K Number
K131515
Manufacturer
Date Cleared
2013-08-14

(78 days)

Product Code
Regulation Number
862.1700
Reference & Predicate Devices
Predicate For
N/A
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview
Intended Use

The ACE y-GT Reagent is intended for the quantitative determination of gamma-glutamyltransferase activity in serum and lithium heparin plasma using the ACE, ACE Alera, and ACE Axcel Clinical Chemistry Systems. Gamma-glutamyltransferase measurements are used in the diagnosis and treatment of liver diseases such as alcoholic cirrhosis and primary and secondary liver tumors. This test is intended for use in clinical laboratories and physician office laboratories. For in vitro diagnostic use only.

The ACE Lipase Reagent is intended for the quantitative determination of lipase activity in serum and lithium heparin plasma using the ACE, ACE Alera, and ACE Axcel Clinical Chemistry Systems. Lipase measurements are used in diagnosis and treatment of diseases of the pancreas such as acute pancreatitis and obstruction of the pancreatic duct. This test is intended for use in clinical laboratories and physician office laboratories. For in vitro diagnostic use only.

The ACE T4 Reagent is intended for the quantitative determination of total thyroxine (T4) in serum and lithium heparin plasma using the ACE, ACE Alera, and ACE Axcel Clinical Chemistry Systems. Total thyroxine measurements are used in the diagnosis and treatment of thyroid diseases. This test is intended for use in clinical laboratories and physician office laboratories. For in vitro diagnostic use only.

Device Description

In the ACE γ-GT Reagent assay, γ-GT in serum or heparin plasma catalyzes the transfer of the γ-glutamyl group from L-γ-glutamyl-3-carboxy-4-nitroanilide to glycylglycine in the reagent. The product, 5-amino-2-nitrobenzoate, absorbs strongly at 408 nm. The rate of increase in absorbance, monitored bichromatically at 408 nm/486 nm, is directly proportional to the γ-GT activity in the sample.

In the ACE Lipase Reagent Assay, lipase in serum or heparin plasma acts on a natural substrate, 1,2-diglyceride, to liberate 2-monoglyceride. This is hydrolyzed by monoglyceride lipase (a highly specific enzyme for monoglyceride) into glycerol and free fatty acid. Glycerol kinase acts on glycerol to form glycerol-3-phosphate, which is in turn acted on by glycerol-3-phosphate oxidase to generate hydrogen peroxide. Peroxidase converts the hydrogen peroxide, 4-Aminoantipyrine and TOOS (N-ethyl-N-(2-hydroxy-3-sulfopropyl)-m-toluidine) into a quinine dye. The rate of formation of the dye, determined bichromatically at an absorbance of 573 nm/692 nm, is proportional to the lipase activity in the sample.

The ACE T4 Assay is a homogeneous enzyme immunoassay using ready-to-use liquid ACE T4 Reagent. The assay uses 8-anilino-1-naphthalene sulfonic acid (ANS) to dissociate thyroxine from the plasma binding proteins. Using specific antibodies to thyroxine, this assay is based on the competition of glucose-6-phosphate dehydrogenase (G6PD) labeled thyroxine and the dissociated thyroxine in the sample for a fixed amount of specific antibody binding sites. In the absence of thyroxine from the sample, the thyroxine labeled G6PD in the second reagent is bound by the specific antibody in the first reagent, inhibiting the enzyme's activity. The enzyme G6PD catalyzes the oxidation of glucose-6-phosphate (G6P) with nicotinamide adenine dinucleotide (NADT) to form 6-phosphogluconate and reduced nicotinamide adenine dinucleotide (NADH). NADH strongly absorbs at 340 nm whereas NAD does not. The rate of conversion, determined by measuring the increase in absorbance bichromatically at 340 nm/505 nm during a fixed time interval, is directly proportional to the amount of thyroxine in the sample. The concentration of thyroxine is determined automatically by the ACE Clinical Chemistry Systems using a logarithmic calibration curve established with calibrators, which are provided separately.

AI/ML Overview

The information provided describes the performance of the ACE γ-GT, ACE Lipase, and ACE T4 Reagents on the ACE, ACE Alera, and ACE Axcel Clinical Chemistry Systems. This is not an AI/ML device, however, I will address the other requested points to the best of my ability with the provided text.

Here's a breakdown of the acceptance criteria and study information, where applicable:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state "acceptance criteria" in a separate table. However, it provides performance data for precision, matrix comparison (serum vs. plasma), detection limits, linearity, and interference. Based on the "Conclusions" section, the goal was to demonstrate "substantial equivalence" of the reagents for lithium heparin plasma samples (compared to serum) and the ACE Alera System (compared to the predicate ACE Clinical Chemistry System). The performance data presented are implicitly intended to support this substantial equivalence.

