K Number
K150877
Date Cleared
2015-12-13

(256 days)

Product Code
Regulation Number
864.5400
Reference & Predicate Devices
Predicate For
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview
Intended Use

The ACL TOP Family 50 Series (ACL TOP 750; ACL TOP 750 CTS; ACL TOP 750 LAS; ACL TOP 550 CTS; ACL TOP 350 CTS) are bench top, fully automated, random access analyzers designed specifically for in vitro diagnostic clinical use in the hemostasis laboratory for coagulation and/or fibrinolysis testing in the assessment of thrombosis and/or hemostasis. The systems provide results for both direct hemostasis measurements and calculated parameters.

Device Description

The ACL TOP Family 50 Series are fully automated coagulation analyzers that utilize the same intuitive software, the same consumables, reagents, calibrators and provide the same analytical methodology for routine and specialty assay result reporting as the predicate ACL TOP Family. The ACL TOP Family 50 Series instrument performs the following types of tests, using the same optical measuring wavelengths and test parameters as the predicate ACL TOP Family: Coagulometric (Turbidimetric) Measurements, Chromogenic (Absorbance) Measurements, Immunological Measurements. The ACL TOP Family 50 Series also offers new pre-analytical features not available on the current ACL TOP Family: Pre-Analytical HIL Check, Pre-Analytical Tube Fill Height (THF) Check, and Pre-Analytical Clog Detection.

AI/ML Overview

Acceptance Criteria and Device Performance for ACL TOP Family 50 Series

This document outlines the acceptance criteria and the results of the studies demonstrating that the ACL TOP Family 50 Series coagulation analyzers meet these criteria. The device is intended for in vitro diagnostic clinical use for hemostasis and fibrinolysis testing.


1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for this device are established through internal and external precision, linearity, and method comparison studies, specifically aiming for performance comparable to the predicate device (ACL TOP Family) and within CLSI guidelines. While explicit numeric acceptance criteria are not presented as a single consolidated table, the pass/fail status indicated in the reproducibility study and the strong correlation coefficients/slopes in the method comparison studies serve as de-facto acceptance criteria. The device consistently passed these criteria across various assays and models.

Study TypeAssay/ParameterAcceptance Criteria (Implied)Reported Device Performance
PrecisionWithin-run %CV, Total %CV (various assays and levels)Within CLSI EP05-A2 guidelines (Specific %CVs noted in tables)All reported %CVs (within-run and total) passed acceptance criteria.
LinearitySlope, Y-Intercept, r² (various assays)r² close to 1, slope close to 1, intercept close to 0 (equivalent linearity as predicate)All r² values were >0.9781, slopes were generally close to 1, and intercepts were low, demonstrating strong linearity.
Method ComparisonSlope, Intercept, r (against predicate ACL TOP 500)r > 0.94, slope close to 1, intercept close to 0 (equivalent performance as predicate)All r values were >0.94, slopes were generally close to 1, and intercepts were small across all sites and assays.
Pre-Analytical HIL Check (Hemoglobin, Bilirubin, Lipemia)Strong correlation (r) to reference methodsHemoglobin r: >0.944, Bilirubin r: >0.952, Lipemia: >91% Overall Matching
Functional CheckPre-Analytical Clog DetectionCorrect detection of occluded sample probeAll instrument models correctly detected an occluded sample probe.
Pre-Analytical Tube Fill Height CheckCorrect detection of underfilled tubesAll instrument models correctly detected when tubes were underfilled.

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

  • Precision Study (Internal):

    • Sample Size: 80 replicates per level for each of 12 assays on each instrument model (ACL TOP 350 CTS, ACL TOP 550 CTS, ACL TOP 750 CTS, ACL TOP 750). This involved commercially available assays and their assayed control materials, as well as a prepared patient plasma pool.
    • Data Provenance: Internal, not specified country of origin, retrospective or prospective not explicitly stated but implies prospective as part of a 20-day study.
  • Precision Study (External):

    • Sample Size: 80 replicates per level for each of 11 assays (two levels of control materials) on one ACL TOP 550 CTS model at three external US sites.
    • Data Provenance: Three US external sites, implies prospective as part of a 20-day study.
  • Reproducibility Study (External):

    • Sample Size: 30 replicates per level for each of 12 assays (two levels of control materials) on one ACL TOP 550 CTS model at three external US sites.
    • Data Provenance: Three US external sites, implies prospective as part of a 5-day study.
  • Linearity Study (Internal):

    • Sample Size: Minimum of 9 levels tested in quadruplicate for each of 10 assays on each instrument model (ACL TOP 350 CTS, ACL TOP 550 CTS, ACL TOP 750 CTS, ACL TOP 750). This involved prepared plasma pool panels.
    • Data Provenance: Internal, not specified country of origin, implies prospective.
  • Method Comparison Study (External):

    • Sample Size (Assays): Ranged from 61 to 146 patient samples per assay at each of the three US external sites.
    • Sample Size (HIL Check): Hemoglobin (244-269 samples), Bilirubin (249-267 samples), Lipemia (257-272 samples) at each of the three US external sites.
    • Data Provenance: Three US external sites, patient samples, implies prospective.
  • Pre-Analytical Clog Detection Testing:

    • Sample Size: Not explicitly stated beyond "All instrument models" (2 ACL TOP 350 CTS; 2 ACL TOP 550 CTS; 2 ACL TOP 750; 2 ACL TOP 750 CTS; 1 ACL TOP 750 LAS).
    • Data Provenance: Internal, likely simulated occluded samples.
  • Pre-Analytical Tube Fill Height Check Testing:

    • Sample Size: Not explicitly stated beyond "All instrument models" (2 ACL TOP 350 CTS; 2 ACL TOP 550 CTS; 2 ACL TOP 750; 2 ACL TOP 750 CTS).
    • Data Provenance: Internal, likely simulated underfilled tubes.

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

  • For clinical assays (Precision, Linearity, Method Comparison): The ground truth is established by the calibrated reference methods and control materials themselves, which are well-established in clinical laboratory standards. No human "experts" are explicitly mentioned whose adjudication was required to establish ground truth for these quantitative measurements, as the values are determined by the analytical process and certified controls.
  • For Pre-Analytical HIL Check (Lipemia): "Visual Matching" was used as a reference for Lipemia. While not explicitly stated, this would typically involve trained laboratory personnel or experts in visual assessment of lipemia. The number and qualifications of these individuals are not specified in the provided text.
  • For Pre-Analytical Clog Detection and Tube Fill Height Check: The ground truth for these functional tests was whether the instrument correctly detected the intentionally created conditions (occluded probe, underfilled tube). This doesn't rely on expert human judgment for each instance, but rather on the designed functionality of the system.

4. Adjudication Method for the Test Set

  • For the quantitative clinical assays, there is no indication of an adjudication method involving multiple human readers as the output is a numerical measurement. The CLSI guidelines followed (EP05-A2, EP09-A3) dictate statistical analysis of quantitative results.
  • For the Lipemia "Visual Matching" reference method, no specific adjudication method (e.g., 2+1, 3+1) is mentioned.

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

No MRMC comparative effectiveness study was done, as this device (ACL TOP Family 50 Series) is a fully automated laboratory instrument for coagulation testing, not an AI-assisted diagnostic imaging or interpretation tool that would involve human readers. The new pre-analytical features (HIL Check, Tube Fill Height Check, Clog Detection) are described as alerts to the instrument operator, but there is no mention of an AI component or a study on human reader performance with or without such assistance. The device's primary function is quantitative measurement.


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

Yes, the studies presented are all standalone validations of the instrument's performance. The "ACL TOP Family 50 Series" is a fully automated analyzer. The precision, linearity, and method comparison studies directly evaluate the algorithm's (instrument's) ability to accurately and precisely measure coagulation parameters and detect pre-analytical issues without human intervention in the measurement process itself. The "Pre-Analytical HIL Check," "Pre-Analytical Clog Detection," and "Pre-Analytical Tube Fill Height Check" are new algorithmic features designed to flag samples automatically. The performance of these flags is evaluated in a standalone manner against a reference method (for HIL) or by simply checking if the instrument's detection mechanism worked correctly (for clog and tube fill).


