DIMENSION VISTA IGE FLEX REAGENT CARTRIDGE, PROTEIN 1 CALIBRATOR, PROTEIN 1 CONTROL MEDIUM, AND PROTEIN 1 CONTROL HIGH

{0} Page 1 of 8 # 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: k063425 B. Purpose for Submission: New Device C. Analyte: Immunoglobulin E (IgE) D. Type of Test: Quantitative, Nephelometry E. Applicant: Dade Behring, Inc. F. Proprietary and Established Names: Dimension Vista™ IgE Flex® reagent cartridge Dimension Vista™ Protein 1 Calibrator Dimension Vista™ Protein 1 Control L Dimension Vista™ Protein 1 Control M Dimension Vista™ Protein 1 Control H G. Regulatory Information: 1. Regulation section: 21CFR §866.5510- Immunoglobulin A, G, M, D, and E immunological test system 21CFR §862.1150- Calibrator 21CFR §862.1660- Quality control material, assayed and unassayed 2. Classification: Class II 3. Product Code: DGC- IgE, Antigen, Antiserum, Control JIX- Calibrator, multi-analyte mixture JJY- Multi-analyte controls 4. Panel Immunology (82) H. Intended Use: 1. Intended use(s): Dimension Vista™ IGE Flex® reagent cartridge: The IGE method is an in vitro diagnostic test for the quantitative determination of Immunoglobulin E in human serum, heparinized plasma or EDTA plasma on the Dimension Vista® System. Measurements of IGE aid in the diagnosis of IgE mediated allergic disorders in conjunction with other clinical findings. Dimension Vista™ Protein 1 Calibrator: PROT1 CAL is an in vitro diagnostic product for the calibration of the C3 complement (C3), C4 complement (C4), Immunoglobulin A (IGA), Immunoglobulin E (IGE), Immunoglobulin G (IGG), Immunoglobulin M (IGM), and Prealbumin (PREALB) methods on the Dimension Vista® System. {1} Page 2 of 8 Dimension Vista™ Protein 1 Controls L, M and H: PROT1 CON L, M, and H are assayed intra-laboratory quality controls for assessment of precision and analytical bias in the determination of C3 complement (C3), C4 complement (C4), Immunoglobulin A (IGA), Immunoglobulin E (IGE), Immunoglobulin G (IGG), Immunoglobulin M (IGM), and Prealbumin (PREALB) methods on the Dimension Vista® System. 2. Indication(s) for use: Same as above 3. Special condition for use statement(s): Prescription use only 4. Special instrument Requirements: Dimension Vista® System I. Device Description: Dimension Vista™ IGE Flex® reagent cartridge: IGE Flex® reagent cartridge consists of three reagents: IgE Reagent consists of polystyrene particles coated with monoclonal antibodies to human IgE. IGE Supplement Reagent 1 consists of phosphate buffer, polyethylene glycol, and sorbitan monolaureate. IGE Supplement Reagent 2 consists of mouse immunoglobulin in a phosphate buffer. Dimension Vista™ Protein 1 Calibrator: PROT1 CAL is a multi-analyte, liquid, human serum based product containing C3 complement (C3), C4 complement (C4), immunoglobulin A (IGA), immunoglobulin E (IGE) immunoglobulin G (IGG), immunoglobulin M (IGM), and prealbumin (PREALB) Dimension Vista™ Protein 1 Control L, M and H: PROT1 CON L, M and H are multi-analyte, liquid, human serum based products containing C3 complement (C3), C4 complement (C4), immunoglobulin A (IGA), immunoglobulin E (IGE), immunoglobulin G (IGG), immunoglobulin M (IGM), and prealbumin (PREALB) J. Substantial Equivalence Information: 1. Predicate device name(s) and 510(k) numbers: Dade Behring N Latex IgE mono assay k991787 Dade Behring N Protein Standard SL k012470 Dade Behring N/T Protein Control SL k012468 2. Comparison with predicate: Dimension Vista™ IgE Flex® regent cartridge | Similarities | | | | --- | --- | --- | | Item | Device | Predicate | | Intended Use | For the quantitative determination of Immunoglobulin E in human serum, heparinized plasma or EDTA plasma on the Dimension Vista® System. | For the quantitative in vitro determination of IgE in human serum, EDTA and heparinized plasma by means of particle enhanced immunonephelometry using the BN Systems | | Indications for Use | Measurements aid in the | Same | {2} | Similarities | | | | --- | --- | --- | | Item | Device | Predicate | | | diagnosis of IgE mediated allergic disorders in conjunction with other clinical findings. | | | Method | Immunonephelometry | Same | | Measurement type | Quantitative | Same | | Capture antibody | Mouse monoclonal | Mouse monoclonal | | Reportable range | 18- 1150 IU/mL | Same | | Matrices | Serum, heparin plasma (Li and Na), and EDTA plasma | Same | | Differences | | | | --- | --- | --- | | Item | Device | Predicate | | Instrument system | Dimension Vista® System | BN ProSpec® System | | Stability: opened | 21 days | 4 weeks | Dimension Vista™ Protein 1 Calibrator</table> | Similarities | | | | --- | --- | --- | | Item | Device | Predicate | | Intended Use | For the calibration of the C3 complement (C3), C4 complement (C4), Immunoglobulin A (IGA), Immunoglobulin E (IGE), Immunoglobulin G (IGG), Immunoglobulin M (IGM), and Prealbumin (PREALB) methods on the Dimension Vista® System | For establishment of reference curves for the determination of [26 specific analytes] on the BN Systems, as well as of IgM, C3c, ceruloplasmin and Ig/L-chains (types kappa and lambda) by radial immunodiffusion (RID) using Partigen plates. | | Composition | Pooled Human sera | Same | | Reagent Preparation | Liquid, Ready-for-Use | Same | | Traceability | 2ndIRP 75/502 | Same | | Differences | | | | --- | --- | --- | | Item | Device | Predicate | | Analytes | C3 complement (C3), C4 complement (C4), Immunoglobulin A (IGA), Immunoglobulin | IgG, IgG1, IgG2, IgG3, IgG4, IgA, IgM, IgE, C3c, C4, transferrin, albumin, α1-antitrypsin, | {3} Page 4 of 8 | Differences | | | | --- | --- | --- | | Item | Device | Predicate | | | E (IGE), Immunoglobulin G (IGG), Immunoglobulin M (IGM), and Prealbumin (PREALB) | α2-macroglobulin, haptoglobulin, α1-acid glycoprotein, prealbumin, hemopexin, ceruloplasmin, retinol binding protein, Ig Light chain kappa, Ig Light chain lambda, soluble transferrin receptor, ferritin, β2-microglobulin and total protein, IgM, C3c, ceruloplasmin and Ig/L-chains (types kappa and lambda). | | Instrument system | Dimension Vista® System | BN Systems | | Stability: Open | 9 days 2-8°C | 14 days 2-8°C | ## Dimension Vista™ Protein 1 Control L, M and H | Similarities | | | | --- | --- | --- | | Item | Device | Predicate | | Intended Use | Assayed intra-laboratory quality controls for the assessment of precision and analytical bias in the determination of C3 complement (C3), C4 complement (C4), Immunoglobulin A (IGA), Immunoglobulin E (IGE), Immunoglobulin G (IGG), Immunoglobulin M (IGM), and Prealbumin (PREALB) methods on the Dimension Vista™ System. | Assayed accuracy controls for accuracy and precision controls in the determination of [26] human serum proteins by immunonephelometry with the BN Systems, by immunoturbidimetry with the TurbiTime System and by radial immunodiffusion (RID) with Partigen plates. | | Composition | Pooled human sera | Same | | Reagent Preparation | Liquid, Ready to use | Same | | Concentration Range | Low, Medium and High | Same | | Differences | | | | --- | --- | --- | | Item | Device | Predicate | | Analytes | C3 complement (C3), C4 | IgG, IgG1, IgG2, IgG3, | {4} Page 5 of 8 | Differences | | | | --- | --- | --- | | Item | Device | Predicate | | | complement (C4), Immunoglobulin A (IGA), Immunoglobulin E (IGE), Immunoglobulin G (IGG), Immunoglobulin M (IGM), and Prealbumin (PREALB) methods. | IgG4, IgA, IgM, IgE, C3c, C4, transferrin, albumin, α1-antitrypsin, α2-macroglobulin, haptoglobin, α1-acid glycoprotein, prealbumin, hemopexin, ceruloplasmin, retinol binding protein, Ig Light chain kappa, Ig Light chain lambda, soluble transferrin receptor, ferritin, β2-microglobulin and total protein. | | Instrument system | Dimension Vista® System | BN Systems and the TurbiTime System | | Stability Open | days 2-8°C | 14 days 2-8°C | ## K. Standard/Guidance Document Referenced (if applicable): CLSI Evaluation of Precision Performance of Clinical Chemistry