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K Number
K201440
Device Name
ROTEM sigma Thromboelastometry System
Manufacturer
Tem Innovations GmbH
Date Cleared
2022-07-08

(767 days)

Product Code
JPA
Regulation Number
864.5425
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP Authorized
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 Description
The ROTEM sigma 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 semiquantitative information about the coagulation state of a blood sample. The ROTEM sigma system records the kinetic changes in a sample of 3.2% citrated whole blood during clot formation, as well as when the sample clot retracts and/or lyses. Several parameters are measured and reported for this purpose. The graphical presentation reflects the various physiological results, which describe the interaction between coagulation factors and inhibitors, fibrinogen, platelets, and the fibrinolysis system. Additionally, the effect of certain drugs influencing hemostasis, in particular some anticoagulants (e.g. heparin), can be detected. The ROTEM sigma 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 of 4.75°. The oscillation of the axis is driven by a motor that is connected to the axis via a spring. 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 via a mirror plate at the upper end of the axis, which reflects the light from a diode light source onto a light sensitive sensor. 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. The result is a balance between the spring tension and the tension of the clot. As the clot becomes firmer, the oscillation amplitude of the axis is reduced. The ROTEM sigma assays are based on the principle of either * intrinsic coagulation activation with or without the presence of heparin, or * extrinsic coagulation activation with or without the presence of platelet inhibitors.
More Information

K083842, K101533

Not Found

No
The summary describes a system based on rotational thromboelastometry and does not mention AI or ML. The analysis focuses on physical measurements and established coagulation principles.

No.
Explanation: The device is an in vitro diagnostic (IVD) system used to monitor and analyze a patient's coagulation status, providing information for diagnosis but not directly treating a condition.

Yes

Explanation: The "Intended Use / Indications for Use" section explicitly states "The ROTEM sigma thromboelastometry system is a fully integrated and automated in vitro diagnostic system". Additionally, it consistently refers to its use in assessing patient conditions and for "in vitro Diagnostic Use".

No

The device description clearly details hardware components like a motor, spring, optical detection system (diode light source, light sensitive sensor), and a heated cartridge, indicating it is a physical instrument, not software only.

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

Here's why:

  • Explicit Statement: The "Intended Use / Indications for Use" section explicitly states: "The ROTEM sigma thromboelastometry system is a fully integrated and automated in vitro diagnostic system..." and "For in vitro Diagnostic Use."
  • Device Description: The "Device Description" section also states: "The ROTEM sigma is an in vitro diagnostic (IVD) whole blood hemostasis system..."
  • Function: The device is designed to analyze a patient's coagulation status by measuring the properties of a blood sample outside of the body (in vitro). This is the core function of an IVD.
  • Intended Use: The intended use is to assess peri-operative hemorrhage and/or thrombosis, which is a diagnostic purpose.

N/A

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 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.

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

JPA

Device Description

The ROTEM sigma 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 semiquantitative information about the coagulation state of a blood sample. The ROTEM sigma system records the kinetic changes in a sample of 3.2% citrated whole blood during clot formation, as well as when the sample clot retracts and/or lyses.

Several parameters are measured and reported for this purpose. The graphical presentation reflects the various physiological results, which describe the interaction between coagulation factors and inhibitors, fibrinogen, platelets, and the fibrinolysis system. Additionally, the effect of certain drugs influencing hemostasis, in particular some anticoagulants (e.g. heparin), can be detected.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Not Found

Indicated Patient Age Range

adult patients 21 years and older

Intended User / Care Setting

professional use only / point of care and laboratory settings

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

Not Found

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

Not Found

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

Electrical Safety and Electromagnetic Compatibility (EMC)
The ROTEM sigma system was tested to the following Electrical Safety and EMC standards: IEC 61010-1:2010, AMD1:2016, IEC 61010-2-010:2014, IEC 61010-2-101:2015, IEC 61326-1:2012, IEC 61326-2-6: 2012, and 47 CFR 15 Subpart B:2018. The ROTEM sigma has also been tested to and passes the limits of IEC 60601-1-2:2014.

Precision
An internal precision study was performed on three (3) lots of ROTEM sigma complete + hep cartridges using whole blood (normal, contrived hypocoagulable, contrived hypercoagulable) and three (3) lots each of the controls ROTEM sigma ROTROL N and ROTEM sigma ROTROL P. The control study was run in duplicate, twice a day for twenty (20) days, for a total of eighty (80) replicates per control. The whole blood study was run in triplicate in one (1) day on five (5) ROTEM sigma instruments, for a total of fifteen (15) replicates per sample type.
A second precision study was performed to support the precision of the lysis parameters. This study was performed on three (3) lots of ROTEM sigma complete + hep cartridges using normal whole blood and abnormal hyperfibrinolysis blood. The study was run on five (5) ROTEM sigma instruments with three (3) replicates/instrument, for a total of fifteen (15) replicates per sample type and cartridge lot.
A third precision study was performed to support the precision of the lot-to-lot variability. This study was performed on three (3) lots of the ROTEM sigma complete + hep cartridges using normal donor whole blood. The study was run in triplicate, twice a day for five (5) days, for a total of thirty (30) replicates per cartridge lot.

Reproducibility
Reproducibility studies were performed at three (3) external clinical 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.

Interference
An interference study was performed using normal and hypocoagulable whole blood samples to determine the impact of interferents UF Heparin, LMW Heparin, Tranexamic Acid, E-Aminocaproic Acid, Acetylsalicylic Acid (Aspirin), and Ticagrelor on the INTEM C, EXTEM C, and HEPTEM C assays. For each interferent, testing was performed with eight (8) replicates at three (3) interferent levels (Baseline, Claim, and Greater than Claim) for a total of twenty-four (24) replicates for each blood sample type. Because of its sensitivity to heparin, INTEM C was not tested for heparin interference. Another interference study was performed using normal whole blood samples to determine the impact of lupus anticoagulant on the same assays. This testing was performed with eleven (11) donors, each run on three (3) instruments with one (1) replicate per instrument. Testing confirmed no interference for INTEM C, EXTEM C, FIBTEM C, and HEPTEM C on the ROTEM sigma up to the following concentrations (see Key Metrics for concentrations).