7. The type of ground truth used

  • For clinical assays (Precision, Linearity, Method Comparison): The ground truth is primarily based on reference methods and assayed control materials with known concentrations/values, as per established clinical laboratory standards (e.g., CLSI guidelines). For method comparison, the predicate device (ACL TOP 500) served as the reference for patient samples.
  • For Pre-Analytical HIL Check:
    • Hemoglobin: HemoCue (K000043) was used as the reference device.
    • Bilirubin: Envoy 500 (K945271) was used as the reference device.
    • Lipemia: "Visual Matching" was used as the reference.
  • For Pre-Analytical Clog Detection and Tube Fill Height Check: The ground truth was known induced conditions (occluded probe, underfilled tubes) that the instrument was designed to detect.

8. The sample size for the training set

The provided document describes validation studies (precision, linearity, method comparison) for the ACL TOP Family 50 Series. It does not explicitly mention a "training set" or "test set" in the context of machine learning, implying that the device's algorithms for analytical measurements are based on established physicochemical principles and validated through these performance studies rather than being developed through a machine learning training paradigm. The studies described are for validation of the device's performance, not for training a model.


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

As there is no explicit mention of a "training set" in the context of machine learning for generating the core analytical measurements or the pre-analytical flagging algorithms, the question of how ground truth was established for a training set is not applicable based on the provided information. The device's foundational analytical capabilities would have been developed using known chemical/biological principles and standard calibration processes. The new pre-analytical features are described as programmed detections (e.g., measuring at 535 nm for HIL, pressure transducer for clogs, optical detection for tube fill) and their performance validated against reference methods or known conditions.

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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

December 13, 2015

Instrumentation Laboratory (IL) Co. Carol Marble Regulatory Affairs Director 180 Hartwell Road Bedford, MA 01730

Re: K150877

Trade/Device Name: ACL TOP Family 50 Series Models: ACL TOP 350 CTS, ACL TOP 550 CTS, ACL TOP 750, ACL TOP 750 CTS, ACL TOP 750 LAS Regulation Number: 21 CFR 864.5400 Regulation Name: Coagulation Instrument Regulatory Class: Class II Product Code: GKP Dated: November 12, 2015 Received: November 13, 2015

Dear Ms. Marble:

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. 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 801 and 809); medical device reporting (reporting of

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medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Leonthena R. Carrington -S

Leonthena R. Carrington, MS, MBA, MT(ASCP) Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known)

Device Name

ACL TOP Family 50 Series (ACL TOP 750 CTS; ACL TOP 750 LAS; ACL TOP 750 LAS; ACL TOP 550 CTS; ACL TOP 350 CTS)

Indications for Use (Describe)

The ACL TOP Family 50 Series (ACL TOP 750; ACL TOP 750 CTS; ACL TOP 750 LAS; ACL TOP 550 CTS; ACL TOP 350 CTS) are bench top, fully automated, random access analyzers designed specifically for in vitro diagnostic clinical use in the hemostasis laboratory for coagulation and/or fibrinolysis testing in the assessment of thrombosis and/or hemostasis. The systems provide results for both direct hemostasis measurements and calculated parameters.

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.

Submitter's InformationInstrumentation Laboratory (IL) Co.180 Hartwell RoadBedford, MA 01730, USA
-------------------------------------------------------------------------------------------------------------
Contact PersonCarol Marble, Regulatory Affairs Director
Phone: 781-861-4467
Fax: 781-861-4207
Email: cmarble@ilww.com
Preparation DateNovember 12, 2015
-------------------------------------
Device Trade NamesACL TOP Family 50 Series Models:
• ACL TOP 350 CTS
• ACL TOP 550 CTS
• ACL TOP 750
• ACL TOP 750 CTS
• ACL TOP 750 LAS
Regulatory InformationClassification:Class II
Regulation No.:21 CFR 864.5400
Common Name:Coagulation Instrument
Panel:Hematology (81)
Product Code:GKP
Predicate DeviceACL TOP: K073377; K091980 for LAS model
-----------------------------------------------------------
Device Indications for Use /Intended UseThe ACL TOP Family 50 Series (ACL TOP 750; ACL TOP 750 CTS;ACL TOP 750 LAS; ACL TOP 550 CTS; ACL TOP 350 CTS) arebench top, fully automated, random access analyzers designedspecifically for in vitro diagnostic clinical use in the hemostasislaboratory for coagulation and/or fibrinolysis testing in theassessment of thrombosis and/or hemostasis. The systemsprovide results for both direct hemostasis measurements andcalculated parameters.
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

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Description

The ACL TOP Family 50 Series are fully automated coagulation analyzers that utilize the same intuitive software, the same consumables, reagents, calibrators and provide the same analytical methodology for routine and specialty assay result reporting as the predicate ACL TOP Family.

The ACL TOP Family 50 Series instrument performs the following types of tests, using the same optical measuring wavelengths and test parameters as the predicate ACL TOP Family:

  • . Coagulometric (Turbidimetric) Measurements
  • Chromogenic (Absorbance) Measurements
  • Immunological Measurements

The ACL TOP Family 50 Series also offers new pre-analytical features not available on the current ACL TOP Family as described below. These features are not intended to replace laboratory quality policies. The features simply alert the instrument operator to a potential HIL (Hemoglobin, Icteric and Lipemia) interference situation specific to the assays requested for a sample, underfilled sample tubes or a detected clog. The user will determine how to handle these situations (for example, by not reporting the results, or reporting the results with, or without, additional comments).

Pre-Analytical FeaturesThe Pre-Analytical HIL Check detects and measures interference caused bythe presence of hemoglobin, bilirubin, and light scattering lipids in patientsamples. H – Hemolysis (hemoglobin) I – Icterus (bilirubin) L- Lipemia (turbidity) The Pre-Analytical HIL Check aids the coagulation laboratory in identifyingand handling potential HIL interference issues. This feature flags samples toalert instrument operators of potential HIL interference specific to the testsrequested for a sample.NOTES: There are no analytical claims for hemoglobin, bilirubin or turbidityanalysis with the introduction of the Pre-Analytical HIL Check .Information provided by the check does not replace any interferenceinformation included in the package inserts of IL products.A third measurement wavelength @535 nm and an additional emitter controlchannel (all models) have been introduced to support the new Pre-AnalyticalHIL Check feature.
The Pre-Analytical Tube Fill Height (THF) Check aids laboratories byscreening open and closed tube samples during the first sample aspiration todetermine whether the tube fill meets the minimum level based on the tubemanufacturer's recommendations.The fill height check for each patient sample occurs before the analyticaltesting process begins and thus there is no effect on patient test results.
A Pre-Analytical Clog Detection is performed on all samples duringaspiration.A pre-analytical error or warning for fluidic obstruction is an indication for theuser to review the sample integrity, following established laboratory samplequality procedures.A pressure transducer (all models) has been introduced to support this newPre-Analytical Clog Detection feature.

