about
the contribution of platelets/fibrin to
the overall strength of the clot. | RapidTEG MA is the point of
maximal amplitude of the TEG
tracing, measured in mm, and
reflects the maximum clot strength.
The strength of the clot is primarily
a result of platelet-fibrin interactions
via the GPIIb/IIIa receptors. Clinical
Value: The MA provides
information of platelets and
fibrinogen contribution to the overall
clot strength. A decreased MA is
indicative of low clot strength,
which could be due to decreased
platelet or decreased fibrinogen
contribution; whereas an increased
MA is indicative of high clot
strength, which could be due to
increased platelet or fibrinogen
contribution. |
| Clinical Value of
Citrated: Functional
Fibrinogen with
Heparinase (CFFFH)
Parameter MA (mm) | The maximum amplitude of CFF
provides the functional fibrinogen
contribution to the clot strength.
Provides the overall contribution of
functional fibrinogen to clot | The Functional Fibrinogen reagent
inhibits platelet aggregation via the
GPIIb/IIIa receptor, excluding its
contribution to clot strength (MA),
and thereby primarily measures the |
| | strength. In conjunction with CRT- | functional fibrinogen contribution to |
| Heparinase is | MA, this assay enables an | clot strength. |
| included in the | assessment of the relative | Clinical Value: CFFH - MA provides |
| subject device | contributions of functional | the fibrinogen contribution to clot |
| | fibrinogen and platelets to clot | strength by exclusion of platelet |
| | strength. Results may be valuable | aggregation. In conjunction with |
| | for guiding fibrinogen | CRTH-MA, this assay enables the |
| | supplementation or platelet | contributions of fibrin and platelets to |
| | transfusion. | clot strength to be determined. |

12

13

14

HAEMONET

6. Non-Clinical and/or Clinical Tests Summary & Conclusions

Non-Clinical Performance Testing

A. Reference Ranges
Expected values for test results are within the Reference Ranges for a reference population that were established according to CLSI EP28-A3c. Citrated whole blood from normal donors (representative of normal population distributions - age, gender, race) with no known coagulopathies and not taking any drugs that would potentially affect patient hemostasis was used. Non-parametric method for analysis was used to determine the reference range for each assay parameter. The following tables contain the reference range data for each reagent and parameter.

CK Reference Ranges

Citrated Blood Parameter	N	Range
R (min)	157	4.6-9.1
MA (mm)	151	52-69
CKH Reference Ranges
Citrated Blood Parameter	N	Range
R (min)	155	4.3-8.3
LY30 (%)	148	0-3.2
CRTH Reference Ranges
Citrated Blood Parameter	N	Range
MA (mm)	162	53-69
CFFH Reference Ranges
Citrated Blood Parameter	N	Range
MA (mm)	162	15-34

15

HAEMONET

B. Analytical Precision (Repeatability and Reproducibility)
Several studies were performed to support the Precision (Repeatability and Reproducibility) of the Citrated: K, KH, RTH, FFH assay cartridge. Studies performed with Cartridge Reagent QC Level 1 and Level 2 materials included a multi-site reproducibility study and a single-site repeatability study in accordance with the CLSI-EP05 A3 guideline, and a within lab lot to lot precision study. Two additional studies were performed with normal whole blood samples and contrived hypocoagulable, hypercoagulable and hyperfibrinolytic blood samples.

Citrated: K, KH, RTH, FFH Cartridge Reagent QC Precision

Several test protocols were executed as part of Citrated: K, KH, RTH, FFH assay cartridge (PN 07-604-US) performance verification on the TEG® 6s Hemostasis System with Cartridge Reagent QC Level 1 and Level 2 materials:

Each data set includes evaluation of different sources of variation, these were combined to generate an assessment of the Citrated: K, KH, RTH, FFH assay cartridge combined QC precision for a worst case estimate of total precision.

| Study | Multi-site
TR-DIS-102653-C | Cartridge Lot to Lot
TR-DIS-102583-C | Operator to Operator
TR-DIS-102697-C | Repeatability
TR-DIS-102697-C |
|---------------|-------------------------------|-----------------------------------------|-----------------------------------------|----------------------------------|
| Instrument | 3 in combination per
site | 6 confounded with rep | 1 instrument/control I | 1 instrument/control |
| Operator | | 2 operators | 2 operators | 1 operator |
| Day | 5 days | 10 days | 10 days | 20 days |
| Cartridge Lot | 1 lot | 3 lots | 1 lot | 1 lot |
| QC Lot | 1 lot | 2 lots | 1 lot | 1 lot |
| Run | 1 run/day | 1 run/day | 2 runs | 2 runs |
| Rep | 5 reps/control/site | 1 rep | 2 reps/control | 2 reps/control |
| Total N | 75 | 120 | 80 | 80 |
| Study Design | Nested | Crossed | Nested | Nested |

Cartridge Reagent QC Precision Studies - Overview

Results of the QC precision studies demonstrate that Citrated: K, KH, RTH, FFH assay cartridge achieves repeatability, within laboratory, reproducibility and total precision requirements on all reported parameters for Cartridge Reagent OC Level 1 and Cartridge Reagent OC Level 2.

