ABBOTT AXSYM TESTOSTERONE MICROPARTICLE ENZYME IMMUNOASSAY (MEIA)

K041866 · Axis-Shield Diagnostics, Ltd. · CDZ · Sep 29, 2004 · Clinical Chemistry

Device Facts

• Record ID: K041866
• Device Name: ABBOTT AXSYM TESTOSTERONE MICROPARTICLE ENZYME IMMUNOASSAY (MEIA)
• Applicant: Axis-Shield Diagnostics, Ltd.
• Product Code: CDZ · Clinical Chemistry
• Decision Date: Sep 29, 2004
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1680
• Device Class: Class 1

Indications for Use

AxSYM Testosterone is a Microparticle Enzyme Immunoassay (MEIA) for the quantitative determination of testosterone in human serum and plasma on the AxSYM System. Testosterone monitoring is used clinically to diagnose and differentiate endocrine disorders. In males, these include hypogonadism, testicular failure, infertility, hypopituitarism, and hyperprolactinemia. In females, polycystic ovary syndrome, adrenal hyperplasia, infertility, hirsutism, amenorrhea, obesity, and virilization can cause changes in serum testosterone levels. The AxSYM Testosterone assay is used as an aid in the investigation of infertility in males and of hirsutism and virilization in females. The AxSYM Testosterone Standard Calibrators are for the standard calibration of the AxSYM system when used for the quantitative determination of testosterone in human serum and plasma.

Device Story

AxSYM Testosterone is a quantitative microparticle enzyme immunoassay (MEIA) for serum/plasma testosterone. The device uses an AxSYM analyzer to process samples via a competitive binding reaction: testosterone in the sample competes with testosterone:alkaline phosphatase conjugate for anti-testosterone coated microparticles. The mixture is transferred to a matrix cell where microparticles bind to a glass fiber matrix; unbound substances are washed away. 4-Methylumbelliferyl Phosphate substrate is added; alkaline-phosphatase conjugate catalyzes the removal of a phosphate group, yielding fluorescent 4-Methylumbelliferone. The AxSYM optical assembly measures fluorescence, which is converted to quantitative testosterone units. The device is used in clinical laboratory settings by trained technicians. Results assist clinicians in diagnosing and monitoring endocrine disorders, including infertility, hirsutism, and virilization. The system provides automated quantitative output, enabling objective assessment of testosterone levels compared to reference ranges.

Clinical Evidence

Bench testing only. Precision evaluated per NCCLS EP5-A (n=80 per panel, 20 days). Linearity assessed via serial dilutions (recovery 99.3-134.6%). Analytical sensitivity <0.1 ng/mL; functional sensitivity <0.2 ng/mL. Specificity testing showed <1% cross-reactivity with 25 potential interferents. Method comparison (n=298) vs. predicate showed Passing-Bablock slope 1.03, r=0.98. Comparison vs. GC-MS (n=100) showed slope 1.10, r=0.97. Reference range study conducted on 296 healthy donors.

Technological Characteristics

Microparticle Enzyme Immunoassay (MEIA). Components: Anti-testosterone coated microparticles, Testosterone:Alkaline Phosphatase conjugate, Wash Buffer, and 6-point calibrators (0-15 ng/mL). Sensing principle: Fluorescence measurement of 4-Methylumbelliferone. Requires Abbott AxSYM analyzer. Calibration traceable to USP grade testosterone. Software: Instrument-based 6-point standard curve generation.

Indications for Use

Indicated for quantitative testosterone measurement in human serum/plasma to aid diagnosis of endocrine disorders. Patient population: males with hypogonadism, testicular failure, infertility, hypopituitarism, or hyperprolactinemia; females with polycystic ovary syndrome, adrenal hyperplasia, infertility, hirsutism, amenorrhea, obesity, or virilization.

