ROTEM sigma Thromboelastometry System

K201440 · Tem Innovations GmbH · JPA · Jul 8, 2022 · Hematology

Device Facts

• Record ID: K201440
• Device Name: ROTEM sigma Thromboelastometry System
• Applicant: Tem Innovations GmbH
• Product Code: JPA · Hematology
• Decision Date: Jul 8, 2022
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 864.5425
• Device Class: Class 2

Intended Use

The ROTEM sigma thromboelastometry system is a fully integrated and automated in vitro diagnostic system designed to monitor and analyze a patient’s coagulation status by measuring the viscoelastic properties of a 3.2% citrated venous or arterial whole blood sample. The ROTEM sigma system is indicated for use with adult patients 21 years and older where a semi-quantitative evaluation of their blood coagulation properties is desired, in the point of care and laboratory settings. Coagulation evaluations on the ROTEM sigma instrument, together with the ROTEM sigma complete + hep cartridge, are used to assess peri-operative hemorrhage and/or thrombosis in cardiovascular surgery and liver transplantation. The single use, multichannel cartridge ROTEM sigma complete + hep contains the following assays: INTEM C is a semi-quantitative assay used to monitor coagulation via the intrinsic pathway in citrated whole blood samples. EXTEM C is a semi-quantitative assay used to monitor coagulation via the extrinsic pathway in citrated whole blood samples. FIBTEM C is a semi-quantitative assay used to monitor coagulation via the extrinsic pathway in citrated whole blood samples, after blocking platelet contribution to clot firmness. HEPTEM C is a semi-quantitative assay used to monitor coagulation via the intrinsic pathway in citrated whole blood samples, after inactivating heparin. Results from the ROTEM sigma should not be the sole basis for a patient diagnosis; ROTEM sigma results should be considered along with a clinical assessment of the patient’s condition and other laboratory tests. For in vitro Diagnostic use. For professional use only.

Device Story

ROTEM sigma is a fully integrated, automated in vitro diagnostic system for rotational thromboelastometry; measures viscoelastic properties of 3.2% citrated venous/arterial whole blood. System uses disposable, heated, multichannel cartridges (ROTEM sigma complete + hep) containing lyophilized reagents for intrinsic/extrinsic pathway activation. Principle: oscillating vertical axis with pin in stationary cup; clot formation restricts pin oscillation; optical sensor detects amplitude reduction. Provides real-time graphical "TEMogram" and parameters (CT, A5, A10, A20, MCF, LI60, ML). Used in POC/lab settings by professionals to assess coagulation status, including heparin effects. Output aids clinical decision-making regarding peri-operative hemorrhage/thrombosis in cardiovascular surgery and liver transplantation; results must be interpreted alongside clinical assessment.

Clinical Evidence

Bench testing only. Precision/reproducibility studies (N=270 replicates per control) demonstrated acceptable CVs for CT, A5, A10, A20, and MCF. Interference testing confirmed no interference for heparin, tranexamic acid, aspirin, ticagrelor, and lupus anticoagulant up to claimed concentrations. Method comparison study (N=181 patients) against ROTEM delta showed strong correlation (R=0.78-0.99) across parameters. Matrix comparison (N=74) confirmed equivalence between venous and arterial samples.

Technological Characteristics

Rotational thromboelastometry; fixed cylindrical cup and oscillating vertical axis (4.75° angle). Optical detection via CCD sensor. Temperature controlled at 37°C ± 1°C. Fully integrated, automated system using single-use, multichannel cartridges with lyophilized reagents. Connectivity/software: automated sample transfer, real-time graphical output. Electrical safety: IEC 61010-1, IEC 61010-2-010, IEC 61010-2-101, IEC 60601-1-2.

Indications for Use

Indicated for adult patients 21+ years requiring semi-quantitative blood coagulation evaluation in point-of-care or laboratory settings; specifically for assessing peri-operative hemorrhage and/or thrombosis in cardiovascular surgery and liver transplantation.

Regulatory Classification

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.

Special Controls

*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.

Predicate Devices

• ROTEM delta Thromboelastometry System (K101533, K083842)

Submission Summary (Full Text)

{0}

510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION
DECISION SUMMARY
ASSAY AND INSTRUMENT

I Background Information:

A 510(k) Number
K201440

B Applicant
Tem Innovations GmbH

C Proprietary and Established Names
ROTEM sigma Thromboelastometry System

D Regulatory Information
| Product Code(s) | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| JPA | Class II | 21 CFR 864.5425 - Multipurpose System For In Vitro Coagulation Studies | HE - Hematology |

II Submission/Device Overview:

A Purpose for Submission:
Clearance of a new device, ROTEM sigma Thromboelastometry System

B Measurand:
Clotting Time Parameter:
Clotting Time "CT" (s)
Clot Firmness Parameters:
Amplitude at time 5, 10, 20 minutes "A5", "A10", "A20" (mm)
Maximum Clot Firmness "MCF" (mm)
Clot Lysis Parameters:
Lysis Index "LI60" (%)
Maximum Lysis "ML" (%)

C Type of Test:
Semi-quantitative thromboelastometry

III Intended Use/Indications for Use:

A Intended Use(s):
See Indications for Use below.

{1}

B Indication(s) for Use:

The ROTEM sigma thromboelastometry system is a fully integrated and automated in vitro diagnostic system designed to monitor and analyze a patient’s coagulation status by measuring the viscoelastic properties of a 3.2% citrated venous or arterial whole blood sample. The ROTEM sigma system is indicated for use with adult patients 21 years and older where a semi-quantitative evaluation of their blood coagulation properties is desired, in the point of care and laboratory settings. Coagulation evaluations on the ROTEM sigma instrument, together with the ROTEM sigma complete + hep cartridge, are used to assess peri-operative hemorrhage and/or thrombosis in cardiovascular surgery and liver transplantation.

The single use, multichannel cartridge ROTEM sigma complete + hep contains the following assays:

INTEM C is a semi-quantitative assay used to monitor coagulation via the intrinsic pathway in citrated whole blood samples.

EXTEM C is a semi-quantitative assay used to monitor coagulation via the extrinsic pathway in citrated whole blood samples.

FIBTEM C is a semi-quantitative assay used to monitor coagulation via the extrinsic pathway in citrated whole blood samples, after blocking platelet contribution to clot firmness.

HEPTEM C is a semi-quantitative assay used to monitor coagulation via the intrinsic pathway in citrated whole blood samples, after inactivating heparin.

Results from the ROTEM sigma should not be the sole basis for a patient diagnosis; ROTEM sigma results should be considered along with a clinical assessment of the patient’s condition and other laboratory tests.

For in vitro Diagnostic use. For professional use only.

C Special Conditions for Use Statement(s):

Rx - For Prescription Use Only

D Special Instrument Requirements:

ROTEM sigma instrument

IV Device/System Characteristics:

A Device Description:

The ROTEM sigma Thromboelastometry System is an in vitro diagnostic (IVD) whole blood hemostasis system intended for use in the evaluation of coagulopathies in Point of Care (POC) or laboratory settings. It uses rotational thromboelastometry to provide semi-quantitative information about the coagulation state of a blood sample. The ROTEM sigma system records the kinetic changes in a 3.2% citrated whole blood sample during clot formation, as well as when the sample clot retracts and/or lyses. Several parameters, including clotting time, clot firmness, and clot lysis index, are measured and reported for this purpose. The graphical presentation, or reaction curve (TEMogram) created in real time and displayed along with numerical values of

{2}

associated parameters, reflects the various physiological results, which describe the interaction between coagulation factors and inhibitors, fibrinogen, platelets, and the fibrinolysis system. Additionally, the test can detect the effect of anticoagulant heparin on hemostasis.

The ROTEM sigma Thromboelastometry System consists of:
- ROTEM sigma instrument
- ROTEM sigma cartridges
- ROTEM sigma complete + hep (with assays INTEM C, EXTEM C, FIBTEM C, HEPTEM C)
- ROTEM sigma system QC (Quality Control) cartridge
- ROTEM sigma controls
- ROTEM sigma ROTROL N
- ROTEM sigma ROTROL P

## B Principle of Operation:

The ROTEM sigma Thromboelastometry System technology uses rotational thromboelastometry that is based on a fixed cylindrical cup and an oscillating vertical axis. The axis is supported by a high precision ball bearing and oscillates through an angle. Oscillation of the axis is driven by a motor. For the measurement, the channel's measurement axis engages the plastic pin in the cup of the disposable heated cartridge holding the blood sample. The oscillation is detected optically. If no clotting takes place, the pin movement is not restricted. As a clot forms and attaches itself between the pin and cup surfaces, the pin movement becomes increasingly restricted. As the clot becomes firmer, the oscillation amplitude of the axis is reduced.

## C Instrument Description Information:

1. Instrument Name:
ROTEM sigma

2. Specimen Identification:
The user can scan information from blood samples and ROTROL vials in the instrument using the barcode reader.

3. Specimen Sampling and Handling:
Blood samples are to be collected in accordance with CLSI GP41: Procedures for the Collection of Diagnostic Blood Specimen by Venipuncture; Approved Standard - Seventh Edition.
Samples should be stored at room temperature and not placed on ice. Do not shake or roll sample tubes. Sample pipetting is automated, and the instrument is capable of cap piercing.

4. Calibration:
The ROTEM sigma instrument is factory calibrated.

5. Quality Control:
Different levels of quality control (QC) are implemented to ensure that the ROTEM sigma system functions as intended. This includes internal system QC with the ROTEM sigma system QC cartridge for system functionality testing, and external QC using ROTROL N / ROTROL P:

{3}

- System QC:

System QC checks the functional integrity of the instrument hardware and should be performed weekly or according to local regulations. The system QC cartridge is a cartridge like the assay cartridges, except without needle, reagents, and mixing ball and with more robust fluidic valves to withstand repeated testing. If the ROTEM sigma system QC cartridge is not available, any other unused test cartridge can be used for system QC. In order to ensure the ROTEM sigma is not damaged, it is important to use a new test cartridge when performing the system QC.

- External QC (EQC) with ROTEM sigma ROTROL N and ROTROL P:

Tests with standardized 2-level quality control (QC) materials (ROTEM sigma ROTROL N and ROTROL P) are performed to identify potential issues with the reagents in the ROTEM sigma cartridges. EQC is recommended to be performed on every new cartridge lot, every new cartridge delivery, and after system maintenance/repair.

