INSTRUCTIONS FOR USE

Transcription

1 INSTRUCTIONS FOR USE VITROS Chemistry Products Fe Slides Fe Caution: Rx ONLY Intended Use For in vitro diagnostic use only. VITROS Chemistry Products Fe Slides quantitatively measure iron (Fe) concentration in serum and 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 Most body iron is found in hemoglobin. The serum measurement of iron is useful in the differential diagnosis of anemia, iron deficiency anemia, thalassemia, possible sideroblastic anemia, and iron poisoning. Serum iron is increased in hemosiderosis, hemolytic anemias, thalassemia, sideroblastic anemias, hepatitis, acute hepatic necrosis, hemochromatosis, inappropriate iron therapy, and iron poisoning. Serum iron is decreased in cases of insufficient dietary iron, chronic blood loss, inadequate absorption of iron, impaired release of iron stores (commonly observed in inflammation), infection, and chronic diseases. 1 Principles of the Procedure The VITROS Fe Slide method is performed using the VITROS Fe Slides and the VITROS Chemistry Products Calibrator Kit 4 on VITROS 250/350/950/5,1 FS and 4600 Chemistry Systems and the VITROS 5600 Integrated System. The VITROS Fe 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. (as ferric ion) is removed from transferrin at acidic ph and migrates to the reducing layer, where ascorbic acid reduces iron to the ferrous form. The ferrous ion then is bound to the dye and forms a colored complex in the reagent layer. Following addition of the sample, the slide is incubated and the reflection density measured after 1 and 5 minutes. The difference in reflection density is proportional to the iron concentration in the sample. Test Type and Conditions Test Type Two-point rate 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) 600 nm 10 µl Not all products and systems are available in all countries. Reaction Scheme transferrin - Fe +3 ph 4.0 transferrin + Fe +3 Fe +3 + ascorbic acid Fe +2 Fe +2 + dye Fe +2 dye (colored complex) Warnings and Precautions For in vitro diagnostic use only. Version 9.0 Pub. No. C-211A 1 of 10

2 Fe INSTRUCTIONS FOR USE Reagents 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 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 (BaSO 4 ) Reactive Ingredients per cm 2 Ascorbic acid 160 µg; and N-(4-(2,4-bis(1,1-dimethylpropyl) phenoxy)butyl)- 5-methoxy-6((2,3,6,7-tetrahydro-8-1H, 5Hbenzo-(ij)-quinolizin-9-yl)azo)- 3-pyridine sulfonamide (dye) 5 µg. Other Ingredients Binders, buffer, pigment, surfactants, stabilizer, chelator, dye solubilizer and cross-linking agent. 3. Reducing layer: ascorbic acid 4. Reagent layer buffer, ph 4.0 dye 5. Support layer 6. 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 Fe 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 4 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 Serum 2 of 10 Pub. No. C-211A Version 9.0

3 INSTRUCTIONS FOR USE Testing Procedure Fe Plasma: Heparin IMPORTANT: Certain collection devices have been reported to affect other analytes and tests. 3 Owing to the variety of specimen collection devices available, Ortho-Clinical 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. Specimens Not Recommended Do not use hemolyzed specimens because of the high concentration of iron in hemoglobin. 1 Serum and Plasma Specimen Collection and Preparation Collect specimens using standard laboratory procedures. 4, 5 Note: For details on minimum fill volume requirements, refer to the operating instructions for your system. Patient Preparation No special patient preparation is necessary. Special Precautions Centrifuge specimens and remove the serum or plasma from the cellular material within 4 hours of collection. 6 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 6 Storage Temperature Stability Room temperature C (64 82 F) 4 days Refrigerated 2 8 C (36 46 F) 7 days Frozen -18 C ( 0 F) 3 months Testing Procedure Materials Provided VITROS Chemistry Products Fe Slides Materials Required but Not Provided VITROS Chemistry Products Calibrator Kit 4 Quality control materials, such as VITROS Chemistry Products Performance Verifier I and II -free reagent-grade water 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. Serum and Plasma If iron concentrations exceed the system s measuring (reportable or dynamic) range: Version 9.0 Pub. No. C-211A 3 of 10

