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.

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.

AI/ML Overview

The provided text describes the acceptance criteria and study proving that the "Citrated: K, KH, RTH, FFH" assay cartridge for the TEG 6s Hemostasis System meets these criteria.

Here's a breakdown of the requested information:

1. A table of acceptance criteria and the reported device performance

Acceptance Criteria Category	Specific Criteria	Reported Device Performance	Pass/Fail
Reference Ranges	Expected values within established Reference Ranges (CLSI EP28-A3c) for a normal population.	CK-R (min): 4.6-9.1 (N=157) CK-MA (mm): 52-69 (N=151) CKH-R (min): 4.3-8.3 (N=155) CKH-LY30 (%): 0-3.2 (N=148) CRTH-MA (mm): 53-69 (N=162) CFFH-MA (mm): 15-34 (N=162)	Pass
Analytical Precision (Repeatability and Reproducibility)	CV for all precision tests: - CK-R: < 15% - CK-MA: < 10% - CKH-R: < 15% - CRTH-MA: < 10% - CFFH-MA: < 15%	QC Level 1 & 2: All reported precision (Repeatability, Between Run, Between Day, Between Cartridge Lot, Between QC Lot, Between Site Instrument/Operator, Total) CVs were within the acceptance criteria for all parameters. E.g., Total CV for CK-R (QC Level 1) was 11.9%, CK-MA (QC Level 1) 3.3%, CKH-R (QC Level 1) 12.3%, CRTH-MA (QC Level 1) 4.5%, CFFH-MA (QC Level 1) 4.4%. Whole Blood Repeatability (Normal Samples): All Within Laboratory (= Total Precision) CVs were within acceptance criteria. E.g., CK-R 11.2%, CK-MA 2.1%, CKH-R 10.1%, CRTH-MA 4.8%, CFFH-MA 2.8%. Whole Blood Repeatability (Contrived Abnormal Samples): All Within Laboratory (= Total Precision) CVs were within acceptance criteria for pertinent parameters and samples. E.g., S2 Contrived Hypo-Coagulable: CK-R 11.1%, CKH-R 12.8%, CK-MA 2.6%, CRTH-MA 1.1%, CFFH-MA 1.2%.	Pass
Heparin Neutralization Requirement (Specific for CKH, CRTH, CFFH)	1. Neutralize up to 5.0 IU/mL (+/- 0.1 IU/mL) of heparin. 2. Neutralize up to 0.013 mg/mL (+/- 0.001 mg/mL) of LMWH. 3. Blood treated with 5.0 IU/mL (+/- 0.1 IU/mL) heparin, measured CFFH MA, shall remain within the normal reference range, 90% of the time. 4. Blood treated with 5.0 IU/mL (+/- 0.1 IU/mL) heparin, measured CRTH MA, shall remain within the normal reference range, 90% of the time. 5. 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.	1. The mean result per test specimen condition fell within the respective normal reference range for CKH-R, CRTH-MA, and CFFH-MA for all donors. 2. The mean result per test specimen condition fell within the respective normal reference range for CKH-R, CRTH-MA, and CFFH-MA for all donors. 3. The tolerance interval (95% confidence for 90% of the population) calculated for CFFH-MA for all specimen types fell within the respective normal reference range. 4. The tolerance interval (95% confidence for 90% of the population) calculated for CRTH-MA for all specimen types fell within the respective normal reference range. 5. For all 0.008 mg/mL LMWH contrived samples, the CK-R value was greater than the CKH-R value.	Pass
Method Comparison (Clinical Performance)	Comparability with predicate or comparative device based on: - Bias estimates at decision points within acceptable limits. - Linear regression slope estimates close to 1.0 with 95% CI containing 1.0. - High Pearson correlation coefficients (for Type 1 & 2). - Spearman correlation coefficient demonstrating similar information conveyance (for Type 3).	Type 1 & 2 Parameters (CK-R, CK-MA, CKH-R, CKH-LY30, CRTH-MA): - Predicted bias estimates at lower and upper limits of NRR were within acceptable bias limits. - Entire confidence intervals for predicted biases were within acceptable bias limits. - Linear regression slope estimates ranged from 1.00 to 1.11, with 95% CI containing 1.0. - Pearson correlation coefficients > 0.82 (CK-R: 0.90, CK-MA: 0.95, CKH-R: 0.82, CKH-LY30: 0.99, CRTH-MA: 0.97). Type 3 Parameter (CFFH-MA vs. Clauss Fibrinogen): - Spearman correlation coefficient: 0.79 (95% CI: 0.757; 0.814).	Pass
Electrical Safety & EMC	Compliance with IEC 61010-1, IEC 61010-2-010, IEC 61010-2-101 for safety; and IEC 60601-1-2, IEC/EN61326-1, IEC/EN61326-2-6 for EMC.	"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."	Pass
Software Verification & Validation	Documentation as recommended by FDA guidance for "moderate" level of concern.	"Software verification and validation testing were conducted and documentation was provided as recommended by FDA's Guidance..."	Pass

