K Number
K990346
Manufacturer
Date Cleared
1999-05-21

(106 days)

Product Code
Regulation Number
862.1665
Reference & Predicate Devices
N/A
Predicate For
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview
Intended Use

The ADVIA 1650 Chemistry System is an automated, clinical chemistry analyzer that can run tests on human serum, plasma, or urine in random access, batch, and STAT modes at a throughput rate of 1200 photometric tests per hour and 450 electrolyte tests per hour. The photometric analyzer performs clinical chemistry and immuno-turbidimetric methods. The electrylyte portion of the analyzer measures the sodium, and chloride concentrations in serum, plasma or urine samples based on a potentiometric procedure that uses ion-selective electrodes. The ADVIA 1650 is intended for use in conjunction with certain reagents to measure a variety of analytes contained in human fluids.

Device Description

The ADVIA 1650 Chemistry System is an automated, clinical chemistry analyzer that can run tests on human serum, plasma, or urine in random access, batch, and STAT modes at a throughput rate of 1200 photometric tests per hour and 450 electrolyte tests per hour. The photometric analyzer performs clinical chemistry and immuno-turbidimetric methods. The electrylyte portion of the analyzer measures the sodium, and chloride concentrations in serum, plasma or urine samples based on a potentiometric procedure that uses ion-selective electrodes.

AI/ML Overview

The Bayer ADVIA® 1650 Chemistry System is an automated, clinical chemistry analyzer designed to measure various analytes in human serum, plasma, or urine. The 510(k) submission (K990346) provides performance data for 21 clinical methods, comparing the ADVIA 1650 to predicate devices. This response focuses on the Albumin method as a representative example, as the provided text doesn't explicitly state acceptance criteria in a unified table but rather presents performance characteristics individually for each assay.

1. Table of Acceptance Criteria and Reported Device Performance (Albumin Method)

Since explicit acceptance criteria are not provided, we infer performance metrics based on the comparison with predicate devices and typical clinical laboratory standards. The performance metrics presented below are those reported for the ADVIA 1650 and its predicate device (Technicon DAX) for Albumin, as detailed in the submission.

Performance MetricAcceptance Criteria (Inferred/Typical)ADVIA 1650 PerformancePredicate Device Performance (Technicon DAX)
Imprecision (Total CV %)
Serum (Level 1: ~2.1-2.2 g/dL)Typically < 5%2.4 %3.3 %
Serum (Level 2: ~3.4 g/dL)Typically < 5%1.8 %2.5 %
Serum (Level 3: ~4.8 g/dL)Not available for ADVIA 1650, but common to compare.N/A2.0 %
Correlation to Predicate (R - correlation coefficient)R > 0.95 (commonly accepted standard)0.969 (Serum: MSK)N/A
Correlation to Predicate (Syx - Std Error of Estimate)Close to 0, indicating strong agreement0.19 (Serum: MSK)N/A
Regression Equation (Slope)Close to 1 (indicating proportional agreement)0.86 (Serum: MSK)N/A
Regression Equation (Y-intercept)Close to 0 (indicating absence of constant bias)0.55 (Serum: MSK)N/A
Interfering Substances (Effect %)Generally < 10% (clinically insignificant)Bilirubin: 0.0 %N/A
Hemoglobin: 8.1 %N/A
Lipids (Trig): 7.3 %N/A
Analytical RangeMust cover clinically relevant range1 to 6 g/dLN/A
Expected ValuesMust be consistent with established reference ranges3.4 - 4.8 g/dLN/A

2. Sample Sizes and Data Provenance (for Albumin Method)

  • Test Set Sample Size:

    • Imprecision:
      • Serum: Not explicitly stated, but typically involves multiple replicates run over several days (e.g., 20 days, 2 runs/day, 2 replicates/run = 80 data points per level). The low CV percentages suggest a sufficient number of runs.
    • Correlation:
      • Serum (MSK site): 156 samples
      • Plasma(y), Serum(x) (comparison against ADVIA 1650 itself): 58 samples (likely for method comparison between different specimen types on the same device)
  • Data Provenance: The document generally indicates studies were performed at different sites, for example, "Serum: MSK" (likely Memorial Sloan Kettering or a similar institution) and "Plasma(y), Serum(x) ADVIA 1650". Specific country of origin is not detailed, but the submission is to the FDA (USA), implying studies were conducted according to US regulatory standards. The data appears to be prospective as it's generated specifically for device validation through imprecision and correlation studies.

3. Number of Experts and Qualifications for Ground Truth:

  • For in vitro diagnostic devices measuring analytes like Albumin, the "ground truth" is typically established by reference methods or validated predicate devices. The study compares the ADVIA 1650's results to those obtained from established predicate devices (e.g., Technicon DAX).
  • Therefore, the concept of "number of experts" establishing ground truth in the context of image interpretation or clinical diagnosis by human readers does not apply directly here. The predicate devices are considered the "expert" or "gold standard" for measurement.
  • The qualifications of the laboratory personnel performing these tests are implied to be standard clinical laboratory professionals, but specific details on their years of experience are not provided.

4. Adjudication Method for the Test Set:

  • This concept is not directly applicable to quantitative analytical devices like the ADVIA 1650 when comparing against a predicate or reference method. Adjudication is generally used in studies where human interpretation or consensus is required to establish ground truth (e.g., in imaging studies).
  • For quantitative measurements, statistical methods like regression analysis (as shown by R and Syx values) are used to assess agreement between the new device and the comparison system.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:

  • No, an MRMC comparative effectiveness study was not done. This type of study assesses how human readers perform with and without AI assistance, which is irrelevant for a standalone chemical analyzer like the ADVIA 1650.