4 Fe INSTRUCTIONS FOR USE Calibration Manual Sample Dilution 1. Dilute the sample with iron-free reagent-grade water. 2. Reanalyze. 3. Multiply the results by the dilution factor to obtain an estimate of the original sample s iron concentration. On-Analyzer Sample Dilution (VITROS Integrated, VITROS 5,1 FS/4600 and VITROS 250/350 Systems 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 3 for the dilution. Calibration Required Calibrators VITROS Chemistry Products Calibrator Kit 4 Calibrator Preparation, Handling, and Storage Refer to the Instructions for Use for VITROS Calibrator Kit 4. 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 Fe 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 read at 600 nm at two fixed time points during the incubation period, and the change in reflectance between these two readings is calculated. Once a calibration has been performed for each slide lot, the iron concentration in unknown samples can be determined using the software-resident two-point rate math model and the change in reflectance calculated for 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 Conventional Units SI Units Alternate Units (μg/dl) (μmol/l) (mg/l) For out-of-range samples, refer to Sample Dilution. Traceability of Calibration Values assigned to the VITROS Chemistry Products Calibrator Kit 4 for iron are traceable to the Certified NIST (National Institute of Standards and Technology) Reference Material, SRM (Standard Reference Material) 937. The Ortho-Clinical Diagnostics (OCD) calibration laboratory uses SRM 937 to calibrate the proposed NCCLS standard iron method, 7 modified according to the International Committee for Standardization in Hematology (ICSH) recommendation to use ferene dye, 8 to support iron value assignment for VITROS Calibrator Kit 4. 4 of 10 Pub. No. C-211A Version 9.0

5 INSTRUCTIONS FOR USE Quality Control Fe 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 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 9 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 Fe results in conventional, SI, and alternate units. Conventional Units SI Units Alternate Units µg/dl µmol/l (µg/dl x ) mg/l (µg/dl x 0.01) Limitations of the Procedure Known Interferences The VITROS Fe Slide method was screened for interfering substances following NCCLS Protocol EP7. 10 The substances listed in the table, when tested at the concentrations indicated, caused the bias shown. Desferal (Deferoxamine Mesylate) at a concentration of 250 mg/dl and higher results in iron concentrations below the system range. Imferon ( Dextran) produces a positive iron bias of 5 µg/dl for each 100 µg/dl of Imferon. For substances that were tested and did not interfere, refer to Specificity. Other Limitations Certain drugs and clinical conditions are known to alter concentration in vivo. For additional information, refer to one of the published summaries. 11, 12 Version 9.0 Pub. No. C-211A 5 of 10

6 Fe INSTRUCTIONS FOR USE Expected Values Expected Values Reference Interval This reference interval is the central 95% of results from an internal study of 529 apparently healthy adults from a working population (382 females and 147 males). Conventional Units (μg/dl) SI Units (μmol/l) Alternate Units (mg/l) Females Males 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 serum samples analyzed on the VITROS 750 System with those analyzed using the NCCLS/ICSH Ferene comparative method. 7, 8 Testing followed NCCLS Protocol EP9. 13 The table also shows the results of comparisons with serum samples on the VITROS 250 and 950 Systems with the VITROS 750 System, and comparisons with serum samples on the VITROS 5,1 FS System with the VITROS 950 System. In addition, the table shows the results of comparisons with serum and plasma samples on the VITROS 5600 Integrated System with the VITROS 5,1 FS Chemistry System. The testing followed NCCLS Protocol EP9. 14 Conventional Units SI Units VITROS 750 System (µg/dl) VITROS 750 System (µmol/l) Comparative Method: NCCLS/ICSH Ferene (μg/dl) Comparative Method: NCCLS/ICSH Ferene (μmol/l) n Slope Correlation Coefficient Conventional Units (µg/dl) Range of Sample Conc. Intercept Sy.x SI Units (µmol/l) Range of Sample Conc. Intercept Sy.x 750 vs. comparative method 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. 6 of 10 Pub. No. C-211A Version 9.0