Reference Intervals
A total of one hundred twenty (120) whole blood samples from healthy donors were analyzed on the ROTEM sigma using ROTEM sigma complete + hep cartridges. The nonparametric, 95% reference interval along with two-sided, 90% confidence intervals around each limit were calculated.

Reportable Ranges
The reportable ranges for the ROTEM sigma assays are based on the method comparison and precision studies and presented (see Key Metrics for ranges).

Method Comparison
A method comparison study was conducted at four (4) clinical sites comparing the ROTEM sigma to the predicate device, the ROTEM delta (K083842, K 101533), using 3.2% citrated venous or arterial whole blood patient samples from the intended use populations and contrived samples. Sample size: INTEM C samples=144 for CT, A5, A10, A20, MCF, and 148 for LI60, ML. EXTEM C samples=183 for CT, A5, A10, A20, MCF, and 187 for LI60, ML. FIBTEM C samples=183 for A5, A10, A20, MCF. HEPTEM C samples=182 for CT, A5, A10, A20, MCF.
Results for INTEM C: CT (Slope=0.94, Intercept=20.9, R=0.845), A5 (Slope=0.91, Intercept=3.8, R=0.977), A10 (Slope=0.90, Intercept=4.8, R=0.983), A20 (Slope=0.92, Intercept=4.5, R=0.985), MCF (Slope=0.95, Intercept=2.5, R=0.982), LI60 (Slope=1.00, Intercept=1.0, R=0.990), ML (Slope=1.00, Intercept=-1.0, R=0.990).
Results for EXTEM C: CT (Slope=1.17, Intercept=-4.0, R=0.780), A5 (Slope=0.94, Intercept=5.1, R=0.953), A10 (Slope=0.93, Intercept=5.9, R=0.966), A20 (Slope=0.95, Intercept=4.7, R=0.973), MCF (Slope=1.00, Intercept=2.0, R=0.977), LI60 (Slope=1.00, Intercept=1.0, R=0.982), ML (Slope=1.00, Intercept=-1.0, R=0.982).
Results for FIBTEM C: A5 (Slope=0.86, Intercept=0.4, R=0.920), A10 (Slope=0.89, Intercept=0.3, R=0.921), A20 (Slope=0.91, Intercept=0.3, R=0.923), MCF (Slope=1.00, Intercept=-1.0, R=0.926).
Results for HEPTEM C: CT (Slope=0.91, Intercept=21.4, R=0.484), A5 (Slope=0.92, Intercept=3.1, R=0.940), A10 (Slope=0.93, Intercept=3.6, R=0.947), A20 (Slope=0.95, Intercept=3.0, R=0.959), MCF (Slope=1.00, Intercept=1.0, R=0.966).

Arterial vs. Venous Study
A matrix comparison study using seventy-four (74) matched venous and arterial citrated whole blood samples was performed at two (2) 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 assays. Sample size: 58 for INTEM C CT, 55 for INTEM C A5, A10, A20, MCF (one outlier suppressed for A5, A10, A20), 54 for INTEM C LI60, ML. 73 for EXTEM C all parameters. 71 for FIBTEM C all parameters. 64 for HEPTEM C all parameters.
Results for INTEM C: CT (Mean Difference=1.4%, 95% CI=-5.6% to 8.4%), A5 (Mean Difference=1.6%, 95% CI=-2.4% to 5.6%), A10 (Mean Difference=1.6%, 95% CI=-2.9% to 6.0%), A20 (Mean Difference=1.5%, 95% CI=-3.6% to 6.6%), MCF (Mean Difference=3.3%, 95% CI=-3.4% to 10.1%), LI60 (Mean Difference=-0.7%, 95% CI=-1.0% to -0.4%), ML (Mean Difference=0.7% Lysis, 95% CI=0.4% Lysis to 1.0% Lysis).
Results for EXTEM C: CT (Mean Difference=0.6%, 95% CI=-1.6% to 2.7%), A5 (Mean Difference=1.0%, 95% CI=-0.2% to 2.3%), A10 (Mean Difference=0.4%, 95% CI=-0.6% to 1.3%), A20 (Mean Difference=0.0%, 95% CI=-0.8% to 0.8%), MCF (Mean Difference=-0.2%, 95% CI=-0.9% to 0.5%), LI60 (Mean Difference=-0.2%, 95% CI=-0.4% to 0.0%), ML (Mean Difference=0.2% Lysis, 95% CI=0.0% Lysis to 0.4% Lysis).
Results for FIBTEM C: A5 (Mean Difference=0.9%, 95% CI=-1.0% to 2.9%), A10 (Mean Difference=0.8%, 95% CI=-1.1% to 2.6%), A20 (Mean Difference=0.8%, 95% CI=-0.6% to 2.3%), MCF (Mean Difference=1.1%, 95% CI=-0.6% to 2.9%).
Results for HEPTEM C: CT (Mean Difference=2.9%, 95% CI=-1.2% to 6.9%), A5 (Mean Difference=1.7%, 95% CI=0.5% to 2.9%), A10 (Mean Difference=1.5%, 95% CI=0.6% to 2.4%), A20 (Mean Difference=0.8%, 95% CI=0.1% to 1.5%), MCF (Mean Difference=0.0%, 95% CI=-0.7% to 0.6%).

