K Number
K131975
Date Cleared
2013-10-02

(96 days)

Product Code
Regulation Number
862.1440
Reference & Predicate Devices
Predicate For
N/A
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview
Intended Use

The ACE Direct Total Iron-Binding Capacity (TIBC) Reagent is intended for the quantitative determination of total iron-binding capacity in serum using the ACE Alera Clinical Chemistry System. Iron-binding capacity measurements are used in the diagnosis and treatment of anemia. This test is intended for use in clinical laboratories and physician office laboratories. For in vitro diagnostic use only.

The ACE Total Iron Reagent is intended for the quantitative determination of iron in serum using the ACE Alera Clinical Chemistry System. Iron (non-heme) measurements are used in the diagnosis and treatment of diseases such as iron deficiency anemia, hemochromatosis (a disease associated with widespread deposit in the tissues of two iron-containing pigments, hemosiderin and hemofuscin, and characterized by pigmentation of the skin), and chronic renal disease. This test is intended for use in clinical laboratories and physician office laboratories. For in vitro diagnostic use only.

The ACE LDH-L Reagent is intended for the quantitative determination of lactate dehydrogenase activity in serum using the ACE Alera Clinical Chemistry System. Lactate dehydrogenase measurements are used in the diagnosis and treatment of liver diseases such as acute viral hepatitis, cirrhosis, and metastatic carcinoma of the liver, cardiac diseases such as myocardial infarction and tumors of the lung or kidneys. This test is intended for use in clinical laboratories and physician office laboratories. For in vitro diagnostic use only.

Device Description

In the ACE Direct Total Iron-Binding Capacity (TIBC) Reagent assay, Direct TIBC Color Reagent, an acidic buffer containing an iron-binding dye and ferric chloride, is added to the serum sample. The low pH of Direct TIBC Color Reagent releases iron from transferrin. The iron then forms a colored complex with the dye. The colored complex at the end of the first step represents both the serum iron and excess iron already present in Direct TIBC Color Reagent. Direct TIBC Buffer, a neutral buffer, is then added, shifting the pH and resulting in a large increase in the affinity of transferrin for iron. The serum transferrin rapidly binds the iron by abstracting it from the dye-iron complex. The observed decrease in absorbance of the colored dye-iron complex is directly proportional to the total iron-binding capacity of the serum sample. The absorbance is measured at 647 nm.

In the ACE Total Iron Reagent assay, transferrin-bound iron in serum is released at an acidic pH and reduced from ferric to ferrous ions. These ions react with ferrozine to form a violet colored complex, which is measured bichromatically at 554 nm/692 nm. The intensity of color produced is directly proportional to the serum iron concentration.

In the ACE LDH-L Reagent assay, lactate dehydrogenase catalyzes the conversion of L-lactate to pyruvate. Nicotinamide adenine dinucleotide (NAD+) acts as an acceptor for the hydrogen ions released from the L-lactate and is converted to reduced nicotinamide adenine dinucleotide (NADH). NADH absorbs strongly at 340 nm whereas NAD+ does not. Therefore, the rate of conversion of NAD+ to NADH can be determined by monitoring the increase in absorbance bichromatically at 340 nm/647 nm. This rate of conversion from NAD+ to NADH is directly proportional to the lactate dehydrogenase activity in the sample.

AI/ML Overview

The provided document describes in vitro diagnostic (IVD) reagents (ACE Direct Total Iron-Binding Capacity (TIBC) Reagent, ACE Total Iron Reagent, and ACE LDH-L Reagent) for use on the ACE Alera Clinical Chemistry System. The acceptance criteria and performance data presented relate to the analytical performance of these reagents/systems, specifically their ability to accurately and precisely measure analytes in serum samples.

Crucially, this is not a study about an AI/ML powered medical device. Therefore, many of the typical acceptance criteria and study aspects requested in your prompt regarding AI/ML (e.g., ground truth established by experts, multi-reader multi-case studies, human-in-the-loop performance, training/test set sample sizes for AI, adjudication methods) are not applicable to this type of device and submission.

The "study" described here is a series of analytical performance tests (linearity, precision, method comparison, detection limits, interference) to demonstrate that the new device (ACE Alera system with these reagents) performs comparably to the predicate device (ACE Clinical Chemistry System with the same reagents) and meets established analytical performance specifications for clinical chemistry assays.

Here's a breakdown of the relevant information from the document in the format you requested, with an explanation of why certain AI/ML-centric points are not applicable:


Device: ACE Direct Total Iron-Binding Capacity (TIBC) Reagent, ACE Total Iron Reagent, ACE LDH-L Reagent (for use on ACE Alera Clinical Chemistry System)

1. Table of acceptance criteria and reported device performance:

Since the document does not explicitly present "acceptance criteria" alongside "reported performance" in a single table, I will infer the acceptance criteria from the context of method comparison, linearity, and precision studies, which are standard for IVD device validation, often aiming for performance comparable to predicate devices or within clinically acceptable limits. The reported performance is directly extracted from the tables provided.

