LIAISON TESTOSTERONE; LIAISON TESTOSTERONE CONTROL SET

K122793 · DiaSorin, Inc. · CDZ · Jan 25, 2013 · Clinical Chemistry

Device Facts

• Record ID: K122793
• Device Name: LIAISON TESTOSTERONE; LIAISON TESTOSTERONE CONTROL SET
• Applicant: DiaSorin, Inc.
• Product Code: CDZ · Clinical Chemistry
• Decision Date: Jan 25, 2013
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1680
• Device Class: Class 1

Intended Use

The DiaSorin LIAISON® Testosterone is a direct, competitive, chemiluminescence immunoassay (CLIA) intended for the quantitative determination of testosterone in human serum and plasma on the LIAISON® Analyzer. The assay is intended for in vitro diagnostic use. Measurement of testosterone is used in the diagnosis and treatment of disorders involving the male sex hormones (androgens), including primary and secondary hypogonadism, delayed or precocious puberty, impotence in male subjects and, in female subjects hirsutism (excessive hair) and virilization (masculinization) due to tumors, polycystic ovaries, and adrenogenital syndromes. The DiaSorin LIAISON® Testosterone Control Set is intended for use as assayed quality control samples to monitor the accuracy and precision of the DiaSorin LIAISON® Testosterone immunoassav.

Device Story

LIAISON® Testosterone is a direct, competitive chemiluminescence immunoassay (CLIA) for quantitative testosterone measurement in human serum/plasma. Device uses mouse monoclonal antibodies bound to magnetic particles; testosterone in sample competes with isoluminol-labeled testosterone for antibody binding sites. After incubation and wash, starter reagents initiate flash chemiluminescent reaction. Photomultiplier measures light signal (RLU), inversely proportional to testosterone concentration. Performed on LIAISON® Analyzer; fully automated. Used in clinical laboratories for diagnostic assessment of androgen disorders. Results assist clinicians in diagnosing hypogonadism, puberty disorders, impotence, hirsutism, and virilization. Control set monitors assay accuracy/precision.

Clinical Evidence

No clinical trials performed. Evidence consists of analytical bench testing: precision (N=480 per sample, total CV 7.1-14.0%), linearity (16-1500 ng/dL), LoB (3.1 ng/dL), LoD (9.8 ng/dL), and LoQ (16 ng/dL). Interference and cross-reactivity studies conducted per CLSI EP7-A2. Method comparison against predicate (N=162) yielded Passing-Bablok regression Y = 0.9458x - 1.49, R² = 0.9809. Reference ranges established using 622 healthy adults.

Technological Characteristics

Competitive chemiluminescence immunoassay (CLIA). Mouse monoclonal antibodies on magnetic particles. Photomultiplier detection. Sample matrix: serum and EDTA plasma. Measuring range: 16.0 - 1500 ng/dL. Automated processing on LIAISON® Analyzer. Reagent storage: 2-8°C.

Indications for Use

Indicated for quantitative determination of testosterone in human serum and plasma to aid in diagnosis and treatment of androgen-related disorders, including primary/secondary hypogonadism, delayed/precocious puberty, and impotence in males; and hirsutism and virilization in females due to tumors, polycystic ovaries, or adrenogenital syndromes.

Regulatory Classification

Identification

A testosterone test system is a device intended to measure testosterone (a male sex hormone) in serum, plasma, and urine. Measurement of testosterone are used in the diagnosis and treatment of disorders involving the male sex hormones (androgens), including primary and secondary hypogonadism, delayed or precocious puberty, impotence in males and, in females hirsutism (excessive hair) and virilization (masculinization) due to tumors, polycystic ovaries, and adrenogenital syndromes.

