XL-200 CLINICAL CHEMISTRY ANALYZER, JAS GLUCOSE REAGENT, ISE REAGENT PACK

{0} 1 # 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT COMBINATION TEMPLATE A. 510(k) Number: k130915 B. Purpose for Submission: Adding previously cleared assays on a new instrument C. Measurand: Glucose, Sodium, Potassium and Chloride D. Type of Test: Quantitative, Photometric and Ion Selective Electrode E. Applicant: JAS Diagnostics F. Proprietary and Established Names: XL-200 Clinical Chemistry Analyzer, JAS Glucose Reagent, ISE Reagent Pack G. Regulatory Information: | Product Code | Classification | Regulation Section | Panel | | --- | --- | --- | --- | | CFR | Class II | 21 CFR 862.1345 Glucose Test System | Clinical Chemistry (75) | | JGS | | 21 CFR 862.1665 Sodium Test System | | | CEM | | 21 CFR 862.1600 Potassium Test System | | | CGZ | | 21 CFR 862.1170 Chloride Test System | | | JJE | Class I | 21 CFR 862.2160 Discrete Photometric Analyzer Chemistry For Clinical Use | | H. Intended Use: 1. Intended use(s): {1} See Indications for Use below. 2. **Indication(s) for use:** The XL-200 Clinical Chemistry Analyzer is an automated random access, computer controlled, bench top, clinical analyzer for clinical chemistry tests. The instrument provides in vitro quantitative measurements for glucose, sodium, potassium and chloride in serum. This device is intended for clinical laboratory use. The JAS Glucose Reagent is intended for the in vitro quantitative measurement of glucose in serum on the XL-200 clinical chemistry analyzer. This device is intended for clinical laboratory use. Glucose measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal hypoglycemia and idiopathic hypoglycemia and of pancreatic islet cell Carcinoma. The ISE Reagent Pack is intended for the in vitro quantitative measurement of sodium, potassium, and chloride concentrations in serum on the XL-200 clinical chemistry analyzer. This device is intended for clinical laboratory use. Sodium measurements are used in the diagnosis and treatment of aldosteronism, diabetes insipidus and other diseases involving electrolyte imbalance. Potassium measurements are used to monitor electrolyte balance in the diagnosis and treatment of disease conditions characterized by low or high blood potassium levels. Chloride measurements are used in the diagnosis and treatment of electrolyte and metabolic disorders such as cystic fibrosis and diabetic acidosis. 3. **Special conditions for use statement(s):** - Prescription Use only - Not for point of care use 4. **Special instrument requirements:** - XL-200 Clinical Chemistry Analyzer H. **Device Description:** The XL-200 Clinical Chemistry Analyzer is an automated bench top, random access, open analyzer for clinical chemistry analysis on human serum, including an optional ISE module. The analyzer uses colorimetric, turbidimetric, and ion selective electrode methods for analysis of samples. The analyzer consists of the following main components: {2} Sample and reagent pipette unit, stirrer, auto sampler unit, cuvette rinsing unit, reaction cuvette tray, and reagent tray. The JAS Glucose Reagent is a single vial liquid that is placed for use on the XL-200 Clinical Chemistry Analyzer reagent carousel. The reagent uses the enzymatic (Hexokinase/G-6-P) UV (340nm) method and consists of ATP, NAD, Hexokinase, G-6-PDH and nonreactive stabilizers, fillers and buffers. The JAS Glucose Reagent has been previously cleared in k011900. The ISE Reagent Pack consists of Calibrant A- 520mL: (Sodium 140.0, Potassium 4.00, Chloride 