LIAISON XL HCG

K131037 · DiaSorin, Inc. · DHA · Sep 6, 2013 · Clinical Chemistry

Device Facts

• Record ID: K131037
• Device Name: LIAISON XL HCG
• Applicant: DiaSorin, Inc.
• Product Code: DHA · Clinical Chemistry
• Decision Date: Sep 6, 2013
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1155
• Device Class: Class 2

Intended Use

The DiaSorin LIAISON® XL HCG assay uses chemiluminescent immunoassay (CLIA) technology on the LIAISON® XL Analyzer for the quantitative determination of total human chorionic gonadotropin (hCG and βhCG) in human serum for early detection of pregnancy. Total hCG is the measurement of intact and beta-hCG.

Device Story

LIAISON® XL HCG is an automated in-vitro diagnostic assay for quantitative measurement of total hCG in human serum. Device utilizes sandwich chemiluminescent immunoassay (CLIA) technology on LIAISON® XL Analyzer. Process: patient serum sample incubated with magnetic particles coated with mouse monoclonal anti-hCG antibody; subsequent incubation with isoluminol-antibody conjugate; starter reagents added to induce flash chemiluminescence. Photomultiplier measures light signal (RLU) proportional to hCG concentration. Used in clinical laboratory settings by trained technicians. Output provides hCG concentration (mIU/mL) to assist clinicians in pregnancy detection.

Clinical Evidence

Bench testing only. Precision evaluated per CLSI EP5-A2 (N=160 per sample, total CV 3.0-10.7%). Linearity (R²=0.983) and recovery (91.8-105.9%) verified. LoQ established at 1.5 mIU/mL. Interference testing showed no significant bias for common substances. Method comparison (N=172) against predicate yielded Weighted Deming regression Y = 0.973X - 0.223 (R²=0.993) with 2.7% average bias. Reference range established in 144 healthy subjects.

Technological Characteristics

Sandwich chemiluminescent immunoassay (CLIA). Solid phase: paramagnetic particles coated with monoclonal anti-hCG antibody. Conjugate: isoluminol-labeled monoclonal anti-hCG antibody. Energy source: LIAISON® XL Analyzer (photomultiplier detection). Sample volume: 30 µL. Measuring range: 1.5 - 10,000 mIU/mL. Traceability: 3rd WHO IS 75/537. Automated processing.

Indications for Use

Indicated for the quantitative determination of total hCG (intact and beta-hCG) in human serum for the early detection of pregnancy.

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.

Predicate Devices

• Roche ELECSYS® HCG +Beta Test (K003178)

Submission Summary (Full Text)

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K131037

DiaSorin LIAISON® XL HCG Premarket Notification

#### 5.0 510(k) SUMMARY

## SUBMITTED BY:

Mari Mever Director, Regulatory Affairs DiaSorin Inc. 1951 Northwestern Avenue P.O. Box 285 Stillwater, MN 55082-0285 Phone [phone] Fax [phone] Email: [e-mail]

**SEP**

06

2013

#### NAME OF DEVICE:

Trade Name:

Common Names/Descriptions:

Classification Names:

LIAISON® XL HCG

Human Chorionic Gonadotropin (hCG)

Human Chorionic Gonadotropin (hCG) test system

Product Code:

DHA

PREDICATE DEVICE:

Roche ELECSYS® HCG +Beta Test Reference K003178

## DEVICE DESCRIPTION:

#### INTENDED USE:

The DiaSorin LIAISON® XL HCG assay uses chemiluminescent immunoassay (CLIA) technology on the LIAISON® XL Analyzer for the quantitative determination of total human chorionic gonadotropin (hCG and ßhCG) in human serum for early detection of pregnancy. Total hCG is the measurement of intact and beta-hCG.

#### KIT DESCRIPTION:

The method for the quantitative determination of hCG is a sandwich chemiluminescence immunoassay. A specific mouse monoclonal antibody is coated on the magnetic particles (solid phase); another monoclonal antibody is linked to an isoluminol derivative (isoluminol-antibody conjugate). All assay steps and incubations are performed by the LIAISON® XL Analyzer.

During the first incubation, hCG present in calibrators, samples or controls binds to the solid phase monoclonal antibody, and subsequently after a washing step in a second incubation the antibody conjugate reacts with hCG already bound to the solid phase.

Subsequently, the starter reagents are added and a flash chemiluminescence reaction is thus induced. The light signal, and hence the amount of isoluminol-antibody

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conjugate, is measured by a photomultiplier as relative light units (RLU, relative light units) and is directly related to hCG concentration present in calibrators, samples or controls.