16

HAEMONE'

| Sample | Assay-Parameter | N | Mean | Repeatability | | Between
Run | | Between
Day | | Between
Cartridge
Lot | | Between
QC Lot | | Between Site
Instrument/Operat
or | | Total | | Pass/
Fail |
|---------------------------------------------------|-----------------|------|-------|---------------|------|----------------|------|----------------|------|-----------------------------|------|-------------------|------|-----------------------------------------|------|-------|-------|---------------|
| | | | | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | |
| Cartridge
Reagent
QC Level
1
(07-664) | CK-R (min) | 316 | 6.16 | 0.54 | 8.9% | 0.00 | 0.0% | 0.27 | 4.4% | 0.02 | 0.4% | 0.12 | 2.0% | 0.39 | 6.3% | 0.73 | 11.9% | Pass |
| | CKH-R (min) | 316 | 4.62 | 0.41 | 8.5% | 0.09 | 2.0% | 0.14 | 3.1% | 0.12 | 2.5% | 0.25 | 5.2% | 0.26 | 5.7% | 0.58 | 12.3% | Pass |
| | CK-MA (mm) | 316 | 66.85 | 1.57 | 2.4% | 0.00 | 0.0% | 0.48 | 0.7% | 0.00 | 0.0% | 1.37 | 2.1% | 0.56 | 0.8% | 2.21 | 3.3% | Pass |
| | CRTH-MA (mm) | 316 | 59.36 | 1.81 | 3.0% | 0.00 | 0.0% | 0.95 | 1.6% | 0.00 | 0.0% | 0.00 | 0.0% | 1.76 | 2.9% | 2.70 | 4.5% | Pass |
| | CFFH-MA (mm) | 316 | 63.80 | 1.35 | 2.1% | 0.00 | 0.0% | 1.05 | 1.7% | 0.61 | 1.0% | 0.00 | 0.0% | 2.11 | 3.3% | 2.78 | 4.4% | Pass |
| | CKH LY30 (%) | 196* | 0.00 | 0.00 | n/a | 0.00 | n/a | 0.00 | n/a | 0.00 | n/a | 0.00 | n/a | 0.00 | n/a | 0.00 | n/a | Pass |
| Cartridge
Reagent
QC Level
2
(07-665) | CK-R (min) | 316 | 1.18 | 0.09 | 7.0% | 0.05 | 3.6% | 0.04 | 2.8% | 0.01 | 0.7% | 0.06 | 5.0% | 0.03 | 2.7% | 0.12 | 10.1% | Pass |
| | CKH-R (min) | 316 | 1.18 | 0.09 | 7.2% | 0.02 | 1.5% | 0.03 | 2.4% | 0.00 | 0.0% | 0.07 | 5.7% | 0.03 | 2.8% | 0.12 | 10.0% | Pass |
| | CK-MA (mm) | 313 | 27.64 | 1.51 | 5.4% | 1.01 | 3.7% | 0.84 | 3.1% | 0.23 | 0.8% | 0.72 | 2.6% | 0.51 | 1.8% | 2.20 | 8.0% | Pass |
| | CRTH-MA (mm) | 316 | 29.03 | 1.52 | 5.2% | 0.76 | 2.7% | 0.89 | 3.2% | 0.30 | 1.0% | 0.83 | 2.8% | 0.81 | 2.7% | 2.26 | 7.8% | Pass |
| | CFFH-MA (mm) | 316 | 28.69 | 1.26 | 4.5% | 0.95 | 3.4% | 0.91 | 3.3% | 0.13 | 0.5% | 0.95 | 3.3% | 0.68 | 2.3% | 2.17 | 7.7% | Pass |
| | CKH-Ly30 (%) | 316 | 92.42 | 0.46 | 0.5% | 0.40 | 0.4% | 0.12 | 0.1% | 0.04 | 0.0% | 0.10 | 0.1% | 0.00 | 0.0% | 0.63 | 0.7% | Pass |

CARTRIDGE REAGENT QC PRECISION – SUMMARY OF RESULTS

Citrated: K, KH, RTH, FFH Cartridge Whole Blood Repeatability

Two studies were conducted for Whole Blood Repeatability on the Citrated: K, KH, RTH, FFH assay cartridge. Testing was conducted with normal donor whole blood and contrived hyper-coagulable, hypo-coagulable, and hyper-fibrinolytic whole blood samples. The following table summarizes the sample types evaluated:

| Sample
Type # | Hemostatic State | CK R | CKH R | CK MA | CRTH MA | CFFH MA | CKH
LY30 | Method or Additive for
Contriving* |
|------------------|----------------------------|------|-------|-------|---------|---------|-------------|------------------------------------------|
| 1 | Normal | x | x | x | x | x | x | None |
| 2 | Contrived Hypo-coagulable | x↑ | x↑ | x↓ | x↓ | | | Abciximab and Dabigatran |
| 3 | Contrived Hypo-coagulable | | | | | x↓ | | Dilution and /or Fibrinogen
depletion |
| 4 | Contrived Hyper-coagulable | | | x↑ | x↑ | | | Platelet Rich Plasma and
Fibrinogen |
| 5 | Contrived Hyper-coagulable | | | | | x↑ | | Fibrinogen |

17

6	Contrived Hyper-fibrinolytic				x $ ↑ $	tPA
7	Contrived Hyper-coagulable	x $ ↓ $		x $ ↓ $		Tissue factor

Whole Blood precision testing was conducted at a one (1) location, using two (2) operators, three (3) cartridge lots. For the normal whole blood samples, each operator performed 2 replicates/sample/cartridge lot on each of 2 analyzers for a total N= 12 per operator. For the contrived samples, each operator performed 1 replicate/sample simultaneously on 4 different analyzers/cartridge lot for a total N =12 per operator. Each contrived sample was prepared just prior to execution of testing.

