Total Protein 7D73-20 30-3953/R5

TOTAL PROTEIN 7D73-20 30-3953/R5

TOTAL PROTEIN

This package insert contains information to run the Total Protein assay on the ARCHITECT c Systems™ and the AEROSET System.

NOTE: Changes Highlighted

NOTE: This package insert must be read carefully prior to product use. Package insert instructions must be followed accordingly. Reliability of assay results cannot be guaranteed if there are any deviations from the instructions in this package insert.

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Symbols in Product Labeling

Calibrators 1 and 2 Catalog number/List number

Concentration Serial number Authorized Representative in the Consult instructions for use European Community Ingredients Manufacturer

In vitro diagnostic medical device Temperature limitation

Batch code/Lot number Use by/Expiration date

Reagent 1

1 NAME WARNINGS AND PRECAUTIONS TOTAL PROTEIN Precautions for Users INTENDED USE 1. For in vitro diagnostic use. 2. Do not use components beyond the expiration date. The Total Protein assay is used for the quantitation of total protein in human serum or plasma. 3. Do not mix materials from different kit lot numbers. 4. CAUTION: This product requires the handling of human specimens. SUMMARY AND EXPLANATION OF TEST It is recommended that all human sourced materials be considered potentially infectious and handled in accordance with the OSHA Plasma proteins derive primarily from synthesis in the liver, plasma Standard on Bloodborne Pathogens1. Biosafety Level 22 or other cells, lymph nodes, spleen, and bone marrow. In disease states both appropriate biosafety practices3,4 should be used for materials that the total plasma protein level and the ratio of the individual fractions contain or are suspected of containing infectious agents. may be dramatically altered from their normal values. Hypoproteinemia may be caused by such conditions as nephrotic syndrome, extensive 5. contains sodium hydroxide and copper sulfate and is classified bleeding, sprue (deficient protein absorption), severe burns, salt per applicable European Community (EC) Directives as: Irritant (Xi). retention syndromes, and Kwashiorkor (acute protein starvation). The following are the appropriate Risk (R) and Safety (S) phrases: Hyperproteinemia may be observed in cases of severe dehydration and R38 Irritating to skin. disease states such as multiple myeloma. Changes in the proportions of R41 Risk of severe damage to eyes. the plasma proteins may occur in one or several of the protein fractions R52/53 Harmful to aquatic organisms, may cause and often without alterations in the quantity of the total protein. The A/G long-term adverse effects in the aquatic ratio has commonly been used as an index of the distribution between environment. the albumin and globulin fractions. This ratio can be significantly altered S26 In case of contact with eyes, rinse immediately in such conditions as cirrhosis of the liver, glomerulonephritis, nephrotic with plenty of water and seek medical advice syndrome, acute hepatitis, lupus erythematosis, and in some acute and immediately. chronic infections. S35 This material and its container must be disposed of in a safe way. PRINCIPLES OF PROCEDURE S36/37/39 Wear suitable protective clothing, gloves, and Polypeptides containing at least two peptide bonds react with biuret eye/face protection. reagent. In