INSTRUCTIONS FOR USE

Transcription

1 VITROS Chemistry Products Slides Rx ONLY Intended Use For in vitro diagnostic use only. VITROS Slides quantitatively measure creatine kinase () activity 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 Creatine kinase, also referred to as creatine phosphokinase, is a cellular enzyme with a wide tissue distribution. is found mainly in skeletal and cardiac muscle. s physiological role is associated with ATP generation for contractile or transport systems. Serum is almost always increased following acute myocardial infarction or skeletal muscle damage. The enzyme is commonly elevated in myocarditis of any cause, cerebrovascular accidents, rhabdomyolysis, polymyositis, and acute physical exertion. is also increased in the muscular dystrophies; in Duchenne s muscular dystrophy, elevations of times normal are common. Low may reflect decreased muscle mass or muscle wasting. Reference values for must consider the age, gender, and physical activity of the person. Low serum activities are common in the elderly, in the bedridden, and in patients with advanced malignancy. 1 Principles of the Procedure The VITROS Slide method is performed using the VITROS Slides and the VITROS Chemistry Products Calibrator Kit 3 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. This layer also contains N-acetylcysteine (NAC) to activate without pretreating the sample. When the sample is deposited on the slide, creatine kinase catalyzes the conversion of creatine phosphate and ADP to creatine and ATP. In the presence of glycerol kinase (GK), glycerol is phosphorylated to L-α-glycerophosphate by ATP. Oxidation of L-α-glycerophosphate to dihydroxyacetone phosphate and hydrogen peroxide occurs in the presence of L α glycerophosphate oxidase (α-gpo). Finally, leuco dye is oxidized by hydrogen peroxide in the presence of peroxidase to form a dye. Reflection densities are monitored during incubation. The rate of change in reflection density is then converted to enzyme activity. Test Type and Conditions Test Type Multiple-point rate VITROS System 5600, 4600, 5,1 FS, 950, 250/350 Not all products and systems are available in all countries. Approximate Incubation Time Temperature Wavelength Reaction Sample Volume 5 minutes 37 C (98.6 F) 670 nm 11 µl Version 10.0 Pub. No. MP2-42_EN 1 of 11

2 INSTRUCTIONS FOR USE Warnings and Precautions Reaction Scheme creatine phosphate + ADP NAC, Mg +2 creatine + ATP glycerol + ATP GK L-α-glycerophosphate + ADP L-α-glycerophosphate + O 2 α-gpo dihydroxyacetone phosphate + H 2 O 2 H 2 O 2 + leuco dye peroxidase dye + 2H 2 O Warnings and Precautions For in vitro diagnostic use only. 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. Slide Diagram Slide Ingredients 1. Upper slide mount 2. Spreading layer (TiO 2 ): Reactive Ingredients per cm 2 L-alpha-glycerophosphate oxidase (Aerococcus sp.) 0.4 U; peroxidase (horseradish root) 1.4 U; glycerol kinase (E.coli) 0.5 U; creatine phosphate 170 µg; N acetylcysteine 54 µg; magnesium acetate 20 µg; glycerol 20 µg; 2-(3,5-dimethoxy-4- hydroxyphenyl)-4,5-bis-(4-dimethylaminophenyl) imidazole (leuco dye) 20 µg and adenosine diphosphate 20 µg. Other Ingredients Pigment, binder, buffers, surfactants, inhibitors, stabilizers, cross linking agent, dye solubilizer, scavenger and chelator. N-acetylcysteine 3. Reagent layer buffer, ph 7.0 adenosine diphosphate glycerol, magnesium acetate glycerol kinase, leuco dye peroxidase glycerophosphate oxidase creatine phosphate 4. Support layer 5. Lower slide mouont 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 30 minutes when taken from the refrigerator or 60 minutes from the freezer. 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). 2 of 11 Pub. No. MP2-42_EN Version 10.0

3 Reagent Storage and Stability 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 Refrigerated 2 8 C (36 46 F) 4 weeks Frozen -18 C ( 0 F) Until expiration date Opened On-analyzer System turned on 1 week 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 Plasma: 3 Heparin IMPORTANT: Certain collection devices have been reported to affect other analytes and tests. 4 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 grossly hemolyzed specimens. 5 Serum and Plasma Specimen Collection and Preparation Collect specimens using standard laboratory procedures. 6, 7 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 is unstable in serum. Centrifuge specimens and remove the serum or plasma from the cellular material within 4 hours of collection. 8 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 8 Storage Temperature Stability Room temperature C (64 82 F) 4 hours Refrigerated 2 8 C (36 46 F) 5 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 3 Version 10.0 Pub. No. MP2-42_EN 3 of 11