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Comparison to Predicate
ItemPredicateNew Device
Trade NamesACL TOP Family Models ACL TOP 700 (Base) ACL TOP 700 CTS ACL TOP 700 LAS ACL TOP 500 CTS ACL TOP 300 CTSACL TOP Family 50 Series Models ACL TOP 750 ACL TOP 750 CTS ACL TOP 750 LAS ACL TOP 550 CTS ACL TOP 350 CTS
ManufacturerInstrumentation Laboratory Co.Same
Product CodeGKPSame
Regulation Section864.5400Same
ClassificationClass IISame
Regulation DescriptionCoagulation InstrumentSame
Similarities
Indications for UseThe ACL TOP is a bench top, fullyautomated, random access analyzerdesigned specifically for in vitrodiagnostic clinical use in the hemostasislaboratory for coagulation and/orfibrinolysis testing in the assessment ofthrombosis and/or hemostasis.The system provides results for bothdirect hemostasis measurements andcalculated parameters.The ACL TOP Family 50 Series(ACL TOP 750, ACL TOP 750 CTS,ACL TOP 750 LAS, ACL TOP 550CTS and ACL TOP 350 CTS) arebench top, fully automated,random access analyzersdesigned specifically for in vitrodiagnostic clinical use in thehemostasis laboratory forcoagulation and/or fibrinolysistesting in the assessment ofthrombosis and/or hemostasis.The systems provide results forboth direct hemostasismeasurements and calculatedparameters.
Matrix3.2% Citrated PlasmaSame
MethodologyThe ACL TOP Family performs thefollowing types of tests: Coagulometric (Turbidimetric)Measurements (405 nm or 671 nm) Chromogenic (Absorbance)Measurements (405 nm) Immunological Measurements(405 nm or 671 nm)Same
Test MenuClotting, chromogenic andimmunological assaysSame
Quality ControlAutomated QCSame
Comparison to Predicate (Cont.)
ItemPredicateNew Device
Trade NamesACL TOP Family Models ACL TOP 700 (Base) ACL TOP 700 CTS ACL TOP 700 LAS ACL TOP 500 CTS ACL TOP 300 CTSACL TOP Family 50 Series Models ACL TOP 750 ACL TOP 750 CTS ACL TOP 750 LAS ACL TOP 550 CTS ACL TOP 350 CTS
Differences
Pre-Analytical HIL CheckNot AvailableStandard for All ModelsA third measurement wavelength@535 nm and an additionalemitter control channel (allmodels) have been introduced tosupport this new feature.
Pre-Analytical Tube Fill HeightCheckNot AvailableStandard for All Models
Pre-Analytical Clog DetectionNot AvailableStandard for All ModelsA pressure transducer (all models)has been introduced to supportthis new feature.
SoftwareWindows XPWindows 7
Not ApplicableSupport for new features

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Precision Study – Internal

In compliance with CLSI EP05-A2, an internal 20-day precision study was performed on an ACL TOP 350 CTS, ACL TOP 550 CTS, ACL TOP 750 CTS and ACL TOP 750, using 12 representative commercially available assays and their assayed control materials, as well as a prepared patient plasma pool. All materials were tested in duplicate, twice a day for 20 days, for a total of 80 replicates per level for each assay on each instrument model as summarized below.

HemosIL RecombiPlasTin 2G (K070005)
Measurand:Prothrombin Time (Seconds)
Model:ACL TOP 350 CTS
SampleHemosILNormal ControlHemosILAbnormal ControlHemosIL HighAbnormal ControlPlasma Pool
N80808080
Within-run %CV (Observed)0.70.90.81.0
Total %CV (Observed)1.21.72.21.5
Grand Mean (seconds)11.4722.0338.6730.40
Model:ACL TOP 550 CTS
SampleHemosILNormal ControlHemosILAbnormal ControlHemosIL HighAbnormal ControlPlasma Pool
N80808080
Within-run %CV (Observed)0.60.80.90.7
Total %CV (Observed)1.42.43.01.8
Grand Mean (seconds)11.5922.2138.8230.79
Model:ACL TOP 750 CTS
SampleHemosILNormal ControlHemosILAbnormal ControlHemosIL HighAbnormal ControlPlasma Pool
N80808080
Within-run %CV (Observed)0.60.90.90.7
Total %CV (Observed)1.42.02.91.5
Grand Mean (seconds)11.5122.2538.7630.66
Model:ACL TOP 750
SampleHemosILNormal ControlHemosILAbnormal ControlHemosIL HighAbnormal ControlPlasma Pool
N80808080
Within-run %CV (Observed)0.61.00.60.8
Total %CV (Observed)1.62.43.02.0
Grand Mean (seconds)11.4022.0638.7830.33

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HemosIL RecombiPlasTin 2G (K070005)
Derived Fibrinogen (mg/dL)Measurand:
Model:ACL TOP 350 CTS
SampleHemosILNormal ControlHemosIL LowAbnormal ControlHemosIL LowFibrinogen ControlPlasma Pool
N80808080
Within-run %CV (Observed)1.41.32.92.7
Total %CV (Observed)1.81.73.73.3
Grand Mean (mg/dL)323.8144.1137.6385.4
Model:ACL TOP 550 CTS
SampleHemosILNormal ControlHemosIL LowAbnormal ControlHemosIL LowFibrinogen ControlHemosILNormal Control
N80808080
Within-run %CV (Observed)1.01.34.02.1
Total %CV (Observed)ਹ ਤ1.74.42.2
Grand Mean (mg/dL)320.8143.6137.0379.2
Model:ACL TOP 750 CTS
SampleHemosILNormal ControlHemosIL LowAbnormal ControlHemosIL LowFibrinogen ControlPlasma Pool
N80808080
Within-run %CV (Observed)1.11.54.43.1
Total %CV (Observed)1.41.84.83.6
Grand Mean (mg/dL)323.7144.4141.1389.0
ACL TOP 750Model:
SampleHemosILNormal ControlHemosIL LowAbnormal ControlHemosIL LowFibrinogen ControlPlasma Pool
N80808080
Within-run %CV (Observed)1.01.84.22.3
Total %CV (Observed)1.51.94.22.3
Grand Mean (mg/dL)320.1139.8133.9384.4

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Г

HemosIL SynthASil (K060688)
Measurand: APTT (Seconds)
Model:ACL TOP 350 CTS
SampleHemosILNormal ControlHemosIL LowAbnormal ControlHemosIL HighAbnormal ControlPlasma Pool
N80808080
Within-run %CV (Observed)0.70.80.601.4
Total %CV (Observed)0.90.91.32.5
Grand Mean (seconds)31.6543.9356.5457.21
Model:ACL TOP 550 CTS
SampleHemosILNormal ControlHemosIL LowAbnormal ControlHemosIL HighAbnormal ControlPlasma Pool
N80808080
Within-run %CV (Observed)1.31.51.41.6
Total %CV (Observed)1.41.61.72.0
Grand Mean (seconds)32.0944.6057.6558.46
Model:ACL TOP 750 CTS
SampleHemosILNormal ControlHemosIL LowAbnormal ControlHemosIL HighAbnormal ControlPlasma Pool
N80808080
Within-run %CV (Observed)0.80.91.11.2
Total %CV (Observed)1.21.31.51.6
Grand Mean (seconds)32.0044.4057.0558.12
Model:ACL TOP 750
SampleHemosILNormal ControlHemosIL LowAbnormal ControlHemosIL HighAbnormal ControlPlasma Pool
N80808080
Within-run %CV (Observed)1.31.21.51.7
Total %CV (Observed)1.41.52.12.3
Grand Mean (seconds)32.0144.6057.2658.95

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Precision Study - Internal (Cont.)
HemosIL Fibrinogen-C (K073367)
Measurand: Fibrinogen Clauss (mg/dL)
Model: ACL TOP 350 CTS
SampleHemosILNormal ControlHemosILLow Fibrinogen ControlPlasma Pool
N808080
Within-run %CV (Observed)3.73.42.5
Total %CV (Observed)4.13.82.9
Grand Mean (mg/dL)317.2105.0361.5
Model: ACL TOP 550 CTS
SampleHemosILNormal ControlHemosILLow Fibrinogen ControlPlasma Pool
N808080
Within-run %CV (Observed)2.95.52.3
Total %CV (Observed)3.55.63.4
Grand Mean (mg/dL)327.9104.3374.4
Model: ACL TOP 750 CTS
SampleHemosILNormal ControlHemosILLow Fibrinogen ControlPlasma Pool
N808080
Within-run %CV (Observed)2.44.82.2
Total %CV (Observed)2.94.92.6
Grand Mean (mg/dL)328.7110.3371.8
Model: ACL TOP 750
SampleHemosILNormal ControlHemosILLow Fibrinogen ControlPlasma Pool
N808080
Within-run %CV (Observed)2.44.51.8
Total %CV (Observed)2.74.62.4
Grand Mean (mg/dL)324.6106.9368.8

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Precision Study – Internal (Cont.)