alkaline solution, cupric ion forms a coordination complex S46 If swallowed, seek medical advice immediately with protein nitrogen with very little difference between albumin and and show this container or label. globulin on a protein-nitrogen basis. S61 Avoid release in the environment. Refer to Methodology: Biuret special instructions/safety data sheet. REAGENTS SPECIMEN COLLECTION AND HANDLING Reagent Kit Suitable Specimens 7D73 Total Protein is supplied as a liquid, ready-to-use, single Serum and plasma are acceptable specimens. reagent kit which contains: • Serum: Use serum collected by standard venipuncture techniques 10 x 84 mL into glass or plastic tubes with or without gel barriers. Ensure complete clot formation has taken place prior to centrifugation. Estimated tests per kit: 3,622 Separate serum from red blood cells or gel as soon after collection Calculation is based on the minimum reagent fill volume per kit. as possible. Some specimens, especially those from patients receiving Reactive Ingredients Concentration anticoagulant or thrombolytic therapy, may take longer to complete Sodium Potassium Tartrate 23.4 mmol/L their clotting processes. Fibrin clots may subsequently form in these sera and the clots could cause erroneous test results. Sodium Hydroxide 613 mmol/L • Plasma: Use plasma collected by standard venipuncture techniques Potassium Iodide 6.6 mmol/L into glass or plastic tubes. Acceptable anticoagulants are lithium heparin (with or without gel barrier) and sodium heparin. Ensure Copper Sulfate 13.2 mmol/L centrifugation is adequate to remove platelets. Separate plasma from red blood cells or gel as soon after collection as possible. REAGENT HANDLING AND STORAGE Refer to the specimen collection tube manufacturer’s instructions for Reagent Handling processing and handling requirements. Remove air bubbles, if present in the reagent cartridge, with a new For total sample volume requirements, refer to the instrument-specific applicator stick. Alternatively, allow the reagent to sit at the appropriate ASSAY PARAMETERS section of this package insert and Section 5 of storage temperature to allow the bubbles to dissipate. To minimize the instrument-specific operations manual. volume depletion, do not use a transfer pipette to remove the bubbles. CAUTION: Reagent bubbles may interfere with proper detection of Specimen Storage reagent level in the cartridge, causing insufficient reagent aspiration Serum and plasma: Total protein is stable in serum and plasma for which could impact results. 1 week at room temperature, for at least 1 month when refrigerated, and for up to 2 months at -20°C.5 Reagent Storage An in-house study confirmed total protein is stable in serum for 34 days Unopened reagents are stable until the expiration date when stored at 2 to 8°C. at 15 to 30°C. NOTE: Stored specimens must be inspected for particulates. If present, Reagent stability is 23 days if the reagent is uncapped and onboard. mix and centrifuge the specimen to remove particulates prior to testing. PROCEDURE Materials Provided 7D73 Total Protein Reagent Kit Materials Required but not Provided • 1E65 Multiconstituent Calibrator, 3 x 5 mL • Control Material • Saline (0.85% to 0.90% NaCl) for specimens that require dilution Assay Procedure For a detailed description of how to run an assay, refer to Section 5 of the instrument-specific operations manual.

