HUMAN IGD KIT FOR USE ON SPAPLUS

K092450 · The Binding Site · CZJ · Dec 28, 2009 · Immunology

Device Facts

• Record ID: K092450
• Device Name: HUMAN IGD KIT FOR USE ON SPAPLUS
• Applicant: The Binding Site
• Product Code: CZJ · Immunology
• Decision Date: Dec 28, 2009
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.5510
• Device Class: Class 2

Indications for Use

This kit is intended for measuring human immunoglobulin D (IgD) in serum as an aid in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents. The test results are to be used in conjunction with other clinical and laboratory findings.

Device Story

The Human IgD Kit for use on SPAplus is an in vitro diagnostic assay designed to measure human immunoglobulin D (IgD) levels in serum samples. The device operates on the SPAplus analyzer platform. It is intended for use by laboratory professionals in clinical settings. The test provides quantitative IgD measurements, which clinicians use alongside other clinical and laboratory findings to assess protein metabolism and immune function. By identifying abnormal IgD levels, the device assists in the diagnostic evaluation of patients with suspected protein metabolism disorders or compromised resistance to infectious agents.

Clinical Evidence

No clinical data provided in the document; substantial equivalence is based on the regulatory determination for the immunologic test system.

Technological Characteristics

Quantitative nephelometric immunoassay. Reagents: sheep anti-human IgD antiserum coated polystyrene latex, reaction buffer, calibrators, controls. Preservatives: sodium azide, EACA, benzamidine. Instrument: SPAPLUS analyzer. Detection: photoiodide sensing of transmitted light. Traceability: NIBSC 67/037 British Reference Standard. Software: automated calculation of concentration via calibration curve.

Indications for Use

Indicated for measuring human IgD in serum to aid in diagnosing abnormal protein metabolism and immune deficiency in patients. For prescription use only.

Regulatory Classification

Identification

An immunoglobulins A, G, M, D, and E immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the immunoglobulins A, G, M, D, an E (serum antibodies) in serum. Measurement of these immunoglobulins aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents.

Submission Summary (Full Text)

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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

A. 510(k) Number:
k092450

B. Purpose for Submission:
New device

C. Measurand:
IgD antibody

D. Type of Test:
Quantitative nephelometry

E. Applicant:
The Binding Site, Ltd.

F. Proprietary and Established Names:
Human IgD Kit for use on $\mathrm{SPAPLUS}^{\mathrm{TM}}$

G. Regulatory Information:
1. Regulation section:
21 CFR § 866.5510 Immunoglobulins A, G, M, D, E Immunological Test System
2. Classification:
Class II
3. Product codes:
CZJ, IgD, Antigen, antiserum, control
4. Panel:
Immunology 82

H. Intended Use:
1. Intended use(s):
This kit is intended for measuring human immunoglobulin D (IgD) in serum as an aid in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents. The test results are to be used in conjunction with other clinical and laboratory findings.
2. Indication(s) for use:
Same as intended use.
3. Special conditions for use statement(s):
For prescription use only.
4. Special instrument requirements:
The Binding Site $\mathrm{SPAPLUS}^{\mathrm{TM}}$

I. Device Description:
The device consists of the following: monospecific sheep anti-IgD antiserum coated polystyrene latex in liquid with preservatives; Calibrators 1-6; Low and High controls in liquid form; and IgD reaction buffer. The reagents contain $0.099\%$ sodium azide, $0.1\%$ EACA, and $0.01\%$ benzamidine as preservatives.