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 assay (K964889)

Submission Summary (Full Text)

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

A. 510(k) Number:
k041866

B. Purpose for Submission:
New Device

C. Analyte:
Testosterone

D. Type of Test:
Quantitative Immunoassay

E. Applicant:
Axis-Shield Diagnostics Limited

F. Proprietary and Established Names
Abbott AxSYM Testosterone Microparticle Enzyme Immunoassay (MEIA) test

G. Regulatory Information:

1. Regulation Section:
21 CFR § 862.1150 (Calibrator)
21 CFR § 862.1680 (Testosterone Test System)

2. Classification:
Class II
Class I (reserved)

3. Product Code:
JIS
CDZ

4. Panel:
Clinical Chemistry

H. Intended Use:

1. Intended Use / Indications for Use:
AxSYM Testosterone is a Microparticle Enzyme Immunoassay (MEIA) for the quantitative determination of testosterone in human serum and plasma on the AxSYM System. Testosterone monitoring is used clinically to diagnose and differentiate endocrine disorders. In males, these include hypogonadism, testicular

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failure, infertility, hypopituitarism, and hyperprolactinemia. In females, polycystic ovary syndrome, adrenal hyperplasia, infertility, hirsutism, amenorrhea, obesity, and virilization can cause changes in serum testosterone levels.

The AxSYM Testosterone assay is used as an aid in the investigation of infertility in males and of hirsutism and virilization in females.

The AxSYM Testosterone Standard Calibrators are for the standard calibration of the AxSYM system when used for the quantitative determination of testosterone in human serum and plasma.

2. Special Conditions for Use Statement:

Prescription Use Only

3. Special Instrument Requirements:

The Abbott AxSYM analyzer is required.

I. Device Description:

This device consists of an AxSYM Testosterone Reagent Pack and a set of an AxSYM Testosterone Standard Calibrators. The bar coded Reagent Pack contains three reagents: Anti-testosterone Coated Microparticles, Testosterone:Alkaline Phosphatase Conjugate, and Wash Buffer. The Standard Calibrators consist of six calibrators A through F with testosterone concentrations of 0, 0.2, 1.0, 2.5, 7.0, and 15.0 ng/mL.

J. Substantial Equivalence Information:

1. Predicate device name(s): Roche Elecsys Testosterone
2. Predicate K number(s): K964889
3. Comparison with predicate:

| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Matrix | Same | Serum, plasma |
| Calibrator Range | Same | 0-15 ng/mL |
| Differences | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Methodology | Microparticle Enzyme Immunoassay | Electrochemiluminescence Immunoassay |
| Assay End-Point | Fluorescence | Electrochemiluminescence |
| On-board Reagent Stability | 2 weeks | 4 weeks (Elecsys 1010) |

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| Differences | | |
| --- | --- | --- |
| Item | Device | Predicate |
| | | 8 weeks (Elecsys 2010/E170) |
| Calibration Curve | Results are determined from a six-point standard calibration curve generated and stored on the instrument | Results are determined from a calibration curve generated on the instrument via a two-point calibration and a master curve provided by the reagent bar code |
| Analytical Sensitivity | ≤ 0.1 ng/mL | 0.02 ng/mL |
| Functional Sensitivity | ≤ 0.2 ng/mL | 0.12 ng/mL |

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

NCCLS EP5-A

## L. Test Principle:

The sample, Displacement Agent, and the antibody-coated microparticles are added together, forming the reaction mixture. As the mixture incubates, testosterone in the sample binds to the anti-testosterone on the microparticles, forming an antigen-antibody complex. Next the Testosterone:Alkaline Phosphatase Conjugate is added and incubated with the reaction mixture, during which time it competes for available anti-testosterone binding sites on the microparticles. After incubation, the mixture is transferred to the matrix cell, where the microparticles bind irreversibly to the glass fiber matrix. After washing to remove unbound substances, the 4-Methylumbelliferyl Phosphate substrate is added to the matrix cell. The alkaline-phosphatase labelled conjugate catalyzes the removal of a phosphate group from the substrate, yielding the fluorescent product 4-Methylumbelliferone. The fluorescence is measured by the AxSYM optical assembly and converted to quantitative units.