Implied Acceptance Criteria (based on predicate comparison and performance data) and Reported Performance:

Performance MetricAcceptance Criteria (Implied)Reported Device Performance (Summary)
PrecisionFor In-House Precision (Serum vs. Plasma): Low, Mid, and High analyte concentrations should demonstrate acceptable within-run and total %CV on ACE, ACE Alera, and ACE Axcel systems, comparable to expected values for clinical chemistry assays. For POL Precision: Similar acceptable %CV values for low, mid, and high samples across different POL sites and in-house, on ACE and ACE Alera systems.In-House Precision (Serum vs. Plasma):- γ-GT: Total %CV generally < 3.4% for serum and < 2.4% for plasma across all concentrations and systems.- Lipase: Total %CV generally < 6.7% for serum and < 7.4% for plasma across all concentrations and systems.- T4: Total %CV generally < 4.9% for serum and < 5.4% for plasma across all concentrations and systems.POL Precision:- γ-GT: Total %CV generally < 9.8% for low, < 1.4% for mid, and < 1.3% for high concentrations on ACE and ACE Alera across sites.- Lipase: Total %CV generally < 12.8% for low, < 7.7% for mid, and < 5.0% for high.- T4: Total %CV generally < 5.0% for low, < 4.9% for mid, and < 5.5% for high.
Matrix ComparisonCoefficients of determination (Correlation) close to 1, slopes close to 1, and intercepts close to 0 when comparing serum and lithium heparin plasma samples, indicating equivalence between sample types. Standard error of estimate should be acceptable for clinical use.γ-GT: Correlation > 0.997, Slope 0.960-0.987, Intercept 1.5-4.0 across systems.Lipase: Correlation > 0.994, Slope 0.980-1.024, Intercept -2.5 to -0.9 across systems (for ACE and ACE Alera, Axcel missing intercept CI).T4: Correlation > 0.984, Slope 0.963-1.007, Intercept 0.01-0.35 across systems.
Method Comparison (POL)When comparing results from POL sites to in-house results on the same instrument, correlation coefficients should be high (close to 1), slopes close to 1, and with small intercepts, indicating consistency across testing locations.ACE System:- γ-GT: Correlation > 0.9997, Slope 0.964-0.976, Intercept -2.7 to 0.7.- Lipase: Correlation > 0.9966, Slope 0.994-1.031, Intercept -5.3 to 0.0.- T4: Correlation > 0.9908, Slope 1.010-1.019, Intercept -0.09 to -0.04.ACE Alera System:- γ-GT: Correlation > 0.9996, Slope 0.950-1.028, Intercept 1.9 to 2.9.- Lipase: Correlation > 0.9960, Slope 0.992-1.028, Intercept -3.5 to 3.3.- T4: Correlation > 0.9868, Slope 1.022-1.048, Intercept -0.31 to -0.10.
Detection Limits (ACE Alera)Limits of Blank (LOB), Detection (LOD), and Quantitation (LOQ) should be clinically acceptable.γ-GT: LOB 3 U/L, LOD 5 U/L, LOQ 7 U/L.Lipase: LOB 7 U/L, LOD 11 U/L, LOQ 13 U/L.T4: LOB 0.3 µg/dL, LOD 0.8 µg/dL, LOQ 1.3 µg/dL.
Linearity (ACE Alera)The assay should be linear up to the stated measuring range, with a linear regression equation demonstrating good fit.γ-GT: Linear to 950 U/L ($y = 1.036x + 0.8$).Lipase: Linear to 700 U/L ($y = 0.971x + 0.2$).T4: Linear to 19.6 µg/dL ($y = 1.057x - 0.09$).
Interferences (ACE Alera)No significant interference from common exogenous or endogenous substances at physiologically relevant or elevated concentrations.γ-GT: No significant interference at or below Icterus 14.2 mg/dL, Hemolysis 125 mg/dL, Lipemia 500 mg/dL, Ascorbic Acid 6 mg/dL.Lipase: No significant interference below Icterus 12.5 mg/dL, Hemolysis 1000 mg/dL, Lipemia 803 mg/dL, Ascorbic Acid 6 mg/dL.T4: No significant interference below Icterus 47.2 mg/dL, Hemolysis 1000 mg/dL, Lipemia 1000 mg/dL, Ascorbic Acid 6 mg/dL.Heterophile (T4): HAMA 800 ng/mL, RF 516 IU/mL.Cross-Reactivity (T4): 3,3',5,5'- Tetraiodothyroacetic Acid (18.4%), L-Thyroxine (91.6%), D-Thyroxine (68.0%) at 5 µg/dL.

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

The document does not explicitly use the term "test set" in the context of AI/ML, but rather describes clinical performance studies. The sample sizes for these studies are as follows:

  • In-House Matrix Comparison (Serum vs. Plasma):
    • ACE γ-GT Reagent: 100 pairs (ACE), 97 pairs (ACE Alera), 53 pairs (ACE Axcel)
    • ACE Lipase Reagent: 42 pairs (ACE), 43 pairs (ACE Alera), 62 pairs (ACE Axcel)
    • ACE T4 Reagent: 55 pairs (ACE), 55 pairs (ACE Alera), 55 pairs (ACE Axcel)
  • Method Comparison (POL vs. In-House):
    • ACE System: 50-54 samples per reagent per POL site (3 POL sites)
    • ACE Alera System: 48-51 samples per reagent per POL site (3 POL sites)
  • Precision (In-House and POL): The number of replicates per sample level (Low, Mid, High) is not explicitly stated, but precision studies typically involve multiple runs over several days.
  • Detection Limits, Linearity, Interferences, Cross-Reactivity: Sample sizes for these specific experiments are not detailed but are generally conducted with a sufficient number of replicates and concentrations to statistically establish the parameters.