Data collected for each sample was analyzed separately through an ANOVA for precision. Results are summarized in the tables below:

| Sample | Assay Parameter | N | Mean | Repeatability | | Between Operator | | Between Lot | | Between Device/Day | | Within Laboratory
( = Total Precision) | | Pass
/Fail |
|-----------------------------|-----------------|----|-------|---------------|-------|------------------|------|-------------|-------|--------------------|-------|-------------------------------------------|-------|---------------|
| | | | | SD | CV | SD | CV | SD | CV | SD | CV | SD | CV | |
| S1 Normal Donor Whole Blood | CK R (min) | 24 | 7.50 | 0.44 | 5.9% | 0.00 | 0.0% | 0.65 | 8.7% | 0.28 | 3.8% | 0.83 | 11.2% | Pass |
| | CKH R (min) | 24 | 7.60 | 0.75 | 10.0% | 0.00 | 0.0% | 0.00 | 0.0% | 0.14 | 1.8% | 0.77 | 10.1% | Pass |
| | CK MA (mm) | 24 | 54.80 | 0.96 | 1.7% | 0.32 | 0.6% | 0.54 | 1.0% | 0.25 | 0.5% | 1.17 | 2.1% | Pass |
| | CRTH MA (mm) | 24 | 17.00 | 0.27 | 1.6% | 0.46 | 2.7% | 0.09 | 0.6% | 0.60 | 3.5% | 0.81 | 4.8% | Pass |
| | CFFH MA (mm) | 24 | 57.00 | 1.43 | 2.5% | 0.65 | 1.1% | 0.20 | 0.4% | 0.00 | 0.0% | 1.58 | 2.8% | Pass |
| | CKH LY30 (%) | 24 | 0.30 | 0.13 | 51.0% | 0.00 | 0.0% | 0.10 | 36.5% | 0.08 | 32.1% | 0.18 | 70.4% | Pass |

WHOLE BLOOD PRECISION REPEATABILITY SUMMARY - NORMAL SAMPLE

WHOLE BLOOD PRECISION REPEATABILITY SUMMARY - CONTRIVED ABNORMAL SAMPLES

| Sample | Assay
Parameter | N | Mean | Repeatability* | | Between
Operator | | Between Lot | | Within Laboratory
(= Total Precision) | | Pass
/Fail |
|--------------------------------------------------------|--------------------|----|-------|----------------|-------|---------------------|------|-------------|--------------------|-------------------------------------------|--------|---------------|
| | | | | SD | CV | SD | CV | SD | CV | SD | CV | |
| S2
Contrived
Hypo-
Coagulable
(R↑,
MA↓) | CK R (min) | 24 | 13.29 | 1.47 | 11.1% | 0.00 | 0.0% | 0.00 | 0.0% | 1.47 | 11.1% | Pass |
| | CKH R (min) | 24 | 13.09 | 1.52 | 11.6% | 0.61 | 4.6% | 0.39 | 3.0% | 1.68 | 12.8% | Pass |
| | CK MA (mm) | 24 | 52.78 | 1.04 | 2.0% | 0.00 | 0.0% | 0.89 | 1.7% | 1.37 | 2.6% | Pass |
| | CRTH MA (mm) | 24 | 58.55 | 0.51 | 0.9% | 0.00 | 0.0% | 0.35 | 0.69% | 0.62 | 1.1% | Pass |
| | CFFH MA (mm) | 24 | 18.02 | 0.17 | 1.0% | 0.03 | 0.2% | 0.12 | 0.76% | 0.21 | 1.2% | Pass |
| | CKH LY30 (%) | 24 | 1.18 | 0.19 | 16.1% | 0.00 | 0.0% | 0.00 | 0.0% | 0.19 | 16.1% | Pass |
| S3
Contrived | CK R (min) | 24 | 4.91 | 0.31 | 6.3% | 0.03 | 0.7% | 0.12 | 2.4% | 0.33 | 6.8% | Pass |
| Sample | Assay
Parameter | N | Mean | Repeatability* | | Between
Operator | | Between Lot | | Within Laboratory
( = Total Precision) | | Pass
/Fail |
| | | | | SD | CV | SD | CV | SD | CV | SD | CV | |
| Hypo-
Coagulable
(MA↓) | CKH R (min) | 24 | 4.85 | 0.20 | 4.2% | 0.00 | 0.0% | 0.11 | 2.4% | 0.23 | 4.8% | Pass |
| | CK MA (mm) | 24 | 44.71 | 0.69 | 1.6% | 0.49 | 1.1% | 0.39 | 0.9% | 0.94 | 2.1% | Pass |
| | CRTH MA (mm) | 24 | 43.52 | 1.16 | 2.7% | 0.24 | 0.6% | 0.00 | 0.0% | 1.19 | 2.7% | Pass |
| | CFFH MA (mm) | 24 | 10.08 | 0.83 | 8.2% | 0.24 | 2.4% | 0.33 | 3.3% | 0.92 | 9.2% | Pass |
| S4
Contrived
Hyper-
coagulable
(MA↑) | CKH LY30 (%) | | | | | | | | Data not collected | | | |
| | CK R (min) | 23 | 5.47 | 0.61 | 10.7% | 0.37 | 6.5% | 0.05 | 0.8% | 0.71 | 12.5% | Pass |
| | CKH R (min) | 23 | 5.91 | 0.72 | 12.2% | 0.00 | 0.0% | 0.46 | 7.8% | 0.85 | 14.5% | Pass |
| | CK MA (mm) | 23 | 70.96 | 0.35 | 0.5% | 0.27 | 0.4% | 0.27 | 0.4% | 0.51 | 0.7% | Pass |
| | CFFH MA (mm) | 24 | 51.38 | 0.92 | 1.8% | 0.78 | 1.5% | 2.81 | 5.5% | 3.06 | 6.0% | Pass |
| S5
Contrived
Hyper-
coagulable
(MA↑) | CKH LY30 (%) | | | | | | | | Data not collected | | | |
| | CK R (min) | 24 | 6.60 | 0.51 | 7.7% | 0.10 | 1.5% | 0.24 | 3.6% | 0.57 | 8.6% | Pass |
| | CKH R (min) | 24 | 6.28 | 0.66 | 10.6% | 0.00 | 0.0% | 0.24 | 3.8% | 0.71 | 11.2% | Pass |
| | CK MA (mm) | 24 | 63.85 | 0.75 | 1.2% | 0.00 | 0.0% | 0.19 | 0.3% | 0.77 | 1.2% | Pass |
| | CRTH MA (mm) | 24 | 66.59 | 0.26 | 0.4% | 0.00 | 0.0% | 0.13 | 0.2% | 0.29 | 0.4% | Pass |
| | CFFH MA (mm) | 24 | 32.92 | 0.66 | 2.0% | 0.00 | 0.0% | 0.53 | 1.6% | 0.85 | 2.6% | Pass |
| | CKH LY30 (%) | 24 | 0.45 | 0.44 | 97.1% | 0.00 | 0.0% | 0.14 | 31.0% | 0.46 | 101.9% | Pass |
| S6
Contrived
Hyper-
fibrinolytic
(LY30↑) | CK R (min) | 24 | 6.38 | 0.45 | 7.1% | 0.00 | 0.0% | 0.51 | 8.0% | 0.68 | 10.7% | Pass |
| | CKH R (min) | 24 | 6.53 | 0.54 | 8.3% | 0.00 | 0.0% | 0.00 | 0.0% | 0.54 | 8.3% | Pass |
| | CK MA (mm) | 24 | 58.69 | 0.96 | 1.6% | 0.00 | 0.0% | 0.10 | 0.2% | 0.96 | 1.6% | Pass |
| | CRTH MA (mm) | 24 | 61.56 | 0.68 | 1.1% | 0.38 | 0.6% | 0.00 | 0.0% | 0.78 | 1.3% | Pass |
| | CFFH MA (mm) | 24 | 21.70 | 1.01 | 4.6% | 0.28 | 1.3% | 1.25 | 5.7% | 1.63 | 7.5% | Pass |
| | CKH LY30 (%) | 23 | 15.87 | 1.59 | 9.7% | 0.00 | 0.0% | 0.00 | 0.0% | 1.59 | 9.7% | Pass |
| S7
Contrived
Hyper- | CK R (min) | 24 | 4.41 | 0.17 | 3.8% | 0.00 | 0.0% | 0.13 | 2.9% | 0.21 | 4.8% | Pass |
| | CKH R (min) | 24 | 4.31 | 0.19 | 4.3% | 0.00 | 0.0% | 0.08 | 1.9% | 0.20 | 4.7% | Pass |
| Sample | Assay
Parameter | N | Mean | Repeatability* | | Between
Operator | | Between Lot | | Within Laboratory
(= Total Precision) | | Pass
/Fail |
| | | | | SD | CV | SD | CV | SD | CV | SD | CV | |
| Coagulable
(R↓) | CK MA (mm) | 24 | 64.38 | 0.44 | 0.7% | 0.11 | 0.2% | 0.28 | 0.4% | 0.54 | 0.8% | Pass |
| | CRTH MA (mm) | 24 | 65.65 | 0.40 | 0.6% | 0.16 | 0.2% | 0.00 | 0.0% | 0.43 | 0.6% | Pass |
| | CFFH MA (mm) | 24 | 25.18 | 0.43 | 1.7% | 0.17 | 0.7% | 0.52 | 2.1% | 0.69 | 2.7% | Pass |
| | CKH LY30 (%) | 24 | 0.67 | 0.15 | 23.1% | 0.03 | 4.2% | 0.13 | 20.0% | 0.21 | 30.8% | Pass |

