← Product Code [DEH](/submissions/IM/subpart-f%E2%80%94immunological-test-systems/DEH) · K033811

# FREELITE HUMAN KAPPA AND LAMBDA FREE KITS FOR USE ON THE OLYMPUS AU ANALYZER (K033811)

_The Binding Site, Ltd. · DEH · Jan 30, 2004 · Immunology · SESE_

**Canonical URL:** https://fda.innolitics.com/submissions/IM/subpart-f%E2%80%94immunological-test-systems/DEH/K033811

## Device Facts

- **Applicant:** The Binding Site, Ltd.
- **Product Code:** [DEH](/submissions/IM/subpart-f%E2%80%94immunological-test-systems/DEH.md)
- **Decision Date:** Jan 30, 2004
- **Decision:** SESE
- **Submission Type:** Traditional
- **Regulation:** 21 CFR 866.5550
- **Device Class:** Class 2
- **Review Panel:** Immunology

## Indications for Use

This kit is intended for the quantitation of kappa free light chains in serum and urine on the Olympus AU series analysers. Measurement of the various amounts of the different types of light chains aids in the diagnosis and monitoring of lymphocytic neoplasms, multiple myeloma, Waldenstrom's macroglobulinemia, amyloidosis, light chain deposition disease and connective tissue diseases such as systemic lupus erythematosus.

## Device Story

FREELITE® Human Kappa and Lambda Free Kits are in vitro diagnostic reagents for use on Olympus AU series analyzers. The device quantifies free light chains in serum and urine samples. It functions as an immunoturbidimetric assay; the presence of free light chains in the sample causes agglutination of latex particles coated with specific antibodies, which is measured by the analyzer. The output is a quantitative concentration of kappa or lambda free light chains. Used in clinical laboratories by trained technicians to assist physicians in diagnosing and monitoring conditions such as multiple myeloma, amyloidosis, and connective tissue diseases. The quantitative results inform clinical decision-making regarding disease progression and treatment efficacy.

## Clinical Evidence

No clinical data provided; substantial equivalence is based on analytical performance and technological characteristics of the assay for use on the specified Olympus AU series analyzers.

## Technological Characteristics

Quantitative nephelometric immunoassay. Reagents: specific anti-κ or anti-λ antibodies. Measurement: light scattering intensity proportional to antigen-antibody complex concentration. Form factor: liquid reagents for use on automated Olympus AU™ series analyzers. Connectivity: integrated into clinical chemistry analyzer workflow. Stability: up to 12 months at 2–8°C.

## Regulatory Identification

An immunoglobulin (light chain specific) immunological test system is a device that consists of the reagents used to measure by immunochemical techniques both kappa and lambda types of light chain portions of immunoglobulin molecules in serum, other body fluids, and tissues. In some disease states, an excess of light chains are produced by the antibody-forming cells. These free light chains, unassociated with gamma globulin molecules, can be found in a patient's body fluids and tissues. Measurement of the various amounts of the different types of light chains aids in the diagnosis of multiple myeloma (cancer of antibody-forming cells), lymphocytic neoplasms (cancer of lymphoid tissue), Waldenstrom's macroglobulinemia (increased production of large immunoglobulins), and connective tissue diseases such as rheumatoid arthritis or systemic lupus erythematosus.

## Submission Summary (Full Text)

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K033811
The Binding Site, Ltd.

# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

A. 510(k) Number:
K033811 (bundled)

B. Analyte:
kappa (κ) free light chain, lambda (λ) free light chain

C. Type of Test:
Quantitative (nephelometry)

D. Applicant:
The Binding Site, Ltd.

E. Proprietary and Established Names:
FREELITE® Human Kappa Free Kit for use on the Olympus AU™ series diagnostic test kits

FREELITE® Human Lambda Free Kit for use on the Olympus AU™ series diagnostic test kits

F. Regulatory Information:
1. Regulation section:
21 CFR § 866.5550, Immunoglobulin (light chain specific) immunological test system.
2. Classification:
Class II
3. Product Codes:
DFH [Kappa (κ)]; DEH [Lambda (λ)]
4. Panel:
82

G. Intended Use:
1. Intended use(s):
The FREELITE® Human kappa (κ) free and the FREELITE® Human Lambda (λ) free kits is used to determine the concentration of these light chains in serum and urine on the Olympus AU™ series diagnostic test kits. (The kits are sold separately.)
2. Indication(s) for use:
The quantitation of κ and λ free light chains "...aids in the diagnosis and monitoring of multiple myeloma, lymphocytic neoplasms, Waldestrom's macroglobulinemia, amyloidosis, light chain deposition disease and connective tissue diseases such as systemic lupus erythematosus."

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The Binding Site, Ltd.

3. **Special condition for use statement(s):**
Not applicable.

4. **Special instrument Requirements:**
The test kits are used on the Olympus AU™ series diagnostic test kits.

**H. Device Description:**
Each FREELITE® kit contains the specific anti-free light chain antibody, i.e., either anti-κ or anti-λ, and the reagents needed for assaying serum and urine samples. (Each kit is sold separately.)