J. Substantial Equivalence Information:
1. Predicate device name(s):
Binding Site Human IgD Liquid Reagent Kits for use on the Behring BNII Analyser
2. Predicate K number(s):

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k051299

3. Comparison with predicate:

| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| | Human IgD Kit for use on SPAPLUS™ | Human IgD Liquid Reagent Kits for use on the Behring BNII Analyser |
| Intended Use | Quantitative determination of IgD in serum | Same |
| Detection Method | Nephelometric immunoassay | Same |
| Traceability | Standardized against Human Serum Immunoglobulin D NIBSC 67/037 British Reference Standard | Same |
| Controls | Low and High levels liquid ready to use | Same |
| Sample Matrix | Human serum | Same |
| Antibodies | Sheep Anti-Human IgD | Same |
| Differences | | |
| --- | --- | --- |
| Item | Device | Predicate |
| | Human IgD Kit for use on SPAPLUS™ | Human IgD Liquid Reagent Kits for use on the Behring BNII Analyser |
| Instruments | SPAPLUS™ analyser | BN™ II analyser |
| Measuring range | 7.0 - 210 mg/L at 1:10 dilution 140-4400 mg/L at 1:10 dilution 560 -17600 mg/L at 1:40 dilution (extended dilution with 1:20 off line) | 6.5 – 207.5 mg/L at 1:100 dilution 130 – 4150 mg/L at 1: 2000 dilution |
| Reference Range | 7.7 – 132.1 mg/L | 1.3 – 152.7 mg/L |

K. Standard/Guidance Document Referenced (if applicable):
CLSI (NCCLS) EP-5A: Evaluation of Precision Performance of Clinical Chemistry.
CLSI (NCCLS) EP-17A: Protocols for Determination of LOD and LOQ
CLSI (NCCLS) EP-6A: Evaluation of Linearity of Quantitative Measurements

L. Test Principle:
The determination of soluble antigen concentration by nephelometric methods involves the reaction with specific antisera to form insoluble complexes. When light is passed through the suspension formed, a portion of the light is transmitted and focused onto a photoiodide by an optical lens system. The amount of transmitted light is indirectly proportional to the specific protein concentration in the test sample. Concentrations are automatically calculated by reference to a calibration curve within the instrument.

M. Performance Characteristics (if/when applicable):
1. Analytical performance:
a. Precision/Reproducibility:

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The intra-assay precision was determined by testing three serum samples twenty one times. The inter-assay precision was determined by testing three serum samples tested three times per run and two runs per day for 21 days. Results are summarized below.

Intra-assay:

| Anti-IgD | | | |
| --- | --- | --- | --- |
| n=21 | SD (mg/L) | Mean Concentration (mg/L) | % CV |
| Sample 1 | 2.50 | 169.42 | 1.5 |
| Sample 2 | 1.44 | 122.60 | 1.2 |
| Sample 3 | 0.26 | 11.66 | 2.3 |

Inter-assay:

| Anti-IgD | | | |
| --- | --- | --- | --- |
| n=21 | SD (mg/L) | Mean Concentration (mg/L) | % CV |
| Sample 1 | 1.86 | 169.42 | 1.1 |
| Sample 2 | 1.44 | 122.60 | 0.9 |
| Sample 3 | 0.25 | 11.66 | 2.2 |

b. Linearity/assay reportable range:

Linearity across the assay measuring range (7.0 - 210 mg/L) was confirmed by testing two pooled sera with low range concentrations from 25 - 27 mg/L and two pooled sera with high concentrations from 89-97 mg/L. The samples were serially diluted 1:10 with buffer 11 times to the lower measuring range (7.0 mg/L). The diluted samples were re-assayed on three different lots of IgD kits. The regression equations on the three IgD lots where y is the measured level of IgD concentration and x the theoretical concentration were as follows:

$$
y = 0.9972x - 2.76, R^2 = 0.9983;
$$

$$
y = 1.0223x - 0.8784, R^2 = 0.9992; \text{ and}
$$

$$
y = 0.9988x - 4.7, R^2 = 1.0.
$$

c. Traceability, Stability, Expected values (controls, calibrators, or methods):

The calibrators are traceable to the Human Serum Immunoglobulin D NIBSC 67/037 British Reference Standard.

