BECKMAN COULTER FERRITIN REAGENT, MODEL: OSR61203

K092505 · Beckman Coulter, Inc. · DBF · Dec 11, 2009 · Immunology

Device Facts

• Record ID: K092505
• Device Name: BECKMAN COULTER FERRITIN REAGENT, MODEL: OSR61203
• Applicant: Beckman Coulter, Inc.
• Product Code: DBF · Immunology
• Decision Date: Dec 11, 2009
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.5340
• Device Class: Class 2

Intended Use

The Ferritin Reagent is for the determination of ferritin concentrations in human serum and plasma on the Beckman Coulter family of clinical chemistry analyzers. Serum ferritin is an indicator of body iron stores: it has been shown to correlate with stainable bone marrow iron. Measurements of ferritin aid in the diagnosis of diseases affecting iron metabolism, such as hemochromatosis (iron overload) and iron deficiency anemia.

Device Story

In vitro diagnostic reagent for quantitative ferritin measurement in human serum and plasma; utilizes latex-enhanced immuno-turbidimetric assay principle; antibody-coated latex beads aggregate in presence of ferritin antigen; immune complexes scatter light; turbidimeter measures light scatter proportional to ferritin concentration; used on Beckman Coulter AU series clinical chemistry analyzers; operated by laboratory technicians; output provided as concentration (ng/mL); results assist clinicians in diagnosing iron metabolism disorders; benefits include assessment of body iron stores and correlation with bone marrow iron.

Clinical Evidence

No clinical data provided in the document; substantial equivalence is based on the device's performance as an immunological test system for ferritin.

Technological Characteristics

Latex-enhanced immuno-turbidimetric assay; liquid ready-to-use reagent; compatible with Beckman Coulter AU400/480/640/680/2700/5400 analyzers; standardized to 3rd International Standard for Ferritin (NIBSC 94/572); utilizes photo-optic detection of light scatter; reagent stability 60 days on-board.

Indications for Use

Indicated for the quantitative determination of ferritin in human serum and plasma to aid in the diagnosis of iron metabolism disorders, including hemochromatosis and iron deficiency anemia, in adult patients.

Regulatory Classification

Identification

A ferritin immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the ferritin (an iron-storing protein) in serum and other body fluids. Measurements of ferritin aid in the diagnosis of diseases affecting iron metabolism, such as hemochromatosis (iron overload) and iron deficiency amemia.

Submission Summary (Full Text)

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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

A. 510(k) Number:
k092505

B. Purpose for Submission:
New Device

C. Measurand:
Ferritin

D. Type of Test:
Quantitative, immuno-turbidimetric

E. Applicant:
Beckman Coulter Inc.

F. Proprietary and Established Names:
Ferritin (OSR61203)

G. Regulatory Information:
1. Regulation section:
21 CFR § 866.5340 Ferritin immunological test system
2. Classification:
Class II
3. Product code:
DBF – Ferritin, antigen, antiserum, control
4. Panel:
Immunology (82)

H. Intended Use:
1. Intended use(s):
The Ferritin Reagent is for the determination of ferritin concentrations in human serum and plasma on the Beckman Coulter family of clinical chemistry analyzers. Serum ferritin is an indicator of body iron stores: it has been shown to correlate with stainable bone marrow iron. Measurements of ferritin aid in the diagnosis of diseases affecting iron metabolism, such as hemochromatosis (iron overload) and iron deficiency anemia.
2. Indication(s) for use:
Same as Intended Use.
3. Special conditions for use statement(s):
Prescription use only.
4. Special instrument requirements:
Beckman Coulter AU400/400e/480, AU600/640/640e/680, and AU2700/5400 Chemistry Analyzers.

I. Device Description:
The Beckman Coulter Ferritin reagents are ready-to-use and consist of four 24 mL bottles of the R1 Ferritin Latex reagent and four 12 mL vials of the R2 Ferritin Latex reagent.