T

HemosIL D-Dimer (K073042)
Measurand: D-Dimer (ng/mL)
Model: ACL TOP 350 CTS
SampleHemosILD-Dimer Low ControlHemosILD-Dimer High ControlPlasma Pool
N808080
Within-run %CV (Observed)3.92.98.5
Total %CV (Observed)4.93.09.6
Grand Mean (ng/mL)362.4690.7175.8
Model: ACL TOP 550 CTS
SampleHemosILD-Dimer Low ControlHemosILD-Dimer High ControlPlasma Pool
N808080
Within-run %CV (Observed)6.63.69.2
Total %CV (Observed)7.13.711.4
Grand Mean (ng/mL)367.6698.1175.0
Model: ACL TOP 750 CTS
SampleHemosILD-Dimer Low ControlHemosILD-Dimer High ControlPlasma Pool
N808080
Within-run %CV (Observed)4.32.56.1
Total %CV (Observed)5.22.78.7
Grand Mean (ng/mL)351.6695.0168.0
Model: ACL TOP 750
SampleHemosILD-Dimer Low ControlHemosILD-Dimer High ControlPlasma Pool
N808080
Within-run %CV (Observed)4.53.19.7
Total %CV (Observed)5.63.210.5
Grand Mean (ng/mL)328.4658.8149.3

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HemosIL Liquid Antithrombin (K062431)
Measurand: Antithrombin (%)
Model: ACL TOP 350 CTS
SampleHemosIL Normal ControlHemosIL Special Test Level 1HemosIL Special Test Level 2Plasma Pool
N80808080
Within-run %CV (Observed)2.54.18.92.4
Total %CV (Observed)2.77.811.04.5
Grand Mean (%)101.255.723.1112.9
Model: ACL TOP 550 CTS
SampleHemosIL Normal ControlHemosIL Special Test Level 1HemosIL Special Test Level 2Plasma Pool
N80808080
Within-run %CV (Observed)2.02.65.42.2
Total %CV (Observed)2.85.47.94.0
Grand Mean (%)103.558.628.4114.9
Model: ACL TOP 750 CTS
SampleHemosIL Normal ControlHemosIL Special Test Level 1HemosIL Special Test Level 2Plasma Pool
N80808080
Within-run %CV (Observed)2.02.56.62.0
Total %CV (Observed)2.15.38.23.4
Grand Mean (%)99.657.727.7108.9
Model: ACL TOP 750
SampleHemosIL Normal ControlHemosIL Special Test Level 1HemosIL Special Test Level 2Plasma Pool
N80808080
Within-run %CV (Observed)1.62.06.61.6
Total %CV (Observed)2.24.97.43.1
Grand Mean (%)98.756.726.7109.7

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

Г

HemosIL Protein C (K062430)
Measurand: Protein C (%)
Model:ACL TOP 350 CTS
SampleHemosILNormal ControlHemosIL SpecialTest Level 1HemosIL SpecialTest Level 2Plasma Pool
N80808080
Within-run %CV (Observed)1.61.11.61.2
Total %CV (Observed)2.12.22.21.8
Grand Mean (%)100.659.126.8119.2
Model:ACL TOP 550 CTS
SampleHemosILNormal ControlHemosIL SpecialTest Level 1HemosIL SpecialTest Level 2Plasma Pool
N80808080
Within-run %CV (Observed)1.31.62.01.3
Total %CV (Observed)1.62.12.32.2
Grand Mean (%)101.359.125.9120.2
Model:ACL TOP 750 CTS
SampleHemosILNormal ControlHemosIL SpecialTest Level 1HemosIL SpecialTest Level 2Plasma Pool
N80808080
Within-run %CV (Observed)1.21.21.21.1
Total %CV (Observed)1.41.92.31.7
Grand Mean (%)99.358.727.1117.8
Model:ACL TOP 750
SampleHemosILNormal ControlHemosIL SpecialTest Level 1HemosIL SpecialTest Level 2Plasma Pool
N80808080
Within-run %CV (Observed)1.51.31.91.5
Total %CV (Observed)2.12.32.31.8
Grand Mean (%)100.658.025.3120.0

{14}------------------------------------------------

Г

HemosIL Free Protein S (K010379)
Measurand:Free Protein S (%)
Model:ACL TOP 350 CTS
SampleHemosILNormal ControlHemosIL SpecialTest Level 1HemosIL SpecialTest Level 2Plasma Pool
N80808080
Within-run %CV (Observed)1.31.41.71.1
Total %CV (Observed)2.22.63.22.6
Grand Mean (%)94.6459.5628.4785.12
Model:ACL TOP 550 CTS
SampleHemosILNormal ControlHemosIL SpecialTest Level 1HemosIL SpecialTest Level 2Plasma Pool
N80808080
Within-run %CV (Observed)1.11.41:50.9
Total %CV (Observed)2.82.82.82.6
Grand Mean (%)93.7659.2128.4884.65
Model:ACL TOP 750 CTS
SampleHemosILNormal ControlHemosIL SpecialTest Level 1HemosIL SpecialTest Level 2Plasma Pool
N80808080
Within-run %CV (Observed)0.81.41.80.8
Total %CV (Observed)2.72.82.82.2
Grand Mean (%)97.8760.9729.0387.68
Model:ACL TOP 750
SampleHemosILNormal ControlHemosIL SpecialTest Level 1HemosIL SpecialTest Level 2Plasma Pool
N80808080
Within-run %CV (Observed)0.81.01.61.0
Total %CV (Observed)2.62.42.82.6
Grand Mean (%)96.1059.8128.1086.95

{15}------------------------------------------------

HemosIL Factor V Deficient Plasma (K023839) with HemosIL RecombiPlasTin 2G (K070005)
Measurand: Factor V (%)
Model:ACL TOP 350 CTS
SampleHemosILNormal ControlHemosIL SpecialTest Level 2Plasma Pool
N808080
Within-run %CV (Observed)3.82.93.8
Total %CV (Observed)5.15.610.1
Grand Mean (%)109.3328.277.51
Model:ACL TOP 550 CTS
SampleHemosILNormal ControlHemosIL SpecialTest Level 2Plasma Pool
N808080
Within-run %CV (Observed)4.03.24.5
Total %CV (Observed)5.85.89.1
Grand Mean (%)110.0427.327.79
Model:ACL TOP 750 CTS
SampleHemosILNormal ControlHemosIL SpecialTest Level 2Plasma Pool
N808080
Within-run %CV (Observed)2.62.52.6
Total %CV (Observed)4.85.38.6
Grand Mean (%)108.1828.907.86
Model:ACL TOP 750
SampleHemosILNormal ControlHemosIL SpecialTest Level 2Plasma Pool
N808080
Within-run %CV (Observed)1.91.82.1
Total %CV (Observed)3.94.78.3
Grand Mean (%)108.6528.867.80

{16}------------------------------------------------

HemosIL Factor VII Deficient Plasma (K024082) with HemosIL RecombiPlasTin 2G (K070005)
Measurand:Factor VII (%)
Model:ACL TOP 350 CTS
SampleHemosILNormal ControlHemosIL SpecialTest Level 2Plasma Pool
N808080
Within-run %CV (Observed)3.95.45.0
Total %CV (Observed)4.25.96.2
Grand Mean (%)86.6918.3911.73
Model:ACL TOP 550 CTS
SampleHemosILNormal ControlHemosIL SpecialTest Level 2Plasma Pool
N808080
Within-run %CV (Observed)3.94.85.5
Total %CV (Observed)4.25.46.0
Grand Mean (%)87.7018.4011.89
Model:ACL TOP 750 CTS
SampleHemosILNormal ControlHemosIL SpecialTest Level 2Plasma Pool
N808080
Within-run %CV (Observed)2.53.02.9
Total %CV (Observed)3.24.95.1
Grand Mean (%)83.5919.2712.36
Model:ACL TOP 750
SampleHemosILNormal ControlHemosIL SpecialTest Level 2Plasma Pool
N808080
Within-run %CV (Observed)1.61.72.3
Total %CV (Observed)3.24.04.4
Grand Mean (%)86.3320.0112.91

