(271 days)
The Elecsys FT4 II Assay is for the in vitro quantitative determination of free Thyroxine in human serum and plasma. Measurements obtained by this device are used in the diagnosis and treatment of thyroid diseases.
The electrochemiluminescence immunoassay "ECLIA" is intended for use on Elecsys and cobas e immunoassay analyzers.
Elecsys FT4 II CalSet is used for calibrating the quantitative Elecsys FT4 II assay on the Elecsys and cobas e immunoassay analyzers.
- The Elecsys F4 II Assay is a quantitative test for determination of free thyroxine in human serum and plasma. The total duration of the assay is 18 minutes. Elecsys FT4 II is a two-step competitive immunoassay with streptavidin microparticles, T4-specific polyclonal anti-T4-antibody (sheep) labeled with a sulfonyl-ruthenium complex, and electrochemiluminescence detection. Results are determined via a calibration curve which is instrument-specifically generated by a two-point calibration and a master curve provided via the reagent barcode.
(2) The Elecsys FT4 II CalSet is a ready-for-use buffer/protein (bovine serum albumin) matrix with added L-Thyroxine in two concentration ranges. FT4 II Cal1: 2 bottles, each containing 1.0 mL of calibrator 1 FT4 II Cal2: 2 bottles, each containing 1.0 mL of calibrator 2 Note: The reagent and calibrator are packaged separately.
Here's a breakdown of the acceptance criteria and the study details for the Elecsys FT4 II Assay, based on the provided 510(k) summary:
Acceptance Criteria and Device Performance for Elecsys FT4 II Assay
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Characteristic | Acceptance Criteria | Reported Device Performance (Elecsys FT4 II Assay) |
|---|---|---|
| Precision | Repeatability (Within-run): |
- Concentrations ≤ 0.4 ng/dL: SD ≤ 0.02 ng/dL
- Concentrations > 0.4-7.77 ng/dL: CV ≤ 5%
Intermediate (Within-laboratory): - Concentrations ≤ 0.4 ng/dL: SD ≤ 0.03 ng/dL
- Concentrations > 0.4-7.77 ng/dL: CV ≤ 8% | Repeatability:
- HS 1 (0.138 ng/dL): 4.0% CV (SD 0.006 ng/dL)
- HS 2 (1.03 ng/dL): 1.3% CV (SD 0.013 ng/dL)
- HS 3 (1.90 ng/dL): 1.3% CV (SD 0.024 ng/dL)
- HS 4 (4.93 ng/dL): 1.7% CV (SD 0.082 ng/dL)
- HS 5 (7.09 ng/dL): 1.8% CV (SD 0.127 ng/dL)
Intermediate: - HS 1 (0.138 ng/dL): 7.6% CV (SD 0.011 ng/dL)
- HS 2 (1.03 ng/dL): 2.3% CV (SD 0.023 ng/dL)
- HS 3 (1.90 ng/dL): 2.1% CV (SD 0.040 ng/dL)
- HS 4 (4.93 ng/dL): 3.3% CV (SD 0.163 ng/dL)
- HS 5 (7.09 ng/dL): 4.5% CV (SD 0.319 ng/dL)
(All results meet specifications) |
| Limit of Blank (LoB) | Claim will be set to ≤ 0.03 ng/dL. | LoB claim will be set to ≤ 0.03 ng/dL. (Study determined this value) |
| Limit of Detection (LoD)| Claim will be set to ≤ 0.05 ng/dL. | LoD claim will be set to ≤ 0.05 ng/dL. (Study determined this value) |
| Limit of Quantitation (LoQ) / Functional Sensitivity | Interassay coefficient of variation ≤ 20%. | Lot MP02: 0.059 ng/dL
Lot P2: 0.069 ng/dL
Lot P3: 0.080 ng/dL.
Claim will be set to 0.1 ng/dL. (All lots show functional sensitivity below the claimed LoQ) |
| Linearity | Significance level for deviation to higher order polynomial: 5%.