18

19

HAEMONET

Repeatability for contrived abnormal samples includes analyzer variation

Summarized Precision for each channel is as follows:

CK Precision

The precision of the Kaolin test was evaluated according to CLSI EP5-A3. Precision testing was performed with Cartridge Reagent QC Level 1 and Level 2, normal and contrived hyper-coagulable, hypo-coagulable, and hyper-fibrinolytic whole blood samples using multiple donors, cartridge lots, operators and analyzers. Results included Coefficient of Variance (CV) values for all precision tests. The CV of the test results for the Kaolin assay was less than 15% for the R parameter and less than 10% for the MA parameter.

CKH Precision

The precision of the Kaolin with heparinase test was evaluated according to CLSI EPS-A3. Precision testing was performed with Cartridge Reagent QC Level 1 and Level 2, normal and contrived hyper-coagulable, hypo-coagulable, and hyper-fibrinolytic whole blood samples using multiple donors, cartridge lots, operators and analyzers. Results included Coefficient of Variance (CV) values for all precision tests. The CV of the test results for the Kaolin with heparinase assay was less than 15% for the R parameter.

CRTH Precision

The precision of the RapidTEG with heparinase test was evaluated according to CLSI EP5-A3. Precision testing was performed with Cartridge Reagent QC Level 1 and Level 2, normal and contrived hyper-coagulable, hypo-coagulable, and hyper-fibrinolytic whole blood samples using multiple donors, cartridge lots, operators and analyzers. Results included Coefficient of Variance (CV) values for all precision tests. The CV of the test results for the RapidTEG with heparinase assay was less than 10% for the MA parameter.

20

CFFH Precision

The precision of the Functional Fibrinogen test with heparinase was evaluated according to CLSI EP5-A3. Precision testing was performed with Cartridge Reagent QC Level 1 and Level 2, normal and contrived hyper-coagulable, hypo-coagulable, and hyperfibrinolytic whole blood samples using multiple donors, cartridge lots, operators and analyzers. Results included Coefficient of Variance (CV) values for all precision tests. The CV of the test results for the Functional Fibrinogen with heparinase assay was less than 15% for the MA parameter.

