DIMENSION VISTA FERRITIN FLEX REAGENT CARTRIDGE (FERR)

K070552 · Dade Behring, Inc. · JIT · Apr 30, 2007 · Clinical Chemistry

Device Facts

• Record ID: K070552
• Device Name: DIMENSION VISTA FERRITIN FLEX REAGENT CARTRIDGE (FERR)
• Applicant: Dade Behring, Inc.
• Product Code: JIT · Clinical Chemistry
• Decision Date: Apr 30, 2007
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1150
• Device Class: Class 2

Indications for Use

The FERR method is an in-vitro diagnostic test for the quantitative measurement of ferritin in human serum and plasma (lithium or sodium heparin and EDTA) on the Dimension Vista™ system. Measurements of ferritin aid in the diagnosis of diseases affecting iron metabolism, such as hemochromatosis (iron overload) and iron deficiency anemia. The LOCI 4 Calibrator is an in vitro diagnostic product for the calibration of the Ferritin (FERR) method on the Dimension Vista™ system.

Device Story

Dimension Vista™ Ferritin Flex® reagent cartridge is a homogenous, sandwich chemiluminescent immunoassay using LOCI™ technology. Input: human serum or plasma sample (2 µL). Process: sample incubated with biotinylated anti-ferritin antibody and Chemibeads (coated with anti-ferritin antibody and chemiluminescent dye); Sensibeads (streptavidin-coated with photosensitizer dye) added to form bead-pair immunocomplexes. Illumination at 680 nm triggers singlet oxygen diffusion from Sensibeads to Chemibeads, inducing chemiluminescence measured at 612 nm. Output: ferritin concentration. Used in clinical laboratory settings by trained technicians. Output aids clinicians in diagnosing iron metabolism diseases. Benefits include rapid, automated quantitative assessment of ferritin levels.

Clinical Evidence

Clinical performance established via split-sample method comparison between the subject device and the predicate. Study included 158 clinical patient samples. Results showed a correlation coefficient (r) of 0.996, a slope of 1.01, and an intercept of 1.48 ng/mL, confirming substantial equivalence.

Technological Characteristics

Sandwich chemiluminescent immunoassay (LOCI™ technology). Reagents: synthetic bead reagents (Sensibeads, Chemibeads) and biotinylated monoclonal antibody fragments. Detection: 680 nm excitation, 612 nm emission. Matrix: bovine serum albumin. Calibrator: 5-level liquid, traceable to WHO standard 3rd IS 94/572. Automated clinical chemistry system platform.

Indications for Use

Indicated for quantitative measurement of ferritin in human serum and plasma to aid in diagnosis of iron metabolism diseases, including hemochromatosis and iron deficiency anemia. Prescription use only.

Regulatory Classification

Identification

A calibrator is a device intended for medical purposes for use in a test system to establish points of reference that are used in the determination of values in the measurement of substances in human specimens. (See also § 862.2 in this part.)

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 § 862.9.

Predicate Devices

• Ferritin (FERR) Flex® reagent cartridge for the Dimension® clinical chemistry system (K963498)
• Dimension FERR Calibrator (K983548)

Submission Summary (Full Text)

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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

A. 510(k) Number:
k070552

B. Purpose for Submission:
New Device

C. Analyte:
Ferritin

D. Type of Test:
Semi-quantitative, Chemiluminescence

E. Applicant:
Dade Behring, Inc.

F. Proprietary and Established Names:
Dimension Vista™ (FERR) Flex® reagent cartridge
Dimension Vista™ LOCI 4 Calibrator

G. Regulatory Information:

1. Regulation section:
21CFR §866.5340 Ferritin immunological test system
21CFR §862.1150 Calibrator

2. Classification:
Class II

3. Product Code:
DBF-Ferritin, antigen, antiserum, control
JIT-Calibrator, secondary

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

H. Intended Use:

1. Intended use(s):
Dimension Vista™ (FERR) Flex® reagent cartridge- The FERR method is an in vitro diagnostic device for the quantitative measurement of ferritin in human serum and plasma (lithium or sodium heparin, and EDTA) on the Dimension Vista® System. Measurements of ferritin aid in the diagnosis of diseases affecting iron metabolism, such as hemochromatosis (Iron overload) and iron deficiency anemia.

