← Product Code [CFN](/productcode/CFN) · K073487

# OLYMPUS IGM REAGENT (K073487)

_Olympus America, Inc. · CFN · Feb 11, 2008 · Immunology · SESE_

**Canonical URL:** https://fda.innolitics.com/device/K073487

## Device Facts

- **Applicant:** Olympus America, Inc.
- **Product Code:** [CFN](/productcode/CFN.md)
- **Decision Date:** Feb 11, 2008
- **Decision:** SESE
- **Submission Type:** Traditional
- **Regulation:** 21 CFR 866.5510
- **Device Class:** Class 2
- **Review Panel:** Immunology

## Indications for Use

System reagent for the quantitative determination of IgM immunoglobulins in human serum and plasma on OLYMPUS analyzers. For in vitro diagnostic use.

## Device Story

Quantitative immunoturbidimetric assay for IgM measurement; utilizes R1 buffer (Tris, PEG 6000) and R2 (goat anti-IgM antiserum). Sample mixed with reagents; human IgM reacts with anti-IgM antibodies to form insoluble aggregates. Analyzer measures decrease in transmitted light intensity (absorbance increase) proportional to aggregate concentration. Used in clinical laboratories on Olympus AU400/400e, 600/640/640e, and 2700/5400 analyzers. Output is IgM concentration (mg/dL). Results aid clinicians in assessing protein metabolism and immune function. Supports serum and plasma (Li heparin/EDTA) matrices.

## Clinical Evidence

Bench testing only. Precision studies (n=80) showed total %CV 2.60–4.08%. Linearity confirmed 20–500 mg/dL. LoQ <10 mg/dL; LoD ≤2 mg/dL. Interference testing (bilirubin, lipids, hemoglobin) showed ≤10% interference. Method comparison with predicate (n=107-110) showed slopes 0.978–1.027 and r=0.999–1.000. Matrix comparison (n=45) confirmed equivalence between serum and plasma (Li heparin/EDTA) with r=1.000.

## Technological Characteristics

Immunoturbidimetric assay; liquid reagents (Tris buffer, PEG 6000, goat anti-IgM antiserum); sodium azide preservative. Measuring range 20-500 mg/dL. Traceable to CRM 470. On-board stability 90 days. Analyzers: Olympus AU series.

## Regulatory 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.

## Predicate Devices

- Olympus IgM reagent (OSR6X46) (k950900)

## Submission Summary (Full Text)

> This content was OCRed from public FDA records by [Innolitics](https://innolitics.com). If you use, quote, summarize, crawl, or train on this content, cite Innolitics at https://innolitics.com.
>
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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

A. 510(k) Number:
k073487

B. Purpose for Submission:
Addition of plasma (Li heparin/EDTA) matrix claim to the predicate device

C. Measurand:
Immunoglobulin M (IgM)

D. Type of Test:
Quantitative immunoturbidimetric assay

E. Applicant:
Olympus America, Inc.

F. Proprietary and Established Names:
Olympus IgM reagent (OSR6X173)

G. Regulatory Information:

|  Product Code | Classification | Regulation Section | Panel  |
| --- | --- | --- | --- |
|  CFN Method, Nephelometric, Immunoglobulins (G, A, M) | Class II | 21 CFR 866.5510
Immunoglobulins A, G, M, D, E
Immunological Test System | Immunology (IM82)  |

H. Intended Use:

1. Intended use(s):
System reagent for the quantitative determination of IgM immunoglobulins in human serum and plasma on OLYMPUS analyzers

2. Indication(s) for use:
The spectrum of abnormalities in serum immunoglobulin concentration is broad. Abnormal concentrations range from a virtual absence of one or more of the three major classes of immunoglobulins (IgA, IgG and IgM) to polyclonal increases in one or more immunoglobulins. Measurement of these immunoglobulins aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents.

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

4. Special instrument requirements:
OLYMPUS analyzers: AU400/400ᵉ, 600/640/640ᵉ and 2700/5400

I. Device Description:
The device consists of two reagents: R1 buffer (Tris buffer pH 7.2, polyethylene glycol 6000) and R2 (goat anti-IgM antiserum). The reagents contain sodium azide as preservative.