C. Interference

Testing for interfering factors was conducted according to CLSI EP07-A3 using whole blood from normal donor, contrived hyperfibrinolytic, and contrived hypocoagulable specimens. Potential interferents and levels tested are indicated in the following table:

| Interfering
Factors

(levels)	Specimen Type	Highest Concentration with No Interference
		CK - R	CK - MA	CKH - R	CKH -
LY30	CRTH -
MA	CFFH -
MA
No Discard
Tube	Normal	NI	NI	NI	NI	NI	NI
	Hypocoagulable	NI	NI	NI	NI	NI	NI
	Hyperfibrinolytic	NI	NI	NI	Yes	NI	NI
Hemolysis (0,
50, 100,
200, 400
mg/dL)	Normal	400	400	400	200	400	400
	Hypocoagulable	400	400	400	400	400	400
	Hyperfibrinolytic	400	400	200	0	100	400
Short Draw (%
fill in a 3.2%
sodium citrate
Vacutainer®
tube: 100, 90,
80, 70 and
60% )	Normal	60% Fill	60% Fill	60% Fill	60% Fill	70% Fill	60% Fill
	Hypocoagulable	60% Fill	60% Fill	70% Fill	60% Fill	60% Fill	60% Fill
	Hyperfibrinolytic	60% Fill	60% Fill	60% Fill	70% Fill	60% Fill	60% Fill
Dilution
(0%, 20%,
30%, 40%,
50%)	Normal	50%	20%	50%	50%	20%	40%
	Hypocoagulable	50%	0%	50%	50%	0%	40%
	Hyperfibrinolytic	50%	0%	50%	0%	0%	20%
Dabigatran
(0, 45, 90,
135, 180 ng/
mL)	Normal	0	180	0	90	180	180
	Hypocoagulable	NT	NT	NT	NT	NT	NT
	Hyperfibrinolytic	0	90	0	0	180	180
Rivaroxaban
(0, 50, 100,
200, 400 ng/
mL)	Normal	50	400	50	400	400	400
	Hypocoagulable	NT	NT	NT	NT	NT	NT
	Hyperfibrinolytic	50	200	50	400	400	400
Aspirin	Normal	6.5	6.5	6.5	6.5	6.5	6.5
Interfering
Factors
(levels)	Specimen Type	Highest Concentration with No Interference
		CK - R	CK - MA	CKH - R	CKH -
LY30	CRTH -
MA	CFFH -
MA
(0, 6.5 mg/
dL)	Hypocoagulable	NT	NT	NT	NT	NT	NT
	Hyperfibrinolytic	6.5	6.5	6.5	0	6.5	6.5
Ticagrelor
(0, 1.8 ug/
mL)	Normal	1.8	1.8	1.8	1.8	1.8	1.8
	Hypocoagulable	NT	NT	NT	NT	NT	NT
	Hyperfibrinolytic	1.8	1.8	1.8	1.8	1.8	1.8
Alcohol (0,
40, 80,
160, 320
mg/dL)	Normal	320	320	320	320	320	320
	Hypocoagulable	320	320	320	320	320	320
	Hyperfibrinolytic	320	320	320	320	320	320
Lipemia
(0, 150, 300,
450, 600
mg/dL)	Normal	600	600	600	600	600	600
	Hypocoagulable	600	600	600	600	600	600
	Hyperfibrinolytic	600	600	600	600	600	600
TXA
(0, 100, 200
ug/mL)	Normal	200	200	200	200	200	200
	Hypocoagulable	200	200	200	200	200	200
	Hyperfibrinolytic	NT	NT	NT	NT	NT	NT
EACA
(0, 300, 600
ug/mL)	Normal	600	600	600	600	600	600
	Hypocoagulable	600	600	600	600	600	600
	Hyperfibrinolytic	NT	NT	NT	NT	NT	NT
Mycophenolic
Acid (21, 42
ug/mL) (5, 10,
21, 42 (ug/mL))	Normal	42	42	42	42	42	42
	Hypocoagulable	42	42	42	42	42	42
	Hyperfibrinolytic	42	42	42	42	42	42
Tacrolimus (70,
144 ng/mL)	Normal	144	144	144	144	144	144
	Hypocoagulable	144	144	144	144	144	144
	Hyperfibrinolytic	144	144	144	144	144	144
Prednisone (45,
99 ng/mL)	Normal	99	99	99	99	99	99
	Hypocoagulable	99	99	99	99	99	99
	Hyperfibrinolytic	99	99	99	99	99	99
Rifaximin (20,
40.5 ng/mL) (5,
10, 20, 40.5
ng/mL)	Normal	40.5	40.5	40.5	40.5	40.5	40.5
	Hypocoagulable	40.5	40.5	40.5	40.5	40.5	40.5
	Hyperfibrinolytic	40.5	40.5	40.5	40.5	40.5	40.5
Lactulose
(6, 12 ug/mL)	Normal	12	12	12	12	12	12
	Hypocoagulable	12	12	12	12	12	12
	Hyperfibrinolytic	12	12	12	12	12	12

21

Legend:

NI - No Interference
NT - Not Tested

NT - Not Tested

22

D. Measurement Interpretation Guidance

The measurement interpretation guidance table that follows is based on in vitro studies that examined individual values of assays and parameters with respect to their reference ranges. Only one or a few variables influencing TEG results were systematically varied while other variables were kept constant.