The Dimension Vista™ LOCI 4 Calibrator is an in vitro diagnostic device intended to be used to calibrate the ferritin (FERR) assay on the Dimension Vista™.

2. Indication(s) for use:
Same as intended use.

3. Special condition for use statement(s):
Prescription use only

4. Special instrument Requirements:

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Dimension Vista® System

I. Device Description:

Dimension Vista™ FERR Flex® reagent cartridge assay is a homogeneous, sandwich chemiluminescent immunoassay using LOCI™ reagents: Sensibeads (bead reagent coated with streptavidin and containing a photosensitizer dye), Chemibeads (bead reagent coated with murine anti-ferritin monoclonal antibody and containing a chemiluminescent dye), and a biotinylated murine anti-ferritin monoclonal antibody fragment. Buffers, preservatives and stabilizers are also included in the cartridge.

Dimension Vista™ LOCI 4 Calibrator is a five level, liquid calibrator kit consisting of 10 vials (two vials for each level). The product matrix is 6% bovine serum albumin with buffer, stabilizer, and preservatives. Levels A through E contains ferritin at the following target concentrations: A~0 ng/mL, B~26 ng/mL, C~210 ng/mL, D~1050 ng/mL, E~2000 ng/mL.

J. Substantial Equivalence Information:

1. Predicate device name(s):
Dimension® Ferritin Flex® reagent cartridge
Dimension® Ferritin calibrator

2. Predicate K number(s):
k963498
k983548

3. Comparison with predicate:

| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| | Dimension Vista™ Ferritin Flex ® reagent cartridge (K6440) | Dimension® Ferritin Flex® reagent cartridge (RF440) |
| Intended Use | The FERR method is an in vitro diagnostic device for the quantitative measurement of ferritin in human serum and plasma (lithium or sodium heparin, and EDTA) on the Dimension Vista® System. | The Ferritin Flex® reagent cartridge used on the Dimension® clinical chemistry system with the heterogeneous immunoassay module is an in vitro diagnostic test intended to quantitatively measure ferritin in serum and heparinized plasma. |
| Indications for Use | Measurements of ferritin aid in the diagnosis of diseases affecting iron metabolism, such as hemochromatosis (Iron overload) and iron deficiency anemia. | Same |
| Measurement type | Quantitative | Same |

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| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| | Dimension Vista™ Ferritin Flex ® reagent cartridge (K6440) | Dimension® Ferritin Flex® reagent cartridge (RF440) |
| Capture antibody | Mouse monoclonal | Same |
| Reference intervals | Males 26-388 ng/mL
Females 8-252 ng/mL
All adults 8-388 ng/mL | Same |
| Stability: Sealed & On-board | 30 days | Same |
| Differences | | |
| Item | Device | Predicate |
| Instrument | Dimension Vista ® System | Dimension® Clinical Chemistry System |
| Solid phase | Chemibeads and Sensibeads | Ferritin antibody coated chromium dioxide particles |
| Conjugate reagent | None | β galactosidase labeled anti-ferritin monoclonal antibody |
| Substrate | None | Chlorophenol red-β-d-galactopyranoside |
| Detection method | Chemiluminescence | Colorimetric |
| Measurement absorbance | 680 and 612 nm | 577 and 700 nm |
| Sample type | Serum, heparinized and EDTA plasma | Serum, heparinized plasma |
| Sample size | 2 μL | 40 μL |
| Measuring Range | 0.5 ng/mL- 2000 ng/mL | 1-1000 ng/mL |
| Stability: Open | 7 days for wells 1-12 | Varies from 3-10 days |
| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| | Dimension Vista™ LOCI 4 Calibrator | Dimension ® Ferritin Calibrator |
| Intended Use | To calibrate the ferritin method | Same |
| Composition | Ferritin from human liver in bovine serum albumin | Same |
| Reagent Preparation | Liquid, Ready-to-use | Same |
| Traceability | WHO, 3rdIS 94/572 | Same |
| Levels | 1 without ferritin, 4 with different concentrations of ferritin | Same |