6. Standalone Performance:

  • Yes, standalone performance was done. The imprecision data (Total CV %) for the ADVIA 1650 itself, without comparison to a human-in-the-loop, directly demonstrates the algorithm's performance in terms of repeatability and reproducibility. The "Analytical Range" and "Interfering Substances" also represent standalone performance evaluations.

7. Type of Ground Truth Used:

  • The ground truth used for the test set is based on the measurements obtained from established predicate devices (e.g., Technicon DAX) which are considered validated and clinically acceptable methods for measuring Albumin. This falls under the category of comparison to a reference method or predicate device.

8. Sample Size for the Training Set:

  • For this type of in vitro diagnostic device, the concept of a "training set" in the context of machine learning (where algorithms learn from large datasets) does not apply. The ADVIA 1650 is a pre-programmed chemistry analyzer; its methods are developed and validated through chemical principles and instrument design, not through iterative machine learning on a training set of patient data.
  • The data presented (imprecision, correlation, interference) are part of the validation and verification studies to ensure the device performs as intended, not a machine learning "training" process.

9. How the Ground Truth for the Training Set was Established:

  • As explained above, there is no "training set" in the machine learning sense for this device. The methods employed by the ADVIA 1650 are based on established analytical chemistry principles and reagent formulations. The "ground truth" for developing and calibrating these methods would be based on reference materials, calibrators with known concentrations, and established chemical reaction kinetics, all validated through rigorous laboratory practices rather than through a ground truth established by experts or pathology for a training dataset.

{0}------------------------------------------------

1990346

MAY 2 1

SUMMARY OF SAFETY AND EFFECTIVENESS

This section contains performance comparisons for 21 clinical methods. For each method, Advia 1650 was compared to a similar device (or devices) that was granted clearance of substantial equivalence. The table below lists the predicate devices and part numbers.

ADVIA 1650Reagent Part #SpecimenTypePredicate DeviceNamePredicate DeviceReagent Part #
Method
AlbuminB01-4121-01SerumTechnicon DAX®T01-1337-B3
Alkaline Phosphatase - AMPB01-4134-01SerumTechnicon DAX®T01-1814
AmylaseB01-4136-01SerumBeckman Synchron CX®442775
UrineBeckman Synchron CX7®442775
Aspartate AminotransferaseB01-4139-01SerumTechnicon DAX®T01-1750
SerumTechnicon DAX®T01-1476
CalciumB01-4145-01UrineDuPont DimensionDF23A
UrineBeckman Synchron CX3®450214, 472095
SerumTechnicon DAX®T152-17
ChlorideB01-4171-01SerumBeckman Synchron CX7®450214, 472095
UrineBeckman Synchron CX3/7®450214, 472095
Creatine KinaseB01-4137-01SerumTechnicon DAX®T01-1882
SerumBeckman Synchron CX7®443794
Creatinine, JaffeB01-4126-01SerumTechnicon DAX®T01-1927
UrineHitachi®1040847
Creatinine, EnzymaticB01-4127-01SerumTechnicon DAX®T01-1927
Bilirubin, DirectB01-4123-01SerumTechnicon DAX®T01-1565
SerumHitachi®1109774
Glucose - HexokinaseB01-4129-01SerumTechnicon DAX®T11-1832
UrineHitachi®1447521
Glucose - OxidaseB01-4130-01SerumTechnicon DAX®T01-1492-56
UrineBeckman Synchron CX3/7®443355
HDL CholesterolB01-4125-01SerumBoehringer Mannheim on RA-XT543004
SerumTechnicon DAX®T01-1303
Inorganic PhosphorusB01-4144-01SerumBeckman Synchron CX7®465145
UrineCobas Fara®44031
IronB01-4147-01SerumTechnicon DAX®150-26E, 150-26F
SerumSigma RA1000565-1, 565-3
MagnesiumB01-4148-01SerumTechnicon DAX®T01-2878
Serum/UrineHitachi®1273582
PotassiumB01-4171-01SerumTechnicon DAX®T01-3161
UrineBeckman Synchron CX3®443325, 443315
SodiumB01-4171-01SerumTechnicon DAX®T01-3161
UrineBeckman Synchron CX3®450124, 472095
Bilirubin. TotalB01-4122-01SerumTechnicon DAX®T01-1963
SerumTechnicon DAX®T01-2577
Uric AcidB01-4131-01UrineBeckman Synchron CX7®442785
UrineCobas Fara®828475
Urea NitrogenB01-4132-01SerumTechnicon DAX®T01-1823
UrineBeckman Synchron CX3/7®443350

Gabriel J. Muraca, Jr. Manager, Regulatory Affairs Bayer Corporation 511 Benedict Ave. Tarrytown, NY 10591-5097

Date

{1}------------------------------------------------

Albumin Method for the Bayer ADVIA 1650 (g/dL)

Intended Use

This in vitro diagnostic assay is intended to measure albumin concentration in human serum and plasma on the ADVIA® 1650 Chemistry System. Such measurements are used in the diagnosis and treatment of chronic inflammatory diseases, collagen diseases, and liver and kidney disorders.

Imprecision

Advia 1650

SpecimentypeLevelTotalCV (%)
Serum2.12.4
Serum3.41.8
Technicon DAX
LevelTotal CV (%)
2.23.3
3.42.5
4.82.0

Correlation (Y=ADVIA 1650, X=comparison system)

Specimen type: SiteComparison System (X)NRegression EquationSyxRSample Range
Serum: MSKDAX156Y=0.86X+0.550.190.9691.6-5.3
Plasma(y), Serum(x)ADVIA 165058Y=0.96X+0.290.050.9784.5-5.7

Interfering Substances

InterferingSubstanceInterferingSub. Conc.(mg/dL)Analyteconc.Effect
Bilirubin254.20.00.0
Hemoglobin5003.70.38.1
Lipids (Trig)5004.10.37.3

Analytical Range

1 to 6 g/dL

Expected Values

3.4 - 4.8 g/dL

{2}------------------------------------------------

2. ALP-AMP

SUMMARY OF SAFETY AND EFFECTIVENESS

Alkaline Phosphatase AMP Method for the Bayer ADVIA 1650 (U/L)

Intended Use

This in vitro diagnostic assay is intended to measure alkaline phosphatase activity in human serum and plasma on an ADVIA® 1650 Chemistry System. Such measurements are used mainly in the diagnosis and treatment of hepatobiliary and bone disease.