Data Provenance: The studies are described as "In-House" and "POL" (Physician Office Laboratory) studies. This indicates that the data was collected at the manufacturer's facility ("In-House") and potentially at various POL sites. The country of origin is not explicitly stated, but given the 510(k) submission to the FDA, it is likely the studies align with US regulatory requirements and are potentially from US-based labs. The studies are prospective in nature, as they involve newly generated data to demonstrate the performance of the devices.

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

This section is not applicable as the device is a clinical chemistry reagent and not an AI/ML device that generates interpretations requiring expert ground truth for image or diagnostic data. The "ground truth" in this context refers to the measured analyte concentrations obtained from established laboratory methods, calibrators, and reference materials.

4. Adjudication Method for the Test Set

This section is not applicable as the device is a clinical chemistry reagent. Adjudication methods like 2+1 or 3+1 are used in contexts like human reader studies for diagnostic imaging, where discordant interpretations need resolution by additional experts.

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

This section is not applicable as the device is a clinical chemistry reagent. MRMC studies are designed to assess the performance of diagnostic devices or AI algorithms by multiple human readers across multiple cases, especially in imaging.

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

This section is not applicable as the device is a clinical chemistry reagent. This term is relevant for AI/ML diagnostic tools. The "performance" of this device is inherently standalone in that the instrument processes samples and generates quantitative results without human intervention in the measurement process itself, beyond sample loading and general operation.

7. The Type of Ground Truth Used

The "ground truth" for the performance studies presented is based on quantitative chemical measurements of the specific analytes (gamma-glutamyltransferase, lipase, total thyroxine) in control materials, patient samples, and comparison with established reference methods or predicate devices. This includes:

  • Known concentrations: For precision, linearity, detection limits, and interference studies, samples with known or spiked concentrations are used.
  • Comparison to predicate device: For method comparison studies, the results from the new device/system are compared against the results from the legally marketed predicate device/system.
  • Reference materials/calibrators: The accuracy and calibration of the assays depend on traceable reference materials and calibrators.

8. The Sample Size for the Training Set

This section is not applicable as the device is a clinical chemistry reagent and not an AI/ML device. There is no "training set" in the context of machine learning model development.

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

This section is not applicable for the same reasons as #8.

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KIBISTS

510(k) SUMMARY

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510(k) Owner:Alfa Wassermann Diagnostic Technologies, LLC4 Henderson DriveWest Caldwell, NJ 07006
Contact:Hyman Katz, Ph.D.Phone: 973-852-0158Fax: 973-852-0237AUG 1 4 2013
Date SummaryPrepared:August 5, 2013
Device:Trade Name:ACE γ-GT Reagent
Classification:Class 1
Common/Classification Name:Colorimetric Method, Gamma-GlutamylTranspeptidase(21 C. F.R. § 862.1360)Product Code JPZ
Trade Name:ACE Lipase Reagent
Classification:Class 1
Common/Classification Name:Lipase-Esterase, Enzymatic, Photometric, Lipase(21 C. F.R. § 862.1465)Product Code CHI
Trade Name:ACE T4 Reagent
Classification:Class 2
Common/Classification Name:Enzyme Immunoassay, Non-Radiolabeled, TotalThyroxine(21 C. F.R. § 862.1700)Product Code KLI
PredicateDevices:Manufacturer for reagent system predicates:Alfa Wassermann ACE Clinical Chemistry Systemand ACE Reagents (K930104, K981377, K113253, K113382, K113438, K113437)
DeviceDescriptions:In the ACE γ-GT Reagent assay, γ-GT in serum or heparin plasma catalyzes the transferof the γ-glutamyl group from L-γ-glutamyl-3-carboxy-4-nitroanilide to glycylglycine inthe reagent. The product, 5-amino-2-nitrobenzoate, absorbs strongly at 408 nm. The rateof increase in absorbance, monitored bichromatically at 408 nm/486 nm, is directlyproportional to the γ-GT activity in the sample.

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In the ACE Lipase Reagent Assay, lipase in serum or heparin plasma acts on a natural substrate, 1,2-diglyceride, to liberate 2-monoglyceride. This is hydrolyzed by monoglyceride lipase (a highly specific enzyme for monoglyceride) into glycerol and free fatty acid. Glycerol kinase acts on glycerol to form glycerol-3-phosphate, which is in turn acted on by glycerol-3-phosphate oxidase to generate hydrogen peroxide. Peroxidase converts the hydrogen peroxide, 4-Aminoantipyrine and TOOS (N-ethyl-N-(2-hydroxy-3-sulfopropyl)-m-toluidine) into a quinine dye. The rate of formation of the dye, determined bichromatically at an absorbance of 573 nm/692 nm, is proportional to the lipase activity in the sample.

