(252 days)
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.
The ARCHITECT 2nd Generation Testosterone Reagent Kit consists of 100 (1 x 100) or 400 (4 x 100) tests. Each kit contains 1 or 4 bottle(s) each of Microparticles. Conjugate. Assay Specific Diluent, and Specimen Diluent.
Microparticles 1 or 4 Bottle(s) (6.6 mL) Anti-Testosterone (sheep, monoclonal) coated . microparticles in BIS Tris buffer with protein (bovine) stabilizer. Minimum concentration: 0.1% solids. Preservative: ProClin 300.
. Conjugate -1 or 4 Bottle(s) (6.9 mL) Testosterone acridinium-labeled conjugate in BIS Tris buffer with surfactant stabilizer. Minimum concentration: 6.5 nmol/L. Preservative: ProClin 300.
. Assay Specific Diluent - 1 or 4 Bottle(s) (25.0 mL) Testosterone Assay Diluent containing phosphate and glycine in citrate buffer. Preservative: ProClin 300.
. Specimen Diluent - 1 or 4 Bottle(s) (12.2 mL) Testosterone Specimen Diluent containing PBS buffer. Preservative: ProClin 300.
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 in PBS buffer. All calibrators contain a protein (bovine) stabilizer. Preservative: ProClin 300.
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 in PBS buffer with a protein (bovine) stabilizer. Preservative: ProClin 300.
Here's an analysis of the acceptance criteria and the study proving the device meets them, based on the provided text:
Device: ARCHITECT 2nd Generation Testosterone assay, Calibrators, and Controls.
1. A table of acceptance criteria and the reported device performance
| Performance Characteristic | Acceptance Criteria | Reported Device Performance (ARCHITECT 2nd Generation Testosterone) |
|---|---|---|
| Precision | Within-laboratory (total) imprecision of ≤ 10% CV for samples with testosterone concentrations ≥ 14.4 ng/dL to 1009 ng/dL. | All reported within-laboratory (total) %CV values were ≤ 5.2%, well within the ≤ 10% CV acceptance criterion for the control levels (9.02-229.95 ng/dL) and the human serum panel (60.72-62.35 ng/dL) tested. Specific values range from 2.6% to 5.2%. |
| Limit of Quantitation (LoQ) | LoQ of ≤ 4.33 ng/dL with an inter-assay imprecision of < 20%. | Observed LoQ: 4.33 ng/dL with an inter-assay CV of 15.6%. This meets the acceptance criterion. |
| Limit of Blank (LoB) | Not explicitly stated as an acceptance criterion in this section, but a value is presented. | Observed LoB: 1.73 ng/dL. |
| Limit of Detection (LoD) | Not explicitly stated as an acceptance criterion in this section, but a value is presented. | Observed LoD: 2.67 ng/dL. |
| Measuring Interval (Reportable Range) | Measuring interval from 4.33 ng/dL (LoQ) to 1500.00 ng/dL. | Demonstrated range: 4.33 ng/dL (LoQ) to 1500.00 ng/dL. This matches the acceptance criterion. |
| Linearity | Linear range supporting the Measuring Interval (4.33 ng/dL to 1500 ng/dL), with an absolute deviation from linearity of 3.605 ng/dL for ≤ 14.4 ng/dL and 10% for > 14.4 ng/dL. | Demonstrated linear range: 3.82 - 1862.27 ng/dL. This supports the claimed measuring interval. |
| Interference (Endogenous Substances) | Potential interference from bilirubin, hemoglobin, total protein, triglycerides, biotin, and SHBG to be < 10%. | All tested endogenous substances showed % Interference < 10%. Specific values ranged from -7.0% to 4.4%. |
| Method Comparison (vs. LCMS) | Slope of 1.0 ± 0.2 and a correlation coefficient (r) of ≥ 0.95 for samples with testosterone concentrations ranging from 4.33 ng/dL (LoQ) to 1500.00 ng/dL. | Overall (n=138): Slope 1.00 (95% CI: 0.98, 1.03), r = 0.994. Meets criteria. Female Specimens (n=73): Slope 0.82 (95% CI: 0.77, 0.88), r = 0.985. Meets r criterion, but slope is at the lower end of the criterion. Male Specimens (n=65): Slope 1.10 (95% CI: 1.07, 1.13), r = 0.990. Meets criteria. |
2. Sample sized used for the test set and the data provenance
- Precision (Within-Laboratory): 80 replicates per control level/panel, instrument, and reagent lot combination. This means 4 (control/panel levels) * 2 (instruments) * 2 (reagent lots) = 16 combinations, so 16 * 80 = 1280 individual measurements for controls and 1 human serum panel.
