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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
Type
Traditional
Panel
Hematology
Reference & Predicate Devices
K083842,K101533
Predicate For
N/A
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview
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.
AI/ML Overview

Here's an analysis of the provided text to extract information about the acceptance criteria and the study proving the device meets them.

It's important to note that this document is a 510(k) summary for an In Vitro Diagnostic (IVD) device, specifically a Thromboelastometry System (ROTEM sigma). The "acceptance criteria" here refer to performance specifications (e.g., precision, reproducibility, method comparison) for the device's measurements, not typical "acceptance criteria" for an AI/ML model's diagnostic accuracy (like sensitivity/specificity against a ground truth). Similarly, "expert consensus" or "adjudication" in the context of IVDs refers to establishing the accepted values of controls or comparing to a reference method, not to human image interpretation.

Acceptance Criteria and Device Performance for ROTEM sigma Thromboelastometry System

The ROTEM sigma Thromboelastometry System is an in vitro diagnostic device for assessing blood coagulation. Its performance is demonstrated through various analytical studies. The acceptance criteria are implicit in the presentation of the study results, where the variability and agreement with reference methods are shown to be within acceptable ranges for an IVD.

1. Table of Acceptance Criteria and Reported Device Performance

Given that this is an IVD device, the "acceptance criteria" are typically defined by ranges of acceptable precision (CV%), reproducibility (SD/CV%), and correlation with a predicate device (slope, intercept, R-value). The document presents the results of these studies, and the implicit acceptance criteria are met if these results fall within expected performance ranges for such devices.

Summary of Key Performance Parameters (Implicit Acceptance Criteria and Reported Performance)

Performance StudyParameterAcceptance Criteria (Implicit)Reported Device Performance (Worst Case/Overall)
Precision%CV (Within-Laboratory)Should be low, indicating consistent results for identical samples.Highest %CV observed:
(Whole Blood)INTEM C: CT, A5, A10, A20, MCFGenerally < 10-15% for clinical assays, depending on parameter.CT: 6.8% (Hypocoag.), A5: 4.2% (Normal), A10: 3.3% (Normal), A20: 2.6% (Hypocoag.), MCF: 2.8% (Hypocoag.)
EXTEM C: CT, A5, A10, A20, MCFCT: 13.6% (Hypocoag./Hypercoag.), A5: 5.2% (Hypocoag.), A10: 4.1% (Hypocoag.), A20: 3.9% (Hypocoag.), MCF: 4.8% (Hypocoag.)
FIBTEM C: A5, A10, A20, MCFA5: 25.9% (Normal), A10: 25.8% (Normal), A20: 25.0% (Normal), MCF: 25.6% (Normal)
HEPTEM C: CT, A5, A10, A20, MCFCT: 9.4% (Hypocoag), A5: 9.5% (Hypocoag), A10: 8.4% (Hypocoag), A20: 8.5% (Hypocoag), MCF: 7.9% (Hypocoag)
Lysis PrecisionSD/ %CV (Within-Laboratory)Should be low, indicating consistent results for lysis parameters.INTEM C LI60: 1.5% (Normal), ML: 1.4 SD (Normal); EXTEM C LI60: 1.4% (Normal), ML: 1.4 SD (Normal)
Lot-to-Lot VariabilityBetween-Lot SD/%CVSD or %CV for between-lot variability should be minimal.CT (HEPTEM C) shows 0.4 SD, 0.2% CV. All others report 0.0 SD/CV, implying negligible between-lot variability.
Reproducibility (All Sites - Control N/P)Reproducibility SD/%CV (across sites, runs, days)Should be acceptable for a clinical device, demonstrating consistent performance in various settings.Highest Reproducibility %CV (within control lot):
(Control N)INTEM C: 7.2%
EXTEM C: 10.7%
FIBTEM C: 3.5%
HEPTEM C: 6.4%
(Control P)INTEM C: 4.7%
EXTEM C: 5.5%
FIBTEM C: 5.5%
HEPTEM C: 6.1%
InterferenceNo significant interference observed within tested concentrations.Measured values should not be significantly impacted by common interferents within specified limits.Confirmed no interference for tested interferents (UF Heparin, LMW Heparin, Tranexamic Acid, etc.) up to specific concentrations.
Reference Intervals95% RI establishedReference intervals for healthy individuals must be established for clinical interpretation.Established 95% non-parametric reference intervals for CT, A5, A10, A20, MCF, LI60, ML for all assays.
Reportable RangesDefined operating rangeThe device should accurately measure parameters across a clinically relevant range.Defined reportable ranges for CT, A5, A10, A20, MCF, LI60, ML for all assays.
Method Comparison(ROTEM sigma vs. ROTEM delta)Slope close to 1, Intercept close to 0, R-value close to 1 for strong correlation.Ranges observed:
Slope0.86 - 1.17
Intercept-4.0 - 21.4
R-value0.484 - 0.990
Arterial vs. Venous StudyMean Difference (Percentage or Absolute)Minimal/acceptable difference between arterial and venous samples to ensure applicability.Mean differences generally less than 3% in most cases, with calculated confidence intervals.

