(338 days)
Immunoassay for the in vitro quantitative determination of testosterone in human serum and plasma.
The electrochemiluminescence immunoassay "ECLIA" is intended for use on the cobas e 601 immunoassay analyzer.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) due to tumors, polycystic ovaries, and adrenogenital syndromes.
The Elecsys Testosterone II immunoassay makes use of a competitive test principle using streptavidin-coated microparticles and electrochemiluminescence detection. Results are determined using a calibration curve that is generated specifically on each instrument by a 2point calibration and master curve provided with the reagent bar code. The Elecsys Testosterone II reagent kit consists of a Reagent Pack (R1, R2, and M (Streptavidin-coated microparticles)).
The Elecsys Testosterone II device is an immunoassay for the in vitro quantitative determination of testosterone in human serum and plasma. The device is intended for use on the cobas e 601 immunoassay analyzer.
1. Acceptance Criteria and Reported Device Performance
The acceptance criteria for the Elecsys Testosterone II are based on various analytical performance characteristics. The table below summarizes some of the key performance criteria and the reported performance of the candidate device (Elecsys Testosterone II, K211685) in comparison to its predicate device (Elecsys Testosterone II, K093421).
| Feature | Acceptance Criteria (Predicate) | Reported Performance (Candidate) |
|---|---|---|
| Precision | Refer to CLSI EP05-A | 21-day precision: Evaluated according to CLSI guideline EP05-A3. Protocol: 2 replicates of 2 controls and 5 samples, 2 runs/day over 21 days with 1 reagent lot. Repeatability and intermediate precision calculated. 5-day precision: Evaluated on one cobas e 601 analyzer according to CLSI guideline EP05-A3. Protocol: 5 aliquots of each control (PreciControl Universal Level 1 & 2) and human serum samples per run, 1 run/day for 5 days with 3 lots. Repeatability and intermediate precision calculated. |
| LoB | 1.2 ng/dL | 1.50 ng/dL or 0.052 nmol/L |
| LoD | Same as predicate | 2.50 ng/dL or 0.087 nmol/L |
| LoQ | Same as predicate | 12.0 ng/dL or 0.416 nmol/L |
| Measuring Range | 2.50-1500 ng/dL or 0.087-52.0 nmol/L | 2.50-1500 ng/dL or 0.087-52.0 nmol/L (defined by Limit of Detection and maximum of master curve). |
| Cross-Reactivity | Various specific values | DHEA-S: 0.003%, Androstenedione: 3.15%, Danazol: 0.504%, Estradiol: 0.211%, Ethisterone: 3.57%, 19-Norethisterone: 5.51%, Norgestrel: 0.539%, △5-Androstene-3β17β-diol: 0.289%, Testosterone propionate: 0.718%, 5α-Androstane-3β, 17β-diol: 2.15%, 5α-Dihydrotestosterone: 1.30%, 11β-OH-Testosterone: 20.6%, 11keto-Testosterone: 4.87%, Prednisone: n.d., Prednisolone: n.d., Progesterone: 0.009%, Cortisol: n.d., Cortisone: n.d., Dexamethasone: n.d., Estrone: n.d., DHEA: 0.014%. |
| Biotin Interference | < 30 ng/mL | No biotin interference in serum concentrations up to 1200 ng/mL. |
| Special Drug Interference | None | Testosterone Undecanoate or Nandrolone strongly interfered with Testosterone and produced elevated recovery values. |
| Method Comparison | Passing/Bablok: y = 0.961x - 0.015, T = 0.975; Linear regression: y = 0.958x - 0.006, r = 0.999 | Passing/Bablok: y = 0.948x + 0.023, T = 0.976; Linear regression: y = 0.950x - 0.871, r = 0.998. The data from analytical studies demonstrate the device is as safe, as effective, and performs as well as or better than the predicate. |
2. Sample Size Used for the Test Set and Data Provenance
- Precision (5-Day): 5 aliquots of each control (PreciControl Universal Level 1 and Level 2) and human serum samples per run, 1 run per day for 5 days with 3 lots. (Implies multiple individual human serum samples but the exact number isn't specified, and the controls are commercial products).
- Precision (21-Day): 2 replicates of 2 controls and 5 samples, 2 runs per day over 21 days using 1 reagent lot. (Implies 5 individual human serum samples, plus two controls).
- Linearity: One human serum sample with high analyte content was serially diluted (25 steps).