Interference:
The acceptance criterion for interference studies in IVD assays is typically that the interferent, up to a specified concentration, does not cause a "significant interference" (e.g., a bias exceeding a defined clinical or analytical threshold). The document lists the concentrations at which no significant interference was observed.

InterferentNo Significant Interference at or below (Acceptance Criteria Implicit)Reported Device Performance (Concentration where no significant interference was observed)
TIBC
IcterusAssumes standard limits for non-interference59 mg/dL
HemolysisAssumes standard limits for non-interference188 mg/dL*
LipemiaAssumes standard limits for non-interference1000 mg/dL
Ascorbic AcidAssumes standard limits for non-interference3 mg/dL
Iron
IcterusAssumes standard limits for non-interference59 mg/dL
HemolysisAssumes standard limits for non-interference125 mg/dL*
LipemiaAssumes standard limits for non-interference125 mg/dL
Ascorbic AcidAssumes standard limits for non-interference6 mg/dL
LDH-L
IcterusAssumes standard limits for non-interference50 mg/dL
HemolysisAssumes standard limits for non-interference<31 mg/dL*
LipemiaAssumes standard limits for non-interference1000 mg/dL
Ascorbic AcidAssumes standard limits for non-interference6 mg/dL

Note: The asterisk on hemolysis results typically implies a specific consideration or limitation, which would be detailed in the full study report but is not fully elaborated here.

Linearity:
The acceptance criterion for linearity is typically a correlation coefficient (r²) very close to 1 and a slope close to 1 with an intercept close to 0, indicating a proportional relationship between the measured value and the true concentration across the claimed measuring range.

ReagentLow Level TestedHigh Level TestedClaimed Linear to (Acceptance Criteria)Reported Linear Regression EquationReported r²
TIBC34 µg/dL740 µg/dL700 µg/dLy = 1.020x + 3.10.9981
Iron6 µg/dL666 µg/dL600 µg/dLy = 1.030x + 1.90.9986
LDH-L8 U/L895 U/L850 U/Ly = 1.050x - 0.70.9981

Precision (In-House):
Acceptance criteria for precision are typically defined by maximum allowable standard deviation (SD) or coefficient of variation (%CV) at different concentration levels. These are usually set based on clinical utility or comparison to commercially available assays or predicate devices. The reported values are directly shown.

ReagentSample LevelMeanReported Within-Run Precision (SD, %CV)Reported Total Precision (SD, %CV)
TIBC (µg/dL)Low2174.1, 1.9%6.7, 3.1%
Mid2703.7, 1.4%7.1, 2.6%
High3105.0, 1.6%8.6, 2.8%
Iron (µg/dL)Low623.2, 5.2%4.6, 7.3%
Mid1452.2, 1.5%4.2, 2.9%
High2264.1, 1.8%5.0, 2.2%
LDH-L (U/L)1773.8, 4.9%4.2, 5.5%
21195.1, 4.3%5.2, 4.3%
32704.5, 1.7%5.8, 2.1%
465112.6, 1.9%13.5, 2.1%

Method Comparison (In-House ACE (x) vs. In-House ACE Alera (y)):
The acceptance criteria are typically a slope close to 1, an intercept close to 0, and a high correlation coefficient (e.g., >0.99), ideally with the confidence intervals for slope encompassing 1 and for intercept encompassing 0. This indicates analytical equivalence between the two systems.

Reagentn (samples)Range (of samples tested)Reported SlopeReported InterceptReported Correlation CoefficientCI SlopeCI Intercept
TIBC5059 to 676 µg/dL0.9873.60.99600.962 to 1.013-7.2 to 14.4
Iron4813 to 549 µg/dL0.9930.90.99950.984 to 1.003-0.6 to 2.3
LDH-L5820 to 799 U/L0.997-3.60.99910.985 to 1.008-6.1 to -1.1

Precision (POL - Point of Care/Physician Office Lab):
Similar to in-house precision, specific %CV or SD limits would be the acceptance criteria. The data shows results from 3 POLs compared to in-house.