2. Sample Size Used for the Test Set and Data Provenance

The document describes several studies, each with specific sample sizes:

  • Precision (Internal Study):
    • Controls (ROTEM sigma ROTROL N and P): Twenty (20) days of testing, run in duplicate, twice a day, resulting in 80 replicates per control per lot (3 lots => 240 replicates per control type).
    • Whole Blood (Normal, Contrived Hypocoagulable, Contrived Hypercoagulable): Run in triplicate, in one (1) day, on five (5) instruments, resulting in 15 replicates per sample type per lot (3 lots => 45 replicates per sample type).
    • Lysis Precision (Normal Whole Blood & Hyperfibrinolysis Blood): Fifteen (15) replicates per sample type per cartridge lot (3 lots => 45 reps per type).
    • Lot-to-Lot Variability (Normal Donor Whole Blood): Thirty (30) replicates per cartridge lot (3 lots => 90 replicates).
  • Reproducibility (External Clinical Sites):
    • Three (3) external clinical sites.
    • Four (4) ROTEM sigma instruments per site.
    • Three (3) lots of controls (ROTEM sigma ROTROL N and P).
    • Run in triplicate, twice a day for five (5) days, resulting in thirty (30) replicates per control per site (90 replicates per control across all sites).
  • Interference:
    • Various Interferents (Heparins, Acids, Ticagrelor): Eight (8) replicates at three (3) interferent levels for normal and hypocoagulable whole blood samples.
    • Lupus Anticoagulant: Eleven (11) donors, each run on three (3) instruments with one (1) replicate per instrument.
  • Reference Intervals: One hundred twenty (120) whole blood samples from healthy donors.
  • Method Comparison:
    • Number of samples for each assay parameter: INTEM C (144-148), EXTEM C (183-187), FIBTEM C (183), HEPTEM C (182).
    • Data provenance: Patient samples from the "intended use populations and contrived samples." Conducted at four (4) clinical sites. No specific country of origin is mentioned beyond "internal precision study" and "external clinical sites" (implicitly within the regulatory region/country this submission applies to). The studies are prospective in the sense that they involve planned laboratory testing and data collection.
  • Arterial vs. Venous Study: Seventy-four (74) matched venous and arterial citrated whole blood samples. Performed at two (2) external clinical sites.

Data Provenance (Summary):
The studies include data from internal testing and multiple external clinical sites. The samples include healthy donors, patient samples (intended use populations), and contrived samples (e.g., hypocoagulable, hypercoagulable). The studies are analytical performance studies, not clinical outcome studies. These are prospective laboratory studies designed to evaluate technical performance. No specific countries are listed, but the context of an FDA 510(k) submission suggests either U.S. or international data accepted by the FDA.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

For an IVD device like the ROTEM sigma, "ground truth" is established by controlled laboratory methods and comparison to existing, cleared predicate devices, rather than human interpretation or expert consensus in the typical sense for image-based AI.