- Provenance: "human serum panel" is mentioned, implying human origin. The study was conducted based on NCCLS document EP5-A2 guidance. Retrospective/prospective is not specified, but typically lab performance studies use carefully controlled, often prepared, samples.
- Limit of Quantitation (LoQ), Limit of Blank (LoB), Limit of Detection (LoD): The sample size specific to the LoQ study design (NCCLS document EP17-A) is not explicitly stated, but the resulting LoQ was determined.
- Linearity: The sample size for the linearity study (NCCLS document EP6-A) is not explicitly stated.
- Interference (Endogenous Substances): Sample size for the interference study (CLSI protocol EP7-A2) is not explicitly stated for each substance, but evaluation was performed.
- Interference (Potentially Interfering Drugs and Other Compounds): Sample size for this interference study (CLSI document EP7-A2) is not explicitly stated for each compound.
- Tube Type Matrix Comparison: N = 54 samples for each evaluation tube type to compare against the control tube type.
- Expected Values:
- Males (21-49 years): 129 samples
- Males (≥ 50 years): 71 samples
- Females (21-49 years): 129 samples
- Females (≥ 50 years): 52 samples
- Provenance: All from "apparently healthy individuals". Country of origin/retrospective/prospective is not specified.
- Method Comparison (vs. LCMS): n = 138 total samples (73 female specimens, 65 male specimens).
- Provenance: Human samples are implied as "female specimens" and "male specimens" were analyzed. Retrospective/prospective is not specified.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
This is an in vitro diagnostic (IVD) device for measuring a quantitative analyte (testosterone). The "ground truth" for such devices is typically established through reference methods or highly accurate analytical techniques, not through expert consensus in the way image-based diagnostics might.
- For Method Comparison: Liquid Chromatography - Tandem Mass Spectrometry (LCMS) was used as the reference method. LCMS is a highly precise and accurate analytical technique, often considered a "gold standard" for quantitative biochemical measurements. The "experts" in this context would be the skilled laboratory personnel operating and validating the LCMS system. No specific number or qualifications of "experts" are provided in the document for the LCMS ground truth, as it's an analytical measurement rather than a subjective interpretation.
4. Adjudication method for the test set
Not applicable for this type of quantitative diagnostic device. Adjudication methods (like 2+1 or 3+1) are typically used in studies where human experts interpret results (e.g., radiology images) and a consensus is needed to establish ground truth. For an IVD, the ground truth is established by a reference analytical method (LCMS in this case).
5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
Not applicable. This is not an AI-assisted diagnostic device where human readers interact with AI. It is a standalone immunoassay measuring testosterone levels.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, the studies presented demonstrate the standalone performance of the ARCHITECT 2nd Generation Testosterone assay. The device directly measures testosterone concentrations in samples, with performance characteristics (precision, sensitivity, linearity, interference, method comparison) evaluated solely based on the assay's output against established analytical standards and reference methods. There is no human interpretation or intervention in the generation of the primary testosterone measurement result.
7. The type of ground truth used
- Analytical Standards/Known Concentrations: For precision, LoQ, LoB, LoD, linearity, and interference studies, the ground truth often comes from prepared samples with known, spiked concentrations of testosterone and/or interfering substances.
- Reference Method: For the method comparison study, Liquid Chromatography - Tandem Mass Spectrometry (LCMS) was used as the ground truth.
- Known Clinical Status: For "Expected Values" (reference ranges), the ground truth was based on samples from "apparently healthy individuals" categorized by age and sex. This is a clinical rather than an analytical ground truth.
8. The sample size for the training set
This document describes performance validation studies for an established immunoassay technology. Immunoassay development typically involves extensive optimization and characterization during the R&D phase, which would involve numerous samples. However, the document does not distinguish between a "training set" and a "test set" in the context of machine learning, as this is a chemical assay, not an AI model. The sample sizes listed in point #2 above pertain to the performance evaluation studies used to demonstrate the device meets its acceptance criteria. No separate "training set" for an algorithm is mentioned as there is no AI algorithm.