ReagentLabSample LevelMeanWithin-Run SD, %CVTotal SD, %CV
Direct TIBCIn-House13305.1, 1.5%5.8, 1.8%
POL 112848.3, 2.9%9.6, 3.4%
POL 212595.6, 2.2%8.5, 3.3%
POL 312769.1, 3.3%16.7, 6.0%
In-House24504.9, 1.1%6.8, 1.5%
POL 124646.3, 1.4%6.6, 1.4%
POL 224444.2, 1.0%5.4, 1.2%
POL 324533.2, 0.7%15.5, 3.4%
In-House35309.4, 1.8%10.8, 2.0%
POL 135448.2, 1.5%8.3, 1.5%
POL 235205.0, 1.0%9.0, 1.7%
POL 3353312.6, 2.4%20.2, 3.8%
Total IronIn-House11191.8, 1.5%2.5, 2.1%
POL 111192.7, 2.3%3.2, 2.7%
POL 211223.1, 2.6%3.1, 2.6%
POL 311163.2, 2.8%3.4, 3.0%
In-House22223.8, 1.7%5.1, 2.3%
POL 122292.0, 0.9%2.5, 1.1%
POL 222352.3, 1.0%2.4, 1.0%
POL 322293.4, 1.5%3.9, 1.7%
In-House34125.2, 1.3%5.7, 1.4%
POL 134244.0, 0.9%4.6, 1.1%
POL 234352.4, 0.5%5.3, 1.2%
POL 3342811.1, 2.6%11.1, 2.6%
LDH-LIn-House11182.9, 2.4%5.7, 4.8%
POL 111161.7, 1.5%4.9, 4.3%
POL 211183.0, 2.5%5.1, 4.3%
POL 311243.4, 2.7%4.7, 3.8%
In-House24334.7, 1.1%6.5, 1.5%
POL 124372.9, 0.7%5.8, 1.3%
POL 224493.7, 0.8%5.2, 1.2%
POL 324465.8, 1.3%6.6, 1.5%
In-House36995.3, 0.8%8.5, 1.2%
POL 136988.6, 1.2%11.5, 1.6%
POL 237265.4, 0.8%10.0, 1.4%
POL 3371614.3, 2.0%16.9, 2.4%

Method Comparison (POLs vs. In-House (ACE Alera (x) vs. POL ACE Alera (y))):
Similar to the in-house method comparison, the acceptance criteria are for slopes to be near 1, intercepts near 0, and high correlation coefficients (e.g., >0.99), indicating consistent performance across different lab environments.

ReagentLab Comparisonn (samples)RangeReported RegressionReported CorrelationCI SlopeCI Intercept
TIBCIn-House vs. POL 15059 to 676y = 0.994x + 12.40.99340.961 to 1.027-1.7 to 26.5
In-House vs. POL 25059 to 676y = 0.973x + 0.10.99540.946 to 1.001-11.4 to 11.6
In-House vs. POL 35059 to 676y = 1.005x + 9.00.98980.963 to 1.047-8.7 to 26.6
IronIn-House vs. POL 14813 to 549y = 0.976x + 1.00.99860.960 to 0.991-1.4 to 3.3
In-House vs. POL 24813 to 549y = 0.976x + 2.30.99810.959 to 0.994-0.4 to 5.0
In-House vs. POL 34813 to 549y = 0.951x + 0.80.99660.927 to 0.974-2.7 to 4.4
LDH-LIn-House vs. POL 15174 to 799y = 0.992x + 3.50.99860.977 to 1.008-0.1 to 7.1
In-House vs. POL 25174 to 799y = 1.027x + 3.40.99891.013 to 1.0410.2 to 6.7
In-House vs. POL 35174 to 799y = 1.010x + 2.50.99840.994 to 1.026-1.3 to 6.2

2. Sample sizes used for the test set and the data provenance:

  • Sample Sizes for analytical performance studies (Test Set):

    • Method Comparison:
      • TIBC: 50 samples
      • Iron: 48 samples
      • LDH-L: 58 (in-house comparison) / 51 (POL comparison) samples
    • Linearity: The number of samples/levels for linearity is not explicitly stated as 'n', but standard practice involves multiple levels (typically 5-7) prepared from diluted/spiked samples.
    • Precision: Standard runs (e.g., 2 runs per day for 20 days for total precision, with replicates per run for within-run precision) would involve a substantial number of measurements (e.g., 20 days x 2 runs/day x 2 replicates/run = 80 measurements per level). The POL precision data shows n=20, likely referring to 20 days of testing.
    • Interference: The number of samples used for interference studies is not explicitly stated.
  • Data Provenance: "In-House" and "POL" (Physician Office Laboratories). The specific country of origin is not explicitly stated, but given the company's location (New Jersey, USA) and FDA 510(k) submission, it's highly likely to be United States. The studies are prospective analytical validation studies, meaning the data was collected specifically to demonstrate the performance of the device.

3. Number of experts used to establish the ground truth for the test set and qualifications of those experts:

Not applicable. This is an in vitro diagnostic (IVD) chemistry analyzer and reagent system. "Ground truth" for IVD analytical performance is established by reference methods, certified reference materials, or highly accurate comparative methods, not by human expert consensus or radiologists. The performance is assessed against quantitative values, not qualitative interpretations requiring expert review.

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

Not applicable. Adjudication methods like 2+1 or 3+1 are used in studies involving human interpretation (e.g., imaging studies where radiologists disagree). For analytical performance of a chemistry analyzer, the "ground truth" is typically the quantitative value obtained from a reference method or the predicate device, and differences are assessed statistically (e.g., bias, correlation).

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:

Not applicable. MRMC studies are specific to evaluating the impact of a device on human readers' performance, typically in diagnostic imaging with AI assistance. This device is an automated chemistry analyzer, not an AI-assisted diagnostic imaging tool. There are no human "readers" in the context of this device's operation.

