DIMENSION VISTA B2MIC FLEX REAGENT CARTRIDGE, PROTEIN 1 CALIBRATOR, CONTROL MEDIUM, CONTROL HIGH

K063272 · Dade Behring, Inc. · JZG · Jan 26, 2007 · Immunology

Device Facts

• Record ID: K063272
• Device Name: DIMENSION VISTA B2MIC FLEX REAGENT CARTRIDGE, PROTEIN 1 CALIBRATOR, CONTROL MEDIUM, CONTROL HIGH
• Applicant: Dade Behring, Inc.
• Product Code: JZG · Immunology
• Decision Date: Jan 26, 2007
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.5630
• Device Class: Class 2

Indications for Use

Dimension Vista™ B2MIC Flex® reagent cartridge: The B2MIC method is an in vitro diagnostic test for the quantitative determination of β2-microglobulin in human serum, or heparinized or EDTA plasma on the Dimension Vista® System. Measurements of ß2-microglobulin aid in the diagnosis of renal dysfunction. Dimension Vista™ Protein 1 Calibrator: PROT1 CAL is an in vitro diagnostic product for the calibration of the ßmicroglobulin (B2MIC), C3 Complement (C3), C4 Complement (C4), lmmunoglobulin A (IGA), Immunoglobulin G (IGG), Immunoglobulin M (IGM) and Prealbumin / Transthyretin (PREALB) methods on the Dimension Vista® System. Dimension Vista™ Protein 1 Control M and H: PROT1 CON M and H are assayed intralaboratory quality controls for assessment of precision and analytical bias in the determination of ß2microglobulin (B2MIC), C3 Complement (C3), C4 Complement (C4), immunoglobulin A (IGA), immunoglobulin G (IGG), immunoglobulin M (IGM) and prealbumin / transthyretin (PREALB) on the Dimension Vista® System.

Device Story

Device uses immunonephelometry to quantify human β2-Microglobulin in serum or plasma samples. Input: patient serum/plasma sample mixed with polystyrene particles coated with mouse monoclonal anti-β2-Microglobulin antibodies. Principle: antibody-coated particles aggregate upon binding to β2-Microglobulin; light scattering intensity is measured, which is proportional to protein concentration. Output: quantitative β2-Microglobulin concentration. Used in clinical laboratory settings on the Dimension Vista® System; operated by laboratory technicians. Results aid clinicians in diagnosing renal dysfunction. System includes reagent cartridges, multi-analyte calibrators, and quality controls.

Clinical Evidence

Bench testing only. Precision evaluated per CLSI EP5-A2 (intra-assay CV 1.97-3.01%; inter-assay CV 2.94-4.08%). Linearity confirmed 0.66–37.42 mg/L. Interference testing per CLSI EP7-A2 showed no significant interference from common substances. Method comparison (n=143) against predicate showed high correlation (r=0.998, slope 0.942). No clinical data required.

Technological Characteristics

Immunoturbidimetric assay using polystyrene particles coated with anti-human β2-microglobulin antibodies. Measures light scatter intensity proportional to protein concentration. System-based automated analysis. Reagents include liquid human serum-based calibrators and controls.

Indications for Use

Indicated for quantitative determination of β2-microglobulin in human serum, heparinized plasma, or EDTA plasma to aid in the diagnosis of renal dysfunction.

Regulatory Classification

Identification

A beta-2-microglobulin immunological test system is a device that consists of the reagents used to measure by immunochemical techniques beta-2-microglobulin (a protein molecule) in serum, urine, and other body fluids. Measurement of beta-2-microglobulin aids in the diagnosis of active rheumatoid arthritis and kidney disease.

Special Controls

*Classification.* Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 866.9.