The ACE T4 Assay is a homogeneous enzyme immunoassay using ready-to-use liquid ACE T4 Reagent. The assay uses 8-anilino-1-naphthalene sulfonic acid (ANS) to dissociate thyroxine from the plasma binding proteins. Using specific antibodies to thyroxine, this assay is based on the competition of glucose-6-phosphate dehydrogenase (G6PD) labeled thyroxine and the dissociated thyroxine in the sample for a fixed amount of specific antibody binding sites. In the absence of thyroxine from the sample, the thyroxine labeled G6PD in the second reagent is bound by the specific antibody in the first reagent, inhibiting the enzyme's activity. The enzyme G6PD catalyzes the oxidation of glucose-6-phosphate (G6P) with nicotinamide adenine dinucleotide (NADT) to form 6-phosphogluconate and reduced nicotinamide adenine dinucleotide (NADH). NADH strongly absorbs at 340 nm whereas NAD does not. The rate of conversion, determined by measuring the increase in absorbance bichromatically at 340 nm/505 nm during a fixed time interval, is directly proportional to the amount of thyroxine in the sample. The concentration of thyroxine is determined automatically by the ACE Clinical Chemistry Systems using a logarithmic calibration curve established with calibrators, which are provided separately.

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Intended Use:Indications for Use:
The ACE y-GT Reagent is intended for the quantitative determination of gamma-glutamyltransferase activity in serum and lithium heparin plasma using the ACE,ACE Alera, and ACE Axcel Clinical Chemistry Systems. Gamma-glutamyltransferasemeasurements are used in the diagnosis and treatment of liver diseases such as alcoholiccirrhosis and primary and secondary liver tumors. This test is intended for use in clinicallaboratories and physician office laboratories. For in vitro diagnostic use only.
The ACE Lipase Reagent is intended for the quantitative determination of lipase activityin serum and lithium heparin plasma using the ACE, ACE Alera, and ACE AxcelClinical Chemistry Systems. Lipase measurements are used in diagnosis and treatmentof diseases of the pancreas such as acute pancreatitis and obstruction of the pancreaticduct. This test is intended for use in clinical laboratories and physician officelaboratories. For in vitro diagnostic use only.
The ACE T4 Reagent is intended for the quantitative determination of total thyroxine(T4) in serum and lithium heparin plasma using the ACE, ACE Alera, and ACEAxcel Clinical Chemistry Systems. Total thyroxine measurements are used in thediagnosis and treatment of thyroid diseases. This test is intended for use in clinicallaboratories and physician office laboratories. For in vitro diagnostic use only.
TechnologicalCharacteristics:The ACE y-GT Reagent consists of two reagent bottles (y-GT Buffer and y-GTSubstrate). The reagent contains L-y-glutamyl-3-carboxy-4-nitroanilide, glycylglycineand buffer.
The ACE Lipase Reagent is composed of two reagent bottles (Lipase Reagent andLipase Activator). The Lipase Reagent (R1) contains: 1,2-diglyceride, monoglyceridelipase, glycerol kinase, glycerol-3-phosphate oxidase, N-ethyl-N-(2-hydroxy-3-sulfopropyl)-m-toluidine, ATP, peroxidase, colipase, human serum albumin, ascorbateoxidase, cholic acid and buffer. The Lipase Activator contains: deoxycholate, 4-aminoantipyrene and buffer.
The ACE T4 Reagent is composed of two reagent bottles (Antibody/Substrate Reagentand Enzyme Conjugate Reagent). The Antibody/Substrate Reagent (R1) contains:mouse monoclonal anti-thyroxine antibody, 8-anilino-1-naphthalene sulfonic acid,glucose-6-phosphate, nicotinamide adenine dinucleotide and Tris buffer. The EnzymeConjugate Reagent (R2) contains: glucose-6-phosphate dehydrogenase labeled withthyroxine and Tris buffer.

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Device Comparison with Predicate

Comparison of similarities and differences with predicate device

ACE y-GT Reagent

γ-GTCandidate DevicePredicate DeviceK930104(ACE γ-GT Reagent)
IntendedUse/Indications forUseThe ACE γ-GT Reagent is intended.forthe quantitative determination of gamma-glutamyltransferase activity.Same
PlatformsACE, ACE Alera® and ACE AxcelClinical Chemistry SystemsACE Clinical ChemistrySystem
MethodPhotometricSame
Calibration StabilityNot a calibrated testSame
On Board Stability30 daysSame
Sample TypeSerum and lithium heparin plasmaSerum
Sample Volume5 μLSame
Reaction Volume170 μLSame
Expected valuesMale: 13-68 U/LFemale: 11-48 U/LSame
Measuring range7-950 U/LSame
Sample StabilitySeparated from cells, gamma-glutamyltransferase is stable 7 days at4-8°C and up to 1 year at -20°C.Same

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ACE Lipase Reagent
LipaseCandidate DevicePredicate DeviceK930104(ACE Lipase Reagent)
IntendedUse/Indications forUseThe ACE Lipase Reagent is intended forthe quantitative determination of lipaseactivity.Same
PlatformsACE, ACE Alera® and ACE AxcelClinical Chemistry SystemsACE Clinical ChemistrySystem
MethodPhotometricSame
Calibration Stability20 daysSame
On Board Stability20 daysSame
Sample TypeSerum and lithium heparin plasmaSerum
Sample Volume3 µLSame
Reaction Volume263 µLSame
Expected values<60 U/LSame
Measuring range15-700 U/LSame
Sample StabilityStable for 7 days at 20-25°C, three weeksat 4-8°C and at -20°C for one year.Same