# V Substantial Equivalence Information:

A Predicate Device Name(s):

ROTEM delta Thromboelastometry System

B Predicate 510(k) Number(s):

K101533, K083842

C Comparison with Predicate(s):

| Device & Predicate Device(s): | K201440 | K083842 | K101533 |
| --- | --- | --- | --- |
| Device Trade Name | ROTEM sigma Thromboelastometry System | ROTEM delta Thromboelastometry System | ROTEM delta Thromboelastometry System |
| General Device Characteristic Similarities | | | |
| Instrument | Fully Integrated Thromboelastometry Instrument | Same | Same |
| Measuring Technique | Shear elasticity of a coagulating sample by motion of a pin | Same | Same |
| Measuring Channels Utilized | 4 | Same | Same |
| Signal Generation | Oscillating pin in a stationary cup | Same | Same |
| Signal Transducer | Optical system with CCD sensor | Same | Same |

{4}

| Sample | 3.2 % citrated whole blood | Same | Same |
| --- | --- | --- | --- |
| Measurement Station Temperature | 37°C ± 1°C | Same | Same |
| Graphical Presentation of Results | Presents each assay reaction curve and parameters in real time “TEMogram” | Same | Same |
| Intended Use/Indications For Use | The ROTEM sigma thromboelastometry system is a fully integrated and automated in vitro diagnostic system designed to monitor and analyze a patient’s coagulation status by measuring the viscoelastic properties of a 3.2% citrated venous or arterial whole blood sample. The ROTEM sigma system is indicated for use with adult patients 21 years and older where a semi-quantitative evaluation of their blood coagulation properties is desired, in the point of care and laboratory settings. Coagulation evaluations on the ROTEM sigma instrument, together with the ROTEM sigma complete + hep cartridge, are used to assess peri-operative hemorrhage and/or thrombosis in cardiovascular surgery and liver transplantation.The single use, multichannel cartridge ROTEM sigma complete + hep contains the following assays:INTEM C is a semi-quantitative assay used to | The ROTEM delta Thromboelastometry System is designed for in vitro diagnostic use by professionals in a laboratory environment. The ROTEM® delta is intended to provide a qualitative and quantitative indication of the coagulation state of a blood sample. For this purpose the ROTEM delta records the clot firmness changes in a sample of citrated whole blood as the sample clots, retracts and lyses in real time. The analyzer output consists of a qualitative graphical representation (mirrored coagulation curve – clot firmness over time) and several defined numerical parameters describing the curve quantitatively.The in-TEM assay is a semi-quantitative in vitro diagnostic assay used to monitor the coagulation process via the intrinsic pathway in citrated whole blood specimens. Clotting characteristics are | The EXTEM assay is a semi-quantitative in vitro diagnostic assay used to monitor the coagulation process via the extrinsic pathway in citrated whole blood specimens on the ROTEM delta Thromboelastometry System. Clotting characteristics are described by the functional parameters Clotting Time (CT), Speed of Clot formation (CFT and alpha angle), Clot Firmness (A20/MCF) and Clot Lysis (LOT, ML, LI(x)). CFT and alpha (Speed of Clot Formation) are complementary parameters and should be used in conjunction with the main parameters Clotting Time (CT) and Clot Firmness (A20/MCF).The FIBTEM assay is a semi-quantitative in vitro diagnostic assay on the ROTEM delta Thromboelastometry System to monitor the clot firmness of a citrated whole blood specimen after blocking |

{5}

| | monitor coagulation via the intrinsic pathway in citrated whole blood samples. EXTEM C is a semi-quantitative assay used to monitor coagulation via the extrinsic pathway in citrated whole blood samples. FIBTEM C is a semi-quantitative assay used to monitor coagulation via the extrinsic pathway in citrated whole blood samples, after blocking platelet contribution to clot firmness. HEPTEM C is a semi-quantitative assay used to monitor coagulation via the intrinsic pathway in citrated whole blood samples, after inactivating heparin. Results from the ROTEM sigma should not be the sole basis for a patient diagnosis; ROTEM sigma results should be considered along with a clinical assessment of the patient's condition and other laboratory tests. For in vitro Diagnostic use. For professional use only. | described by the functional parameters Clotting Time (CT), Speed of Clot formation (CFT and alpha angle), Clot Firmness (A20/MCF) and Clot Lysis (LOT, ML, LI(x)). The assay is intended for professional use in the clinical laboratory on the ROTEM® delta Instrument. The hep-TEM assay is a semi-quantitative in vitro diagnostic assay used to monitor the coagulation process via the intrinsic pathway in the presence of heparin, in citrated whole blood specimens. Clotting characteristics are described by the functional parameters Clotting Time (CT), Speed of Clot formation (CFT and alpha angle), Clot Firmness (A20/MCF) and Clot Lysis (LOT, ML, LI(x)). The assay is intended for professional use in the clinical laboratory on the ROTEM delta Instrument. The NATEM assay is a semi-quantitative in vitro diagnostic assay used to monitor the coagulation process contact activated by the surface of the measurement cell, in | platelet contribution to the clot firmness. The fibTEM® is always used in conjunction with exTEM. Clotting characteristics are described by the functional parameter Clot Firmness (A20/MCF). The APTEM assay is a semi-quantitative in vitro diagnostic assay on the ROTEM delta Thromboelastometry System to monitor the clot firmness of a citrated whole blood specimen after blocking hyperfibrinolysis by aprotinin. The ap-TEM is always used in conjunction with exTEM. Clotting characteristics are described by the functional parameters Clotting Time (CT), Speed of Clot formation (CFT and alpha angle), Clot Firmness (A20/MCF) and Clot Lysis (LOT, ML, LI(x)). CFT and alpha (Speed of Clot Formation) are complementary parameters and should be used in conjunction with the main parameters Clotting Time (CT) and Clot Firmness (A20/MCF). Each assay, APTEM, EXTEM and FIBTEM is performed on the ROTEM delta analyzer |
| --- | --- | --- | --- |

{6}

| | | citrated whole blood specimens. Clotting characteristics are described by the functional parameters Clotting Time (CT), Speed of Clot formation (CFT and alpha angle), Clot Firmness (A20/MCF) and Clot Lysis (LOT, ML, LI(x)). The assay is intended for professional use in the clinical laboratory on the ROTEM delta Instrument. The star-TEM reagent is intended for use as recalcification reagent in the NATEM and in-TEM on the ROTEM delta Thromboelastometry System. The ROTEM delta Thromboelastometry System is a non-invasive diagnostic instrument designed to monitor and analyze the coagulation state of a blood sample in order to assist in the assessment of patient clinical hemostasis conditions. The indication for ROTEM delta is with adult patients where an evaluation of their blood coagulation properties is desired. Coagulation evaluations with the ROTEM delta System are commonly used to assess clinical | which has the following indication for use: The indication for ROTEM delta is in adult patients when an evaluation of their blood coagulation properties is desired. Coagulation evaluations with the ROTEM delta system are commonly used to assess clinical conditions in organ transplantation, cardiovascular surgery, cardiology procedures and trauma to access post-operative hemorrhage and/or thrombosis. |
| --- | --- | --- | --- |

{7}

| | | conditions such as peri-operative hemostasis. | |
| --- | --- | --- | --- |
| General Device Characteristic Differences | | | |
| Cups & Pins | Cups and pins are integrated into assay cartridges | Cups and pins need to be installed in instrument for each test | Cups and pins need to be installed in instrument for each test |
| Sample Handling | Automated sample transfer | Manual pipetting, electronic pipette | Manual pipetting, electronic pipette |
| Sample Volume | ≥ 2.7 mL sample tube for four assays | 300 μL per assay | 300 μL per assay |
| Supply Voltage | 110/240 VAC, 60/50 Hz, max. 210 VA | 115/230 VAC, 60/50 Hz, max. 350 VA | 115/230 VAC, 60/50 Hz, max. 350 VA |
| Environment | • Temperature Operating: 18–30°C Storage: 0–50°C
• Relative Humidity Operating: 40–60% Storage: 20–85%
• Operable to 3000 m above sea level | • Temperature Operating: 15–30°C Storage: 0–50°C
• Relative Humidity 20–85%
• Operable to 2000 m above sea level | • Temperature Operating: 15–30°C Storage: 0–50°C
• Relative Humidity 20–85%
• Operable to 2000 m above sea level |
| Reported Parameters* | • Clotting Time “CT”
• Amplitude “A(x)” (A5, A10, A20)
• Maximum Clot Firmness “MCF”
• Lysis Index “LI(x)” (LI60)
• Maximum Lysis “ML” | • Clotting Time “CT”
• Clot Formation Time “CFT”
• Alpha angle “α”
• Amplitude “A(x)” (A10, A20)
• Maximum Clot Firmness “MCF”
• Lysis Index “LI(x)” (LI30, LI60)
• Maximum Lysis “ML”
• Lysis Onset Time “LOT” | • Clotting Time “CT”
• Clot Formation Time “CFT”
• Alpha angle “α”
• Amplitude “A(x)” (A10, A20)
• Maximum Clot Firmness “MCF”
• Lysis Index “LI(x)” (LI30, LI60)
• Maximum Lysis “ML”
• Lysis Onset Time “LOT” |
| Controls | • ROTEM sigma ROTROL N (Level 1 Control)
• ROTEM sigma ROTROL P (Level 2 Control)
• ROTEM sigma System QC cartridge | • ROTROL N (Level 1 Control)
• ROTROL P (Level 2 Control) | • ROTROL N (Level 1 Control)
• ROTROL P (Level 2 Control) |

{8}

| Assays | • INTEM C
• EXTEM C
• FIBTEM C
• HEPTEM C | • INTEM
• EXTEM
• FIBTEM
• APTEM
• HEPTEM
• NATEM | • INTEM
• EXTEM
• FIBTEM
• APTEM
• HEPTEM
• NATEM |
| --- | --- | --- | --- |
| Assay Format | All four assays (reagents) provided ready-to-use in single-use ROTEM sigma complete + hep cartridge. | Assay reagents provided in separate vials.
Preparation required to create the desired assay. | Assay reagents provided in separate vials.
Preparation required to create the desired assay. |
| Reagent Form | Lyophilized beads | Liquid or lyophilisate with a diluent (HEPTEM only) | Liquid or lyophilisate with a diluent (HEPTEM only) |
| Reagent Handling | Cartridges containing the assay reagents are stored at room temperature. No warmup required. | Assay reagents require refrigeration, 5-15 min warmup required (depending on room temperature). | Assay reagents require refrigeration, 5-15 min warmup required (depending on room temperature). |

* ROTEM sigma does not utilize CFT or α angle. They are secondary parameters. Equivalent information is gained from early amplitude parameter A5. This is not a difference of the assay but of the instrument software. The functional parameters describing the clotting characteristics of the two assays are similar.

VI Standards/Guidance Documents Referenced:

CLSI EP05-A3, Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline – Third Edition.

CLSI EP07, Interference Testing in Clinical Chemistry; Third Edition.

CLSI EP25-A, Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline.

CLSI EP28-A3c, Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory; Approved Guideline – Third Edition.

CLSI EP37, Supplemental Tables for Interference Testing in Clinical Chemistry; First Edition.

IEC 60601-1-2:2014, Medical electrical equipment - Part 1-2: General requirements for basic safety and essential performance - Collateral Standard: Electromagnetic disturbances - Requirements and tests.

IEC 61010-1, Safety requirements for electrical equipment for measurement control and laboratory use - Part 1: General requirements.

VII Performance Characteristics (if/when applicable):

A Analytical Performance:

1. Precision/Reproducibility:

Repeatability

{9}

Precision Studies Using Control and Whole Blood - CT, A5, A10, A20, and MCF

To evaluate the precision performance of the new ROTEM sigma instrument and its assays with ROTROL controls, whole blood samples, and contrived whole blood samples, an internal repeatability study was performed on three lots of ROTEM sigma complete + hep cartridges. The control repeatability study involved three lots of each of the controls ROTEM sigma ROTROL N and ROTEM sigma ROTROL P. The whole blood repeatability study involved native donor normal whole blood samples and contrived hypocoagulable and hypercoagulable samples. The control study was run in duplicate, twice a day for 20 days, for a total of 80 replicates per control, using five instruments and four operators. The whole blood study was run in triplicate in one day on five instruments, for a total of 15 replicates per sample type. Due to the sample stability, the whole blood repeatability study was performed in one day and one run. For each assay type, except for FIBTEM C, the CT, A5, A10, A20, and MCF parameters were evaluated. CT is not a claimed parameter for FIBTEM C assay and was not evaluated in the repeatability study. The study mean, total SD and total $\% \mathrm{CV}$ for each precision parameter on each instrument were calculated for CT, A5, A10, A20, and A30 (controls) or MCF (whole blood).