Devices; Approved Guideline: EP5-A, CLSI Interference Testing in Clinical Chemistry; Approved Guideline EP7-A2. ## L. Test Principle: Polystyrene particles coated with antibodies specific to human IgE are aggregated when mixed with samples containing IgE. These aggregates scatter a beam of light passed through a sample. The intensity of the scattered light is proportional to the concentration of the respective protein in the sample. The result is evaluated by comparison with a standard of known concentration. ## M. Performance Characteristics (if/when applicable): ### 1. Analytical performance: a. Precision/Reproducibility: Precision testing was done in accordance with CLSI Approved Guideline EP5-A2. Controls (PROT1 CON L, M, and H) and six samples (4 derived from serum pools and 2 derived from plasma pools), representing IgE concentrations across the measuring range and near the clinical decision points, were analyzed in duplicate, for 20 days, two times per day. The repeatability and within-lab standard deviations (SD) and percent coefficient of variation (% CV) were calculated. Repeatability imprecision was ≤3.5%, and within-lab imprecision was ≤7.0%. | Material | Mean IU/mL | Repeatability | | Within-Lab | | | --- | --- | --- | --- | --- | --- | | | | SD | %CV | SD | %CV | | PROT1 CON L | 52.1 | 1.7 | 3.3 | 3.6 | 7.0 | | PROT1 CON M | 187.6 | 4.9 | 2.6 | 10.2 | 5.4 | | PROT1 CON H | 449.4 | 10.8 | 2.4 | 25.7 | 5.7 | {5} | Material | Mean IU/mL | Repeatability | | Within-Lab | | | --- | --- | --- | --- | --- | --- | | | | SD | %CV | SD | %CV | | Serum pool | 15.7 | 0.2 | 1.3 | 0.3 | 1.8 | | Serum pool | 16.9 | 0.2 | 1.1 | 0.3 | 1.6 | | Serum pool | 64.0 | 2.2 | 3.5 | 4.0 | 6.2 | | Serum pool | 889.8 | 16.3 | 1.8 | 41.7 | 4.7 | | Plasma pool | 54.2 | 1.7 | 3.2 | 3.0 | 5.6 | | Plasma pool | 223.9 | 5.6 | 2.5 | 12.5 | 5.6 | b. Linearity/assay reportable range: Linearity across the assay measuring range (18 - 1150 IU/mL) was confirmed by testing a calibrator with a high concentration of immunoglobulin E. The calibrator was serially diluted with System Diluent in 5, approximately two-fold increments. The range of IgE values in the study was 14.7 to 1368.7 IU/mL. Each dilution was tested in replicates of three. Data were analyzed using linear regression analysis. The acceptance criteria for confidence intervals around the slope (0.9 and 1.1) and correlation coefficient $(\geq 0.95)$ were met. Regression analysis of theoretical concentration versus measured concentration produced the following results: | Slope | Intercept | R | n | | --- | --- | --- | --- | | 0.951 | 14.490 | 0.996 | 21 | The method used to fit the linear regression line was Passing-Bablok. Recovery of protein reference material 2nd IRP 75/502 ranged from $98.7 - 100.6\%$ with a mean recovery of $100.0\%$ . c. Traceability (controls, calibrators, or method): The Calibrator is referenced to the second international reference preparation for human serum IgE, $2^{\mathrm{nd}}$ IRP 75/502. Detailed description of the value assignments for Calibrator and Controls was provided. d. Detection limit: Analytical sensitivity was determined by assaying analyte-free System Diluent 20 times and determining the mean value plus two SDs: $0.953\mathrm{IU / mL}$ . Package insert states the limit of detection represents the lower limit of the reportable range and is reported as $3.6\mathrm{IU / mL}$ . e. Analytical specificity: i. Interference Studies: Interference testing was performed according to CLSI EP7-A2, to determine the effect of various endogenous and exogenous substances on the Dimension Vista™ IgE assay. For the following interferents, the percent bias was determined by testing a control sample without the interferent and comparing it to the value obtained from a test sample to which the potential interferent was added: bilirubin (conjugated and unconjugated, $60\mathrm{mg / dL}$ ), hemoglobin $(1000\mathrm{mg / dL})$ , creatinine $(30\mathrm{mg / dL})$ , albumin $(6\mathrm{g / dL})$ , urea $(500\mathrm{mg / dL})$ , cholesterol $(500\mathrm{mg / dL})$ , uric acid $(20\mathrm{mg / dL})$ . Sample concentrations represented the lowest and highest clinical decision points $\sim 15$ IU/mL and $\sim 260 - 310$ IU/mL. Interference $(&lt; 9\%)$ was within the acceptance criteria $\pm 10\%$ . Triglyceride interference {6} Page 7 of 8 was evaluated by testing five samples containing known amount of triglyceride and comparing the results to the same sample after centrifugation. The study demonstrated that clarified samples produced the same results as original samples (% CV &lt; 6%) but did not demonstrate that assay performance is not affected by triglycerides since the baseline IgE concentrations in these samples without triglycerides were not known. A statement that lipemic samples should be avoided was placed in the specimen handling section. Additionally, 41 potentially interfering drugs were also assayed and shown to exhibit minimal interference (&lt;10%). ii. Cross-reactivity with autoimmune antibodies common to other systemic autoimmune diseases was not tested. iii. Antigen Excess: The effect of antigen excess was evaluated using a serum sample with a high concentration of IgE (above the assay range). No prozone effect was observed up to at least 34,327 IU/mL. Samples whose values exceed 1150 IU/mL using the initial 1:20 dilution are reported as "exceeds assay range" to alert the user to repeat the assay using a higher dilution. f. Assay cut-off: See Expected Values. 2. Comparison studies: a. Method comparison with predicate device: Information regarding age and clinical status of the samples are not available. The Dimension Vista™ IGE assay was compared to the Dade Behring N Latex IgE mono assay on the BN ProSpec® System by evaluating 68 serum and 52 plasma samples with concentrations ranging from 18.2 IU/mL to 1126.5 IU/mL. Regression analysis of these results yielded the following results: | Comparative Method | Slope (95% CI) | Y-Intercept IU/mL (95% CI) | Correlation Coefficient r | n | | --- | --- | --- | --- | --- | | IGE on the BN ProSpec® | 1.041 (1.034-1.046) | 0.151 (0.899-1.092) | 0.999 | 120 | b. Matrix comparison: Ten matched samples of serum, EDTA, lithium heparin and sodium heparin plasma containing concentrations of IgE spanning the measuring range (25.88 to 923.73 IU/mL), were assayed and compared. Regression analysis between the four matrices yielded the following information: | % recovery vs. serum | | Slope (95%CI) | Y-Intercept (IU/mL) | Correlation Coefficient | n | | --- | --- | --- | --- | --- | --- | | Lithium heparin plasma | Mean = -0.6% (Range = -6.4%-7.5%) | 1.04 (1.00-1.08) | -14.31 | 0.998 | 10 | | Sodium heparin plasma | Mean = 1.6% (Range = -1.7%-8.0%) | 1.02 (0.986-1.06) | -3.38 | 0.998 | 10 | {7} Page 8 of 8 | EDTA | Mean = -0.5% (Range = -6.5%-4.5%) | 1.02 (0.991-1.04) | -7.93 | 0.999 | 10 | | --- | --- | --- | --- | --- | --- | 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: See Expected values. 5. Expected values/Reference range: Neonates &lt; 1.5 IU/mL Infants in first year of life &lt; 15 IU/mL Children (1 - 5 years) &lt; 60 IU/mL Children (6 - 9 years) &lt; 90 IU/mL Children (10 - 15 years) &lt; 200 IU/mL Adults &lt; 100 IU/mL These reference values were established using an EIA method in a comprehensive study (448 children, 200 adults) conducted in Europe. In clinically healthy adult subjects, IgE levels exhibit a wide distribution range and do not follow a normal distribution. IgE concentrations in children are highly dependent on age. Adult values are achieved at about 7 to 10 years of age. Higher values occur at about 10 to 15 years of age. Concentrations of up to approximately 100 IU/mL in adults can be considered the upper limit of the reference range. N. Proposed Labeling: The labeling is sufficient and satisfies the requirements of 21 CFR Part 809.10 O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision.