TESTOSTERONE TEST SYSTEM; CALIBRATOR; AND QUALITY CONTROL MATERIAL (ASSAYED AND UNASSAYED)

K120009 · Abbott Laboratories · CDZ · Sep 11, 2012 · Clinical Chemistry

Device Facts

• Record ID: K120009
• Device Name: TESTOSTERONE TEST SYSTEM; CALIBRATOR; AND QUALITY CONTROL MATERIAL (ASSAYED AND UNASSAYED)
• Applicant: Abbott Laboratories
• Product Code: CDZ · Clinical Chemistry
• Decision Date: Sep 11, 2012
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1680
• Device Class: Class 1

Indications for Use

The ARCHITECT 2nd Generation Testosterone assay is a chemiluminescent microparticle immunoassay (CMIA) for the quantitative determination of testosterone in human serum and plasma. Measurements 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. The ARCHITECT 2nd Generation Testosterone Calibrators are for the calibration of the ARCHITECT i System when used for the quantitative determination of testosterone in human serum and plasma. The ARCHITECT 2nd Generation Testosterone Controls are for the verification of the accuracy and precision of the ARCHITECT i System when used for the quantitative determination of testosterone in human serum and plasma.

Device Story

The ARCHITECT 2nd Generation Testosterone assay is a chemiluminescent microparticle immunoassay (CMIA) performed on the ARCHITECT i System. It uses anti-testosterone monoclonal antibodies coated on microparticles and an acridinium-labeled testosterone conjugate. The system measures chemiluminescence to quantify testosterone levels in human serum and plasma. It is intended for use by clinical laboratory professionals. The output provides quantitative testosterone concentrations, which clinicians use to diagnose and monitor androgen-related conditions. The device includes calibrators and controls to ensure accuracy and precision. Benefits include standardized, automated measurement of testosterone levels to support clinical decision-making for endocrine disorders.

Clinical Evidence

Bench testing only. Precision studies (NCCLS EP5-A2) showed within-laboratory CVs ≤ 10%. Sensitivity (NCCLS EP17-A) established LoQ of 4.33 ng/dL. Linearity (EP6-A) confirmed range of 4.33–1500 ng/dL. Interference studies (CLSI EP7-A2) evaluated endogenous substances and drugs. Method comparison (CLSI EP9-A2-IR) against LC-MS (n=138) demonstrated correlation (r=0.994) and slope of 1.0.

Technological Characteristics

Chemiluminescent microparticle immunoassay (CMIA). Reagents: anti-testosterone (sheep, monoclonal) coated paramagnetic microparticles, acridinium-labeled conjugate, BIS Tris buffer, ProClin 300 preservative. Platform: ARCHITECT i 2000 SR system. Measuring range: 4.33–1500 ng/dL. Calibration: 6-level synthetic matrix. Controls: 3-level synthetic matrix. Connectivity: ARCHITECT i system.

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 hypogonadism, puberty disorders, and impotence in males, and hirsutism and virilization in females.

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 Elecsys Testosterone II assay (k093421)

Submission Summary (Full Text)

{0}

1

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

A. 510(k) Number:
k120009

B. Purpose for Submission:
New device

C. Measurand:
Testosterone

D. Type of Test:
Quantitative, Chemiluminescence assay

E. Applicant:
Abbott Laboratories

F. Proprietary and Established Names:
Abbott ARCHITECT 2nd Generation Testosterone

G. Regulatory Information:

1. Regulation section:
21 CFR § 862.1680
21 CFR § 862.1150
21 CFR § 862.1660

2. Classification:
Class I, reserved
Class II
Class I, reserved

3. Product code:
CDZ
JIT
JJX

4. Panel:
Clinical Chemistry (75)

H. Intended Use:

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

{1}

2. Indication(s) for use:

The ARCHITECT 2nd Generation Testosterone assay is a chemiluminescent microparticle immunoassay (CMIA) for the quantitative determination of testosterone in human serum and plasma. Measurements 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.

