INSTRUCTIONS FOR USE

Transcription

1 VITROS Chemistry Products Slides Rx ONLY Intended Use For in vitro diagnostic use only. VITROS Chemistry Products Slides quantitatively measure lactate () concentration in plasma using VITROS 250/350/950/5,1 FS and 4600 Chemistry Systems and the VITROS 5600 Integrated System. Summary and Explanation of the Test is the end product of the anaerobic metabolism of glucose. The concentration of lactate in the blood is dependent on the rate of production in muscle cells and erythrocytes and the rate of metabolism in the liver. Lactic acidosis usually results from overproduction or underutilization of lactate. Elevated lactate levels can occur as a result of tissue hypoxia; diabetes mellitus; phenformin therapy; malignancies; glycogen storage disease; ethanol, methanol, or salicylate ingestion; and metabolic acidosis. 1 Principles of the Procedure The VITROS Slide method is performed using the VITROS Slides and the VITROS Chemistry Products Calibrator Kit 1 on VITROS 250/350/950/5,1 FS and 4600 Chemistry Systems and the VITROS 5600 Integrated System. The VITROS Slide is a multilayered, analytical element coated on a polyester support. A drop of patient sample is deposited on the slide and is evenly distributed by the spreading layer to the underlying layers. in the sample is oxidized by lactate oxidase to pyruvate and hydrogen peroxide. The hydrogen peroxide generated oxidizes the 4-aminoantipyrine, 1,7-dihydroxynaphthalene dye system in a horseradish peroxidase catalyzed reaction and results in a dye complex. The slide is incubated and the intensity of the dye complex is measured spectrophotometrically. Test Type and Conditions Test Type Colorimetric VITROS System 5600, 4600, 5,1 FS, 950, 250/350 Approximate Incubation Time Temperature Wavelength Reaction Sample Volume 5 minutes 37 C (98.6 F) 540 nm 10 µl Not all products and systems are available in all countries. Reaction Scheme L-(+)-lactic acid + O 2 lactate oxidase pyruvate + H 2 O 2 2H 2 O aminoantipyrine + 1,7- dihydroxynaphthalene peroxidase red dye Warnings and Precautions For in vitro diagnostic use only. WARNING: Take care when handling materials and samples of human origin. Since no test method can offer complete assurance that infectious agents are absent, consider all clinical specimens, controls, and calibrators potentially infectious. Handle specimens, solid and liquid waste, and test components in accordance with local Version 11.0 Pub. No. C-212_EN 1 of 11

2 INSTRUCTIONS FOR USE Reagents regulations and CLSI Guideline M29 2 or other published biohazard safety guidelines. For specific warnings and precautions for calibrators, quality control materials, and other components, refer to the Instructions for Use for the appropriate VITROS product, or to other manufacturer s product literature. Reagents Slide Diagram Slide Ingredients 1. Upper slide mount 2. Spreading layer (TiO 2 ) Reactive Ingredients per cm 2 oxidase(pediococcus sp.)0.3 U; peroxidase (horseradish root) 1.5 U; 1,7-dihydroxynapthalene (dye precursor) 43 µg; and 4-aminoantipyrine hydrochloride (dye precursor) 65 µg. Other Ingredients Pigment, binders, buffer, stabilizers, cross-linking agent, surfactants and enzyme cofactor. 3. Reagent layer lactate oxidase peroxidase dye precursors buffer, ph Support layer 5. Lower slide mount Reagent Handling Caution: Do not use slide cartridges with damaged or incompletely sealed packaging. Inspect the packaging for signs of damage. Be careful when opening the outer packaging with a sharp instrument so as to avoid damage to the individual product packaging. Reagent Preparation IMPORTANT: The slide cartridge must reach room temperature, C (64 82 F), before it is unwrapped and loaded into the slide supply. 1. Remove the slide cartridges from storage. 2. Warm the wrapped cartridge at room temperature for 60 minutes. 3. Unwrap and load the cartridge into the slide supply. Note: Load the cartridges within 24 hours after they reach room temperature, C (64 82 F). Reagent Storage and Stability VITROS Slides are stable until the expiration date on the carton when they are stored and handled as specified. Do not use beyond the expiration date. Reagent Storage Condition Stability Unopened Frozen -18 C ( 0 F) Until expiration date Opened On-analyzer System turned on 2 weeks On-analyzer System turned off 2 hours Verify performance with quality control materials: If the system is turned off for more than 2 hours. After reloading cartridges that have been removed from the slide supply and stored for later use. Specimen Collection, Preparation and Storage Specimens Recommended Plasma: 3 Fluoride oxalate Heparinized plasma is acceptable, but precautions must be taken to retard glycolysis by keeping the whole blood on ice. 4 IMPORTANT: Certain collection devices have been reported to affect other analytes and tests. 5 Owing to the variety of specimen collection devices available, Ortho-Clinical 2 of 11 Pub. No. C-212_EN Version 11.0