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

Yes, in essence. The performance data provided (linearity, precision, detection limits, interference, method comparison) represents the "standalone" analytical performance of the automated chemistry system (ACE Alera with the new reagents) in measuring the target analytes in patient samples. There isn't an "algorithm only" in the AI sense, but the chemical reactions and photometric measurements are entirely automated by the device. The data shown is the raw analytical output.

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

The "ground truth" for these analytical studies is primarily:

  • Highly characterized samples: For linearity, samples with known, precise concentrations (often prepared by dilution of high-concentration materials or spiking low-concentration materials).
  • Comparative method/Predicate device: For method comparison, the results generated by the predicate device (ACE Clinical Chemistry System) are treated as the reference or comparative method against which the new ACE Alera system's results are compared. This is a common and accepted "ground truth" for chemical analyzers seeking substantial equivalence.
  • Reference materials/controls: For precision and detection limits, control materials with established target values are used.

8. The sample size for the training set:

Not applicable. This is a traditional IVD device (chemical reagents and analyzer), not an AI/ML device that requires a "training set" in the context of machine learning model development. The reagents perform chemical reactions, and the analyzer reads photometric changes; it does not "learn" from data.

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

Not applicable, as there is no training set in the AI/ML sense for this device.

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K131975

510(k) Summary

510(k) Owner:Alfa Wassermann Diagnostic Technologies, LLC4 Henderson DriveWest Caldwell, NJ 07006
Contact:HKatz@AlfaWassermannUS.comHyman Katz, Ph.D.Phone: 973-852-0158Fax: 973-852-0237OCT 0 2 2013
Date Summary Prepared:September 26, 2013
Device:Trade Name:ACE Direct Total Iron-Binding Capacity (TIBC)Reagent
Classification:Class 1
Common/Classification Name:Direct Total Iron-Binding Capacity (TIBC)(21 C.F.R. § 862.1415)Product Code JMO
Trade Name:ACE Total Iron Reagent
Classification:Class 1
Common/Classification Name:Photometric Method, Iron (Non-Heme)(21 C.F.R. § 862.1410)Product Code JIY
Trade Name:ACE LDH-L Reagent
Classification:Class 2
Common/Classification Name:NAD Reduction/NADH Oxidation, LactateDehydrogenase(21 C. F.R. § 862.1440)Product Code CFJ

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PredicateDevices:Manufacturer for reagent system predicates:Alfa Wassermann ACE Clinical Chemistry System and ACE Reagents (K930104,K944911, K931786)Intended Use:Indications for Use:
DeviceDescriptions:In the ACE Direct Total Iron-Binding Capacity (TIBC) Reagent assay, Direct TIBCColor Reagent, an acidic buffer containing an iron-binding dye and ferric chloride, isadded to the serum sample. The low pH of Direct TIBC Color Reagent releases iron fromtransferrin. The iron then forms a colored complex with the dye. The colored complex atthe end of the first step represents both the serum iron and excess iron already present inDirect TIBC Color Reagent. Direct TIBC Buffer, a neutral buffer, is then added, shiftingthe pH and resulting in a large increase in the affinity of transferrin for iron. The serumtransferrin rapidly binds the iron by abstracting it from the dye-iron complex. Theobserved decrease in absorbance of the colored dye-iron complex is directly proportionalto the total iron-binding capacity of the serum sample. The absorbance is measured at647 nm.The ACE Direct Total Iron-Binding (TIBC) Reagent is intended for the quantitativedetermination of total iron-binding capacity in serum using the ACE Alera ClinicalChemistry System. Iron-binding capacity measurements are used in the diagnosis andtreatment of anemia. This test is intended for use in clinical laboratories and physicianoffice laboratories. For in vitro diagnostic use only.
In the ACE Total Iron Reagent assay, transferrin-bound iron in serum is released at anacidic pH and reduced from ferric to ferrous ions. These ions react with ferrozine to forma violet colored complex, which is measured bichromatically at 554 nm/692 nm. Theintensity of color produced is directly proportional to the serum iron concentration.The ACE Total Iron Reagent is intended for the quantitative determination of iron inserum using the ACE Alera Clinical Chemistry System. Iron (non-heme) measurementsare used in the diagnosis and treatment of diseases such as iron deficiency anemia,hemochromatosis (a disease associated with widespread deposit in the tissues of twoiron-containing pigments, hemosiderin and hemofuscin, and characterized bypigmentation of the skin), and chronic renal disease. This test is intended for use inclinical laboratories and physician office laboratories. For in vitro diagnostic use only.
In the ACE LDH-L Reagent assay, lactate dehydrogenase catalyzes the conversion of L-lactate to pyruvate. Nicotinamide adenine dinucleotide (NAD+) acts as an acceptor forthe hydrogen ions released from the L-lactate and is converted to reduced nicotinamideadenine dinucleotide (NADH). NADH absorbs strongly at 340 nm whereas NAD+ doesnot. Therefore, the rate of conversion of NAD+ to NADH can be determined bymonitoring the increase in absorbance bichromatically at 340 nm/647 nm. This rate ofconversion from NAD+ to NADH is directly proportional to the lactate dehydrogenaseactivity in the sample.The ACE LDH-L Reagent is intended for the quantitative determination of lactatedehydrogenase activity in serum using the ACE Alera Clinical Chemistry System.Lactate dehydrogenase measurements are used in the diagnosis and treatment of liverdiseases such as acute viral hepatitis, cirrhosis, and metastatic carcinoma of the liver,cardiac diseases such as myocardial infarction and tumors of the lung or kidneys. Thistest is intended for use in clinical laboratories and physician office laboratories. For invitro diagnostic use only.
TechnologicalCharacteristics:The ACE Direct Total Iron-Binding Capacity (TIBC) Reagent is composed of tworeagent bottles (Direct TIBC Color Reagent and Direct TIBC Buffer). The Direct TIBCColor Reagent (R1) contains: Chromazurol B, Cetrimide, ferric chloride andacetate buffer. The Direct TIBC Buffer (R2) contains: sodium bicarbonate buffer.
The ACE Total Iron Reagent is composed of two reagent bottles (Buffer and ColorReagent). The Buffer (R1) contains: hydroxylamine hydrochloride,acetate buffer (pH 4.5) and surfactant. The Color Reagent (R2) contains: ferrozine andhydroxylamine hydrochloride.
The ACE LDH-L Reagent is composed of two reagent bottles (Substrate and CoenzymeReagent). The reagents contain L-lactic acid and nicotinamide adenine dinucleotide.