The ARCHITECT 2nd Generation Testosterone Calibrators are for the calibration of the ARCHITECT i System when used for the quantitative determination of testosterone in human serum and plasma.

The ARCHITECT 2nd Generation Testosterone Controls are for the verification of the accuracy and precision of the ARCHITECT i System when used for the quantitative determination of testosterone in human serum and plasma.

3. Special conditions for use statement(s):

For Prescription use only

4. Special instrument requirements:

ARCHITECT i 2000 SR system

I. Device Description:

Each ARCHITECT 2nd Generation Testosterone Reagent Kit contains 1 bottle each of Microparticles, Conjugate, Assay Specific Diluent, and Specimen Diluent.

Microparticles (1 or 4 bottles) contain 6.6 mL Anti-Testosterone (sheep, monoclonal) coated microparticles in BIS Tris buffer with protein (bovine) stabilizer and ProClin 300 preservative.

Conjugate (1 or 4 bottles) contains 6.9 mL Testosterone acridinium-labeled conjugate in BIS Tris buffer with surfactant stabilizer and ProClin 300 preservative.

Assay Specific Diluent (1 or 4 bottles) contains 25.0 mL Testosterone Assay Diluent consisting of phosphate and glycine in citrate buffer and ProClin 300 preservative.

Specimen Diluent (1 or 4 bottles) contains 12.2 mL Testosterone Specimen Diluent consisting of PBS buffer and ProClin 300 preservative.

Each ARCHITECT 2nd Generation Testosterone Calibrator Kit contains 6 Bottles (4.0 mL each) of ARCHITECT 2nd Generation Testosterone Calibrators A-F. Calibrator A contains PBS buffer. Calibrators B through F contain testosterone (synthetic) in PBS buffer. All calibrators contain a protein (bovine) stabilizer and ProClin 300 preservative.

2

{2}

Each ARCHITECT 2nd Generation Testosterone Control Kit contains 3 Bottles (8.0 mL each) of ARCHITECT 2nd Generation Testosterone Controls. The Low, Medium, and High Controls contain testosterone (synthetic) in PBS buffer with a protein (bovine) stabilizer and ProClin 300 preservative.

## J. Substantial Equivalence Information:

1. Predicate device name(s): Roche Elecsys Testosterone II
2. Predicate 510(k) number(s): k093421
3. Comparison with predicate:

| Similarities and Differences for Testosterone Assay | | |
| --- | --- | --- |
| Item | Candidate Device ARCHITECT 2^{nd} Generation Testosterone | Predicate Device Roche Elecsys Testosterone II (k093421) |
| Intended Use/Indications for Use | Immunoassay for the in vitro quantitative determination of testosterone in human serum and plasma. | Same |
| Platform | ARCHITECT i System (immunoassay analyzer) | Elecsys and cobas e immunoassay analyzer |
| Methodology | Chemiluminescence (CMIA) | Electrochemiluminescence (ECLIA) |
| Specimen type | Serum and plasma | Same |
| Measuring range | 4.33 – 1500 mg/dL | 2.50 - 1500 ng/dL |
| Calibrator Levels | 6 | 2 |
| Control Levels | 3 | 2 |
| Similarities and Differences for Testosterone Calibrators | | |
| --- | --- | --- |
| Item | Candidate Device ARCHITECT 2^{nd} Generation Testosterone Calibrators | Predicate Device Roche Elecsys Testosterone II (k093421)- The Elecsys Testosterone CalSetII |
| Intended Use/Indications for Use | For the calibration of the quantitative testosterone assay. | Same |