2 PROCEDURE (Continued) EXPECTED VALUES Specimen Dilution Procedures Reference Range The ARCHITECT c Systems and the AEROSET System have automatic Serum6 dilution features; refer to Section 2 of the instrument-specific operations manual for additional information. Range (g/dL) Range (g/L) Serum and plasma: Specimens with total protein values exceeding Premature 3.6 to 6.0 36 to 60 18.4 g/dL (184 g/L) are flagged and may be diluted using the Automated Dilution Protocol or the Manual Dilution Procedure. Newborn 4.6 to 7.0 46 to 70 Automated Dilution Protocol Cord 4.8 to 8.0 48 to 80 If using the Automated Dilution Protocol, the system performs a dilution 1 week 4.4 to 7.6 44 to 76 of the specimen and automatically corrects the concentration by 7 months to 1 year 5.1 to 7.3 51 to 73 multiplying the result by the appropriate dilution factor. To set up the automatic dilution feature, refer to Section 2 of the instrument-specific 1 to 2 years 5.6 to 7.5 56 to 75 operations manual for additional information. ≥ 3 years 6.0 to 8.0 60 to 80 Manual Dilution Procedure Adult, Ambulatory 6.4 to 8.3 64 to 83 Manual dilutions should be performed as follows: Adult, Recumbent 6.0 to 7.8 60 to 78 • Use saline (0.85% to 0.90% NaCl) to dilute the sample. > 60 years lower by ~ 0.2 lower by ~ 2 • The operator must enter the dilution factor in the patient or control order screen. The system uses this dilution factor to automatically To convert results from g/dL to g/L, multiply g/dL by 10. correct the concentration by multiplying the result by the entered factor. Plasma • If the operator does not enter the dilution factor, the result must Plasma values are generally 0.3 to 0.5 g/dL higher than serum values be multiplied by the appropriate dilution factor before reporting the due to the presence of fibrinogen.7 This difference has been shown to result. vary among specific populations.8 NOTE: If a diluted sample result is flagged indicating it is less than the It is recommended that each laboratory determine its own reference linear low limit, do not report the result. Rerun using an appropriate range based upon its particular locale and population characteristics. dilution. For detailed information on ordering dilutions, refer to Section 5 of the SPECIFIC PERFORMANCE CHARACTERISTICS instrument-specific operations manual. Linearity CALIBRATION Total Protein is linear up to 18.4 g/dL (184 g/L). Linearity was verified using Clinical and Laboratory Standards Institute (CLSI) protocol Calibration is stable for approximately 23 days (552 hours) and is NCCLS EP6-P.9 required with each change in reagent lot number. Verify calibration with at least two levels of controls according to the established quality control Limit of Detection (LOD) requirements for your laboratory. If control results fall outside acceptable The LOD for Total Protein is 0.5 g/dL (5.0 g/L). The LOD is the mean ranges, recalibration may be necessary. concentration of an analyte-free sample + 2 SD, where SD = the For a detailed description of how to calibrate an assay, refer to Section 6 pooled, within-run standard deviation of the analyte-free sample. of the instrument-specific operations manual. A study performed on an ARCHITECT c System and an AEROSET For information on calibrator standardization, refer to the Multiconstituent System produced an LOD for Total Protein of 0.07 g/dL (0.7 g/L). Calibrator package insert. Limit of Quantitation (LOQ) The LOQ for Total Protein is 0.76 g/dL (7.6 g/L). The LOQ is the analyte QUALITY CONTROL concentration at which the CV = 20%. The following is the recommendation of Abbott Laboratories for quality control. As appropriate, refer to your laboratory standard operating Interfering Substances10 procedure(s) and/or quality assurance plan for additional quality control Interference studies were conducted using CLSI protocol NCCLS requirements and potential corrective actions. EP7-P.11 Interference effects were assessed by Dose Response and • Two levels of controls (normal and abnormal) are to be run every Paired Difference methods, at the medical decision level of the analyte. 24 hours. Interfering Interferent Concentration N Target Observed • If more frequent control monitoring is required, follow the established Substance quality control procedures for your laboratory. (g/dL) (% of Target) • If quality control results do not meet the acceptance criteria 30 mg/dL (513 μmol/L) 3 6.6 96.2 Bilirubin defined by your laboratory, patient values may be suspect. Follow 60 mg/dL (1,026 μmol/L) 3 6.6 93.4 the established quality control procedures for your laboratory. Recalibration may be necessary. 125 mg/dL (1.25 g/L) 3 5.2 106.2 Hemoglobin • Review quality control results and acceptance criteria following a 250 mg/dL (2.50 g/L) 3 5.2 112.1 change of reagent or calibrator lot. Human 750 mg/dL (8.5 mmol/L) 4 8.9 100.2 RESULTS triglyceride 1,000 mg/dL (11.3 mmol/L) 4 8.9 99.5 Refer to the instrument-specific operations manual for information on results calculations. Bilirubin solutions at the above concentrations were prepared by addition of a bilirubin stock to human serum pools. Hemoglobin solutions at the • ARCHITECT System Operations Manual—Appendix C above concentrations were prepared by addition of hemolysate to human • AEROSET System Operations Manual—Appendix A serum pools. Human triglyceride solutions at the above concentrations Representative performance data are given in the EXPECTED VALUES were prepared by mixing a high triglyceride level human serum pool with and SPECIFIC PERFORMANCE CHARACTERISTICS sections of this a normal triglyceride level human serum pool. package insert. Results obtained in individual laboratories may vary. LIMITATIONS OF THE PROCEDURE Refer to the SPECIMEN COLLECTION AND HANDLING and SPECIFIC PERFORMANCE CHARACTERISTICS sections of this package insert.