Predicate Devices

• Roche Cobas® Testosterone II Test (k093421)
• Roche PreciControl Universal 1 and 2 (k090541)

Submission Summary (Full Text)

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122793

DiaSorin LIAISON® Testosterone Premarket Notification

# JAN 2 5 2013

#### 5.0 510(k) SUMMARY

SUBMITTED BY:

Sandra M. Zimniewicz Requlatory Affairs Specialist DiaSorin Inc. 1951 Northwestern Avenue P.O. Box 285 Stillwater, MN 55082-0285 Phone [phone] Fax [phone] Email: [e-mail]

# NAME OF DEVICE:

Trade Name:

LIAISON® Testosterone LIAISON® Testosterone Control Set

Common Names/Descriptions:

Classification:

Testosterone Assay

Class I, reserved, 21 CFR 862.1680. Testosterone Test System, Clinical Chemistry (75)

Class I, reserved, 21 CFR 862,1660, Quality Control Material, Clinical Chemistry (75)

Product Code:

PREDICATE DEVICE:

CDZ. JJX

Roche Cobas® Testosterone II Test Reference K093421 Roche Elecsys® PreciControl Universal Reference K090541

#### DEVICE DESCRIPTION:

#### INTENDED USE:

The DiaSorin LIAISON® Testosterone is a direct, competitive, chemiluminescence immunoassay (CLIA) intended for the quantitative determination of testosterone in human serum and plasma on the LIAISON® Analyzer. The assay is intended for in vitro diagnostic use.

Measurement of testosterone is used in the diagnosis and treatment of disorders involving the male sex hormones (androgens), including primary and secondary hypogonadism, delayed or precocious puberty, impotence in male subjects and, in female subjects hirsutism (excessive hair) and virilization (masculinization) due to tumors, polycystic ovaries, and adrenogenital syndromes.

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·The DiaSorin LIAISON® Testosterone Control Set is intended for use as assayed quality control samples to monitor the accuracy and precision of the DiaSorin LIAISON® Testosterone immunoassav.

## KIT DESCRIPTION:

The LIAISON® Testosterone assay's method for quantitative determination of testosterone is a direct, competitive, chemiluminescence immunoassay (CLIA). Specific antibody to testosterone is bound to magnetic particles (solid phase) and testosterone is linked to an isoluminol derivative. During the incubation, testosterone is dissociated from its binding protein and competes with labeled testosterone for binding sites on the antibody. After the incubation, the unbound material is removed with a wash cycle, Subsequently, the starter reagents are added and a flash chemiluminescent reaction is initiated. The light signal is measured by a photomultiplier as relative light units (RLU) and is inversely proportional to the concentration of testosterone present in calibrators, controls, or samples. All assay steps and incubations are performed by the LIAISON® Analvzer.

Two point kit calibrators are used to establish specific working curves based on assay master curves stored on the Analyzer.

The LIAISON® Testosterone reagent kit consists of a reagent intrgral which contains antibody coated magnetic particles (2.3 mL), conjugate (12 mL) and assay buffer (12 mL) reagents. Two levels of ready to use calibrators (2 vials each level, 2.0 mL per vial) are provided with each kit. Each kit consists of 100 tests.

## COMPARISON TO PREDICATE DEVICE:

The DiaSorin LIAISON® Testosterone is substantially equivalent in principle and performance to the Roche Cobas® Testosterone II Test (K093421) which was FDA cleared 4/28/2010.

| Characteristic | LIAISON® Testosterone | Roche Cobas®Testosterone II<br>(K093421) |
|------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | Intended for the in vitro<br>quantitative determination of<br>testosterone in human serum<br>and EDTA plasma. | Intended for the in vitro<br>quantitative determination of<br>testosterone in human serum<br>and plasma. |
| Indications for<br>Use | Measurement of testosterone is<br>used in the diagnosis and<br>treatment of disorders involving<br>the male sex hormones<br>(androgens), including primary<br>and secondary hypogonadism,<br>delayed or precocious puberty,<br>impotence in males and, in<br>females hirsutism (excessive<br>hair) and virilization<br>(masculinization) due to | Measurements of testosterone<br>are used in the diagnosis and<br>treatment of disorders involving<br>the male sex hormones<br>(androgens), including primary<br>and secondary hypogonadism,<br>delayed or precocious puberty,<br>impotence in males and, in<br>females hirsutism (excessive<br>hair) and virilization<br>(masculinization) due to |