9. How the ground truth for the training set was established
Not applicable as there is no training set mentioned in the context of an AI algorithm. For the development of the assay itself, the ground truth for optimizing antibodies and assay parameters would historically come from highly purified testosterone standards and well-characterized clinical samples, leveraging similar analytical reference methods (e.g., LCMS) to define true concentrations.
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K12009
SEP
1 1 2012
510(k) Summary (Summary of Safety and Effectiveness)
This summary of the 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
1. Applicant Name
John Rizos, Regulatory Affairs Project Manager Regulatory Affairs Abbott Laboratories Diagnostics Division Dept 9V6, AP5N-2 100 Abbott Park Road Abbott Park, IL 60064 Telephone Number: (847) 935-1813 Fax Number: (847) 937-4836 Date Summary prepared: September 7, 2012
2. Device Name
ARCHITECT 2nd Generation Testosterone ARCHITECT 2nd Generation Testosterone Calibrators ARCHITECT 2nd Generation Testosterone Controls
Reagents
Classification Name: Testosterone test system Trade Name: ARCHITECT 2nd Generation Testosterone Common Name: Testosterone Governing Regulation: 862.1680 Device Classification: Class I, reserved Classification Panel: Clinical Chemistry Product Code: CDZ
Calibrators
Classification Name: Calibrator Trade Name: ARCHITECT 2nd Generation Testosterone Calibrators Common Name: Calibrator Governing Regulation: 862.1150 Device Classification: Class II Classification Panel: Clinical Chemistry Product Code: JIT
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Controls
Classification Name: Quality Control Material (assayed and unassayed) Trade Name: ARCHITECT 2nd Generation Testosterone Controls Common Name: Control Governing Regulation: 862.1660 Device Classification: Class I , reserved Classification Panel: Clinical Chemistry Product Code: JJX
3. Predicate Device
Roche Elecsys Testosterone II assay (K093421)
4. Intended Use of Device
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.
5. Description of Device
ARCHITECT 2nd Generation Testosterone Reagents
The ARCHITECT 2nd Generation Testosterone Reagent Kit consists of 100 (1 x 100) or 400 (4 x 100) tests. Each kit contains 1 or 4 bottle(s) each of Microparticles. Conjugate. Assay Specific Diluent, and Specimen Diluent.
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- Microparticles 1 or 4 Bottle(s) (6.6 mL) Anti-Testosterone (sheep, monoclonal) coated . microparticles in BIS Tris buffer with protein (bovine) stabilizer. Minimum concentration: 0.1% solids. Preservative: ProClin 300.
- . Conjugate -1 or 4 Bottle(s) (6.9 mL) Testosterone acridinium-labeled conjugate in BIS Tris buffer with surfactant stabilizer. Minimum concentration: 6.5 nmol/L. Preservative: ProClin 300.
- . Assay Specific Diluent - 1 or 4 Bottle(s) (25.0 mL) Testosterone Assay Diluent containing phosphate and glycine in citrate buffer. Preservative: ProClin 300.
- . Specimen Diluent - 1 or 4 Bottle(s) (12.2 mL) Testosterone Specimen Diluent containing PBS buffer. Preservative: ProClin 300.
ARCHITECT 2nd Generation Testosterone Calibrators
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 in PBS buffer. All calibrators contain a protein (bovine) stabilizer. Preservative: ProClin 300.
| Concentration | |||
|---|---|---|---|
| Calibrator | nmol/L | ng/dL | ng/mL |
| Cal A | 0.00 | 0.00 | 0.00 |
| Cal B | 0.10 | 2.88 | 0.03 |
| Cal C | 0.20 | 5.77 | 0.06 |
| Cal D | 1.60 | 46.14 | 0.46 |
| Cal E | 12.50 | 360.50 | 3.60 |
| Cal F | 30.00 | 865.20 | 8.64 |
The calibrators are manufactured at the following concentrations:
ARCHITECT 2nd Generation Testosterone Controls
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 in PBS buffer with a protein (bovine) stabilizer. Preservative: ProClin 300.