{3}

| Similarities and Differences for Testosterone Calibrators | | |
| --- | --- | --- |
| Item | Candidate Device ARCHITECT 2ndGeneration Testosterone Calibrators | Predicate Device Roche Elecsys Testosterone II (k093421)- The Elecsys Testosterone CalSetII |
| Calibrator Levels | 6 levels:A: 0 pg/dLB: 2.88 ng/dLC: 250 ng/dLD: 500 ng/dLE: 1,000 ng/dLF: 2,000 ng/dL | 2 levels |
| Components | 6 Bottles (4.0 mL each) of ARCHITECT 2ndGeneration Testosterone Calibrators A-F. Calibrator A contains PBS buffer. Calibrators B through F contain testosterone in PBS buffer. All calibrators contain a protein (bovine) stabilizer. Preservative: ProClin 300. | Lyophilized human serum with 2 testosterone concentration levels |
| Similarities and Differences for Testosterone Controls | | |
| --- | --- | --- |
| Item | Candidate Device ARCHITECT 2ndGeneration Testosterone Controls | Predicate Device Roche Elecsys Testosterone II (k093421)- The Elecsys PreciControl Universal 1 and 2 |
| Intended Use/Indications for Use | For verification the accuracy and precision of testosterone assay. | Same |
| Control Levels | 3 levels:Targets:Low: 8.94Medium: 69.79High:218.61 | 2 levels (multi-constituent, concentration variable on lot-to-lot basis) |
| Matrix and Components | 3 Bottles (8.0 mL each) of ARCHITECT 2ndGeneration Testosterone | Lyophilized control serum based on human serum |

{4}

| Similarities and Differences for Testosterone Controls | | |
| --- | --- | --- |
| Item | Candidate Device ARCHITECT 2^{nd} Generation Testosterone Controls | Predicate Device Roche Elecsys Testosterone II (k093421)- The Elecsys PreciControl Universal 1 and 2 |
| | Controls. Low, Medium, and High Controls contain testosterone in PBS buffer with a protein (bovine) stabilizer. Preservative: ProClin 300. | |

K. Standard/Guidance Document Referenced (if applicable):
- CLSI EP5-A2; Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline – Second Edition
- CLSI EP6-A; Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline
- CLSI EP7-A2; Interference Testing in Clinical Chemistry; Approved Guideline – Second Edition
- CLSI EP9-A2-IR; Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline – Second Edition (Interim Revision)
- CLSI EP17-A; Protocols for Determination of Limits of Detection and Limits of Quantitation; Approved Guideline

L. Test Principle:
The ARCHITECT 2nd Generation Testosterone immunoassay is based on a competitive test principle with anti-testosterone (sheep, monoclonal) coated paramagnetic microparticles and chemiluminescence detection. In the first step, sample, assay specific diluent and anti-testosterone (sheep, monoclonal) coated paramagnetic microparticles are combined. Testosterone present in the sample binds to the anti-testosterone coated microparticles. After incubation, testosterone acridinium-labeled conjugate is added to the reaction mixture. After further incubation and washing, Pre-Trigger and Trigger solutions are added to the reaction mixture. The resulting chemiluminescent reaction is measured as relative light units (RLUs). The concentration of testosterone is interpolated from a calibration curve established with calibrators of known testosterone concentration.

M. Performance Characteristics (if/when applicable):

1. Analytical performance:
a. Precision/Reproducibility:
Precision was determined following CLSI EP5-A2 guidance. Testing was

{5}

conducted using two instruments, two reagent kit lots, and one lot each of calibrators and controls. Four levels of controls and 1 human serum panel were assayed with a minimum of 2 replicates at 2 separate times per day for 20 different days. The results are summarized in the table below.