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

Interference Summary
UF Heparin: EXTEM C 5 IU/mL, FIBTEM C 5 IU/mL, HEPTEM C 7 IU/mL
LMW Heparin: EXTEM C 3 IU/mL, FIBTEM C 3 IU/mL, HEPTEM C 3 IU/mL
Tranexamic Acid: INTEM C 60 µg/mL, EXTEM C 60 µg/mL, FIBTEM C 60 µg/mL, HEPTEM C 60 µg/mL
ε-Aminocaproic Acid: INTEM C 600 µg/mL, EXTEM C 600 µg/mL, FIBTEM C 600 µg/mL, HEPTEM C 600 µg/mL
Acetylsalicylic Acid: INTEM C 3 mg/dL, EXTEM C 3 mg/dL, FIBTEM C 3 mg/dL, HEPTEM C 3 mg/dL
Ticagrelor: INTEM C 0.1881 mg/dL, EXTEM C 0.1881 mg/dL, FIBTEM C 0.1881 mg/dL, HEPTEM C 0.1881 mg/dL
Lupus Anticoagulant (dRVVT Screen/Confirm Ratio): INTEM C 1.34, EXTEM C 1.34, FIBTEM C 1.34, HEPTEM C 1.34

Reference Intervals Summary
INTEM C: CT (139 - 205 s), A5 (36 - 54 mm), A10 (46 - 63 mm), A20 (53 - 68 mm), MCF (55 - 70 mm), LI60 (93 - 100 %), ML (0 - 7 %)
EXTEM C: CT (51 - 73 s), A5 (33 - 52 mm), A10 (45 - 62 mm), A20 (54 - 69 mm), MCF (57 - 72 mm), LI60 (94 - 100 %), ML (0 - 6 %)
FIBTEM C: A5 (5 - 16 mm), A10 (6 - 17 mm), A20 (6 - 18 mm), MCF (6 - 19 mm)
HEPTEM C: CT (141 - 215 s), A5 (33 - 51 mm), A10 (44 - 61 mm), A20 (52 - 67 mm), MCF (54 - 69 mm)

Reportable Ranges
INTEM C: CT (123-365 s), A5 (11-66 mm), A10 (16-74 mm), A20 (21-78 mm), MCF (24-79 mm), LI60 (0-100 %), ML (0-100 %)
EXTEM C: CT (45-172 s), A5 (13-69 mm), A10 (18-77 mm), A20 (23-81 mm), MCF (25-82 mm), LI60 (0-100 %), ML (0-100 %)
FIBTEM C: A5 (2-33 mm), A10 (2-36 mm), A20 (2-38 mm), MCF (2-41 mm)
HEPTEM C: CT (122-376 s), A5 (10-59 mm), A10 (15-68 mm), A20 (20-73 mm), MCF (24-75 mm)

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

K083842, K101533

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

Not Found

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

Not Found

§ 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.

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July 8, 2022

Tem Innovations GmbH David Jacob Head of Quality Assurance and Regulatory Affairs, PBM Martin-Kollar-Strasse 15 Munich, Bavaria 81829 DEU

Re: K201440

Trade/Device Name: ROTEM sigma Thromboelastometry System Regulation Number: 21 CFR 864.5425 Regulation Name: Multipurpose system for in vitro coagulation studies Regulatory Class: Class II Product Code: JPA Dated: May 29, 2020 Received: June 1, 2020

Dear David Jacob:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

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

1

801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

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

Sincerely,

Min Wu 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) K201440

Device Name

ROTEM sigma Thromboelastometry System

Indications for Use (Describe)

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.

Type of Use (Select one or both, as applicable)
☑ Prescription Use (Part 21 CFR 801 Subpart D)☐ Over-The-Counter Use (21 CFR 801 Subpart C)

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510(K) SUMMARY

This 510(k) Summary of Safety and Effectiveness is being submitted in accordance with the requirements of the Safe Medical Device Act of 1990 and 21 CFR 807.92.

Summary Information

| Submitter's Information: | Tem Innovations GmbH
Martin-Kollar-Strasse 15
81829 Munich, Germany | |
|--------------------------|-------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------|
| Contact Person: | David Jacob
Phone: +49 89 45 42 95 23
Fax: +49 89 45 42 95 22
Email: djacob@werfen.com | |
| Preparation Date: | 7 July 2022 | |
| Device Trade Names: | Instrument: | ROTEM sigma |
| | Assay Cartridge: | ROTEM sigma complete + hep |
| Regulatory Information: | Common or Usual Name: | Thromboelastometry System |
| | Classification Name: | Multipurpose System for In Vitro Coagulation
Studies (21 CFR 864.5425) |
| | Regulatory Class: | Class II |
| | Product Code: | JPA |
| | Classification Panel: | Hematology (81) |
| Predicate Device: | K083842: ROTEM delta Thromboelastometry System
K101533: EX-TEM, FIB-TEM, and AP-TEM for ROTEM delta
Thromboelastometry System | |

Device Information

Device Description: The ROTEM sigma 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 semiquantitative information about the coagulation state of a blood sample. The ROTEM sigma system records the kinetic changes in a sample of 3.2% citrated whole blood during clot formation, as well as when the sample clot retracts and/or lyses.

Several parameters are measured and reported for this purpose. The graphical presentation reflects the various physiological results, which describe the interaction between coagulation factors and inhibitors, fibrinogen, platelets, and the fibrinolysis system. Additionally, the effect of certain drugs influencing hemostasis, in particular some anticoagulants (e.g. heparin), can be detected.

4

Test Principle:The ROTEM sigma 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 of 4.75°. The oscillation of the axis is driven by a motor that is connected to the axis via a spring. 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 via a mirror plate at the upper end of the axis, which reflects the light from a diode light source onto a light sensitive sensor. 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. The result is a balance between the spring tension and the tension of the clot. As the clot becomes firmer, the oscillation amplitude of the axis is reduced.
The ROTEM sigma assays are based on the principle of either
intrinsic coagulation activation with or without the presence of heparin, orextrinsic coagulation activation with or without the presence of platelet inhibitors.
Indications for Use / 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.