2. Sample sized used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

Sample Sizes (Clinical Performance - Method Comparison):
- CK-R: 617 samples
- CK-MA: 539 samples
- CKH-R: 829 samples
- CKH-LY30: 828 samples
- CRTH-MA: 870 samples
- CFFH-MA: 883 samples
Data Provenance:
- Country of Origin: United States ("All studies were performed in the United States.")
- Retrospective or Prospective: Prospective clinical trials (indicated by "patients undergoing liver transplantation, cardiovascular surgery, or cardiology procedures. Blood samples were drawn before, during, and after the procedures"). These samples were collected at eight clinical trial sites.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

This information is not provided in the document. The comparability study uses predicate devices (TEG 6s with Citrated Multichannel Cartridge and Clauss Fibrinogen) as comparators, not expert consensus on ground truth conditions.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

This information is not provided in the document. The study uses comparison to predicate devices/methods rather than a ground truth established by an adjudication process.

5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

Was an MRMC study done? No.
Effect size of human readers improvement with/without AI: Not applicable, as this is an in-vitro diagnostic device for blood hemostasis properties, not an AI-assisted diagnostic tool for human readers interpreting images or data.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

Yes, the device operates in a standalone manner, providing semi-quantitative results for blood hemostasis properties. The clinical performance testing is a method comparison study, where the device's results are compared to those of predicate devices/established methods, without explicit human interpretation as part of the primary performance metric. The results are numerical values and graphs. The device's output is "not 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," indicating that a human interprets the device's standalone results, rather than the human being part of the measurement process itself.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

The ground truth for the clinical performance study (method comparison) was primarily based on:

Comparison to legally marketed predicate devices (TEG 6s with the Citrated Multichannel Cartridge) for most parameters (CK-R, CK-MA, CKH-R, CKH-LY30, CRTH-MA using CKH-MA from the predicate as an equivalent channel).
Comparison to Clauss Fibrinogen plasma concentration for CFFH-MA, as an established method for measuring fibrinogen contribution to clot formation.

8. The sample size for the training set

This information is not explicitly provided as a "training set" in the context of machine learning. However, reference ranges were established using 148-162 samples from "normal donors" (see section 14.A. Reference Ranges), and various precision studies involved hundreds of measurements using QC materials and normal/contrived whole blood samples. This constitutes data used for establishing operational parameters and validating performance characteristics, which is analogous to a training or development set for IVDs.

9. How the ground truth for the training set was established

For the establishment of reference ranges, "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." A non-parametric method for analysis was used to determine the reference range for each assay parameter. For precision studies, QC materials with known values and contrived blood samples simulating various hemostatic states (hypo-coagulable, hyper-coagulable, hyper-fibrinolytic) were used. The "ground truth" for these samples refers to their classification as normal or contrived states and the expected behavior based on the additives.

Summary

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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 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 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).

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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CONTINUE ON A SEPARATE PAGE IF NEEDED.

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510(k) Summary

Submitter:	Haemonetics Corporation125 Summer StreetBoston MA 02110 United States
Contact:	Julie BergemanSenior Regulatory Affairs Specialist262-693-8368jbergeman@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

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TEG® 6s Measurement Technique

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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.

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® 6sParameter	Definition	Parameter Relation toHemostasis
	R	R is the time from the start of the test until initialfibrin formation. This represents the enzymaticportion of coagulation.
MA	MA, or Maximum Amplitude, represents themaximum firmness of the clot during the test.	Normal / reduced / increasedclot elasticity/strength
LY30	LY30 is a measurement of the rate of fibrinolysis30 minutes after MA is reached. The LY30measurement is based on the reduction of thetracing area that occurs between the time that MA is measured until 30 minutes after the MA is	Normal / reduced clotstability; clot dissolution

Table 1. TEG® 6s parameter definitions

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defined.
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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

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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

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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.