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Device Comparison with Predicate

Comparison of similarities and differences with predicate device

ACE Direct Total Iron-Binding Capacity (TIBC) Reagent

ACE Direct TIBC ReagentCandidate DevicePredicate Device K930104 (ACE Direct TIBC Reagent)
Intended Use/ Indications for UseThe ACE Direct Total Iron-Binding Capacity (TIBC) Reagent is intended for the quantitative determination of total iron-binding capacity in serum using the ACE Alera Clinical Chemistry System. Iron-binding capacity measurements are used in the diagnosis and treatment of anemia. This test is intended for use in clinical laboratories and physician office laboratories. For in vitro diagnostic use only.The ACE Direct Total Iron-Binding Capacity (TIBC) Reagent is intended for the quantitative determination of total iron-binding capacity in serum using the ACE Clinical Chemistry System. Iron-binding capacity measurements are used in the diagnosis and treatment of anemia. This test is intended for use in clinical laboratories. For in vitro diagnostic use only.
MethodPhotometricSame
Calibration Stability30 daysSame
On Board Stability30 daysSame
Sample TypeSerumSame
Sample Volume16 μLSame
Reaction Volume291 μLSame
Expected values250-425 μg/dL250-450 μg/dL
Measuring range52-700 μg/dLFrom the lowest calibrator concentration to 700 μg/dL
Sample StabilitySeparated from cells, serum TIBC is stable for 4 days at 18-26°C and 1 week at 2-8°C.Same

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ACE Total IronReagentCandidate DevicePredicate DeviceK944911: (ACE Total Iron Reagent)
IntendedUse/Indications forUseThe ACE Total Iron Reagent is intendedfor the quantitative determination of ironin serum using the ACE Alera ClinicalChemistry System. Iron (non-heme)measurements are used in the diagnosisand treatment of diseases such as irondeficiency anemia, hemochromatosis (adisease associated with widespreaddeposit in the tissues of two iron-containing pigments, hemosiderin andhemofuscin, and characterized bypigmentation of the skin), and chronicrenal disease. This test is intended for usein clinical laboratories and physicianoffice laboratories. For in vitrodiagnostic use only.The ACE Total Iron Reagentis intended for thequantitative determination ofiron in serum using the ACEClinical Chemistry System.Iron (non-heme)measurements are used in thediagnosis and treatment ofdiseases such as irondeficiency anemia,hemochromatosis (a diseaseassociated with widespreaddeposit in the tissues of twoiron-containing pigments,hemosiderin and hemofuscinand characterized bypigmentation of the skin),and chronic renal disease.This test is intended for usein clinical laboratories. Forin vitro diagnostic use only.
MethodPhotometricSame
Calibration Stability30 daysSame
On Board Stability30 daysSame
Sample TypeSerumSame
Sample Volume50 µLSame
Reaction Volume335 µLSame
Expected valuesMale: 65-175 µg/dLFemale: 50-170 µg/dLSame
Measuring range9.15-600 µg/dL2-600 µg/dL
Sample StabilitySeparated from cells, serum iron is stablefor 7 days at room temperature (20-25°C)Separated from cells, serumiron is stable for 4 days atroom temperature (15-30°C)