# DiaSorin LIAISON® Testosterone Similarities and Differences

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| | tumors, polycystic ovaries, and<br>adrenogenital syndromes. | tumors, polycystic ovaries, and<br>androgenital syndromes. |
|-----------------------------|-------------------------------------------------------------|-------------------------------------------------------------|
| Assay Type | Chemiluminescent<br>Immunoassay | Electrochemiluminescence<br>Immunoassay "ECLIA" |
| Analyte | Testosterone | Testosterone |
| Calibration | Two-point verification of stored<br>master curve. | Same |
| Sample Handling | Automated | Same |
| Unit of Measure | ng/mL,ng/dL or nmol/L | Same |
| Controls | 2 levels | 2 levels |
| Measurement System | Photomultiplier (flash<br>chemiluminescence reader) | Photomultiplier (flash<br>chemiluminescence reader) |
| Calibrators | Included with kit | Provided separately |
| Capture Antibody | Mouse monoclonal antibodies<br>to testosterone | Biotinylated sheep monoclonal<br>antibodies to testosterone |
| Measuring range | 16.0 - 1500 ng/dL | 2.5 - 1500 ng/dL |
| Sample size | 100 uL | 20 uL |
| Sample matrix | Serum and EDTA plasma | Serum and plasma (Li-heparin,<br>K2-EDTA, and K3 EDTA |
| Reagent Storage | In refrigerator @ 2-8° C. | On analyzer or in refrigerator<br>@ 2-8°C. |
| Open Storage @<br>2-8° C | 4 weeks | 12 weeks |
| Open Storage on<br>analyzer | NA | 8 weeks |

# DiaSorin LIAISON® Testosterone Control Set Similarities and Differences

| Characteristic | LIAISON® Testosterone<br>Control Set | Roche PreciControl Universal<br>1 and 2 (K090541) |
|------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------|
| Intended Use | Intended for use as assay<br>quality control samples to<br>monitor the accuracy and<br>precision of the DiaSorin<br>LIAISON® Testosterone<br>immunoassay. | Intended for use as quality<br>control of Elecsys®<br>immunoassays on the Elecsys®<br>and Cobas® immunoassay<br>analyzers® |
| Matrix | Human serum | Same |
| Levels | Two concentrations :<br>low and high | Same |
| Reagent Format | Liquid<br>2 vials x 3.5 mL each level | Lyophilized<br>2 vials x 3.0 ml each level |
| Handling | Ready to use | Reconstitute with distilled water<br>and allow 30 minutes for<br>reconstitution. |
| Storage @ 2-8° C | Unopened store at 2-8° C until<br>expiration date | Same |

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# PERFORMANCE DATA:

# Method Comparison:

The method comparison included one hundred eighty four (184) serum samples that spanned the reportable range of each assay (n = 184). Samples were tested by the DiaSorin LIAISON® Testosterone assay (expressed as ng/dL) and the predicate device Roche Cobas® Testosterone II Test (K093421) on the Elecsys analyzer (expressed as ng/dL). The method comparison study was performed according to CLSI EP9-A2 quidelines.

One hundred sixty two (162) of the 184 serum samples tested were analyzed. One sample read above the upper limit of the reportable range and 21 samples read below the measuring range of the LIAISON® Testosterone assay and therefore, were not included in the analysis. Individual testosterone results were plotted.

Passing & Bablok linear regression analysis was performed on the results across the measuring range of LIAISON® Testosterone assay yielding agreement of y = 0.9458x -0.1002, R = 0.990. The 95% confidence interval for the slope was 0.92 to 0.96, and the 95% confidence interval for the intercept was -1.88 to 1.80 ng/dL.

## LoB/LoD/LoQ

The Limit of Blank, Limit of Detection, and Limit of Quantitation were determined according to CLSI EP17-A: Protocols for Determination of Limits of Detection and Limits of Quantitation.