| Sample | Instrument | Reagent Lot | n | Mean ng/dL | Within Run | | Within - Laboratory (Total) | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | | | | SD | %CV | SD | %CV |
| Control Level 1 | 1 | 1 | 80 | 9.88 | 0.456 | 4.6 | 0.477 | 4.8 |
| | | 2 | 80 | 9.24 | 0.358 | 3.9 | 0.472 | 5.1 |
| | 2 | 1 | 80 | 9.56 | 0.390 | 4.1 | 0.439 | 4.6 |
| | | 2 | 80 | 9.02 | 0.459 | 5.1 | 0.468 | 5.2 |
| Control Level 2 | 1 | 1 | 80 | 76.07 | 2.339 | 3.1 | 2.734 | 3.6 |
| | | 2 | 80 | 72.07 | 2.277 | 3.2 | 2.361 | 3.3 |
| | 2 | 1 | 80 | 74.24 | 2.492 | 3.4 | 2.661 | 3.6 |
| | | 2 | 80 | 72.86 | 1.769 | 2.4 | 2.684 | 3.7 |
| Control Level 3 | 1 | 1 | 80 | 228.38 | 4.811 | 2.1 | 5.993 | 2.6 |
| | | 2 | 80 | 226.67 | 4.643 | 2.0 | 6.008 | 2.7 |
| | 2 | 1 | 80 | 227.22 | 5.732 | 2.5 | 7.496 | 3.3 |
| | | 2 | 80 | 229.95 | 5.504 | 2.4 | 6.391 | 2.8 |
| Control Level 4 | 1 | 1 | 80 | 944.73 | 20.617 | 2.2 | 23.101 | 2.8 |
| | | 2 | 80 | 932.20 | 20.262 | 2.2 | 21.183 | 2.6 |
| | 2 | 1 | 80 | 931.44 | 21.325 | 2.3 | 25.752 | 3.2 |
| | | 2 | 80 | 927.69 | 19.806 | 2.1 | 25.494 | 3.2 |
| Panel | 1 | 1 | 80 | 62.35 | 2.287 | 3.7 | 2.379 | 3.8 |
| | | 2 | 80 | 60.72 | 1.285 | 2.1 | 1.796 | 3.0 |
| | 2 | 1 | 80 | 61.30 | 1.888 | 3.1 | 2.184 | 3.6 |
| | | 2 | 80 | 61.53 | 1.558 | 2.5 | 2.028 | 3.3 |

## b. Linearity/assay reportable range:

Linearity studies were performed following CLSI EP6-A guideline. Three samples were diluted to produce 3 sets of 9 evenly distributed sample pools covering assay measuring range of 4.33 to $1500\mathrm{ng / dL}$. The linearity samples were tested with a minimum of 2 replicates on two $i$ $2000_{\mathrm{SR}}$ instruments over the

{6}

range of 3.82 to 1862.27 ng/dL. The measured vs. expected linear regression analysis generated a linear regression as follows: y= 0.98x + 0.12, r²=0.998.

The data support the sponsor’s claim that the measuring range for the device is 4.33 to 1500 ng/dL.

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

Traceability:

Calibrators: Abbott manufactures Testosterone internal standards (primary calibrators) gravimetrically using USP Testosterone at each concentration level. The Testosterone calibrators (market calibrators) are manufactured and tested against these internal standards.

Primary Testosterone Calibrators are prepared in a phosphate buffer synthetic matrix containing Sodium Chloride, Bovine Serum Albumin (BSA) and an antimicrobial agent. Calibrators are prepared gravimetrically to target 0, 2.88, 5.77, 46.14, 360.50, and 865.20 ng/dL Analyte containing calibrators are prepared with a 1154 ng/dL (40 nmol/L) Testosterone stock solution.

Market versions of the Testosterone Calibrators are prepared the same way as the Primary testosterone Calibrators. Each of the Market Calibrators is prepared with testosterone stock solution and 2nd Generation Testosterone Calibrator/Control Diluent to target concentrations 0, 2.88, 5.77, 46.14, 360.50, and 865.20 ng/dL (0, 0.1, 0.2, 1.6, 12.5, and 30.0 nmol/L).