**I. Substantial Equivalence Information:**

1. **Predicate device name(s):**
FREELITE® BNII test kits.

2. **Predicate K number(s):**
K010440 AND K010441

3. **Comparison with Predicate:**
The kits in this submission are identical to those in the predicate devices. The only difference is that the kits will be used in another test system.

**J. Standard/Guidance Document Referenced (if applicable):**
Not applicable.

**K. Test Principle:**
The concentration of the soluble antigen is assessed by nephelometry. The test sample is mixed with the appropriate antibody in a solution inside a cuvette. As the antigen-antibody complex forms, a beam of light is passed through the cuvette. The degree of scattering of this light increases with the increase in the concentration of insoluble immune complexes. An excess of antibody is placed in the cuvette so that the amount of immune complex formed is proportional to the antigen concentration. Measurement of the light intensity at an angle away from the incident light is used to monitor the light scattering. A Calibration curve of measured light scatter vs. antigen concentration is generated using a series of Calibrators of known antigen concentration, and the results read from this curve for samples of unknown antigen concentration.

**L. Performance Characteristics (if/when applicable):**
1. **Analytical performance:**
a. **Precision/Reproducibility:**
Repetitive assays of clinical sera at three different concentration levels, i.e., low, medium, and high, were performed, i.e., 10 measurements made on one day run for within run precision, and 10 separate assays using the same batch of antisera for between run precision. The data summarized below show consistent results across all three levels with an acceptable percentage Coefficient of Variation (%CY).

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K033811
The Binding Site, Ltd.

Within run Precision:

|   | Kappa (κ) [mg/mL] |   |   | Lambda (λ) [mg/mL]  |   |   |
| --- | --- | --- | --- | --- | --- | --- |
|  Level | 1 | 2 | 3 | 1 | 2 | 3  |
|  Mean | 22.05 | 40.83 | 153.26 | 31.43 | 66.10 | 183.09  |
|  %CV | 1.97 | 1.24 | 1.89 | 1.64 | 0.77 | 6.79  |

Between run Precision:

|   | Kappa (κ) [mg/mL] |   |   | Lambda (λ) [mg/mL]  |   |   |
| --- | --- | --- | --- | --- | --- | --- |
|  Level | 1 | 2 | 3 | 1 | 2 | 3  |
|  Mean | 22.23 | 41.35 | 135.38 | 29.63 | 62.92 | 177.91  |
|  %CV | 5.78 | 5.17 | 6.02 | 5.43 | 4.92 | 4.51  |

b. Linearity/assay reportable range:

Linearity for the Olympus Freelite assays (covalent liquid latex) was confirmed using serially diluted samples covering the lower part of the measuring range, samples at the higher measuring range and at the neat concentration. The regression plot equations where $y$ is the measured level of free chain concentration and $x$ the theoretical concentration were:

$$
y = 0.98 x + 1.68 \text{ (mg/mL)}, r = 1.00, \text{ for } \kappa \text{ chains (1:10 dilution)}
$$

$$
y = 1.08 x - 2.97 \text{ (mg/mL)}, r = 0.98, \text{ for } \lambda \text{ chains (1:10 dilution)}
$$

c. Traceability (controls, calibrators, or method):

Not applicable for the purpose of this submission.

d. Detection limit:

The sensitivity attained is shown below:

|   | Serum (1:5) | Urine (neat)  |
| --- | --- | --- |
|  Both κ and λ | 3.0 mg/L | 0.6 mg/L  |

e. Analytical specificity

Measurement of purified whole immunoglobulins, i.e., IgG, IgA, and IgM, were used to demonstrate analytical specificity for both test kits using control sera consisting of $53\mathrm{mg}\ \kappa/\mathrm{L}$ or $24\mathrm{mg}\ \lambda/\mathrm{L}$ at 1:10 dilution).

Interference (*)

|  Substance | Kappa (κ) |   | Lambda (λ)  |   |
| --- | --- | --- | --- | --- |
|   |  Conc. | % Int * | Conc. | % Int *  |
|  Bilirubin | 200 mg/L | -4.8 | 200mg/L | -1.6  |
|  Hemoglobin | 1g/L | +5.9 | 3g/L | +8.9  |
|  Chyle | 1930# | -10.7 | 1930# | +0.77  |

# formazine turbidity units

As shown above, interference of the substances tested was minimal. The values reported in this submission are consistent with the results of similar studies reviewed for clearance of K010440 and K010441.

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K033811
The Binding Site, Ltd.

f. Assay cut-off.

The approximate measuring ranges when using a 1: 10 sample dilution are 6 - 150mg/L for κ free light chains, and 8.1 -260 mg/L for A free light chains.

g. Stability.