Imprecision

Advia 1650

Technicon DAX
Address to a status and and and and and and the collection
SpecimentypeLevelTotalCV (%)
Serum693.9
Serum1303.1
1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1
Total
LevelCV (%)
792.5
ાં ૪૯2.2
5711.9

Correlation (Y=ADVIA 1650, X=comparison system)

Specimen type: SiteComparison System (X)NRegression EquationSyxRSample Range
Serum: TRYTNDAX43$Y=1.03X-2.1$3.120.99922-346
Plasma(y), Serum(x)ADVIA 165054$Y=1.06X+1.42$5.370.97233-149

Interfering Substances

InterferingSubstanceInterferingSub. Conc.(mg/dL)Analyteconc.Effect
Bilirubin2569.31.72.5
Hemoglobin500100.3-5.6-5.6
Lipids (Trig)50071.01.31.8

Analytical Range

0-1100 U/L

Expected Values

25 to 100 U/L

{3}------------------------------------------------

3. AMY

SUMMARY OF SAFETY AND EFFECTIVENESS

Amylase Method for the Bayer ADVIA 1650 (U/L)

Intended Use

This in vitro diagnostic assay is intended to measure amylase activity in human serum, plasma and urine on an ADVIA® 1650 Chemistry System. Such measurements are used primarily in the diagnosis and monitoring of acute pancreatitis (inflammation of the pancreas).

Imprecision

Advia 1650

SpecimentypeLevelTotalCV (%)
Serum601.2
Serum2421.3
Serum3221.2
Urine7927.2

Beckman CX7=Serum, Urine

Total

LevelCV (%)
85.75.3
2405.3
3205.3
8005.3

Correlation (Y=ADVIA 1650, X=comparison system)

Specimen type: SiteComparison System (X)NRegression EquationSyxRSample Range
Serum: MSKCX4102Y=0.72X+1.913.50.9986-549
Plasma(y), Serum(x)ADVIA 165053Y=1.08X+1.463.90.98518-110
Urine: MSKCX782Y=0.75X+0.7413.40.9932-667

Bias expected in serum and urine correlation when run against Beckman instrument due to the different substrates used in each instrument.

Interfering Substances

InterferingSubstanceInterferingSub. Conc.(mg/dL)Analyteconc.Effect
Bilirubin2568.3-1.6-2.3
Hemoglobin500174.3-2.3-1.3
Lipids (Trig)50066.31.42.1

Analytical Range

Serum/Plasma:0 to 1500 U/L (from reagent stability study)
Urine0 to 1500 U/L (from reagent stability study)
Serum:20-104 U/L
Urine:1-17 U/h (timed)

{4}------------------------------------------------

4. AST

SUMMARY OF SAFETY AND EFFECTIVENESS

Aspartate Aminotransferase Method for the Bayer ADVIA 1650 (U/L)

Intended Use

This in vitro diagnostic assay is intended to measure aspartate aminotransferase activity in human serum and plasma on an ADVIA® 1650 Chemistry System. Such measurements are used mainly to determine the progress and prognosis of patients with myocardial infarction and the diagnosis and monitoring of liver disease.

Imprecision

Advia 1650

SpecimentypeLevelTotalCV (%)
Serum323.9
Serum1461.7
Technicon DAX
LevelTotal CV (%)
555.4
2032.5
4713.3

Correlation (Y=ADVIA 1650, X=comparison system)

Specimen type: SiteComparisonSystem (X)NRegressionEquationSyxRSampleRange
Serum: BERLINDAX111Y=0.99X-6.33.630.9999.8-607.2
Plasma(y), Serum (x)ADVIA 165054Y=1.00X-2.93.010.95416-85

Interfering Substances

InterferingSubstanceInterferingSub. Conc.(mg/dL)Analyteconc.Effect
Bilirubin2531.0-3.7-11.9
Hemoglobin50074.718.624.9
Lipids (Trig)50029.7-4.4-14.8

Hemolyzed samples should not be used due to effect by RBC.

Analytical Range

0-1000 U/L (from reagent stability study)

Expected Values

M: 15 - 40 U/L. F: 13 - 35 U/L.

{5}------------------------------------------------

Calcium Method for the Bayer ADVIA 1650 (mg/dL)

Intended Use

This in vitro diagnostic assay is intended to measure calcium concentration in human serum, plasma and urine on an ADVIA® 1650 Chemistry System. Such measurements are used in the diagnosis and treatment of parathyroid disease, a variety of bone diseases, chronic renal disease, and tetany.