# Repeatability Results Summary - CT, A5, A10, A20, and MCF

In the summary tables below, the highest $\% \mathrm{CV}$ for individual assay parameters from the repeatability studies using ROTROL N, ROTROL P and whole blood samples on three lots of cartridges are presented. Overall, the study results demonstrated performance repeatability of the ROTEM sigma system with respect to measuring CT, A5, A10, A20, and MCF parameters for control and whole blood samples.

| Repeatability Summary - ROTEM sigma complete + hep | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Assay | Parameter | ROTROL N | | ROTROL P | | Normal Whole Blood | Contrived Hypocoagulable Samples | Contrived Hypercoagulable Samples |
| | | % CV (Within-Run) | % CV (Within-Laboratory) | % CV (Within-Run) | % CV (Within-Laboratory) | % CV (Within-Laboratory) | % CV (Within-Laboratory) | % CV (Within-Laboratory) |
| INTEM C | CT (s) | 7.7 | 8.7 | 4.6 | 4.9 | 3.8 | 6.8 | 4.5 |
| | A5 (mm) | 2.0 | 2.1 | 7.0 | 7.2 | 4.2 | 3.5 | 3.9 |
| | A10 (mm) | 2.0 | 2.0 | 6.1 | 6.2 | 2.9 | 3.2 | 2.8 |
| | A20 (mm) | 1.6 | 1.6 | 7.9 | 8.2 | 1.9 | 2.6 | 1.6 |
| | MCF* (mm) | 1.5 | 1.6 | 8.5 | 8.7 | 1.8 | 2.8 | 1.4 |
| EXTEM C | CT (s) | 9.6 | 9.7 | 6.5 | 7.1 | 6.8 | 13.6 | 13.6 |
| | A5 (mm) | 2.4 | 2.8 | 4.9 | 5.2 | 5.0 | 5.2 | 3.0 |
| | A10 (mm) | 1.8 | 2.2 | 4.3 | 4.4 | 3.3 | 4.1 | 2.4 |
| | A20 (mm) | 1.6 | 1.7 | 5.1 | 5.3 | 2.6 | 3.9 | 1.9 |
| | MCF* (mm) | 1.4 | 1.5 | 5.6 | 5.9 | 2.3 | 4.8 | 1.4 |
| FIBTEM C | A5 (mm) | 2.6 | 2.8 | 7.2 | 7.3 | 10.2 | N/A | 4.7 |
| | A10 (mm) | 2.2 | 2.6 | 5.4 | 5.4 | 9.7 | N/A | 4.7 |
| | A20 (mm) | 2.0 | 2.2 | 4.5 | 4.5 | 7.4 | N/A | 4.2 |
| | MCF* (mm) | 1.7 | 1.8 | 5.2 | 5.3 | 9.8 | N/A | 4.6 |

{10}

*While the whole blood study used MCF, the controls study used as time point 30 minutes after CT because ROTROL controls reach maximum amplitude (MCF) by that time. A30 is not claimed as a reportable parameter for ROTROL or whole blood.

Pooled ROTROL N Precision Results

| Assay | Parameter | N | Mean | Repeatability (Within Run) | | Between Run | | Between Day | | Within Control Lot | | Between Control Lot | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | | | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| INTEM C | CT (s) | 240 | 338.4 | 18.8 | 5.6 | 0.0 | 0.0 | 8.3 | 2.5 | 20.6 | 6.1 | 12.0 | 3.6 |
| | A5 (mm) | 240 | 41.8 | 0.7 | 1.7 | 0.0 | 0.0 | 0.3 | 0.6 | 0.8 | 1.9 | 0.7 | 1.6 |
| | A10 (mm) | 240 | 45.7 | 0.7 | 1.6 | 0.0 | 0.0 | 0.2 | 0.5 | 0.8 | 1.7 | 0.5 | 1.0 |
| | A20 (mm) | 240 | 49.6 | 0.7 | 1.4 | 0.0 | 0.0 | 0.2 | 0.4 | 0.7 | 1.5 | 0.4 | 0.9 |
| | MCF* (mm) | 240 | 51.9 | 0.7 | 1.3 | 0.0 | 0.0 | 0.3 | 0.6 | 0.8 | 1.5 | 0.5 | 1.1 |
| EXTEM C | CT (s) | 240 | 124.1 | 9.5 | 7.7 | 1.2 | 1.0 | 3.0 | 2.4 | 10.0 | 8.1 | 5.2 | 4.2 |
| | A5 (mm) | 240 | 42.9 | 0.8 | 2.0 | 0.3 | 0.8 | 0.0 | 0.0 | 0.9 | 2.1 | 0.5 | 1.2 |
| | A10 (mm) | 240 | 46.9 | 0.8 | 1.6 | 0.3 | 0.6 | 0.0 | 0.0 | 0.8 | 1.7 | 0.5 | 1.2 |
| | A20 (mm) | 240 | 51.4 | 0.7 | 1.3 | 0.3 | 0.6 | 0.0 | 0.0 | 0.7 | 1.4 | 0.6 | 1.1 |
| | MCF* (mm) | 240 | 54.2 | 0.7 | 1.2 | 0.0 | 0.0 | 0.1 | 0.2 | 0.7 | 1.2 | 0.5 | 0.9 |
| FIBTEM C | A5 (mm) | 240 | 38.8 | 0.9 | 2.3 | 0.3 | 0.8 | 0.4 | 0.9 | 1.0 | 2.6 | 0.4 | 1.0 |
| | A10 (mm) | 240 | 43.3 | 0.9 | 2.1 | 0.4 | 0.9 | 0.2 | 0.5 | 1.0 | 2.4 | 0.3 | 0.8 |
| | A20 (mm) | 240 | 48.2 | 0.8 | 1.7 | 0.3 | 0.7 | 0.2 | 0.5 | 0.9 | 1.9 | 0.3 | 0.6 |
| | MCF* (mm) | 240 | 51.2 | 0.8 | 1.5 | 0.2 | 0.4 | 0.3 | 0.5 | 0.9 | 1.7 | 0.3 | 0.5 |
| HEPTEM C | CT (s) | 240 | 323.8 | 11.6 | 3.6 | 1.9 | 0.6 | 5.3 | 1.6 | 12.9 | 4.0 | 10.8 | 3.3 |
| | A5 (mm) | 240 | 43.1 | 0.7 | 1.6 | 0.0 | 0.0 | 0.2 | 0.6 | 0.7 | 1.7 | 0.6 | 1.4 |
| | A10 (mm) | 240 | 46.8 | 0.7 | 1.5 | 0.0 | 0.0 | 0.1 | 0.3 | 0.7 | 1.6 | 0.7 | 1.4 |
| | A20 (mm) | 240 | 50.8 | 0.7 | 1.4 | 0.0 | 0.0 | 0.2 | 0.4 | 0.7 | 1.4 | 0.6 | 1.3 |
| | MCF* (mm) | 240 | 53.3 | 0.7 | 1.3 | 0.0 | 0.0 | 0.2 | 0.3 | 0.7 | 1.3 | 0.6 | 1.1 |

* While the whole blood study used MCF, the controls study used as time point 30 minutes after CT because ROTROL controls reach maximum amplitude (MCF) by that time.

Pooled ROTROL P Precision Results

| Assay | Parameter | N | Mean | Repeatability (Within Run) | | Between Run | | Between Day | | Within Control Lot | | Between Control Lot | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | | | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| INTEM C | CT (s) | 240 | 370.1 | 13.8 | 3.7 | 4.6 | 1.3 | 3.2 | 0.9 | 14.9 | 4.0 | 54.6 | 14.7 |
| | A5 (mm) | 240 | 23.2 | 1.1 | 4.8 | 0.0 | 0.0 | 0.3 | 1.2 | 1.2 | 5.0 | 0.6 | 2.5 |
| | A10 (mm) | 240 | 26.0 | 1.1 | 4.4 | 0.2 | 0.9 | 0.2 | 0.7 | 1.2 | 4.5 | 0.7 | 2.6 |
| | A20 (mm) | 240 | 28.1 | 1.5 | 5.2 | 0.0 | 0.0 | 0.5 | 1.7 | 1.5 | 5.5 | 0.4 | 1.4 |
| | MCF* (mm) | 240 | 29.4 | 1.6 | 5.6 | 0.0 | 0.0 | 0.4 | 1.2 | 1.7 | 5.7 | 0.4 | 1.4 |
| EXTEM C | CT (s) | 240 | 144.2 | 8.9 | 6.2 | 2.8 | 2.0 | 0.0 | 0.0 | 9.3 | 6.5 | 7.0 | 4.8 |
| | A5 (mm) | 240 | 23.5 | 1.1 | 4.6 | 0.0 | 0.0 | 0.3 | 1.3 | 1.1 | 4.8 | 0.7 | 3.0 |

{11}

| Assay | Parameter | N | Mean | Repeatability (Within Run) | | Between Run | | Between Day | | Within Control Lot | | Between Control Lot | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | | | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| | A10 (mm) | 240 | 26.3 | 1.1 | 4.2 | 0.0 | 0.0 | 0.2 | 0.9 | 1.1 | 4.3 | 0.8 | 2.9 |
| | A20 (mm) | 240 | 28.9 | 1.2 | 4.3 | 0.0 | 0.0 | 0.3 | 0.9 | 1.3 | 4.4 | 0.8 | 2.8 |
| | MCF* (mm) | 240 | 30.4 | 1.3 | 4.4 | 0.0 | 0.0 | 0.4 | 1.3 | 1.4 | 4.6 | 0.9 | 3.0 |
| FIBTEM C | A5 (mm) | 240 | 23.7 | 1.2 | 5.2 | 0.1 | 0.3 | 0.0 | 0.0 | 1.2 | 5.2 | 0.3 | 1.2 |
| | A10 (mm) | 240 | 26.6 | 1.2 | 4.5 | 0.2 | 0.8 | 0.0 | 0.0 | 1.2 | 4.5 | 0.3 | 1.1 |
| | A20 (mm) | 240 | 29.3 | 1.2 | 4.1 | 0.2 | 0.7 | 0.0 | 0.0 | 1.2 | 4.2 | 0.4 | 1.5 |
| | MCF* (mm) | 240 | 30.8 | 1.3 | 4.4 | 0.1 | 0.2 | 0.0 | 0.0 | 1.4 | 4.4 | 0.5 | 1.6 |
| HEPTEM C | CT (s) | 240 | 374.0 | 16.6 | 4.4 | 8.2 | 2.2 | 0.0 | 0.0 | 18.5 | 4.9 | 63.0 | 16.8 |
| | A5 (mm) | 240 | 24.5 | 1.1 | 4.5 | 0.3 | 1.4 | 0.0 | 0.0 | 1.2 | 4.7 | 1.2 | 4.9 |
| | A10 (mm) | 240 | 27.2 | 1.2 | 4.3 | 0.1 | 0.5 | 0.0 | 0.0 | 1.2 | 4.3 | 1.1 | 4.2 |
| | A20 (mm) | 240 | 29.6 | 1.3 | 4.5 | 0.2 | 0.5 | 0.0 | 0.0 | 1.4 | 4.6 | 1.1 | 3.7 |
| | MCF* (mm) | 240 | 31.0 | 1.5 | 4.7 | 0.0 | 0.0 | 0.2 | 0.8 | 1.5 | 4.8 | 1.1 | 3.6 |

* While the whole blood study used MCF, the controls study used as time point 30 minutes after CT because ROTROL controls reach maximum amplitude (MCF) by that time.