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T4Candidate DevicePredicate DeviceK981377(ACE T4 Reagent)
IntendedUse/Indicationsfor UseACE T4 Reagent is intended forthe quantitative determination oftotal thyroxine (T4).Same
PlatformsACE, ACE Alera and ACE AxcelClinical Chemistry SystemsACE Clinical ChemistrySystem
MethodPhotometricSame
Calibration Stability5 daysSame
On Board Stability30 daysSame
Sample TypeSerum and lithium heparin plasmaSerum
Sample Volume5 µLSame
Reaction Volume315 µLSame
Expected values5.0 - 12.0 µg/dLSame
Measuring range1.3-19.6 µg/dLSame
Sample StabilitySpecimen stable for 7 days at 4-8°CSame

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Performance Data:

In-House Precision -Serum vs. Plasma

Performance data for the Alfa Wassermann ACE Reagents run on the Alfa Wassermann ACE, ACE Alera and ACE Axcel Clinical Chemistry Systems

In-House Precision: Serum vs. Plasma - ACE y-GT Reagent

Precision (SD, %CV)
γ-GTU/LACEACE AleraACE Axcel
MeanWithin-RunTotalMeanWithin-RunTotalMeanWithin-RunTotal
Serum Low380.9, 2.4%1.2, 3.1%390.9, 2.4%1.0, 2.5%370.7, 1.8%0.9, 2.3%
Plasma Low380.4, 1.0%0.8, 2.2%400.7, 1.9%0.7, 1.9%380.7, 2.0%0.9, 2.4%
Serum Mid3132.4, 0.8%2.8, 0.9%3143.9, 1.3%4.5, 1.4%3182.0, 0.6%2.6, 0.8%
Plasma Mid3162.4, 0.8%3.0, 0.9%3171.7, 0.5%2.4, 0.8%3192.6, 0.8%2.9, 0.9%
Serum High6022.3, 0.4%2.6, 0.4%6014.2, 0.7%6.1, 1.0%6064.2, 0.7%5.4, 0.9%
Plasma High6053.6, 0.6%4.4, 0.7%6044.3, 0.7%4.9, 0.8%6084.4, 0.7%5.9, 1.0%

In-House Precision: Serum vs. Plasma - ACE Lipase Reagent

Precision (SD, %CV)
Lipase U/LMeanACE Within-RunACE TotalACE Alera Within-RunACE Alera TotalACE Axcel MeanACE Axcel Within-RunACE Axcel Total
Serum Low471.7, 3.6%3.2, 6.7%1.6, 3.5%2.9, 6.4%442.8, 6.3%3.0, 6.9%
Plasma Low482.2, 4.6%3.2, 6.6%1.5, 3.2%3.5, 7.4%482.6, 5.5%3.1, 6.4%
Serum Mid2835.1, 1.8%13.1, 4.6%3.8, 1.3%19.1, 6.7%2803.3, 1.2%4.0, 1.4%
Plasma Mid2782.6, 0.9%11.5, 4.1%2.2, 0.8%20.0, 7.2%2724.8, 1.8%6.8, 2.5%
Serum High5453.9, 0.7%24.3, 4.5%4.3, 0.8%37.5, 6.9%5345.5, 1.0%9.5, 1.8%
Plasma High5245.9, 1.1%18.9, 3.6%5.0, 1.0%31.7, 6.0%5185.8, 1.1%10.2, 2.0%

In-House Precision: Serum vs. Plasma – ACE T4 Reagent

Precision (SD, %CV)
T4ACEACE AleraACE Axcel
µg/dLMeanWithin-RunTotalMeanWithin-RunTotalMeanWithin-RunTotal
Serum Low7.70.17, 2.2%0.35, 4.5%7.70.15, 2.0%0.19, 2.4%7.90.18, 2.3%0.21, 2.6%
Plasma Low7.80.28, 3.5%0.29, 3.8%7.80.14, 1.9%0.21, 2.7%8.00.15, 1.9%0.21, 2.7%
Serum Mid12.70.46, 3.6%0.63, 4.9%12.50.24, 1.9%0.48, 3.9%12.90.30, 2.3%0.43, 3.4%
Plasma Mid13.10.24, 1.8%0.50, 3.8%12.90.28, 2.2%0.67, 5.2%13.20.19, 1.5%0.71, 5.4%
Serum High17.30.50, 2.9%0.74, 4.3%17.10.27, 1.6%0.57, 3.3%17.50.50, 2.9%0.75, 4.3%
Plasma High17.60.76, 4.3%0.76, 4.3%17.40.41, 2.4%0.44, 2.6%17.60.60, 3.4%0.60, 3.4%