  • Precision and Reproducibility: Ground truth is inherent in the preparation of controlled samples (normal, contrived hypocoagulable, contrived hypercoagulable, control materials) with known characteristics. The goal is to demonstrate the device's ability to consistently measure these known or expected characteristics. No external human experts are involved in creating this "ground truth" beyond standard laboratory practices and quality control.
  • Method Comparison: The "ground truth" or reference standard for comparison is the predicate device, the ROTEM delta (K083842, K101533). The performance is assessed by correlating the ROTEM sigma's measurements with those of the legally marketed predicate device. This is a comparative study, not one establishing an absolute "ground truth" with human experts.

There is no mention of experts establishing ground truth in the way one would for an AI in medical imaging (e.g., radiologists annotating images).

4. Adjudication Method for the Test Set

For IVD analytical performance studies, traditional "adjudication" (e.g., 2+1, 3+1 for discordant reads) is not applicable. The measurements are quantitative. For method comparison, if there were significant discrepancies between the new device and the predicate, further investigation would occur to understand the cause, but it's not an adjudication process of human interpretation. The consistency across multiple instruments and sites is shown in the reproducibility studies.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done

No. An MRMC study is typically for evaluating the diagnostic performance of software, often AI, sometimes with and without human assistance (e.g., radiologists reading images). This document describes the analytical performance of an in vitro diagnostic instrument that measures blood coagulation properties. It does not involve human readers interpreting "cases" in a diagnostic context. Therefore, there's no "effect size of how much human readers improve with AI vs without AI assistance" to report here, as AI is not assisting human interpretation in this context; it is the measurement device.

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

The ROTEM sigma is inherently a "standalone" device in its primary function. It's an automated system that measures coagulation parameters. The performance studies (precision, reproducibility, method comparison) are all "algorithm only" in the sense that they evaluate the device's ability to produce consistent and accurate measurements on its own. Human intervention during operation involves sample loading and system maintenance, but the measurement process itself is automated ("fully integrated and automated").

7. The Type of Ground Truth Used

The "ground truth" in this context refers to established values or reference methods:

  • Established Reference Materials/Controls: For precision, reproducibility, and lot-to-lot variability, the "ground truth" is based on the known or expected values of the control materials and the stability of the whole blood samples used.
  • Predicate Device (ROTEM delta): For method comparison, the ROTEM delta serves as the reference standard or "ground truth" for evaluating the clinical equivalence of the ROTEM sigma's measurements.
  • Healthy Donor Samples: For reference interval establishment, samples from healthy individuals are used to define the typical range of values, which then serve as a clinical "ground truth" for normalcy.
  • Contrived Samples: For some studies (precision, method comparison), samples are artificially manipulated (e.g., hypocoagulable, hypercoagulable) to represent different physiological states. The "ground truth" for these is the known manipulation.

There is no "pathology" or "outcomes data" ground truth in the direct sense of a diagnostic accuracy study. The device provides semi-quantitative measurements that aid in diagnosis, but it does not provide a definitive diagnosis itself.

8. The Sample Size for the Training Set

This document describes the validation of a medical device, not the training of an AI/ML model. Therefore, there is no "training set" in the context of machine learning. The device determines coagulation parameters based on a physical principle (rotational thromboelastometry) and built-in algorithms, not from a data-driven training process in the AI sense.

9. How the Ground Truth for the Training Set Was Established

Since there is no "training set" for an AI/ML model, this question is not applicable.