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| Control | Target Concentration / Range | ||
|---|---|---|---|
| nmol/L | ng/dL | ng/mL | |
| Control L | 0.310.16 - 0.46 | 8.944.61 - 13.27 | 0.090.05 - 0.13 |
| Control M | 2.421.52 - 3.32 | 69.7943.62 - 95.96 | 0.700.44 - 0.96 |
| Control H | 7.584.74 - 10.42 | 218.61136.63 - 300.59 | 2.181.37 - 2.99 |
The controls are at the following concentrations:
6. Comparison of Technological Characteristics
The ARCHITECT 2nd Generation Testosterone assay utilizes chemiluminescent microparticle immunoassay (CMIA) technology for the quantitative determination of testosterone in human serum and plasma. The Roche Elecsys Testosterone II assay utilizes electrochemiluminescence immunoassay technology ("ECLIA") and is intended for use on Elecsys and cobas e immunoassay analyzers.
| Reagent Kit Similarities and Differences | ||
|---|---|---|
| Characteristics | Submission DeviceARCHITECT 2ndGeneration Testosterone | Predicate DeviceRoche ElecsysTestosterone II (K093421) |
| Intended Use andIndications for Use | Immunoassay for the in vitroquantitative determination oftestosterone in human serumand plasma.Measurements of testosteroneare used in the diagnosis andtreatment of disordersinvolving the male sexhormones (androgens),including primary andsecondary hypogonadism,delayed or precociouspuberty, impotence in malesand, in females, hirsutism(excessive hair) andvirilization (masculinization)due to tumors, polycysticovaries, and adrenogenitalsyndromes. | Same |
| Reagent Kit Similarities and Differences | ||
| Characteristics | Submission DeviceARCHITECT 2ndGeneration Testosterone | Predicate DeviceRoche ElecsysTestosterone II (K093421) |
| Platform | ARCHITECT i System(immunoassay analyzer) | Elecsys and cobas eimmunoassay analyzers |
| Methodology | Chemiluminescence(CMIA) | Electrochemiluminescence(ECLIA) |
| Specimen type | Serum and plasma | Serum and plasma |
| Expected Values | • Males (21-49) :47.01 - 980.56 ng/dL• Males (≥ 50 years of age):127.18-1020.36 ng/dL• Females (21-49):7.21-79.31 ng/dL• Females (≥ 50 years of age):8.65-36.92 ng/dL | • Males (20-49):249 - 836 ng/dL• Males (≥ 50):193 - 740 ng/dL• Females (20-49):8.40 - 48.1 ng/dL• Females (≥ 50):2.90 - 40.8 ng/dLIn addition, a reference rangestudy using pediatricpopulation (95 males and 100females) under 18 years old,who were in goodendocrinological health wasperformed. |
| Measuring Interval | Measuring interval is definedas the range of values inng/dL (nmol/L) which meetsthe acceptable performancefor both imprecision and biasacross all available assay filedilutions. The range was4.33 ng/dL (0.15 nmol/L)(Limit of Quantitation - LoQ)to 1500.00 ng/dL(52.01 nmol/L). | Measuring Range:2.50 - 1500 ng/dL or0.087 - 52.0 nmol/L(defined by the limit ofdetection and the maximumof the master curve). Valuesbelow the limit of detectionare reported as < 2.50 ng/dLor < 0.087 nmol/L. Valuesabove the measuring range arereported as > 1500 ng/dL or >52.0 nmol/L |
| LoB | LoB: 1.73 ng/dL (0.06nmol/L) | LoB: 1.20 ng/dL or 0.42nmol/L |
| LoD | ||
| Reagent Kit Similarities and Differences | ||
| Submission DeviceARCHITECT 2ndGeneration Testosterone | Predicate DeviceRoche ElecsysTestosterone II (K093421) | |
| Characteristics | ||
| LoQ | LoD: 2.67 ng/dL (0.10 nmol/L)LoQ: 4.33 ng/dL (0.15 nmol/L) | LoD: 2.50 ng/dL or 0.087 nmol/LLoQ: 12.0 ng/dL or 0.416 nmol/L |
| Components: | ||
| 1 | Microparticles:1 or 4 Bottle(s) (6.6 mL)Anti-Testosterone (sheep, monoclonal) coatedmicroparticles in BIS Tris buffer with protein (bovine) stabilizer. Minimumconcentration: 0.1% solids.Preservative: ProClin 300. | M:Streptavidin-coated microparticles (transparent cap), 1 bottle, 6.5mL:Streptavidin-coated microparticles 0.72 mg/mL,preservative. |