3 SPECIFIC PERFORMANCE CHARACTERISTICS BIBLIOGRAPHY (Continued) 1. US Department of Labor, Occupational Safety and Health Administration. 29 CFR Part 1910.1030, Occupational Exposure to Precision Bloodborne Pathogens. The imprecision of the Total Protein assay is ≤ 3% Total CV. 2. US Department of Health and Human Services. Biosafety in Representative data from studies using CLSI protocol NCCLS EP5-A12 Microbiological and Biomedical Laboratories. HHS Publication are summarized below. (CDC), 4th ed. Washington, DC: US Government Printing Office, May 1999. Control Level 1 Level 2 3. World Health Organization. Laboratory Biosafety Manual. Geneva: N8080World Health Organization, 2004. Mean (g/dL) 6.5 4.1 4. Sewell DL, Bove KE, Callihan DR, et al. Protection of Laboratory Workers from Occupationally Acquired Infections; Approved SD 0.01 0.01 Guideline—Third Edition (M29-A3). Wayne, PA: Clinical and Within Run %CV 0.2 0.4 Laboratory Standards Institute, 2005. 5. Kaplan LA, Pesce AJ, editors. Clinical Chemistry Theory, Analysis, SD 0.03 0.02 Between Run and Correlation, 2nd ed. St. Louis, MO: CV Mosby; 1989:1059. %CV 0.4 0.4 6. Burtis CA, Ashwood ER, editors. Tietz Textbook of Clinical SD 0.09 0.08 Chemistry, 2nd ed. Philadelphia, PA: WB Saunders; 1994:2204–5. Between Day 7. Dawnay AB, Hirst AD, Perry DE, et al. A critical assessment of %CV 1.4 1.8 current analytical methods for the routine assay of serum total SD 0.09 0.08 protein and recommendations for their improvement. Ann Clin Total Biochem 1991;28:556–67. %CV 1.4 1.9 8. Bakker AJ, Gorgels J, Draaisma J, et al. Simple method for correcting total protein in plasma for actual fibrinogen content. Clin Method Comparison Chem 1992;38(11):2221–3. Correlation studies were performed using CLSI protocol NCCLS 13 9. Passey RB, Bee DE, Caffo A, et al. Evaluation of the Linearity EP9-A. of Quantitative Analytical Methods; Proposed Guideline (EP6-P). Serum results from the Total Protein assay on the AEROSET System Villanova, PA: The National Committee for Clinical Laboratory were compared with those from a commercially available biuret reaction Standards, 1986. methodology. 10. Young DS. Effects of Drugs on Clinical Laboratory Tests, 4th ed. Serum results from the Total Protein assay on an ARCHITECT Washington, DC: AACC Press; 1995:3-500–3-506. c System were compared with those from the Total Protein assay on 11. Powers DM, Boyd JC, Glick MR, et al. Interference Testing in an AEROSET System. Clinical Chemistry; Proposed Guideline (EP7-P). Villanova, PA: The AEROSET vs. ARCHITECT National Committee for Clinical Laboratory Standards, 1986. Comparative Method vs. AEROSET 12. Kennedy JW, Carey RN, Coolen RB, et al. Evaluation of Precision Performance of Clinical Chemistry Devices; Approved Guideline N 80 100 (EP5-A). Wayne, PA: The National Committee for Clinical Y - Intercept 0.167 0.000 Laboratory Standards, 1999. 13. Kennedy JW, Carey RN, Coolen RB, et al. Method Comparison and Correlation Coefficient 0.984 1.000 Bias Estimation Using Patient Samples; Approved Guideline (EP9-A). Slope 1.020 0.989 Wayne, PA: The National Committee for Clinical Laboratory Range (g/dL)* 2.20 to 11.46 1.94 to 16.77 Standards, 1995. *AEROSET range TRADEMARKS AEROSET and ARCHITECT are registered trademarks of Abbott Laboratories. c System is a trademark of Abbott Laboratories. All other trademarks, brands, product names, and trade names are the property of their respective companies.