Imprecision

Advia 1650Technicon DAX = SerumDupont Dimension=Urine
SpecimentypeLevelTotalCV (%)LevelTotal CV (%)LevelBetween Day CV (%)
Serum5.92.77.72.38.80.6
Serum10.82.910.31.614.52.6
Serum12.03.512.51.5
Urine6.22.4
Urine21.22.5

Correlation (Y=ADVIA 1650, X=comparison system)

Specimen typeComparison System (X)NRegression EquationSyxRSample Range
Serum - ARIDAX100Y=0.99X + 0.130.2230.9717.0 - 13.2
Plasma(y), Serum(x)ADVIA 165059Y=0.94X + 0.820.0940.9639.0 - 10.8
Urine - ARIDimension32Y=1.2X - 2.250.1650.9993.7 - 14.5
Urine - MSKCX363Y=1.07X + 0.030.5580.9882.1 - 14.7

Interfering Substances

InterferingSubstanceInterferingSub. Conc.(mg/dL)Analyteconc.Effect
conc.%
Bilirubin258.00.00.0
Hemoglobin5008.80.22.3
Lipids (Trig)5008.00.33.8

Analytical Range

Serum/Plasma:1 to 15 mg/dL
Urine:1 to 15 mg/dL
Serum/Plasma:8.6 to 10.0 mg/dL
Urine:100 to 300 mg/d

{6}------------------------------------------------

Chloride Method for the Bayer ADVIA 1650 (mmol/L)

Intended Use

This in vitro diagnostic assay is intended to measure chloride concentration in human serum, plasma and urine on an ADVIA® 1650 Chemistry System. Such measurements are used for their inferential value and are helpful in diagnosing disorders of acid-base and water balance. It is especially important to measure chloride during the correction of hypokalemic alkalosis and also during severe, prolonged vomiting, which can lower the serum chloride level.

Imprecision

Advia1650
SpecimentypeLevelTotalCV (%)
Serum88.41.6
Serum111.82.0
Urine86.81.7
Urine290.43.8
Beckman CX7=Serum,Urine
LevelTotal CV (%)
801.3
118.81.1
89.43.4
2501.5

Technicon DAX=Serum

LevelTotal CV (%)
971.5
1121.8

Correlation (Y=ADVIA 1650, X=comparison system)

Specimen typeComparison System (X)NRegression EquationSyxRSample Range
Serum - ARICX7115$Y=1.00X + 1.3$1.60.98576 - 128
Serum - MSKDAX154$Y=0.98X + 3.3$2.20.91486 - 122
Plasma(y), Serum(x)ADVIA 165069$Y=0.86X+15.9$1.200.944102-118
Urine - ARICX776$Y=1.05X - 0.9$4.90.99629 - 280

Interfering Substances

InterferingSubstanceInterferingSub. Conc.(mg/dL)Analyteconc.Effect
Bilirubin2585.00.40.5
Hemoglobin50082.70.00.0
Lipids (Trig)50083.32.42.9

Analytical Range

Serum/Plasma:15 to 200 mmol/L
Urine:15 to 400 mmol/L
Serum:98 - 107 mEq/L
Urine:110 – 250 mmol/d

{7}------------------------------------------------

7. СК

SUMMARY OF SAFETY AND EFFECTIVENESS

Creatine Phosphokinase Method for the Bayer ADVIA 1650 (U/L)

Intended Use

This in vitro diagnostic assay is intended to measure creatine kinase activity in human serum and plasma on an ADVIA® 1650 Chemistry System. Such measurements are used mainly in the diagnosis and treatment of myocardial infarction and muscle diseases such as Duchenne progressive muscular dystrophy.

Imprecision

Advia 1650Technicon DAXBeckman CX7
Specimen typeLevelTotal CV (%)Level (U/L)Total CV (%)LevelTotal CV (%)
Serum1392.71774.81445.3
Serum4493.05902.54605.3

Correlation (Y=ADVIA 1650, X=comparison system)

Specimen type: SiteComparison System (X)NRegression EquationSyxRSample Range
Serum: MSKDAX151Y=0.97X+1.193.30.9996-700
Serum: ARICX7145Y=1.01X+0.86.501.00013-1187
Plasma(y), Serum(x)ADVIA 165056Y=1.05X-9.027.880.99741-507

Interfering Substances

InterferingSubstanceInterferingSub. Conc.(mg/dL)Analyteconc.Effect
Bilirubin2570.02.73.9
Hemoglobin50098.024.324.8
Lipids (Trig)50065.06.09.2

Analytical Range

0-1300 U/L

Expected Values

M: 38 - 174 U/L. F: 26 - 140 U/L.

{8}------------------------------------------------

8. CREAT

SUMMARY OF SAFETY AND EFFECTIVENESS

Creatinine Method for the Bayer ADVIA 1650 (mg/dL)

Intended Use

This in vitro diagnostic assay is intended to measure creatinine concentration in human serum, plasma and urine on the ADVIA® 1650 system. Such measurements are used in the diagnosis and treatment of renal diseases, and in monitoring renal dialysis.

Imprecision

Advia 1650Technicon DAX=Serum
SpecimenTotalTotal
typeLevelCV %LevelCV (%)
Serum1.83.81.84.3
Serum8.43.75.04.5
Urine84.62.910.53.7
Urine209.34.0

Correlation (Y=ADVIA 1650, X=comparison system)

Specimen type: SiteComparison System (X)NRegression EquationSyxRSample Range
Serum: BERLINDAX112Y=0.92X+0.060.150.9950.33-8.3
Plasma(y), Serum(x)ADVIA 165058Y=1.02X+0.040.020.9920.9-1.4
Urine: BERLINHITACHI86Y=1.13X+0.402.610.99521-160

Interfering Substances

InterferingSubstanceInterferingSub. Conc.(mg/dL)Analyteconc.Effectconc.Effect%
Bilirubin251.0-0.8-80.0
Hemoglobin5007.30.11.4
Lipids (Trig)5001.00.04.5

Analytical Range

Serum/Plasma: 0 - 25 mg/dL Urine: 17 - 160 mg/dL

Serum:M: 0.9 - 1.3 mg/dL
F: 0.6 - 1.1 mg/dL.
Urine:M: 14 - 26
F: 11 - 20

{9}------------------------------------------------

9. CREAT-E

SUMMARY OF SAFETY AND EFFECTIVENESS

Creatinine-Enzymatic Method for the Bayer ADVIA 1650 (mg/dL)

Intended Use

This in vitro diagnostic assay is intended to measure creatinine concentration in human serum and plasma on an ADVIA® 1650 Chemistry System. Such measurements are used in the diagnosis and treatment of renal diseases, and in monitoring renal dialysis.