- Endogenous Interferences: Not explicitly stated, but implies analysis of testosterone concentrations with and without spiked interfering substances.
- Biotin Interference: Not explicitly stated, but implies multiple testosterone samples spiked with biotin.
- Common Drug Interferences: Not explicitly stated, but implies multiple samples tested with common drugs.
- Special Drug Interferences: Samples (with testosterone concentrations near 0.5 ng/mL and near 5.0 ng/mL) were divided into aliquots and spiked with Testosterone Undecanoate. The number of samples is not explicitly stated.
- Analytical Specificity/Cross-Reactivity: One testosterone level (0.5 ng/mL) in human serum matrix was spiked with potential cross-reactants. The number of samples is not explicitly stated.
- Sample Matrix Comparison: At least 40 serum/plasma pairs (Native or spiked samples).
- Method Comparison to Predicate: 168 samples (Native single samples and spiked single samples).
Data Provenance: The studies used human serum and plasma samples, as well as control materials. The specific country of origin is not explicitly stated, but Roche Diagnostics has facilities in Indianapolis, IN (USA), Mannheim, Germany, and Penzberg, Germany, suggesting a potential international origin or a combination of origins for their sample collection. The studies described are analytical performance evaluations, which are typically prospective in design for device validation.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This device is an in vitro diagnostic (IVD) quantitative assay for testosterone. The "ground truth" for such assays typically refers to the reference method (e.g., ID-GC/MS) or the established value of control materials. It does not involve expert readers reviewing images or clinical data to establish a diagnostic truth. Therefore, the concept of "experts" in the context of interpretation of results is not directly applicable here. The establishment of ground truth for accuracy and calibration is based on:
- Traceability/Standardization: ID-GC/MS ("Isotope Dilution - Gas Chromatography/Mass Spectrometry"). This is a highly accurate and precise analytical method that serves as a reference.
- Calibrators: Testosterone II CalSet II (Calibrators 1 and 2) are used, which are themselves traceable to the ID-GC/MS method.
4. Adjudication Method for the Test Set
Not applicable. As described above, this is an IVD assay, not an imaging-based diagnostic where adjudication of expert readings would be necessary. The performance is assessed by comparing results to reference methods or known concentrations, or through statistical analyses of precision and linearity.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No MRMC comparative effectiveness study was mentioned. This type of study is typically relevant for interpretative diagnostic devices (e.g., radiology AI tools) where human readers interpret cases with and without AI assistance. The Elecsys Testosterone II is a laboratory assay that provides a quantitative numerical result, and therefore, does not involve human readers interpreting "cases" in the same way.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done
The performance studies described (Precision, LoB, LoD, LoQ, Linearity, Interferences, Cross-Reactivity, Sample Matrix Comparison, Method Comparison) are all standalone performance evaluations of the assay system (reagents + instrument) without human-in-the-loop interpretation. The device's primary function is to quantitatively measure testosterone, and its performance is assessed directly against analytical standards and reference methods.
7. The Type of Ground Truth Used
- Reference Method: ID-GC/MS (Isotope Dilution - Gas Chromatography/Mass Spectrometry) serves as the primary reference method for traceability and standardization.
- Known Concentrations: Control materials (e.g., PreciControl Universal) and spiked samples with known concentrations of analytes and interferents are used.
- Predetermined Clinical Values: Samples for method comparison include those that span the measuring range, implying a range of clinically relevant testosterone levels.
8. The Sample Size for the Training Set
The document describes analytical performance studies for validation (test set), but does not explicitly mention a "training set" in the context of algorithm development. Immunoassays like the Elecsys Testosterone II are typically developed and optimized using a range of samples during the research and development phase to establish reagent formulations, reaction kinetics, and calibration curves. However, the exact sample sizes for this initial developmental "training" are not usually detailed in 510(k) summaries, which focus on the validation data.
9. How the Ground Truth for the Training Set Was Established
Similar to point 8, the document does not detail the "training set" for algorithm development. For IVD assays, the "training" involves establishing the master curve and optimizing reagents to accurately measure testosterone across its dynamic range. This optimization would rely on:
- Characterized reference materials: Samples with known testosterone concentrations, often established by highly accurate reference methods like ID-GC/MS.
- Clinical samples: A broad range of human serum and plasma samples from various populations (males, females, different age groups, healthy, and those with relevant disorders) would be used to ensure the assay performs reliably across the intended use population.
- Spiked samples: Samples with known additions of testosterone or interfering substances to evaluate various aspects of assay performance.