The following limits were determined with the LIAISON® Testosterone assay:

Limit of Blank: ≤ 3.1 ng/dL Limit of Detection: 9.8 ng/dL Limit of Quantitation: 16.0 ng/dL

# Reference Range/Expected Values:

The reference range study was performed according to CLSI Approved Guideline C28-A3. Human serum samples from apparently healthy adults were tested to determine the reference range for the LIAISON® Testosterone assay into the follwoing gender and age groups.

| Population | N | Median Testosterone<br>Conc. ng/mL (ng/dL) | Central 95% Interval<br>ng/mL (ng/dL) |
|---------------------|-----|--------------------------------------------|---------------------------------------|
| Males 18-49 years | 161 | 4.39 (439) | 1.20 - 10.19 (120 – 1019) |
| Males ≥ 50 years | 132 | 4.53 (453) | 1.95 - 8.95 (195 – 895) |
| Females 18-49 years | 202 | 0.24 (24.0) | < 0.16 - 0.73 (<16.0 – 73.0) |
| Females ≥ 50 years | 127 | 0.22 (22.0) | < 0.16 - 0.51 (<16.0 – 51.0) |

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#### Reproducibility/Precision:

A twenty day reproducibility/precision study was performed at DiaSorin Inc. and 2 external sites. A coded panel comprised of 6 frozen serum samples was prepared by DiaSorin. The coded panel contained 2 of each of low, medium and high level samples which spanned the measuring range of the assay. The LIAISON® Testosterone Controls (2 levels) were also tested in the study. The CLSI document EP5-A2 was consulted in the preparation of the testing protocol.

#### Results:

The twenty day results for all three sites are summarized in Table 1 as sample overall mean testosterone concentration in ng/dL, computed SDs and %CVs for within run and total across lots and across sites.

| Sample<br>ID | N | Mean<br>(ng/dL) | Within Run<br>SD | Within Run<br>%CV | Total<br>Across Lots / Across<br>Sites SD | Total<br>Across Lots / Across<br>Sites %CV |
|--------------|-----|-----------------|------------------|-------------------|-------------------------------------------|--------------------------------------------|
| Level 1 | 480 | 219 | 8.0 | 3.4% | 2.0 | 9.1% |
| Level 2 | 480 | 781 | 22.0 | 2.8% | 55.0 | 7.1% |
| POOL 1 | 480 | 37.0 | 3.0 | 7.3% | 5.0 | 14.0% |
| POOL 2 | 480 | 83.0 | 5.0 | 5.5% | 9.0 | 10.5% |
| POOL 3 | 480 | 237 | 11.0 | 4.5% | 20.0 | 8.6% |
| POOL 4 | 480 | 418 | 18.0 | 4.3% | 38.0 | 9.2% |
| POOL 5 | 480 | 1048 | 37.0 | 3.5% | 94.0 | 9.0% |
| POOL 6 | 480 | 1325 | 42.0 | 3.2% | 105 | 7.9% |

## Table 1: Reproducibility/Precision Results – 20 day Combined 3 Sites

#### Dilution Linearity:

Three (3) samples of each sample type, serum, SST serum, and EDTA plasma were diluted with calibrator matrix or a low human serum or plasma sample to yield sample concentrations that spanned the measuring range (16.0 – 1500 ng/dL) and analyzed by the LIAISON® Testosterone following CLSI EP6-A.

The mean results for each sample type were analyzed by a linear regression of Observed Testosterone Concentration versus Expected Testosterone Concentration in ng/dL with the following resulting equations:

> Serum: v = 1.0269x - 0.6135. R2= 0.9862 SST Serum: y = 1.0096x - 0.3.297, R2= 0.9907 EDTA plasma: y = 0.9986x + 15.91, R2= 0.9847

#### Specificity

The cross-reactivity of the LIAISON® Testosterone assay was evaluated by adding the following substances to serum pools containing testosterone at 2 concentrations. The

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samples were analyzed and the percent (%) cross-reactivity calculated using the following formula:

% Cross-reactivity'= (Corrected Assay value/Concentration Spiked)*100

The observed cross-reactivities are listed below:

| | Spiked Concentration | % Cross |
|----------------------------|----------------------|------------|
| Cross reactant | ng/mL | reactivity |
| Androstenedione | 100 | < 4.27 |
| Cortisol | 1000 | < 0.03 |
| Cortisone | 2000 | < 0.01 |
| Danazol | 1000 | <0.02 |
| Dexamethasone | 2000 | < 0.01 |
| DHEA | 1000 | < 0.02 |
| DHEA-S | 50000 | < 0.01 |
| D-5-Androstene-3B-17B-diol | 1000 | < 0.06 |
| Estrone | 1000 | < 0.03 |
| Ethisterone | 1000 | < 0.43 |
| Nandrolone | 100 | < 3.33 |
| Norgesterel | 1000 | < 0.02 |
| Testosterone propionate | 50 | < 7.48 |
| 5-a-Androstane-3B,17B-diol | 500 | < 0.81 |
| 5-a-Dihydrotestosterone | 500 | < 2.37 |
| 11-B-Hydroxytestosterone | 50 | < 15.28 |
| 11-Keto-testosterone | 10 | < 37.70 |
| Prednisone | 1000 | < 0.03 |
| Prednisolone | 1000 | < 0.04 |
| Progesterone | 1000 | < 0.12 |
| 17-a-Estradiol | 1000 | < 0.02 |

### Interfering Substances

Controlled studies of potentially interfering substances at two testosterone levels showed no interference at the concentration for each substance listed below in the LIAISON® Testosterone assay. The testing was based on CLSI-EP07-A2.

| Substance | Tested Concentration |
|--------------------|----------------------|
| Hemoglobin | 600 mg/dL |
| Bilirubin (unconj) | 20 mg/dL |
| Triglycerides | 1000 mg/dL |
| Cholesterol | 500 mg/dL |
| HAMA | Up to 1753 ng/mL |

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# CONCLUSION:

The material submitted in this premarket notification is complete and supports the basis for substantial equivalence to the Roche Cobas® Testosterone II Test (K093421). The labelling is sufficient and satisfies the requirements of 21 CFR 809.10.

·

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#### DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/7/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features the department's name arranged in a circular fashion around a symbol. The symbol is a stylized depiction of an eagle or bird-like figure with three wing-like extensions. The text reads "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA".

#### Public Health Service

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

#### January 25, 2013

Diasorin, Inc. c/o Mr. John Eskdale 1951 Northwestern Ave. Stillwater, MN 55082

Re: k122793

Trade/Device Name: LIAISON Testosterone LIAISON Testosterone Control Set Regulation Number: 21 CFR 862.1680 Regulation Name: Testosterone test system Regulatory Class: Class I, reserved . x x = = = = 16% Product Code: CDZ, JJX Dated: December 14, 2012 Received: December 17, 2012

Dear Mr. Eskdale:

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 Part 801); 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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Page 2-Mr. Eskdale

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please go to http://www.fda.gov/AboutFDA/CentersOffices/CDRH/CDRHOffices/ucm115809.htm for the Center for Devices and Radiological Health's (CDRH's) Office of Compliance. 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/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Carol C. Benson 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): k122793

Device Name: LIAISON® Testosterone and LIAISON® Testosterone Control Set

Indications for Use:

The DiaSorin LIAISON® Testosterone assay is a direct, competitive, chemiluminescence immunoassay (CLIA) intended for the quantitative determination of testosterone in human serum and plasma on the LIAISON®Analyzer. The assay is intended for in vitro diagnostic use.

Measurement of testosterone is used in the diagnosis and treatment of disorders involving the male sex hormones (androgens), including primary and secondary hypogonadism, delayed or precocious puberty, impotence in male subjects and, in female subjects hirsutism (excessive hair) and virilization (masculinization) due to tumors, polycystic ovaries, and adrenogenital syndromes.

The DiaSorin LIAISON® Testosterone Control Set is intended for use as assayed quality control samples to monitor the accuracy and precision of the DiaSorin LIAISON® Testosterone immunoassay.

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)

Yung W. Chan -S

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

510(k) k122793