Imprecision

Advia 1650

Technicon DAX
SpecimentypeLevelTotal CV (%)LevelTotal CV (%)
Serum0.96.41.84.3
Serum6.12.35.04.5
Serum9.52.010.53.7

Correlation (Y=ADVIA 1650, X=comparison system)

Specimen type: SiteComparisonSystem (X)NRegressionEquationSyxRSampleRange
Serum: MSKDAX155$Y=0.99X-0.06$0.160.9550.3-3.9
Plasma(y), Serum(x)ADVIA 165057$Y=0.96X+0.16$0.070.9250.7-1.4

Interfering Substances

InterferingSubstanceInterferingSub. Conc.(mg/dL)Analyteconc.Effect
Bilirubin250.7-0.2-28.6
Hemoglobin5007.8-0.1-1.3
Lipids (Trig)5000.7-1.2-171.4

Analytical Range

0-30 mg/dL

Expected Values

M: 0.9 - 1.3 mg/dL, F: 0.6 - 1.1 mg/dL.

{10}------------------------------------------------

10. DBILI

SUMMARY OF SAFETY AND EFFECTIVENESS

Direct Bilirubin Method for the Bayer ADVIA 1650 (mg/dL)

Intended Use

This in vitro diagnostic assay is intended to measure direct bilirubin concentration in human serum and plasma on the ADVIA® 1650 Chemistry System. Such measurements are used in the diagnosis of common bile duct obstruction caused by a stone and of patients with Dubin-Johnson syndrome.

Total CV (%)

** 5.7 2.3

Imprecision

Advia 1650

Advia 1650Technicon DAX
Specimen typeLevelTotal CV (%)Level
Serum0.34.60.2
Serum1.64.41.5
4.0

** Value not significant when level approaches zero.

Correlation (Y=ADVIA 1650, X=comparison system)

Specimen typeComparisonSystem (X)NRegression EquationSyxRSample Range
Serum - TRYTNDAX145$Y=1.34X - 0.10$0.180.9940 - 6.12
Serum - BERLINHITACHI92$Y=1.07X + 0.06$0.140.9970.02 - 9.26
Plasma (y), Serum (x)ADVIA 165049$Y=0.98X-0.01$0.020.9880.1 - 0.6

Interfering Substances

InterferingSubstanceInterferingSub. Conc.(mg/dL)Analyteconc.Effect
Hemoglobin2000.3-0.6.
Hemoglobin5000.3-1.5.
Lipids (Trig)5000.2-0.5.

Analytical Range

0 - 10 mg/dL (from reagent stability study)

Expected Values

<0.2 mg/dL

{11}------------------------------------------------

11. GLU-HEX

SUMMARY OF SAFETY AND EFFECTIVENESS

Glucose-Hexokinase Method for the Bayer ADVIA 1650 (mg/dL)

Intended Use

This in vitro diagnostic assay is intended to measure glucose in human serum, plasma and urine on an ADVIA® 1650 Chemistry System. Such measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal hypoglycemia, idiopathic hypoglycemia, and insulin overdose.

Imprecision

Advia 1650Technicon DAX=Serum
Specimen typeLevelTotal CVLevelTotal CV (%)
Serum772.4714.2
Serum2793.32622.1
Urine423.53671.7
Urine2853.6

Correlation (Y=ADVIA 1650, X=comparison system)

Specimen typeComparison System (X)NRegression EquationSyxRSample Range
Serum - BERLINDAX109Y= 1.05X - 2.85.420.99519 - 262
Urine - BERLINHITACHI81Y= 0.99X - 11.29.880.9974 - 476
Plasma (y) Serum (x)ADVIA 165060Y= 1.03X - 6.69.000.98636 - 384

Interfering Substances

AnalyteInterferingSubstanceInterferingSub. Conc.(mg/dL)Analyteconc.Effectconc.Effect%
GLU-HEXBilirubin1095.5-8.2-8.6
GLU-HEXBilirubin2595.5-24.4-25.5
GLU-HEXHemoglobin20095.9-22.2-23.1
GLU-HEXHemoglobin50095.9-59.9-62.5
GLU-HEXLipids (Trig)900189.02.21.2

Analytical Range

Serum/Plasma:0 - 700 mg/dL
Urine:0 - 700 mg/dL
Serum/Plasma74 – 106 mg/dL
Urine:<0.5 g/day

{12}------------------------------------------------

12. GLU-OX

SUMMARY OF SAFETY AND EFFECTIVENESS

Glucose-Oxidase Method for the Bayer ADVIA 1650 (mg/dL)

Intended Use

This in vitro diagnostic assay is intended to measure glucose in human serum, plasma and urine on an ADVIA® 1650 Chemistry System. Such measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal hypoglycemia, idiopathic hypoglycemia and insulin overdose.

Imprecision

Advia1650
-------------
Advia 1650Technicon DAX=Serum
Specimen typeLevelTotal CV (%)LevelTotal CV (%)
Serum771.5742.1
Serum2941.42931.5
Urine481.5
Urine2771.4

Correlation (Y=ADVIA 1650, X=comparison system)

Specimen type: SiteComparison System (X)NRegression EquationSyxRSample Range
Serum: MSKDAX155Y=0.98X-3.03.40.99641-323
Plasma(y), Serum(x)ADVIA 165048Y=0.99X+2.92.210.99960-381
Urine: MSKCX387Y=1.06X-1.24.80.9890-249

Interfering Substances

AnalyteInterferingSubstanceInterfering Sub. Conc.(mg/dL)Analyteconc.Effectconc.Effect%
GLU-OXBilirubin1091.9-3.5-3.8
GLU-OXBilirubin2591.9-13.6-14.8
GLU-OXHemoglobin50086.76.17.0
GLU-OXLipids (Trig)900187.0-5.8-3.1

Analytical Range

Serum/Plasma:0 - 750 mg/dL
Urine:0 - 750 mg/dL
Serum:74 - 106 mg/dL
Urine:<0.5 g/day

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

  1. HDL

SUMMARY OF SAFETY AND EFFECTIVENESS

High Density Lipoprotein Method for the Bayer ADVIA 1650 (mg/dL)

Intended Use

This in vitro diagnostic assay is intended to measure HDL Cholesterol in human serum and plasma on an ADVIA® 1650 Chemistry System. Such measurements are used in the risk assessment of coronary artery disease.

