OLYMPUS TOTAL BHCG TEST SYSTEN

K080094 · Olympus Life Science Research Europa GmbH (Europa) · DHA · Sep 3, 2008 · Clinical Chemistry

Device Facts

• Record ID: K080094
• Device Name: OLYMPUS TOTAL BHCG TEST SYSTEN
• Applicant: Olympus Life Science Research Europa GmbH (Europa)
• Product Code: DHA · Clinical Chemistry
• Decision Date: Sep 3, 2008
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1155
• Device Class: Class 2

Intended Use

The Olympus βhCG assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of total beta human chorionic gonadotropin (intact βhCG and free β) levels in human serum using the Olympus AU3000i Immunoassay System. Total βhCG is used for the early detection of pregnancy. For in vitro diagnostic use only. The Olympus βhCG Calibrator is for calibrating the quantitative Olympus βhCG assay on the Olympus AU3000i Immunoassay System. The Olympus βhCG Control is used for quality control of the Olympus βhCG assay on the Olympus AU3000i Immunoassay System.

Device Story

The Olympus Total βhCG Test System is a quantitative chemiluminescent immunoassay for serum βhCG. It utilizes a two-step sandwich principle: samples are incubated with monoclonal anti-βhCG antibody-coated paramagnetic particles; a second alkaline phosphatase-conjugated monoclonal anti-βhCG antibody is added to form a sandwich complex. After washing, a chemiluminescent substrate is added; light emission is proportional to βhCG concentration. The system is designed for use on the Olympus AU3000i clinical chemistry analyzer. Reagents, calibrators, and controls are identified via barcodes, which link components to lot-specific master curve data. The system automatically calculates concentrations in IU/L or mIU/mL. Healthcare providers use these results as an aid in the assessment of pregnancy status. The device benefits patients by providing automated, quantitative pregnancy testing in a clinical laboratory setting.

Clinical Evidence

No clinical data provided in the document; substantial equivalence is based on performance characteristics of the immunoassay system.

Technological Characteristics

Paramagnetic particle, chemiluminescent immunoassay. Designed for use on the Olympus AU3000i Immunoassay System. Quantitative measurement of intact BhCG and free ß subunits in human serum.

Indications for Use

Indicated for the quantitative determination of total beta human chorionic gonadotropin (intact βhCG and free β) in human serum for the early detection of pregnancy. For prescription use only.

Regulatory Classification

Identification

A human chorionic gonadotropin (HCG) test system is a device intended for the early detection of pregnancy is intended to measure HCG, a placental hormone, in plasma or urine. A human chorionic goadotropin (HCG) test system is a device intended for any uses other than early detection of pregnancy (such as an aid in the diagnosis, prognosis, and management of treatment of persons with certain tumors or carcinomas) is intended to measure HCG, a placental hormone, in plasma or urine.

Submission Summary (Full Text)

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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE

A. 510(k) Number:
k080094

B. Purpose for Submission:
New device

C. Measurand:
Total beta human chorionic gonadotrophin (intact βhCG and free β)

D. Type of Test:
Quantitative chemiluminescent immunoassay

E. Applicant:
Olympus Life and Material Science Research Europa, GmbH

F. Proprietary and Established Names:
Olympus Total βhCG Test System

G. Regulatory Information:

1. Regulation section:
21 CFR §862.1155 Human chorionic gonadotropin test system
21 CFR §862.1150 Calibrators
21 CFR §862.1660 Quality control material (assayed and unassayed)

2. Classification:
Class II
Class I (reserved)

3. Product code:
DHA Human chorionic gonadotropin (HCG) test system
JIT Calibrator
JJX Control material

4. Panel:
Chemistry (75)

H. Intended Use:

1. Intended use(s):
See Indications for Use below.

2. Indication(s) for use:
The Olympus βhCG assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of total beta human chorionic gonadotropin (intact βhCG and free β) levels in human serum using the Olympus

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AU3000i Immunoassay System. Total $\beta\mathrm{hCG}$ is used for the early detection of pregnancy. For in vitro diagnostic use only.

The Olympus $\beta\mathrm{hCG}$ Calibrator is for calibrating the quantitative Olympus $\beta\mathrm{hCG}$ assay on the Olympus AU3000i Immunoassay System.