Predicate Devices

• Dade Behring N Latex β₂-Microglobulin assay (k002731)
• Dade Behring N Protein Standard SL (k012470)
• Dade Behring N/T Protein Controls SL (k012468)

Submission Summary (Full Text)

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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

A. 510(k) Number:
k063272

B. Purpose for Submission:
New devices

C. Measurand:
Human $\beta_{2}$-microglobulin

D. Type of Test:
Quantitative, immunonephelometry

E. Applicant:
Dade Behring, Inc.

F. Proprietary and Established Names:
Dimension Vista® $\beta_{2}$-Microglobulin Flex® reagent cartridge (B2MIC)
Dimension Vista® Protein 1 Calibrator (CAL)
Dimension Vista® Protein 1 Control Medium (M)
Dimension Vista® Protein 1 Control High (H)

G. Regulatory Information:

1. Regulation section:
21 CFR § 866.5630 Beta-2-Microglobulin Immunological Test System
21 CFR § 862.1150, Calibrator
21 CFR § 862.1660, Quality Control Material (Assayed and Unassayed)

2. Classification:
Class II, Devices and Calibrator
Class I, Quality Control Material

3. Product code:
JZG, System, Test, Beta-2-Microglobulin Immunological
JIX, Calibrator, Multi-Analyte Mixture
JJY, Multi-Analyte Controls, All kinds (Assayed and Unassayed)

4. Panel:
Immunology (82)
Chemistry (75)

H. Intended Use:

1. Intended use(s):
Dimension Vista® System $\beta_{2}$-Microglobulin Flex® reagent cartridge:
The B2MIC method is an *in vitro* diagnostic test for the quantitative
determination of $\beta_{2}$-Microglobulin in human serum or heparinized or EDTA
plasma on the Dimension Vista® System. Measurements of $\beta_{2}$-Microglobulin aid
in the diagnosis of renal dysfunction.

Dimension Vista® System Protein 1 Calibrator:
PROT 1 CAL is an *in vitro* diagnostic product for the calibration of the $\beta_{2}$-
Microglobulin (B2MIC), C3 complement (C3), C4 complement (C4),
Immunoglobulin A (IGA), Immunoglobulin G (IGG), Immunoglobulin M (IGM),
Prealbumin/Transthyretin (PREALB) methods on the Dimension Vista® System.

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Dimension Vista® System Protein 1 Control M (medium):
PROT1 CON M is an assayed intralaboratory quality control for assessment of precision and analytical bias in the determination of β₂-Microglobulin (B2MIC), C3 complement (C3), C4 complement (C4), Immunoglobulin A (IGA), Immunoglobulin G (IGG), Immunoglobulin M (IGM), Prealbumin/Transthyretin (PREALB) on the Dimension Vista® System.

Dimension Vista® System Protein 1 Control H (high):
PROT1 CON H is an assayed intralaboratory quality control for assessment of precision and analytical bias in the determination of β₂-Microglobulin (B2MIC), C3 complement (C3), C4 complement (C4), Immunoglobulin A (IGA), Immunoglobulin G (IGG), Immunoglobulin M (IGM), Prealbumin/ Transthyretin (PREALB) on the Dimension Vista® System.

Calibrators and controls are not included in the device and are sold separately.

2. Indication(s) for use:
Same as Intended Use.

3. Special conditions for use statement(s):
For prescription use only.

4. Special instrument requirements:
Dimension Vista® System (k051087)

I. Device Description:
Dimension Vista® System B2MIC Flex® reagent cartridge carton contains 2 cartridges (12 wells per cartridge which generates approximately 100 tests/cartridge) with mouse monoclonal antiserum to human β₂-Microglobulin, phosphate buffer, and polyethylene glycol sorbitan monolaurate. Reagent is in ready-to-use liquid form.

Dimension Vista® System Protein 1 Calibrator carton contains 6 vials (2 mL per vial), with a multi-analyte human serum based product containing β₂-Microglobulin, C3, C4, IgA, IgG, IgM and Prealbumin. Reagent is in ready-to-use liquid form.

Dimension Vista® System Protein 1 Control M, and Control H cartons contain 6 vials per carton (2 mL per vial), with a multi-analyte human serum based products containing β₂-Microglobulin, C3, C4, IgA, IgG and IgM and Prealbumin. Reagents are ready-to-use liquid form.