Imprecision

Advia 1650

RA-XT

SpecimentypeLevelTotalCV (%)LevelBetweenDay CV (%)
Serum283.815.55.1
Serum533.252.31.9

Correlation (Y=ADVIA 1650, X=comparison system)

Specimen type: SiteComparison System (X)NRegression EquationSyxRSample Range
Serum: MSKRA-XT121Y=1.03X+3.912.50.98712-94
Plasma(y), Serum(x)ADVIA 165079Y=1.09X-1.94.500.96026-98

Interfering Substances

InterferingSubstanceInterfering Sub. Conc.(mg/dL)Analyteconc.Effect
Bilirubin2529.7-0.4-1.3
Hemoglobin50029.2-5.6-19.2

Analytical Range

10-135 mg/dL

Expected Values (years: mg/dL)

Male, Ages 30 – 50:27.8 to 52.89 mg/dL
Female, Ages 30 - 50:33.9 to 86.87 mg/dL

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

14. IPHOS

SUMMARY OF SAFETY AND EFFECTIVENESS

Inorganic Phosphorus Method for the Bayer ADVIA 1650 (mg/dL)

Intended Use

This in vitro diagnostic assay is intended to measure inorganic phosphorus concentration in human serum, plasma and urine on the ADVIA® 1650 system. Such measurements are used in the diagnosis and treatment of kidney diseases, parathyroid gland disorders, and Vitamin D imbalance.

Imprecision

Advia 1650

Technicon DAX=Serum
-------------------------

Total CV (%) 3.0 2.3 2.1

SpecimentypeLevelTotalCV (%)Level
Serum3.01.73.2
Serum5.72.66.7
Serum7.72.09.4
Urine32.01.6
Urine170.60.7

Correlation (Y=ADVIA 1650, X=comparison system)

Specimen type: SiteComparisonSystem (X)NRegressionEquationSyxRSampleRange
Serum: MSKDAX154Y=0.93X+0.200.180.9781.1-7.3
Serum: ARICX7152Y=1.01X+0.300.250.9831.4-10.0
Plasma(y), Serum(x)ADVIA 165050Y=0.98X-0.230.110.9752.0-4.1
Urine: MSKCobas Fara92Y=1.02X-0.21.30.9985-87

Interfering Substances

AnalyteInterferingSubstanceInterferingSub. Conc.(mg/dL)Analyteconc.conc.Effect%
IPHOSBilirubin253.40.0-0.6
IPHOSHemoglobin5002.70.933.3
IPHOSLipids (Trig)5003.4-0.2-5.9

Analytical Range

Serum/Plasma: 0 - 20 mg/dL Urine: 5 - 100 mg/dL

Expected Values

2.7 - 4.5 mg/dL Serum: Urine: 0.4 - 1.3 g/d

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

Iron Method for the Bayer ADVIA 1650 (ug/dL)

Intended Use

This in vitro diagnostic method is intended to measure iron concentration in human serum and plasma on an ADVIA® 1650 Chemistry System. Measurements are used in the diagnosis and treatment of iron deficiency anemias and hemochromatosis.

Imprecision

Advia 1650

Technicon DAX

SpecimentypeLevelTotal CV (%)LevelTotal CV (%)
Serum643.1815.5
Serum1752.61943.2
Serum2952.23223.1

Correlation (Y=ADVIA 1650, X=comparison system)

Specimen typeComparisonSystem (X)NRegression EquationSyxRSample Range
Serum - MSKDAX40$Y=0.88X + 4.5$4.80.9976 - 253
Plasma(y), Serum(x)ADVIA 165057$Y=0.96X+15.5$6.90.97840 - 186

Interfering Substances

InterferingSubstanceInterferingSub. Conc.(mg/dL)Analyteconc.Effect
conc.%
Bilirubin25111.61.91.7
Hemoglobin500N/AN/AN/A
Lipids (Trig)500107.9-11.1-10.3

Analytical Range

0 to 1000 µg/dL

Expected Values

Males: 65 to 175 µg/dL Females: 50 to 170 µg/dL

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

Magnesium Method for the Bayer ADVIA 1650 (mg/dL)

Intended Use

This in vitro diagnostic assay is intended to measure magnesium concentration in human serum. plasma and urine on an ADVIA® 1650 Chemistry System. Such measurements are used in the diagnosis and treatment of hypermagnesemia and monitoring of patients receiving prolonged magnesium-free intravenous therapy.