For professional use only.

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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 CitratedMultichannel Cartridge (Predicate)Analyzer	Citrated: K, KH, RTH, FFH
TechnologicalPurpose	Monitoring the physical response ofa clot to low levels of applied strain(resonance frequency)	Same
Measurement	Changes in physical clot elasticityover time	Same
Matrix	3.2% citrated whole blood	Same
Initial Warm UpTime	5 minutes	Same

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

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Item	K150041 TEG 6s with the CitratedMultichannel Cartridge (Predicate)	Citrated: K, KH, RTH, FFH
Analyzer-Hardware	Fully integratedThromboelastography analyzer	Same
	Analyzer-MeasuringTechnique	Non-contact optical measurement ofshear elasticity of a coagulatingsample	Same
Measurement Output		Graphical tracings of resonantfrequency per reagent type; table ofparameters	Same
	Assay and Reagents
	Assays	CK, CKH, CRT, CFF	CK, CKH, CRTH, CFFHSame with inclusion of heparinasefor the CRT and CFF channels
Assay Reagents	CK – kaolin and CaCl2CKH – kaolin and CaCl2 withheparinaseCRT – tissue factor, kaolin andCaCl2CFF – abciximab, tissue factor andCaCl2	Same with inclusion of heparinasefor the CRT and CFF channels
Assay ParametersReported	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 1Cartridge 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 CitratedMultichannel Cartridge (Predicate)	Citrated: K, KH, RTH, FFH
Use Location	N/A	The TEG® 6s Hemostasis Systemwith Citrated: K, KH, RTH, FFHassay cartridge can be used in thelaboratory or at the point-of-care.
Patient Populationfrom Intended Use	Hemostasis evaluations arecommonly used to assess clinicalconditions in cardiovascular surgeryand cardiology procedures to assesshemorrhage or thrombosis	The Citrated: K, KH, RTH, FFHassay cartridge is intended to beused in patients whereheparin/heparinoids may be presentand who are at an increased risk ofcoagulopathy. Hemostasis
	conditions before, during and	evaluations are indicated to assess
	following the procedure.	clinical conditions in cardiovascularsurgery, cardiovascular procedures(e.g. minimally invasive valvereplacement or repairs) and livertransplantation to assess hemorrhageor thrombosis conditions before,during and following the procedure.
Clinical Value Comparisons
Clinical Value ofCitrated: Kaolin(CK)Parameter R (min)	Initiation phase of coagulationtriggered by enzymatic clottingfactors and culminating with theinitial fibrin formation. A prolongedR value is indicative of slow clotformation, due to coagulation factordeficiencies or heparin.	Kaolin R is the time in minuteselapsing between sampleactivation and the point in timewhere clotting provides enoughresistance to produce a 2 mmamplitude reading on the TEGanalyzer tracing. The CK - Rparameter represents the initiationphase of coagulation triggered byenzymatic clotting factors andculminating with the initial fibrinformation. A prolonged R value isindicative of slow clot formation,and a shortened R value isindicative of fast clot formation.Clinical Value . A prolonged R value isindicative of slow clot formation, due tocoagulation factor deficiencies, heparin,or other anticoagulants.
Clinical Value ofCitrated: Kaolin(CK)Parameter MA (mm)	MA, or Maximum Amplitude,represents the maximum firmness ofthe clot during the test. The MAprovides information about thecontribution of platelets/fibrin to theoverall strength of the clot.	The maximal strength of the clotwhen activated with kaolin. Thisrepresents the combination of thecontribution of fibrinogen andplatelets to clot strength.Clinical Value : The MA providesinformation of platelets and fibrinogento the overall clot strength withoutexcluding the influence of heparin. Adecreased MA is indicative of low clotstrength, which could be due todecreased platelet contribution ordecreased fibrinogen; whereas, anincreased MA is indicative of high clotstrength, which could be due toincreased platelet or fibrinogencontribution.
Clinical Value ofCitrated: Kaolin withHeparinase (CKH)Parameter R (min)Heparinase isincluded in thepredicate andsubject device	Initiation phase of coagulationtriggered by enzymatic coagulationfactors and culminating with theinitial fibrin formation.A prolonged R value is indicative ofslow clot formation, due tocoagulation factor deficiencies orheparin. Inclusion of heparinase inthe blood chamber channel of thecartridge provides ability tocompare R (min) without the effectof heparin on the clot.	The reaction time betweeninitiation of the clot (via kaolin)and the point where the tracingreaches 2mm of amplitude, withheparinase being used toneutralize the effect of heparin.Clinical Value: A prolonged R value isindicative of slow clot formation, due tocoagulation factor deficiencies or non-heparin anticoagulant. A shortening ofthe CKH-R compared to the CK-Rindicates effect of heparin in the bloodsample.
Clinical Value ofCitrated: Kaolin withHeparinase (CKH)Parameter LY30 (%)	Parameter LY30 (%) is not reportedfor the predicate device.	Clot lysis, in a sample withheparinase to neutralize effects ofheparin, expressed as a percentreduction in clot strength 30 minutesafter the MA is reached. ClinicalValue: LY30 provides informationabout fibrinolytic activity.
Clinical Value ofCitrated: RapidTEGwith Heparinase(CRTH) ParameterMA (mm)Heparinase isincluded in thesubject device	RapidTEG™ MA is the point atwhich clot strength reaches itsmaximum and reflects the end resultof minimal platelet-fibrin interactionvia the GPIIb/IIIa receptors. Due tofaster coagulation activation, clotstrength is measured faster thanCitrated: Kaolin (K) activatedsamples. Same results as CKmaximum amplitude (CK-MA).The MA provides information aboutthe contribution of platelets/fibrin tothe overall strength of the clot.	RapidTEG MA is the point ofmaximal amplitude of the TEGtracing, measured in mm, andreflects the maximum clot strength.The strength of the clot is primarilya result of platelet-fibrin interactionsvia the GPIIb/IIIa receptors. ClinicalValue: The MA providesinformation of platelets andfibrinogen contribution to the overallclot strength. A decreased MA isindicative of low clot strength,which could be due to decreasedplatelet or decreased fibrinogencontribution; whereas an increasedMA is indicative of high clotstrength, which could be due toincreased platelet or fibrinogencontribution.
Clinical Value ofCitrated: FunctionalFibrinogen withHeparinase (CFFFH)Parameter MA (mm)	The maximum amplitude of CFFprovides the functional fibrinogencontribution to the clot strength.Provides the overall contribution offunctional fibrinogen to clot	The Functional Fibrinogen reagentinhibits platelet aggregation via theGPIIb/IIIa receptor, excluding itscontribution 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.