3 Testing Procedure Diagnostics is unable to provide a definitive statement on the performance of its products with these devices. Confirm that your collection devices are compatible with this test. Plasma Specimen Collection and Preparation Collect specimens using standard laboratory procedures. 6, 7 Venous specimens should be obtained without the use of a tourniquet or immediately after the tourniquet is applied. Alternatively, the tourniquet should be removed after the puncture has been performed, and the blood should be allowed to circulate for several minutes before the sample is withdrawn. 4 Note: For details on minimum fill volume requirements, refer to the operating instructions for your system. Patient Preparation The patient should avoid any exercise of the arm or hand before or during collection of the specimen. 4 Special Precautions For fluoride oxalate plasma, specimens must be collected in tubes that are at least half full. Smaller volumes can result in negative biases. Centrifuge specimens and remove the plasma from the cellular material within 15 minutes of collection. 3 Specimen Handling and Storage Handle and store specimens in stoppered containers to avoid contamination and evaporation. Mix samples by gentle inversion and bring to room temperature, C (64 82 F), prior to analysis. Specimen Storage and Stability for: Plasma 3 Storage Temperature Stability Room temperature C (64 82 F) 8 hours Refrigerated 2 8 C (36 46 F) 14 days Frozen -18 C ( 0 F) 1 month Testing Procedure Materials Provided VITROS Chemistry Products Slides Materials Required but Not Provided VITROS Chemistry Products Calibrator Kit 1 Quality control materials, such as VITROS Chemistry Products Performance Verifier I and II Isotonic saline Reagent-grade water VITROS Chemistry Products FS Diluent Pack 2 (BSA/Saline) or VITROS Chemistry Products FS Diluent Pack 3 (Specialty Diluent/Water) (for on-analyzer dilution) Operating Instructions Check reagent inventories at least daily to ensure that quantities are sufficient for the planned workload. For additional information, refer to the operating instructions for your system. IMPORTANT: Sample Dilution Bring all fluids and samples to room temperature, C (64 82 F), prior to analysis. Plasma If lactate concentrations exceed the system s measuring (reportable or dynamic) range: Version 11.0 Pub. No. C-212_EN 3 of 11

4 INSTRUCTIONS FOR USE Calibration Manual Sample Dilution 1. Dilute the sample with isotonic saline or reagent-grade water. 2. Reanalyze. 3. Multiply the results by the dilution factor to obtain an estimate of the original sample s lactate concentration. On-Analyzer Sample Dilution (VITROS Integrated, VITROS 5,1 FS/4600 and VITROS 250/350 only) Refer to the operating instructions for your system for more information on the On-Analyzer Dilution Procedure. For VITROS Integrated and VITROS 5,1 FS/4600 Chemistry Systems, use VITROS Chemistry Products FS Diluent Pack 2 or VITROS Chemistry Products FS Diluent Pack 3 for the dilution. Calibration Required Calibrators VITROS Chemistry Products Calibrator Kit 1 Calibrator Preparation, Handling, and Storage Refer to the Instructions for Use for VITROS Calibrator Kit 1. Calibration Procedure Refer to the operating instructions for your system. When to Calibrate Calibrate: When the slide lot number changes. When critical system parts are replaced due to service or maintenance. When government regulations require. For example, in the USA, CLIA regulations require calibration or calibration verification at least once every six months. The VITROS test may also need to be calibrated: If quality control results are consistently outside acceptable range. After certain service procedures have been performed. For additional information, refer to the operating instructions for your system. Calculations Reflectance from the slide is measured at 540 nm after the fixed incubation time. Once a calibration has been performed for each slide lot, lactate concentration in unknown samples can be determined using the software-resident endpoint colorimetric math model and the response obtained from each unknown test slide. Validity of a Calibration Calibration parameters are automatically assessed by the system against a set of quality parameters detailed in the Coefficients and Limits screen on VITROS 250/350/950 Systems (on the VITROS Integrated and VITROS 5,1 FS/4600 Systems, see the Review Assay Data screen). Failure to meet any of the pre-defined quality parameters results in a failed calibration. The calibration report should be used in conjunction with quality control results to determine the validity of a calibration. Measuring (Reportable or Dynamic) Range Alternate Units (mg/dl) For out-of-range samples, refer to Sample Dilution. Traceability of Calibration Values assigned to the VITROS Chemistry Products Calibrator Kit 1 for lactate are traceable to gravimetrically prepared standards using USP (U.S. Pharmacopeia) certified sodium lactate. 8 The Ortho-Clinical Diagnostics calibration laboratory uses the gravimetrically prepared standard to calibrate an HPLC method for lactate 9 to support value assignment for VITROS Calibrator Kit 1. 4 of 11 Pub. No. C-212_EN Version 11.0