The Olympus $\beta\mathrm{hCG}$ Control is used for quality control of the Olympus $\beta\mathrm{hCG}$ assay on the Olympus AU3000i Immunoassay System.

3. Special conditions for use statement(s):

For prescription use only.

4. Special instrument requirements:

For use on the Olympus AU3000i clinical chemistry system.

I. Device Description:

The Olympus BhCG test system consists of Reagent 1, Reagent 2, one calibrator, one control and a septum. The Reagent 1, Reagent 2, calibrator and control display bar codes. When a new reagent is added, the system recognizes it from the barcode. The one dimensional barcode on Reagent 1, QC sample and calibrator links the kit components to the corresponding Reagent 2. The Reagent 2 includes a two dimensional barcode that contains information on the lot specific counts of the master curve and the values for calibrators and QC samples.

J. Substantial Equivalence Information:

1. Predicate device name(s):

ADVIA Centaur total hCG

2. Predicate K number(s):

k925277 and k971418

3. Comparison with predicate:

| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Intended Use | The Olympus BhCG assay is a paramagnetic particle, Chemiluminescent immunoassay for the quantitative determination of total beta human chorionic gonadotropin (intact BhCG and free β) levels in human serum using the Olympus AU3000i Immunoassay System. Total BhCG is used for the early detection of pregnancy. For in vitro diagnostic use only. | For the in vitro use in the quantitative determination of human chorionic gonadotropin in serum using the ADVIA Centaur system. The results obtained from hCG specimens are used as an aid in the assessment of pregnancy status. This assay detects the intact hCG molecule and the free beta subunit of the hCG molecule. |

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| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Assay Principle | Competitive immunoassay | Same |
| | | |
| Sample Type | Serum | Same |
| Reagent Form | Liquid ready-to-use | Same |
| Calibration | Master curve provided via barcode | Same |
| Calibration Interval | 28 days | Same |
| Control Matrix | Human matrix with added antigen | Same |
| Differences | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Traceability/Standardization | 4th WHO reference standard 75/589. | 3rd WHO reference standard 75/537 |
| Control Levels | 1 | 3 |
| Open Stability | 28 days | various |
| Measuring Range (mIU/mL) | 0.53 – 1000 | 2.0 - 1000 |
| Antibody | Monoclonal anti-βhCG antibody | Monoclonal and polyclonal anti-hCG antibody |

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

CLSI - EP05-A2 - Evaluation of Precision Performance of Clinical Chemistry Devices
CLSI - EP09-A2 - Method Comparison and Bias Estimation Using Patient Samples
CLSI - C28-A2 - How to Define and Determine Reference Intervals in the Clinical Laboratory; Approved Guideline Second edition

# L. Test Principle:

The Olympus BhCG assay is a two step paramagnetic particle enzyme immunoassay based on the sandwich principle. Samples are incubated with monoclonal anti- $\beta$ hCG antibody bound to paramagnetic particles. After a wash step, a second monoclonal anti- $\beta$ hCG antibody conjugated with alkaline phosphatase is added. The $\beta$ hCG reacts with the paramagnetic particles and the conjugated antibody to form a sandwich complex. Washing steps remove the unbound material. The chemiluminescent substrate is added to the assay cuvette and reacts with the alkaline phosphatase; the resulting light emission is proportional to the quantity of $\beta$ hCG in the sample. Results are calculated from a pre-defined calibration curve. The Olympus AU3000i system

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automatically calculates the $\beta \mathrm{hCG}$ concentration of each sample in IU/L or mIU/mL.

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

# 1. Analytical performance:

# a. Precision/Reproducibility:

A precision study was conducted using pooled human sera according to CLSI protocol EP5-A. Samples were run twice a day in duplicate for 20 days $(n = 80)$ on the Olympus AU 3000i analyzer. The precision results are shown below:

Olympus Total $\beta$ hCG Assay: Precision

| Sample | | Within run | | Total | |
| --- | --- | --- | --- | --- | --- |
| | Mean [mIU/mL] | SD [mIU/mL] | CV [%] | SD [IU/mL] | CV [%] |
| 1 | 6.48 | 0.19 | 2.9 | 0.21 | 3.3 |
| 2 | 33.18 | 0.74 | 2.2 | 1.05 | 3.2 |
| 3 | 569.07 | 11.64 | 2.0 | 16.81 | 3.0 |

# b. Linearity/assay reportable range:

The reportable range for this assay is $0.53 - 1000\mathrm{mIU / mL}$ . This claim was supported by a study that measured dilutions of a high sample across the range following CLSI EP-6A. The eleven dilutions, each measured in quadruplicate, all recovered within $\pm 5\%$ of the expected value.