J. Substantial Equivalence Information:

1. Predicate device name(s):
Dade Behring N Latex β₂-Microglobulin assay
Dade Behring N Protein Standard SL
Dade Behring N/T Protein Controls SL

2. Predicate 510(k) number:
k002731 (Antisera)
k012470 (Protein Standard)
k012468 (Controls)

3. Comparison with predicate:

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| Similarities | | |
| --- | --- | --- |
| Item | Dimension Vista® System β2-Microglobulin Flex® reagent cartridge | Dade Behring N Latex β2-Microglobulin assay |
| Intended Use/Indication for Use | An in vitro diagnostic test for the quantitative determination of β2-Microglobulin to aid in the diagnosis of renal dysfunction | Same |
| Technology | Immunonephelometry | Same |
| β2-Microglobulin antisera mammal source | Mouse Monoclonal | Same |
| Differences | | |
| --- | --- | --- |
| Item | Dimension Vista® System β2-Microglobulin Flex® reagent cartridge | Dade Behring N Latex β2-Microglobulin assay |
| Sample type | Serum and plasma (EDTA; lithium and sodium heparin) | Serum, plasma (EDTA; sodium, lithium and ammonium heparin), urine and CSF |
| Reportable range for serum and plasma | 0.72 – 23.0 mg/L | 0.70 – 23.0 mg/L |
| Reportable range for urine | Urine is not a matrix | 0.2 – 6.0 mg/L |
| International Reference standard material | Traceable to Highly purified proteins 1stInternational Standard (NIBSC) | Traceable to Highly Purified Proteins |
| Storage conditions | Unopened product: Refrigerate at 2-8°C until expired. Opened product: stable for 21 days on board analyzer | Unopened product: Refrigerate at 2-8°C until expired. Opened product: stable for 4 weeks at 2-8°C |
| Analyzer | Dimension Vista® System | Dade Behring BN™ Systems |
| Similarities | | |
| --- | --- | --- |
| Item | Dimension Vista® System Protein 1 Calibrator | Dade Behring N Protein Standard SL |
| Intended Use/Indication for Use | For the calibration of specific serum protein assays | Establishment of the reference curves for the determination of specific serum protein assays |

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| Similarities | | |
| --- | --- | --- |
| Item | Dimension Vista® System Protein 1 Calibrator | Dade Behring N Protein Standard SL |
| Material source | Human serum | Same |
| Reagent preparation | Ready-to-use, liquid | Same |
| Differences | | |
| --- | --- | --- |
| Item | Dimension Vista® System Protein 1 Calibrator | Dade Behring N Protein Standard SL |
| Analytes | 7 analytes: β2-Microglobulin, C3, C4, IgA, IgG, IgM and Prealbumin | 27 analytes: IgG, IgG1, IgG2, IgG3, IgG4, IgA, IgM, IgE, C3c, C4, Transferrin, Albumin, α1-antitrypsin, α2-macroglobulin, haptoglobin, α1-acid glycoprotein, Prealbumin, hemopexin, ceruloplasmin, RbP, Ig/L-chain Kappa, Ig/L-chain Lambda, soluble transferrin receptor, ferritin, β2-microglobulin, total protein |
| International Reference standard material | Traceable to Highly purified proteins 1stInternational Standard (NIBSC) | Traceable to Highly Purified Proteins |
| Storage conditions | Unopened product: Refrigerate at 2-8°C until expired. Opened product: stable for 9 days on board analyzer | Unopened product: Refrigerate at 2-8°C until expired. Opened product: stable for 14 days at 2-8°C |
| Analyzer | Dimension Vista® System | Dade Behring BN™ Systems |
| Similarities | | |
| --- | --- | --- |
| Item | Dimension Vista® System Protein 1 Control | Dade Behring N/T Protein Controls SL |
| Intended Use/Indication for Use | Assayed intralaboratory quality controls for assessment of precision and analytical bias in the determination of specific protein assays | For use as assayed accuracy controls and precision controls in the determination of specific serum protein assays |
| Material source | Human serum | Same |

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| Similarities | | |
| --- | --- | --- |
| Item | Dimension Vista® System Protein 1 Control | Dade Behring N/T Protein Controls SL |
| Reagent preparation | Ready-to-use, liquid | Same |
| Differences | | |
| --- | --- | --- |
| Item | Dimension Vista® System Protein 1 Control | Dade Behring N/T Protein Controls SL |
| Analytes | 7 analytes: β2-Microglobulin, C3, C4, IgA, IgG, IgM and Prealbumin | 27 analytes: IgG, IgG1, IgG2, IgG3, IgG4, IgA, IgM, IgE, C3c, C4, Transferrin, Albumin, α1-antitrypsin, α2-macroglobulin, haptoglobin, α1-acid glycoprotein, Prealbumin, hemopexin, ceruloplasmin, RbP, Ig/L-chain Kappa, Ig/L-chain Lambda, soluble transferrin receptor, ferritin, β2-microglobulin, total protein |
| Storage conditions | Unopened product: Refrigerate at 2-8°C until expired. Opened product: stable for 9 days on board analyzer | Unopened product: Refrigerate at 2-8°C until expired. Opened product: stable for 14 days at 2-8°C |
| Analyzer | Dimension Vista® System | Dade Behring BN™ Systems |
| Levels | Medium and High | Low, Medium, and High |