4 INSTRUCTIONS FOR USE Calibration Quality control materials, such as VITROS Chemistry Products Performance Verifier I and II or VITROS Chemistry Products Isoenzyme Performance Verifier I and II VITROS Chemistry Products 7% BSA VITROS Chemistry Products FS Diluent Pack 2 (BSA/Saline) (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 creatine kinase activity exceeds the system s measuring (reportable or dynamic) range: Manual Sample Dilution 1. Dilute the sample with VITROS 7% BSA. 2. Reanalyze. 3. Multiply the results by the dilution factor to obtain an estimate of the original sample s creatine kinase activity. Sample dilution results in higher creatine kinase activities than expected. 10 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 5,1 FS/4600 Chemistry Systems, use VITROS Chemistry Products FS Diluent Pack 2 for the dilution. Calibration Required Calibrators VITROS Chemistry Products Calibrator Kit 3 Calibrator Preparation, Handling, and Storage Refer to the Instructions for Use for VITROS Calibrator Kit 3. 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 Based on sequential readings of the slide s reflectance at 670 nm over the defined incubation period, a rate of change in reflectance is determined. This rate is used in the software-resident multi-point rate calibration model to compute enzyme activity. Once a calibration has been performed for each slide lot, creatine kinase activity in unknown samples can be determined from the rate of change in reflectance measured 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. 4 of 11 Pub. No. MP2-42_EN Version 10.0

5 Quality Control Measuring (Reportable or Dynamic) Range Conventional and SI Units Alternate Units (U/L) (μkat/l) For out-of-range samples, refer to Sample Dilution. Traceability of Calibration Values assigned to the VITROS Chemistry Products Calibrator Kit 3 for creatine kinase () are traceable to a modification of the Scandinavian Committee on Enzymes recommended method for the determination of creatine kinase at 37 C (98.6 F). 11, 12 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 creatine kinase 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 VITROS Chemistry Products Isoenzyme 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, or alternate units. Conventional and SI Units Alternate Units U/L µkat/l (U/L x ) Limitations of the Procedure Known Interferences The VITROS Slide method was screened for interfering substances following NCCLS Protocol EP7. 23, 24 Carbon dioxide at a level of 40 mmol/l may cause up to a 30% negative bias in creatine kinase. For substances that were tested and did not interfere, refer to Specificity. Version 10.0 Pub. No. MP2-42_EN 5 of 11

6 INSTRUCTIONS FOR USE Expected Values Other Limitations Certain drugs and clinical conditions are known to alter creatine kinase activity in vivo. For additional information, refer to one of the published summaries. 17, 18 Expected Values Reference Interval Reference Interval 13 Conventional and SI Units (U/L) Alternate Units (μkat/l) Females Males The upper limit of the reference interval is reported to be affected by population characteristics such as the degree of physical activity 14 and race. 15 Distributions of values from normal, healthy subjects often demonstrate a positive skew 16 which leads to variable upper reference limit estimates. 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 a modification of the comparative method recommended by the Scandinavian Committee on Enzymes 11, 12 at 37 C (98.6 F). Testing followed NCCLS Protocol EP9. 19 The tables also show the results of comparisons of serum samples on the VITROS 250 and 950 Systems and the VITROS 750 System, and comparisons of serum samples on the VITROS 5,1 FS System with the VITROS 950 System. In addition, the table shows the results of a comparison of serum and plasma samples on the VITROS 5600 Integrated System and the VITROS 5,1 FS Chemistry System. Testing followed NCCLS Protocol EP9. 20 Conventional and SI Units Alternate Units VITROS 750 System (U/L) VITROS 750 System (µkat/l) Comparative Method: Modification-Scandinavian Committee on Enzymes (U/L) Comparative Method: Modification-Scandinavian Committee on Enzymes (μkat/l) 6 of 11 Pub. No. MP2-42_EN Version 10.0