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In-House Matrix Comparison: Serum vs. Plasma – ACE γ-GT Reagent
SystemRangeResults - Serum vs. Plasma
ACE100 pairs9 - 886 U/LSlope: 0.972Intercept: 1.5Correlation: 0.9990Std. Error Est: 7.9Confidence Interval Slope: 0.964 to 0.981Confidence Interval Intercept: -0.3 to 3.3
ACE Alera97 pairs9 - 841 U/LSlope: 0.960Intercept: 2.8Correlation: 0.9989Std. Error Est: 8.2Confidence Interval Slope: 0.951 to 0.969Confidence Interval Intercept: 0.8 to 4.7
ACE Axcel53 pairs10 - 910 U/LSlope: 0.987Intercept: 4.0Correlation: 0.9973Std. Error Est: 16.5Confidence Interval Slope: 0.967 to 1.008Confidence Interval Intercept: -1.8 to 9.8
In-House Matrix Comparison: Serum vs. Plasma – ACE Lipase Reagent
SystemRangeResults - Serum vs. Plasma
ACE42 pairs16 - 642 U/LSlope: 1.024Intercept: -2.5Correlation: 0.9992Std. Error Est: 6.4Confidence Interval Slope: 1.011 to 1.038Confidence Interval Intercept: -5.0 to -0.1
ACE Alera43 pairs19 - 640 U/LSlope: 1.022Intercept: -0.9Correlation: 0.9994Std. Error Est: 5.5Confidence Interval Slope: 1.010 to 1.033Confidence Interval Intercept: -3.0 to 1.2
ACE Axcel62 pairs15 - 627 U/LSlope: 0.980Intercept: -2.0Correlation: 0.9947Std. Error Est: 13.2Confidence Interval Slope: 0.954 to 1.007
SystemRangeResults - Serum vs. Plasma
ACE55 pairs2.0 - 19.3 $ \mu $ g/dLSlope: 0.963Intercept: 0.35Correlation: 0.9847Std. Error Est: 0.54Confidence Interval Slope: 0.916 to 1.009Confidence Interval Intercept: -0.03 to 0.7
ACE Alera55 pairs1.9 - 18.6 $ \mu $ g/dLSlope: 0.976Intercept: 0.17Correlation: 0.9870Std. Error Est: 0.49Confidence Interval Slope: 0.933 to 1.019Confidence Interval Intercept: -0.18 to 0.5
ACE Axcel55 pairs2.1 - 17.6 $ \mu $ g/dLSlope: 1.007Intercept: 0.01Correlation: 0.9841Std. Error Est: 0.55Confidence Interval Slope: 0.958 to 1.057Confidence Interval Intercept: -0.38 to 0.4

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Performance Data:Precision - POLPOL – Precision for ACE and ACE Alera Clinical Chemistry Systems(Note: Refer to previously cleared submissions K113382, K113438 and K113437 for ACE Axcel POL data)
γ-GTACE ResultU/L SD, %CVACE Alera ResultU/L SD, %CV
LabSampleMeanWithin-RunTotalMeanWithin-RunTotal
In-House1190.94.6%1.79.2%191.47.1%1.57.9%
POL 11171.16.4%1.79.8%180.74.2%0.95.2%
POL 21150.64.0%1.06.8%180.94.8%1.05.6%
POL 31160.84.9%1.06.2%180.95.2%1.05.3%
In-House22972.00.7%2.00.7%2983.31.1%3.71.2%
POL 122863.01.0%3.31.1%2872.20.8%2.60.9%
POL 222842.50.9%2.91.0%3151.90.6%2.30.7%
POL 322872.20.8%4.11.4%2992.70.9%2.81.0%
In-House35235.21.0%5.91.1%5242.60.5%3.30.6%
POL 135023.10.6%4.00.8%5034.50.9%4.50.9%
POL 235005.51.1%5.61.1%5613.50.6%3.50.6%
POL 334964.60.9%6.31.3%5283.00.6%4.60.9%

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ACE ResultACE Alera ResultPerformance Data:Precision -POLT4ACE Resultµg/dL SD, %CVACE Alera Resultµg/dL SD, %CV
LipaseU/L SD, %CVU/L SD, %CVLabSampleMeanWithin-RunTotalMeanWithin-RunTotal
LabSampleMeanWithin-RunTotalMeanWithin-RunTotalIn-House14.20.102.5%0.174.1%4.10.092.2%0.174.3%
In-House1231.98.2%2.510.9%242.08.7%2.08.7%POL 114.00.092.3%0.112.7%4.30.092.2%0.153.5%
POL 11242.39.4%3.112.8%232.29.6%2.712.0%POL 214.20.122.8%0.143.3%4.10.122.8%0.184.3%
POL 21210.94.5%1.46.8%211.88.5%1.98.9%POL 314.20.112.7%0.112.7%3.90.174.4%0.205.0%
POL 31241.56.3%2.08.0%221.15.0%2.310.5%In-House210.20.151.5%0.191.9%10.10.141.4%0.333.2%
In-House21612.81.7%4.22.6%1582.41.5%3.01.9%POL 129.90.191.9%0.272.7%10.30.414.0%0.434.2%
POL 121672.51.5%6.84.0%1543.82.5%7.75.0%POL 2210.60.403.8%0.524.9%10.10.252.5%0.292.9%
POL 221341.71.3%5.44.1%1543.82.5%3.92.5%POL 3210.50.141.3%0.201.9%10.10.313.1%0.494.9%
POL 321523.32.2%5.53.6%1481.91.3%5.23.5%In-House316.30.352.2%0.835.1%16.00.271.7%0.412.6%
In-House33214.31.3%7.62.4%3152.80.9%11.53.7%POL 1316.10.271.7%0.412.5%16.40.583.5%0.895.4%
POL 133277.72.3%12.33.8%2929.93.4%14.55.0%POL 2317.10.281.7%0.814.7%16.30.462.8%0.764.7%
POL 232654.91.8%13.35.0%3102.50.8%6.32.0%POL 3317.30.281.6%0.331.9%17.60.794.5%0.975.5%
POL 332893.31.2%8.73.0%2934.21.4%12.34.2%