5 Quality Control Quality Control Quality Control Material Selection IMPORTANT: VITROS Performance Verifiers are recommended for use with the VITROS Chemistry and Integrated Systems. Evaluate the performance of other commercial control fluids for compatibility with this test before using for quality control. Control materials other than VITROS Performance Verifiers may show a difference when compared with other lactate methods if they: Depart from a true human matrix. Contain high concentrations of preservatives, stabilizers, or other nonphysiological additives. Do not use control materials stabilized with ethylene glycol. Quality Control Procedure Recommendations Choose control levels that check the clinically relevant range. Analyze quality control materials in the same manner as patient samples, before or during patient sample processing. To verify system performance, analyze control materials: After calibration. According to local regulations or at least once each day that the test is being performed. After specified service procedures are performed. Refer to the operating instructions for your system. If control results fall outside your acceptable range, investigate the cause before deciding whether to report patient results. For general quality control recommendations, refer to Statistical Quality Control for Quantitative Measurements: Principles and Definitions; Approved Guideline Third Edition 10 or other published guidelines. For additional information, refer to the operating instructions for your system. Quality Control Material Preparation, Handling, and Storage Refer to the Instructions for Use for VITROS Chemistry Products Performance Verifier I and II or to other manufacturer's product literature. Results Reporting Units and Unit Conversion The VITROS Chemistry and Integrated Systems may be programmed to report results in conventional, SI, and alternate units. Alternate Units mmol/l mg/dl (mmol/l x 9.01) Limitations of the Procedure Known Interferences: Plasma The VITROS Chemistry Products Slide method was screened for interfering substances following NCCLS Protocol EP7. 18, 19 The substance listed in the table, when tested in plasma at the concentrations indicated, caused the bias shown. Interferent claims were cited whenever the maximum bias became equal to or exceeded the specificity requirement for. Materials exhibiting biases less than the specificity requirement have been cited as substances that do not interfere. Version 11.0 Pub. No. C-212_EN 5 of 11

6 INSTRUCTIONS FOR USE Expected Values Known Interferences: Lowest Interfering Concentration Levels Interferent * N-Acetylcysteine Interferent Concentration Concentration Average Bias ** Conv. and SI Alternate (mg/dl) Conv. and SI Alternate (mg/dl) 21.5 mg/dl (1.3 mmol/l) mg/dl (1.3 mmol/l) * It is possible that other interfering substances may be encountered. These results are representative; however, your results may differ somewhat due to test-to-test variation. The degree of interference at concentrations other than those listed might not be predictable. ** For each lactate concentration, the bias was determined using the maximum 95% confidence interval of the linear regression of the bias vs. the concentration of the interfering substance. Bias exceeding the specificity requirement (+/-0.24 mmol/l (+/ mg/dl) at lactate concentrations at or below 2.6 mmol/l (23.4 mg/dl) or +/-9.2% at lactate concentrations >2.6 mmol/l (23.4 mg/dl) is considered interference. Other Limitations Certain drugs and clinical conditions are known to alter lactate concentration in vivo. For additional information, refer to one of the published summaries. 12, 13 Expected Values Reference Interval This reference interval is based on an external study. 11 Alternate Units (mg/dl) Each laboratory should confirm the validity of these intervals for the population it serves. Performance Characteristics Method Comparison The plots and table show the results of a comparison of samples analyzed on the VITROS 750 System with those analyzed using the Ion Exchange Chromatography comparative method. 9 Testing followed NCCLS Protocol EP9. 14 The table also shows the results of comparisons of the VITROS 250 and 950 Systems with the VITROS 750 System, and comparisons of the 5,1 FS System with the 950 System. In addition, the table shows the results of comparisons with plasma samples on the VITROS 5600 Integrated System and the VITROS 5,1 FS Chemistry System. The testing followed NCCLS Protocol EP9. 15 Alternate Units VITROS 750 System VITROS 750 System (mg/dl) Comparative Method: Ion Exchange Chromatography Comparative Method: Ion Exchange Chromatography (mg/dl) 6 of 11 Pub. No. C-212_EN Version 11.0