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{13}------------------------------------------------

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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

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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-siteTR-DIS-102653-C	Cartridge Lot to LotTR-DIS-102583-C	Operator to OperatorTR-DIS-102697-C	RepeatabilityTR-DIS-102697-C
Instrument	3 in combination persite	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.

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HAEMONE'

Sample	Assay-Parameter	N	Mean	Repeatability		BetweenRun		BetweenDay		BetweenCartridgeLot		BetweenQC Lot		Between SiteInstrument/Operator		Total		Pass/Fail
				SD	%CV	SD	%CV	SD	%CV	SD	%CV	SD	%CV	SD	%CV	SD	%CV
CartridgeReagentQC Level1(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
CartridgeReagentQC Level2(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:

SampleType #	Hemostatic State	CK R	CKH R	CK MA	CRTH MA	CFFH MA	CKHLY30	Method or Additive forContriving*
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 Fibrinogendepletion
4	Contrived Hyper-coagulable			x↑	x↑			Platelet Rich Plasma andFibrinogen
5	Contrived Hyper-coagulable					x↑		Fibrinogen

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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	AssayParameter	N	Mean	Repeatability*		BetweenOperator		Between Lot		Within Laboratory(= Total Precision)		Pass/Fail
				SD	CV	SD	CV	SD	CV	SD	CV
S2ContrivedHypo-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
S3Contrived	CK R (min)	24	4.91	0.31	6.3%	0.03	0.7%	0.12	2.4%	0.33	6.8%	Pass
Sample	AssayParameter	N	Mean	Repeatability*		BetweenOperator		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
S4ContrivedHyper-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
S5ContrivedHyper-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
S6ContrivedHyper-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
S7ContrivedHyper-	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	AssayParameter	N	Mean	Repeatability*		BetweenOperator		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

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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.