5

Comparison to Predicates

The ROTEM sigma thromboelastometry system is compared below to the predicate device, the ROTEM delta thromboelastometry system (K083842, K101533).

| Characteristic | Subject Device
ROTEM sigma | Predicate Device
ROTEM delta
(K083842, K101533) |
|--------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Similarities | | |
| Instrument | Fully Integrated Thromboelastometry Instrument | |
| Measuring Technique | Shear elasticity of a coagulating sample by motion of a pin | |
| Measuring Channels
utilized | 4 | |
| Signal Generation | Oscillating pin in a stationary cup | |
| Signal Transducer | Optical system with CCD sensor | |
| Sample | 3.2 % citrated whole blood | |
| Measurement Station
Temperature | 37 °C ± 1 °C | |
| Graphical Presentation
of Results | Presents each assay reaction curve and parameters in real time "TEMogram" | |
| Differences | | |
| Cups & Pins | Cups and pins are integrated into assay
cartridges | Cups and pins need to be installed in
instrument for each test |
| Sample Handling | Automated sample transfer | Manual pipetting, electronic pipette |
| Sample Volume | ≥ 2.7 mL sample tube for four assays | 300 µL per assay |
| Supply Voltage | 110/240 VAC, 60/50 Hz, max. 210 VA | 115/230 VAC, 60/50 Hz, max. 350 VA |
| Environment | • Temperature
o Operating: 18 °C - 30 °C
o Storage: 0 °C - 50 °C
• Relative Humidity
o Operating: 40 % - 60 %
o Storage: 20% - 85%
• Operable to 3000 m above sea level | • Temperature
o Operating: 15 °C - 30 °C
o Storage: 0 °C - 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 "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" |
| Characteristic | Subject Device
ROTEM sigma | Predicate Device
ROTEM delta
(K083842, K101533) |
| 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) |
| Assays | • INTEM C
• EXTEM C
• FIBTEM C
• HEPTEM C | • INTEM
• EXTEM
• FIBTEM
• APTEM
• HEPTEM
• NATEM |
| Assay Format | All four assays (reagents) provided
ready-to-use in the single-use ROTEM
sigma complete + hep cartridge. | 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) |
| Reagent Handling | Cartridges containing assay reagents are
stored at room temperature. No warmup
required. | Assay reagents require refrigeration,
5-15 min warmup required (depending on
room temperature). |
| Characteristic | Subject Device
ROTEM sigma | Predicate Device
ROTEM delta
(K083842/K101533) |
| Assay Name | INTEM C | INTEM |
| | Similarities | |
| Activation Principle | Intrinsic coagulation activation
• Recalcification of a sample
• Activation of the intrinsic coagulation pathway | |
| Activation Reagents | • CaCl2
• Ellagic Acid | |
| Assay Name | EXTEM C | EXTEM |
| | Similarities | |
| Activation Principle | Extrinsic coagulation activation
• Recalcification of a sample
• Activation of the extrinsic coagulation pathway | |
| Activation Reagents | • CaCl2
• Recombinant Tissue Factor
• Heparin Inhibitor | |
| Assay Name | FIBTEM C | FIBTEM |
| | Similarities | |
| Activation Principle | Extrinsic coagulation activation in the presence of platelet inhibitors
• Recalcification of a sample
• Activation of the extrinsic pathway
• In vitro inhibition of platelets | |
| Activation Reagents | • CaCl2
• Recombinant Tissue Factor
• Heparin Inhibitor
• Platelet Inhibitors | |
| Assay Name | HEPTEM C | HEPTEM |
| | Similarities | |
| Activation Principle | Intrinsic coagulation activation in the presence of heparin
• Recalcification of a sample
• Activation of the intrinsic coagulation pathway
• In vitro inactivation of heparin | |
| Activation Reagents | • CaCl2
• Ellagic Acid
• Heparin Inhibitor | |

Comparison of Technological Characteristics with the Predicate Device - System

6

7

Comparison of Technological Characteristics with the Predicate Device - Assays

8

Performance Summary

Electrical Safety and Electromagnetic Compatibility (EMC)

The ROTEM sigma system was tested to the following Electrical Safety and EMC standards: IEC 61010-1:2010, AMD1:2016, IEC 61010-2-010:2014, IEC 61010-2-101:2015, IEC 61326-1:2012, IEC 61326-2-6: 2012, and 47 CFR 15 Subpart B:2018. The ROTEM sigma has also been tested to and passes the limits of IEC 60601-1-2:2014.

Precision

An internal precision study was performed on three (3) lots of ROTEM sigma complete + hep cartridges using whole blood (normal, contrived hypocoagulable, contrived hypercoagulable) and three (3) lots each of the controls ROTEM sigma ROTROL N and ROTEM sigma ROTROL P. The control study was run in duplicate, twice a day for twenty (20) days, for a total of eighty (80) replicates per control. The whole blood study was run in triplicate in one (1) day on five (5) ROTEM sigma instruments, for a total of fifteen (15) replicates per sample type. The highest % CV of the three (3) lots for the parameters CT, A5, A10, A20, and MCF are summarized below.

Precision Summary

| | | | ROTROL N | | ROTROL P | | Normal Whole
Blood | Contrived
Hypocoagulable
Samples | Contrived
Hypercoagulable
Samples |
|----------|-----------|--|--------------------------|---------------------------------|--------------------------|---------------------------------|---------------------------------|----------------------------------------|-----------------------------------------|
| Assay | Parameter | | % CV
(Within-
Run) | % CV
(Within-
Laboratory) | % CV
(Within-
Run) | % CV
(Within-
Laboratory) | % CV
(Within-
Laboratory) | % CV
(Within-
Laboratory) | % CV
(Within-
Laboratory) |
| | CT (s) | | 7.7 | 8.7 | 4.6 | 4.9 | 3.8 | 6.8 | 4.5 |
| INTEM C | 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 |
| HEPTEM C | CT (s) | | 4.1 | 4.3 | 4.7 | 5.6 | 3.9 | 9.4 | 2.3 |
| | A5 (mm) | | 1.9 | 2.1 | 5.5 | 5.5 | 5.7 | 9.5 | 3.5 |
| | A10 (mm) | | 1.8 | 1.9 | 5.6 | 5.7 | 3.9 | 8.4 | 2.5 |
| | A20 (mm) | | 1.6 | 1.7 | 6.1 | 6.1 | 2.9 | 8.5 | 1.6 |
| | MCF* (mm) | | 1.3 | 1.5 | 6.6 | 6.7 | 2.5 | 7.9 | 1.6 |

  • 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.

9

Precision (Cont.)

A second precision study was performed to support the precision of the lysis parameters. This study was performed on three (3) lots of ROTEM sigma complete + hep cartridges using normal whole blood and abnormal hyperfibrinolysis blood. The study was run on five (5) ROTEM sigma instruments with three (3) replicates/instrument, for a total of fifteen (15) replicates per sample type and cartridge lot. The highest SD and/or % CV of the three (3) lots for the parameters LI60 and ML are summarized below.