Stability: The expiration date claims are 13 months for the IgD unopened kit and 28 days for on-board IgD kit.

d. Detection limit:

The detection limit was determined by testing a blank sample, the lowest calibrator, and a sample with value close to the blank sample (0.6 mg/L) 60 times each. The limit of quantification for this assay is defined as the lowest

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point of the calibration curve: 6.33 mg/L.

e. Analytical specificity:

Interference by endogenous and other substances: A serum sample with known IgD concentration was tested in triplicate with the following interferents: 4.8 mg/L hemoglobin, 200 mg/dL bilirubin and 1560 FTU of chyle. No significant interference by these substances was observed. The package insert states that "microbial contaminated, lipemic, hemolyzed or samples containing particulate matter should not be used".

Antigen excess effect:

No antigen excess effect up to 1680 mg/L of IgD was observed.

f. Assay cut-off:

The assay cut-off was determined to be the upper limit of 120 sera from normal healthy adults in the United Kingdom and was 132.1 mg/L. To validate the cut-off, fifteen IgD myeloma samples were tested and all had IgD concentrations >132.1 mg/L.

2. Comparison studies:

a. Method comparison with predicate device:

Testing was performed on 97 sera samples (50 normal and 47 clinical samples) with the new device "The Binding Site Human IgD kit for use on Spa plus™" and the predicate device "The Binding Site Human IgD Liquid reagent Kit for use on the Behring BN™ II analyser". The IgD concentration ranged from 7.7- 51,352 mg/L. Forty six of the 50 normal samples had normal IgD levels and 4 had elevated IgD. Seventeen of the 47 clinical samples were from IgD myeloma clinic and had elevated IgD. Thirty of the 47 clinical samples were from general clinic and all 30 had normal IgD levels.

The regression analysis of the comparison study is summarized below:

| | n | Slope | 95% CI | Intercept | 95% CI | r |
| --- | --- | --- | --- | --- | --- | --- |
| The Binding Site Spa plus™ vs BN™ II analyser | 97 | 0.950 | 0.91 – 1.01 | - 0.590 | 1.62 – 0.42 | 0.995 |

Positive, negative and overall percent agreements between the two devices were 100% (see table below):

| | BN™ II analyser | | | |
| --- | --- | --- | --- | --- |
| | | Elevated (>152.7 mg/L) | Normal (<152.7 mg/L) | Total |
| The Binding Site Spa plus™ | Elevated (>132.1 mg/L) | 21 | 0 | 21 |
| | Normal (<132.1 mg/L) | 0 | 76 | 76 |
| | Total | 21 | 76 | 97 |

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b. In addition, Matrix comparison: Both assays use human serum as a matrix.

3. Clinical studies:

a. Clinical Sensitivity and specificity: The clinical sensitivity and specificity were evaluated on the same 97 samples used in the method comparison study. Out of 17 IgD myeloma clinical samples, 15 were from patients diagnosed IgD multiple myeloma and 2 were "unknown", but had elevated IgD levels. All 17 samples had elevated levels of &gt;132.1 mg/L. On the other hand, all 30 non-myeloma general clinic samples had normal levels of &lt;132.1 mg/L IgD. Of the 50 normal samples, 46 had normal IgD levels of &lt;132.1 mg/L and 4 had elevated results of 136.5; 137.2; 166.3; and 221.3 mg/L.

IgD myeloma rarely occurs (&lt;1% of multiple myeloma cases). Elevated levels of IgD have been associated with both 'IgD myeloma' and 'Syndromes with Hypergammaglobulinemia D (hyper IgD) and periodic fever'.

b. Other clinical supportive data (when a. is not applicable): Not applicable.

4. Clinical cut-off: See Assay cut-off.

5. Expected values/Reference range: Adult normal range was assessed on a total 120 healthy adult UK blood donors sera samples. The assays were performed on the Binding Site SPAplus™. A non-parametric distribution of IgD results were seen that gave a 95 percentile reference interval of 7.7- 132.1 mg/L with a mean of 49.4 mg/L and a median of 42.8 mg/L.

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.