Who can help prepare an FDA 510(k) submission like TESTOSTERONE TEST SYSTEM; CALIBRATOR; AND QUALITY CONTROL MATERIAL (ASSAYED AND UNASSAYED)?

Innolitics — a medical-device software consultancy — provides regulatory and engineering support for FDA 510(k) submissions. See https://innolitics.com/services/510ks/ or contact https://innolitics.com/contact.

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

Q: Who is the manufacturer of TESTOSTERONE TEST SYSTEM; CALIBRATOR; AND QUALITY CONTROL MATERIAL (ASSAYED AND UNASSAYED)?

Abbott Laboratories filed the 510(k) submission for TESTOSTERONE TEST SYSTEM; CALIBRATOR; AND QUALITY CONTROL MATERIAL (ASSAYED AND UNASSAYED) (K120009).

Q: What is the FDA product code for TESTOSTERONE TEST SYSTEM; CALIBRATOR; AND QUALITY CONTROL MATERIAL (ASSAYED AND UNASSAYED)?

CDZ. It is classified under 21 CFR 862.1680 as a Class 1 device in the Clinical Chemistry panel.

Q: What is the regulatory pathway for TESTOSTERONE TEST SYSTEM; CALIBRATOR; AND QUALITY CONTROL MATERIAL (ASSAYED AND UNASSAYED)?

510(k) clearance (submission type: Traditional).

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

Intended 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)

Related Devices

K152155 — ARCHITECT 2nd Generation Testosterone · Abbott Laboratories · Dec 17, 2015
K983212 — ABBOTT ARCHITECT TESTOSTERONE · Abbott Laboratories · Nov 18, 1998
K093421 — ELECSYS TESTOSTERONE II IMMUNOASSAY · Roche Diagnostics Corp. · Apr 23, 2010

Submission Summary (Full Text)