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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:

InterferingFactors(levels)	Specimen Type	Highest Concentration with No Interference
		CK - R	CK - MA	CKH - R	CKH -LY30	CRTH -MA	CFFH -MA
No DiscardTube	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, 400mg/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 citrateVacutainer®tube: 100, 90,80, 70 and60% )	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
InterferingFactors(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, 320mg/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, 600mg/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, 200ug/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, 600ug/mL)	Normal	600	600	600	600	600	600
	Hypocoagulable	600	600	600	600	600	600
	Hyperfibrinolytic	NT	NT	NT	NT	NT	NT
MycophenolicAcid (21, 42ug/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, 40.5ng/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

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Legend:

NI - No Interference
NT - Not Tested

NT - Not Tested

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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)	ParameterReadout	HemostaticSignificanceof IndividualParameter	Interpretation ofParameter Readout forConsideration
CK	R (min)	4.6 - 9.1	CK-R > RR	Hypocoagulable	↓Coagulation factoractivity and/orpresence of heparinat sufficiently highconcentrations
			CK-R < RR	Hypercoagulable
	MA (mm)	52 - 69	CK-MA < RR	Hypocoagulable	↓Fibrinogen or↓Platelet Contribution
			CK-MA > RR	Hypercoagulable	↑Fibrinogen or↑Platelet Contribution
CKH	R (min)	4.3 - 8.3	CK-R > CKH-R	Heparin Effect	Indicative of heparineffect
			CKH-R > RR	Hypocoagulable	↓Coagulationfactor 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	Hypocoagulable	↓Fibrinogen or↓Platelet Contribution
			CRTH-MA > RR	Hypercoagulable	↑Fibrinogen or↑Platelet Contribution
CFFH	MA (mm)	15 - 34	CFFH-MA < RR	Hypocoagulable	↓Fibrinogen
			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.

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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.

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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.

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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
ContrivedHypo-coagulable	0	N/A	100 %
	0.1	100 %	N/A
	0.15	100 %	N/A
	0.2	100 %	N/A
ContrivedHyper-coagulable	0	N/A	100 %
	0.1	100 %	N/A
	0.15	100 %	N/A
	0.2	100 %	N/A
ContrivedHyper-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	LowerAMR	CalculatedCV (%)	UpperAMR	CalculatedCV (%)
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.

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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	LowerAMR	UpperAMR
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	AcceptanceCriteria Pass/Fail
The CKH, CRTH, and CFFH assays shall be able to neutralizeup to 5.0 IU/mL (+/- 0.1IU/mL) of heparin. (CTQ)	Pass
The CKH, CRTH, and CFFH assays shall be able to neutralizeup 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	AcceptanceCriteria Pass/Fail
Blood treated with 5.0 IU/ml (+/- 0.1IU/mL) of heparin,measured CFFH MA, shall remain within the normal referencerange, 90% of the time. (CTQ)	Pass

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Blood treated with 5.0 IU/ml (+/- 0.1IU/mL), measured CRTHMA, shall remain within the normal reference range, 90% ofthe 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	AcceptanceCriteria Pass/Fail
CK R shall be greater than CKH R when at least 0.2 IU/mL ofheparin or at least 0.008 mg/mL LMWH is present in the bloodsample. (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.

AssayParameter	N ofSamples	Intercept[95% CI]	Slope[95% CI]	Pearson Corr.[95% CI]	SpearmanCorr.[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

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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 DeviceDescription
1	CK-RCK-MACKH-RCKH-LY30	The parameters in the predicate areidentical with the Citrated: K, KH, RTH,FFH assay cartridge
2	CRTH-MA	The CKH-MA on the predicate device is anequivalent channel
3	CFFH-MA	Clauss fibrinogen plasma concentrationallows comparison of contribution offibrinogen 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.

11. References

Previtali E. Bucciarelli P. Passamonti SM. Martinelli I Risk factors for venous and arterial 1. thrombosis. Blood Transfus. 2011 Apr; 9(2):120-38.

Ak K, Isbir CS, Tetik S, Atalan N, Tekeli A, Aljodi M, et al. Thromboelastography- based 2. transfusion algorithm reduces blood product use after elective CABG: a prospective

randomized study. J Card Surg. 2009; 24: 404- 10.