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| Stability | 30 days at 2-8°C | Same |
| --- | --- | --- |
| Differences | | |
| Item | Device | Predicate |
| Analytes | Multi-analyte | Ferritin |
| Instrument system | Dimension Vista ® System | Dimension® Clinical Chemistry System |
| Storage | Frozen -10 to -20°C | Refrigerated -2 to-8°C |

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

CLSI Evaluation of Precision Performance of Clinical Devices; Approved Guideline: EP5-A2, CLSI Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline EP9-A2, CLSI Interference Testing in Clinical Chemistry; Approved Guideline EP7-A2. CLSI Evaluation of the Linearity of Quantitative Analytical Methods; Approved Guideline EP6-A.

## L. Test Principle:

The FERR method is a homogenous, sandwich chemiluminescent immunoassay. Ferritin in a sample is incubated with biotinylated murine monoclonal and beads that are coated with anti-ferritin mouse monoclonal and containing a chemiluminescent dye (Chemibeads) to form a particle/ferritin/biotin-antibody sandwich. A second set of beads (Sensibeads), coated with streptavidin and containing a photosensitizer dye is added and bind to the biotin to form bead-pair immunocomplexes. The sample is illuminated at 680nm, generating a single oxygen from the Sensibeads that diffuses into the Chemibeads and triggering a chemiluminescent reaction. The resulting signal is measured at 612 nm and is a direct indication of the ferritin concentration in the sample.

## M. Performance Characteristics (if/when applicable):

### 1. Analytical performance:

#### a. Precision/Reproducibility:

Precision testing was done in accordance with CLSI Approved Guideline EP5-A2. Three serum pools and one plasma sample representing the measuring range were analyzed in duplicate, twice a day, for 20 days. Two commercially available controls were also evaluated. The standard deviation (SD) and coefficient of variation (%CV) for repeatability and within-lab precision are reported below. Overall repeatability was greater than 98% and within-lab reproducibility was greater than 96%.

| | Mean (ng/mL) | Repeatability | | Within-lab | |
| --- | --- | --- | --- | --- | --- |
| | | SD | %CV | SD | %CV |
| Anemia Control Level 1 | 6.2 | 0.11 | 1.7 | 0.24 | 3.8 |
| Control Level 2 | 161.1 | 2.02 | 1.3 | 3.72 | 2.3 |
| Serum Pool 1 | 8.8 | 0.16 | 1.8 | 0.31 | 3.5 |
| Serum Pool 2 | 436.4 | 5.58 | 1.3 | 14.33 | 3.3 |
| Serum Pool 3 | 1696.3 | 27.18 | 1.6 | 57.44 | 3.4 |
| Plasma Pool | 9.0 | 0.16 | 1.8 | 0.28 | 3.1 |

#### b. Linearity/assay reportable range:

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The linear range of the assay (0.5 – 2000 ng/mL) was confirmed by testing five replicates of each dilution (7 total) prepared from a patient serum sample, as described in CLSI protocol EP-6-A. Ferritin concentrations in the sample ranged from 0.0 to 2136.6 ng/mL. The mean of the observed values for each dilution were plotted versus the expected values. Least squares regression analysis generated the following data:

| Slope | Y-intercept (ng/mL) | Correlation Coefficient | n |
| --- | --- | --- | --- |
| 1.00 | 2.1 ng/mL | 1.00 | 35 |