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

### 1. Analytical Performance:

#### a. Precision/Reproducibility:

The precision performance of this device was evaluated using NCCLS protocol EP5-A. Five plasma-based panels were tested, in replicates of two, at two separate times per day, for twenty days. Two AxSYM analyzers were used. A single lot of reagent was used and each analyzer was calibrated only once. Results were as follows:

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PANEL 1

| | | | Within Run | | Total | |
| --- | --- | --- | --- | --- | --- | --- |
| Analyzer | n | Mean (ng/mL) | SD | %CV | SD | %CV |
| 1 | 80 | 0.84 | 0.07 | 7.9 | 0.11 | 13.7 |
| 2 | 80 | 0.82 | 0.07 | 8.3 | 0.10 | 12.7 |

PANEL 2

| | | | Within Run | | Total | |
| --- | --- | --- | --- | --- | --- | --- |
| Analyzer | n | Mean (ng/mL) | SD | %CV | SD | %CV |
| 1 | 80 | 2.15 | 0.13 | 5.9 | 0.19 | 8.9 |
| 2 | 80 | 2.09 | 0.12 | 5.5 | 0.17 | 8.1 |

PANEL 3

| | | | Within Run | | Total | |
| --- | --- | --- | --- | --- | --- | --- |
| Analyzer | n | Mean (ng/mL) | SD | %CV | SD | %CV |
| 1 | 80 | 3.82 | 0.20 | 5.3 | 0.26 | 6.8 |
| 2 | 80 | 3.76 | 0.17 | 4.6 | 0.31 | 8.4 |

PANEL 4

| | | | Within Run | | Total | |
| --- | --- | --- | --- | --- | --- | --- |
| Analyzer | n | Mean (ng/mL) | SD | %CV | SD | %CV |
| 1 | 80 | 4.28 | 0.24 | 5.5 | 0.40 | 9.3 |
| 2 | 80 | 4.15 | 0.21 | 5.2 | 0.37 | 8.9 |

PANEL 5

| | | | Within Run | | Total | |
| --- | --- | --- | --- | --- | --- | --- |
| Analyzer | n | Mean (ng/mL) | SD | %CV | SD | %CV |
| 1 | 80 | 9.68 | 0.38 | 3.9 | 0.58 | 6.0 |
| 2 | 80 | 9.89 | 0.39 | 3.9 | 0.71 | 7.2 |

## b. Linearity/assay reportable range:

To assess linearity, five serum samples were selected ranging in testosterone concentration from 5.38 to $14.4\mathrm{ng / mL}$. Each sample was analyzed undiluted and at a dilution factor of X2, X4, X8, and X16, in triplicate. The $\%$ recovery was calculated by:

$$
\% \text{ recovery} = \text{observed value (ng/mL) / expected value (ng/mL)} \times 100
$$

The observed value was the mean of the three replicate measurements.

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Results were as follows:

| 1 | Dilution Factor | Observed Value | % Recovery |
| --- | --- | --- | --- |
| | Undiluted | 7.91 | --- |
| | X2 | 4.14 | 104.6 |
| | X4 | 2.18 | 110.0 |
| | X8 | 0.98 | 99.3 |
| | X16 | 0.54 | 108.8 |
| 2 | Undiluted | 5.38 | --- |
| | X2 | 3.01 | 112.0 |
| | X4 | 1.55 | 114.9 |
| | X8 | 0.86 | 128.5 |
| | X16 | 0.36 | 108.3 |
| 3 | Undiluted | 6.59 | --- |
| | X2 | 3.62 | 110.0 |
| | X4 | 1.83 | 111.0 |
| | X8 | 0.85 | 103.2 |
| | X16 | 0.48 | 116.6 |
| 4 | Undiluted | 14.40 | --- |
| | X2 | 7.30 | 101.3 |
| | X4 | 3.79 | 105.4 |
| | X8 | 1.88 | 104.3 |
| | X16 | 1.05 | 116.4 |
| 5 | Undiluted | 7.87 | --- |
| | X2 | 4.46 | 113.3 |
| | X4 | 2.39 | 121.4 |
| | X8 | 1.22 | 124.2 |
| | X16 | 0.66 | 134.6 |

c. Traceability, Stability, Expected Values (controls, calibrators, or method): The calibrators for this assay are traceable to USP grade testosterone. A testosterone stock solution is first prepared gravimetrically by spiking in USP grade testosterone into testosterone free defibrinated plasma. This stock solution is assigned a value by assaying against calibrators which had been verified by GC-MS. Reference calibrators are prepared gravimetrically from the stock solution, and the standard kit calibrators are rate-matched to the reference calibrators. The overall acceptable rate mean ratio is 0.98 – 1.02.