Donor Whole Blood Results – CT, A5, A10, A20, and MCF

| Precision – Normal Whole Blood 1 | | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Assay | Parameter | N | Mean | Repeatability (Within-Instrument) | | Between-Instrument | | Within-Laboratory (Total) | |
| | | | | SD | %CV | SD | %CV | SD | %CV |
| INTEM C | CT | 15 | 161.4 | 5.8 | 3.6 | 2.2 | 1.3 | 6.2 | 3.8 |
| | A5 | 15 | 43.9 | 1.8 | 4.2 | 0.0 | 0.0 | 1.8 | 4.2 |
| | A10 | 15 | 54.1 | 1.6 | 2.9 | 0.0 | 0.0 | 1.6 | 2.9 |
| | A20 | 15 | 60.7 | 1.1 | 1.8 | 0.4 | 0.7 | 1.2 | 1.9 |
| | MCF | 15 | 62.7 | 0.9 | 1.4 | 0.7 | 1.2 | 1.1 | 1.8 |
| EXTEM C | CT | 15 | 60.1 | 3.3 | 5.5 | 1.8 | 3.0 | 3.8 | 6.3 |
| | A5 | 15 | 41.5 | 1.7 | 4.0 | 0.0 | 0.0 | 1.7 | 4.0 |
| | A10 | 15 | 52.3 | 1.5 | 2.8 | 0.3 | 0.7 | 1.5 | 2.9 |
| | A20 | 15 | 59.7 | 1.3 | 2.2 | 0.0 | 0.0 | 1.3 | 2.2 |
| | MCF | 15 | 62.1 | 1.3 | 2.1 | 0.5 | 0.9 | 1.4 | 2.3 |
| FIBTEM C | A5 | 15 | 9.3 | 0.5 | 5.5 | 0.8 | 8.5 | 0.9 | 10.2 |
| | A10 | 15 | 10.2 | 0.6 | 5.7 | 0.8 | 7.9 | 1.0 | 9.7 |
| | A20 | 15 | 10.5 | 0.4 | 4.2 | 0.6 | 6.1 | 0.8 | 7.4 |
| | MCF | 15 | 10.6 | 0.6 | 5.4 | 0.9 | 8.1 | 1.0 | 9.8 |
| HEPTEM C | CT | 15 | 160.7 | 4.2 | 2.6 | 2.1 | 1.3 | 4.7 | 2.9 |
| | A5 | 15 | 39.4 | 2.1 | 5.3 | 0.8 | 2.1 | 2.3 | 5.7 |
| | A10 | 15 | 50.4 | 1.8 | 3.6 | 0.8 | 1.6 | 2.0 | 3.9 |
| | A20 | 15 | 58.0 | 1.4 | 2.5 | 0.9 | 1.5 | 1.7 | 2.9 |
| | MCF | 15 | 60.5 | 1.1 | 1.8 | 1.0 | 1.7 | 1.5 | 2.5 |

{12}

| Precision – Normal Whole Blood 2 | | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Assay | Parameter | N | Mean | Repeatability (Within-Instrument) | | Between-Instrument | | Within-Laboratory (Total) | |
| | | | | SD | %CV | SD | %CV | SD | %CV |
| INTEM C | CT | 15 | 193.3 | 5.3 | 2.8 | 0.7 | 0.4 | 5.4 | 2.8 |
| | A5 | 15 | 47.7 | 0.4 | 0.9 | 1.0 | 2.1 | 1.1 | 2.3 |
| | A10 | 15 | 56.9 | 0.7 | 1.2 | 0.8 | 1.5 | 1.1 | 1.9 |
| | A20 | 15 | 62.6 | 0.4 | 0.6 | 1.0 | 1.6 | 1.1 | 1.7 |
| | MCF | 15 | 63.1 | 0.7 | 1.1 | 0.8 | 1.2 | 1.0 | 1.6 |
| EXTEM C | CT | 15 | 57.2 | 3.9 | 6.8 | 0.0 | 0.0 | 3.9 | 6.8 |
| | A5 | 15 | 46.2 | 1.7 | 3.7 | 1.5 | 3.3 | 2.3 | 5.0 |
| | A10 | 15 | 56.8 | 1.3 | 2.3 | 1.4 | 2.4 | 1.9 | 3.3 |
| | A20 | 15 | 64.1 | 1.0 | 1.6 | 1.3 | 2.1 | 1.7 | 2.6 |
| | MCF | 15 | 66.5 | 0.7 | 1.1 | 0.9 | 1.4 | 1.2 | 1.8 |
| FIBTEM C | A5 | 15 | 10.5 | 0.5 | 4.9 | 0.4 | 3.9 | 0.7 | 6.3 |
| | A10 | 15 | 11.3 | 0.4 | 3.2 | 0.8 | 6.8 | 0.8 | 7.5 |
| | A20 | 15 | 12.2 | 0.4 | 3.0 | 0.7 | 6.0 | 0.8 | 6.7 |
| | MCF | 15 | 12.3 | 0.5 | 4.2 | 0.5 | 4.4 | 0.8 | 6.1 |
| HEPTEM C | CT | 15 | 193.3 | 6.5 | 3.4 | 3.9 | 2.0 | 7.6 | 3.9 |
| | A5 | 15 | 45.6 | 1.2 | 2.7 | 1.4 | 3.0 | 1.8 | 4.0 |
| | A10 | 15 | 56.0 | 1.1 | 2.0 | 1.2 | 2.1 | 1.6 | 2.9 |
| | A20 | 15 | 62.2 | 0.8 | 1.3 | 1.4 | 2.2 | 1.6 | 2.6 |
| | MCF | 15 | 63.5 | 0.5 | 0.8 | 1.2 | 1.9 | 1.3 | 2.1 |
| Precision – Normal Whole Blood 3 | | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Assay | Parameter | N | Mean | Repeatability (Within-Instrument) | | Between-Instrument | | Within-Laboratory (Total) | |
| | | | | SD | %CV | SD | %CV | SD | %CV |
| INTEM C | CT | 15 | 177.1 | 5.3 | 3.0 | 2.4 | 1.3 | 5.8 | 3.3 |
| | A5 | 15 | 52.1 | 1.5 | 2.8 | 0.0 | 0.0 | 1.5 | 2.8 |
| | A10 | 15 | 61.6 | 1.0 | 1.6 | 0.0 | 0.0 | 1.0 | 1.6 |
| | A20 | 15 | 67.6 | 0.6 | 0.9 | 0.4 | 0.6 | 0.8 | 1.1 |
| | MCF | 15 | 68.9 | 0.4 | 0.6 | 0.6 | 0.9 | 0.8 | 1.1 |
| EXTEM C | CT | 15 | 55.6 | 3.0 | 5.4 | 1.3 | 2.3 | 3.3 | 5.9 |
| | A5 | 15 | 52.6 | 1.6 | 3.0 | 1.1 | 2.1 | 1.9 | 3.7 |
| | A10 | 15 | 62.2 | 1.2 | 1.9 | 0.9 | 1.5 | 1.5 | 2.4 |
| | A20 | 15 | 68.5 | 1.0 | 1.4 | 0.8 | 1.2 | 1.3 | 1.9 |
| | MCF | 15 | 70.8 | 0.7 | 1.0 | 0.6 | 0.8 | 0.9 | 1.3 |
| FIBTEM C | A5 | 15 | 12.7 | 0.4 | 2.9 | 0.5 | 4.0 | 0.6 | 4.9 |
| | A10 | 15 | 14.1 | 0.3 | 1.8 | 0.7 | 5.0 | 0.8 | 5.4 |
| | A20 | 15 | 15.1 | 0.4 | 3.0 | 0.6 | 4.2 | 0.8 | 5.2 |
| | MCF | 15 | 15.5 | 0.5 | 3.3 | 0.7 | 4.6 | 0.9 | 5.7 |
| HEPTEM C | CT | 15 | 179.5 | 6.2 | 3.5 | 0.0 | 0.0 | 6.2 | 3.5 |
| | A5 | 15 | 48.3 | 2.0 | 4.2 | 0.0 | 0.0 | 2.0 | 4.2 |

{13}

| Precision – Normal Whole Blood 3 | | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Assay | Parameter | N | Mean | Repeatability (Within-Instrument) | | Between-Instrument | | Within-Laboratory (Total) | |
| | | | | SD | %CV | SD | %CV | SD | %CV |
| | A10 | 15 | 58.7 | 1.7 | 2.8 | 0.6 | 0.9 | 1.8 | 3.0 |
| | A20 | 15 | 65.2 | 1.2 | 1.8 | 0.3 | 0.4 | 1.2 | 1.9 |
| | MCF | 15 | 67.4 | 0.9 | 1.4 | 0.7 | 1.0 | 1.1 | 1.7 |
| Precision – Hypocoagulable Whole Blood 1 | | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Assay | Parameter | N | Mean | Repeatability (Within-Instrument) | | Between-Instrument | | Within-Laboratory (Total) | |
| | | | | SD | %CV | SD | %CV | SD | %CV |
| INTEM C | CT | 15 | 322.3 | 10.9 | 3.4 | 2.3 | 0.7 | 11.1 | 3.4 |
| | A5 | 15 | 20.5 | 0.3 | 1.3 | 0.5 | 2.4 | 0.5 | 2.7 |
| | A10 | 15 | 28.2 | 0.6 | 2.0 | 0.7 | 2.5 | 0.9 | 3.2 |
| | A20 | 15 | 33.4 | 0.4 | 1.1 | 0.7 | 2.1 | 0.8 | 2.3 |
| | MCF | 15 | 34.4 | 0.6 | 1.7 | 0.8 | 2.2 | 1.0 | 2.8 |
| EXTEM C | CT | 15 | 95.5 | 8.6 | 9.0 | 8.3 | 8.7 | 12.0 | 12.5 |
| | A5 | 15 | 21.8 | 0.7 | 3.3 | 0.3 | 1.3 | 0.8 | 3.6 |
| | A10 | 15 | 29.5 | 0.5 | 1.8 | 0.4 | 1.4 | 0.7 | 2.2 |
| | A20 | 15 | 35.5 | 0.6 | 1.6 | 0.5 | 1.4 | 0.8 | 2.2 |
| | MCF | 15 | 36.9 | 0.5 | 1.4 | 0.7 | 1.8 | 0.8 | 2.3 |
| FIBTEM C | A5 | 15 | 3.4 | 0.0 | 0.0 | 0.5 | 16.1 | 0.5 | 16.1 |
| | A10 | 15 | 3.7 | 0.4 | 10.0 | 0.9 | 24.2 | 1.0 | 26.2 |
| | A20 | 15 | 4.1 | 0.3 | 6.2 | 0.9 | 20.7 | 0.9 | 21.6 |
| | MCF | 15 | 4.0 | 0.4 | 9.1 | 0.9 | 23.0 | 1.0 | 24.7 |
| HEPTEM C | CT | 15 | 314.0 | 13.4 | 4.3 | 17.9 | 5.7 | 22.3 | 7.1 |
| | A5 | 15 | 19.8 | 0.4 | 2.3 | 1.8 | 8.9 | 1.8 | 9.2 |
| | A10 | 15 | 27.7 | 0.3 | 0.9 | 2.3 | 8.3 | 2.3 | 8.4 |
| | A20 | 15 | 33.3 | 0.4 | 1.1 | 2.4 | 7.3 | 2.5 | 7.4 |
| | MCF | 15 | 34.3 | 0.6 | 1.8 | 2.4 | 7.1 | 2.5 | 7.4 |
| Precision – Hypocoagulable Whole Blood 2 | | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Assay | Parameter | N | Mean | Repeatability (Within-Instrument) | | Between-Instrument | | Within-Laboratory (Total) | |
| | | | | SD | %CV | SD | %CV | SD | %CV |
| INTEM C | CT | 15 | 341.7 | 12.9 | 3.8 | 8.1 | 2.4 | 15.2 | 4.5 |
| | A5 | 15 | 26.2 | 0.6 | 2.2 | 0.4 | 1.5 | 0.7 | 2.6 |
| | A10 | 15 | 35.0 | 0.4 | 1.0 | 0.8 | 2.4 | 0.9 | 2.6 |
| | A20 | 15 | 41.7 | 0.4 | 0.9 | 0.7 | 1.6 | 0.8 | 1.8 |
| | MCF | 15 | 43.3 | 0.4 | 1.0 | 0.5 | 1.1 | 0.6 | 1.5 |
| EXTEM C | CT | 15 | 82.8 | 4.5 | 5.5 | 2.1 | 2.6 | 5.0 | 6.1 |
| | A5 | 15 | 28.1 | 0.7 | 2.4 | 0.6 | 2.2 | 0.9 | 3.3 |
| | A10 | 15 | 37.0 | 0.5 | 1.4 | 0.9 | 2.5 | 1.1 | 2.9 |