Controls: Primary controls are prepared in a phosphate buffer synthetic matrix containing sodium chloride, BSA and an antimicrobial agent. Controls are prepared gravimetrically to target 8.7, 57.7, and 201.9 ng/dL (0.3, 2.0, and 7.0 nmol/L). Analyte containing controls are prepared with a 1154 ng/dL (40 nmol/L) Testosterone stock solution.

Market versions of the Testosterone Controls are prepared the same way as the Primary testosterone Controls. Each of the Market Controls is prepared with testosterone stock solution and 2nd Generation Testosterone Calibrator/Control Diluent to target to target 8.7, 57.7, and 201.9 ng/dL (0.3, 2.0, and 7.0 nmol/L)

Value assignment: The concentrations of each Market Testosterone Calibrator are determined by comparison of the relative light unit (RLU) values against the corresponding Primary Testosterone Calibrators using the ARCHITECT 2nd Generation Testosterone i System. The Market Calibrator is compared to the corresponding Primary Calibrator using a sample/reference ratio of the grand mean RLU results. The concentrations are adjusted, if necessary, by adding either testosterone stock solution or Calibrator A until they match the Primary Calibrator concentrations within the specification limits.

7

{7}

Value assignment for the Market Testosterone Controls follow the same procedure as for Market Testosterone Calibrators, please see above.

Stability: The sponsor provided the stability study protocol for reagent, calibrators and controls. The protocol and acceptance criteria were reviewed and found to be adequate. The real time stability studies are on going. The sponsor claims shelf-life and open-vial stability 12 months for calibrators, 11 months for controls. The on board stability for the reagent is claimed to be 9 months.

d. Detection limit:

The Limit of Blank (LoB), Limit of detection (LoD) and Limit of Quantitation (LoQ) were determined in accordance with CLSI EP17-A guideline.

The zero-level samples (for determination of the LoB) and the low-level samples (for determination of the LoD) were tested with a minimum of 2 replicates for the zero-level samples and 1 replicate for the low-level samples in 5 separate runs over a minimum of 3 days. Testing was performed on 2 ARCHITECT i 2000SR instruments using 2 lots of ARCHITECT 2nd Generation Testosterone Reagents, 2 lots of ARCHITECT 2nd Generation Testosterone Calibrators and 1 lot of Controls. Samples on both instruments were tested with both reagent lots. The LoB was determined to be 1.73 ng/dL (0.06 nmol/L) and the LoD was determined to be 2.67 ng/dL (0.10 nmol/L). The LoQ is defined as the lowest analyte concentration that meets an inter-assay imprecision of < 20%. The LoQ was observed to be 4.33 ng/dL with an inter-assay CV of 15.6%.

The claimed measuring range of the device is 4.33 to 1500 ng/dL.

e. Analytical specificity:

Potential interference was evaluated following CLSI EP7-A2 guidance.

Test samples were prepared by spiking each compound at the concentration level listed in the tables into a serum sample with each level of testosterone (201.9 and 700.8 ng/dL). Reference samples were prepared by adding solvent that was used to prepare the compound stocks to a serum sample of each of the two levels of testosterone (201.9 and 700.8 ng/dL). Spiked samples and reference samples were tested in a minimum of 12 replicates on one i 2000SR instrument using one lot each of ARCHITECT 2nd Generation Testosterone Reagents, Calibrators, and Controls.

Results of the spiked samples were compared with the reference samples and % recovery was calculated. Non-significant interference was defined as recovery of < ±10% of control value. Based on the data the sponsor claims no significant interference for the substances and concentrations listed below.