Results from two stability studies were submitted to support modifications to the storage times for both kits. The stability of Free Kappa and Free Lambda Freelite® Olympus kits was established by testing three lots of each at the time of manufacture and at 3, 6, 9 and 12 months at recommended storage conditions. The results provide reasonable assurance that the kits are stable for up to 12 months at the recommended storage conditions. In addition, the stability of partially used kits stored for five months was assessed. Based on the percentage difference in the values obtained at t₀ and after storage the reagents are stable for up to five months after opening when stored at 2–8°C.

2. Comparison studies:

a. Method comparison with predicate device:

The applicant submitted the results of a study where they tested samples from normal subjects and from disease state samples with both the Olympus AU™ and the BNII assays to establish equivalence. The data, including regression analysis results, are summarized below:

κ free light chains*

|  Sample Type | N | BNII |   | Olympus AU™ |   | Y intercept | slope | r  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |   |  Low | Max. | Low | Max  |   |   |   |
|  Normal serum | 100 | 4.10 | 31.20 | 8.03 | 34.56 | 21.18mg/L | 0.95 | 0.95  |
|  SLE** | 8 | 13.9 | 44.7 | 18.02 | 29.64  |   |   |   |
|  κ myeloma | 28 | 12.75 | 2615.00 | 17.44 | 2637.00  |   |   |   |
|  λ myeloma | 25 | 0.12 | 29.15 | 0.90 | 16.5  |   |   |   |

* Normal adult serum ranges were established for BNII.
** System lupus erythemoatosus

λ free light chains*

|  Sample Type | N | BNII |   | Olympus AU™ |   | Y intercept | slope | r  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |   |  Low | Max. | Low | Max  |   |   |   |
|  Normal serum | 100 | 6.06 | 34.30 | 9.87 | 37.38 | 11.75mg/L | 0.88 | 0.99  |
|  SLE** | 8 | 18.00 | 68.35 | 15.16 | 66.25  |   |   |   |
|  κ myeloma | 40 | 30.50 | 3917.50 | 25.52 | 3133.00  |   |   |   |
|  λ myeloma | 28 | 0.84 | 20.87 | 3.25 | 23.08  |   |   |   |

* Normal adult serum ranges were established for BNII.
** System lupus erythemoatosus

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K033811
The Binding Site, Ltd.

Normal Urine Ranges (Olympus AU™) [N=16 healthy adults]

|   | Free κ (mg/mL) | Free λ (mg/mL) | κ/λ ratio (mg/mL)  |
| --- | --- | --- | --- |
|  Mean conc. | 6.06 | 2.88 | 2.10  |
|  Median conc. | 3.45 | 2.22 | 1.86  |
|  95 Percentile Range | 0.35 – 20.30 | 0.52 – 6.82 | 0.99 – 3.62  |

Conclusion from these studies: The r values obtained for the serum samples were 0.95 and 0.99, which suggest that the linear regression analyses provides reasonable estimates of the slope and y intercept. The data provide reasonable assurance of comparable performance of the FREELITE® kits with both systems. However, it should be noted that some level of systematic error (SE) is detected when comparisons are made at the concentration limits that border the 95 Percentile ranges (normal serum range) for both types of free chains.

b. Matrix comparison:
Established in original device clearance.

3. Clinical studies:

a. Clinical sensitivity:
(Established in original device clearance.)

b. Clinical specificity:
(Established in original device clearance.)

c. Other clinical supportive data (when a and b are not applicable):
Not applicable.

4. Clinical cut-off:
See comments to items L.1.f above and N.5 below.

5. Expected values/Reference range:
The expected values and reference ranges for both free κ and free λ chains in adult serum were established for the FREELITE® BNII. The applicant provided data in this submission to establish comparable performance of the kits in the BNII and Olympus AU™ series assays, and that the established ranges are applicable to use of the kits in the new device. The device labeling contains a statement alerting the user that these ranges “...have been obtained from a limited number of samples and are intended for guidance purposes only.” The manufacturer recommends in the labeling that users generate local ranges.

M. Conclusion:

A single 510K statement [as required in 21 CFR 807.93 (a)], a 510(k) Truthful and Accurate statement [as required by 21 CFR 807.87(k)], and a single copy of the Indications for Use statement [as required by 21 CFR § 807.92 (a) (5)] were provided for both test kits.

The purpose of this 510(k) was to seek clearance to market the FREELITE® Human

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K033811
The Binding Site, Ltd.

Kappa and Lambda Free Kit for use on the Olympus AU™ series diagnostic test kits. The data submitted in this 510(k) substantiate a good level of agreement between the results obtained with both test kits and confirms the level of performance previously demonstrated for the FREELITE® BNII test (K040441). Based on the review of the information provided each FREELITETM kit performs equally in both the Olympus AU™ and the predicate device in the assessment of the concentration of either Kappa or Lambda free light chains for those conditions specified in the Indications for Use statement. Therefore, the applicant provided acceptable supporting evidence to establish substantial equivalence.

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**Source:** [https://fda.innolitics.com/submissions/IM/subpart-f%E2%80%94immunological-test-systems/DEH/K033811](https://fda.innolitics.com/submissions/IM/subpart-f%E2%80%94immunological-test-systems/DEH/K033811)

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