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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
May 6, 2022
Roche Diagnostics Justin Davis Regulatory Affairs Manager 9115 Hague Road, PO Box 50416 Indianapolis, Indiana 46250
Re: K211685
Trade/Device Name: Elecsys Testosterone II Regulation Number: 21 CFR 862.1680 Regulation Name: Testosterone Test System Regulatory Class: Class I, reserved Product Code: CDZ Dated: February 4, 2022 Received: February 7, 2022
Dear Justin Davis:
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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's
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requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Marianela Perez-Torres, Ph.D. Deputy Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K211685
Device Name
Elecsys Testosterone II
Indications for Use (Describe)
Immunoassay for the in vitro quantitative determination of testosterone in human serum and plasma.
The electrochemiluminescence immunoassay "ECLIA" is intended for use on the cobas e 601 immunoassay analyzer.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) due to tumors, polycystic ovaries, and adrenogenital syndromes.
X Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)
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Elecsys Testosterone II 510(k) Summary
K211685
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR 807.92.
In accordance with 21 CFR 807.87, Roche Diagnostics hereby submits official notification as required by Section 510(k) of the Federal Food, Drug and Cosmetics Act of our intention to market the device described in this Premarket Notification 510(k).
The purpose of this Traditional 510(k) Premarket Notification is to obtain FDA review and clearance for the Elecsys Testosterone II on the cobas e 601.
| Submitter Name | Roche Diagnostics |
|---|---|
| Address | 9115 Hague RoadP.O. Box 50416Indianapolis, IN 46250-0457 |
| Contact | Justin DavisPhone: (317) 521-6204Email: justin.davis@roche.com |
| Date Prepared | May 27, 2021 |
| Proprietary Name | Elecsys Testosterone II |
| Common Name | Testosterone II Assay |
| Classification Name | Radioimmunoassay, Testosterones And Dihydrotestosterone |
| Product Codes,Regulation Numbers | CDZ21 CFR 862.1680 |
| Predicate Devices | Elecsys Testosterone II (K093421) |
| Establishment Registration | Roche Diagnostics GmbH Mannheim, Germany: 9610126Roche Diagnostics GmbH Penzberg, Germany: 9610529Roche Diagnostics Indianapolis, IN United States: 1823260 |
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1. DEVICE DESCRIPTION
The Elecsys Testosterone II immunoassay makes use of a competitive test principle using streptavidin-coated microparticles and electrochemiluminescence detection. Results are determined using a calibration curve that is generated specifically on each instrument by a 2point calibration and master curve provided with the reagent bar code. The Elecsys Testosterone II reagent kit consists of a Reagent Pack (R1, R2, and M (Streptavidin-coated microparticles)).
2. INDICATIONS FOR USE
Immunoassay for the in vitro quantitative determination of testosterone in human serum and plasma.
The electrochemiluminescence immunoassay "ECLIA" is intended for use on the cobas e 601 immunoassay analyzer.
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.
TECHNOLOGICAL CHARACTERISTICS 3.
The reagent working solutions include:
Rack Pack (kit placed on the analyzer).
- . M Streptavidin-coated microparticles (transparent cap), 1 bottle, 6.5 mL: Streptavidincoated microparticles 0.72 mg/mL; preservative.
- R1 Anti-testosterone-Ab~biotin (gray cap), 1 bottle, 10 mL: Biotinylated monoclonal . anti-testosterone antibody (sheep) 40 ng/mL: releasing reagent 2-bromoestradiol: MES buffer 50 mmol/L, pH 6.0; preservative.
- R2 Testosterone-peptide~Ru(bpy)=+ (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.
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The following table compares the updated Elecsys Testosterone II with its predicate device, the current Elecsys Testosterone II (K093421).