8

{8}

| Potentially Interfering Endogenous Substance | Highest interferent Concentrations tested |
| --- | --- |
| Bilirubin (unconjugated) | 20 mg/dL |
| Bilirubin (conjugated) | 20 mg/dL |
| Hemoglobin | 500 mg/dL |
| Total Protein | 12 g/dL |
| Triglycerides | 2000 mg/dL |
| Biotin | 30 ng/mL |
| SHBG | 200 nmol/L |

In addition, common pharmaceutical compounds (exogenous substances) were tested for interference at two levels of testosterone (201.9 and 700.8 ng/dL) and based on the sponsor's definition of non-significant interference ( $\leq \pm 10\%$ of control value), the sponsor claims no interference for the compounds and concentrations listed in the table below.

| Compounds tested | Concentrations |
| --- | --- |
| Acetylcystein | 150 mg/L |
| Ampicillin | 1000 mg/L |
| Ascorbic acid | 300 mg/L |
| Ca-Dobesilate | 200 mg/L |
| Cyclosporine | 5 mg/L |
| Cefoxitin | 2500 mg/L |
| Heparin | 5000 U |
| Levodopa | 20 mg/L |
| Methyldopa | 20 mg/L |
| Metronidazole | 200 mg/L |

{9}

| Phenylbutazone | 400 mg/L |
| --- | --- |
| Doxycyclin | 50 mg/L |
| Acetylsalicylic Acid | 1000 mg/L |
| Rifampicin | 60 mg/L |
| Acetaminophen | 200 mg/L |
| Ibuprofen | 50 mg/L |
| Theophilline | 100 mg/L |
| Heparin Clexane* | 5000 U |
| Dexamethasone | 20 mg/L |

* Low molecular weight heparin was used

Cross-reactivity study was performed by spiking two level testosterone serum samples (201.9 and $700.8\mathrm{ng / dL}$ ) with potential cross-reactant compounds. Based on the sponsor's definition of non-significant interference ( $\leq \pm 10\%$ of control value), the sponsor claims no cross-reactivity for the compounds and concentrations listed in the table below.

| Test Compounds (Drugs) | Concentration (ng/mL) |
| --- | --- |
| Danazol | 1,000 |
| Dexamethasone | 2,000 |
| Ethisterone | 1,000 |
| Mestranol (17a-Ethynylestradiol 3 methyl ether) | 1,000 |
| D(-) Norgestrel | 20 |
| 19-nortestosterone (Nandrolone) | 30 nmol/L |
| Prednisolone | 1,000 |
| Prednisone | 1,000 |
| Spironolactone | 500 |
| Testosterone Propionate | 100 |
| 5a-Androstane-3b,17b-diol | 1,000 |
| Androstenediol | 1,000 |
| Androstenedione | 100 |
| Cortisol | 1,000 |
| Cortisone | 2,000 |
| DHEA | 1,000 |

{10}

| DHEAS | 50,000 |
| --- | --- |
| Dihydrotestosterone | 500 |
| Epitestosterone | 100 nmol/L |
| Estradiol (17b-Estradiol) | 1,000 |
| Estrone | 1,000 |
| Ethynodiol diacetate | 50 |
| 17a-Ethynyl estradiol | 1000 |
| 11b-Hydroxytestosterone | 100 |
| 11-Ketotestosterone | 1,000 |
| Progesterone | 1,000 |

Ethristone (1000 ng/mL), 11b-hydroxytestosterone (100 ng/mL), 11-ketotestosterone (1000 ng/mL), D-Norgesterel (1000 ng/mL) and 19-nortestosterone (Nandrolone, 30 nmol/L) tested above the measuring range and their percent cross-reactivity could not be calculated. Therefore, these compounds were included in the package insert,

The sponsor has the following limitations in their labeling:

"Specimens from patients who have received preparations of mouse monoclonal antibodies for diagnosis or therapy may contain human anti-mouse antibodies (HAMA). Specimens containing HAMA may produce anomalous values when tested with assay kits such as ARCHITECT 2nd Generation Testosterone."

"A strong interaction with D-Norgestrel (1000 ng/ml), 19-nortestosterone (Nandrolone), Ethisterone, 11b-Hydroxytestosterone, and 11-Ketotestosterone was found. Do not use samples from patients receiving these compounds."