7 Performance Characteristics n Slope Correlation Coefficient Conventional and SI Units (U/L) Range of Sample Activity Intercept Sy.x Alternate Units (µkat/l) Range of Sample Activity 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. Precision Precision was evaluated with quality control materials on VITROS 250, 750, 950, and 5,1 FS Systems following NCCLS Protocol EP5. 21 Precision was evaluated with quality control materials on VITROS 5600 Integrated System following NCCLS protocol EP5. 22 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 and SI Units (U/L) Alternate Units (µkat/l) Within Mean Activity Within Day SD * Within Lab SD ** Mean Activity Within Day SD * Within Lab SD ** 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 Slides and found not to interfere, bias <38 U/L (0.63 µkat/l), for analyte activities 300 U/L or 12.8% activity>300 U/L, at the concentrations shown. Version 10.0 Pub. No. MP2-42_EN 7 of 11

8 INSTRUCTIONS FOR USE References Compound Concentration Compound Concentration Adenylate kinase 200 U/L 200 U/L Hemoglobin 150 mg/dl 1.5 g/l Ascorbic acid 3 mg/dl 170 µmol/l Intralipid 800 mg/dl 8 g/l Bilirubin 40 mg/dl 684 µmol/l Isoniazid 0.5 mg/dl 36 µmol/l Creatine 15 mg/dl 1 mmol/l L-dopa 0.6 mmol/l 0.6 mmol/l Ethanol 300 mg/dl 65 mmol/l 6-Mercaptopurine 1.5 mg/dl 99 µmol/l Gentisic acid 0.5 mg/dl 32 µmol/l N-Acetylcysteine mg/dl 10.2 mmol/l Glutathione 1 mg/dl 33 µmol/l Salicylic acid 35 mg/dl 3 mmol/l References 1. Tietz NW (ed). Fundamentals of Clinical Chemistry. ed. 3. Philadelphia: WB Saunders; ; 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; Doumas BT, et al. Differences Between Values for Plasma and Serum in Tests Performed in the Ektachem 700 XR Analyzer, and Evaluation of Plasma Separator Tubes (PST). Clin. Chem. 35:1: ; Calam RR. Specimen Processing Separator Gels: An Update. J Clin Immunoassay. 11:86-90; Tietz NW (ed). Fundamentals of Clinical Chemistry. ed. 3. Philadelphia: WB Saunders; ; CLSI. Procedures for the Collection of Diagnostic Blood Specimens by Venipuncture; Approved Standard Sixth Edition. NCCLS document H3-A6 (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, Clinical Laboratory Handbook for Patient Preparation and Specimen Handling. Fascicle VI: Chemistry/Clinical Microscopy. Northfield, IL: College of American Pathologists: 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; Tietz NW (ed). Textbook of Clinical Chemistry. ed. 3. Philadelphia: WB Saunders; 662; Scandinavian Committee on Enzymes: Recommended Method for the Determination of in Blood. Scand. J. Clin. Lab. Invest. 39:1-5; Scandinavian Committee on Enzymes: Recommended Method for the Determination of in Blood. Scand. J. Clin. Lab. Invest. 36: ; Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Philadelphia: WB Saunders; 2088; Krahn J. Upper Reference Limit for. Clin. Chem. 31(1):158; Black HR. Quallich H-D, and Garlect CB. Racial Difference in Serum Levels. Amer. J. Med. 81: ; Miller WG. Chinchilli HD, Nance WD. Sampling from a Skewed Population Distribution as Exemplified by Estimation of the Upper Reference Limit. Clin. Chem. 30(1): 18 23; 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; CLSI. Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline. CLSI 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-A2 [ISBN ]. CLSI, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania USA; CLSI. User Evaluation of Precision Performance with Clinical Chemistry Devices. CLSI 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. MP2-42_EN Version 10.0

9 Glossary of Symbols Glossary of Symbols Revision History Date of Revision Version Description of Technical Changes* Known Interferences: updated references Specificity: updated references and added N-acetylcysteine References: updated Reactive Ingredients: removed enzyme EC codes and updated enzyme source 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 10.0 Pub. No. MP2-42_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 Method Comparison Added information on sample types References Updated Glossary of Symbols Updated Minor wording and formatting changes Added VITROS 5,1 FS Chemistry System Specimen Requirements, Special Precautions wording update Quality Control updated reference Specificity added Intralipid, updated Bilirubin References updated data Glossary of Symbols updated data New organization and sections consistent with IVD Directive Sample Dilution added that dilution results in higher activities than expected Method comparison updated data for all comparisons Precision updated data for 750 System References added 3, 5, 9, and APR New format, technically equivalent to 11/96. * 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. MP2-42_EN Version 10.0

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 10.0 Pub. No. MP2-42_EN 11 of 11