# K. Standard/Guidance Document Referenced (if applicable):

CLSI/NCCLS, EP 5-A2: Evaluation of Precision Performance of Clin Chem Devices
CLSI/NCCLS, EP 7-A2: Interference Testing in Clinical Chemistry
CLSI/NCCLS, EP 9-A2: Method Comparison and Bias Estimation

# L. Test Principle:

Polystyrene particles coated with specific antibodies to human $\beta_{2}$ -Microglobulin are aggregated when mixed with samples containing human $\beta_{2}$ -Microglobulin. These aggregates scatter a beam of light passed through the 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:

Reproducibility testing was done in accordance with CLSI/NCCLS document

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EP5-A2, 'Approved Guideline for Evaluation of Precision Performance of Clinical Devices'. The intra-assay reproducibility was determined by testing six samples in duplicate twice a day for 20 days. The samples included the M and H controls ( $\beta_{2}$ -Microglobulin concentration of 1.88 and $4.86\mathrm{mg/L}$ respectively), two serum pools (concentrations of 2.13 and $20.35\mathrm{mg/L}$ ) and two plasma pools (concentrations of 1.76 and $5.69\mathrm{mg/L}$ ). The controls had $\% \mathrm{CV}$ ranging from $2.07\%$ to $2.57\%$ , the serum pools $2.13\%$ to $3.01\%$ and the plasma pools $1.97\%$ to $2.22\%$ .

The inter-assay reproducibility was determined by testing the same six samples in duplicate twice a day for 20 days. The $\% \mathrm{CV}$ for the controls ranged from $3.10\%$ to $3.56\%$ , the sera pools $3.23\%$ to $4.08\%$ and the plasma pools $2.94\%$ to $3.28\%$ . The data are summarized below:

| Material | Mean mg/L | Intra-assay | | Inter-assay | |
| --- | --- | --- | --- | --- | --- |
| | | SD | %CV | SD | %CV |
| PROT 1 CON M | 1.88 | 0.048 | 2.57 | 0.067 | 3.56 |
| PROT 1 CON H | 4.86 | 0.101 | 2.07 | 0.151 | 3.10 |
| Serum pool | 2.13 | 0.045 | 2.13 | 0.069 | 3.23 |
| Serum pool | 20.35 | 0.612 | 3.01 | 0.831 | 4.08 |
| Plasma pool | 1.76 | 0.039 | 2.22 | 0.052 | 2.94 |
| Plasma pool | 5.69 | 0.112 | 1.97 | 0.186 | 3.28 |

# b. Linearity/assay reportable range:

Linearity across the assay range was confirmed by testing a calibrator with high concentration $(37.42\mathrm{mg / L})$ of $\beta_{2}$ -Microglobulin. This calibrator was serially diluted 6 times with System Diluent down to the lower measuring range $(0.66\mathrm{mg / L})$ . Each dilution was tested in replicates of three.

The linear regression analysis was performed. The acceptance criteria for the slope (0.9 and 1.1) and correlation of coefficient $\geq 0.95$ were met. (Slope = 0.973, Intercept = 0.087, Correlation coefficient = 1.00. See figure below). Linearity was observed between 0.66 to $37.42\mathrm{mg / L}$ .

Reportable range for the device was set at $0.72 - 23.0\mathrm{mg / L}$

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B2MIC Assay Range Verification

## High Dose Hook Effect:

The possibility of hook occurring when using the Dimension Vista ® B2MIC assay was evaluated with serum sample above the assay range. The sample was analyzed on both the BN ProSpec® System and the Dimension Vista® System and results indicated no hook effect was observed up to 122 mg/L.

c. Traceability, Stability, Expected values (controls, calibrators, or methods): The calibrator is traceable to the reference material Highly Purified Protein 1st International Standard (3/17/04 NIBSC).