In addition to real-time stability studies, the calibrators are subjected to freeze/thaw and heat stress conditions. After stressing calibrator performance is compared to the sponsor's acceptance criteria to determine the failure point. Both real-time and accelerated testing is used to establish claimed shelf-life stability.

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d. Detection limit:

The sponsor calculated both an analytical and functional sensitivity.

Analytical sensitivity was defined as the concentration at two standard deviations from the mean of Calibrator A rates, and represents the lowest measurable concentration of analyte that can be distinguished from zero. Calibrator A was run in replicates of 10, on two AxSYM analyzers, using two lots of reagent. A total of 12 runs were performed, and the sponsor reports an analytical sensitivity of &lt;0.1 ng/mL.

Functional sensitivity was defined as the lowest measurable concentration of analyte that can be measured with an inter-assay coefficient of variation less than or equal to 20%. To assess functional sensitivity, 7 human serum samples, ranging in concentration from 0.11 to 0.46 ng/mL, were tested once per day, in replicates of 5, on one analyzer, for 5 days. Results were as follows:

| Sample ID | 1 | 2 | 3 | 4 | 5 | 6 | 7 |
| --- | --- | --- | --- | --- | --- | --- | --- |
| Mean | 0.10492 | 0.13996 | 0.17036 | 0.22376 | 0.31324 | 0.3794 | 0.4585 |
| SD | 0.01842 | 0.02868 | 0.04127 | 0.04049 | 0.05702 | 0.05055 | 0.06091 |
| CV% | 18 | 20 | 24 | 18 | 18 | 13 | 13 |

The calculated % CV was plotted against the mean concentration of each sample. The functional sensitivity was determined to be &lt;0.2 ng/L, as the concentration corresponding to a CV of 20% on a fitted curve.

e. Analytical specificity:

The sponsor evaluated the potential for interference from similar compounds by spiking calibrator A (0.0 ng/mL testosterone) and calibrator D (2.5 ng/mL testosterone) with the following potential cross-reactants:

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| Potential Cross-reactant | Calibrator A | |
| --- | --- | --- |
| | Test Concentration (ng/mL) | % Cross-reactivity |
| Androstenedione | 200 | <± 1% |
| 5α-dihydrotestosterone | 100 | <± 1% |
| 5 α-androstane-3,17-dione | 1000 | <± 1% |
| Oxymetholone | 100 | <± 1% |
| Methyltestosterone | 100 | <± 1% |
| 17B-Estradiol | 1000 | <± 1% |
| Androsterone | 1000 | <± 1% |
| Cortisol | 1000 | <± 1% |
| Cyproterone acetate | 1000 | <± 1% |
| Danazol | 1000 | <± 1% |
| DHEA-sulfate | 1000 | <± 1% |
| 11-deoxycortisol | 1000 | <± 1% |
| Dexamethasone | 1000 | <± 1% |
| Estrone | 1000 | <± 1% |
| Progesterone | 1000 | <± 1% |
| 17 α-Ethynylestradiol 3 methyl ether | 1000 | <± 1% |
| 17 α-Ethynyl estradiol | 1000 | <± 1% |
| Cortisone | 1000 | <± 1% |
| Deoxycorticosterone | 1000 | <± 1% |
| Estriol | 1000 | <± 1% |
| Ethynodiol diacetate | 50 | <± 1% |
| Norethindrone acetate | 50 | <± 1% |
| D(-) Norgestrel | 50 | <± 1% |
| Spironolactone | 1000 | <± 1% |
| Corticosterone | 1000 | <± 1% |