Limits for deviation of higher order polynomial regression: - 0.1 - 0.388 ng/dL: ±0.078 ng/dL
-
0.388 - 7.77 ng/dL: ± 10%
Repeatability for linearity: - 0.1 - 0.388 ng/dL: ±0.039 ng/dL
-
0.388 - 7.77 ng/dL: ± 5% | Linearity was confirmed in the range from 0.096 to 8.20 ng/dL. (Meets acceptance criteria) |
| Exogenous Interferences - Drugs | Recovery of 100 ± 10% of the reference value (unspiked sample). | All compounds tested, except Levothyroxine and Furosemide, were found to be non-interfering. Levothyroxine and Furosemide will be listed as interfering substances. (Meets criteria for most, with noted exceptions) |
| Exogenous Interferences - Anticoagulants | For regression analysis: - Slope: 0.9 - 1.1
- Intercept: 0.3 – 7.77 ng/dL: 100 ± 10 % | No direct results given, but the study description implies successful demonstration up to 28 days for using Day 0 calibration. (Implies criteria were met) |
| Reagent On-Board Stability | Recovery of samples compared to Day 1: - LoD to 0.3 ng/dL: ± 0.05 ng/dL
-
0.3 to 7.77 ng/dL: 100±10% | Reagent kits can be stored on board for up to 28 days, and for 56 days with alternative storage (max 120 hours onboard). A new calibration is recommended every 7 days. (Implies criteria were met within these guidelines) |
| Reagent Accelerated Stability | Recovery of samples compared to Day 0: - LoD to 0.3 ng/dL: ± 0.05 ng/dL
-
0.3 to 7.77 ng/dL: 100 ± 10% | No direct results given, but used to support a 12-month shelf life claim. (Implies criteria were met for 3 weeks at 35°C, extrapolating to 12 months shelf life) |
| Reagent Real-Time Stability | Recovery of 90-110% of the reference value. | In ongoing study, data for 0, 7, 10, 13, 16, 19, and 25 months will be available. Supports a 12-month shelf life claim based on both accelerated and initial real-time data. Study will continue for 24 months. (On-going, current data supports 12 months) |
| Reagent Stability after first opening (2-8°C) | Recovery of samples compared to Day 0: - ≤ 0.3 ng/dL: ± 0.05 ng/dL
-
0.3 - 7.77 ng/dL: 100 ± 10 % | Supports 84 days (12 weeks) when stored at 2-8ºC. (Implies criteria were met up to 85 days in the study) |
| Reference Range Validation | No more than 6 (10%) of the 60 tested subjects should fall outside of the established reference range of 0.93-1.7 ng/dL. | 2 of 60 subjects fell outside the established reference range (0.93-1.7 ng/dL). Acceptance criteria met. The reference range can be transferred. (Meets acceptance criteria) |
2. Sample Sizes Used for the Test Set and Data Provenance
The document describes several performance studies, each with its own sample size:
- Precision (CLSI EP5-A2):
- Sample Size: 84 determinations for each of 5 human serum samples (HS 1-5) and 2 PreciControl Universal (PCU 1-2). Tested in 2 replicates per sample/control per run, 2 runs per day for 21 days.
- Data Provenance: Human sera (HS) and PreciControl Universal (PCU). No explicit country of origin is stated, but standard CLSI guidelines imply well-characterized, often commercially sourced, samples. The study is prospective in nature for assessing device performance.
- Limit of Blank (LoB) (CLSI EP17-A2):
- Sample Size: 60 determinations of one analyte-free human serum sample (5-fold determination in each run, 1-2 runs/day for 4 days).
- Data Provenance: Analyte-free human serum (T4 depleted).
- Limit of Detection (LoD) (CLSI EP17-A2):
- Sample Size: Single measurement per run for four days on five low-level human serum samples. Total determinations not explicitly summed, but would be 5 samples * 1 measurement * (1-2 runs/day) * 4 days.
- Data Provenance: Low-level human serum samples.
- Limit of Quantitation (LoQ) / Functional Sensitivity (CLSI EP17-A2):
- Sample Size: 8 low-level human serum samples tested in single replicates for four days, 1-2 runs per day. Total determinations not explicitly summed.
- Data Provenance: Native human serum samples diluted with analyte-free human serum matrix.
- Linearity (CLSI EP6-A):
- Sample Size: 3 high analyte serum sample pools. For each pool, 13 concentrations (11 dilutions) across the measuring range were prepared and assayed in 3-fold determination within a single run.
- Data Provenance: Human serum samples (spiked with L-Thyroxine) and fT4 depleted human serum.
- Specificity/Cross Reactivity:
- Sample Size: Not explicitly stated, but compounds were tested in duplicate.
- Data Provenance: Native human serum samples or human serum samples spiked with L-Thyroxine (single donors) spiked with potential cross-reactant compounds.
- Exogenous Interferences - Drugs:
- Sample Size: 2 human serum samples approximately 1.1 ng/dL and 2.6 ng/dL of fT4. Each was spiked with 17 pharmaceutical compounds and 12 thyroid drugs/Furosemide. Spiked aliquots tested in triplicate, reference aliquot in 6-fold determination.
- Data Provenance: Human serum samples (pools spiked with L-Thyroxine).
- Exogenous Interferences - Anticoagulants:
- Sample Size: Between 53 and 63 serum/plasma pairs per sample material (presumably per type of anticoagulant). Tested in single determination.
- Data Provenance: Native samples or samples spiked with L-Thyroxine (single donors) drawn into various primary tubes (serum, Li-Heparin, K2-EDTA, K3-EDTA-plasma, Li-Heparin Plasma Separation Tubes).