J. Substantial Equivalence Information:

1. Predicate device name(s):
Olympus IgM reagent (OSR6X46)

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2. Predicate 510(k) number(s): k950900
3. Comparison with predicate:

|  Similarities  |   |   |
| --- | --- | --- |
|  Item | Device | Predicate  |
|   | Olympus IgM reagent (OSR6X173) | Olympus IgM reagent (OSR6X46)  |
|  Intended Use | System reagent for the quantitative determination of IgM immunoglobulins in human serum and plasma on Olympus analyzers | Same but in serum only  |
|  Indications for Use | Aid in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infection | Same  |
|  Test principle | Immunoturbidimetric | Same  |
|  Antibody | Goat anti-IgM | Same  |
|  Reagent form and storage | Liquid, on-board storage | Same  |
|  On-board reagent stability | 90 days | Same  |
|  Calibrator | Olympus Serum Protein Multi-calibrator | Same  |
|  Calibrator traceability | International Reference Preparation CRM 470 | Same  |
|  Calibration frequency | 90 days | Same  |
|  Expected values | 45-281 mg/dL | Same  |
|  Differences  |   |   |
| --- | --- | --- |
|  Item | Device | Predicate  |
|   | Olympus IgM reagent (OSR6X173) | Olympus IgM reagent (OSR6X46)  |
|  Matrix | Serum, plasma (Li heparin or EDTA) | Serum only  |

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

EN14971 (2000) ISO Medical Devices – Application of Risk Management to Medical Devices; EP7-A2 (2005) CLSI Interference Testing in Clinical Chemistry; EP5-A2 (2004) CLSI Evaluation of Precision Performance of Clinical Chemistry Devices; EP9-A2 (2002) CLSI Method Comparison and Bias Estimation Using Patient Samples; CEN 13640 (2002) Stability Testing of In Vitro Diagnostic Reagents; C28-A2 (2000) CLSI How to Define and Determine Reference Intervals in the Clinical Laboratory; EP6-A (2003) CLSI Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; FDA: Draft Guidance document for 510(k) Submission of Immunoglobulins A, G, M, D and E Immunoglobulin Test System In Vitro Devices

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L. Test Principle:

When a sample is mixed with R1 buffer and R2 antiserum solution, human IgM reacts specifically with anti-human IgM antibodies to yield insoluble aggregates. Immune complexes formed in solution scatter light in proportion to their size, shape and concentration. The Olympus analyzer measures the decrease in intensity of light transmitted (increase in absorbance) through particles suspended in solution as a result of complexes formed during the antigen-antibody reaction.

M. Performance Characteristics (if/when applicable):

1. Analytical performance:

a. Precision/Reproducibility:

Assays of 3 human serum pools (high, low and medium) were assayed in duplicate for 2 runs per day for 20 days (n=80) on the AU400/400#, AU600/640/640#, and AU2700/5400. The acceptance criteria for the within-run and total %CV were &lt;4.2% and &lt;10% respectively. The within-run precision covering the instrument platforms ranged from 1.12–2.19% and the total precision ranged from 2.60–4.08%.

AU400/400

|  N=80 | Within-run |   | Total  |   |
| --- | --- | --- | --- | --- |
|  Mean (mg/dL) | SD | %CV | SD | %CV  |
|  48 | 1 | 1.95 | 2 | 4.03  |
|  117 | 2 | 1.40 | 3 | 2.95  |
|  234 | 3 | 1.19 | 6 | 2.60  |

AU600/640/640

|  N=80 | Within-run |   | Total  |   |
| --- | --- | --- | --- | --- |
|  Mean (mg/dL) | SD | %CV | SD | %CV  |
|  48 | 1 | 1.69 | 2 | 3.44  |
|  114 | 2 | 1.36 | 4 | 3.29  |
|  217 | 5 | 2.19 | 8 | 4.08  |

AU2700/5400

|  N=80 | Within-run |   | Total  |   |
| --- | --- | --- | --- | --- |
|  Mean (mg/dL) | SD | %CV | SD | %CV  |
|  48 | 1 | 1.52 | 2 | 3.79  |
|  114 | 1 | 1.12 | 4 | 3.31  |
|  218 | 3 | 1.30 | 8 | 3.52  |

Auto dilution:

To validate the accuracy and precision of automated sample dilution protocol, three auto-dilution samples were diluted manually and run on the instrument. The same samples were diluted automatically by the AU640. Accuracy (%difference) and precision (%CV) were determined.