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

Reagent stability is claimed as 12 months based on an accelerated stability study; real time studies are underway. The assay components (i.e. reagent, calibrator, and control) were shown to be stable for 28 days on-board the instrument.

The lot-specific calibrator is prepared by addition of $\beta \mathrm{hCG}$ to a bovine calf serum matrix. The concentration of the calibrator is verified by using one instrument calibrated with the master calibrators testing 45 replicates. The calibrator master lot is made by adding quantities of purified $\beta \mathrm{hCG}$ into bovine calf serum with preservatives. The master lot is traceable to the WHO standard for HCG, $4^{\text{th}}$ IS, 75/589.

# d. Detection limit:

The limit of detection (LoD) was determined by measuring a blank sample 20 times and a low sample five times with three different lots of reagents. The LoD was calculated by multiplying the standard deviation of the mean of the samples by two and adding it to the absolute value of the mean. The LoD determined for all three lots $0.05\mathrm{mIU / mL}$ .

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The Limit of Quantitation (LoQ) was determined to be 0.53 mIU/mL as determined by the lowest concentration at which samples had a CV<20%.

e. Analytical specificity:

Cross reactivity: Thyroid stimulating hormone (TSH), luteinizing hormone (LH), follicle stimulating hormone (FSH), and human growth hormone (hGH) were spiked into serum to evaluate cross-reactivity. No detectable cross-reactivity was observed for 2500 µIU/mL TSH, 1000 mIU/mL LH, 2000 mIU/mL FSH, and 1000 ng/mL hGH.

Interference: The assay was evaluated for interference.

Hemoglobin (5 g/L), Bilirubin (unconjugated at 40 mg/dL) and Lipids (1000 mg/dL) did not affect the performance of the assay when samples containing various concentrations of βhCG were tested. The sponsor defines interference as results exceeding +/-10% of the expected value. Other substances, including various prescription and over-the-counter drugs, were tested and shown not to interfere with this assay. No hook effect was seen up to 100,000 mIU/mL. Sera containing Rheumatoid Factor (RF) or human anti-mouse antibodies (HAMA) were shown not to interfere with the assay. The sponsor includes a discussion of these factors in the product labeling.

f. Assay cut-off:

Not applicable; this is a quantitative assay.

2. Comparison studies:

a. Method comparison with predicate device:

118 patient serum samples were used to compare the results of the Olympus Total βhCG assay run on the Olympus AU3000i analyzer to those of the Advia Centaur total hCG assay; the experiment was based on the CLSI protocol EP9-A. Results of regression by Passing-Bablok analysis are shown below:

| N | Range of sample concentrations [mIU/mL] | Intercept [mIU/mL] (95% CI) | Slope | Correlation Coefficient |
| --- | --- | --- | --- | --- |
| 118 | 2.2 – 969.3 | 0.175 (0.91, 0.96) | 0.93 | 0.988 |

b. Matrix comparison:

Not applicable. This assay is indicated for serum only.

3. Clinical studies:

a. Clinical Sensitivity:

Not applicable.

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b. Clinical specificity:
Not applicable.

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

4. Clinical cut-off:
Not applicable.

5. Expected values/Reference range:
The sponsor used procedures in CLSI C28-A2 to bridge the transference of a reference range established with the predicate method in Snyder et al. (Clinical Chemistry 51:1830 – 1835, 2005) to the Olympus AU3000i Total βhCG assay. Snyder et al. established a hCG range in 240 women in the same age group as < 2.0 to 4.6 mIU/mL where the 97.5 percentile value was 2.5 mIU/mL (2.0 mIU/mL was the LoD of the predicate method). In the sponsor’s bridging study, serum from 86 women 18 – 40 years of age was tested; all samples tested were below the LoQ of the device (i.e., below 0.53 mIU/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.