| Feature | Candidate DeviceElecsys Testosterone II (K211685) | Predicate DeviceElecsys Testosterone II (K093421) |
|---|---|---|
| Intended Use | Immunoassay for the in vitro quantitativedetermination of testosterone in humanserum and plasma.The electrochemiluminescenceimmunoassay “ECLIA” is intended for useon the cobas e 601 immunoassay analyzer | Same |
| Indications forUse | Measurements of testosterone are used inthe diagnosis and treatment of disordersinvolving the male sex hormones(androgens), including primary andsecondary hypogonadism, delayed orprecocious puberty, impotence in malesand, in females hirsutism (excessive hair)and virilization (masculinization) due totumors, polycystic ovaries, andadrenogenital syndromes. | Same |
| Assay Method | Competitive Principle | Same |
| DetectionMethod | Electrochemiluminescence immunoassay(ECLIA) | Same |
| InstrumentPlatform | cobas e 601 | Same |
| SampleType/Matrix | Human serum, plasma | Same |
| Traceability/Standardization | ID-GC/MS ("Isotope Dilution - GasChromatography/Mass Spectrometry"). | Same |
| SampleAnticoagulants | Li-heparin, K2-EDTA and K3-EDTAplasma. | Same |
| Calibrator | Testosterone II CalSet IICalibrators 1 and 2 | Same |
| CalibrationMethod | Traceability: This method has beenstandardized via ID-GC/MS (“IsotopeDilution - Gas Chromatography/MassSpectrometry”). Every Elecsys reagent sethas a barcoded label containing specificinformation for calibration of the particularreagent lot. The predefined master curve isadapted to the analyzer using the relevantCalSet. | Same |
| Feature | Candidate DeviceElecsys Testosterone II (K211685) | Predicate DeviceElecsys Testosterone II (K093421) |
| CalibrationInterval | Calibration must be performed once perreagent lot using fresh reagent (i.e. notmore than 24 hours since the reagent kitwas registered on the analyzer). Calibrationinterval may be extended based onacceptable verification of calibration by thelaboratory.Renewed calibration is recommended asfollows:• after 1 month (28 days) when using thesame reagent lot• after 7 days (when using the same reagentkit on the analyzer)• as required: e.g. quality control findingsoutside the defined limits. | Same |
| Controls | Controls for the various concentrationranges should be run individually at leastonce every 24 hours when the test is in use,once per reagent kit, and following eachcalibration.The control intervals and limits should beadapted to each laboratory's individualrequirements. Values obtained should fallwithin the defined limits. Each laboratoryshould establish corrective measures to betaken if values fall outside the definedlimits. | Same |
| ReagentStability | unopened at 2-8 °C up to the statedexpiration dateafter opening at 2-8 °C 12 weekson the analyzer 8 weeks | Same |
| MeasuringRange | 2.50-1500 ng/dL or 0.087-52.0 nmol/L(defined by the Limit of Detection and themaximum of the master curve). | Same |
Technical Characteristics Comparison Table between updated Table 1: Elecsys Testosterone II and current Elecsys Testosterone II
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| Feature | Candidate DeviceElecsys Testosterone II (K211685) | Predicate DeviceElecsys Testosterone II (K093421) |
|---|---|---|
| Precision | Precision was evaluated on one cobas e601 analyzer according to CLSI guidelineEP05-A3. The protocol consisted of testing5 Aliquots of each control (PreciControlUniversal level 1 and PreciControlUniversal level 2) and human serumsamples (HS1-HS5) per run, 1 run per dayfor 5 days with 3 lots. Repeatability andintermediate precision (SD and CV values)were calculated according to CLSIEP05-A3. | Precision was evaluated on one 2010analyzer according to CLSI guideline EP05-A. The protocol consisted of testing 5Aliquots of each control (PreciControlUniversal level 1 and PreciControl Universallevel 2) and human serum samples (HS1-HS5) per run, 1 run per day for 5 days with 3lots. Repeatability and intermediate precision(SD and CV values) were calculatedaccording to CLSI EP05-A. |