| 2 | Conjugate: 1 or 4 Bottle(s) (6.9 mL) Testosteroneacridinium-labeled conjugate in BIS Tris buffer withsurfactant stabilizer.Minimum concentration: 6.5 nmol/L. Preservative:ProClin 300. | R1:Anti-testosterone-Ab ${\sim}$ biotin (gray cap), 1 bottle, 10mL:Biotinylated monoclonal anti-testosterone antibody (sheep) 40 ng/mL; releasing reagent2-bromoestradiol; MES buffer 50 mmol/L, pH 6.0;preservative. |
| 3 | Assay Specific Diluent:1 or 4 Bottle(s) (25.0 mL)Testosterone Assay Diluent containing phosphate andglycine in citrate buffer.Preservative: ProClin 300. | R2:Testosterone-peptide${\sim}$ Ru(bpy)5+ (black cap), 1bottle, 9 mL: Testosterone derivative, labeled withruthenium complex 1.5ng/mL; MES buffer 50mmol/L, pH 6.0; preservative. |
| 4 | Specimen Diluent:1 or 4 Bottle(s) (12.2 mL)Testosterone SpecimenDiluent containing PBSbuffer. Preservative:ProClin 300 | NA |
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| Calibrators: Similarities and Differences: | |||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Characteristics | Submission DeviceARCHITECT 2ndGeneration Testosterone | Predicate Device ·Roche ElecsysTestosterone II (K093421) | |||||||||||||||||||||||||||
| Intended use | The ARCHITECT 2ndGeneration TestosteroneCalibrators are for thecalibration of theARCHITECT i System whenused for the quantitativedetermination of testosteronein human serum and plasma. | The Elecsys TestosteroneCalSetII is intended for thecalibration of the quantitativetestosterone assay on theElecsys immunoassayanalyzer systems. | |||||||||||||||||||||||||||
| Levels | 6 levels | The calibration curve isinstrument-specificallygenerated by 2-pointcalibration and a master curveprovided via the reagentbarcode. Testosterone IICalSet II -2 levels. | |||||||||||||||||||||||||||
| nmol/Lng/dLng/mLA0.000.000.00B0.102.880.03C0.205.770.06D1.6046.140.46E12.50360.503.60F30.00865.208.64 | |||||||||||||||||||||||||||||
| Components | 6 Bottles (4.0 mL each) ofARCHITECT 2ndGeneration TestosteroneCalibrators A-F. Calibrator Acontains PBS buffer.Calibrators B through Fcontain testosterone in PBSbuffer. All calibrators containa protein (bovine) stabilizer.Preservative: ProClin 300. | Lyophilized human serumwith 2 testosteroneconcentration levels | |||||||||||||||||||||||||||
| Standardization/Traceability | Abbott manufactures internalreference standards forARCHITECT 2ndGeneration Testosteroneusing Testosterone ReferenceStandard (USP).Testosterone calibrators aremanufactured gravimetricallyand tested against theseinternal reference standards. | This method has beenstandardized via ID-GC/MS(Isotope Dilution-GasChromatography/MassSpectrometry). |
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| Controls: Similarities and Differences: | ||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Characteristics | Submission DeviceARCHITECT 2ndGeneration Testosterone | Predicate DeviceRoche ElecsysTestosterone II (K093421) | ||||||||||||||
| Intended use | The ARCHITECT 2ndGeneration TestosteroneControls are for theverification of the accuracyand precision of theARCHITECT i System whenused for the quantitativedetermination of testosteronein human serum and plasma. | The Elecsys PreciControlUniversal 1 and 2, are usedfor monitoring the accuracyand precision of Elecsysimmunoassays. | ||||||||||||||
| Matrix andComponents | 3 Bottles (8.0 mL each) ofARCHITECT 2ndGeneration TestosteroneControls. Low, Medium, andHigh Controls containtestosterone in PBS bufferwith a protein (bovine)stabilizer. Preservative:ProClin 300. | Lyophilized control serumbased on human serum | ||||||||||||||
| Levels | 3 levels: Low. Medium, andHighTargets: | |||||||||||||||
| nmol/L ng/dL ng/mL L 0.31 8.94 0.09 M 2.42 69.79 0.70 H 7.58 218.61 2.18 |
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7. Summary of Nonclinical Performance
SPECIFIC PERFORMANCE CHARACTERISTICS
Precision
The ARCHITECT 2nd Generation Testosterone assay is designed to have a within-laboratory (total) imprecision of ≤ 10% CV for samples with testosterone concentrations ≥ 14.4 ng/dL to 1009 ng/dL.