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ACE LDH-L Reagent
ACE LDH-L ReagentCandidate DevicePredicate DeviceK931786(ACE LDH-L Reagent)
IntendedUse/Indicationsfor UseThe ACE LDH-L Reagent isintended for the quantitativedetermination of lactatedehydrogenase activity in serumusing the ACE Alera ClinicalChemistry System. Lactatedehydrogenase measurements areused in the diagnosis andtreatment of liver diseases such asacute viral hepatitis, cirrhosis, andmetastatic carcinoma of the liver,cardiac diseases such asmyocardial infarction and tumorsof the lung or kidneys. This test isintended for use in clinicallaboratories and physicianoffice laboratories. For in vitrodiagnostic use only.The ACE LDH-L Reagent isintended for the quantitativedetermination of lactatedehydrogenase activity inserum using the ACE ClinicalChemistry System. Lactatedehydrogenase measurementsare used in the diagnosis andtreatment of liver diseases suchas acute viral hepatitis,cirrhosis, and metastaticcarcinoma of the liver, cardiacdiseases such as myocardialinfarction and tumors of thelung or kidneys. This test isintended for use in clinicallaboratories. For in vitrodiagnostic use only.
MethodPhotometricSame
Calibration StabilityNot a calibrated testSame
On Board Stability30 daysSame
Sample TypeSerumSame
Sample Volume5 µLSame
Reaction Volume170 µLSame
Expected values100-190 U/LSame
Measuring range18-850 U/L17-850 U/L
Sample StabilitySeparated from cells, LDH activityis stable for 7 days at 20-25°C, 4days at 4-8°C and 6 weeks at -20°C.Loss of activity after freezing hasalso been notedSeparated from cells, LDHactivity is stable for 3 days atboth 2-8°C and roomtemperature. Loss of activityafter freezing has also beennoted.

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Reportable Range

Performance data for the Alfa Wassermann ACE Reagents on the Alfa Wassermann ACE Alera Clinical Chemistry System

Detection Limits - ACE Alera Clinical Chemistry System

TIBCIronLDH-L
LoB11 µg/dL0 µg/dL11 U/L
LoD24 µg/dL1 µg/dL18 U/L
LoQ52 µg/dL9.15 µg/dL18 U/L

Linearity - ACE Alera Clinical Chemistry System

ReagentLow LevelTestedHigh LevelTestedLinear to:Linear Regressionequation
TIBC34 µg/dL740 µg/dL700 µg/dL$y = 1.020x + 3.1$ $r² = 0.9981$
Iron6 µg/dL666 µg/dL600 µg/dL$y = 1.030x + 1.9$ $r² = 0.9986$
LDH-L8 U/L895 U/L850 U/L$y = 1.050x - 0.7$ $r² = 0.9981$

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InterferentNo Significant Interference at or below:TIBCIronLDH-L
Icterus59 mg/dL59 mg/dL50 mg/dL
Hemolysis188 mg/dL*125 mg/dL*<31 mg/dL*
Lipemia1000 mg/dL125 mg/dL1000 mg/dL
Ascorbic Acid3 mg/dL6 mg/dL6 mg/dL

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PerformanceData:Precision - ACE Alera Clinical Chemistry System
Precision -In-HousePrecision (SD, %CV)
ACE AleraMeanWithin-RunTotal
TIBCµg/dLLow2174.1, 1.9%6.7, 3.1%
Mid2703.7, 1.4%7.1, 2.6%
High3105.0, 1.6%8.6, 2.8%
Ironµg/dLLow623.2, 5.2%4.6, 7.3%
Mid1452.2, 1.5%4.2, 2.9%
High2264.1, 1.8%5.0, 2.2%
LDH-U/L1773.8, 4.9%4.2, 5.5%
21195.1, 4.3%5.2, 4.3%
32704.5, 1.7%5.8, 2.1%
465112.6, 1.9%13.5, 2.1%

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Method

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Comparison -In-House

Method Comparison - ACE Alera Clinical Chemistry System

In-House ACE (x) vs. In-House ACE Alera (y)

TIBCIronLDH-L
n504858
Range59 to 676 µg/dL13 to 549 µg/dL20 to 799 U/L
Slope0.9870.9930.997
Intercept3.60.9-3.6
CorrelationCoefficient0.99600.99950.9991
Std. Error9.23.66.8
CI Slope0.962 to 1.0130.984 to 1.0030.985 to 1.008
CI Intercept-7.2 to 14.4-0.6 to 2.3-6.1 to -1.1

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POL - Precision for ACE and ACE Alera Clinical Chemistry Systems

Precision -

POL

Direct TIBC"n=20ACE Resultµg/dL SD, %CVACE Alera Resultµg/dL SD, %CV
LabSampleMeanWithin-RunTotalMeanWithin-RunTotal
In-House13362.90.9%5.51.6%3305.11.5%5.81.8%
POL 1129010.83.7%15.65.4%2848.32.9%9.63.4%
POL 212753.51.3%11.44.1%2595.62.2%8.53.3%
POL 312955.41.8%5.51.9%2769.13.3%16.76.0%
In-House24555.01.1%8.11.8%4504.91.1%6.81.5%
POL 1245210.22.3%10.42.3%4646.31.4%6.61.4%
POL 224425.91.3%12.52.8%4444.21.0%5.41.2%
POL 324654.71.0%5.31.1%4533.20.7%15.53.4%
In-House35399.81.8%12.82.4%5309.41.8%10.82.0%
POL 1353117.13.2%20.43.8%5448.21.5%8.31.5%
POL 235307.41.4%14.12.7%5205.01.0%9.01.7%
POL 335514.60.8%5.91.1%53312.62.4%20.23.8%