| Precision | Precision was determined using Elecsysreagents, human serum and controls in aprotocol (EP05-A3) of the CLSI (Clinicaland Laboratory Standards Institute): 2 runsper day in duplicate each for 21 days (n =84). | Precision was determined using Elecsysreagents, pooled human sera and controls in aseparate study according to protocol (EP5-A)of the CLSI (Clinical and LaboratoryStandards Institute): 2 runs per day induplicate each for 21 days (n = 84). |
| LoB | 1.50 ng/dL or 0.052 nmol/L | Limit of Blank: 1.2 ng/dL |
| LoD | 2.50 ng/dL or 0.087 nmol/L | Same |
| LoQ | 12.0 ng/dL or 0.416 nmol/L | Same |
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| Feature | Candidate DeviceElecsys Testosterone II (K211685) | Predicate DeviceElecsys Testosterone II (K093421) | ||||
|---|---|---|---|---|---|---|
| Cross Reactivity | Cross-Reactant | Concentration(ng/mL) | Cross-Reactivity[%] | Cross-Reactant | Concentration(ng/mL) | Cross-Reactivity[%] |
| DHEA-S | 50000 | 0.003 | DHEA-S | 50000 | < 0.003 | |
| Androstenedione | 100 | 3.15 | Androstenedione | 100 | < 2.50 | |
| Danazol | 1000 | 0.504 | Danazol | 1000 | < 0.500 | |
| Estradiol | 5000 | 0.211 | Estradiol | 1000 | < 0.160 | |
| Ethisterone | 300 | 3.57 | Ethisterone | 1000 | < 2.40 | |
| 19-Norethisterone | 40 | 5.51 | 19-Norethisterone | 40 | < 6.00 | |
| Norgestrel | 1000 | 0.539 | Norgestrel | 1000 | < 0.910 | |
| △5-Androstene-3β17β-diol | 1000 | 0.289 | △5-Androstene-3β17β-diol | 1000 | < 0.290 | |
| Testosteronepropionate | 100 | 0.718 | Testosteronepropionate | 100 | < 2.46 | |
| 5α-Androstane-3β, 17β-diol | 500 | 2.15 | 5α-Androstane-3β, 17β-diol | 1000 | < 2.11 | |
| 5α-Dihydrotestosterone | 500 | 1.30 | 5α-Dihydrotestosterone | 500 | < 0.860 | |
| 11β-OH-Testosterone | 50 | 20.6 | 11β-OH-Testosterone | 100 | < 18.0 | |
| 11keto-Testosterone | 200 | 4.87 | 11keto-Testosterone | 1000 | < 3.22 | |
| Prednisone | 5000 | n.d. | Prednisone | 1000 | n.d. | |
| Prednisolone | 5000 | n.d. | Prednisolone | 1000 | n.d. | |
| Progesterone | 5000 | 0.009 | Progesterone | 1000 | < 0.002 | |
| Cortisol | 5000 | n.d. | Cortisol | 1000 | <0.010 | |
| Cortisone | 5000 | n.d. | Cortisone | 2000 | n.d. | |
| Dexamethasone | 5000 | n.d. | Dexamethasone | 2000 | n.d. | |
| Estrone | 5000 | n.d. | Estrone | 1000 | <0.004 | |
| DHEA | 5000 | 0.014 | DHEA | 1000 | < 0.016 | |
| Biotin | This assay has no biotin interference inserum concentrations up to1200 ng/mL | < 30 ng/mL | ||||
| Special DrugInterference | Testosterone Undecanoate or Nandrolone.Both strongly interfered with Testosteroneand produced elevated recovery values. | None | ||||
| MethodComparison | Updated Elecsys Testosterone II Biotinassay on the cobas e 601 analyzer (y)compared to current Elecsys Testosterone IIassay on the cobas e 601 analyzer (x). | Elecsys Testosterone II assay on thecobas e 801 analyzer (y) with the ElecsysTestosterone II assay on the cobas e 601analyzer (x). |
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| Feature | Candidate DeviceElecsys Testosterone II (K211685) | Predicate DeviceElecsys Testosterone II (K093421) | ||
|---|---|---|---|---|
| Passing/Bablok | Linear regression | Passing/Bablok | Linear regression | |
| $y = 0.948x + 0.023$$T = 0.976$ | $y = 0.950x - 0.871$$r = 0.998$ | $y = 0.961x - 0.015$$T = 0.975$ | $y = 0.958x - 0.006$$r = 0.999$ |
NON-CLINICAL PERFORMANCE EVALUATION 4.
The non-clinical performance studies for Elecsys Testosterone II are summarized below. The following performance data are provided in support of the substantial equivalence determination:
- Precision (5-Day and 21-Day) according to CLSI EP5-A3 .
- Analytical Sensitivity: LoB, LoD and LoQ according to CLSI EP17-A2 .
- Linearity according to CLSI EP6-A .
- Endogenous Interferences Hemoglobin, Intralipid, Bilirubin, and Rheumatoid Factors .
- Biotin Interference (CLSI EP07-A3) .
- Common Drug Interferences .
- Special Drug Interferences .
- Analytical Specificity/ Cross Reactivity (CLSI EP17-A2) .
- Matrix Comparison Anticoagulants .
- Method Comparison to Predicate .
- Reagent Stability (CLSI EP25-A) .
- . Lot Calibration Stability (CLSI EP25-A)
All performance specifications were met.
4.1. Precision
21 Day Precision 4.1.1.
Precision was evaluated on one cobas e 601 analyzer according to CLSI guideline EP05-A3. The protocol consisted of testing 2 replicates of 2 controls and 5 samples.