{14}

| Precision – Hypocoagulable Whole Blood 2 | | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Assay | Parameter | N | Mean | Repeatability (Within-Instrument) | | Between-Instrument | | Within-Laboratory (Total) | |
| | | | | SD | %CV | SD | %CV | SD | %CV |
| | A20 | 15 | 44.3 | 0.4 | 0.8 | 0.9 | 2.0 | 1.0 | 2.2 |
| | MCF | 15 | 46.7 | 0.5 | 1.1 | 0.9 | 1.9 | 1.0 | 2.2 |
| FIBTEM C | A5 | 15 | 3.5 | 0.4 | 10.5 | 0.4 | 11.4 | 0.5 | 15.5 |
| | A10 | 15 | 3.7 | 0.4 | 9.8 | 0.5 | 13.5 | 0.6 | 16.7 |
| | A20 | 15 | 4.3 | 0.5 | 11.9 | 0.5 | 12.6 | 0.8 | 17.4 |
| | MCF | 15 | 4.1 | 0.6 | 14.0 | 0.5 | 12.2 | 0.8 | 18.6 |
| HEPTEM C | CT | 15 | 349.9 | 8.7 | 2.5 | 8.8 | 2.5 | 12.4 | 3.5 |
| | A5 | 15 | 25.5 | 0.9 | 3.4 | 1.7 | 6.8 | 1.9 | 7.5 |
| | A10 | 15 | 34.5 | 0.8 | 2.4 | 2.4 | 6.8 | 2.5 | 7.2 |
| | A20 | 15 | 41.5 | 0.8 | 2.0 | 2.4 | 5.7 | 2.5 | 6.0 |
| | MCF | 15 | 43.4 | 0.8 | 1.8 | 2.3 | 5.3 | 2.4 | 5.6 |
| Precision – Hypocoagulable Whole Blood 3 | | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Assay | Parameter | N | Mean | Repeatability (Within-Instrument) | | Between-Instrument | | Within-Laboratory (Total) | |
| | | | | SD | %CV | SD | %CV | SD | %CV |
| INTEM C | CT | 15 | 233.1 | 14.0 | 6.0 | 7.6 | 3.2 | 15.9 | 6.8 |
| | A5 | 15 | 20.9 | 0.5 | 2.5 | 0.5 | 2.5 | 0.7 | 3.5 |
| | A10 | 15 | 28.4 | 0.4 | 1.6 | 0.6 | 2.2 | 0.8 | 2.7 |
| | A20 | 15 | 33.1 | 0.4 | 1.4 | 0.7 | 2.2 | 0.8 | 2.6 |
| | MCF | 15 | 33.7 | 0.5 | 1.5 | 0.8 | 2.4 | 0.9 | 2.8 |
| EXTEM C | CT | 15 | 98.0 | 12.4 | 12.7 | 4.8 | 4.9 | 13.3 | 13.6 |
| | A5 | 15 | 20.7 | 1.1 | 5.2 | 0.0 | 0.0 | 1.1 | 5.2 |
| | A10 | 15 | 28.1 | 1.2 | 4.1 | 0.0 | 0.0 | 1.2 | 4.1 |
| | A20 | 15 | 34.0 | 1.3 | 3.8 | 0.2 | 0.7 | 1.3 | 3.9 |
| | MCF | 15 | 35.2 | 1.5 | 4.3 | 0.7 | 2.0 | 1.7 | 4.8 |
| FIBTEM C | A5 | 15 | 2.7 | 0.4 | 16.4 | 0.1 | 3.9 | 0.5 | 16.8 |
| | A10 | 15 | 2.9 | 0.4 | 15.2 | 0.1 | 3.6 | 0.5 | 15.7 |
| | A20 | 15 | 3.2 | 0.3 | 9.2 | 0.3 | 8.3 | 0.4 | 12.3 |
| | MCF | 15 | 2.9 | 0.4 | 15.6 | 0.3 | 9.7 | 0.5 | 18.4 |
| HEPTEM C | CT | 15 | 242.3 | 11.8 | 4.9 | 19.5 | 8.0 | 22.8 | 9.4 |
| | A5 | 15 | 20.4 | 0.4 | 1.8 | 1.9 | 9.4 | 1.9 | 9.5 |
| | A10 | 15 | 28.1 | 0.4 | 1.6 | 2.3 | 8.3 | 2.4 | 8.4 |
| | A20 | 15 | 32.7 | 0.7 | 2.1 | 2.7 | 8.2 | 2.8 | 8.5 |
| | MCF | 15 | 33.5 | 0.7 | 2.2 | 2.6 | 7.6 | 2.7 | 7.9 |

{15}

| Precision – Hypercoagulable Whole Blood 1 | | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Assay | Parameter | N | Mean | Repeatability (Within-Instrument) | | Between-Instrument | | Within-Laboratory (Total) | |
| | | | | SD | %CV | SD | %CV | SD | %CV |
| INTEM C | CT | 15 | 195.5 | 5.3 | 2.7 | 0.0 | 0.0 | 5.3 | 2.7 |
| | A5 | 15 | 51.9 | 1.8 | 3.4 | 0.9 | 1.8 | 2.0 | 3.9 |
| | A10 | 15 | 62.8 | 1.5 | 2.4 | 0.0 | 0.0 | 1.5 | 2.4 |
| | A20 | 15 | 69.7 | 1.1 | 1.6 | 0.2 | 0.3 | 1.1 | 1.6 |
| | MCF | 15 | 71.5 | 0.4 | 0.5 | 0.8 | 1.1 | 0.9 | 1.2 |
| EXTEM C | CT | 15 | 50.7 | 4.7 | 9.3 | 0.0 | 0.0 | 4.7 | 9.3 |
| | A5 | 15 | 56.5 | 1.1 | 1.9 | 0.9 | 1.5 | 1.4 | 2.5 |
| | A10 | 15 | 65.8 | 1.1 | 1.7 | 1.1 | 1.7 | 1.6 | 2.4 |
| | A20 | 15 | 72.2 | 0.9 | 1.2 | 1.1 | 1.5 | 1.4 | 1.9 |
| | MCF | 15 | 74.2 | 0.6 | 0.8 | 0.9 | 1.2 | 1.1 | 1.4 |
| FIBTEM C | A5 | 15 | 27.9 | 0.7 | 2.5 | 1.1 | 4.0 | 1.3 | 4.7 |
| | A10 | 15 | 30.3 | 0.6 | 1.9 | 1.3 | 4.3 | 1.4 | 4.7 |
| | A20 | 15 | 32.4 | 0.7 | 2.1 | 1.2 | 3.7 | 1.4 | 4.2 |
| | MCF | 15 | 35.6 | 0.9 | 2.5 | 1.1 | 3.1 | 1.4 | 4.0 |
| HEPTEM C | CT | 15 | 191.4 | 3.9 | 2.0 | 0.0 | 0.0 | 3.9 | 2.0 |
| | A5 | 15 | 48.5 | 1.6 | 3.4 | 0.4 | 0.9 | 1.7 | 3.5 |
| | A10 | 15 | 59.5 | 1.4 | 2.3 | 0.5 | 0.9 | 1.5 | 2.5 |
| | A20 | 15 | 67.2 | 0.9 | 1.3 | 0.5 | 0.8 | 1.0 | 1.5 |
| | MCF | 15 | 70.0 | 0.4 | 0.6 | 1.0 | 1.5 | 1.1 | 1.6 |
| Precision – Hypercoagulable Whole Blood 2 | | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Assay | Parameter | N | Mean | Repeatability (Within-Instrument) | | Between-Instrument | | Within-Laboratory (Total) | |
| | | | | SD | %CV | SD | %CV | SD | %CV |
| INTEM C | CT | 15 | 204.0 | 5.7 | 2.8 | 0.0 | 0.0 | 5.7 | 2.8 |
| | A5 | 15 | 56.1 | 1.3 | 2.3 | 1.0 | 1.8 | 1.6 | 2.9 |
| | A10 | 15 | 66.6 | 1.2 | 1.8 | 0.7 | 1.1 | 1.4 | 2.1 |
| | A20 | 15 | 72.7 | 0.8 | 1.1 | 0.7 | 0.9 | 1.1 | 1.5 |
| | MCF | 15 | 74.3 | 0.7 | 0.9 | 0.6 | 0.9 | 0.9 | 1.3 |
| EXTEM C | CT | 15 | 50.5 | 4.0 | 7.9 | 0.0 | 0.0 | 4.0 | 7.9 |
| | A5 | 15 | 57.9 | 1.5 | 2.6 | 0.4 | 0.7 | 1.5 | 2.7 |
| | A10 | 15 | 67.3 | 1.0 | 1.5 | 0.8 | 1.2 | 1.3 | 2.0 |
| | A20 | 15 | 73.5 | 0.9 | 1.2 | 0.5 | 0.6 | 1.0 | 1.4 |
| | MCF | 15 | 75.7 | 0.9 | 1.1 | 0.6 | 0.9 | 1.1 | 1.4 |
| FIBTEM C | A5 | 15 | 26.5 | 0.4 | 1.4 | 1.0 | 3.8 | 1.1 | 4.0 |
| | A10 | 15 | 28.6 | 0.4 | 1.3 | 1.2 | 4.3 | 1.3 | 4.4 |
| | A20 | 15 | 30.5 | 0.4 | 1.2 | 1.2 | 4.0 | 1.3 | 4.2 |
| | MCF | 15 | 32.5 | 0.6 | 1.8 | 1.4 | 4.3 | 1.5 | 4.6 |
| HEPTEM C | CT | 15 | 206.6 | 4.8 | 2.3 | 0.0 | 0.0 | 4.8 | 2.3 |
| | A5 | 15 | 52.2 | 1.8 | 3.4 | 0.0 | 0.0 | 1.8 | 3.4 |