4 ARCHITECT c SYSTEMS ASSAY PARAMETERS

Total Protein Serum/Plasma—Conventional and SI Units Configure assay parameters — General Configure assay parameters — SmartWash ● General о Calibration о SmartWash о Results о Interpretation о General о Calibration ● SmartWash о Results о Interpretation Assay: TP Type: Photometric Version: 1 Assay: TP Number: 1014 COMPONENT REAGENT / ASSAY WASH Volume Replicates ● Reaction definition о Reagent / Sample о Validity checks Cuvette Trig 10% Detergent B*** 345 Reaction mode: End up Primary Secondary Read times *** Select “Detergent B” for software prior to version 2.2. Wavelength: 572 / 660 Main: 14 – 16 Last required read: 16 Total Protein Serum/Plasma—Conventional Units Absorbance range: ___ – ___ Color correction: ___ – ___ Sample blank type: None Configure assay parameters — Results о General о Calibration о SmartWash ● Results о Interpretation о Reaction definition ● Reagent / Sample о Validity checks Assay: TP Result units: g/dL R1 Assay defaults: Reagent: TP000 Reagent volume: 200 Low-Linearity: 0.8† Diluent: Saline Water volume: ___ High-Linearity: 18.4 Diluent dispense mode: Type 0 Dispense mode: Type 0 Gender and age specific ranges: Diluted Default GENDER AGE (UNITS) NORMAL EXTREME Dilution name Sample sample Diluent Water Dilution factor dilution Either 0 – 130 (Y) 6.4 – 8.3 STANDARD : 4.0 ______= 1:1.00 ● ______: ______= о ______: ______= о Configure result units Assay: TP о Reaction definition о Reagent / Sample ● Validity checks Version: 1 Reaction check: None Result units: g/dL Maximum absorbance variation: ___ Decimal places: 1 [Range 0 – 4] Correlation factor: 1.0000 Intercept: 0.0000 Configure assay parameters — Calibration о General ● Calibration о SmartWash о Results о Interpretation Assay: TP Calibration method: Linear Total Protein Serum/Plasma—SI Units Configure assay parameters — Results ● Calibrators о Volumes о Intervals о Validity checks Calibrator set: Calibrator level: Concentration: о General о Calibration о SmartWash ● Results о Interpretation MCC Blank: Water 0†† Assay: TP Result units: g/L Cal 1: MCC1 ‡ Assay defaults: Replicates: 3 [Range 1 – 3] Cal 2: MCC2 ‡ Low-Linearity: 8† High-Linearity: 184 Gender and age specific ranges: Calibrators Volumes Intervals Validity checks о ● о о GENDER AGE (UNITS) NORMAL EXTREME Calibrator: MCC Diluted Calibrator level Sample sample Diluent Water Either 0 – 130 (Y) 64 – 83 Blank: Water 4.0 ______Cal 1: MCC1 4.0 ______Cal 2: MCC2 4.0 ______Configure result units Assay: TP о Calibrators о Volumes ● Intervals о Validity checks Version: 1 Calibration intervals: Result units: g/L Full interval: 552 (hours) Decimal places: 0 [Range 0 – 4] Calibration type: Correlation factor: 1.0000 Adjust type: None Intercept: 0.0000

о Calibrators о Volumes о Intervals ● Validity checks Blank absorbance range: _____ – _____ Span: Blank – Blank Span absorbance range: _____ – _____ Expected cal factor: 0.00 Expected cal factor tolerance %: 0

† The linear low value (Low-Linearity) is LOQ rounded up to the number of decimal places defined in the decimal places parameter field. ‡ Refer to concentration specified on calibrator labeling or value sheet. †† Displays the number of decimal places defined in the decimal places parameter field.

5 AEROSET SYSTEM ASSAY PARAMETERS

Total Protein Serum/Plasma—Conventional Units Total Protein Serum/Plasma—SI Units Assay Configuration: Outline Page Assay Configuration: Outline Page Assay Name Assay # Line Assay Name Assay # Line TP 14 B-Line TP 14 B-Line Quantitative Ranges Quantitative Ranges Min Text Min Panic-L L-Reference-H Panic-H Max Max Text Min Text Min Panic-L L-Reference-H Panic-H Max Max Text * 0.0* 0.0 6.4 8.3 0.0 0.0* * * 0.0* 0.0 64 83 0.0 0.0* * 0.8** L-Linear Range-H 18.4 8** L-Linear Range-H 184 Reference Ranges* Reference Ranges* Age Male Female Age Male Female 0 Year 0.0 – 0.0 0.0 – 0.0 0 Year 0.0 – 0.0 0.0 – 0.0 0.0 – 0.0 0.0 – 0.0 0.0 – 0.0 0.0 – 0.0 0 Year 0 Year 0.0 – 0.0 0.0 – 0.0 0.0 – 0.0 0.0 – 0.0 0 Year 0.0 – 0.0 0.0 – 0.0 0 Year 0.0 – 0.0 0.0 – 0.0 Qualitative Ranges N/A Qualitative Ranges N/A