The measurement interpretation guidance table is not intended to be comprehensive of all variables that could influence test results, but addresses key variables based on literature review and clinical experience. As with any hemostasis test, TEG® 6s test results should not be the sole basis for a patient diagnosis, but should be evaluated together with the patient's medical history, the clinical picture and, if necessary, further hemostasis tests.

| Assay | Parameter
(Units) | Ref Range
(RR) | Parameter
Readout | Hemostatic
Significance
of Individual
Parameter | Interpretation of
Parameter Readout for
Consideration |
|-------|----------------------|-------------------|----------------------|----------------------------------------------------------|---------------------------------------------------------------------------------------------------------|
| CK | R (min) | 4.6 - 9.1 | CK-R > RR | Hypocoagulable | ↓Coagulation factor
activity and/or
presence of heparin
at sufficiently high
concentrations |
| | | | CK-R RR | Hypercoagulable | ↑Fibrinogen or
↑Platelet Contribution |
| CKH | R (min) | 4.3 - 8.3 | CK-R > CKH-R | Heparin Effect | Indicative of heparin
effect |
| | | | CKH-R > RR | Hypocoagulable | ↓Coagulation
factor activity and/
or presence of non-
heparin anticoagulants |
| | LY30 (%) | 0 - 3.2 | CKH-LY30 > RR | Hypocoagulable | Hyperfibrinolysis |
| CRTH | MA (mm) | 53 - 69 | CRTH-MA RR | Hypercoagulable | ↑Fibrinogen or
↑Platelet Contribution |
| CFFH | MA (mm) | 15 - 34 | CFFH-MA RR | Hypercoagulable | ↑Fibrinogen |

Citrated Kaolin (CK)

The Citrated Kaolin TEG assay uses kaolin for activation of coagulation. Kaolin activation has traditionally been described as intrinsic pathway activation.

23

CK - R

Kaolin R is the time in minutes elapsing between sample activation and the point in time where clotting provides enough resistance to produce a 2 mm amplitude reading on the TEG® 6s analyzer tracing. The CK - R parameter represents the initiation phase of coagulation triggered by enzymatic clotting factors and culminating with the initial fibrin formation. A prolonged R value is indicative of slow clot formation, and a shortened R value is indicative of fast clot formation.

Clinical Value: A prolonged R value is indicative of slow clot formation, due to coagulation factor deficiencies, heparin, or other anticoagulants.

CK-MA

The maximal strength of the clot when activated with kaolin. This represents the combination of the contribution of fibrinogen and platelets to clot strength.

Clinical Value: The MA provides information of platelets and fibrinogen to the overall clot strength without excluding the influence of heparin. A decreased MA is indicative of low clot strength, which could be due to decreased platelet contribution or decreased fibrinogen; whereas, an increased MA is indicative of high clot strength, which could be due to increased platelet or fibrinogen contribution.

Citrated Kaolin with Heparinase (CKH)

CKH - R

The reaction time between initiation of the clot (via kaolin) and the point where the tracing reaches 2 mm of amplitude, with heparinase being used to neutralize the effect of heparin.

Clinical Value: A prolonged R value is indicative of slow clot formation, due to coagulation factor deficiencies or non-heparin anticoagulant. A shortening of the CKH-R compared to the CK-R indicates effect of heparin in the blood sample.

CKH - LY30

Clot lysis, in a sample with heparinase to neutralize effects of heparin, expressed as a percent reduction in clot strength 30 minutes after the MA is reached.

Clinical Value: LY30 provides information about fibrinolytic activity.

Citrated RapidTEGTM with Heparinase (CRTH)

The RapidTEG assay incorporates both tissue factor and kaolin, which simultaneously activate the extrinsic and intrinsic coagulation pathways. The assay accelerates coagulation compared to the conventional Kaolin test. Heparinase is added to neutralize heparin in the sample.

24

CRTH - MA

RapidTEG MA is the point of maximal amplitude of the TEG tracing, measured in mm, and reflects the maximum clot strength. The strength of the clot is primarily a result of platelet-fibrin interactions via the GPIIb/IIIa receptors.

Clinical Value: The MA provides information of platelets and fibrinogen to the overall clot strength. A decreased MA is indicative of low clot strength, which could be due to decreased platelet contribution or decreased fibrinogen; whereas, an increased MA is indicative of high clot strength, which could be due to increased platelet or fibrinogen contribution.

Citrated Functional Fibrinogen with Heparinase (CFFH)

The Citrated Functional Fibrinogen assay activates the extrinsic pathway using tissue factor and inhibits platelet aggregation using a platelet inhibitor that binds to GPIIb/IIIa receptors. Heparinase is added to neutralize heparin in the sample.

CFFH - MA

The Functional Fibrinogen reagent inhibits platelet aggregation via the GPIIb/IIIa receptor, excluding its contribution to clot strength (MA), and thereby primarily measures the functional fibrinogen contribution to clot strength.

Clinical Value: CFFH - MA provides the fibrinogen contribution to clot strength by exclusion of platelet aggregation. In conjunction with CRTH-MA, this assay enables the contributions of fibrin and platelets to clot strength to be determined.

E. CK Sensitivity and Specificity
Two studies were performed to define the sensitivity and specificity for the CK channel. Blood samples were collected from four normal donors and from four donors (four unique donors for each condition) and contrived to simulate hypocoagulable, hypercoagulable and hyperfibrinolytic conditions. Final heparin concentration in tested samples were 0, 0.1, 0.15 and 0.2 IU.

For Normal donors, a 95% specificity in samples without heparin and a 95% sensitivity for detection of heparin at 0.2 IU/ml was calculated using blood samples from four donors. All contrived hypo-coagulable, hyper-coagulable and hyper-fibrinolytic samples without heparin showed 100% specificity and all samples spiked at 0.2 IU/ml showed 100% sensitivity for the detection of heparin. A summary of cumulative results is shown in the table below.