{16}

| Precision – Hypercoagulable Whole Blood 2 | | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Assay | Parameter | N | Mean | Repeatability (Within-Instrument) | | Between-Instrument | | Within-Laboratory (Total) | |
| | | | | SD | %CV | SD | %CV | SD | %CV |
| | A10 | 15 | 63.0 | 1.4 | 2.2 | 0.4 | 0.6 | 1.5 | 2.3 |
| | A20 | 15 | 70.2 | 0.9 | 1.2 | 0.7 | 1.0 | 1.1 | 1.6 |
| | MCF | 15 | 72.6 | 0.6 | 0.8 | 0.9 | 1.2 | 1.0 | 1.4 |
| Precision – Hypercoagulable Whole Blood 3 | | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Assay | Parameter | N | Mean | Repeatability (Within-Instrument) | | Between-Instrument | | Within-Laboratory (Total) | |
| | | | | SD | %CV | SD | %CV | SD | %CV |
| INTEM C | CT | 15 | 182.9 | 8.2 | 4.5 | 0.9 | 0.5 | 8.3 | 4.5 |
| | A5 | 15 | 43.1 | 1.1 | 2.5 | 1.2 | 2.7 | 1.6 | 3.7 |
| | A10 | 15 | 54.5 | 1.0 | 1.8 | 1.1 | 2.1 | 1.5 | 2.8 |
| | A20 | 15 | 63.6 | 0.9 | 1.5 | 0.3 | 0.5 | 1.0 | 1.6 |
| | MCF | 15 | 67.7 | 0.6 | 0.9 | 0.7 | 1.0 | 0.9 | 1.4 |
| EXTEM C | CT | 15 | 63.4 | 8.6 | 13.6 | 0.0 | 0.0 | 8.6 | 13.6 |
| | A5 | 15 | 48.1 | 1.4 | 3.0 | 0.0 | 0.0 | 1.4 | 3.0 |
| | A10 | 15 | 59.1 | 0.9 | 1.6 | 0.0 | 0.0 | 0.9 | 1.6 |
| | A20 | 15 | 66.7 | 0.7 | 1.0 | 0.3 | 0.4 | 0.7 | 1.1 |
| | MCF | 15 | 69.4 | 0.4 | 0.6 | 0.5 | 0.7 | 0.7 | 0.9 |
| FIBTEM C | A5 | 15 | 24.5 | 0.3 | 1.1 | 1.1 | 4.5 | 1.1 | 4.7 |
| | A10 | 15 | 27.0 | 0.5 | 1.9 | 0.9 | 3.4 | 1.1 | 3.9 |
| | A20 | 15 | 29.0 | 0.4 | 1.5 | 1.0 | 3.6 | 1.1 | 3.9 |
| | MCF | 15 | 31.5 | 0.6 | 2.0 | 0.8 | 2.6 | 1.0 | 3.3 |
| HEPTEM C | CT | 15 | 189.0 | 3.0 | 1.6 | 1.7 | 0.9 | 3.4 | 1.8 |
| | A5 | 15 | 40.4 | 0.8 | 2.0 | 0.1 | 0.4 | 0.8 | 2.1 |
| | A10 | 15 | 52.0 | 0.9 | 1.6 | 0.7 | 1.3 | 1.1 | 2.1 |
| | A20 | 15 | 61.3 | 0.6 | 1.0 | 0.5 | 0.9 | 0.8 | 1.3 |
| | MCF | 15 | 66.1 | 0.3 | 0.4 | 0.8 | 1.2 | 0.9 | 1.3 |

# Lysis Precision Study - LI60 and ML

In an internal lysis precision study, the lysis parameters, LI60 and ML, were assessed for the INTEM C and EXTEM C assays of the ROTEM sigma complete + hep cartridge using normal donor whole blood and abnormal hyperfibrinolysis blood. This study was performed with three (3) lots of ROTEM sigma complete + hep cartridges. One donor per sample type and cartridge lot was tested on five instruments, with three replicates per instrument ( $N = 5$ instruments x 3 replicates/instrument). Overall, the lysis precision study demonstrated the performance of the ROTEM sigma complete + hep cartridge and the associated assays in measuring the lysis parameters LI60 and ML. The highest SD and $\%$ CV of the three cartridge lots for the parameters LI60 and ML are summarized below.

{17}

| Assay | Parameter | Within Instrument Normal Whole Blood | | Within Instrument Abnormal Hyperfibrinolysis Blood | |
| --- | --- | --- | --- | --- | --- |
| | | SD | %CV | SD | %CV |
| INTEM C | LI60 | NA | 1.5 | 0.7 | NA |
| | ML* | 1.4 | NA | NA | 0.7 |
| EXTEM C | LI60 | NA | 1.4 | 1.4 | NA |
| | ML* | 1.3 | NA | NA | 1.5 |

*Calculated at 60 minutes after CT

# Lot-to-Lot Variability Study with Normal Donor Whole Blood.

To assess performance variability between lots of ROTEM sigma complete + hep cartridges, a precision study was conducted using donor whole blood. The study was for five days, with two runs per day, three replicates per run per cartridge lot. For each run, the same donor sample is used across all three cartridge lots. Ten different donor samples were used for the five-day study. Data was analyzed using a two-factor nested ANOVA with donor nested within lot. Overall, the data shows that similar results can be expected for different cartridge lots when running the same sample.

| Lot-to-Lot Precision Summary - ROTEM sigma complete + hep | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| Assay | Parameter | N | Mean | Within-Lot | | Between-Lot | |
| | | | | SD | %CV | SD | %CV |
| INTEM C | CT | 90 | 183.8 | 9.0 | 4.9 | 0.0 | 0.0 |
| | A5 | 90 | 43.9 | 3.9 | 8.9 | 0.0 | 0.0 |
| | A10 | 90 | 54.1 | 4.1 | 7.5 | 0.0 | 0.0 |
| | A20 | 90 | 60.5 | 4.4 | 7.3 | 0.0 | 0.0 |
| | MCF | 90 | 62.0 | 5.1 | 8.1 | 0.0 | 0.0 |
| | LI60 | 90 | 96.9 | 2.1 | 2.2 | 0.0 | 0.0 |
| | ML* | 90 | 3.1 | 2.1 | 67.9 | 0.0 | 0.0 |
| EXTEM C | CT | 90 | 58.3 | 5.1 | 8.8 | 0.0 | 0.0 |
| | A5 | 90 | 44.2 | 3.9 | 8.9 | 0.0 | 0.0 |
| | A10 | 90 | 54.5 | 4.1 | 7.4 | 0.0 | 0.0 |
| | A20 | 90 | 61.6 | 4.2 | 6.7 | 0.0 | 0.0 |
| | MCF | 90 | 63.9 | 4.7 | 7.4 | 0.0 | 0.0 |
| | LI60 | 90 | 97.6 | 1.7 | 1.8 | 0.0 | 0.0 |
| | ML* | 90 | 2.4 | 1.7 | 73.1 | 0.0 | 0.0 |
| FIBTEM C | A5 | 90 | 11.7 | 3.0 | 25.9 | 0.0 | 0.0 |
| | A10 | 90 | 12.7 | 3.3 | 25.8 | 0.0 | 0.0 |
| | A20 | 90 | 13.5 | 3.4 | 25.0 | 0.0 | 0.0 |
| | MCF | 90 | 13.8 | 3.5 | 25.6 | 0.0 | 0.0 |
| HEPTEM C | CT | 90 | 182.7 | 10.3 | 5.6 | 0.4 | 0.2 |
| | A5 | 90 | 41.1 | 3.6 | 8.7 | 0.0 | 0.0 |

{18}

| Lot-to-Lot Precision Summary - ROTEM sigma complete + hep | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| Assay | Parameter | N | Mean | Within-Lot | | Between-Lot | |
| | | | | SD | %CV | SD | %CV |
| | A10 | 90 | 51.8 | 3.7 | 7.1 | 0.0 | 0.0 |
| | A20 | 90 | 58.9 | 4.0 | 6.8 | 0.0 | 0.0 |
| | MCF | 90 | 60.9 | 4.7 | 7.7 | 0.0 | 0.0 |

*Calculated at 60 minutes after CT

# Reproducibility

To assess the device's performance reproducibility, reproducibility studies were performed at three (3) external point of care sites on one (1) lot of ROTEM sigma complete + hep cartridges using four (4) ROTEM sigma instruments per site and three (3) lots each of the controls ROTEM sigma ROTROL N and ROTEM sigma ROTROL P. The study was run in triplicate twice a day for five (5) days, for a total of thirty (30) replicates per control.

Estimates of reproducibility based on the aggregate data were obtained via a three-way nested ANOVA. The pooled data from three (3) external sites for each control lot are presented below. Overall, the performance across all three sites lies within the specified acceptance criteria.

Pooled Reproducibility - All Sites - ROTROL N

| Assay | Parameter | N | Mean | Repeatability | | Between Run | | Between Day | | Between Site | | Within Control Lot / Reproducibility | | Between Control Lot | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | | | SD | CV | SD | CV | SD | CV | SD | CV | SD | CV | SD | CV |
| INTEM C | CT (s) | 270 | 344.8 | 24.6 | 7.1% | 0.0 | 0.0% | 1.4 | 0.4% | 3.6 | 1.0% | 24.9 | 7.2% | 9.0 | 2.6% |
| | A5 (mm) | 270 | 43.8 | 0.7 | 1.6% | 0.1 | 0.2% | 0.2 | 0.4% | 0.3 | 0.7% | 0.8 | 1.8% | 0.0 | 0.0% |
| | A10 (mm) | 270 | 47.4 | 0.7 | 1.4% | 0.0 | 0.0% | 0.3 | 0.6% | 0.5 | 1.0% | 0.9 | 1.9% | 0.0 | 0.0% |
| | A20 (mm) | 270 | 51.2 | 0.7 | 1.4% | 0.0 | 0.1% | 0.3 | 0.5% | 0.6 | 1.1% | 1.0 | 1.9% | 0.0 | 0.0% |
| | MCF (mm) | 270 | 55.0 | 0.8 | 1.4% | 0.4 | 0.7% | 0.2 | 0.4% | 0.7 | 1.3% | 1.1 | 2.1% | 0.0 | 0.0% |
| EXTEM C | CT (s) | 270 | 130.2 | 13.6 | 10.4% | 2.9 | 2.2% | 0.0 | 0.0% | 1.7 | 1.3% | 14.0 | 10.7% | 3.3 | 2.5% |
| | A5 (mm) | 270 | 43.6 | 0.9 | 2.1% | 0.3 | 0.7% | 0.0 | 0.0% | 0.2 | 0.4% | 1.0 | 2.3% | 0.4 | 0.9% |
| | A10 (mm) | 270 | 47.7 | 0.9 | 1.8% | 0.3 | 0.6% | 0.0 | 0.0% | 0.1 | 0.3% | 0.9 | 2.0% | 0.4 | 0.8% |
| | A20 (mm) | 270 | 52.1 | 0.8 | 1.5% | 0.3 | 0.5% | 0.0 | 0.0% | 0.2 | 0.4% | 0.8 | 1.6% | 0.3 | 0.6% |
| | MCF (mm) | 270 | 56.9 | 0.9 | 1.6% | 0.2 | 0.4% | 0.0 | 0.0% | 0.3 | 0.6% | 1.0 | 1.7% | 0.2 | 0.3% |
| FIBTEM C | A5 (mm) | 269* | 37.8 | 1.2 | 3.2% | 0.4 | 1.1% | 0.0 | 0.0% | 0.3 | 0.9% | 1.3 | 3.5% | 0.7 | 1.9% |
| | A10 (mm) | 269* | 42.3 | 1.2 | 2.8% | 0.4 | 1.0% | 0.0 | 0.0% | 0.3 | 0.7% | 1.3 | 3.1% | 0.7 | 1.6% |
| | A20 (mm) | 269* | 47.1 | 1.1 | 2.3% | 0.4 | 0.9% | 0.0 | 0.0% | 0.3 | 0.7% | 1.2 | 2.6% | 0.5 | 1.2% |
| | MCF (mm) | 269* | 52.9 | 1.1 | 2.0% | 0.4 | 0.8% | 0.0 | 0.0% | 0.6 | 1.1% | 1.3 | 2.5% | 0.3 | 0.5% |
| HEPTEM C | CT (s) | 270 | 332.6 | 20.8 | 6.3% | 0.0 | 0.0% | 5.1 | 1.5% | 0.0 | 0.0% | 21.4 | 6.4% | 10.7 | 3.2% |
| | A5 (mm) | 270 | 43.1 | 0.8 | 1.9% | 0.0 | 0.0% | 0.0 | 0.0% | 0.7 | 1.6% | 1.1 | 2.5% | 0.0 | 0.0% |
| | A10 (mm) | 270 | 46.9 | 0.9 | 1.8% | 0.0 | 0.0% | 0.1 | 0.3% | 0.8 | 1.8% | 1.2 | 2.5% | 0.0 | 0.0% |
| | A20 (mm) | 270 | 51.0 | 0.8 | 1.6% | 0.0 | 0.0% | 0.1 | 0.2% | 0.8 | 1.6% | 1.1 | 2.2% | 0.0 | 0.0% |
| | MCF (mm) | 270 | 54.9 | 0.8 | 1.5% | 0.3 | 0.5% | 0.1 | 0.1% | 0.9 | 1.6% | 1.2 | 2.3% | 0.0 | 0.0% |