7 INSTRUCTIONS FOR USE References Fe Precision Precision was evaluated with quality control materials on VITROS 250, 750, 950, and 5,1 FS Systems following NCCLS Protocol EP5. 15 Precision was also evaluated with quality control materials on the VITROS 5600 Integrated System following NCCLS Protocol EP5. 16 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. Conventional Units (µg/dl) Mean Conc. Within Day SD * Within Lab SD ** Mean Conc. SI Units (µmol/l) Within Day SD * Within Lab SD ** Within Lab CV% ** No. Observ ,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. No. Days 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 Fe Slides at an iron concentration of 40 µg/dl (7 µmol/l) following NCCLS Protocol EP7 10 and found not to interfere, bias <2.6 µg/dl (<0.5 µmol/l), at the concentration shown. Compound Concentration Compound Concentration Acetoacetic acid 30 mg/dl 3 mmol/l Isoniazid 0.4 mg/dl 29 µmol/l Acetaminophen 5 mg/dl 331 µmol/l Isosorbide 16 mg/dl 1 mmol/l Barium 80 µg/dl 6 µmol/l Lidocaine 6 mg/dl 256 µmol/l Bilirubin 27 mg/dl 462 µmol/l Magnesium 15 mg/dl 6 mmol/l Caffeine 10 mg/dl 515 µmol/l Methicillin 20 mg/dl 497 µmol/l Cefotaxime 90 mg/dl 2.0 mmol/l Nickel 2.5 µg/dl 426 nmol/l Cephalexin 32 mg/dl 921 µmol/l Ranitidine 20 mg/dl 638 µmol/l Copper 300 µg/dl 47 µmol/l Salicylic acid 35 mg/dl 3 mmol/l Folic acid 17 mg/dl 385 µmol/l Sulfasalazine 20 mg/dl 502 µmol/l Furosemide 2 mg/dl 60 µmol/l Tolbutamide 22 mg/dl 814 µmol/l Gentisic acid 0.5 mg/dl 32 µmol/l Total protein 4 g/dl 40 g/l Hypaque 500 mg/dl 8 mmol/l Total protein 10 g/dl 100 g/l Ibuprofen 40 mg/dl 2 mmol/l Zinc 260 µg/dl 40 µmol/l Intralipid 800 mg/dl 8 g/l References 1. Tietz NW (ed). Fundamentals of Clinical Chemistry. ed. 3. Philadelphia: WB Saunders; ; CLSI. Protection of Laboratory Workers from Occupationally Acquired Infections; Approved Guideline Third Edition. CLSI document M29-A3 [ISBN ]. CLSI, 940 West Valley Road, Suite 1400, Wayne, PA USA; Calam RR. Specimen Processing Separator Gels: An Update. J Clin Immunoassay. 11:86 90; Version 9.0 Pub. No. C-211A 7 of 10

8 Fe INSTRUCTIONS FOR USE Glossary of Symbols 4. CLSI. Procedures for the Collection of Diagnostic Blood Specimens by Venipuncture; Approved Standard-Sixth Edition. CLSI document H3-A6 (ISBN ). CLSI, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania 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, PA USA; Clinical Laboratory Handbook for Patient Preparation and Specimen Handling. Fascicle VI: Chemistry/Clinical Microscopy. Northfield, IL: College of American Pathologists; NCCLS. The Determination of Serum and Total iron binding-capacity; Proposed Standard. NCCLS Document H17- P. CLSI, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania USA; Panel of the International Committee for Standardization in Haematology. Revised Recommendations for the Measurements of Serum In Human Blood. Br J Haematology. 75: ; 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; NCCLS. Interference Testing in Clinical Chemistry. NCCLS Document EP7. CLSI, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania USA; 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, Pennsylvania USA; NCCLS. Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline- Second Edition. NCCLS document EP9-A2 [ISBN ]. CLSI, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania USA; NCCLS. User Evaluation of Precision Performance with Clinical Chemistry Devices. NCCLS Document EP5. CLSI, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania 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, Pennsylvania USA; Glossary of Symbols 8 of 10 Pub. No. C-211A Version 9.0

9 INSTRUCTIONS FOR USE Revision History Fe Revision History Date of Revision Version Description of Technical Changes* Updated EC Representative address. Added USA to legal manufacture address Prescription Use Statement added Glossary of Symbols: added Date of Manufacture Glossary of Symbols: updated Added information for the VITROS 4600 Chemistry System Added information for the VITROS 5600 Integrated System Test Type and Conditions Added statement Measuring (Reportable or Dynamic) Range Updated Method Comparison Added information on sample types; updated data References Updated Glossary of Symbols Updated Minor wording and formatting changes Limitations of the Procedure corrected spelling: added ( Dextran) Added VITROS 5,1 FS Chemistry System Principles of the Procedure wording update Specificity added Intralipid; updated Bilirubin Glossary of Symbols updated data New organization and sections consistent with IVD Directive Known Interferences removed statement regarding cupramine; updated bias value for imferon Method Comparison updated data for all comparisons and the plots Precision updated data for the 750 System; updated within lab data for the 950 System Specificity updated concentration for cefotaxime References added 2, 3, 10, 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 Version 9.0 Pub. No. C-211A 9 of 10

10 Fe INSTRUCTIONS FOR USE 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., of 10 Pub. No. C-211A Version 9.0