Lysis Precision Summary

| Assay | Parameter | Normal
Whole Blood
Within-Laboratory
%CV | Abnormal
Hyperfibrinolysis
Blood
Within-Laboratory
SD |
|---------|-----------|---------------------------------------------------|-------------------------------------------------------------------|
| INTEM C | LI60 (%) | 1.5 | 0.6 |
| EXTEM C | | 1.4 | 1.4 |

| Assay | Parameter | Normal
Whole Blood
Within-Laboratory
SD | Abnormal
Hyperfibrinolysis
Blood
Within-Laboratory
%CV |
|---------|-----------|--------------------------------------------------|--------------------------------------------------------------------|
| INTEM C | ML* (%) | 1.4 | 0.6 |
| EXTEM C | | 1.3 | 1.4 |

10

Precision (Cont.)

A third precision study was performed to support the precision of the lot-to-lot variability. This study was performed on three (3) lots of the ROTEM sigma complete + hep cartridges using normal donor whole blood. The study was run in triplicate, twice a day for five (5) days, for a total of thirty (30) replicates per cartridge lot. The results are summarized below.

Within-LotBetween-Lot
AssayParameterNMeanSD%CVSD%CV
INTEM CCT (s)90183.89.04.90.00.0
A5 (mm)9043.93.98.90.00.0
A10 (mm)9054.14.17.50.00.0
A20 (mm)9060.54.47.30.00.0
MCF (mm)9062.05.18.10.00.0
LI60 (%)9096.92.12.20.00.0
ML* (%)903.12.167.90.00.0
EXTEM CCT (s)9058.35.18.80.00.0
A5 (mm)9044.23.98.90.00.0
A10 (mm)9054.54.17.40.00.0
A20 (mm)9061.64.26.70.00.0
MCF (mm)9063.94.77.40.00.0
LI60 (%)9097.61.71.80.00.0
ML* (%)902.41.773.10.00.0
FIBTEM CA5 (mm)9011.73.025.90.00.0
A10 (mm)9012.73.325.80.00.0
A20 (mm)9013.53.425.00.00.0
MCF (mm)9013.83.525.60.00.0
HEPTEM CCT (s)90182.710.35.60.40.2
A5 (mm)9041.13.68.70.00.0
A10 (mm)9051.83.77.10.00.0
A20 (mm)9058.94.06.80.00.0
MCF (mm)9060.94.77.70.00.0

Lot-to-Lot Variability Summary

11

Reproducibility

Reproducibility studies were performed at three (3) external clinical 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. The pooled data from three (3) external sites for all sites together and each individual site are presented below.

| Assay | Parameter | N | Mean | Repeatability | | Between-Run | | Between-Day | | Between-Site | | Reproducibility
(Within-
Control Lot) | | Between-
Control Lot | |
|----------|-----------|------|-------|---------------|------|-------------|-----|-------------|-----|--------------|-----|---------------------------------------------|------|-------------------------|-----|
| | | | | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| | 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 |
| INTEM C | 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 |
| | 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 |
| EXTEM C | 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 |
| | 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 |
| FIBTEM C | 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 |

Reproducibility Summary - All Sites - ROTROL N

  • No FIBTEM data provided for one sample.

Reproducibility Summary - All Sites - ROTROL P

AssayParameterNMeanRepeatabilityBetween-RunBetween-DayBetween-SiteReproducibility (Within-Control Lot)Between-Control Lot
SD%CVSD%CVSD%CVSD%CVSD%CVSD%CV
INTEM CCT (s)270365.39.62.64.51.22.30.63.50.911.43.163.017.2
A5 (mm)27024.31.14.40.41.60.00.00.31.11.24.80.00.0
A10 (mm)27027.01.14.10.52.00.00.00.20.71.34.60.00.0
A20 (mm)27029.51.24.10.62.00.00.00.30.91.44.70.00.0
MCF(mm)27031.71.34.20.61.90.00.00.31.01.54.70.00.0
EXTEM CCT (s)270146.76.04.10.00.02.41.63.82.67.55.10.70.5
A5 (mm)27024.81.35.10.52.10.00.00.20.71.45.50.20.7
A10 (mm)27027.71.34.80.62.30.00.00.31.01.55.40.00.0
A20 (mm)27030.31.44.60.72.30.00.00.20.81.65.20.10.5
MCF(mm)27032.71.54.60.72.20.00.00.10.21.75.10.20.7
FIBTEM CA5 (mm)27024.81.25.00.41.80.00.00.41.51.45.50.00.0
A10 (mm)27027.71.34.80.51.90.00.00.41.51.55.40.00.0
A20 (mm)27030.41.54.80.51.80.00.00.51.61.65.40.00.0
MCF(mm)27033.11.64.70.72.00.00.00.31.01.75.20.00.0
HEPTEM CCT (s)270367.410.72.94.71.32.30.69.02.514.94.166.818.2
A5 (mm)27025.11.14.50.51.80.00.00.93.71.56.10.00.0
A10 (mm)27027.91.24.30.41.50.00.00.93.11.55.50.00.0
A20 (mm)27030.41.34.20.62.00.00.00.82.61.65.30.00.0
MCF(mm)27032.51.44.20.72.10.00.00.82.61.75.40.00.0

12

Reproducibility (Cont.)