25

HAEMONET

Cumulative Results (total N=20, 4 Donors/condition evaluated)
Sample Condition	Heparin Concentration
(IU/mL)	Sensitivity %	Specificity %
Normal	0	N/A	95 %
	0.1	95%	N/A
	0.15	100 %	N/A
	0.2	95%	N/A
Contrived
Hypo-coagulable	0	N/A	100 %
	0.1	100 %	N/A
	0.15	100 %	N/A
	0.2	100 %	N/A
Contrived
Hyper-coagulable	0	N/A	100 %
	0.1	100 %	N/A
	0.15	100 %	N/A
	0.2	100 %	N/A
Contrived
Hyper-fibrinolytic	0	N/A	100 %
	0.1	95%	N/A
	0.15	100 %	N/A
	0.2	100 %	N/A

F. Assay Measuring Range

The Assay Measuring Range (AMR) study was performed to establish the analytical measurement ranges for MA (CRTH and CFFH channels) and LY30 (CKH channel) for the Citrated: K, KH, RTH, FFH assay cartridge and to demonstrate verification of required %CV for each parameter. The high and low boundaries of AMR values for MA and LY30 obtained from the study are as follows:

| Parameter | Lower
AMR | Calculated
CV (%) | Upper
AMR | Calculated
CV (%) |
|-----------|--------------|----------------------|--------------|----------------------|
| CRTH-MA | 20 | 2.8 | 78 | 0.9 |
| CFFH-MA | 6 | 8.7 | 61 | 1.4 |
| CKH-LY30 | 0 | 0 | 30 | 5.1 |

As there are no changes in assay composition and formulation of CK and CKH channels in the Citrated: K, KH, RTH, FFH assay cartridge compared to existing channels in the Citrated Multichannel Cartridge (CM), previously established AMR values for CK-R (lower AMR of 0.4 and upper AMR of 17), CK-MA (lower AMR of 40 and upper AMR of 70) and CKH-R (lower AMR of 0.3 and upper AMR of 17) parameters, will also be used for the Citrated: K, KH, RTH, FFH assay cartridge.

26

The Assay Measuring Range values available from the TEG 6s with the Citrated Multichannel Cartridge (K150041, 07-601-US) are being retained for the Citrated: K, KH, RTH, FFH assay cartridge.

| Parameter | Lower
AMR | Upper
AMR |
|-----------|--------------|--------------|
| CK-R | 0.4 | 17 |
| CK-MA | 40 | 75 |
| CKH-R | 0.3 | 17 |

G. Heparin Neutralization Requirement Verification

The use of heparinase neutralizes the effect of heparin in the blood sample. Tests were performed using Unfractionated Heparin (UFH) and Low Molecular Weight Heparin (LMWH) spiked samples and un-spiked samples. All tests reported R parameter values within the normal range, confirming the neutralization effectiveness of the assay. Functional performance of the cartridges were verified against heparin neutralization requirements. A total of 200 cartridges were tested across four donors, and 10 replicates.

The mean result per test specimen condition fell within the respective normal reference range for CRTH-MA, CFFH-MA, CKH-R, and CKH-LY30 for all donors. The study acceptance criteria were met and has verified the defined heparin neutralization performance requirements:

| Requirement Description | Acceptance
Criteria Pass/Fail |
|------------------------------------------------------------------------------------------------------------------|----------------------------------|
| The CKH, CRTH, and CFFH assays shall be able to neutralize
up to 5.0 IU/mL (+/- 0.1IU/mL) of heparin. (CTQ) | Pass |
| The CKH, CRTH, and CFFH assays shall be able to neutralize
up to 0.013 mg/mL (+/- 0.001 mg/mL) of LMWH. (CTQ) | Pass |

The tolerance interval (95% confidence for 90% of the population) calculated for CFFH-MA, and CRTH-MA for all specimen types fell within the respective normal reference range. The study acceptance criteria were met and has verified the following heparin neutralization performance requirements:

| Requirement Description | Acceptance
Criteria Pass/Fail |
|--------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------|
| Blood treated with 5.0 IU/ml (+/- 0.1IU/mL) of heparin,
measured CFFH MA, shall remain within the normal reference
range, 90% of the time. (CTQ) | Pass |

27

| Blood treated with 5.0 IU/ml (+/- 0.1IU/mL), measured CRTH
MA, shall remain within the normal reference range, 90% of
the time.

(CTQ)	Pass
------------------------------------------------------------------------------------------------------------------------------------------------	------

For all 0.008 mg/mL LMWH contrived samples, the CK-R value was greater than the CKH-R value. The study acceptance criteria were met and has verified the following heparin neutralization performance requirement for the LMWH sample condition:

| Requirement Description | Acceptance
Criteria Pass/Fail |
|----------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------|
| CK R shall be greater than CKH R when at least 0.2 IU/mL of
heparin or at least 0.008 mg/mL LMWH is present in the blood
sample. (CTQ) | Pass |

Clinical Performance Testing

Clinical Performance - Method Comparison

A Method Comparison study was conducted with patient samples collected at eight clinical trial sites, following CLSI EP09-A3 guidelines. The subjects enrolled were patients undergoing liver transplantation, cardiovascular surgery, or cardiology procedures. Blood samples were drawn before, during, and after the procedures and were analyzed using TEG® 6s analyzers with the Citrated: K, KH, RTH, FFH (Global Hemostasis - HN) cartridge, as well as the TEG 6s with the associated Cartridge (Citrated Multichannel Cartridge) and Clauss Fibrinogen as the comparators. Summary statistics are presented below.

| Assay
Parameter | N of
Samples | Intercept
[95% CI] | Slope
[95% CI] | Pearson Corr.
[95% CI] | Spearman
Corr.
[95% CI] |
|--------------------|-----------------|---------------------------|------------------------|---------------------------|-------------------------------|
| CK - R | 617 | -0.45
[-0.769; -0.125] | 1.08
[1.041; 1.126] | 0.90
[0.878; 0.910] | -- |
| CK - MA | 539 | -3.43
[-5.127; -1.731] | 1.05
[1.022; 1.082] | 0.95
[0.939; 0.956] | -- |
| CKH - R | 829 | -0.17
[-0.538; 0.193] | 1.01
[0.960; 1.055] | 0.82
[0.800; 0.844] | -- |
| CKH - LY30 | 828 | -0.01
[-0.095; 0.071] | 1.00
[0.988; 1.010] | 0.99
[0.985; 0.989] | -- |
| CRTH - MA | 870 | -5.54
[-6.626; -4.459] | 1.11
[1.094; 1.133] | 0.97
[0.962; 0.971] | -- |
| CFFH - MA * | 883 | -78.71
[-98.9; -58.53] | 1.32
[1.25; 1.40] | -- | 0.79
[0.757; 0.814] |