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| Potential Cross-reactant | Calibrator D | |
| --- | --- | --- |
| | Test Concentration (ng/mL) | % Cross-reactivity |
| 5α-dihydrotestosterone | 100 | <± 1% |
| Oxymetholone | 100 | <± 1% |
| Methyltestosterone | 100 | <± 1% |
| 17B-Estradiol | 1000 | <± 1% |
| Androsterone | 1000 | <± 1% |
| Cortisol | 1000 | <± 1% |
| Cyproterone acetate | 1000 | <± 1% |
| Danazol | 1000 | <± 1% |
| DHEA-sulfate | 1000 | <± 1% |
| 11-deoxycortisol | 1000 | <± 1% |
| Dexamethasone | 1000 | <± 1% |
| Estrone | 1000 | <± 1% |
| Progesterone | 1000 | <± 1% |
| 17 α-Ethynylestradiol 3 methyl ether | 1000 | <± 1% |
| 17 α-Ethynyl estradiol | 1000 | <± 1% |
| 5 α-androstane-3,17-dione | 1000 | <± 1% |
| Cortisone | 1000 | <± 1% |
| Deoxycorticosterone | 1000 | <± 1% |
| Estriol | 1000 | <± 1% |
| Ethynodiol diacetate | 50 | <± 1% |
| Norethindrone acetate | 50 | <± 1% |
| D(-) Norgestrel | 50 | <± 1% |
| Spironolactone | 1000 | <± 1% |
| Corticosterone | 1000 | <± 1% |
| Androstenedione | 200 | <± 1% |

The sponsor also evaluated the potential for positive or negative interference from endogenous compounds by spiking in potential interferents to human serum samples and observing the change from the unspiked samples. Results were as follows:

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| Unspiked conc (ng/mL) | Spiked with 750 mg/dL Hemoglobin (ng/mL) | % Interference |
| --- | --- | --- |
| 0.86 | 0.88 | 2.3 |
| 0.64 | 0.67 | 4.7 |
| 2.98 | 3.28 | 10.1 |
| 5.12 | 5.24 | 2.3 |
| 6.52 | 6.91 | 6.0 |
| 4.89 | 5.09 | 4.1 |
| Unspiked conc (ng/mL) | Spiked with 20 mg/dL Bilirubin (ng/mL) | % Interference |
| --- | --- | --- |
| 12.16 | 13.02 | 7.0 |
| 11.77 | 11.40 | -3.1 |
| 12.30 | 12.78 | 3.9 |
| 10.25 | 11.30 | 10.2 |
| 0.15 | 0.17 | 10.4 |
| 0.96 | 1.10 | 15.0 |
| Unspiked conc (ng/mL) | Spiked with 500 mg/dL Triglyceride (ng/mL) | % Interference |
| --- | --- | --- |
| 14.88 | 14.25 | -4.3 |
| 6.71 | 6.00 | -10.5 |
| 10.73 | 10.36 | -3.5 |
| 6.21 | 5.95 | -4.2 |
| 0.58 | 0.51 | -13.1 |
| 2.66 | 2.66 | 0.1 |
| 12.54 | 12.87 | 2.6 |
| 4.89 | 4.75 | -2.9 |
| Unspiked conc (ng/mL) | Spiked with 90 nmol/L SHBG (ng/mL) | % Interference |
| --- | --- | --- |
| 2.65 | 2.79 | 5.2 |
| 3.10 | 2.92 | -5.7 |
| 4.69 | 4.61 | -1.6 |
| 7.89 | 7.28 | -7.8 |
| 8.38 | 8.29 | -1.1 |
| 10.39 | 8.87 | -14.7 |
| Unspiked conc (ng/mL) | Spiked with 10 g/dL Protein (ng/mL) | % Interference |
| --- | --- | --- |
| 0.193 | 0.174 | -9.8 |
| 3.061 | 3.068 | 0.3 |
| 5.320 | 5.291 | -0.5 |
| 12.092 | 10.836 | -10.4 |

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| Unspiked conc (ng/mL) | Spiked with 0.4% v/v RBCs (ng/mL) | % Interference |
| --- | --- | --- |
| 9.05 | 8.69 | -3.9 |
| 6.51 | 6.06 | -6.9 |
| 10.1 | 9.77 | -3.3 |
| 7.76 | 7.33 | -5.5 |
| 0.50 | 0.56 | 12.0 |
| 0.63 | 0.64 | 1.1 |

f. Assay cut-off:
Not applicable.

2. Comparison studies:

a. Method comparison with predicate device:
The sponsor did a method comparison study versus both the predicate device and gas chromatography – mass spectrometry.