Avidan MS, Alcock EL, Da Fonseca J, Ponte J, Desai JB, Despotis GJ, et al. Comparison 3. of structured use of routine laboratory tests or near-patient assessment with clinical judgement in the management of bleeding after cardiac surgery. Br J Anaesth. 2004; 92: 178-86
Cui Y, Hei F, Long C, Feng Z, Zhao J, Yan F, et al. Perioperative monitoring of 4. thromboelastograph on blood protection and recovery for severely cyanotic patients undergoing complex cardiac surgery. Artif Organs. 2010; 34: 955-60
న. De Pietri L. Bianchini M. Montalti R. De Maria N. Di Maira T. Begliomini B. et al. Thrombelastography-guided blood product use before invasive procedures in cirrhosis with severe coagulopathy: a randomized, controlled trial. Hepatology. 2016; 63: 566- 7
1. Nuttall GA, Oliver WC, Santrach PJ, Bryant S, Dearani JA, Schaff HV, et al. Efficacy of a simple intraoperative transfusion algorithm for nonerythrocyte component utilization after cardiopulmonary bypass. Anesthesiology. 2001: 94:773-81.
1. Royston D, von Kier S. Reduced haemostatic factor transfusion using heparinasemodified thrombelastography during cardiopulmonary bypass. Br J Anaesth. 2001; 86: 575- 8.
1. Wang SC, Shieh JF, Chang KY, Chu YC, Liu CS, Loong CC, et al. Thromboelastographyguided transfusion decreases intraoperative blood transfusion during orthotopic liver transplantation: randomized clinical trial. Transplant Proc. 2010; 42: 2590-

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Westbrook AJ, Olsen J, Bailey M, Bates J, Scully M, Salamonsen RF. Protocol based on 9. thromboelastograph (TEG) out-performs physician preference using laboratory coagulation tests to guide blood replacement during and after cardiac surgery: a pilot study. Heart Lung Circ. 2009: 18: 277- 88.
1. Shore-Lesserson L, Manspeizer HE, DePerio M, Francis S, Vela-Cantos F, Ergin MA. Thromboelastography-guided transfusion algorithm reduces transfusions in complex cardiac surgery. Anesth Analg. 1999; 88: 312- 19.
Chen Z. Ma Y. Li O. Deng Z. Zheng O. The application of thromboelastography in risk 11. stratification for selective thromboembolism prophylaxis after total joint arthroplasty in Chinese: a randomized controlled trial. Ann Palliat Med. Sep 2020;9(5):2498-2507
1. Vuyyuru SK, Singh AD, Gamanagatti SR, Rout G, Gunjan D, Shalimar. A Randomized Control Trial of Thromboelastography-Guided Transfusion in Cirrhosis for High-Risk Invasive Liver-Related Procedures. Dig Dis Sci. Jul 2020;65(7):2104- 2111.Chen Z, Ma Y, Li Q, Deng Z, Zheng Q. The application of thromboelastography in risk stratification for selective thromboembolism prophylaxis after total joint arthroplasty in Chinese: a randomized controlled trial. Ann Palliat Med. Sep 2020; 9(5):2498-2507
1. Kovalic AJ, Khan MA, Malaver D, et al. Thromboelastography versus standard coagulation testing in the assessment and reversal of coagulopathy among cirrhotics: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol. Mar 2020;32(3):291-302.
1. Hartmann J, Dias JD, Pivalizza EG, Garcia-Tsao G. Thromboelastography-Guided Therapy Enhances Patient Blood Management in Cirrhotic Patients: A Meta-analysis Based on Randomized Controlled Trials. Semin Thromb Hemost. Sep 2 2022
1. Dias JD, Sauaia A, Achneck HE, Hartmann J, Moore EE. Thromboelastography- guided therapy improves patient blood management and certain clinical outcomes in elective cardiac and liver surgery and emergency resuscitation: A systematic review and analysis. J Thromb Haemost. Jun 2019;17(6):984-994
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1. Gonzalez E, Moore EE, Moore HB, Chapman MP, Chin TL, Ghasabyan A, et al. Goaldirected hemostatic resuscitation of trauma-induced coagulopathy: a pragmatic randomized clinical trial comparing a viscoelastic assay to conventional coagulation assays. Ann Surg. 2016;263:1051-9.
1. Hoffman M., M. D. (2001). A cell-based model of hemostasis. Thromb Haemost, 85:958-
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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.