AssayParameterNMeanRepeatabilityBetween-RunBetween-DayWithin-Control LotBetween-Control Lot
SD%CVSD%CVSD%CVSD%CVSD%CV
INTEM CCT (s)90345.332.79.50.00.03.61.132.99.513.84.0
A5 (mm)9043.40.81.90.30.60.00.00.92.00.10.2
A10 (mm)9046.80.71.50.00.00.10.30.71.60.10.3
A20 (mm)9050.50.81.60.30.60.10.20.91.70.00.0
MCF(mm)9054.20.81.40.30.50.00.00.81.50.10.2
EXTEM CCT (s)90132.014.210.75.84.41.51.115.411.75.44.1
A5 (mm)9043.40.81.90.30.70.00.00.92.00.20.6
A10 (mm)9047.70.91.80.40.70.00.00.91.90.20.4
A20 (mm)9052.10.71.30.30.50.00.00.71.40.00.0
MCF(mm)9056.70.71.30.30.50.00.00.81.30.20.4
FIBTEM CA5 (mm)9037.81.54.00.00.00.00.01.54.00.71.9
A10 (mm)9042.31.43.40.00.00.00.01.43.40.61.5
A20 (mm)9047.01.32.70.00.00.00.01.32.70.40.9
MCF(mm)9052.51.22.30.00.00.20.51.22.30.40.7
HEPTEM CCT (s)90333.024.17.20.00.05.11.524.67.414.24.3
A5 (mm)9042.90.81.90.00.00.00.00.81.90.20.4
A10 (mm)9046.50.81.70.00.00.00.00.81.70.10.2
A20 (mm)9050.60.81.60.00.00.00.00.81.60.10.2
MCF(mm)9054.50.71.30.00.00.00.00.71.30.20.4

Reproducibility Summary - Site 1 - ROTROL N

Reproducibility Summary - Site 1 - ROTROL P

AssayParameterNMeanRepeatabilityBetween-RunBetween-DayWithin-Control LotBetween-Control Lot
SD%CVSD%CVSD%CVSD%CVSD%CV
INTEM CCT (s)90365.78.52.31.80.51.30.38.72.463.317.3
INTEM CA5 (mm)9024.20.93.60.62.30.00.01.04.30.20.7
INTEM CA10 (mm)9027.00.93.40.72.60.00.01.24.30.10.5
INTEM CA20 (mm)9029.61.03.50.72.50.00.01.34.30.20.6
INTEM CMCF(mm)9031.61.13.40.82.60.00.01.44.30.30.9
EXTEM CCT (s)90146.26.14.10.00.01.30.96.24.22.31.6
EXTEM CA5 (mm)9025.01.24.80.72.70.00.01.45.50.20.9
EXTEM CA10 (mm)9028.11.24.20.82.80.00.01.45.10.31.0
EXTEM CA20 (mm)9030.71.34.30.72.40.00.01.55.00.41.2
EXTEM CMCF(mm)9033.01.34.00.82.50.00.01.64.70.41.3
FIBTEM CA5 (mm)9025.21.03.90.72.90.00.01.24.90.00.0
FIBTEM CA10 (mm)9028.21.03.60.82.70.00.01.34.50.00.0
FIBTEM CA20 (mm)9030.91.13.70.82.50.00.01.44.50.00.0
FIBTEM CMCF(mm)9033.51.23.60.92.70.00.01.54.50.00.0
HEPTEM CCT (s)90369.49.62.63.20.90.00.010.12.765.517.7
HEPTEM CA5 (mm)9024.40.93.60.62.30.00.01.04.30.31.2
HEPTEM CA10 (mm)9027.20.83.10.72.60.00.01.14.00.31.0
HEPTEM CA20 (mm)9029.71.03.40.92.90.00.01.34.40.30.9
HEPTEM CMCF(mm)9031.71.13.40.92.80.00.01.44.40.41.2

13

Reproducibility (Cont.)

AssayParameterNMeanRepeatabilityBetween-RunBetween-DayWithin-Control LotBetween-Control Lot
SD%CVSD%CVSD%CVSD%CVSD%CV
INTEM CCT (s)90346.118.25.36.01.70.00.019.25.58.52.5
INTEM CA5 (mm)9043.90.61.40.00.00.30.60.71.50.00.0
INTEM CA10 (mm)9047.60.71.40.00.00.30.60.71.60.00.0
INTEM CA20 (mm)9051.40.71.40.00.00.20.50.81.50.00.0
INTEM CMCF(mm)9055.20.61.10.30.60.40.70.81.50.00.0
EXTEM CCT (s)90130.512.79.72.21.70.00.012.99.91.61.3
EXTEM CA5 (mm)9043.50.92.10.51.20.00.01.12.40.40.9
EXTEM CA10 (mm)9047.60.81.70.40.90.00.00.91.90.40.8
EXTEM CA20 (mm)9051.90.81.50.40.70.00.00.81.60.40.7
EXTEM CMCF(mm)9056.80.91.50.00.00.40.60.91.70.20.4
FIBTEM CA5 (mm)9037.50.92.50.72.00.00.01.23.21.02.6
FIBTEM CA10 (mm)9042.01.02.30.81.90.00.01.33.00.92.2
FIBTEM CA20 (mm)9047.01.02.10.71.50.00.01.22.60.91.8
FIBTEM CMCF(mm)9052.71.01.90.51.00.20.41.12.10.81.5
HEPTEM CCT (s)90333.116.54.92.20.71.80.516.75.08.52.6
HEPTEM CA5 (mm)9042.60.81.90.10.30.20.50.82.00.00.0
HEPTEM CA10 (mm)9046.30.92.00.00.00.20.50.92.00.00.0
HEPTEM CA20 (mm)9050.40.81.60.00.00.20.50.81.70.00.0
HEPTEM CMCF(mm)9054.30.81.50.40.80.30.51.01.80.00.0

Reproducibility Summary - Site 2 - ROTROL N

Reproducibility Summary Site 2 - ROTROL P

AssayParameterNMeanRepeatabilityBetween-RunBetween-DayWithin-Control LotBetween-Control Lot
SD%CVSD%CVSD%CVSD%CVSD%CV
INTEM CCT (s)90368.610.32.82.60.71.60.410.72.961.816.8
INTEM CA5 (mm)9024.01.56.10.41.60.00.01.56.30.00.0
A10 (mm)9026.81.55.70.51.80.00.01.66.00.00.1
A20 (mm)9029.31.75.90.62.10.00.01.86.20.10.2
MCF(mm)9031.41.85.70.41.20.30.81.95.90.00.0
EXTEM CCT (s)90150.75.23.42.21.40.00.05.63.70.80.5
A5 (mm)9024.61.66.50.52.20.00.01.76.90.00.0
A10 (mm)9027.51.76.30.82.80.00.01.96.90.00.0
A20 (mm)9030.21.86.10.82.70.00.02.06.60.00.0
MCF(mm)9032.62.06.10.92.60.00.02.26.60.00.0
FIBTEM CA5 (mm)9024.51.66.70.20.80.00.01.66.70.10.6
A10 (mm)9027.41.86.70.41.40.00.01.96.80.00.0
A20 (mm)9030.12.06.70.31.10.00.02.06.80.20.7
MCF(mm)9032.92.26.60.51.40.00.02.26.70.00.0
HEPTEM CCT (s)90374.810.42.82.80.74.11.111.53.169.818.6
A5 (mm)9024.81.55.90.62.30.00.01.66.30.31.3
A10 (mm)9027.61.65.90.31.00.00.01.76.00.00.0
A20 (mm)9030.21.75.70.62.10.00.01.86.10.00.0
MCF(mm)9032.31.85.60.72.30.00.02.06.00.00.0