125.0 mmol/L), and Calibrant B- 190mL: (Sodium 70.0, Potassium 8.00, Chloride 41.0 mmol/L) The ISE Reagent Pack has been previously cleared in k070057. ## J. Substantial Equivalence Information: 1. Predicate device name(s): Beckman Coulter Olympus AU400 clinical chemistry analyzer including glucose and ISE assays 2. Predicate 510(k) number(s): k981743 3. Comparison with predicate: Instrument | Item | XL-200 Clinical Chemistry Analyzer (candidate device) | OLYMPUS AU400 (Predicate Device: k981743) | | --- | --- | --- | | Similarities | | | | Intended Use | Random access, computer controlled, counter top, clinical analyzer for clinical chemistry. This instrument provides quantitative measurements for glucose, sodium, potassium and chloride. | Same | | QC/Calibration | Automatic and Manual | Same | | LIS external connectivity | YES | Same | {3} | Barcode | Samples Reagents | Same | | --- | --- | --- | | Re-dilution on abnormals | YES | Same | | Mode of detection | Photometric /ISE | Same | | Analytical Methods | Endpoint, Kinetic, Ion Selective Electrodes | Same | | Calibration | Linear and non linear | Same | | Measurement modes | Absorbance | Same | | Optical modes | Biochromatic, turbidimetric | Same | | Linear absorbance | 0.0 to 2.5 A | Same | | Light source | halogen lamp | Same | | Reagent refrigeration | Yes | Same | | Temperature | Room, 30°C, 37°C | Same | | Environmental Conditions | 15 to 30°C Humidity 40 to 80% | Same | | Differences | | | | Throughput | 200 test/hour | 400 test/hour | | Wavelengths | 340nm, 405nm, 505nm, 546nm, 578nm, 600nm, 660nm, 700nm | 304nm, 380nm, 410nm, 450nm, 480nm, 520nm, 540nm, 570nm, 600nm, 660nm, 700nm, 750nm, 800nm | | ISE sample type | Serum | Serum, Urine | | Reaction cuvettes | 45 quartz semi- disposable | 88 quartz semi-disposable | | Reaction volume | 180 to 570 μl | 180 to 610 μl | | Path length | Calculated at 10mm | 10mm conversion | {4} 5 | Reagent positions | 25 for Rgt1, 50ml bottles 25 for Rgt2, 20mL bottles | 38 for Rgt1, 60ml bottles 38 for Rgt2, 15 & 30mL bottles | | --- | --- | --- | | Sample positions | 39 | 48 | | Pipetter system | plunger, stepper motor driven | Micro-syringe, motor driven | | Mixing | Immersion mixing by rotating mixers | Rotating mix bar | | Sample dispensing | 2 - 70 μl | 2 - 50 μl | | Power | AC220V. 50 Hz or 110v, 60Hz | AC210V, 60Hz (U.S.) | ## Glucose Reagent | Item | Candidate Device JAS Glucose Reagent | OLYMPUS AU400 (Predicate Device: k981743) | | --- | --- | --- | | Intended Use | For the quantitative measurement of glucose | Same | | Method | enzymatic (Hexokinase I G-6-P), UV (340nm) | Same | | Sample Type | Serum | Serum, plasma or urine | | Measuring range (serum) | 9 to 500 mg/dL | 10 to 800 mg/dL | | Reference range (serum) | 74-106 mg/dL | 70 -105 mg/dL | ## ISE Reagent | Item | Candidate Device ISE Reagent Pack | OLYMPUS AU400 (Predicate Device: k981743) | | --- | --- | --- | | Intended Use | For the quantitative measurement of sodium, potassium and chloride concentrations | For the quantitative measurement of sodium, potassium and chloride concentrations | | Method | Ion Selective Electrodes (ISEs) | Same | | Sample Type | Serum | Serum, plasma, and urine | {5} | Measuring range (serum) | Sodium: 100 to 200 mmol/L Potassium: 1.0 to 10.0 mmol/L Chloride: 50 to 150 mmol/L | Sodium: 50 to 200 mmol/L Potassium: 1.0 to 10.0 mmol/L Chloride: 50 to 200 mmol/L | | --- | --- | --- | | Reference range (serum) | Sodium: 136 to 145 mmol/L Potassium: 3.5 to 5.1 mmol/L Chloride: 98 to 107 mmol/L | Sodium: 136 