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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

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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 GmbHMartin-Kollar-Strasse 1581829 Munich, Germany
Contact Person:David JacobPhone: +49 89 45 42 95 23Fax: +49 89 45 42 95 22Email: 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 CoagulationStudies (21 CFR 864.5425)
Regulatory Class:Class II
Product Code:JPA
Classification Panel:Hematology (81)
Predicate Device:K083842: ROTEM delta Thromboelastometry SystemK101533: EX-TEM, FIB-TEM, and AP-TEM for ROTEM deltaThromboelastometry 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.

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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.

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Comparison to Predicates

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

CharacteristicSubject DeviceROTEM sigmaPredicate DeviceROTEM delta(K083842, K101533)
Similarities
InstrumentFully Integrated Thromboelastometry Instrument
Measuring TechniqueShear elasticity of a coagulating sample by motion of a pin
Measuring Channelsutilized4
Signal GenerationOscillating pin in a stationary cup
Signal TransducerOptical system with CCD sensor
Sample3.2 % citrated whole blood
Measurement StationTemperature37 °C ± 1 °C
Graphical Presentationof ResultsPresents each assay reaction curve and parameters in real time "TEMogram"
Differences
Cups & PinsCups and pins are integrated into assaycartridgesCups and pins need to be installed ininstrument for each test
Sample HandlingAutomated sample transferManual pipetting, electronic pipette
Sample Volume≥ 2.7 mL sample tube for four assays300 µL per assay
Supply Voltage110/240 VAC, 60/50 Hz, max. 210 VA115/230 VAC, 60/50 Hz, max. 350 VA
Environment• Temperatureo Operating: 18 °C - 30 °Co Storage: 0 °C - 50 °C• Relative Humidityo Operating: 40 % - 60 %o Storage: 20% - 85%• Operable to 3000 m above sea level• Temperatureo Operating: 15 °C - 30 °Co 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"
CharacteristicSubject DeviceROTEM sigmaPredicate DeviceROTEM 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 FormatAll four assays (reagents) providedready-to-use in the single-use ROTEMsigma complete + hep cartridge.Assay reagents provided in separate vials.Preparation required to create the desiredassay.
Reagent FormLyophilized beadsLiquid or lyophilisate with a diluent(HEPTEM only)
Reagent HandlingCartridges containing assay reagents arestored at room temperature. No warmuprequired.Assay reagents require refrigeration,5-15 min warmup required (depending onroom temperature).
CharacteristicSubject DeviceROTEM sigmaPredicate DeviceROTEM delta(K083842/K101533)
Assay NameINTEM CINTEM
Similarities
Activation PrincipleIntrinsic coagulation activation• Recalcification of a sample• Activation of the intrinsic coagulation pathway
Activation Reagents• CaCl2• Ellagic Acid
Assay NameEXTEM CEXTEM
Similarities
Activation PrincipleExtrinsic coagulation activation• Recalcification of a sample• Activation of the extrinsic coagulation pathway
Activation Reagents• CaCl2• Recombinant Tissue Factor• Heparin Inhibitor
Assay NameFIBTEM CFIBTEM
Similarities
Activation PrincipleExtrinsic 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 NameHEPTEM CHEPTEM
Similarities
Activation PrincipleIntrinsic 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

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Comparison of Technological Characteristics with the Predicate Device - Assays