14

Reproducibility (Cont.)

| Assay | Parameter | N | Mean | Repeatability | | Between-Run | | Between-Day | | Within-
Control Lot | | Between-
Control Lot | |
|----------|-----------|-----|-------|---------------|------|-------------|-----|-------------|-----|------------------------|------|-------------------------|-----|
| | | | | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| INTEM C | CT (s) | 90 | 343.0 | 20.3 | 5.9 | 0.0 | 0.0 | 3.9 | 1.1 | 20.7 | 6.0 | 6.4 | 1.9 |
| INTEM C | A5 (mm) | 90 | 44.1 | 0.6 | 1.4 | 0.0 | 0.0 | 0.3 | 0.6 | 0.7 | 1.5 | 0.0 | 0.0 |
| INTEM C | A10 (mm) | 90 | 47.7 | 0.6 | 1.3 | 0.0 | 0.0 | 0.4 | 0.8 | 0.7 | 1.5 | 0.0 | 0.0 |
| INTEM C | A20 (mm) | 90 | 51.6 | 0.6 | 1.2 | 0.0 | 0.0 | 0.4 | 0.7 | 0.7 | 1.4 | 0.0 | 0.0 |
| INTEM C | MCF(mm) | 90 | 55.5 | 0.9 | 1.7 | 0.5 | 1.0 | 0.2 | 0.4 | 1.1 | 2.0 | 0.2 | 0.3 |
| EXTEM C | CT (s) | 90 | 128.2 | 13.9 | 10.8 | 0.0 | 0.0 | 1.3 | 1.0 | 13.9 | 10.8 | 2.9 | 2.2 |
| EXTEM C | A5 (mm) | 90 | 43.9 | 1.0 | 2.3 | 0.0 | 0.0 | 0.0 | 0.0 | 1.0 | 2.3 | 0.5 | 1.2 |
| EXTEM C | A10 (mm) | 90 | 47.9 | 1.0 | 2.0 | 0.0 | 0.0 | 0.0 | 0.0 | 1.0 | 2.0 | 0.5 | 1.1 |
| EXTEM C | A20 (mm) | 90 | 52.2 | 0.8 | 1.6 | 0.2 | 0.4 | 0.0 | 0.0 | 0.9 | 1.7 | 0.5 | 1.0 |
| EXTEM C | MCF(mm) | 90 | 57.3 | 1.1 | 1.8 | 0.4 | 0.7 | 0.0 | 0.0 | 1.1 | 2.0 | 0.3 | 0.5 |
| FIBTEM C | A5 (mm) | 89* | 38.2 | 1.1 | 2.9 | 0.4 | 1.0 | 0.0 | 0.0 | 1.2 | 3.1 | 0.5 | 1.4 |
| FIBTEM C | A10 (mm) | 89* | 42.6 | 1.1 | 2.6 | 0.5 | 1.1 | 0.0 | 0.0 | 1.2 | 2.9 | 0.5 | 1.2 |
| FIBTEM C | A20 (mm) | 89* | 47.5 | 1.1 | 2.2 | 0.5 | 1.0 | 0.0 | 0.0 | 1.2 | 2.5 | 0.4 | 0.8 |
| FIBTEM C | MCF(mm) | 89* | 53.6 | 1.1 | 2.0 | 0.7 | 1.3 | 0.0 | 0.0 | 1.3 | 2.3 | 0.2 | 0.3 |
| HEPTEM C | CT (s) | 90 | 331.8 | 21.2 | 6.4 | 0.0 | 0.0 | 6.9 | 2.1 | 22.3 | 6.7 | 8.4 | 2.5 |
| HEPTEM C | A5 (mm) | 90 | 43.9 | 0.9 | 2.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.9 | 2.0 | 0.2 | 0.5 |
| HEPTEM C | A10 (mm) | 90 | 47.9 | 0.9 | 1.8 | 0.0 | 0.0 | 0.1 | 0.3 | 0.9 | 1.8 | 0.2 | 0.4 |
| HEPTEM C | A20 (mm) | 90 | 51.9 | 0.8 | 1.5 | 0.0 | 0.0 | 0.0 | 0.0 | 0.8 | 1.5 | 0.1 | 0.2 |
| HEPTEM C | MCF(mm) | 90 | 55.9 | 1.0 | 1.8 | 0.3 | 0.5 | 0.0 | 0.0 | 1.0 | 1.9 | 0.1 | 0.1 |

Reproducibility Summary - Site 3 - ROTROL N

  • No FIBTEM data provided for one sample.