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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)
γ-GTnRangeRegressionCorrelationStd. Error Est.CI SlopeCI Intercept5115 to 866$y = 0.964x + 0.7$0.99974.20.958 to 0.971-0.7 to 2.05115 to 866$y = 0.976x - 2.7$0.99984.20.970 to 0.982-4.0 to -1.35115 to 866$y = 0.971x - 0.8$0.99992.60.967 to 0.975-1.6 to 0.1
LipasenRangeRegressionCorrelationStd. Error Est.CI SlopeCI Intercept5415 to 644$y = 1.002x + 0.0$0.99869.60.988 to 1.017-3.1 to 3.15115 to 676$y = 0.994x - 5.3$0.996611.60.970 to 1.017-9.1 to -1.55115 to 676$y = 1.031x - 2.3$0.99877.51.016 to 1.047-4.8 to 0.2
T4nRangeRegressionCorrelationStd. Error Est.CI SlopeCI Intercept501.5 to 18.6$y = 1.010x - 0.04$0.99360.270.977 to 1.043-0.29 to 0.22501.5 to 18.6$y = 1.019x - 0.07$0.99080.330.979 to 1.059-0.38 to 0.24501.5 to 18.6$y = 1.017x - 0.09$0.99210.310.980 to 1.054-0.38 to 0.19

:

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PerformanceData:POL – Method Comparison for ACE Alera Clinical Chemistry System
MethodComparison -POL on ACEAleraReagentStatisticIn-House (x)vs.ACE Alera POL 1(y)In-House (x)vs.ACE Alera POL 2(y)In-House (x)vs.ACE Alera POL 3(y)
γ-GTnRangeRegressionCorrelationStd. Error Est.CI SlopeCI Intercept5115 to 866$y = 0.950x + 1.9$0.99983.70.945 to 0.9560.7 to 3.15115 to 866$y = 1.028x + 2.9$0.99965.41.020 to 1.0361.2 to 4.75115 to 866$y = 0.996x + 2.4$0.99974.60.990 to 1.0030.9 to 3.9
LipasenRangeRegressionCorrelationStd. Error Est.CI SlopeCI Intercept5115 to 676$y = 1.028x + 3.3$0.996013.11.001 to 1.054-1.0 to 7.65015 to 676$y = 1.017x - 3.5$0.996911.40.993 to 1.040-7.3 to 0.35115 to 676$y = 0.992x - 2.9$0.99886.90.978 to 1.006-5.2 to -0.7
T4nRangeRegressionCorrelationStd. Error Est.CI SlopeCI Intercept501.5 to 18.6$y = 1.022x - 0.14$0.99260.300.986 to 1.058-0.42 to 0.13501.5 to 18.6$y = 1.048x - 0.31$0.99090.341.007 to 1.089-0.63 to 0.01481.5 to 18.6$y = 1.033x - 0.10$0.98680.360.983 to 1.083-0.47 to 0.27

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Performance Data:

ACE Alera

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

Detection Limits - ACE Alera Clinical Chemistry System

γ-GTLipaseT4
LOBOriginal Data3 U/L7 U/L0.3 µg/dL
LODOriginal Data5 U/L11 U/L0.8 µg/dL
LOQ2012 Data7 U/L13 U/L1.3 µg/dL

Linearity - ACE Alera Clinical Chemistry System

ReagentLow LevelTestedHigh LevelTestedLinear to:Linear Regressionequation
γ-GT4 U/L993 U/L950 U/L$y = 1.036x + 0.8$
Lipase11 U/L739 U/L700 U/L$y = 0.971x + 0.2$
T41.2 µg/dL19.7 µg/dL19.6 µg/dL$y = 1.057x - 0.09$

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Performance Data:

ACE Alera

Interferences - ACE Alera Clinical Chemistry System

InterferentNo Significant Interference at or below:
γ-GTLipaseT4
Icterus14.2 mg/dL12.5 mg/dL47.2 mg/dL
Hemolysis125 mg/dL1000 mg/dL1000 mg/dL
Lipemia500 mg/dL803 mg/dL1000 mg/dL
Ascorbic Acid6 mg/dL6 mg/dL6 mg/dL

Heterophile Interferences – ACE T4 on the ACE Alera Clinical Chemistry System

HeterophileNo Clinically Interfering Conditionat or below:
Human Anti-MouseAntibody (HAMA)800 ng/mL
Rheumatoid Factor516 IU/mL

Cross-Reactivity – ACE T4 on the ACE Alera Clinical Chemistry System

Cross-ReactantConcentrationTested (µg/dL)% Cross-Reactivity
3,3',5,5'- Tetraiodothyroacetic Acid518.4
L-Thyroxine591.6
D-Thyroxine568.0