## COMPARISON TO PREDICATE DEVICE:

The DiaSorin LIAISON XL HCG assay is substantially equivalent in principle and performance to the Roche Elecsys® HCG +Beta Test (K003178) which was FDA cleared December 14, 2002.

| Table 1: Table of Similarities | | |
|-----------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Characteristic | New Device<br>LIAISON® XL HCG | Predicate Device<br>Roche ELECSYS® HCG + Beta<br>Test System (K003178) |
| Intended Use | In-vitro assay for the quantitative<br>determination of total human<br>chorionic gonadotropin (hCG and<br>βhCG) in human serum for early<br>detection of pregnancy using the<br>LIAISON® XL Analyzer. | Immunoassay for the in-vitro<br>quantitative determination of the sum<br>of human chorionic gonadotropin<br>(hCG) plus the hCG Beta subunit in<br>human serum and plasma. |
| Indications for<br>Use | For the early detection of<br>pregnancy. | For the early detection of pregnancy. |
| Measured<br>Analyte | human chorionic gonadotropin<br>(hCG) plus the hCG Beta subunit | human chorionic gonadotropin (hCG)<br>plus the hCG Beta subunit |
| Assay Type | Chemiluminescent Immunoassay | Electrochemiluminescent<br>Immunoassay |
| Test principle | Sandwich chemiluminescent<br>Immunoassay | Sandwich chemiluminescent<br>Immunoassay |
| Solid Support | Paramagnetic particles coated with<br>recombinant hCG | Paramagnetic particles coated with<br>streptavidin and coupled to<br>biotinylated monoclonal hCG-specific<br>antibodies |
| Reagent Integral<br>Storage | On-board or in refrigerator@ 2-8°C | On-board or in refrigerator@ 2-8°C |
| Sample<br>Handling/Process<br>ing | Automated | Automated |
| Unit of Measure | mlU/mL | mlU/mL |
| Traceability | 3rd WHO reference standard IS<br>75/537. | 3rd WHO reference standard IS<br>75/537. |

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| Table 2 : Table of Differences | | |
|--------------------------------|----------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------|
| Characteristic | New Device<br>LIAISON® HCG | Predicate Device<br>Roche ELECSYS® HCG + Beta<br>Test System (K003178) |
| Instrument | LIAISON® XL Analyzer | Roche Elecsys® Immunoassay<br>analyzer |
| Calibration | Two-point calibrator verification of<br>stored master curve.<br>Included with the kit. | Two-point calibrator verification of<br>stored master curve. Not included<br>with the kit. |
| Measuring range | 1.5 - 10,000 mIU/mL | 0.100 - 10,000 mIU/mL |
| Sample Matrix | Human serum | Human serum and plasma |
| Sample size | 30 μL | 10 μL |
| Conjugate<br>Antibody | Anti-hCG antibodies (mouse)<br>labeled with isoluminol | Biotinylated monoclonal anti-hCG<br>antibodies (mouse) |
| Open storage<br>2-8°C | 4 weeks | 12 weeks |
| Controls | No Controls Provided | 2 Levels |

## PERFORMANCE DATA:

### Method Comparison:

One hundred sixty-three (163) serum samples, that spanned the reportable range of the assay, were tested and analyzed by Weighted Deming Regression. The method comparison study was performed according to CLSI EP9-A2 guideline.

#### Results:

Weighted Deming Regression analysis was performed on the results across the range of LIAISON® XL HCG assay yielding agreement of y= 0.973x _0.2233; R2 = 0.9933.

#### Reference Range/Expected Values:

The reference range study was performed according to CLSI Approved Guideline C28-A3. Human serum samples from apparently healthy non-pregnant premenopausal and postmenopausal subjects were tested to determine the reference range for the LIAISON® XL HCG assay. The results are listed below:

· In a study performed on 74 healthy, non-pregnant premenopausal women (<50 years old), 97.5% of the values obtained were below 1.54 mIU/mL hCG.

· In a study performed on 70 healthy, postmenopausal women (≥ 50 years old). 97.5% of the values obtained were below 6.67 mlU/mL hCG.

Consider these limits as guidelines only. It is important for each laboratory to establish its own reference range, representative of its typical population.

#### Reproducibility/Precision:

A twenty day reproducibility/precision study was performed at DiaSorin Inc. A coded panel comprised of 6 frozen serum samples was prepared by DiaSorin Inc. The coded panel contained levels of low, medium and high samples. Commercial controls (3

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levels) were also tested in the study. The CLSI document EP05-A2 was consulted in the preparation of the testing protocol.

#### Results

The twenty day results are summarized in the following table as sample overall mean HCG concentration in mIU/mL, computed SDs and %CVs for within run and total across lots.

| Panel<br>ID# | N | mean<br>mlU/mL | Between Lot<br>SD | Between Lot<br>%CV | Total<br>SD | Total<br>%CV |
|--------------|-----|----------------|-------------------|--------------------|-------------|--------------|
| QC1 | 160 | 6.4 | 0.02 | 0.3% | 0.68 | 10.7% |
| QC2 | 160 | 23.3 | 0.07 | 0.3% | 1.41 | 6.0% |
| QC3 | 160 | 175.1 | 2.31 | 1.3% | 6.04 | 3.5% |
| HCG-11 | 160 | 60.2 | 0.01 | 0.0% | 2.95 | 4.9% |
| HCG-12 | 160 | 25.5 | 0.31 | 1.2% | 1.60 | 6.3% |
| HCG-13 | 160 | 431.4 | 6.44 | 1.5% | 13.03 | 3.0% |
| HCG-14 | 160 | 893.2 | 15.85 | 1.8% | 28.97 | 3.2% |
| HCG-15 | 160 | 4169.0 | 72.01 | 1.7% | 153.66 | 3.7% |
| HCG-16 | 160 | 9607.6 | 29.89 | 0.3% | 298.61 | 3.2% |

#### Dilution Linearity:

Two serum pools containing high hCG concentrations were tested neat and after serially diluting following CLSI EP6-A.