Reproducibility Summary Site 3 - ROTROL P

AssayParameterNMeanRepeatabilityBetween-RunBetween-DayWithin-Control LotBetween-Control Lot
SD%CVSD%CVSD%CVSD%CVSD%CV
INTEM CCT (s)90361.510.02.87.12.03.40.912.73.563.917.7
INTEM CA5 (mm)9024.60.72.70.10.60.00.20.72.80.20.9
INTEM CA10 (mm)9027.30.72.60.41.40.00.00.83.00.20.7
INTEM CA20 (mm)9029.80.72.20.41.40.00.00.82.60.10.5
INTEM CMCF(mm)9032.00.92.80.51.60.00.01.03.20.31.0
EXTEM CCT (s)90143.46.64.60.00.03.92.77.75.43.82.7
EXTEM CA5 (mm)9024.70.83.30.21.00.41.40.93.80.31.1
EXTEM CA10 (mm)9027.50.93.30.10.50.31.11.03.50.10.5
EXTEM CA20 (mm)9030.10.82.80.51.50.31.01.03.30.20.6
EXTEM CMCF(mm)9032.61.03.10.41.20.20.61.13.40.31.1
FIBTEM CA5 (mm)9024.61.04.00.20.90.31.31.04.30.10.5
FIBTEM CA10 (mm)9027.51.03.60.31.20.20.61.13.80.30.9
FIBTEM CA20 (mm)9030.21.13.50.41.40.00.01.13.80.31.1
FIBTEM CMCF(mm)9032.91.13.20.61.80.00.01.23.70.41.2
HEPTEM CCT (s)90357.911.93.36.91.92.90.814.03.965.818.4
HEPTEM CA5 (mm)9026.11.03.70.00.00.41.41.03.90.00.0
HEPTEM CA10 (mm)9028.91.03.30.00.00.41.41.03.60.00.0
HEPTEM CA20 (mm)9031.31.03.10.00.00.41.31.13.40.00.0
HEPTEM CMCF(mm)9033.41.13.30.30.80.30.91.23.50.10.3

15

Interference

An interference study was performed using normal and hypocoagulable whole blood samples to determine the impact of interferents UF Heparin, LMW Heparin, Tranexamic Acid, E-Aminocaproic Acid, Acetylsalicylic Acid (Aspirin), and Ticagrelor on the INTEM C, EXTEM C, and HEPTEM C assays. For each interferent, testing was performed with eight (8) replicates at three (3) interferent levels (Baseline, Claim, and Greater than Claim) for a total of twenty-four (24) replicates for each blood sample type. Because of its sensitivity to heparin, INTEM C was not tested for heparin interference. Another interference study was performed using normal whole blood samples to determine the impact of lupus anticoagulant on the same assays. This testing was performed with eleven (11) donors, each run on three (3) instruments with one (1) replicate per instrument. Testing confirmed no interference for INTEM C, EXTEM C, FIBTEM C, and HEPTEM C on the ROTEM sigma up to the following concentrations:

InterferentINTEM CEXTEM CFIBTEM CHEPTEM C
UF HeparinN/A5 IU/mL5 IU/mL7 IU/mL
LMW HeparinN/A3 IU/mL3 IU/mL3 IU/mL
Tranexamic Acid60 µg/mL60 µg/mL60 µg/mL60 µg/mL
ε-Aminocaproic
Acid600 µg/mL600 µg/mL600 µg/mL600 µg/mL
Acetylsalicylic
Acid3 mg/dL3 mg/dL3 mg/dL3 mg/dL
Ticagrelor0.1881 mg/dL0.1881 mg/dL0.1881 mg/dL0.1881 mg/dL
Lupus
Anticoagulant
(dRVVT Screen/
Confirm Ratio)1.341.341.341.34

Interference Summary

16

Reference Intervals

A total of one hundred twenty (120) whole blood samples from healthy donors were analyzed on the ROTEM sigma using ROTEM sigma complete + hep cartridges. The nonparametric, 95% reference interval along with two-sided, 90% confidence intervals around each limit were calculated.

Parameter\AssayINTEM CEXTEM CFIBTEM CHEPTEM C
CT (s)139 - 20551 - 73N/A141 - 215
A5 (mm)36 - 5433 - 525 - 1633 - 51
A10 (mm)46 - 6345 - 626 - 1744 - 61
A20 (mm)53 - 6854 - 696 - 1852 - 67
MCF (mm)55 - 7057 - 726 - 1954 - 69
LI60 (%)93 - 10094 - 100N/AN/A
ML* (%)0 - 70 - 6N/AN/A

Reference Intervals Summary

  • calculated at 60 minutes after CT

Reportable Ranges

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

Reportable Ranges

Parameter\AssayINTEM CEXTEM CFIBTEM CHEPTEM C
CT (s)123-36545-172N/A122-376
A5 (mm)11-6613-692-3310-59
A10 (mm)16-7418-772-3615-68
A20 (mm)21-7823-812-3820-73
MCF (mm)24-7925-822-4124-75
LI60 (%)0-1000-100N/AN/A
ML* (%)0-1000-100N/AN/A

17

Method Comparison

A method comparison study was conducted at four (4) clinical sites comparing the ROTEM sigma to the predicate device, the ROTEM delta (K083842, K 101533), using 3.2% citrated venous or arterial whole blood patient samples from the intended use populations and contrived samples.

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

AssayParameterNSlopeInterceptR
INTEM CCT (s)1440.9420.90.845
A5 (mm)1440.913.80.977
A10 (mm)1440.904.80.983
A20 (mm)1440.924.50.985
MCF (mm)1440.952.50.982
LI60 (%)1481.001.00.990
ML* (%)1481.00-1.00.990
EXTEM CCT (s)1831.17-4.00.780
A5 (mm)1830.945.10.953
A10 (mm)1830.935.90.966
A20 (mm)1830.954.70.973
MCF (mm)1831.002.00.977
LI60 (%)1871.001.00.982
ML* (%)1871.00-1.00.982
FIBTEM CA5 (mm)1830.860.40.920
A10 (mm)1830.890.30.921
A20 (mm)1830.910.30.923
MCF (mm)1831.00-1.00.926
HEPTEM CCT (s)1820.9121.40.484
A5 (mm)1820.923.10.940
A10 (mm)1820.933.60.947
A20 (mm)1820.953.00.959
MCF (mm)1821.001.00.966

Method Comparison Summary

18

Arterial vs. Venous Study

A matrix comparison study using seventy-four (74) matched venous and arterial citrated whole blood samples was performed at two (2) 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 assays. The summary results for the pooled data are presented in the table below.

| 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% |
| | 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% |

Arterial vs. Venous Study Summary

1 Mean difference is calculated from Bland-Altman plot.

2 Outlier suppressed.

19

Conclusion

The technological and functional characteristics of the new ROTEM sigma system as described above are substantially equivalent to those of the predicate device (ROTEM delta, K083842/K101533).

The analytical and clinical study results demonstrate that the ROTEM sigma is safe and effective for its intended purpose and equivalent in performance to the predicate device (ROTEM delta, K083842/ K101533).