Page 11 of 15

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POL - Precision for ACE and ACE Alera Clinical Chemistry Systems

Precision -POL

Total Ironn=20ACE Resultµg/dL SD, %CVACE Alera Resultµg/dL SD, %CV
LabSampleMeanWithin-RunTotalMeanWithin-RunTotal
In-House11171.41.2%2.62.2%1191.81.5%2.52.1%
POL 111206.45.4%6.95.8%1192.72.3%3.22.7%
POL 211206.35.3%6.65.5%1223.12.6%3.12.6%
POL 311214.43.7%4.43.7%1163.22.8%3.43.0%
In-House22232.91.3%5.62.5%2223.81.7%5.12.3%
POL 122273.41.5%3.91.7%2292.00.9%2.51.1%
POL 222272.61.1%5.12.2%2352.31.0%2.41.0%
POL 322251.30.6%1.90.8%2293.41.5%3.91.7%
In-House34168.72.1%9.12.2%4125.21.3%5.71.4%
POL 134205.01.2%5.61.3%4244.00.9%4.61.1%
POL 234236.61.6%9.32.2%4352.40.5%5.31.2%
POL 334225.61.3%6.01.4%42811.12.6%11.12.6%

Page 12 of 15

1

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Performance

POL - Precision for ACE and ACE Alera Clinical Chemistry Systems

Data: Precision -

POL

LDH-Ln=20ACE ResultU/L SD, %CVACE Alera ResultU/L SD, %CV
LabSampleMeanWithin-RunTotalMeanWithin-RunTotal
In-House11212.82.3%4.33.6%1182.92.4%5.74.8%
POL 111132.11.9%5.44.8%1161.71.5%4.94.3%
POL 211142.52.2%6.45.6%1183.02.5%5.14.3%
POL 311172.11.8%2.72.3%1243.42.7%4.73.8%
In-House24465.81.3%6.91.5%4334.71.1%6.51.5%
POL 124335.81.3%8.11.9%4372.90.7%5.81.3%
POL 224334.81.1%5.71.3%4493.70.8%5.21.2%
POL 324374.51.0%5.21.2%4465.81.3%6.61.5%
In-House371510.11.4%11.91.7%6995.30.8%8.51.2%
POL 1369910.01.4%18.02.6%6988.61.2%11.51.6%
POL 2369812.71.8%12.71.8%7265.40.8%10.01.4%
POL 336977.61.1%8.81.3%71614.32.0%16.92.4%

Page 13 of 15

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PerformanceData:POL - Method Comparison for ACE Clinical Chemistry System
MethodComparison -POL on ACEReagentStatisticIn-House (x) vs.ACE POL 1 (y)In-House (x) vs.ACE POL 2 (y)In-House (x) vs.ACE POL 3 (y)
TIBCn505050
Range59 to 67659 to 67659 to 676
Regression$y = 0.979x + 4.3$$y = 0.974x + 8.7$$y = 1.006x - 1.4$
Correlation0.99720.99660.9966
Std. Error Est.7.78.48.7
CI Slope0.958 to 1.0000.951 to 0.9980.982 to 1.030
CI Intercept-4.8 to 13.3-1.2 to 18.5-11.6 to 8.8
Ironn484848
Range13 to 54913 to 54913 to 549
Regression$y=0.977x - 1.3$$y = 0.992x - 0.8$$y = 0.992x + 0.9$
Correlation0.99900.99940.9994
Std. Error Est.5.03.83.8
CI Slope0.964 to 0.9900.982 to 1.0030.982 to 1.002
CI Intercept-3.3 to 0.6-2.3 to 0.7-0.6 to 2.4
LDH-Ln515151
Range74 to 79974 to 79974 to 799
Regression$y = 0.996x + 1.3$$y=1.010x - 5.3$$y = 0.978x + 7.2$
Correlation0.99790.99890.9989
Std. Error Est.10.67.77.6
CI Slope0.978 to 1.0140.996 to 1.0230.964 to 0.991
CI Intercept-3.0 to 5.6-8.5 to -2.24.2 to 10.3