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Precision (SD, %CV)
MeanWithin-RunTotal
Low291.0, 3.4%1.3, 4.7%
γ-GTU/LMid711.4, 2.0%2.4, 3.4%
High1051.9, 1.8%3.6, 3.4%
Low636.2, 9.8%6.2, 9.9%
LipaseU/LMid37910.5, 2.8%15.4, 4.1%
High65720.4, 3.1%24.4, 3.7%
Low6.00.19, 3.1%0.34, 5.6%
T4µg/dLMid10.60.26, 2.4%0.37, 3.5%
High17.10.56, 3.3%0.66, 3.9%
Method Comparison - ACE Alera Clinical Chemistry SystemIn-House ACE (x) vs. In-House ACE Alera (y)
γ-GTLipaseT4
n514950
Range15 to 866 U/L15 to 676 U/L1.5 to 18.6 µg/dL
Slope0.9751.0381.004
Intercept4.3-4.8-0.08
CorrelationCoefficient0.99990.99950.9937
Std. Error2.74.60.27
CI Slope0.972 to 0.9791.029 to 1.0480.972 to 1.037

. : ・

,

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Conclusions:Based on the foregoing data, the device is safe and effective for use in clinicallaboratories and physician office laboratories. These data indicate substantialequivalence for lithium heparin plasma sample collection tubes to the predicate device'suse of serum sample collection tubes. These data also indicate that the ACE AleraClinical Chemistry System is substantially equivalent to the predicate device ACEClinical Chemistry System.
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

the submit and the submit of the submit of the submit of the subsequence of

and the comments of the comments of the comments of the comments of

and the comments of the comments of the comments of

.

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Image /page/18/Picture/0 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized depiction of an eagle or bird-like figure with three curved lines representing its wings or feathers. The logo is surrounded by the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged in a circular fashion.

DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G60 Silver Spring, MD 20993-0002

August 14, 2013

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

Re: K131515 Trade/Device Name: ACE T4 Reagent

ACE Lipase Reagent ACE y-GT Reagent Regulation Number: 21 CFR 862.1700 Regulation Name: Total thyroxine test system Regulatory Class: II Product Code: KLI, CHI, JPZ Dated: May 24, 2013 Received: May 28, 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 includions for use stated in the enclosure) to legally marketed predicate devices marketed in intestate 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 Fored, Or to and Cosmetic Act (Act) that do not require approval of a premarket approval application (DMA), 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, insting of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contractly ability warranties. We remind you, however, that device labeling must be truth to mighting

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, EDA max 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. Your must comply with all the Act's requirements, including, but not limited to: registration and liating (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements set forth in the quality systems (QS) regulation (2) CFR Part 820); and if applicable, the election is product radiation control provisions (Sections 531-542 of the Act); 21 CFR 100-1050.

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

Page 2-Dr. Katz

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please go to http://www.fda.gov/AboutFDA/CentersOffices/CDRHOITTCT CFR Part 0017, please the Center for Devices and Radiological Health's (CDRH's) Office of Compliance. Also, please note the regulation entitled, "Misbranding by relevence to premarket notification" (21CFR Part 807.97). For questions regarding of rolerence of premated indineation (21CFR Part Personalion (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 tribution inc (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/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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Indications for Use

510(k) Number (if known):_k131515

Device Name: ACE y-GT Reagent

Indications for Use: The ACE y-GT Reagent is intended for the quantitative determination of gamma-glutamyltransferase activity in serum and lithium heparin plasma using the ACE, ACE Alera, and ACE Axcel Clinical Charm Systems. Gamma-glutamyltransferase measurements are used in the diagnosis and treatment of liver discases such as alcoholic circhosis and primary and secondary liver tumors. This test is intended for use in clinical laboratories and physician office laboratories. For in vitro diagnostic use only.

Device Name: ACE Lipase Reagent

Indications for Use: The ACE Lipase Reagent is intended for the quantitative determination of lipase activity in serum and lithium heparin plasma using the ACE, ACE Alera, and ACE Axcel Clinical Chemistry Systems. Inj mo mcasurements are used in diagnosis and treatment of diseases of the pancreas such as acute pancreatitis and obstruction of the pancreation of the This test is intended for use in clinical laboratories and physiciant office laboratories. For in vitro diagnostic use only.

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

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

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

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

Ruth A. Chesler -S

Division Sign-Off Office of In Vitro Devices or Radiological Health 510(k) K131515

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

510(k) Number (if known); k 131515

Device Name: ACE T4 Reagent

Indications for Use: The ACE T4 Reagent is intended for the quantitative determination of total thyroxine (T4) in serum and lithium heparin plasma using the ACE, ACE Alera, and ACE Axcel Clinical Chemistry Systems. Total thyroxine measurements are used in the diagnosis and treatment of thyroid diseases. 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)

Ruth A. Chesler -S

Division Sign-Off Office of In Vitro Devices or Radiological Health 510(k) K131515

§ 862.1700 Total thyroxine test system.

(a)
Identification. A total thyroxine test system is a device intended to measure total (free and protein bound) thyroxine (thyroid hormone) in serum and plasma. Measurements obtained by this device are used in the diagnosis and treatment of thyroid diseases.(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 the limitations in § 862.9.