to 145 mmol/L Potassium: 3.5 to 5.1 mmol/L Chloride: 98 to 104 mmol/L | | ISE Principle | Ion selective, direct measurement | Same | | Detector | Silicone photodiode array | Silicon photodiode | | Available ISE tests | Na, K, CI | Same | | ISE calibration | Two-point and single point | Same | | Sample size | 70 uL | Same | K. Standard/Guidance Document Referenced (if applicable): IEC61010-1 Safety requirements for Electrical Equipment and Measurement, Control and Laboratory. IS014971 - Medical Devices - Application of risk management to medical devices CLSI - EP05-A2. Evaluation of precision performance of Clinical Chemistry Devices. CLSI - EP06-A. Evaluation of linearity of Quantitative analytical methods. CLSI - EP07-A2. Interference testing in Clinical Chemistry CLSI - EP09-A2 Method comparison and bias estimation using patient samples CLSI - EP17-A Protocols for the determination of Limits of Quantitation L. Test Principle: The XL-200 Glucose (Hexokinase) method is based on a modification of Slein, using Hexokinase and glucose-6-phosphate-dehydrogenase to catalyze the reaction. Glucose is phosphorylated with adenosine triphosphate (ATP) in the reaction catalyzed by Hexokinase (HK). The product, glucose-6-phosphate (G6P) is then oxidized with the concomitant reduction of nicotinamide adenine dinucleotide (NAD) to NADH in the reaction catalyzed by {6} glucose-6-phosphatedehygrogenase (G6PDH). The formation of NADH caused an increasing in absorbance at $340\mathrm{nm}$ . The increase is proportional to the amount of glucose in the sample. The ISE method uses ion selective principles to measure the sodium, potassium, and chloride. The ISE module measures the potentials developed when the sample is positioned in the electrodes. Next, Calibrant A is positioned in the electrodes. The difference in the two potentials is related logarithmically to the concentration of the measured ions in the sample divided by their respective concentrations in the Calibrant solution. # M. Performance Characteristics (if/when applicable): # 1. Analytical performance: # a. Precision/Reproducibility: Precision studies were performed according to CLSI document EP5-A2, Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline. Three levels of JAS serum based controls were tested on the XL-200 Clinical Chemistry Analyzer for each analyte in one run of 20 replicates to obtain the within run precision $(N = 20)$ . Three levels of JAS serum based controls were tested in duplicate twice per day for 20 days to obtain the total precision $(N = 80)$ . Results are summarized in the tables below: Glucose | | | Within Run | | Total Precision | | | --- | --- | --- | --- | --- | --- | | Level | Mean (mg/dL) | S.D. (mg/dL) | C.V. (%) | S.D. (mg/dL) | C.V. (%) | | 1 | 49.8 | 0.9 | 1.7 | 1.3 | 2.6 | | 2 | 96.2 | 1.1 | 1.2 | 1.8 | 1.8 | | 3 | 303.4 | 3.6 | 1.2 | 3.8 | 1.3 | Sodium | | | Within Run | | Total Precision | | | --- | --- | --- | --- | --- | --- | | Level | Mean (mmol/L) | S.D. (mmol/L) | C.V. (%) | S.D. (mmol/L) | C.V. (%) | | 1 | 118.2 | 0.34 | 0.3 | 0.81 | 0.7 | | 2 | 131.5 | 0.40 | 0.3 | 1.08 | 0.8 | | 3 | 166.6 | 0.82 | 0.5 | 1.36 | 0.8 | Potassium | | | Within Run | | Total Precision | | | --- | --- | --- | --- | --- | --- | | Level | Mean (mmol/L) | S.D. (mmol/L) | C.V. (%) | S.D. (mmol/L) | C.V. (%) | | 1 | 1.84 | 0.035 | 1.9 | 0.038 | 2.1 | | 2 | 3.43 | 0.011 | 0.3 | 0.026 | 0.8 | | 3 | 6.13 | 0.038 | 0.6 | 0.066 | 1.1 | {7} Chloride | | | Within Run | | Total Precision | | | --- | --- | --- | --- | --- | --- | | Level | Mean (mmol/L) | S.D. (mmol/L) | C.V. (%) | S.D. (mmol/L) | C.V. (%) | | 1 | 88.3 | 0.45 | 0.5 | 0.73 | 0.8 | | 2 | 108.5 | 0.68 | 0.6 | 0.80 | 0.7 | | 3 | 120.0 | 0.30 | 0.3 | 0.56 | 0.5 | # b. Linearity/assay reportable range: Linearity studies were performed on the XL-200 Clinical Chemistry Analyzer using commercially available ready to use multilevel linearity standard materials. Nine levels of linearity standards were analyzed in duplicate. The observed values were compared to the expected values and the results of linear regression are summarized in the table below: | Analyte | Claimed Measuring Range | Slope | Intercept | Sample Range Tested | | --- | --- | --- | --- | --- | | Glucose | 9 – 500 mg/dL | 1.01 | -0.1 | 9.0 – 500 mg/dL | | Sodium | 100 – 200 mmol/L | 0.990 | 1.1 | 99-204 mmol/L | | Potassium | 1.0 - 10.0 mmol/L | 1.011 | -0.2 | 1.0- 11.8 mmol/L | | Chloride | 50 – 150 mmol/L | 0.985 | 1.8 | 47 – 154 mmol/L | # c. Traceability, Stability, Expected values (controls, calibrators, or methods): The glucose and ISE calibrator material is traceable to a commercially available reference material which is traceable to NIST standards. The glucose calibrator material (JAS multi analyte Calibrator) was previously cleared under k020454. The ISE calibrator material for sodium, potassium and chloride (Calibrant A and B) was previously cleared under k070057. # d. Detection limit: # Glucose: The Level of Blank (LoB) study was performed using a protein based material with a low level of glucose run 30 times/day over three days on the XL-200 Clinical Chemistry Analyzer resulting in a LoB of $0.1\mathrm{mg / dL}$ . The Limit of Detection (LoD) was determined to be $1.0\mathrm{mg / dL}$ using low analyte samples run 30 times/day over three days. Following CLSI EP17-A, the Limit of Quantitation (LoQ) was determined to be $1.0\mathrm{mg / dL}$ . | | LoB | LoD | LoQ | Claimed measuring range | | --- | --- | --- | --- | --- | | Glucose | 0.1 mg/dL | 1.0 mg/dL | 1.0 mg/dL | 9 to 500 mg/dL | {8} Sodium, Potassium and Chloride: Linearity studies were used to support the measuring ranges for Sodium, Potassium and Chloride. Please see M.1.b. linearity section above. The sponsor's claimed measuring range: | Analyte | Claimed Measuring Range | | --- | --- | | Sodium | 100 – 200 mmol/L | | Potassium | 1.0 - 10.0 mmol/L | | Chloride | 50 – 150 mmol/L | # e. Analytical specificity: Interference studies were performed according to CLSI EP-7A (Interference testing in Clinical Chemistry) to determine the effects from potential interferents on the JAS Glucose and the ISE assays. Various concentrations of interferents were spiked into two levels, (normal and abnormal concentrations) of each analyte. Testing was performed in duplicate using 2 lots of reagent on the XL-200 Clinical Chemistry Analyzer. Nine levels of each interferent were tested for each analyte. The sponsor states that interference is considered to be non-significant if the bias between the tested and control samples are within $+/-10\%$ . The highest concentration tested that shows non-significant interference are summarized below: | Reagent | Hemoglobin | Lipemia | Bilirubin | Ascorbic Acid | | --- | --- | --- | --- | --- | | Glucose | 400 mg/dL | 412 mg/dL | 21.4 mg/dL | 10.0 mg/dL | | Sodium | * | 1084 mg/dL | 22.5 mg/dL | testing not performed | | Potassium | * | 1084 mg/dL | 22.5 mg/dL | testing not performed | | Chloride | * | 1084 mg/dL | 22.5 mg/dL | testing not performed | *Do not use hemolyzed samples The labeling for the ISE Reagent