Assay Configuration: Base Page Assay Configuration: Base Page Reaction Mode Wavelength-Prim/Sec Read time-Main/Flex AbsMaxVar Reaction Mode Wavelength-Prim/Sec Read time-Main/Flex AbsMaxVar END UP 572 / 660 14 – 16 / 0 – 0 0.0 END UP 572 / 660 14 – 16 / 0 – 0 0.0 Sample Blank Test Blank Read Time Abs Window Abs Limits Sample Blank Test Blank Read Time Abs Window Abs Limits _____ ( ___ ) 0 – 0 0 – 0 0.0 – 0.0 _____ ( ___ ) 0 – 0 0 – 0 0.0 – 0.0 S.Vol DS.Vol D.Vol W.Vol S.Vol DS.Vol D.Vol W.Vol Standard 4.0 0.0 0 0 Rgt Name/Pos Standard 4.0 0.0 0 0 Rgt Name/Pos Dil 1 4.0 0.0 0 0 Diluent: ______–__* Dil 1 4.0 0.0 0 0 Diluent: ______–__* Dil 2 4.0 0.0 0 0 Type# 0 Dil 2 4.0 0.0 0 0 Type# 0 Rgt Name/Pos R.Vol W.Vol Type# Rgt Name/Pos R.Vol W.Vol Type# Reagent 1 TP00061 – ___* 200 0 0 Reagent 1 TP00061 – ___* 200 0 0 Reaction Check Read Time – A/B Range Minimum Reaction Check Read Time – A/B Range Minimum ______1 – 1 / 1 – 1 0.0 – 0.0 0.0 ______1 – 1 / 1 – 1 0.0 – 0.0 0.0 Factor/Intercept Decimal Places Units Factor/Intercept Decimal Places Units 1.0 / 0.0 1 g/dL 1.0 / 0.0 0 g/L

Assay Configuration: Calibration Page Assay Configuration: Calibration Page Calib Mode Interval (H) Calib Mode Interval (H) Linear 552 Linear 552 Blank/Calib Replicates Extrapolation % Span Span Abs Range Blank/Calib Replicates Extrapolation % Span Span Abs Range 3 / 3 0 BLK – 1 0.0 – 0.0 3 / 3 0 BLK – 1 0.0 – 0.0 Sample S.Vol DS.Vol D.Vol W.Vol Blk Abs Range Sample S.Vol DS.Vol D.Vol W.Vol Blk Abs Range BLK Water 4.0 0.0 0 0 0.0 – 0.0 BLK Water 4.0 0.0 0 0 0.0 – 0.0 C1 MCC 1 4.0 0.0 0 0 Cal Deviation C1 MCC 1 4.0 0.0 0 0 Cal Deviation C2 MCC 2 4.0 0.0 0 0 0.0 C2 MCC 2 4.0 0.0 0 0 0.0 FAC Limit (%) FAC Limit (%) 10 10

Assay Configuration: SmartWash Page Assay Configuration: SmartWash Page Rgt Probe Rgt Probe Reagent Wash Vol Reagent Wash Vol ——— ——— Cuvette Cuvette Assay Name Wash Vol Assay Name Wash Vol ——— ——— Sample Probe Sample Probe Wash Wash — —

Refer to Assay Configuration in Section 2 of the AEROSET System Operations Manual for information regarding assay parameters. * User defined or instrument defined. ** The linear low value (L-Linear Range) is LOQ rounded up to the number of decimal places defined in the decimal places parameter field.

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