The comparison with the predicate included 298 samples, which included 205 adult males and 93 adult females. The range of data as measured by the AxSYM was 0.05 – 12.05 ng/mL and by the predicate was 0.14 – 9.79 ng/mL. A Passing-Bablock regression analysis was done on the data, which produced the following line equation and correlation coefficient:

Slope = 1.03 (95% Confidence Interval 1.01 to 1.06)

y-intercept = -0.121 (95% Confidence Interval -0.14 to -0.09)

Correlation Coefficient 0.98

For the second comparison, 100 samples were chosen from the group of 298 and analyzed by GC-MS. This group included 50 males and 50 females. The range of data as measured by the AxSYM was 0.05 – 12.05 and by GC-MS was 0.10 – 12.82 ng/mL. A Passing-Bablock regression analysis was done on the data, which produced the following line equation and correlation coefficient:

Slope = 1.10 (95% Confidence Interval 1.01 to 1.16)

y-intercept = -0.06 (95% Confidence Interval -0.10 to -0.02)

Correlation Coefficient 0.97

b. Matrix comparison:
The sponsor recommends the use of serum or plasma with this assay. To demonstrate equivalence, 10 matched human serum and plasma specimens

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were collected in the following tube types: serum clot tube with no additive (control), serum separator tube, EDTA plasma, sodium heparin plasma, and lithium heparin plasma. Results were as follows:

| Sample # | Testosterone Concentration (ng/mL) | | | | | % Difference | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | Serum Clot Tubes | Serum SST | Plasma EDTA | Plasma Li Heparin | Plasma Na Heparin | Serum Clot Tubes | Serum SST | Plasma EDTA | Plasma Li Heparin | Plasma Na Heparin |
| FS1 | 0.414 | 0.405 | 0.412 | 0.413 | 0.427 | --- | -2.2 | -0.6 | -0.3 | 3.1 |
| FS2 | 0.203 | 0.198 | 0.193 | 0.148 | 0.192 | --- | -2.4 | -4.7 | -27.0 | -5.2 |
| FS3 | 0.211 | 0.188 | 0.241 | 0.218 | 0.196 | --- | -10.9 | 13.8 | 3.1 | -7.3 |
| FS4 | 0.178 | 0.200 | 0.222 | 0.186 | 0.200 | --- | 12.4 | 24.7 | 4.5 | 12.4 |
| FS5 | 0.377 | 0.356 | 0.386 | 0.374 | 0.397 | --- | -5.6 | 2.4 | -0.8 | 5.3 |
| MS1 | 2.088 | 2.061 | 2.096 | 1.968 | 1.921 | --- | -1.3 | 0.4 | -5.7 | -8.0 |
| MS2 | 7.758 | 7.872 | 7.870 | 7.298 | 7.811 | --- | 1.5 | 1.4 | -5.9 | 0.7 |
| MS3 | 7.014 | 6.959 | 6.962 | 7.578 | 7.048 | --- | -0.8 | -0.7 | 8.0 | 0.5 |
| MS4 | 8.054 | 7.890 | 7.731 | 7.399 | 7.695 | --- | -2.0 | -4.0 | -8.1 | -4.5 |
| MS5 | 2.734 | 2.700 | 2.634 | 2.456 | 2.636 | --- | -1.2 | -3.7 | -10.2 | -3.6 |
| Mean | 2.90 | 2.88 | 2.87 | 2.81 | 2.85 | --- | -1.3 | 2.9 | -4.2 | -0.7 |

3. Clinical Studies:

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

4. Clinical Cutoff:

Not applicable.

5. Expected Values/Reference Range:

The sponsor performed their own reference range study with samples from 296 apparently healthy adult donors. The study included 92 females (age range 18 - 62) and 204 males (age range 18 - 70). Results were as follows:

| | | | | | Percentile | |
| --- | --- | --- | --- | --- | --- | --- |
| | | Testosterone (ng/mL) | | | 2.5% | 97.5% |
| Specimen | n | Median | Minimum | Maximum | (ng/mL) | (ng/mL) |
| Females | 92 | 0.23 | 0.05 | 0.73 | 0.05 | 0.62 |
| Males | 204 | 4.21 | 1.95 | 11.38 | 2.25 | 9.72 |

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N. Conclusion:

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.