* No FIBTEM data provided for one sample

Pooled Reproducibility - All Sites - ROTROL P

| Assay | Parameter | N | Mean | Repeatability | | Between Run | | Between Day | | Between Site | | Within Control Lot / Reproducibility | | Between Control Lot | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | | | SD | CV | SD | CV | SD | CV | SD | CV | SD | CV | SD | CV |
| INTEM C | CT (s) | 270 | 365.3 | 9.6 | 2.6% | 4.5 | 1.2% | 2.3 | 0.6% | 3.5 | 0.9% | 11.4 | 3.1% | 63.0 | 17.2% |
| | A5 (mm) | 270 | 24.3 | 1.1 | 4.4% | 0.4 | 1.6% | 0.0 | 0.0% | 0.3 | 1.1% | 1.2 | 4.8% | 0.0 | 0.0% |

{19}

| Assay | Parameter | N | Mean | Repeatability | | Between Run | | Between Day | | Between Site | | Within Control Lot / Reproducibility | | Between Control Lot | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | | | SD | CV | SD | CV | SD | CV | SD | CV | SD | CV | SD | CV |
| | A10 (mm) | 270 | 27.0 | 1.1 | 4.1% | 0.5 | 2.0% | 0.0 | 0.0% | 0.2 | 0.7% | 1.3 | 4.6% | 0.0 | 0.0% |
| | A20 (mm) | 270 | 29.5 | 1.2 | 4.1% | 0.6 | 2.0% | 0.0 | 0.0% | 0.3 | 0.9% | 1.4 | 4.7% | 0.0 | 0.0% |
| | MCF (mm) | 270 | 31.7 | 1.3 | 4.2% | 0.6 | 1.9% | 0.0 | 0.0% | 0.3 | 1.0% | 1.5 | 4.7% | 0.0 | 0.0% |
| EXTEM C | CT (s) | 270 | 146.7 | 6.0 | 4.1% | 0.0 | 0.0% | 2.4 | 1.6% | 3.8 | 2.6% | 7.5 | 5.1% | 0.7 | 0.5% |
| | A5 (mm) | 270 | 24.8 | 1.3 | 5.1% | 0.5 | 2.1% | 0.0 | 0.0% | 0.2 | 0.7% | 1.4 | 5.5% | 0.2 | 0.7% |
| | A10 (mm) | 270 | 27.7 | 1.3 | 4.8% | 0.6 | 2.3% | 0.0 | 0.0% | 0.3 | 1.0% | 1.5 | 5.4% | 0.0 | 0.0% |
| | A20 (mm) | 270 | 30.3 | 1.4 | 4.6% | 0.7 | 2.3% | 0.0 | 0.0% | 0.2 | 0.8% | 1.6 | 5.2% | 0.1 | 0.5% |
| | MCF (mm) | 270 | 32.7 | 1.5 | 4.6% | 0.7 | 2.2% | 0.0 | 0.0% | 0.1 | 0.2% | 1.7 | 5.1% | 0.2 | 0.7% |
| FIBTEM C | A5 (mm) | 270 | 24.8 | 1.2 | 5.0% | 0.4 | 1.8% | 0.0 | 0.0% | 0.4 | 1.5% | 1.4 | 5.5% | 0.0 | 0.0% |
| | A10 (mm) | 270 | 27.7 | 1.3 | 4.8% | 0.5 | 1.9% | 0.0 | 0.0% | 0.4 | 1.5% | 1.5 | 5.4% | 0.0 | 0.0% |
| | A20 (mm) | 270 | 30.4 | 1.5 | 4.8% | 0.5 | 1.8% | 0.0 | 0.0% | 0.5 | 1.6% | 1.6 | 5.4% | 0.0 | 0.0% |
| | MCF (mm) | 270 | 33.1 | 1.6 | 4.7% | 0.7 | 2.0% | 0.0 | 0.0% | 0.3 | 1.0% | 1.7 | 5.2% | 0.0 | 0.0% |
| HEPTEM C | CT (s) | 270 | 367.4 | 10.7 | 2.9% | 4.7 | 1.3% | 2.3 | 0.6% | 9.0 | 2.5% | 14.9 | 4.1% | 66.8 | 18.2% |
| | A5 (mm) | 270 | 25.1 | 1.1 | 4.5% | 0.5 | 1.8% | 0.0 | 0.0% | 0.9 | 3.7% | 1.5 | 6.1% | 0.0 | 0.0% |
| | A10 (mm) | 270 | 27.9 | 1.2 | 4.3% | 0.4 | 1.5% | 0.0 | 0.0% | 0.9 | 3.1% | 1.5 | 5.5% | 0.0 | 0.0% |
| | A20 (mm) | 270 | 30.4 | 1.3 | 4.2% | 0.6 | 2.0% | 0.0 | 0.0% | 0.8 | 2.6% | 1.6 | 5.3% | 0.0 | 0.0% |
| | MCF (mm) | 270 | 32.5 | 1.4 | 4.2% | 0.7 | 2.1% | 0.0 | 0.0% | 0.8 | 2.6% | 1.7 | 5.4% | 0.0 | 0.0% |

# 2. Linearity:

Not applicable

# 3. Analytical Specificity/Interference:

# Interference - UF Heparin, LMW Heparin, Tranexamic acid, $\varepsilon$ -Aminocaproic acid, Acetylsalicylic Acid (Aspirin), Ticagrelor, and Lupus Anticoagulant

Interference studies were conducted to assess the interference of UF Heparin, LMW Heparin, Tranexamic acid, $\varepsilon$ -Aminocaproic acid, Acetylsalicylic Acid (Aspirin), Ticagrelor, and lupus anticoagulant on the ROTEM sigma with each of the sigma assays (INTEM C, EXTEM C, FIBTEM C, and HEPTEM C). Three interference levels were evaluated (baseline, claim and greater than claim) for each interference substance. For all interferent except lupus anticoagulant, normal donor whole blood and abnormal hypocoagulable whole blood were used. For each interferent and blood sample type, a single pool was prepared from whole blood from one donor. This pool was distributed evenly into baseline, claim, and above claim levels. Each level was spiked with the interferent to the desired concentration and evenly aliquoted. The results of each interferent level were compared to the results at baseline (normal) level. If the $\%$ difference from baseline exceeded the predetermined acceptance criteria, then interference has occurred.

Another interference study was performed using normal whole blood samples to determine the impact of lupus anticoagulant on the same assays. Eleven normal whole blood samples were used. Each donor sample was run on three instruments with one replicate per instrument. Three interferent levels were tested, including baseline, claim, and greater than claim as shown in the table below.

Lupus Anticoagulant Interference Level

Mean dRVVT Screen/Confirm Test Ratio

{20}

| Baseline | 1.05 |
| --- | --- |
| Claim | 1.34 |
| Greater Than Claim | 1.59 |

Each donor's citrated whole blood pool created samples for all interferent levels, dRVVT screen and confirm tests. Prior to interference testing, two replicates of plasma from each donor were run for each interferent level on dRVVT screen and dRVVT confirm assays.

# Interference Claims

Testing confirmed no interference for INTEM C, EXTEM C, FIBTEM C, and HEPTEM C assays on the ROTEM sigma up to the following concentrations:

| Interferent | INTEM C | EXTEM C | FIBTEM C | HEPTEM C |
| --- | --- | --- | --- | --- |
| UF Heparin | N/A | 5 IU/mL | 5 IU/mL | 7 IU/mL |
| LMW Heparin | N/A | 3 IU/mL | 3 IU/mL | 3 IU/mL |
| Tranexamic Acid | 60 μg/mL | 60 μg/mL | 60 μg/mL | 60 μg/mL |
| ε-Aminocaproic Acid | 600 μg/mL | 600 μg/mL | 600 μg/mL | 600 μg/mL |
| Aspirin | 3 mg/dL | 3 mg/dL | 3 mg/dL | 3 mg/dL |
| Ticagrelor | 0.1881 mg/dL | 0.1881 mg/dL | 0.1881 mg/dL | 0.1881 mg/dL |
| Lupus Anticoagulant (dRVVT Screen/Confirm Ratio) | 1.34 | 1.34 | 1.34 | 1.34 |

# Interference - Hematocrit

Whole blood samples with three different hematocrit (Hct) levels (low-23% Hct, normal-40% Hct and high-55% Hct) were evaluated. The results for low and high hematocrit samples were compared to the results for normal hematocrit sample. The study results showed that compared to normal hematocrit samples, low hematocrit samples showed little change or a shortening of CT and an increase in amplitude parameters (A5, A10, A20, MCF), while compared to normal hematocrit samples, high hematocrit samples showed a prolongation of CT and a decrease in amplitude parameters (A5, A10, A20, MCF).

# 4. Assay Reportable Range:

The reportable ranges for the ROTEM sigma assays are based on the data of the method comparison and precision studies and presented below.

| Parameter\Assay | INTEM C | EXTEM C | FIBTEM C | HEPTEM C |
| --- | --- | --- | --- | --- |
| CT (s) | 123–365 | 45–172 | N/A | 122–376 |

{21}

| Parameter\Assay | INTEM C | EXTEM C | FIBTEM C | HEPTEM C |
| --- | --- | --- | --- | --- |
| A5 (mm) | 11–66 | 13–69 | 2–33 | 10–59 |
| A10 (mm) | 16–74 | 18–77 | 2–36 | 15–68 |
| A20 (mm) | 21–78 | 23–81 | 2–38 | 20–73 |
| MCF (mm) | 24–79 | 25–82 | 2–41 | 24–75 |
| LI60 (%) | 0–100 | 0–100 | N/A | N/A |
| ML* (%) | 0–100 | 0–100 | N/A | N/A |

* Calculated at 60 minutes after CT

5. Traceability, Stability, Expected Values (Controls, Calibrators, or Methods):

## Shelf-Life Stability

A study was conducted to evaluate the shelf-life stability of the ROTEM sigma complete + hep cartridge. The study tested three lots of cartridge using normal whole blood and contrived whole blood samples and two lots of normal control ROTROL N. The trended ROTROL N testing was performed to ensure that the base set of reagents in the extrinsic and intrinsic assays were stable over time independently of the inhibitors that are present in the other assays. The test cartridges were stored at 25°C and tested at different time points. Overall, the shelf-life test results support a 24-month shelf-life claim for ROTEM sigma complete + hep cartridges at 25°C.

## In-Use Stability

An in-use stability study was performed to support the claim that the ROTEM sigma cartridges are stable if they are used within 10 minutes of opening the sealed pouch. One lot of ROTEM sigma complete + hep cartridge was tested. Sample type included normal whole blood, abnormal hypocoagulable blood, and abnormal hypercoagulable blood. Opened sample cartridges were stored in a temperature and humidity-controlled chamber set to room temperature (21.6–23.5°C) and 55.3–59.6% relative humidity. Cartridges were used at three time points. Overall, the study results support the cartridge in-use stability claim of 10 minutes at room temperature.

## Transport Stability

To assess transport stability for the reagents used in the ROTEM sigma cartridges, a study simulating the influence of elevated and freezing temperatures, which might occur during transport, by subjecting the cartridges to different stressing conditions including no precondition room temperature (15–25°C), low temperature preconditioning (≤ -20°C for at least 24 hours) and high temperature preconditioning (40°C for 5 days), was conducted. The study evaluated one lot of ROTEM sigma complete + hep cartridge using normal whole blood samples, contrived whole blood samples and one lot of normal control (ROTROL N). Each test run consists of three cartridges, each having undergone a different preconditioning as described above. The results with temperature precondition were compared to the results without precondition. Overall, the transport stress testing for the ROTEM sigma complete +

{22}

hep cartridge met the predefined criteria. The results demonstrate transport stability of ROTEM sigma complete + hep cartridge at temperatures ≤-20°C for 24 hours and 40°C for 5 days.