{0}------------------------------------------------ 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 {1}------------------------------------------------ ## 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. {2}------------------------------------------------ - 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. {3}------------------------------------------------ | Control | Target Concentration / Range | | | |-----------|------------------------------|---------------------------|---------------------| | | nmol/L | ng/dL | ng/mL | | Control L | 0.31 0.16 - 0.46 | 8.94 4.61 - 13.27 | 0.09 0.05 - 0.13 | | Control M | 2.42 1.52 - 3.32 | 69.79 43.62 - 95.96 | 0.70 0.44 - 0.96 | | Control H | 7.58 4.74 - 10.42 | 218.61 136.63 - 300.59 | 2.18 1.37 - 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 Device ARCHITECT 2nd Generation Testosterone | Predicate Device Roche Elecsys Testosterone II (k093421) | | Intended Use and Indications for Use | Immunoassay for the in vitro 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. | Same | | Reagent Kit Similarities and Differences | | | | Characteristics | Submission Device ARCHITECT 2nd Generation Testosterone | Predicate Device Roche Elecsys Testosterone II (k093421) | | Platform | ARCHITECT i System (immunoassay analyzer) | Elecsys and cobas e immunoassay 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/dL In addition, a reference range study using pediatric population (95 males and 100 females) under 18 years old, who were in good endocrinological health was performed. | | Measuring Interval | Measuring interval is defined as the range of values in ng/dL (nmol/L) which meets the acceptable performance for both imprecision and bias across all available assay file dilutions. The range was 4.33 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 or 0.087 - 52.0 nmol/L (defined by the limit of detection and the maximum of the master curve). Values below the limit of detection are reported as < 2.50 ng/dL or < 0.087 nmol/L. Values above the measuring range are reported as > 1500 ng/dL or > 52.0 nmol/L | | LoB | LoB: 1.73 ng/dL (0.06 nmol/L) | LoB: 1.20 ng/dL or 0.42 nmol/L | | LoD | | | | Reagent Kit Similarities and Differences | | | | | Submission Device ARCHITECT 2nd Generation Testosterone | Predicate Device Roche Elecsys Testosterone 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/L LoQ: 12.0 ng/dL or 0.416 nmol/L | | Components: | | | | 1 | 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. | 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) Testosterone acridinium-labeled conjugate in BIS Tris buffer with surfactant 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 reagent 2-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 and glycine in citrate buffer. Preservative: ProClin 300. | R2: Testosterone-peptide ${\sim}$ Ru(bpy)5+ (black cap), 1 bottle, 9 mL: Testosterone derivative, labeled with ruthenium complex 1.5 ng/mL; MES buffer 50 mmol/L, pH 6.0; preservative. | | 4 | Specimen Diluent: 1 or 4 Bottle(s) (12.2 mL) Testosterone Specimen Diluent containing PBS buffer. Preservative: ProClin 300 | NA | {4}------------------------------------------------ . · {5}------------------------------------------------ . {6}------------------------------------------------ | Calibrators: Similarities and Differences: | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |--------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--| | Characteristics | Submission Device ARCHITECT 2nd Generation Testosterone | Predicate Device · Roche Elecsys Testosterone II (k093421) | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Intended use | 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 Elecsys Testosterone CalSetII is intended for the calibration of the quantitative testosterone assay on the Elecsys immunoassay analyzer systems. | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Levels | 6 levels | The calibration curve is instrument-specifically generated by 2-point calibration and a master curve provided via the reagent barcode. Testosterone II CalSet 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) 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. | Lyophilized human serum with 2 testosterone concentration levels | | | | | | | | | | | | | | | | | | | | | | | | | | | | Standardization/ Traceability | Abbott manufactures internal reference standards for ARCHITECT 2nd Generation Testosterone using Testosterone Reference Standard (USP). Testosterone calibrators are manufactured gravimetrically and tested against these internal reference standards. | This method has been standardized via ID-GC/MS (Isotope Dilution-Gas Chromatography/Mass Spectrometry). | | | | | | | | | | | | | | | | | | | | | | | | | | | | . . . {7}------------------------------------------------ | Controls: Similarities and Differences: | | | | | | | | | | | | | | | | | |-----------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------|--|--|--|--|--|--|--|--|--|--|--|--|--|--| | Characteristics | Submission Device ARCHITECT 2nd Generation Testosterone | Predicate Device Roche Elecsys Testosterone II (k093421) | | | | | | | | | | | | | | | | Intended use | 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 Elecsys PreciControl Universal 1 and 2, are used for monitoring the accuracy and precision of Elecsys immunoassays. | | | | | | | | | | | | | | | | Matrix and Components | 3 Bottles (8.0 mL each) of ARCHITECT 2nd Generation Testosterone Controls. Low, Medium, and High Controls contain testosterone in PBS buffer with a protein (bovine) stabilizer. Preservative: ProClin 300. | Lyophilized control serum based on human serum | | | | | | | | | | | | | | | | Levels | 3 levels: Low. Medium, and High Targets: | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | 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 | | | | | | | | | | | | | | | | : . - . . . : · {8}------------------------------------------------ ## 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 | {9}------------------------------------------------ ## 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 Endogenous Substance | Interferent Concentration | % Interference Testosterone 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 | {10}------------------------------------------------ ## 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. | Test Compound (Drugs) | Test Compound Conc. 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 Compound Conc. ng/mL | Testosterone Concentration 201.9 ng/dL | | Testosterone Concentration 700.8 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 | {11}------------------------------------------------ ** 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) | Evaluation Tube Range (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 {12}------------------------------------------------ ## 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. | Category Apparently Healthy | n | Age Range (years) | 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 (\$\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 Range ng/dL | | Correlation Coefficient (r) | Intercept ng/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 Range ng/dL | | Correlation Coefficient (r) | Intercept ng/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 Range ng/dL | | Correlation Coefficient (r) | Intercept ng/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 {16}------------------------------------------------ ## 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)