{17}------------------------------------------------

HemosIL Factor VIII Deficient Plasma (K034007) with HemosIL SynthASil (K060688)
Measurand: Factor VIII (%)
Model:ACL TOP 350 CTS
SampleHemosILNormal ControlHemosIL SpecialTest Level 2Plasma Pool
N808080
Within-run %CV (Observed)3.43.33.8
Total %CV (Observed)3.94.27.6
Grand Mean (%)87.6624.396.91
Model:ACL TOP 550 CTS
SampleHemosILNormal ControlHemosIL SpecialTest Level 2Plasma Pool
N808080
Within-run %CV (Observed)3.94.04.9
Total %CV (Observed)5.35.77.9
Grand Mean (%)85.1022.756.68
Model:ACL TOP 750 CTS
SampleHemosILNormal ControlHemosIL SpecialTest Level 2Plasma Pool
N808080
Within-run %CV (Observed)3.33.33.1
Total %CV (Observed)4.14.76.8
Grand Mean (%)86.4924.607.09
Model:ACL TOP 750
SampleHemosILNormal ControlHemosIL SpecialTest Level 2Plasma Pool
N808080
Within-run %CV (Observed)2.23.43.6
Total %CV (Observed)3.94.26.4
Grand Mean (%)86.4225.827.35

{18}------------------------------------------------

HemosIL Factor IX Deficient Plasma (K031829) with HemosIL SynthASil (K060688)
Measurand:Factor IX (%)
ACL TOP 350 CTSModel:
SampleHemosILNormal ControlHemosIL SpecialTest Level 2Plasma Pool
N808080
Within-run %CV (Observed)3.83.03.5
Total %CV (Observed)4.64.04.6
Grand Mean (%)110.4029.4410.14
Model:ACL TOP 550 CTS
SampleHemosILNormal ControlHemosIL SpecialTest Level 2Plasma Pool
N808080
Within-run %CV (Observed)4.93.84.6
Total %CV (Observed)6:54.85.8
Grand Mean (%)107.0629.0310.74
Model:ACL TOP 750 CTS
SampleHemosILNormal ControlHemosIL SpecialTest Level 2Plasma Pool
N808080
Within-run %CV (Observed)3.94.33.7
Total %CV (Observed)4.24.84.6
Grand Mean (%)110.5031.3911.45
ACL TOP 750Model:
SampleHemosILNormal ControlHemosIL SpecialTest Level 2Plasma Pool
N808080
Within-run %CV (Observed)2.53.22.9
Total %CV (Observed)2.93.64.5
Grand Mean (%)108.7231.2911.64

{19}------------------------------------------------

Linearity Study – Internal

An internal linearity study was performed on an ACL TOP 350 CTS, ACL TOP 550 CTS, ACL TOP 750 CTS and ACL TOP 750, using 10 representative commercially available assays* and prepared plasma pool panels at a minimum of 9 levels. Each of the different panel levels was tested in quadruplicate on each instrument model with the resultant data supporting equivalent linearity range claims to the current ACL TOP Family.

HemosIL RecombiPlasTin 2G (K070005)
Derived Fibrinogen (mg/dL)Measurand:
Instrument ModelACL TOP 350 CTSACL TOP 550 CTSACL TOP 750 CTSACL TOP 750
Slope1.02221.01521.01471.015
Y-Intercept15.29613.27215.90116.143
0.98940.99270.9910.991
Range (mg/dL)59-72254-75460-73158-732
HemosIL Fibrinogen-C (K073367)
Fibrinogen Clauss (mg/dL)Measurand:
Instrument ModelACL TOP 350 CTSACL TOP 550 CTSACL TOP 750 CTSACL TOP 750
Slope1.05291.08321.06911.0804
Y-Intercept8.15561.57635.18155.3006
r20.99130.98910.98730.987
Range (mg/dL)27-120730-121626-116530-1154
HemosIL D-Dimer (K073042)
Measurand:D-Dimer (ng/mL)
Instrument ModelACL TOP 350 CTSACL TOP 550 CTSACL TOP 750 CTSACL TOP 750
Slope0.98981.01951.03121.0217
Y-Intercept143.8393.58883.20374.254
0.97810.98380.98370.9877
Range (ng/mL)133-5415122-5362106-538395-5296

*NOTE: Linearity is not applicable to PT and APTT assays.

{20}------------------------------------------------

HemosIL Liquid Antithrombin (K062431)
Measurand:Antithrombin (%)
Instrument ModelACL TOP 350 CTSACL TOP 550 CTSACL TOP 750 CTSACL TOP 750
Slope0.94270.9960.9680.9652
Y-Intercept3.4053-1.38150.68260.6046
r20.99870.99970.99710.9993
Range (%)9.3-158.06.0-152.06.5-157.86.8-159.0
HemosIL Protein C (K062430)
Measurand:Protein C (%)
Instrument ModelACL TOP 350 CTSACL TOP 550 CTSACL TOP 750 CTSACL TOP 750
Slope0.99561.00430.99721.0049
Y-Intercept-1.1765-2.6449-2.3988-1.4761
r20.99910.99910.99910.9995
Range (%)5.5-160.54.0-158.84.5-163.85.8-166.5
HemosIL Free Protein S (K010379)
Measurand:Free Protein S (%)
Instrument ModelACL TOP 350 CTSACL TOP 550 CTSACL TOP 750 CTSACL TOP 750
Slope1.031.04611.04141.0455
Y-Intercept-4.8376-6.169-6.0499-6.4417
r20.99830.99630.99740.998
Range (%)10.4-325.39.8-318.19.7-309.19.3-309.8
HemosIL Factor V Deficient Plasma (K023839) with HemosIL RecombiPlasTin 2G (K070005)
Measurand:Factor V (%)
Instrument ModelACL TOP 350 CTSACL TOP 550 CTSACL TOP 750 CTSACL TOP 750
Slope0.9740.9720.9240.9328
Y-Intercept0.16070.47783.09723.6627
r20.99910.99840.99660.9969
Range (%)0.4-157.60.3-151.20.3-159.60.3-154.3
HemosIL Factor VII Deficient Plasma (K024082) with HemosIL RecombiPlasTin 2G (K070005)
Measurand:Factor VII (%)
Instrument ModelACL TOP 350 CTSACL TOP 550 CTSACL TOP 750 CTSACL TOP 750
Slope0.95330.96980.92330.9136
Y-Intercept1.40913.17704.40444.5945
r20.99870.99720.99650.9962
Range (%)0.3-159.50.4-170.00.2-163.20.3-159.6

{21}------------------------------------------------

Linearity Study – Internal (Cont.)

HemosIL Factor VIII Deficient Plasma (K034007) with HemosIL SynthASil (K060688)
Measurand: Factor VIII (%)
Instrument ModelACL TOP 350 CTSACL TOP 550 CTSACL TOP 750 CTSACL TOP 750
Slope0.98421.05970.99030.9586
Y-Intercept-0.8923-2.42080.31182.1453
0.99910.9990.99920.9969
Range (%)0.2-151.60.3-159.90.1-160.50.3-150.6
HemosIL Factor IX Deficient Plasma (K031829) with HemosIL SynthASil (K060688)
Measurand: Factor IX (%)
Instrument ModelACL TOP 350 CTSACL TOP 550 CTSACL TOP 750 CTSACL TOP 750
Slope0.99790.99130.97190.9999
Y-Intercept-1.7626-1.78050.6774-0.8352
0.99930.99770.99890.9996
Range (%)0.2-161.80.3-163.00.5-158.10.5-153.4

{22}------------------------------------------------

Precision Study – External

An external 20-day precision study was performed at the same three US external sites on an ACL TOP 550 CTS by three different operators, using 11 representative commercially available assays each with two levels of assayed control materials were tested in duplicate, twice a day for 20 days, for a total of 80 replicates per level for each assay on each model as summarized below.