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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 NROTROL PNormal WholeBloodContrivedHypocoagulableSamplesContrivedHypercoagulableSamples
AssayParameter% CV(Within-Run)% CV(Within-Laboratory)% CV(Within-Run)% CV(Within-Laboratory)% CV(Within-Laboratory)% CV(Within-Laboratory)% CV(Within-Laboratory)
CT (s)7.78.74.64.93.86.84.5
INTEM CA5 (mm)2.02.17.07.24.23.53.9
A10 (mm)2.02.06.16.22.93.22.8
A20 (mm)1.61.67.98.21.92.61.6
MCF* (mm)1.51.68.58.71.82.81.4
EXTEM CCT (s)9.69.76.57.16.813.613.6
A5 (mm)2.42.84.95.25.05.23.0
A10 (mm)1.82.24.34.43.34.12.4
A20 (mm)1.61.75.15.32.63.91.9
MCF* (mm)1.41.55.65.92.34.81.4
FIBTEM CA5 (mm)2.62.87.27.310.2N/A4.7
A10 (mm)2.22.65.45.49.7N/A4.7
A20 (mm)2.02.24.54.57.4N/A4.2
MCF* (mm)1.71.85.25.39.8N/A4.6
HEPTEM CCT (s)4.14.34.75.63.99.42.3
A5 (mm)1.92.15.55.55.79.53.5
A10 (mm)1.81.95.65.73.98.42.5
A20 (mm)1.61.76.16.12.98.51.6
MCF* (mm)1.31.56.66.72.57.91.6
  • 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

AssayParameterNormalWhole BloodWithin-Laboratory%CVAbnormalHyperfibrinolysisBloodWithin-LaboratorySD
INTEM CLI60 (%)1.50.6
EXTEM C1.41.4
AssayParameterNormalWhole BloodWithin-LaboratorySDAbnormalHyperfibrinolysisBloodWithin-Laboratory%CV
INTEM CML* (%)1.40.6
EXTEM C1.31.4

{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.

AssayParameterNMeanRepeatabilityBetween-RunBetween-DayBetween-SiteReproducibility(Within-Control Lot)Between-Control Lot
SD%CVSD%CVSD%CVSD%CVSD%CVSD%CV
CT (s)270344.824.67.10.00.01.40.43.61.024.97.29.02.6
A5 (mm)27043.80.71.60.10.20.20.40.30.70.81.80.00.0
INTEM CA10 (mm)27047.40.71.40.00.00.30.60.51.00.91.90.00.0
A20 (mm)27051.20.71.40.00.10.30.50.61.11.01.90.00.0
MCF(mm)27055.00.81.40.40.70.20.40.71.31.12.10.00.0
CT (s)270130.213.610.42.92.20.00.01.71.314.010.73.32.5
A5 (mm)27043.60.92.10.30.70.00.00.20.41.02.30.40.9
EXTEM CA10 (mm)27047.70.91.80.30.60.00.00.10.30.92.00.40.8
A20 (mm)27052.10.81.50.30.50.00.00.20.40.81.60.30.6
MCF(mm)27056.90.91.60.20.40.00.00.30.61.01.70.20.3
A5 (mm)269*37.81.23.20.41.10.00.00.30.91.33.50.71.9
A10 (mm)269*42.31.22.80.41.00.00.00.30.71.33.10.71.6
FIBTEM CA20 (mm)269*47.11.12.30.40.90.00.00.30.71.22.60.51.2
MCF(mm)269*52.91.12.00.40.80.00.00.61.11.32.50.30.5
HEPTEM CCT (s)270332.620.86.30.00.05.11.50.00.021.46.410.73.2
A5 (mm)27043.10.81.90.00.00.00.00.71.61.12.50.00.0
A10 (mm)27046.90.91.80.00.00.10.30.81.81.22.50.00.0
A20 (mm)27051.00.81.60.00.00.10.20.81.61.12.20.00.0
MCF(mm)27054.90.81.50.30.50.10.10.91.61.22.30.00.0

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.)