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PerformanceData:POL – Method Comparison for ACE Alera Clinical Chemistry System
MethodComparison -POL on ACEAleraReagentStatisticIn-House (x)vs.ACE AleraPOL 1 (y)In-House (x)vs.ACE AleraPOL 2 (y)In-House (x)vs.ACE AleraPOL 3 (y)
TIBCn505050
Range59 to 67659 to 67659 to 676
Regressiony = 0.994x + 12.4y = 0.973x + 0.1y = 1.005x + 9.0
Correlation0.99340.99540.9898
Std. Error Est.12.09.815.1
CI Slope0.961 to 1.0270.946 to 1.0010.963 to 1.047
CI Intercept-1.7 to 26.5-11.4 to 11.6-8.7 to 26.6
Ironn484848
Range13 to 54913 to 54913 to 549
Regressiony = 0.976x + 1.0y = 0.976x + 2.3y = 0.951x + 0.8
Correlation0.99860.99810.9966
Std. Error Est.5.96.88.9
CI Slope0.960 to 0.9910.959 to 0.9940.927 to 0.974
CI Intercept-1.4 to 3.3-0.4 to 5.0-2.7 to 4.4
LDH-Ln515151
Range74 to 79974 to 79974 to 799
Regressiony = 0.992x + 3.5y = 1.027x + 3.4y = .1.010x + 2.5
Correlation0.99860.99890.9984
Std. Error Est.8.88.19.3
CI Slope0.977 to 1.0081.013 to 1.0410.994 to 1.026
CI Intercept-0.1 to 7.10.2 to 6.7-1.3 to 6.2
Conclusions:Based on the foregoing data, the device is safe and effective for use in clinicallaboratories and physician office laboratories. These data indicate that the ACE AleraClinical Chemistry System is substantially equivalent to the predicate device ACEClinical Chemistry System.

י .

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/15/Picture/1 description: The image shows a logo for the U.S. Department of Health & Human Services. The logo features the department's name in a circular arrangement around a symbol. The symbol consists of a stylized caduceus, which is a traditional symbol of medicine, with a single staff entwined by two snakes.

Public Ficality Service

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

October 2, 2013

Alfa Wassermann Diagnostic Technologies, LLC c/o Hyman Katz, Ph.D. 4 Henderson Drive WEST CALDWELL NJ 07006

Re: K131975

Trade/Device Name: ACE LDH-L Reagent ACE Direct Total Iron-Binding Capacity (TIBC) Reagent ACE Total Iron Reagent Regulation Number: 21 CFR 862,1440 Regulation Name: Lactate dehydrogenase test system Regulatory Class: II, exempt, meets limitations of excmption per 21 CFR 862.9 (c)(9) Product Code: CFJ, JMO, JIY Dated: August 30, 2013

Received: September 4, 2013

Dear Dr. Katz:

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

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If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Small Manufacturers, International and Consumer Assistance 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. 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/ReportalProblem/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 Small Manufacturers, International and Consumer Assistance 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.

Sincerely yours,

Carol C. Benson -S for

Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Page 1 of 2

Indications for Use

510(k) Number : K131975

Device Name: ACE Direct Total Iron-Binding Capacity (TIBC) Reagent

Indications for Use: The ACE Direct Total Iron-Binding Capacity (TIBC) Reagent is intended for the quantitative determination of total iron-binding capacity in serum using the ACE Alera Clinical Chemistry System. Iron-binding capacity measurements are used in the diagnosis and treatment of anemia. This test is intended for use in clinical laboratories and physician office laboratories. For in vitro diagnostic use only.

Device Name: ACE Total Iron Reagent

Indications for Use: The ACE Total Iron Reagent is intended for the quantitative determination of iron in serum using the ACE Alera Clinical Chemistry System. Iron (non-heme) measurements are used in the diagnosis and treatment of diseases such as iron deficiency anemia. hemochromatosis (a disease associated with widespread deposit in the tissues of two iron-containing pigments, hemosiderin and hemofuscin, and characterized by pigmentation of the skin), and chronic renal disease. This test is intended for use in clinical laboratories and physician office laboratories. For in vitro diagnostic use only.

Prescription Use X (21 CFR Part 801 Subpart D)

Over-The-Counter Use. (21 CFR Part 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)

AND/OR

Concurrence of CDRH, Office of In Vitro Devices or Radiological Health (OIR)

Yung W. Chan -S

Division Sign-Off Office of In Vitro Devices or Radiological Health 510(k) K131975

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Indications for Use

510(k) Number : K131975

Device Name: ACE LDH-L Reagent

Indications for Use: The ACE LDH-L Reagent is intended for the quantitative determination of lactate dehydrogenase activity in serum using the ACE Alera Clinical Chemistry System. Lactate dehydrogenase measurements are used in the diagnosis and treatment of liver diseases such as acute viral hepatitis, cirrhosis, and metastatic carcinoma of the liver, cardiac diseases such as myocardial infarction and tumors of the lung or kidneys. This test is intended for use in clinical laboratories and physician office laboratories. For in vitro diagnostic use only.

Prescription Use X (21 CFR Part 801 Subpart D) AND/OR

Over-The-Counter Use. (21.CFR Part 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Devices or Radiological Health (OIR)

Yung W. Chan -S

Division Sign-Off Office of In Vitro Devices or Radiological Health 510(k) ki31975

§ 862.1440 Lactate dehydrogenase test system.

(a)
Identification. A lactate dehydrogenase test system is a device intended to measure the activity of the enzyme lactate dehydrogenase in serum. Lactate dehydrogenase measurements are used in the diagnosis and treatment of liver diseases such as acute viral hepatitis, cirrhosis, and metastatic carcinoma of the liver, cardiac diseases such as myocardial infarction, and tumors of the lung or kidneys.(b)
Classification. Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 862.9.