The results were analyzed by a Weighted Deming fit of observed hCG concentration versus expected hCG concentration.

Both sample sets yielded similar linear regressions. An example is shown below:Y(obtained mIU/mL) = 1.0158X(expected mIUmL) - 0.1450

## LoB/LoD/LoQ:

The Limit of Blank, Limit of Detection and Limit of Quantitation were determined according to CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures: Approved Guideline June 2012- Second Edition.

## Results:

Limit of Blank: 0.17 mIU/L Limit of Detection: 0.36 mIU/L Limit of Quantitation: 1.5 mIU/L

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DiaSorin LIAISON® XL HCG Premarket Notification

#### Recovery

A recovery study using five levels of spiked samples, which were prepared by adding the targeting amount of WHO 30 reference standard into five human sera and tested in duplicates using one lot of reagents on one instrument, was conducted. The overall % recovery for each spiked level was determined and are tabulated below.

| Spiked level (mIU/mL) | Overall %recovery |
|-----------------------|-------------------|
| 5 | 91.8 |
| 25 | 105.9 |
| 500 | 94.9 |
| 5000 | 92.9 |
| 9000 | 96.9 |

## Interfering Substances:

Controlled studies of potentially interfering substances at two hCG levels showed no interference at the concentration for each substance listed below in the LIAISON® XL HCG assay. The testing was based on CLSI-EP7-A2.

| Substance | Highest Concentration Tested |
|------------------------------------|------------------------------|
| Triglycerides | 3000 mg/dL |
| Hemoglobin | 1000 mg/dL |
| Unconjugated bilirubin | 20 mg/dL |
| Conjugated bilirubin | 20 mg/dL |
| Albumin | 6 g/dL |
| Rheumatoid Factor | 194 IU/L |
| Luteinizing Hormone (LH) | 500 mIU/mL |
| Follicle-stimulating hormone (FSH) | 500 mIU/mL |
| Human Growth Hormone (hGH) | 100 ng/mL |
| TSH | 200 mIU/mL |
| Acetaminophen | 20 mg/dL |
| Acetylsalicylic Acid | 20 mg/dL |
| Ascorbic Acid | 20 mg/dL |
| Atropine | 20 mg/dL |
| Caffeine | 20 mg/dL |
| EDTA | 80 mg/dL |
| Ethanol | 1% |
| Gentisic Acid | 20 mg/dL |
| Glucose | 2 g/dL |
| Salicylic Acid | 20 mg/dL |

## CONCLUSION:

The material submitted in this premarket notification is complete and supports the basis for substantial equivalence to the Roche ELECSYS® HCG + Beta Test System (K003178). The labelling is sufficient and satisfies the requirements of 21 CFR Part 809.10.

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#### DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/5/Picture/1 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo consists of a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized symbol that resembles a caduceus, a traditional symbol of medicine, but with a more abstract and modern design.

Public Health Service

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

September 6, 2013

DiaSorin Inc. C/O Mari Meyer Director, Regulatory Affairs 1951 Northwestern Avenue P.O. Box 285 STILLWATER MN 55082

Re: K131037

Trade/Device Name: DiaSorin LIASON® XL HCG Regulation Number: 21 CFR 862.1155 Regulation Name: Human chorionic gonadotropin (HCG) test system Regulatory Class: II Product Code: DHA Dated: August 14, 2013 Received: August 21, 2013

Dear Ms. Meyer:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number [phone] or [phone] or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number [phone] or [phone] or at its Internet address http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm.

Sincerely yours,

# Carol C. Benson -S for

Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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## Indications for Use

510(k) Number (if known): k131037

Device Name: LIAISON® XL HCG

Indications for Use: The DiaSorin LIAISON® XL HCG assay uses chemiluminescent immunoassay (CLIA) technology on the LIAISON® XL Analyzer for the quantitative determination of total human chorionic gonadotropin (hCG and BhCG) in human serum for early detection of pregnancy. Total hCG is the measurement of intact and betahCG.

Prescription Use X (21 CFR Part 801 Subpart D) And/Or

Over the Counter Use (21 CFR Part 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostics and Radiological Health (OIR)

Denise Johnson-lyles -S 2013.09.06 07:55:38 -04'00'

Division Sign-Off Office of In Vitro Diagnostics and Radiological Health

510(k)_k131037_