Imprecision

Advia 1650

SpecimentypeLevelTotalCV (%)
Serum1.92.3
Serum3.42.0
Urine8.711.9
LevelTotal CV (%)
2.45.6
3.93.6

Correlation (Y=ADVIA 1650, X=comparison system)

Specimen typeComparisonSystem (X)NRegression EquationSyxRSample Range
Serum - TRYTNDAX193$Y=0.91X + 0.10$0.1310.9730.9 - 5.3
Serum - BERLINHITACHI112$Y=0.95X + 0.25$0.1240.9161.5 - 3.1
Plasma(y), Serum(x)ADVIA 165051$Y=0.97X + 0.02$0.0320.9631.6 - 2.1
Urine - BERLINHITACHI97$Y=0.99X + 0.31$0.2530.9971.4 - 15.0

Interfering Substances

InterferingSubstanceInterferingSub. Conc.(mg/dL)Analyteconc.Effect
Bilirubin252.60.414.0
Hemoglobin5002.70.27.4
Lipids (Trig)5001.81.055.6

Analytical Range

Serum/Plasma: 1.6 to 6 mg/dL Urine: 1.6 to 25 mg/dL

Expected Values (values in Tietz converted to mg/dL)

Serum/Plasma:1.6 – 2.6 mg/dL
Urine:7.3 – 12.2 mg/d

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

17. K

SUMMARY OF SAFETY AND EFFECTIVENESS

Potassium Method for the Bayer ADVIA 1650 (mmol/L)

Intended Use

This in vitro diagnostic assay is intended to measure potassium concentration in human serum, plasma and urine on an ADVIA® 1650 Chemistry System. Such measurements are used mainly to monitor electrolyte balance in the diagnosis and treatment of primary aldosteronism, metabolic alkalosis, diarrhea, severe vomiting, diuretic administration, diabetic ketoacidosis, and other diseases.

Imprecision

Advia 1650Technicon DAX=Serum
Specimen typeLevelTotal CV (%)LevelTotal CV (%)
Serum3.03.03.41.6
Serum6.42.77.51.7
Urine28.56.1
Urine102.94.8

Correlation (Y=ADVIA 1650, X=comparison system)

Specimen typeComparison System (X)NRegression EquationSyxRSample Range
Serum - MSKDAX156$Y=1.09X - 0.2$0.080.9952.2 - 8.1
Plasma(y), Serum(x)ADVIA 165049$Y=0.92X-0.01$0.160.8903.4 - 4.8
Urine - MSKCX399$Y=1.01X-0.2$1.20.9997 - 116

Interfering Substances

InterferingSubstanceInterferingSub. Conc.(mg/dL)Analyteconc.Effect
Bilirubin253.30.00.3
Hemoglobin500N/AN/AN/A
Lipids (Trig)5003.30.26.1

Analytical Range

Serum/Plasma:1 to 10 mmol/L
Urine:3 to 300 mmol/L
Serum:3.5 – 5.1 mmol/L
Plasma Males:3.5 – 4.5 mmol/L
Plasma Females:3.4 – 4.4 mmol/L
Urine:25 – 125 mmol/d (varies with diet)

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

Sodium Method for the Bayer ADVIA 1650 (mmol/L)

Intended Use

This in vitro diagnostic assay is intended to measure sodium concentration in human serum, plasma and urine on an ADVIA® 1650 Chemistry System. Such measurements are used mainly in the diagnosis and treatment of gross changes in water and salt balance, aldosteronism, diabetes insipidus, adrenal hypertension, Addison's disease, dehydration, inappropriate antidiuretic hormone secretion, diabetic acidosis, severe diarrhea, or other diseases involving electrolyte imbalance.

Imprecision

Advia 1650Technicon DAX=Serum
SpecimenTotalTotal
typeLevelCV (%)LevelCV (%)
Serum1191.7। । ર0.9
Serum1431.81410.9
Urineર્ભરે રેણવાડી તેમ જ દૂધની ડેરી જેવી સવલતો પ્રાપ્ય થયેલી છે. આ ગામનાં લોકોનો મુખ્ય વ્યવસાય ખેતી, ખેતમજૂરી તેમ જ પશુપાલન છે. આ ગામમાં મુખ્યત્વે આવેલું એક ગામના લોકોનો મુખ્ય વ1.9ો ર્ણ્1.2
Urine2082.0

Correlation (Y=ADVIA 1650, X=comparison system)

Specimen typeComparison System (X)NRegression EquationSyxRSample Range
Serum - MSKDAX156Y=1.02X - 0.21.080.970121 - 154
Plasma(y), Serum(x)ADVIA 165069Y=0.92X+11.61.450.964139 - 156
Urine - MSKCX397Y=0.95X + 6.230.99720 - 202

Interfering Substances

InterferingSubstanceInterferingSub. Conc.(mg/dL)Analyteconc.Effect
Bilirubin25122.80.00.0
Hemoglobin500128.72.31.8
Lipids (Trig)500117.33.12.6

Analytical Range

Serum/Plasma:100 to 200 mmol/L
Urine:10 to 400 mmol/L
Serum/Plasma:136 – 145 mEq/L
Urine:40 – 220 mmol/d

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

Total Bilirubin Method for the Bayer ADVIA 1650 (mg/dL)

Intended Use

This in vitro diagnostic assay is intended to measure total bilirubin concentration in human serum and plasma on an ADVIA® 1650 Chemistry System. Such measurements are used in the diagnosis and treatment of hemolytic, biliary, and liver disorders, including hepatitis and cirrhosis.

Imprecision

Advia 1650

Advia 1650Technicon DAX
SpecimentypeLevelTotalCV (%)LevelC
Serum1.07.60.7
Serum5.04.15.1
Serum7.72.212.5

Total CV (%) le ** 2.3 2.2

** Value not significant when level approaches zero.

Correlation (Y=ADVIA 1650, X=comparison system)

Specimen typeComparisonSystem (X)NRegression EquationSyxRSample Range
Serum - MSKDAX156$Y=1.10X+ 0.08$0.1940.9990.1 - 29.5
Serum/PlasmaADVIA 165051$Y=0.94X+ 0.16$0.0710.9540.3 - 1.4

Interfering Substances

InterferingSubstanceInterferingSub. Conc.(mg/dL)Analyteconc.Effect
Hemoglobin2000.9-0.5-61.6
Hemoglobin5000.9-1.1-122.1
Lipids (Trig)5000.90.555.6

Analytical Range

0 to 30 mg/dL

Expected Values

0.3 to 1.2 mg/dL

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

Uric Acid Method for the Bayer ADVIA 1650 (mg/dL)

Intended Use

This in vitro diagnostic assay is intended to measure uric acid concentration in human serum, plasma and urine on an ADVIA® 1650 Chemistry System. Such measurements are used in the diagnosis and treatment of renal failure, gout, and eclampsia.