J. Substantial Equivalence Information:
1. Predicate device name(s):
Olympus Ferritin Reagent

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2. Predicate K number(s):
k030124

3. Comparison with predicate:

| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Intended Use/Indications for Use | The Ferritin reagent for the determination of ferritin concentrations in human serum using the Beckman Coulter family of AU clinical chemistry analyzers. For in vitro diagnostic use only.
Serum ferritin is an indicator of body iron stores: it has been shown to correlate with stainable bone marrow iron. Measurements of ferritin aid in the diagnosis of diseases affecting iron metabolism, such as hemochromatosis (iron overload) and iron deficiency anemia. | Same |
| Measurement | Quantitative | Same |
| Operating Principle | Latex enhanced immuno-turbidimetric | Same |
| Calibrator | Olympus Serum Protein Multi-Calibrator (ODR3021) | Same |
| Traceability/Standardization | 3rd International Standard for Ferritin, Recombinant NIBSC code: 94/572. | Same |
| Reagent Form | Liquid ready to use | Same |
| Assay Range | 8.0 – 450.0 ng/mL | Same |
| Instrument | Beckman Coulter AU400/400e/480, AU600/640/640e/680, and AU2700/5400 Chemistry Analyzers | Same (instruments’ name change only) |
| Differences | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Specimens | Serum, Li-heparin plasma & EDTA plasma | Serum |
| Reagent on Board Stability | Opened reagents are stable for 60 days when stored in the refrigerated compartment of the analyzer. | 30 days |

K. Standard/Guidance Document Referenced (if applicable):
CLSI EP5-A2, Method Comparison and Bias Estimation Using Patient Samples
CLSI EP6-A, Evaluation of the linearity of quantitative measurement
CLSI EP7-A2, Interference Testing in Clinical Chemistry
CLSI EP9-A2, Method Comparison and Bias Estimation Using Patient Samples
CLSI EP17-A, Protocols for determination of limits of detection and limits of quantitation
CLSI C28-A3, Defining, establishing, and verifying reference intervals in the clinical

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laboratory

L. Test Principle:
The Beckman Coulter Ferritin reagent is an immuno-turbidimetric test for the quantitative determination of Ferritin in human serum and plasma. Latex agglutination reactions occur as a result of antibody-coated latex beads aggregating if antigen is present in sufficient quantity. Immune complexes formed in solution scatter light in proportion to their size, shape and concentration. Under conditions of antibody excess, increasing amounts of antigen result in higher scatter. Turbidimeters measure the reduction of incident light due to reflection, absorption, or scatter.

M. Performance Characteristics (if/when applicable):

1. Analytical performance:

a. Precision/Reproducibility:
Three pooled samples, created from serum based control material were tested in duplicate, twice a day for 20 days on each of 3 instruments, yielding 80 observations for each sample. The low and high levels were created from human serum pools and the medium level pool represents a commercial control sample.

| Sample | AU400 | | | AU640 | | | AU2700 | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | Mean (ng/mL) | Within-Run % CV | Total precision % CV | Mean (ng/mL) | Within-Run % CV | Total precision % CV | Mean (ng/mL) | Within-Run % CV | Total precision % CV |
| Low | 25.61 | 6.76 | 10.87 | 24.49 | 4.7 | 4.92 | 23.98 | 4.84 | 5.28 |
| Medium | 144.75 | 1.95 | 2.72 | 146.5 | 0.74 | 1.23 | 143.26 | 1.51 | 1.74 |
| High | 429.52 | 0.78 | 1.25 | 436.59 | 0.43 | 1.00 | 436.2 | 0.7 | 0.79 |

A second precision study was performed with sample values at the low end of the assay range and run on the AU400 and AU2700 instruments. The mean values and within-run precision were 10.9 ng/mL (4.42 %CV) on the AU400 and 9.8 ng/mL (7.29 %CV) on the AU2700.

Lot-to-Lot:
Lot-to-lot reproducibility was assessed using two manufactured lots and tested on three instrument family members using commercial controls. In all cases a less than 10% variation in recovery values was observed.

b. Linearity/assay reportable range:
High and low linearity pools were prepared from in-house samples. The high sample pool was spiked with a commercial material (containing human liver Ferritin) to approximately 10% above the dynamic range. The low pool was prepared with 0.9% saline. The high and low pools were mixed from 0 up to 100% using a protocol consistent with CLSI EP6-A. Each sample was run four times. The reagent was determined to be linear from ~1 to 490 ng/mL and the final claimed linearity range is 8-450 ng/mL, as this is consistent with the predicate product. The regression equation provided for the representative instrument AU400 series was y = 1.00x - 0.991 (r² = 0.99).

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c. Traceability, Stability, Expected values (controls, calibrators, or methods): The Ferritin values assigned to the calibrators are traceable to the 3rd International Standard for Ferritin, Recombinant NIBSC code: 94/572.