7 Performance Characteristics 750 vs. comparative method n Slope Correlation Coefficient Range of Sample Conc. Intercept Sy.x Alternate Units (mg/dl) Range of Sample Conc. Intercept Sy.x vs vs ,1 FS vs vs. 5,1 FS Analytical processing hardware and software algorithms on the VITROS 4600 Chemistry System are designed to the same specifications as those applied to the VITROS 5,1 FS Chemistry System. Assay performance on the VITROS 4600 System has been demonstrated to be comparable to that on the VITROS 5,1 FS System. All performance characteristics for VITROS 5,1 FS System are therefore applicable to the VITROS 4600 System. Precision Precision was evaluated with quality control materials on VITROS 250, 750, 950, and 5,1 FS Systems following NCCLS Protocol EP5. 16 Precision was also evaluated with quality control materials on VITROS 5600 Integrated System following NCCLS protocol EP5. 17 The data presented are a representation of test performance and are provided as a guideline. Variables such as sample handling and storage, reagent handling and storage, laboratory environment, and system maintenance can affect reproducibility of test results Mean Conc. Within Day SD * Within Lab SD ** Mean Conc. Alternate Units (mg/dl) Within Day SD * Within Lab SD ** Within Lab CV% ** No. Observ. No. Days ,1 FS Specificity * Within Day precision was determined using two runs/day with two to three replications. ** Within Lab precision was determined using a single lot of slides and calibrating weekly. Analytical processing hardware and software algorithms on the VITROS 4600 Chemistry System are designed to the same specifications as those applied to the VITROS 5,1 FS Chemistry System. Assay performance on the VITROS 4600 System has been demonstrated to be comparable to that on the VITROS 5,1 FS System. All performance characteristics for VITROS 5,1 FS System are therefore applicable to the VITROS 4600 System. Substances that Do Not Interfere The substances listed in the table were tested with VITROS Slides at a lactate concentration of 2.6 mmol/l following NCCLS Protocol EP7 18, 19 and found not to interfere, bias <0.24 mmol/l, at the concentration shown. Version 11.0 Pub. No. C-212_EN 7 of 11

8 INSTRUCTIONS FOR USE References Compound Concentration Compound Concentration Acetoacetic acid 30 mg/dl 3 mmol/l D-Glyceraldehyde 300 mg/dl 33 mmol/l Acetone 30 mg/dl 5 mmol/l Glycerol 7 mg/dl 0.75 mmol/l Acetaminophen 5 mg/dl 331 µmol/l Hemoglobin 800 mg/dl 8 g/l Acetylsalicylic acid 30 mg/dl 2 mmol/l α-hydroxybutyrate 30 mg/dl 3 mmol/l p-aminosalicylic acid 23 mg/dl 2 mmol/l β-hydroxybutyrate 200 mg/dl 19 mmol/l Ascorbic acid 3 mg/dl 170 µmol/l Hypaque 500 mg/dl 8 mmol/l Bilirubin 20 mg/dl 342 µmol/l Intralipid 800 mg/dl 8 g/l Chlorothiazide 3 mg/dl 101 µmol/l Isoniazid 0.4 mg/dl 29 µmol/l Dextran 1000 mg/dl 250 µmol/l D- 135 mg/dl 15 mmol/l L-Dihydroxyacetone 30 mg/dl 3 mmol/l Meprobamate 2 mg/dl 92 µmol/l L-Dopa 0.6 mg/dl 30 µmol/l 6-Mercaptopurine 1.5 mg/dl 99 µmol/l Ethanol 300 mg/dl 65 mmol/l Pyruvate 5 mg/dl 574 µmol/l Galactose 60 mg/dl 3 mmol/l Salicylic acid 35 mg/dl 3 mmol/l Gentisic acid 60 mg/dl 4 mmol/l Sulfathiazole 6 mg/dl 235 µmol/l Glutathione 1 mg/dl 33 µmol/l Tyrosine 24 mg/dl 1 mmol/l References 1. Oliva PB. Am. J. Med. 48: ; CLSI. Protection of Laboratory Workers from Instrument Biohazards and Infectious Diseases Transmitted by Blood, Body Fluids and Tissue; Approved Guideline Fourth Edition; CLSI Document M29-A4, Wayne, PA: Clinical and Laboratory Standards Institute; Clinical Laboratory Handbook for Patient Preparation and Specimen Handling. Fascicle VI: Chemistry/Clinical Microscopy. Northfield, IL: College of American Pathologists; Tietz NW (ed). Fundamentals of Clinical Chemistry. ed. 5. Philadelphia: WB Saunders; 451; Calam RR. Specimen Processing Separator Gels: An Update. J Clin Immunoassay. 11:86 90; CLSI. Procedures for the Collection of Diagnostic Blood Specimens by Venipuncture; Approved Standard Sixth Edition. CLSI document H3-A5 [ISBN ]. CLSI, 940 West Valley Road, Suite 1400, Wayne, PA USA; NCCLS. Procedures and Devices for the Collection of Diagnostic Capillary Blood Specimens; Approved Standard Fifth Edition. NCCLS document H4-A5 [ISBN ]. CLSI, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania USA, Sodium, U.S. Pharmacopeia, CAT. No Smith JW, Ambrose RT. Determination of Lactic Acid in Human Serum by Ion Exchange Chromatography. Internal Eastman Kodak Company Report CLSI. Statistical Quality Control for Quantitative Measurements: Principles and Definitions; Approved Guideline Third Edition. CLSI document C24-A3 [ISBN ]. CLSI, 940 West Valley Road, Suite 1400, Wayne, PA USA; Solberg HE. A Guide to IFCC Recommendations on Reference Values. JIFCC; Volume 5, Issue 4: ; Young DS. Effects of Drugs on Clinical Laboratory Tests. ed. 4. Washington D.C.: AACC Press; Friedman RB, Young DS. Effects of Disease on Clinical Laboratory Tests. Washington, D.C.: AACC Press; NCCLS. Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline. NCCLS Document EP9. CLSI, 940 West Valley Road, Suite 1400, Wayne, PA USA; NCCLS. Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline. NCCLS Document EP9-2A [ISBN ]. CLSI, 940 West Valley Road, Suite 1400, Wayne, PA USA; NCCLS. User Evaluation of Precision Performance with Clinical Chemistry Devices. NCCLS Document EP5. CLSI, 940 West Valley Road, Suite 1400, Wayne, PA USA; NCCLS. Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline Second Edition. NCCLS document EP5-A2 [ISBN ]. CLSI, 940 West Valley Road, Suite 1400, Wayne, PA USA; NCCLS. Interference Testing In Clinical Chemistry; Proposed Guideline. NCCLS document EP7-P (ISBN ). NCCLS, 940 West Valley Road, Wayne, Pennsylvania , CLSI. Interference Testing in Clinical Chemistry; Approved Guideline Second Edition. CLSI Document EP7-A2. Wayne, PA: Clinical and Laboratory Standards Institute; of 11 Pub. No. C-212_EN Version 11.0