Imprecision

Advia 1650Technicon DAX=SerumBeckman CX7=Urine
Specimen typeLevelTotal CV (%)TotalTotal
Serum3.91.9LevelCV (%)LevelCV (%)
Serum8.61.65.23.0123
Serum10.02.38.52.7243
Urine12.42.310.02.6
Urine23.95.2

Correlation (Y=ADVIA 1650, X=comparison system)

Specimen typeComparisonSystem (X)NRegression EquationSyxRSample Range
Serum - MSKDAX154Y=1.05X + 0.480.270.9940.2 - 18.0
Plasma(y), Serum(x)ADVIA 165061Y=1.03X + 0.020.0630.9992.4 - 8.9
Urine - ARICX730Y=1.03X - 0.53.060.9898-91

Interfering Substances

InterferingSubstanceInterferingSub. Conc.(mg/dL)Analyteconc.Effect
Bilirubin254.5-0.2-4.2
Hemoglobin5006.20.23.2
Lipids (Trig)5004.3-0.4-9.3

Analytical Range

Serum/Plasma:0 to 20 mg/dL
Urine:0 to 180 mg/dL
Males/Serum:3.5 to 7.2 mg/dL
Females/Serum:2.6 to 6.0 mg/dL
Urine:250 to 750 mg/dL

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

21. UN

SUMMARY OF SAFETY AND EFFECTIVENESS

Urea Nitrogen Method for the Bayer ADVIA 1650 (mg/dL)

Intended Use

This in vitro diagnostic assay is intended to measure urea nitrogen (an end product of nitrogen metabolism) concentration in human serum, plasma and urine on a ADVIA® 1650 Chemistry system. Such measurements are used in the diagnosis and treatment of kidney disease, urinary tract obstruction, and acute or chronic renal failure.

Imprecision

Advia 1650Technicon DAX=SerumBeckman CX3=Urine
SpecimentypeLevelTotalCVLevelTotal CV (%)LevelTotal CV (%)
Serum182.4213.54607.5
Serum502.2591.86207.5
Serum861.71021.7
Urine4614.6
Urine6182.3

Correlation (Y=ADVIA 1650, X=comparison system)

Specimen typeComparison System (X)NRegression EquationSyxRSample Range
Serum - MSKDAX34Y=1.12X - 0.81.010.9978 - 64
Plasma(y), Serum(x)ADVIA 165054Y=1.0X - 0.20.220.9977 - 22
Urine - MSKCX379Y=1.03X + 24.834.80.99067 - 988

Interfering Substances

InterferingSubstanceInterferingSub. Conc.(mg/dL)Analyteconc.Effect
Bilirubin2516.3-0.2-1.2
Hemoglobin50020.2-0.6-3.0
Lipids (Trig)50015.80.74.4

Analytical Range

Serum/Plasma:5 to 150 mg/dL
Urine:35 to 1000 mg/dL

Expected Values

6 to 20 mg/dL

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

DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/22/Picture/1 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 with three curved lines representing its head and wings. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular fashion around the bird symbol.

MAY 21 1999

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Gabriel J. Muraca, Jr. Manager Requlatory Affairs BAYER CORPORATION 511 Benedict Avenue Tarrytown, NY 10591-5097

Re: K990346

Trade Name: Bayer ADVIA® 1650 Chemistry System Regulatory Class: II Product Code: JGS, CEM, CGZ, JJE Dated: April 21, 1999 Received: April 28, 1999

Dear Mr. Muraca:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to leqally 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). 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.

If your device is classified (see above) into either class II (Special Controls) or class III (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Requlations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. this response to your premarket notification Please note: submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.

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

Page 2

Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770) 488-7655.

This letter will allow you to begin marketing your device as described in your 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification"(21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll-free number (800) 638-2041 or (301) 443-6597, or at its internet address "http://www.fda.gov/cdrh/dsma/dsmamain.html".

Sincerely yours,

Steven Butman

Steven I. Gutman, M.D. M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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

Attachment 10

Page 1 of 1

510(k) Number (if known): K990346

Device Name: Bayer ADVIA® 1650 Chemistry System

Indications For Use:

The ADVIA 1650 Chemistry System is an automated, clinical chemistry analyzer that can run tests on human serum, plasma, or urine in random access, batch, and STAT modes at a throughput rate of 1200 photometric tests per hour and 450 electrolyte tests per hour. The photometric analyzer performs clinical chemistry and immuno-turbidimetric methods. The electrylyte portion of the analyzer measures the sodium, and chloride concentrations in serum, plasma or urine samples based on a potentiometric procedure that uses ion-selective electrodes. The ADVIA 1650 is intended for use in conjunction with certain reagents to measure a variety of analytes contained in human fluids.

Jean Cooper
(Division Sign-Off)

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use : (Per 21 CFR 801.109)

OR

Over-The-Counter Use

(Optional Format 1-2-96)

§ 862.1665 Sodium test system.

(a)
Identification. A sodium test system is a device intended to measure sodium in serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of aldosteronism (excessive secretion of the hormone aldosterone), diabetes insipidus (chronic excretion of large amounts of dilute urine, accompanied by extreme thirst), adrenal hypertension, Addison's disease (caused by destruction of the adrenal glands), dehydration, inappropriate antidiuretic hormone secretion, or other diseases involving electrolyte imbalance.(b)
Classification. Class II.