Within-Laboratory Precision
A study was performed based on guidance from the National Committee for Clinical Laboratory Standards (NCCLS) document EP5-A2. Testing was conducted using two instruments, two ARCHITECT 2nd Generation Testosterone Reagent Kit lots, and one lot each of ARCHITECT 2nd Generation Testosterone Calibrators and Controls. Three 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 data are summarized in the following table.
| 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 | ||
| 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 |
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Sensitivitv
Limit of Quantitation
The ARCHITECT 2nd Generation Testosterone assay is designed to have a Limit of Quantitation (LoQ) of ≤ 4.33 ng/dL. The LoQ is defined as the lowest analyte concentration that meets an inter-assay imprecision of < 20%. The LoQ study design was based on guidance from NCCLS document EP17-A. The observed LoQ for the ARCHITECT 2nd Generation Testosterone assay was 4.33 ng/dL with an inter-assay CV of 15.6%.
Limit of Blank and Limit of Detection
In the same study, the Limit of Blank (LoB) and Limit of Detection (LoD) were determined. The LoB was 1.73 ng/dL and the LoD was 2.67 ng/dL.
Measuring Interval (Reportable Range)
Measuring interval is defined as the range of values in ng/dL which meets the acceptable performance for both imprecision and bias across all available assay file dilutions. The range was 4.33 ng/dL (Limit of Quantitation) to 1500.00 ng/dL.
Linearity
A study was performed based on guidance from the NCCLS document EP6-A. Using an absolute deviation from linearity of 3.605 ng/dL for samples with concentrations of ≤ 14.4 ng/dL, and 10% for samples with concentrations > 14.4 ng/dL, a linear range of 3.82 - 1862.27 ng/dL was demonstrated for the ARCHITECT 2nd Generation Testosterone assay which supports the Measuring Interval (Reportable Range) of 4.33 ng/dL to 1500 ng/dL.
Interference
Potentially Interfering Endogenous Substances
Potential interference in the ARCHITECT 2nd Generation Testosterone assay from billirubin. hemoglobin, total protein, triglycerides, biotin, and Sex Hormone Binding Globulin (SHBG) was evaluated to be < 10%. Interference was demonstrated by a study based on guidance from the CLSI protocol EP7-A2. The data are summarized in the following table.
| Potentially Interfering EndogenousSubstance | InterferentConcentration | % InterferenceTestosterone Concentration | |
|---|---|---|---|
| 201.9 ng/dL | 700.8 ng/dL | ||
| Bilirubin (unconjugated) | 20 mg/dL | -0.2 | 1.9 |
| Bilirubin (conjugated) | 20 mg/dL | -2.0 | 4.4 |
| Hemoglobin | 500 mg/dL | 2.5 | 2.2 |
| Total Protein | 12 g/dL | -4.6 | -7.0 |
| Triglycerides | 2000 mg/dL | -6.5 | -1.1 |
| Biotin | 30 ng/mL | -2.1 | -0.8 |
| SHBG | 200 nmol/L | -5.3 | -9.1 |
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Potentially Interfering Drugs and Other Compounds
A study was performed based on guidance from the CLSI document
EP7-A2. Potentially interfering drugs and other compounds were evaluated to determine whether testosterone concentrations were affected when using the ARCHITECT 2nd Generation Testosterone assay. The data are summarized in the following table. NOTE: Test compound concentration is in ng/mL unless noted otherwise.