Recovery studies were also performed using six serum samples with ferritin concentrations ranging from 4.5 - 151 ng/mL. Samples were spiked with 10 ng/mL of ferritin. The percent recovery ranged from 87% to 104% with a mean recovery of 95%.

c. Traceability (controls, calibrators, or method):
Value assignments for the calibrators are made from a master pool that is referenced to the WHO standard for ferritin 3rd IS 94/572.

d. Detection limit:
The limit of blank was determined from the mean of 20 replicates of the zero-level calibrator plus 2 standard deviations. The value obtained was 0.13 ng/mL. The limit of blank claim is 0.5 ng/mL.

e. Analytical specificity:
i. Interference studies: Interference testing was performed according to CLSI Approved Guideline EP7-A2 to determine the effect of various exogenous substances of the Dimension Vista™ FERR method. Minimal interference (<10%) was observed when pooled human serum samples representing two concentrations of ferritin (20 ng/mL and 502.7 ng/mL) containing the following interferents were compared to a control without interferent: hemoglobin (500 mg/dL), unconjugated bilirubin (20 mg/dL), conjugated bilirubin (60 mg/dL), Intralipid (3000 mg/dL) rheumatoid factor (510 IU/mL). An additional panel of 41 exogenous substances were evaluated for interference and were shown to exhibit minimal interference (<10%).

ii. Cross-reactivity
Not applicable.

iii. Antigen excess- The effect of antigen excess in the Dimension Vista™ FERR assay was evaluated using the zero-level calibrator spiked with 250,000 ng/mL of human ferritin. The test result was reported as “exceeds assay range.” Samples greater than 2000 ng/mL are reported as exceeding assay range.

f. Assay cut-off:
See Expected values/reference range.

2. Comparison studies:
a. Method comparison with predicate device:

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CLSI Approved Guideline for Method Comparison and Bias Estimation Using Patient Samples; EP9-A2 was followed. The Dimension Vista™ FERR method on the Dimension Vista™ System was compared to the predicate Dimension® Ferritin Flex® reagent cartridge on the Dimension® RxL instrument by assaying 158 serum samples with concentrations ranging from 4.4 ng/mL to 1573.3 ng/mL on both systems and comparing the results. Ordinary least squares linear regression statistics are as follows:

| Comparative Method | Slope | Y-Intercept (ng/mL) | Correlation coefficient (r) | N |
| --- | --- | --- | --- | --- |
| Dimension RxL System | 1.01 | 1.48ng/mL | 0.996 | 158 |

Passing-Bablok non-parametric linear regression analysis yielded the following statistics: Slope 1.02 (95% CI: 1.00 to 1.03), Y-intercept -0.95 (95% CI -1.81 to -0.47).

b. Matrix comparison:

Ten matched serum, Na-heparin plasma, Li-heparin plasma, EDTA-plasma samples containing ferritin concentrations ranging 5.3 -1978.5 ng/mL, were assayed and compared. Least squared regression analysis demonstrated that there was no significant bias between the two matrices and yielded the following statistics:

| Sample type compared to serum | Slope | Y-intercept | Correlation coefficient |
| --- | --- | --- | --- |
| Na-heparin plasma | 1.03 | -2.1 | 1.00 |
| Li-heparin plasma | 1.01 | -4.0 | 1.00 |
| EDTA-plasma 1.00 | 1.00 | -4.6 | 1.00 |

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/reference range

5. Expected values/Reference range:

The reference intervals were transferred from those previously obtained using the predicate Dimension® system. They represent the central 95% of results determined from a population of healthy adults (n=296; 118 males, and 178 females). The original determination and transference were done in accordance with protocol CLSI C28-A2, How to Define and Determine Reference Intervals in the Clinical Laboratory. Pediatric samples were not evaluated.

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| Sample | 95% Reference Interval |
| --- | --- |
| Males | 26-388 ng/mL |
| Females | 8-252 ng/mL |
| All adults | 8-388 ng/mL |

# 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.