*Clauss Fibrinogen comparator

28

HAEMON

Three assessment types were assigned due to the differing comparisons that were to be made for the parameters of the assays in the Citrated: K, KH, RTH, FFH assay cartridge.

| Assessment Type | Citrated: K, KH, RTH,
FFH Parameters | Predicate/Comparative Device
Description |
|-----------------|-----------------------------------------|----------------------------------------------------------------------------------------------------------------|
| 1 | CK-R
CK-MA
CKH-R
CKH-LY30 | The parameters in the predicate are
identical with the Citrated: K, KH, RTH,
FFH assay cartridge |
| 2 | CRTH-MA | The CKH-MA on the predicate device is an
equivalent channel |
| 3 | CFFH-MA | Clauss fibrinogen plasma concentration
allows comparison of contribution of
fibrinogen to clot formation |

The assessment of equivalency between the CK, CKH, CRTH, and CFFH channels on the cartridge with its comparators was primarily based on the assessment of the bias at the medical decision points relative to the acceptable limits of the bias and the analysis of the relationship between the device parameters and their respective comparators.

For each parameter of Type 1 and Type 2, the predicted bias estimates at the lower and upper limits of the normal reference range (NRR) were within the acceptable bias limits. The entire confidence intervals for the predicted biases of all parameters were contained within the acceptable bias limits at the lower and upper limits of the NRR for all parameters, passing and exceeding pre-established bias acceptance criteria at the medical decision points and indicating excellent agreement. In summary, for all parameters, the assessment of the predicted bias and its 95% confidence interval relative to the preestablished bias acceptance criteria at the medical decision points suggested equivalence according to the CLSI EP09-A3.

The linear regression slope estimates, for all primary between-device comparisons of Type 1 and 2 parameters, were close to 1.0 with their respective 95% confidence intervals containing 1.0 with Pearson correlation coefficients greater than 0.82 in all cases. Slope estimates for the primary parameters (CKH-R, CKH-LY30, CRTH-MA) ranged from 1.00 to 1.11. The origin was contained in the 95% confidence interval of the intercept for each of the Type 1 and Type 2 parameters.

Type 3 parameters were defined as parameters that measure a different physical property,

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i.e., the maximum amplitude on the CFFH channel (CFFH-MA) than the comparator, the Clauss fibrinogen plasma concentration. However, the two parameters were expected to convey similar information, i.e., the contribution of fibrinogen to clot formation. There was no expectation of a perfect linear relationship between the two parameters as viscoelastic testing measures the functionality of large parts of the coagulation cascade and not an individual analyte, i.e., fibrinogen. Regression analysis for the Type 3 parameter, CFFH-MA on the Citrated: K, KH, RTH, FFH assay cartridge, with its comparator, Clauss fibrinogen plasma concentration, yielded a Spearman correlation coefficient of 0.79 [0.757; 0.814] .

Secondary within-device comparison analysis confirmed that the entire confidence intervals for the predicted biases of all parameters were contained within the acceptable bias limits at the lower and upper limits of the NRR for all parameters, passing and exceeding pre-established bias acceptance criteria at the medical decision points and indicating excellent reproducibility.

Repeatability for all parameters (i.e., Replicate 2 vs. Replicate 1, measured with two Citrated: K, KH, RTH, FFH cartridges) resulted in Pearson linear correlation coefficients that were above 0.88 for all parameters. Another important outcome of the study was that the new heparinase-containing parameters CRTH-MA and CFFH-MA yielded over 90% of samples contributing to the final data set at each of the three time points, irrespective of whether heparin was typically present at theses time points or not and similar to the percentage of samples contributing in the CKH-channels. This high number of contributing samples suggests that the incidence of heparin-induced data quality issues was reduced in these channels versus non-heparinase containing channels, suggesting the feasibility of coagulation assessment under conditions of the presence of heparin and/or its reversal agents.

Method comparison data supports the equivalency of the Citrated: K, KH, RTH, FFH assay cartridge parameters and their respective comparators. Within-device replicability was excellent in each case. The data suggests that the feasibility of obtaining diagnostic information with the novel CRTH-MA and CFFH-MA parameters enables the measurement of these parameters in the presence of heparin and/or its reversal agents.

7. Electrical safety and electromagnetic compatibility (EMC)

Electrical safety and EMC testing were conducted on the TEG® 6s hemostasis analyzer. The system complies with the IEC 61010-1, IEC 61010-2-010, IEC 61010-2-101, standards for safety and the IEC 60601-1-2, IEC/ EN61326-1, IEC/ EN61326-2-6, standards for EMC.

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8. Software Verification and Validation Testing

Software verification and validation testing were conducted and documentation was provided as recommended by FDA's Guidance for Industry and FDA Staff, "Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices." The software for this device was considered as a "moderate" level of concern since there is no direct patient contact, any possible injury to a patient is indirect.

9. Conclusions drawn from Performance Testing

The performance data and information provided in this submission support a substantial equivalence determination for the TEG® 6s Hemostasis System assay cartridges Citrated: K, KH, RTH, FFH and the predicate device K150041 TEG 6s with the Citrated Multichannel Cartridge.

10. Location of Studies

All studies were performed in the United States.

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