AssayParameterNMeanRepeatabilityBetween-RunBetween-DayWithin-Control LotBetween-Control Lot
SD%CVSD%CVSD%CVSD%CVSD%CV
INTEM CCT (s)90343.020.35.90.00.03.91.120.76.06.41.9
INTEM CA5 (mm)9044.10.61.40.00.00.30.60.71.50.00.0
INTEM CA10 (mm)9047.70.61.30.00.00.40.80.71.50.00.0
INTEM CA20 (mm)9051.60.61.20.00.00.40.70.71.40.00.0
INTEM CMCF(mm)9055.50.91.70.51.00.20.41.12.00.20.3
EXTEM CCT (s)90128.213.910.80.00.01.31.013.910.82.92.2
EXTEM CA5 (mm)9043.91.02.30.00.00.00.01.02.30.51.2
EXTEM CA10 (mm)9047.91.02.00.00.00.00.01.02.00.51.1
EXTEM CA20 (mm)9052.20.81.60.20.40.00.00.91.70.51.0
EXTEM CMCF(mm)9057.31.11.80.40.70.00.01.12.00.30.5
FIBTEM CA5 (mm)89*38.21.12.90.41.00.00.01.23.10.51.4
FIBTEM CA10 (mm)89*42.61.12.60.51.10.00.01.22.90.51.2
FIBTEM CA20 (mm)89*47.51.12.20.51.00.00.01.22.50.40.8
FIBTEM CMCF(mm)89*53.61.12.00.71.30.00.01.32.30.20.3
HEPTEM CCT (s)90331.821.26.40.00.06.92.122.36.78.42.5
HEPTEM CA5 (mm)9043.90.92.00.00.00.00.00.92.00.20.5
HEPTEM CA10 (mm)9047.90.91.80.00.00.10.30.91.80.20.4
HEPTEM CA20 (mm)9051.90.81.50.00.00.00.00.81.50.10.2
HEPTEM CMCF(mm)9055.91.01.80.30.50.00.01.01.90.10.1

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-AminocaproicAcid600 µg/mL600 µg/mL600 µg/mL600 µg/mL
AcetylsalicylicAcid3 mg/dL3 mg/dL3 mg/dL3 mg/dL
Ticagrelor0.1881 mg/dL0.1881 mg/dL0.1881 mg/dL0.1881 mg/dL
LupusAnticoagulant(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

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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

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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.

AssayParameterNVenousMeanArterialMeanMeanDifference¹95% ConfidenceInterval
INTEM CCT (s)58480.5449.21.4%-5.6%8.4%
A5 (mm)5543.944.611.1%-8.4%30.6%
A5 (mm)25444.544.51.6%-2.4%5.6%
A10 (mm)5553.854.57.5%-5.2%20.2%
A10 (mm)25454.654.41.6%-2.9%6.0%
A20 (mm)5559.960.55.1%-3.7%13.9%
A20 (mm)25460.660.41.5%-3.6%6.6%
MCF (mm)5561.461.73.3%-3.4%10.1%
LI60 (%)5496.495.7-0.7%-1.0%-0.4%
ML (%)543.64.30.7% Lysis0.4% Lysis1.0% Lysis
EXTEM CCT (s)7372.172.30.6%-1.6%2.7%
A5 (mm)7346.246.51.0%-0.2%2.3%
A10 (mm)7356.556.60.4%-0.6%1.3%
A20 (mm)7363.163.10.0%-0.8%0.8%
MCF (mm)7365.164.9-0.2%-0.9%0.5%
LI60 (%)7397.497.2-0.2%-0.4%0.0%
ML (%)732.62.80.2% Lysis0.0% Lysis0.4% Lysis
FIBTEM CA5 (mm)7114.214.30.9%-1.0%2.9%
A10 (mm)7115.715.80.8%-1.1%2.6%
A20 (mm)7117.017.10.8%-0.6%2.3%
MCF (mm)7117.617.81.1%-0.6%2.9%
HEPTEM CCT (s)64183.5185.52.9%-1.2%6.9%
A5 (mm)6443.043.71.7%0.5%2.9%
A10 (mm)6453.454.21.5%0.6%2.4%
A20 (mm)6460.260.70.8%0.1%1.5%
MCF (mm)6462.362.20.0%-0.7%0.6%

Arterial vs. Venous Study Summary

1 Mean difference is calculated from Bland-Altman plot.

2 Outlier suppressed.

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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).

§ 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.