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Each control and sample underwent 2 runs per day over 21 days using 1 reagent lot. Repeatability and intermediate precision were calculated according to CLSI EP05-A3. Assay calibration was done as specified in the package insert.
4.1.2. 5 Day Precision
Precision was evaluated on one cobas e 601 analyzer according to CLSI guideline EP05-A3. The protocol consisted of testing 5 Aliquots of each control (PreciControl Universal Level 1 and Level 2) and human serum samples per run, 1 run per day for 5 days with 3 lots.
Repeatability and intermediate precision were calculated according to CLSI EP05-A3. Assay calibration was done as specified in the package insert.
Analytical Sensitivity 4.2.
Analytical Sensitivity limits (LoB, LoQ) were determined using CLSI EP17-A2.
These studies and acceptance criteria have been reviewed and found to be acceptable. These data support the LoB, LoD, LoQ claims as reported in the package labeling.
Linearity/Assay Reportable Range 4.3.
For linearity, one lot was tested on one cobas e 601 with one run. One human serum sample with high analyte content above the measuring range was diluted to the lower end of the measuring range with various amounts of human serum sample without analyte content. The dilution series contained 25 steps. Samples were assayed in 3-fold determinations. Data Analysis was determined according to CLSI EP06-A.
Endogenous Interferences 4.4.
The effect on quantitation of analyte in the presence of endogenous interfering substances was determined for testosterone concentrations and a dilution set of the added interfering substances.
The endogenous interference study and acceptance criteria have been reviewed and found to be acceptable. These data supports the endogenous interferences claims as reported in the package labeling.
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Biotin Interference 4.5.
One aliguot of each testosterone sample was spiked with biotin up to 3600 ng/mL. Another aliquot of the sample was spiked with the same volume of the interfering endogenous substance (without interfering substance). The recovery (absolute deviation or % recovery) was calculated for each sample compared to the expected value. Data supports the biotin interference claim of to ≤ 1200 ng/mL, as reported in the package labeling.
4.6. Common Drug Interferences
The common drug interference study and acceptance criteria have been reviewed and found to be acceptable. These data supports the common drug interferences claims as reported in the package labeling.
Special Drug Interferences 4.7.
The effect on quantitation of analyte in the presence of drugs was determined by comparing values obtained from samples spiked with one special pharmaceutical compound with the reference sample (unspiked). All samples used were Native sample pools. Samples (with testosterone concentrations near 0.5 ng/mL and near 5.0 ng/mL) were divided into aliquots and spiked with the special drug interferents, Testosterone Undecanoate. The reference sample without drug was spiked with the respective amount of solvent.
Analytical Specificity/Cross-Reactivity 4.8.
The analytical specificity of the Elecsys Testosterone II assay was determined with one reagent lot on one cobas e 601 analyzer using a human serum matrix with one testosterone level (0.5 ng/mL). The sample aliquots were spiked with potential cross-reactants. These data supports the analytical specificity claims as reported in the package labeling.
Sample Matrix Comparison 4.9.
The effect on quantitation of analyte in the presence of anticoagulants on the Elecsys Testosterone II assay were determined. All samples used were Native or spiked samples. Values obtained from serum samples (reference) were compared to Li-Heparin, K2-EDTA and K3-EDTA plasma. At least 40 serum/plasma pairs were tested in one run on one cobas e 601 analyzer. Data was assessed by Passing/Bablok regression analysis.
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4.10. Method Comparison to Predicate
Serum samples were measured internally using both the current and updated reagent formulations. One hundred sixty eight (168) samples that span the measuring range were tested with one run per sample (no replicates). To sufficiently cover the measuring range, Native single samples and spiked single samples were used. Equivalence of the current Elecsys Testosterone II (K093421) assay and the updated Elecsys Testosterone II assay were evaluated using:
• Calculation: Scatter-plot of numerical values of the current assay (x-axis) versus the updated assay (y-axis).
• Passing-Bablok analysis for slope and intercept was performed for the updated lot against the current lot.
4.11. Stability Studies
The stability studies and acceptance criteria have been reviewed and found to be acceptable. The stability data supports the claims as reported in the package labeling.
5. CONCLUSIONS
The information provided in this 510(k) Premarket Notification will support a determination of substantial equivalence for the Elecsys Testosterone II. The data from the analytical studies demonstrate that the device is as safe, as effective, and performs as well as or better than the predicate device.
§ 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.