  • NOTE: Precision data for derived fibrinogen with HemosIL RecombiPlasTin 2G were not collected under the scope of this study
External Site No. 1
AssayMeasurandControlNMeanWithin-runCV%TotalCV%
HemosIL RecombiPlasTin 2G(K070005)ProthrombinTime (seconds)HemosIL Normal ControlHemosIL High Abnormal808011.540.81.0%1.4%1.6%3.5%
HemosIL SynthASil(K060688)APTT(Seconds)HemosIL Normal ControlHemosIL High Abnormal808029.952.51.0%1.4%1.2%1.9%
HemosIL Fibrinogen-C(K073367)FibrinogenClauss (mg/dL)HemosIL Normal ControlHemosIL Low Fibrinogen8080264904.3%4.3%4.5%4.7%
HemosIL D-Dimer(K073042)D-Dimer(ng/mL)HemosIL D-Dimer LowHemosIL D-Dimer High80803447396.9%2.8%11.2%4.4%
HemosIL Liquid Antithrombin(K062431)Antithrombin(%)HemosIL Normal ControlSpecial Test Level 28080100232.1%6.0%2.5%7.7%
HemosIL Protein C(K062430)Protein C(%)HemosIL Normal ControlSpecial Test Level 2808099261.4%3.8%2.3%4.0%
HemosIL Free Protein S(K010379)Free Protein S(%)HemosIL Normal ControlSpecial Test Level 2808099301.9%3.0%6.3%9.1%
HemosIL Factor V DeficientPlasma (K023839) withHemosIL RecombiPlasTin 2G(K070005)Factor V(%)HemosIL Normal ControlSpecial Test Level 28080102323.6%4.5%6.7%6.7%
HemosIL Factor VII DeficientPlasma (K024082) withHemosIL RecombiPlasTin 2G(K070005)Factor VII(%)HemosIL Normal ControlSpecial Test Level 28080103263.2%3.8%4.7%5.7%
HemosIL Factor VIII DeficientPlasma (K034007) withHemosIL SynthASil (K060688)Factor VIII(%)HemosIL Normal ControlSpecial Test Level 2808087254.5%4.0%9.1%12.6%
HemosIL Factor IX DeficientPlasma (K031829) withHemosIL SynthASil (K060688)Factor IX(%)HemosIL Normal ControlSpecial Test Level 28080102314.7%9.2%8.4%10.1%

{23}------------------------------------------------

External Site No. 2
AssayMeasurandControlNMeanWithin-runCV%TotalCV%
HemosIL RecombiPlasTin 2G(K070005)ProthrombinTime (seconds)HemosIL Normal ControlHemosIL High Abnormal808011.438.71.7%1.5%2.3%3.2%
HemosIL SynthASil(K060688)APTT(Seconds)HemosIL Normal ControlHemosIL High Abnormal808030.555.91.6%1.6%1.8%1.8%
HemosIL Fibrinogen-C(K073367)FibrinogenClauss (mg/dL)HemosIL Normal ControlHemosIL Low Fibrinogen8080285943.6%3.2%4.4%4.7%
HemosIL D-Dimer(K073042)D-Dimer(ng/mL)HemosIL D-Dimer LowHemosIL D-Dimer High80803337125.0%2.6%7.5%5.1%
HemosIL Liquid Antithrombin(K062431)Antithrombin(%)HemosIL Normal ControlSpecial Test Level 2808093251.7%6.1%3.1%9.0%
HemosIL Protein C(K062430)Protein C(%)HemosIL Normal ControlSpecial Test Level 2808093241.5%1.8%2.5%3.1%
HemosIL Free Protein S(K010379)Free Protein S(%)HemosIL Normal ControlSpecial Test Level 2808092292.4%3.1%5.8%6.0%
HemosIL Factor V DeficientPlasma (K023839) withHemosIL RecombiPlasTin 2G(K070005)Factor V(%)HemosIL Normal ControlSpecial Test Level 2808097305.3%5.1%7.3%6.9%
HemosIL Factor VII DeficientPlasma (K024082) withHemosIL RecombiPlasTin 2G(K070005)Factor VII(%)HemosIL Normal ControlSpecial Test Level 2808090233.2%3.1%5.5%6.2%
HemosIL Factor VIII DeficientPlasma (K034007) withHemosIL SynthASil (K060688)Factor VIII(%)HemosIL Normal ControlSpecial Test Level 2808084263.1%3.9%6.4%7.8%
HemosIL Factor IX DeficientPlasma (K031829) withHemosIL SynthASil (K060688)Factor IX(%)HemosIL Normal ControlSpecial Test Level 28080101314.9%4.8%7.8%7.7%

{24}------------------------------------------------

External Site No. 3
AssayMeasurandControlNMeanWithin-runCV%TotalCV%
HemosIL RecombiPlasTin 2GProthrombinHemosIL Normal Control80। 11.1%2.5%
(K070005)Time (seconds)HemosIL High Abnormal80ਤੇ ਰੋ4.8%5.4%
HemosIL SynthASilAPTTHemosIL Normal Control80311.3%2.2%
(K060688)(Seconds)HemosIL High Abnormal80541.8%2.1%
HemosIL Fibrinogen-CFibrinogenHemosIL Normal Control803203.0%4.6%
(K073367)Clauss (mg/dL)HemosIL Low Fibrinogen801023.6%6.3%
HemosIL D-DimerD-DimerHemosIL D-Dimer Low803984.5%6.1%
(K073042)(ng/mL)HemosIL D-Dimer High807253.8%5.6%
HemosIL Liquid AntithrombinAntithrombinHemosIL Normal Control80ਰੇਖ2.3%3.7%
(K062431)(%)Special Test Level 280225.1%7.4%
HemosIL Protein CProtein CHemosIL Normal Control80ਰੇਖ1.8%3.3%
(K062430)(%)Special Test Level 280242.7%3.8%
HemosIL Free Protein SFree Protein SHemosIL Normal Control80ਰੇਟ3.8%4.3%
(K010379)(%)Special Test Level 280282.0%3.5%
HemosIL Factor V DeficientPlasma (K023839) withHemosIL RecombiPlasTin 2G(K070005)Factor V(%)HemosIL Normal ControlSpecial Test Level 28080100324.1%3.7%7.5%9.6%
HemosIL Factor VII DeficientPlasma (K024082) withHemosIL RecombiPlasTin 2G(K070005)Factor VII(%)HemosIL Normal ControlSpecial Test Level 2808081212.7%2.2%8.0%7.3%
HemosIL Factor VIII DeficientPlasma (K034007) withHemosIL SynthASil (K060688)Factor VIII(%)HemosIL Normal ControlSpecial Test Level 28080ਰੇਖ282.3%3.1%5.4%4.7%
HemosIL Factor IX DeficientPlasma (K031829) withHemosIL SynthASil (K060688)Factor IX(%)HemosIL Normal ControlSpecial Test Level 28080107343.5%4.1%4.8%5.2%

{25}------------------------------------------------

Reproducibility Study - External

An external 5-day precision study was performed at three US sites on an ACL TOP 550 CTS by three different operators, using the same lot of 12 representative commercially available assays, each with two lot of assayed control materials. All materials were tested in triplicate, twice a day for 5 days, for a total of 30 replicates per level for each assay on each model as summarized below.