Accuracy 1:5

|  Level | Automatic dilution (mg/dl) | Manual dilution (mg/dl) | % Difference  |
| --- | --- | --- | --- |
|  1 | 727 | 684 | -6.3  |
|  2 | 592 | 588 | -0.7  |
|  3 | 382 | 374 | -2.1  |

Accuracy 1:10

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|  Level | Automatic dilution (mg/dl) | Manual dilution (mg/dl) | % Difference  |
| --- | --- | --- | --- |
|  1 | 720 | 711 | -1.3  |
|  2 | 566 | 583 | 2.9  |
|  3 | 446 | 450 | 0.9  |

Precision (within run) 1:5

|  Level | Mean (mg/dL) | SD (mg/dL) | CV (%) | Essential Specification  |   |
| --- | --- | --- | --- | --- | --- |
|  1 | 64 | 1 | 1.36 | ≤4.2% CV | Pass  |
|  2 | 85 | 1 | 1.34  |   |   |
|  3 | 107 | 1 | 1.24  |   |   |

Precision (within run) 1:10

|  Level | Mean (mg/dL) | SD (mg/dL) | CV (%) | Essential Specification  |   |
| --- | --- | --- | --- | --- | --- |
|  1 | 32 | 1 | 1.98 | ≤4.2% CV | Pass  |
|  2 | 41 | 1 | 1.75  |   |   |
|  3 | 52 | 1 | 1.77  |   |   |

# b. Linearity/assay reportable range:

The measuring range for the assay is  $20 - 500\mathrm{mg / dL}$ . The procedure used to determine linearity was based on CLSI EP6-A. A series of at least ten analyte concentrations, covering the linear dynamic range was prepared by dilution of a high pool sample. Each dilution was assayed in quadruplicate and the mean analytical results were plotted versus the relative analyte concentrations (\% dilution). Studies were performed on the AU400, AU640 and AU2700 analyzers. The acceptance criteria for deviation from regression line for the  $20 - 80\mathrm{mg / dL}$  and  $80 - 500\mathrm{mg / dL}$  ranges were  $\pm 8\mathrm{mg / dL}$  and  $\pm 10\%$  respectively. The studies showed the assay was linear from  $20 - 500\mathrm{mg / dL}$ . Hook effect may occur with highly elevated IgM samples  $&gt;10,000\mathrm{mg / dL}$ , polyclonal.

c. Traceability, Stability, Expected values (controls, calibrators, or methods): The calibrator is traceable to the International Reference Preparation CRM470 (US designation RPPHS lot 91/0619).

Reagent on-board stability was demonstrated according to internal procedures where the linearity displayed at day 90 and the  $\%$  drift from Day 0 from control recovery were calculated. A change of  $\leq 10\%$  was demonstrated over the 90 days.

# d. Detection limit:

The Limit of Quantitation (LoQ) for the new assay was determined by testing 3 patient pools, 40 fold at an analyte concentration below the lower end of the measuring range on the AU400, AU640 and AU2700. The analyte level with a CV of less than  $20\%$  was determined to be  $&lt; 10 \mathrm{mg} / \mathrm{dL}$ . This was determined using a method based on the CLSI protocol EP17-A.

|   | Mean Concentration (mg/dL) | SD | CV (%)  |
| --- | --- | --- | --- |
|  AU400 | 8.1 | 1.4 | 17.7  |
|  AU600 | 2.4 | 0.4 | 16.1  |
|  AU2700 | 2.4 | 0.4 | 17.0  |