| TestCompound(Drugs) | TestCompoundConc.ng/mL | Testosterone Concentration | |||
|---|---|---|---|---|---|
| 201.9 ng/dL | % Cross-Reactivity | 700.8 ng/dL | % Cross-Reactivity | ||
| Danazol | 1,000 | 724.19 | 0.7 | 606.24 | 0.6 |
| Dexamethasone | 2,000 | 1.12 | 0.0 | -0.58 | 0.0 |
| Ethisterone | 1,000 | ** | NA | ** | NA |
| Mestranol (17a-Ethynylestradiol 3 methyl ether) | 1,000 | -3.75 | 0.0 | 2.31 | 0.0 |
| D(-) Norgestrel | 20 | -16.83 | -0.8 | -12.69 | -0.6 |
| 1000 | 1072.19 | 1.1 | 783.66 | 0.8 | |
| 19-nortestosterone(Nandrolone) | 30 nmol/L | ** | NA | ** | NA |
| Prednisolone | 1,000 | 2.64 | 0.0 | 5.44 | 0.0 |
| Prednisone | 1,000 | 1.92 | 0.0 | -9.59 | 0.0 |
| Spironolactone | 500 | 0.43 | 0.0 | -4.21 | 0.0 |
| Testosterone Propionate | 100 | 2843.19 | 28.4 | 883.00 | 8.8 |
| 5a-Androstane-3b,17b-diol | 1,000 | 477.51 | 0.5 | 348.41 | 0.3 |
| Androstenediol | 1,000 | -3.11 | 0.0 | -7.94 | 0.0 |
| Androstenedione | 100 | 177.29 | 1.8 | 121.47 | 1.2 |
| Cortisol | 1,000 | 0.85 | 0.0 | 15.36 | 0.0 |
| Cortisone | 2,000 | 1.06 | 0.0 | 10.11 | 0.0 |
| DHEA | 1,000 | -13.07 | 0.0 | -9.34 | 0.0 |
| DHEAS | 50,000 | 96.65 | 0.0 | 99.94 | 0.0 |
| Dihydrotestosterone | 500 | 352.85 | 0.7 | 223.05 | 0.4 |
| Epitestosterone | 100 nmol/L | 2.71 | 0.1 | 12.32 | 0.4 |
| Estradiol (17b-Estradiol) | 1,000 | 8.67 | 0.0 | -5.50 | 0.0 |
| Test Compound(Drugs) | Test CompoundConc.ng/mL | Testosterone Concentration201.9 ng/dL | Testosterone Concentration700.8 ng/dL | ||
| Conc.Diff. | % Cross-Reactivity | Conc.Diff. | % Cross-Reactivity | ||
| Estrone | 1,000 | -8.90 | 0.0 | -9.09 | 0.0 |
| Ethynodiol diacetate | 50 | -5.44 | -0.1 | -2.19 | 0.0 |
| 17a-Ethynyl estradiol | 1,000 | -11.79 | 0.0 | 3.23 | 0.0 |
| 11b-Hydroxytestosterone | 100 | ** | NA | ** | NA |
| 11-Ketotestosterone | 1,000 | ** | NA | ** | NA |
| Progesterone | 1,000 | -1.75 | 0.0 | 18.65 | 0.0 |
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** These compounds tested above the measuring interval and the % Cross-reactivity could not be calculated.
Tube Type Matrix Comparison
A study was performed to evaluate the types of blood collection tubes that can be used with the ARCHITECT 2nd Generation Testosterone assay. The tube types were evaluated using the Passing-Bablok regression method to compare each evaluation tube type (N =54) to the control tube type (serum plastic). The data are summarized in the following table.
| Evaluation Tube Type | Control Tube(serum plastic)Range(ng/dL) | EvaluationTubeRange(ng/dL) | ra | Intercept(ng/dL) | Slope |
|---|---|---|---|---|---|
| Serum, glass | 14.61-1430.75 | 14.42-1469.01 | 1.000 | -0.38 | 1.01 |
| Serum separator, plastic | 14.23-1477.86 | 0.999 | -0.42 | 0.99 | |
| Serum separator II Advance | 14.32-1419.41 | 0.999 | -0.07 | 0.98 | |
| Dipotassium EDTA | 13.41-1526.41 | 0.997 | -0.96 | 1.02 |
4 r = Correlation Coefficient
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EXPECTED VALUES
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 following table.
| CategoryApparently Healthy | n | AgeRange(years) | Median | Min. | Max. | 5thpercentile | 95thpercentile |
|---|---|---|---|---|---|---|---|
| Males(21-49 years of age) | 129 | 21-49 | 494.03 | 47.01 | 980.56 | 240.24 | 870.68 |
| Males($\geq$ 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($\geq$ 50 years of age) | 52 | 50-82 | 23.50 | 8.65 | 36.92 | 12.40 | 35.76 |
Method Comparison
The ARCHITECT 2nd Generation Testosterone assay is designed to have a slope of 1.0 ± 0.2 and a correlation coefficient (r) of ≥ 0.95 for samples with testosterone concentrations ranging from 4.33 ng/dL (LoQ) to 1500.00 ng/dL when compared to Liquid Chromatography - Tandem Mass Spectrometry (LCMS). A method comparison study was performed based on guidance from the CLSI document EP9-A2-IR using the Passing-Bablok regression method to compare the ARCHITECT 2nd Generation Testosterone assay to the LCMS testosterone method. The data are summarized in the following tables.