"Heterophilic antibodies in human serum can react with reagent immunoglobulins, interfering with in vitro immunoassays. Patients routinely exposed to animals or to animal serum products can be prone to this interference and anomalous results may be observed. Additional information may be required for diagnosis."

f. Assay cut-off:

Not applicable

2. Comparison studies:

a. Method comparison with predicate device:

{11}

A method comparison study was performed according to the CLSI EP9 guideline using the Passing- Bablok regression method to compare the ARCHITECT 2nd Generation Testosterone assay to the LCMS testosterone method. A total of 138 serum samples ranging from 13.74 to $1429.61\mathrm{ng / dL}$ were used in this study. The data are summarized in the tables below.

| n | ARCHITECT Testosterone (ng/dL) | | LCMS (ng/dL) | | Correlation Coefficient (r) | | Method | Intercept | | Slope | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | Min | Max | Min | Max | r | 95% CL | | Estimate | 95% CI | Estimate | 95% CI |
| 138 | 13.74 | 1429.61 | 6.0 | 1330.0 | 0.994 | 0.992 | Passing Bablok | -3.70 | (-5.00, -1.66) | 1.00 | (0.98, 1.03) |

# b. Matrix comparison:

The sponsor performed a matrix comparison study using 54 sample sets. Each sample set consisted of a control tube type (Plastic serum tube) and at least one of the blood collection tubes (Glass serum tube, Plastic serum separator tube, Plastic serum separator II Advance tube and Plastic dipotassium EDTA tube) collected from one donor during one draw. Samples ranging from 14.61 to $1430.75\mathrm{ng / dL}$ were analyzed on the ARCHITECT i 2000 system. The samples collected in control (Plastic/Serum) tube (x) were compared to the sample from one of the paired comparator tubes (y) and the Passing/Bablok regression analysis results are summarized in the table below:

| Tube type/Anticoagulant | Regression Analysis | |
| --- | --- | --- |
| Glass/Serum | y = 1.01x - 0.01 | r2= 0.999 |
| Plastic/Serum Separator | y = 0.98x - 0.01 | r2= 0.998 |
| Plastic/Serum Separator II Advance | y = 0.98x + 0.01 | r2= 0.999 |
| Plastic/Dipotassium EDTA | y = 1.05x - 0.01 | r2= 0.998 |

The sponsor claimed that serum (including serum collected in serum separator tubes) and plasma $\mathrm{(K_2EDTA)}$ are acceptable collection tubes for use with the Architect $2^{\mathrm{nd}}$ Generation Testosterone assay.

# 3. Clinical studies:

# a. Clinical Sensitivity:

Not applicable

{12}

b. Clinical specificity:

Not applicable

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:

The expected ranges for the ARCHITECT 2nd Generation Testosterone assay were obtained from testing a minimum of 120 samples from apparently healthy individuals in the following categories: normal males, 21-49 years of age with an intact reproductive system, and normal females 21-49 years of age. Additional samples were tested from apparently healthy males and females (> 50 years of age). The data are summarized in the table below.

| Category Apparently healthy | n | Age Range (years) | Testosterone (ng/dL) | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | | Median | Min. | Max. | 5th percentile | 95th percentile |
| Males (21-49 years of age) | 129 | 21-49 | 494.03 | 47.01 | 980.56 | 240.24 | 870.68 |
| Males (> 50 years of age) | 71 | 50-77 | 442.41 | 127.18 | 1020.36 | 220.91 | 715.81 |
| Females (21-49 years of age) | 129 | 21-49 | 24.80 | 7.21 | 79.31 | 13.84 | 53.35 |
| Females (> 50 years of age) | 52 | 50-82 | 23.50 | 8.65 | 36.92 | 12.40 | 35.76 |

It is recommended that each laboratory establish its own reference range that is appropriate for the laboratory's patient population (i.e., a normal range that reflects the type of specimen and demographic variables such as age and sex, as applicable).

{13}

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.

14