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The Limit of Detection (LoD) or the concentration of analyte which is significantly different from zero was determined by testing an analyte free sample twenty-fold on the AU400, AU640 and AU2700. LoD was calculated as the absolute mean + 3SD and the lowest detectable level was determined to be ≤ 2 mg/dL.

|   | Mean Concentration (mg/dL) | SD | LoD (mg/dL)  |
| --- | --- | --- | --- |
|  AU400 | 0.0 | 0.324 | 0.97  |
|  AU600 | -0.29 | 0.293 | 1.17  |
|  AU2700 | 0.30 | 0.336 | 1.31  |

e. Analytical specificity:

The impact of bilirubin, lipids and hemoglobin were assessed in accordance with CLSI EP7-A2.

|  Substance | Levels up to | % Interference  |   |   |
| --- | --- | --- | --- | --- |
|   |   |  AU400/400^{e} | AU600/640/640^{e} | AU2700/5400  |
|  Bilirubin | 40 mg/dL | ≤ 4% | ≤ 3% | ≤ 8%  |
|  Lipids | 300 mg/dL | ≤ 10% | ≤ 10% |   |
|   |  200 mg/dL |  |  | ≤ 10%  |
|  Hemoglobin | 500 mg/dL | ≤ 4% | ≤ 3% | ≤ 3%  |

f. Assay cut-off:

See reference range

2. Comparison studies:

a. Method comparison with predicate device:

|  Y method (new) | AU2700 | AU2700/5400 | AU2700/5400  |
| --- | --- | --- | --- |
|  X method (predicate) | AU2700 | AU400 | AU640/640^{e}  |
|  Slope | 1.006 | 1.027 | 0.978  |
|  Intercept | 2.8 | -2.6 | 2.4  |
|  Correlation coefficient (r) | 1.000 | 0.999 | 0.999  |
|  Number of samples | 107 | 110 | 108  |
|  Range (mg/dL) Y method | 22-468 | 20-468 | 21-468  |
|  Range (mg/dL) X method | 22-467 | 21-443 | 21-469  |

b. Matrix comparison:

Studies were performed based on CLSI EP9-A2.

|  Y method | Li-heparin plasma | EDTA plasma  |
| --- | --- | --- |
|  X method | Serum | Serum  |
|  Slope | 0.96 | 0.942  |
|  Intercept | +0.892 | +0.998  |
|  Correlation coefficient | 1.000 | 1.000  |
|  Number of samples | 45 | 45  |
|  Patient mean value - serum mg/dL | 148.47 | 148.47  |
|  Patient mean value - plasma mg/dL | 143.47 | 140.80  |
|  Reference range - serum mg/dL | 27.46 - 450.23 | 27.46 - 450.23  |
|  Reference range - plasma mg/dL | 26.26 - 436.86 | 25.96 - 429.84  |

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3. Clinical studies:
a. Clinical Sensitivity: Not determined
b. Clinical specificity: Not determined
c. Other clinical supportive data (when a. and b. are not applicable): Not applicable

4. Clinical cut-off: Not applicable

5. Expected values/Reference range: Expected values may vary with age, sex, diet and geographical location. The reference range of 45-281 mg/dL established for the predicate device was re-verified according to CLSI C28-A2 on the Olympus AU400, 600 and 5400.

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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**Source:** [https://fda.innolitics.com/device/K073487](https://fda.innolitics.com/device/K073487)

**Published by [Innolitics](https://innolitics.com)** — a medical-device software consultancy. We help companies design, build, and clear FDA-regulated software and AI/ML devices. If you're preparing [a 510(k)](https://innolitics.com/services/510ks/), [a De Novo](https://innolitics.com/services/regulatory/), [a SaMD](https://innolitics.com/services/end-to-end-samd/), [an AI/ML medical device](https://innolitics.com/services/medical-imaging-ai-development/), or [an FDA regulatory strategy](https://innolitics.com/services/regulatory/), [get in touch](https://innolitics.com/contact).

**Cite:** Innolitics at https://innolitics.com