9 Glossary of Symbols Glossary of Symbols Revision History Date of Revision Version Description of Technical Changes* Known Interferences: Provided new data for N-Acetylcysteine Specificity: added new reference References: updated Reactive Ingredients: removed enzyme EC codes References: updated M29 Glossary of Symbols: added Globally Harmonized Symbols to comply with the Classification, Labelling and Packaging (CLP) Regulations Prescription Use statement added. Updated EC Representative address. Added USA to legal manufacture address Glossary of Symbols: added Date of Manufacture Glossary of Symbols: updated Added information for the VITROS 4600 Chemistry System. Version 11.0 Pub. No. C-212_EN 9 of 11

10 INSTRUCTIONS FOR USE Revision History Date of Revision Version Description of Technical Changes* Added information for the VITROS 5600 Integrated System Test Type and Conditions Added statement References Updated Glossary of Symbols Updated Minor wording and formatting changes Minor wording updates Traceability of the Calibration updated data References Updated M29, H3, H4, C24; added USP Cat. No Added VITROS 5,1 FS Chemistry System Precision updated data Specificity added Intralipid Glossary of Symbols updated data New organization and sections consistent with IVD Directive Specimen Collection and Preparation updated statement regarding use of a tourniquet when drawing the specimen Method comparison updated all data and plots Precision updated data for 750 System Specificity corrected value for glycerol References added 2, 4, 5, 6, 7, 10, 13, APR English New format, technically equivalent to 11/96. only * The change bars indicate the position of a technical amendment to the text with respect to the previous version of the document. When this Instructions For Use is replaced, sign and date below and retain as specified by local regulations or laboratory policies, as appropriate. Signature Obsolete Date 10 of 11 Pub. No. C-212_EN Version 11.0

11 Revision History Ortho-Clinical Diagnostics Felindre Meadows Pencoed Bridgend CF35 5PZ United Kingdom Ortho-Clinical Diagnostics, Inc. 100 Indigo Creek Drive Rochester, NY USA VITROS is a registered trademark of Ortho-Clinical Diagnostics, Inc. Ortho-Clinical Diagnostics, Inc., Version 11.0 Pub. No. C-212_EN 11 of 11