ARCHITECT 2nd Generation Testosterone vs. LCMS
(n = 138)
| Concentration Rangeng/dL | CorrelationCoefficient(r) | Interceptng/dL | 95%CIa | Slope | 95%CIa | |
|---|---|---|---|---|---|---|
| ARCHITECT | LCMS | |||||
| 13.74-1429.61 | 6.0-1330.00 | 0.994 | -3.70 | (-5.00, -1.66) | 1.00 | (0.98, 1.03) |
a CI = Confidence Interval
{13}------------------------------------------------
ARCHITECT 2nd Generation Testosterone vs. LCMS
| Concentration Rangeng/dL | CorrelationCoefficient(r) | Interceptng/dL | 95%CIa | Slope | 95%CIa | |
|---|---|---|---|---|---|---|
| ARCHITECT | LCMS | |||||
| 13.74-349.97 | 6.0-346.5 | 0.985 | 2.77 | (0.53, 4.45) | 0.82 | (0.77, 0.88) |
Female Specimens (n = 73)
ª CI = Confidence Interval
ARCHITECT 2nd Generation Testosterone vs. LCMS
Male Specimens (n = 65)
| Concentration Rangeng/dL | CorrelationCoefficient(r) | Interceptng/dL | 95%CIa | Slope | 95%CIa | |
|---|---|---|---|---|---|---|
| ARCHITECT | LCMS | 0.990 | -48.63 | (-62.25, -32.25) | 1.10 | (1.07, 1.13) |
| 86.93-1429.61 | 115.0-1330.0 |
4 CI = Confidence Interval
8. Conclusion
The data presented in this premarket notification demonstrates that the ARCHITECT 2nd Generation Testosterone assay performs substantially equivalent to the predicate device, the Roche Elecsys Testosterone II assay (K093421). Accuracy was demonstrated by comparison to a Liquid Chromatography - Tandem Mass Spectrometry (LCMS) reference method. The data presented in the premarket notification provide reasonable assurance that the ARCHITECT 2nd Generation Testosterone assay is safe and effective for the stated intended use.
{14}------------------------------------------------
10903 New Hampshire Avenue Silver Spring, MD 20993
Abbott Laboratories Abbott Laboratories Diagnostics Division c/o John Rizos Dept 9V6, AP5N-2 100 Abbott Park Road Abbott Park, IL 60064
7 1 2012
K120009 Re:
Trade Name: ARCHITECT 2nd Generation Testosterone ARCHITECT 2nd Generation Testosterone Calibrators ARCHITECT 2nd Generation Testosterone Controls Regulation Number: 21 CFR §862.1680 Regulation Name: Testosterone Test System Regulatory Class: Class I, reserved Product Codes: CDZ, JIT, JJX Dated: July 27, 2012 Received: July 30, 2012
Dear Mr. Rizos:
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.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting (1 writ), it may of babyest to Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. four device can be four learning 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 moun mat FDP may Federal statutes and regulations administered by other Federal agencies. of the recordly 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 and fishing (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).
Image /page/14/Picture/11 description: The image shows the seal of the Department of Health & Human Services - USA. The seal is circular and contains the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. In the center of the seal is an image of a stylized eagle.
{15}------------------------------------------------
Page 2
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please If you desire specific advice tor your as now in as absation and Safety at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH 's CFK Parl 807.97). For questions regarding positions of Postmarket Surveillance at (301).
Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveilliance a Office of Surveinations regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/Medical
CFK Part 803), prease go to intp://www.htmlgor.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 Tou thay of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-5680 or at its Internet address (000) 030-2641 or (504) MedicalDevices/Resourcesfor You/Industry/default.htm
Sincerely yours,
Courtney H. Lias, Ph.D.
Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known): K120009 Device Name: ARCHITECT 2nd Generation Testosterone ARCHITECT 2nd Generation.Testosterone Calibrators ARCHITECT 2nd Generation Testosterone Controls
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.
Prescription Use X (Part 21 CFR 801 Subpart D) AND/OR
Over-The-Counter Use _ (21 CFR 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)
Yung Chan
Division Sign Off Office of In Vitro Diagnostic Device Evaluation and Safety
< 120009 510(k)
§ 862.1680 Testosterone test system.
(a)
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.(b)
Classification. Class I.