Pack includes the statement: Hemolyzed samples should not be used with sodium, potassium and chloride assays. The sponsor also references Young, D.S. et al, Clin. Chem 21: ID (1975) for drugs and substances that may affect the accuracy of these methods. # f. Assay cut-off: Not Applicable # 2. Comparison studies: # a. Method comparison with predicate device: Method comparison studies were performed following CLSI EP9-A2. Serum samples were run on the XL-200 Clinical Chemistry Analyzer and the results compared to the results run on the predicate device (Beckman Coulter Olympus {9} AU400 clinical chemistry analyzer). Less than 10% of the samples were spiked or diluted to fully span the claimed measuring range of each analyte. The Deming regression analysis results are summarized below. | Analyte | Slope | Intercept | R² | N | Concentration range tested | | --- | --- | --- | --- | --- | --- | | Glucose | 1.002 | 1.8 mg/dL | 0.9970 | 103 | 9 -500 mg/dL | | Sodium | 0.984 | 2.2 mmol/L | 0.9589 | 101 | 103 – 190 mmol/L | | Potassium | 0.999 | 0.05 mmol/L | 0.9954 | 90 | 1.1 – 10.0 mmol/L | | Chloride | 1.070 | -4.3 mmol/L | 0.9856 | 88 | 51 – 145 mmol/L | b. Matrix comparison: Not Applicable 3. Clinical studies: a. Clinical Sensitivity: Not Applicable b. Clinical specificity: Not Applicable c. Other clinical supportive data (when a. and b. are not applicable): Not Applicable 4. Clinical cut-off: Not Applicable 5. Expected values/Reference range: Glucose¹ 74 – 106 mg/dL Sodium¹ 136 - 145 mmol/L Potassium¹ 3.5 – 5.1 mmol/L Chloride¹ 98 – 107 mmol/L ¹Tietz, Textbook of Clinical Chemistry 3rd ed, Philadelphia, W.B. Saunders, (1999) {10} 11 N. Instrument Name: XL-200 Clinical Chemistry Analyzer O. System Descriptions: 1. Modes of Operation: Automated random access analyzer with optional ISE Module 2. Software: FDA has reviewed applicant’s Hazard Analysis and software development processes for this line of product types: Yes ☐ X or No ☐ 3. Specimen Identification: Barcode identification is available for specimen tubes and reagent bottles. Manual entry is used to identify specimen cups. 4. Specimen Sampling and Handling: Samples are manually placed on the instrument either by sample tube or sample cup. The system can run an individual sample or a batch of samples. Once the samples are tested they can be manually removed. 5. Calibration: Glucose calibration frequency should be 14 days or with a change of reagent lot or as indicated by quality control procedures. The recommended calibrator for glucose is the JAS multi-analyte Calibrator previously cleared in k020454. It is mandatory to perform calibration (two points) before ISE measurement at the beginning of the day or if the power switch of analyzer is turned off, eight hours have passed since the last ISE calibration, environmental temperature has changed more than 4 degree C since the last ISE calibration or more than 50 samples are processed after ISE calibration in the morning. The ISE calibrator material for sodium, potassium and chloride (Calibrant A and B) was previously cleared under k070057. 6. Quality Control: The analyzer has a built in quality control program. The labeling recommends the use of two external quality control materials to be assayed according to government guidelines. The two external quality control materials recommended for both glucose and ISE are the JAS Chemistry Controls previously cleared in k042318. {11} P. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. Q. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. 12