## Device Stability

The expiration date claims for the reagents are as follows:

Unopened reagent cartridges and closed vials:

Dimension Vista® B2MIC Flex® reagent cartridge – 24 months

Dimension Vista® Protein 1 Calibrator – 24 months

Dimension Vista® Protein 1 Control M and H – 24 months

On-board Instrument products:

Dimension Vista® B2MIC Flex® reagent sealed cartridge – 90 days

Dimension Vista® B2MIC Flex® open well reagent cartridge – 21 days

Dimension Vista® Protein 1 Calibrator open vial – 9 days

Dimension Vista® Protein 1 Control M and H open vial – 9 days

d. Detection limit:

Detection limit (0.72 mg/L) represents the lower limit of the reportable range of β₂-Microglobulin.

The analytical sensitivity is defined as the minimal detectable level of analyte, which can be distinguished from zero. The value was calculated as the mean value of twenty replicates of System Diluent plus two standard deviations. It was determined to be 0.176 mg/L.

e. Analytical specificity:

Interference testing was performed according to CLSI document EP7A2, 'Interference testing in Clinical Chemistry' guidance. No significant

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interference was observed in the presence of the following interferents: Bilirubin (conjugated and unconjugated) up to 60 mg/dL, Hemoglobin up to 1000 mg/dL, Triglycerides up to 1313 mg/dL, Creatinine up to 30 mg/dL, Albumin up to 6000 mg/L, Immunoglobulin G (IgG) up to 5000 mg/L, Urea up to 500 mg/dL, Cholesterol up to 500 mg/dL, Uric Acid 16 mg/dL, Rheumatoid factor up to 500 IU/mL, Total Protein up to 12 g/L.

Non-interfering substances section of the device package insert provides a list of drugs and other exogenous substances that do not interfere with the assay.

f. Assay cut-off:

Not Applicable.

2. Comparison studies:

a. Method comparison with predicate device:

The table below shows the comparison of 71 serum and 72 plasma samples ranging from 0.81 to 22.69 mg/L β₂-Microglobulin that were tested with the Dimension Vista™ β₂-Microglobulin assay and the predicate device BN ProSpec® System. Regression analysis of these samples is summarized in the table below:

| | N | Slope (95%CI) | Intercept (95%CI) | r |
| --- | --- | --- | --- | --- |
| Dimension Vista® vs. BN ProSpec® | 143 | 0.942 (0.931, 0.954) | -0.029 (-0.062, 0.011) | 0.998 |

b. Matrix comparison:

Sera and plasma (EDTA; lithium and sodium heparin) samples, covering the β₂-Microglobulin assay measuring range (1.01 – 21.78 mg/L) were compared to determine if any significant bias existed between matrices. The correlation coefficients were acceptable and no bias was observed. Regression analyses of the comparison results are summarized below:

| | n | Slope | Intercept | r |
| --- | --- | --- | --- | --- |
| Lithium heparin plasma vs. serum | 11 | 0.98 | 0.11 | 0.998* |
| Sodium heparin plasma vs. serum | 11 | 0.95 | 0.20 | 0.997** |
| EDTA plasma vs. serum | 11 | 0.97 | 0.11 | 0.998*** |

* The range of β₂-Microglobulin values in the correlation study was 1.05-21.78 mg/L
** The range of β₂-Microglobulin values in the correlation study was 1.07-21.08 mg/L
*** The range of β₂-Microglobulin values in the correlation study was 1.01-21.64 mg/L

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3. Clinical studies:

a. Clinical Sensitivity and specificity: Not applicable
b. Other clinical supportive data: Not applicable.

4. Clinical cut-off: Not applicable
5. Expected values/Reference range: The reported expected range for $\beta_{2}$ -Microglobulin in adults $(0.7 - 1.8\mathrm{mg / L})$ is from literature Lammers M, et al Determination of beta2-microglobulin by a particle-enhanced immunonephelometric assay. Clin Chem 2002; 48: A-119.

Each laboratory should establish its own expected values for $\beta_{2}$ -Microglobulin as performed on the Dimension Vista® System.

# N. Proposed Labeling:

The labeling is sufficient and it 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.