Level (unit)NMeanStatusWith-in RunTotal
SiteMeasurand%CVSpec (%CV)Status%CVSpec (%CV)Status
Site 1PTNormal Ctrl (Sec)3011.28PASS0.7%$\le$ 3.0%Pass1.9%$\le$ 3.0%Pass
Site 23011.33PASS0.7%$\le$ 3.0%Pass1.9%$\le$ 3.0%Pass
Site 33011.45PASS0.6%$\le$ 3.0%Pass1.1%$\le$ 3.0%Pass
Site 1PTAbnormal Ctrl (Sec)3038.50PASS2.1%$\le$ 5.0%Pass4.4%$\le$ 8.0%Pass
Site 23040.50PASS2.1%$\le$ 5.0%Pass3.7%$\le$ 8.0%Pass
Site 33039.83PASS1.8%$\le$ 5.0%Pass2.5%$\le$ 8.0%Pass
Site 1Derived FibNormal Ctrl (mg/dL)30324.0PASS1.2%$\le$ 15.0%Pass2.4%$\le$ 15.0%Pass
Site 230329.3PASS1.0%$\le$ 15.0%Pass1.1%$\le$ 15.0%Pass
Site 330337.5PASS0.7%$\le$ 15.0%Pass2.5%$\le$ 15.0%Pass
Site 1Derived FibLow Fib Ctrl (mg/dL)30140.4PASS2.9%$\le$ 15.0%Pass3.8%$\le$ 15.0%Pass
Site 230145.4PASS3.7%$\le$ 15.0%Pass3.9%$\le$ 15.0%Pass
Site 330151.7PASS2.9%$\le$ 15.0%Pass3.0%$\le$ 15.0%Pass
Site 1APTTNormalCtrl (Sec)3031.01PASS1.2%$\le$ 2.5%Pass1.2%$\le$ 3.5%Pass
Site 23030.62PASS1.3%$\le$ 2.5%Pass1.4%$\le$ 3.5%Pass
Site 33030.52PASS0.9%$\le$ 2.5%Pass1.3%$\le$ 3.5%Pass
Site 1APTTAbnormal Ctrl (Sec)3055.55PASS1.4%$\le$ 4.0%Pass1.6%$\le$ 5.0%Pass
Site 23055.58PASS1.3%$\le$ 4.0%Pass1.5%$\le$ 5.0%Pass
Site 33054.99PASS1.7%$\le$ 4.0%Pass1.8%$\le$ 5.0%Pass
Site 1Fib-CNormal Ctrl (mg/dL)30310.1PASS4.8%$\le$ 8.0%Pass4.8%$\le$ 10.0%Pass
Site 230327.0PASS3.0%$\le$ 8.0%Pass4.5%$\le$ 10.0%Pass
Site 330321.3PASS2.9%$\le$ 8.0%Pass4.4%$\le$ 10.0%Pass
Site 1Fib-CLow Fib Ctrl (mg/dL)30100.2PASS3.7%$\le$ 8.0%Pass4.2%$\le$ 10.0%Pass
Site 230105.8PASS5.2%$\le$ 8.0%Pass5.9%$\le$ 10.0%Pass
Site 330106.6PASS3.3%$\le$ 8.0%Pass5.3%$\le$ 10.0%Pass

{26}------------------------------------------------

Reproducibility Study – External (Cont.)

NMeanStatus%CVWith-in RunSpec (%CV)Status%CVTotalSpec (%CV)Status
SiteMeasurandLevel (unit)
Site 1D-DimerD-Dimer High (ng/mL)30710.1PASS3.3%8.0%Pass3.4%10.0%Pass
Site 2D-Dimer High (ng/mL)30723PASS3.6%8.0%Pass4.0%10.0%Pass
Site 3D-Dimer High (ng/mL)30748.8PASS3.6%8.0%Pass3.6%10.0%Pass
Site 1D-DimerD-Dimer Low (ng/mL)29355.9PASS4.9%10.0%Pass5.8%12.0%Pass
Site 2D-Dimer Low (ng/mL)30361.3PASS4.2%10.0%Pass5.6%12.0%Pass
Site 3D-Dimer Low (ng/mL)30397.3PASS4.6%10.0%Pass4.8%12.0%Pass
Site 1AntithrombinNormal Ctrl (%)3096.5PASS1.7%6.0%Pass2.0%8.0%Pass
Site 2Normal Ctrl (%)3097.6PASS1.9%6.0%Pass2.1%8.0%Pass
Site 3Normal Ctrl (%)3094.5PASS1.3%6.0%Pass2.8%8.0%Pass
Site 1AntithrombinSpecial Ctrl Level 2 (%)3023.4PASS7.1%15.0%Pass7.6%15.0%Pass
Site 2Special Ctrl Level 2 (%)3021.9PASS6.8%15.0%Pass7.2%15.0%Pass
Site 3Special Ctrl Level 2 (%)3022.2PASS5.9%15.0%Pass6.2%15.0%Pass
Site 1Protein CNormal Ctrl (%)3097.2PASS1.6%5.0%Pass1.8%6.0%Pass
Site 2Normal Ctrl (%)3098.2PASS1.3%5.0%Pass2.1%6.0%Pass
Site 3Normal Ctrl (%)3097.6PASS1.4%5.0%Pass3.0%6.0%Pass
Site 1Protein CSpecial Ctrl Level 2 (%)3023.9PASS1.9%10.0%Pass2.5%12.0%Pass
Site 2Special Ctrl Level 2 (%)3024.7PASS2.1%10.0%Pass2.5%12.0%Pass
Site 3Special Ctrl Level 2 (%)3024.4PASS1.8%10.0%Pass3.1%12.0%Pass
Site 1Free Protein SNormal Ctrl (%)3095.94PASS1.4%6.0%Pass2.3%8.0%Pass
Site 2Normal Ctrl (%)3097.53PASS1.4%6.0%Pass2.2%8.0%Pass
Site 3Normal Ctrl (%)3096.94PASS1.3%6.0%Pass2.1%8.0%Pass
Site 1Free Protein SSpecial Ctrl Level 2 (%)3025.09PASS3.4%10.0%Pass3.4%12.0%Pass
Site 2Special Ctrl Level 2 (%)3025.44PASS2.1%10.0%Pass2.6%12.0%Pass
Site 3Special Ctrl Level 2 (%)3024.23PASS2.6%10.0%Pass3.8%12.0%Pass

{27}------------------------------------------------

Reproducibility Study – External (Cont.)

SiteMeasurandLevel (unit)NMeanStatusWith-in RunTotal
%CVSpec (%CV)Status%CVSpec (%CV)Status
Site 1Factor VNormal Ctrl (%)3095.01PASS3.3%<10.0%Pass6.6%<10.0%Pass
Site 2Factor VNormal Ctrl (%)3095.39PASS3.2%<10.0%Pass5.2%<10.0%Pass
Site 3Factor VNormal Ctrl (%)30100.87PASS3.7%<10.0%Pass3.8%<10.0%Pass
Site 1Factor VSpecial Ctrl Level 2 (%)3028.33PASS3.4%<12.0%Pass8.1%<14.0%Pass
Site 2Factor VSpecial Ctrl Level 2 (%)3028.96PASS3.7%<12.0%Pass5.0%<14.0%Pass
Site 3Factor VSpecial Ctrl Level 2 (%)3030.73PASS3.8%<12.0%Pass5.8%<14.0%Pass
Site 1Factor VIINormal Ctrl (%)3089.55PASS2.6%<10.0%Pass7.6%<10.0%Pass
Site 2Factor VIINormal Ctrl (%)3081.48PASS2.1%<10.0%Pass5.7%<10.0%Pass
Site 3Factor VIINormal Ctrl (%)3086.39PASS2.8%<10.0%Pass3.4%<10.0%Pass
Site 1Factor VIISpecial Ctrl Level 2 (%)3020.31PASS2.1%<12.0%Pass6.5%<14.0%Pass
Site 2Factor VIISpecial Ctrl Level 2 (%)3019.53PASS1.9%<12.0%Pass5.9%<14.0%Pass
Site 3Factor VIISpecial Ctrl Level 2 (%)3020.37PASS2.0%<12.0%Pass3.9%<14.0%Pass
Site 1Factor VIIINormal Ctrl (%)3093.86PASS4.8%<10.0%Pass4.8%<10.0%Pass
Site 2Factor VIIINormal Ctrl (%)3091.13PASS2.8%<10.0%Pass3.2%<10.0%Pass
Site 3Factor VIIINormal Ctrl (%)3094.68PASS2.9%<10.0%Pass4.0%<10.0%Pass
Site 1Factor VIIISpecial Ctrl Level 2 (%)3027.13PASS5.8%<12.0%Pass9.5%<14.0%Pass
Site 2Factor VIIISpecial Ctrl Level 2 (%)3025.17PASS3.9%<12.0%Pass4.6%<14.0%Pass
Site 3Factor VIIISpecial Ctrl Level 2 (%)3027.20PASS3.4%<12.0%Pass8.5%<14.0%Pass
Site 1Factor IXNormal Ctrl (%)30104.22PASS4.6%<10.0%Pass5.2%<10.0%Pass
Site 2Factor IXNormal Ctrl (%)30104.72PASS3.8%<10.0%Pass4.3%<10.0%Pass
Site 3Factor IXNormal Ctrl (%)3093.91PASS2.7%<10.0%Pass3.7%<10.0%Pass
Site 1Factor IXSpecial Ctrl Level 2 (%)3029.85PASS4.6%<12.0%Pass4.6%<14.0%Pass
Site 2Factor IXSpecial Ctrl Level 2 (%)3029.66PASS3.6%<12.0%Pass3.9%<14.0%Pass
Site 3Factor IXSpecial Ctrl Level 2 (%)3028.83PASS2.9%<12.0%Pass3.5%<14.0%Pass

{28}------------------------------------------------

Method Comparison Study – External

Method comparison studies were conducted at three US external sites on patient samples following CLSI EP09-A3. Testing at each site compared a representative ACL TOP Family 50 Series model (ACL TOP 550 CTS) to an ACL TOP 500 model (predicate), using 12 representative commercially available assays. Summary statistics for each site are presented below.

NOTE: Results outside of the individual assay's linear range, samples with incomplete information and
samples with instrument errors were removed from final calculations.
External Site No. 1
AssayMeasurandUnits# ofSamplesSlopeInterceptr
HemosIL RecombiPlasTin 2G(K070005)Prothrombin Timeseconds1460.93500.73090.997
(K070005)Derived Fibrinogenmg/dL1080.9883-6.1750.997
HemosIL SynthASil(K060688)APTTseconds1461.085-3.3960.998
HemosIL Fibrinogen-C(K073367)Fibrinogen Claussmg/dL1231.047-15.230.983
HemosIL D-Dimer(K073042)D-Dimerng/mL760.972134.710.997
HemosIL Liquid Antithrombin(K062431)Antithrombin%1231.048-3.6270.972
HemosIL Protein C(K062430)Protein C%1180.98420.27670.992
HemosIL Free Protein S(K010379)Free Protein S%1211.003-0.74470.995
HemosIL Factor V DeficientPlasma (K023839) withHemosIL RecombiPlasTin 2G(K070005)Factor V%1201.0650.55480.976
HemosIL Factor VII DeficientPlasma (K024082) withHemosIL RecombiPlasTin 2G(K070005)Factor VII%1201.0061.3000.982
HemosIL Factor VIII DeficientPlasma (K034007) withHemosIL SynthASil (K060688)Factor VIII%861.014-1.4030.975
HemosIL Factor IX DeficientPlasma (K031829) withHemosIL SynthASil (K060688)Factor IX%1040.95911.6800.974

{29}------------------------------------------------

Method Comparison Study – External (Cont.)

External Site No. 2
AssayMeasurandUnits# of SamplesSlopeInterceptr
HemosIL RecombiPlasTin 2G(K070005)Prothrombin Timeseconds1200.94180.39750.996
Derived Fibrinogenmg/dL970.9791-5.8150.997
HemosIL SynthASil(K060688)APTTseconds1210.96231.0620.993
HemosIL Fibrinogen-C(K073367)Fibrinogen Claussmg/dL1110.94250.26880.981
HemosIL D-Dimer(K073042)D-Dimerng/mL610.978115.980.992
HemosIL Liquid Antithrombin(K062431)Antithrombin%1180.95885.1630.990
HemosIL Protein C(K062430)Protein C%1161.0070.63970.992
HemosIL Free Protein S(K010379)Free Protein S%1101.010-0.50870.981
HemosIL Factor V DeficientPlasma (K023839) withHemosIL RecombiPlasTin 2G(K070005)Factor V%1170.96451.2810.986
HemosIL Factor VII DeficientPlasma (K024082) withHemosIL RecombiPlasTin 2G(K070005)Factor VII%1180.87614.3550.976
HemosIL Factor VIII DeficientPlasma (K034007) withHemosIL SynthASil (K060688)Factor VIII%640.9342-1.4710.944
HemosIL Factor IX DeficientPlasma (K031829) withHemosIL SynthASil (K060688)Factor IX%1110.8773-0.38830.962

{30}------------------------------------------------

Method Comparison Study – External (Cont.)

External Site No. 3
AssayMeasurandUnits# ofSamplesSlopeInterceptr
HemosIL RecombiPlasTin 2G(K070005)Prothrombin Timeseconds1270.96580.50890.995
HemosIL RecombiPlasTin 2G(K070005)Derived Fibrinogenmg/dL1241.005-5.5690.996
HemosIL SynthASil(K060688)APTTseconds1331.068-1.8710.998
HemosIL Fibrinogen-C(K073367)Fibrinogen Claussmg/dL1300.948924.930.983
HemosIL D-Dimer(K073042)D-Dimerng/mL741.075-11.650.998
HemosIL LiquidAntithrombin(K062431)Antithrombin%1220.9659-3.3770.978
HemosIL Protein C(K062430)Protein C%1170.9284-0.96010.993
HemosIL Free Protein S(K010379)Free Protein S%1220.94430.62800.997
HemosIL Factor V DeficientPlasma (K023839) withHemosIL RecombiPlasTin 2G(K070005)Factor V%1210.9792-0.13960.987
HemosIL Factor VII DeficientPlasma (K024082) withHemosIL RecombiPlasTin 2G(K070005)Factor VII%1160.95400.71690.991
HemosIL Factor VIIIDeficient Plasma (K034007)with HemosIL SynthASil(K060688)Factor VIII%751.0043.0880.972
HemosIL Factor IX DeficientPlasma (K031829) withHemosIL SynthASil(K060688)Factor IX%1071.0250.85810.979

{31}------------------------------------------------

Method Comparison Study – External (Pre-Analytical HIL Check)

External method comparison studies for the new Pre-Analytical HIL Check feature were also conducted at three US sites on patient samples following CLSI EPO9-A3. Testing at each site compared a representative ACL TOP Family 50 Series model (ACL TOP 550 CTS) to the reference devices listed in the table below.

  • NOTES: The Pre-Analytical HIL Check feature flags sample results to alert instrument operators of potential HIL interference specific to the assays requested for a sample. There are no analytical claims for hemoglobin, bilirubin or turbidity analysis with the introduction of the Pre-Analytical HIL Check.
    Information provided by the check does not replace any interference information included in the package inserts of IL products.
External Site No. 1
InterferentReference# of SamplesUnitsSlopeInterceptr
HemoglobinHemoCue (BK000043)257mg/dL1.0699.0000.944
BilirubinEnvoy 500 (K945271)256mg/dL1.1620.57380.963
LipemiaVisual Matching266% Overall Matching91%
External Site No. 2
InterferentReference# of SamplesUnitsSlopeInterceptr
HemoglobinHemoCue (BK000043)244mg/dL1.06814.920.957
BilirubinEnvoy 500 (K945271)249mg/dL1.1600.89480.973
LipemiaVisual Matching257% Overall Matching93%
External Site No. 3
InterferentReference# of SamplesUnitsSlopeInterceptr
HemoglobinHemoCue (BK000043)269mg/dL1.03115.410.971
BilirubinEnvoy 500 (K945271)267mg/dL1.1270.59770.952
LipemiaVisual Matching272% Overall Matching95%

Pre-Analytical Clog Detection Testing

A Pre-Analytical Clog Detection test was conducted internally on ACL TOP Family 50 Series model instruments (2 ACL TOP 350 CTS models; 2 ACL TOP 550 CTS models; 2 ACL TOP 750 models; 2 ACL TOP 750 CTS models; 1 ACL TOP 750 LAS model). All instrument models correctly detected an occluded sample probe.

Pre-Analytical Tube Fill Height Check Testing

A Pre-Analytical Tube Fill Height Check test was conducted internally on ACL TOP Family 50 Series model instruments (2 ACL TOP 350 CTS models; 2 ACL TOP 550 CTS models; 2 ACL TOP 750 models; 2 ACL TOP 750 CTS models). All instrument models correctly detected when tubes were underfilled.

Conclusion:

Based on the shared indications for use, operating principle, consumables, reagents, controls and calibrators, and considering the above summary performance data, the ACL TOP Family 50 Series with its new pre-analytical features can be concluded to be substantially equivalent to the cleared and currently marketed predicate device, ACL TOP Family.

§ 864.5400 Coagulation instrument.

(a)
Identification. A coagulation instrument is an automated or semiautomated device used to determine the onset of clot formation for in vitro coagulation studies.(b)
Classification. Class II (special controls). A fibrometer or coagulation timer intended for use with a coagulation instrument is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 864.9.