Stability:

On-board (OB) and calibration stability as well as shelf life stability were measured on multiple instruments. Calibration stability is 30 days and on-board reagent stability is 60 days. Shelf life is 10 months.

d. Detection limit:

The LoD and LoB were determined using 60 replicates of a blank sample and 15 replicates of four pools made up based on approximately 4 times the LoB sample value. The LoD is defined as the LoB of the assay + 1.645 times the δ, where δ = √(SD² produced from the replicates of each sample). For the LoQ, seven pools (~8 - 80 ng/mL) with ferritin concentrations at different levels were tested 25 times (5 times/day for 5 days) using 2 different reagent lots on each of the analyzers. The LoQ was determined as the first concentration with a %CV ≤ 20%.

| | LoB (ng/mL) | LoD (ng/mL) | LoQ (ng/mL) | |
| --- | --- | --- | --- | --- |
| | | | Lot 1 | Lot 2 |
| AU400 | 2.17 | 3.45 | 5.43 | 7.76 |
| AU640 | 1.14 | 2.81 | 4.69 | 4.98 |
| AU2700 | 2.56 | 4.34 | 5.2 | 5.55 |

e. Analytical specificity:

i. Potential interference by endogenous substances were performed using a protocol based on CLSI EP7-A2 that uses two levels (20-36 ng/mL and 170-223 ng/mL) of the analyte and tested on two different instruments. Potential endogenous interferents were spiked into the samples at increasing levels and the results were compared to the unspiked sample. Interference was determined if the values of the spiked low level samples exceeded ±5 ng/mL of unspiked sample or more than 10% difference of the unspiked sample for the high level samples. Intralipid interference was tested instead of triglyceride as the analyzers used have sensitive photo-optics and it was believed that Intralipid would give a more accurate picture on whether interference would be seen. An approximate triglyceride equivalent concentration of 1200 mg/dL is included in the package insert. No interference was noted for samples containing less than: hemoglobin (500 mg/dL); bilirubin (40 mg/dL); intralipid (400 mg/dL); and rheumatoid factor (500 IU/mL).

ii. Antigen Excess (Prozone):

A commercial prozone material (containing human liver Ferritin) was used and diluted with saline to assign ferritin concentrations to each of the 24 dilutions. The undiluted material was determined to be approximately 35,500 ng/mL and each diluted sample was run in triplicate on each of the

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analyzers. A critical point of approximately 20,000 ng/mL was established and is the limit of prozone tolerance. Samples giving ferritin values above the upper end of the measuring range are flagged (F-flag) to warn the user to dilute the sample. Samples with a ferritin concentration above the critical point are considered prozone samples and are flagged with a 'Z' flag.

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

2. Comparison studies:

a. Method comparison with predicate device:
Routine patient serum samples were analyzed by the Beckman Coulter Ferritin device and the predicate device. In order to cover the measuring range, four samples spiked with a commercial human liver Ferritin were also included. All specimens were run in duplicate on four different family member analyzers. Results were analyzed by Deming regression and summarized below. The observed positive bias may be due to the OSR61203 having a higher specificity to Ferritin than the antibodies used in OSR6150 predicate.

| Analyzer | N= | % bias | Deming regression | | |
| --- | --- | --- | --- | --- | --- |
| | | | Slope | Intercept | R |
| A2700 | 100 | 8.78 | 1.026 | 4.93 | 0.9977 |
| AU400 | 110 | 14.17 | 1.062 | 6.61 | 0.993 |
| AU640 | 103 | 11.71 | 1.066 | 3.14 | 0.9924 |
| AU680 | 103 | 16.58 | 1.048 | 8.41 | 0.9932 |

b. Matrix comparison:
CLSI EP9-A2 was employed to validate different sample matrices. Forty-seven matched serum, Li Heparin plasma, and EDTA plasma samples covering the majority of the dynamic range were evaluated. The samples were run in duplicate. Comparability between matrices was evaluated by linear regression.

| Matrix compared to serum | Sample range (ng/mL) | Slope | Intercept (ng/mL) | Correlation coefficient (r) |
| --- | --- | --- | --- | --- |
| EDTA plasma | 8.35 – 411.02 | 0.971 | -0.036 | 0.999 |
| Li Heparin | 8.35 – 411.02 | 0.988 | -0.688 | 1.000 |

3. Clinical studies:

a. Clinical Sensitivity:
Not applicable.

b. Clinical specificity:
Not applicable.

4. Clinical cut-off:
See Expected values/Reference range.

5. Expected values/Reference range:

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The reference range was established by assessing ferritin levels from 279 apparently healthy adults (125 females and 154 males) and gave the following results: 10 – 158 ng/mL (female) and 16 – 243 ng/mL (male).

**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.

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