## Sample Stability

A sample stability study was performed to assess the stability of fresh citrated whole blood samples at room temperature used on the ROTEM sigma. Test samples included normal whole blood samples, abnormal hypocoagulable samples, and abnormal hypercoagulable samples. One lot of ROTEM sigma complete + hep cartridge was used. Samples were run at three time points. Overall, the results meet the predetermined acceptance criteria and support the sample stability claim of 4 hours for whole blood samples ran on the ROTEM sigma using the ROTEM sigma complete + hep cartridges.

6. Detection Limit:
Not applicable

7. Assay Cut-Off:
Not applicable

8. Accuracy (Instrument):
Not applicable

9. Carry-Over:
Not applicable

## B Comparison Studies:

1. Method Comparison with Predicate Device:

A method comparison study was conducted at four clinical sites, with a minimum of two trained POC operators at each site, to compare the performance of ROTEM sigma instrument and assays to that of the predicate ROTEM delta instrument and assays using venous or arterial whole blood patient samples from the intended use populations (cardiac surgery and liver transplantation) and contrived samples. Citrated whole blood samples, collected from 181 patients 21 years and older, were used in this method comparison study.

The evaluated ROTEM parameters included CT, A5, A10, A20, MCF, LI60 and ML for EXTEM C and INTEM C assays, A5, A10, A20 and MCF for FIBTEM C assay, and CT, A5, A10, A20, and MCF for HEPTEM C assay. Parameter results were obtained from tests run in singlicate. All evaluated parameters were analyzed using Passing-Bablok regression and Bland-Altman plots. Slopes and intercepts, along with 95% confidence intervals, were calculated from the respective regression fit. Correlation coefficients were also computed. The bias (with 95% confidence intervals) between ROTEM sigma results and the ROTEM delta predicate results was calculated from the regression fit at the extremes of the reference

{23}

interval and is presented along with Bland-Altman difference plots over the entire reference interval. For the FIBTEM assay the parameter CT, LI60, and ML were not evaluated, since they are not claimed parameters for this assay. Also, LI60 and ML were not evaluated for HEPTEM C, as they are not claimed parameters for this assay.

The results for ROTEM sigma with ROTEM sigma complete + hep cartridge versus the ROTEM delta are presented below.

| Method Comparison Results Summary | | | | | |
| --- | --- | --- | --- | --- | --- |
| Assay | Parameter | N | Slope (95% CI) | Intercept (95% CI) | R |
| INTEM | CT | 144 | 0.94 (0.84, 1.02) | 20.9 (3.1, 36.9) | 0.845 |
| | A5 | 144 | 0.91 (0.88, 0.94) | 3.8 (2.8, 4.9) | 0.977 |
| | A10 | 144 | 0.90 (0.88, 0.93) | 4.8 (3.6, 6.1) | 0.983 |
| | A20 | 144 | 0.92 (0.89, 0.95) | 4.5 (2.9, 5.6) | 0.985 |
| | MCF | 144 | 0.95 (0.92, 1.00) | 2.5 (0.0, 4.2) | 0.982 |
| | LI60 | 148 | 1.00 (1.00, 1.01) | 1.0 (0.0, 1.0) | 0.990 |
| | ML* | 148 | 1.00 (1.00, 1.01) | -1.0 (-1.0, 0.0) | 0.990 |
| EXTEM | CT | 183 | 1.17 (1.00, 1.33) | -4.0 (-14.7, 5.0) | 0.780 |
| | A5 | 183 | 0.94 (0.90, 1.00) | 5.1 (3.0, 6.5) | 0.953 |
| | A10 | 183 | 0.93 (0.89, 0.96) | 5.9 (4.3, 7.7) | 0.966 |
| | A20 | 183 | 0.95 (0.92, 1.00) | 4.7 (2.0, 6.6) | 0.973 |
| | MCF | 183 | 1.00 (0.96, 1.00) | 2.0 (2.0, 4.4) | 0.977 |
| | LI60 | 187 | 1.00 (1.00, 1.01) | 1.0 (1.0, 2.0) | 0.982 |
| | ML* | 187 | 1.00 (1.00, 1.01) | -1.0 (-2.0, -1.0) | 0.982 |
| FIBTEM | A5 | 183 | 0.86 (0.82, 0.90) | 0.4 (-0.1, 0.8) | 0.920 |
| | A10 | 183 | 0.89 (0.83, 0.94) | 0.3 (-0.3, 0.9) | 0.921 |
| | A20 | 183 | 0.91 (0.86, 1.00) | 0.3 (-1.0, 0.8) | 0.923 |
| | MCF | 183 | 1.00 (0.90, 1.00) | -1.0 (-1.0, 0.4) | 0.926 |
| HEPTEM | CT | 182 | 0.91 (0.78, 1.06) | 21.4 (-3.4, 45.9) | 0.484 |
| | A5 | 182 | 0.92 (0.88, 0.95) | 3.1 (2.0, 4.1) | 0.940 |
| | A10 | 182 | 0.93 (0.90, 0.97) | 3.6 (2.1, 4.9) | 0.947 |
| | A20 | 182 | 0.95 (0.92, 1.00) | 3.0 (1.0, 4.7) | 0.959 |

{24}

| Method Comparison Results Summary | | | | | |
| --- | --- | --- | --- | --- | --- |
| Assay | Parameter | N | Slope (95% CI) | Intercept (95% CI) | R |
| | MCF | 182 | 1.00 (0.94, 1.00) | 1.0 (1.0, 4.1) | 0.966 |

*Calculated at 60 minutes after CT

# 2. Matrix Comparison:

A matrix comparison study using 74 matched venous and arterial citrated whole blood samples was performed at two external clinical sites to evaluate the difference in test results for venous and arterial blood on the EXTEM C, INTEM C, FIBTEM C, and HEPTEM C and assays. The study was performed using four ROTEM sigma instruments at each site. Seventy-four matched venous and arterial citrated whole blood samples were collected into evacuated collection tubes containing $3.2\%$ sodium citrate and analyzed in singlicate on ROTEM sigma systems using ROTEM sigma complete + hep cartridges.

The pointwise biases of the paired differences were calculated. The pooled data summary results for the ROTEM sigma complete + hep cartridges are presented in the tables below. Overall, the results demonstrated that venous and arterial whole blood samples are equivalent on the ROTEM sigma system with the ROTEM sigma complete + hep cartridges.

Arterial vs. Venous Study Summary

| Assay | Parameter | N | Venous Mean | Arterial Mean | Mean Difference1 | 95% Confidence Interval | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| INTEM C | CT (s) | 58 | 480.5 | 449.2 | 1.4% | -5.6% | 8.4% |
| | A5 (mm) | 55 | 43.9 | 44.6 | 11.1% | -8.4% | 30.6% |
| | A5 (mm)2 | 54 | 44.5 | 44.5 | 1.6% | -2.4% | 5.6% |
| | A10 (mm) | 55 | 53.8 | 54.5 | 7.5% | -5.2% | 20.2% |
| | A10 (mm)2 | 54 | 54.6 | 54.4 | 1.6% | -2.9% | 6.0% |
| | A20 (mm) | 55 | 59.9 | 60.5 | 5.1% | -3.7% | 13.9% |
| | A20 (mm)2 | 54 | 60.6 | 60.4 | 1.5% | -3.6% | 6.6% |
| | MCF (mm) | 55 | 61.4 | 61.7 | 3.3% | -3.4% | 10.1% |
| | LI60 (%) | 54 | 96.4 | 95.7 | -0.7% | -1.0% | -0.4% |
| | ML (%) | 54 | 3.6 | 4.3 | 0.7% Lysis | 0.4% Lysis | 1.0% Lysis |
| EXTEM C | CT (s) | 73 | 72.1 | 72.3 | 0.6% | -1.6% | 2.7% |
| | A5 (mm) | 73 | 46.2 | 46.5 | 1.0% | -0.2% | 2.3% |
| | A10 (mm) | 73 | 56.5 | 56.6 | 0.4% | -0.6% | 1.3% |
| | A20 (mm) | 73 | 63.1 | 63.1 | 0.0% | -0.8% | 0.8% |
| | MCF (mm) | 73 | 65.1 | 64.9 | -0.2% | -0.9% | 0.5% |
| | LI60 (%) | 73 | 97.4 | 97.2 | -0.2% | -0.4% | 0.0% |
| | ML (%) | 73 | 2.6 | 2.8 | 0.2% Lysis | 0.0% Lysis | 0.4% Lysis |
| FIBTEM C | A5 (mm) | 71 | 14.2 | 14.3 | 0.9% | -1.0% | 2.9% |
| | A10 (mm) | 71 | 15.7 | 15.8 | 0.8% | -1.1% | 2.6% |
| | A20 (mm) | 71 | 17.0 | 17.1 | 0.8% | -0.6% | 2.3% |

{25}

| Assay | Parameter | N | Venous Mean | Arterial Mean | Mean Difference¹ | 95% Confidence Interval | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | MCF (mm) | 71 | 17.6 | 17.8 | 1.1% | -0.6% | 2.9% |
| HEPTEM C | CT (s) | 64 | 183.5 | 185.5 | 2.9% | -1.2% | 6.9% |
| | A5 (mm) | 64 | 43.0 | 43.7 | 1.7% | 0.5% | 2.9% |
| | A10 (mm) | 64 | 53.4 | 54.2 | 1.5% | 0.6% | 2.4% |
| | A20 (mm) | 64 | 60.2 | 60.7 | 0.8% | 0.1% | 1.5% |
| | MCF (mm) | 64 | 62.3 | 62.2 | 0.0% | -0.7% | 0.6% |

¹ Mean difference is calculated from Bland-Altman plot.
² Outlier suppressed.

## C Clinical Studies:

1. Clinical Sensitivity:
Not applicable

2. Clinical Specificity:
Not applicable

3. Other Clinical Supportive Data (When 1. and 2. Are Not Applicable):
Not applicable

## D Clinical Cut-Off:

Not applicable

## E Expected Values/Reference Range:

A reference study was conducted to establish the normal range for EXTEM C, FIBTEM C, INTEM C and HEPTEM C assays on ROTEM sigma for ROTEM sigma complete + hep cartridge. One hundred twenty venous samples from healthy normal donors were included in the study. Each whole blood sample was tested in singlicate. The nonparametric, 95% reference interval along with two-sided, 90% confidence intervals around each limit were calculated for each of the assay parameters. The determined reference intervals for ROTEM sigma complete + hep cartridge on the ROTEM sigma instrument are summarized in the tables below.

Reference Intervals Summary

| Parameter\Assay | INTEM C | EXTEM C | FIBTEM C | HEPTEM C |
| --- | --- | --- | --- | --- |
| CT (sec) | 139 – 205 | 51 – 73 | N/A | 141 – 215 |
| A5 (mm) | 36 – 54 | 33 – 52 | 5 - 16 | 33 – 51 |
| A10 (mm) | 46 – 63 | 45 – 62 | 6 - 17 | 44 – 61 |
| A20 (mm) | 53 – 68 | 54 – 69 | 6 - 18 | 52 – 67 |

{26}

| Parameter\Assay | INTEM C | EXTEM C | FIBTEM C | HEPTEM C |
| --- | --- | --- | --- | --- |
| MCF (mm) | 55 – 70 | 57 – 72 | 6 - 19 | 54 – 69 |
| LI60 (%) | 93 – 100 | 94 – 100 | N/A | N/A |
| ML* (%) | 0 – 7 | 0 – 6 | N/A | N/A |

* Calculated at 60 minutes after CT

## VIII Proposed Labeling:

The labeling supports the finding of substantial equivalence for this device.

## IX Conclusion:

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.