- Endogenous Interferences:
- Sample Size: 3 serum samples (low, mid, high fT4 concentrations) for each interfering substance.
- Data Provenance: Pooled human serum samples spiked with L-Thyroxine.
- Method Comparison (vs. predicate):
- Sample Size: 170 human serum samples. Out of these, 11 were spiked with analyte, and 4 diluted with FT4 free serum.
- Data Provenance: Human serum obtained from commercial vendors or remnant clinical samples.
- Calibration Stability:
- Sample Size: 5 human serum samples (spiked with L-Thyroxine) and 2 controls. Each tested in duplicate.
- Data Provenance: Human serum samples and controls.
- Reagent On-Board Stability:
- Sample Size: Not explicitly stated, but refers to testing "samples" and controls at various time points.
- Data Provenance: Human serum samples and controls.
- Reagent Accelerated Stability:
- Sample Size: 5 human serum samples (spiked with L-Thyroxine) and 2 controls. Each tested in two-fold determination.
- Data Provenance: Human serum samples and controls.
- Reagent Real-Time Stability:
- Sample Size: PreciControl Universal 1 and PreciControl Universal 2 tested in duplicate at various time points (0, 7, 10, 13, 16, 19, 25 months).
- Data Provenance: PreciControl Universal 1 and 2 (controls).
- Reagent Stability after first opening (2-8°C):
- Sample Size: 5 human serum samples (spiked with L-Thyroxine) and 2 controls. Each tested in two-fold determination.
- Data Provenance: Human serum samples and controls.
- Reference Range Validation Study (CLSI C28-A3c):
- Sample Size: 60 subjects (30 males and 30 females).
- Data Provenance: Subjects with normal TSH values (presumed healthy individuals). The study is prospective for reference range validation.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This type of immunoassay (Elecsys FT4 II Assay) is a quantitative chemical measurement device. The "ground truth" for its performance is established through comparison to established analytical methods and reference standards, rather than expert interpretation of images or clinical findings.
- For studies like Linearity, Specificity, Interferences, and Analytical Sensitivity, ground truth samples are typically prepared with known concentrations of analytes or interferents, or are compared against validated reference methods.
- For Method Comparison, the ground truth is established by comparing the new device's results against a legally marketed predicate device (Elecsys FT4 Assay, K961489), which itself would have been validated against reference methods or clinical outcomes.
- For the Reference Range Validation Study, the "ground truth" for subject selection was having "normal TSH values" as measured by the Elecsys TSH assay, identifying a healthy population.
Therefore, the concept of "experts establishing ground truth" in the traditional sense (e.g., radiologists reviewing images) is not directly applicable here. The ground truth is inherent in the design of the analytical studies and the use of calibrated standards and reference methods.
4. Adjudication Method for the Test Set
Not applicable. As described above, this is a quantitative chemical measurement device; results are numerical and not subject to human interpretation or adjudication in the way a diagnostic imaging study would be. Deviations from expected values or comparisons to reference methods would be evaluated statistically.
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 a device involving human readers interpreting cases or AI assistance.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was Done
Yes, the device (Elecsys FT4 II Assay) functions as a standalone, automated immunoassay without human intervention in the measurement process itself. All performance studies described (Precision, LoB, LoD, LoQ, Linearity, Specificity, Interferences, Method Comparison, Stability studies) evaluate the algorithm's performance and the device's analytical characteristics directly.
7. The Type of Ground Truth Used (Expert Consensus, Pathology, Outcomes Data, etc.)
The ground truth used across the various studies for this in vitro diagnostic device includes:
- Known concentrations: For studies like LoB, LoD, LoQ, Linearity, Specificity, and Interferences, samples are often prepared with precisely known concentrations of the analyte or interfering substances.
- Predicate device comparison: For method comparison, the results are compared to the legally marketed Elecsys FT4 Assay (K961489), which serves as the established analytical "truth" for substantial equivalence.
- Biological/clinical normality: For the Reference Range Validation Study, the ground truth for inclusion criteria was "normal TSH values" in healthy individuals.
- Calibration standards: The assays rely on accurate calibration using the Elecsys FT4 II CalSet, which is itself traceable to established standards (Enzymun-Test, standardized using equilibrium dialysis for FT4).
8. The Sample Size for the Training Set
Not applicable in the typical sense of machine learning. This is an immunoassay, not an AI or machine learning algorithm that requires a "training set" to learn patterns. The "training" of such a system would involve optimizing assay reagents and parameters during development, based on extensive R&D, but not a distinct "training set" of patient data as understood in AI/ML contexts.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there isn't a "training set" in the context of an immunoassay. The development and optimization of the assay would rely on:
- Analytical chemistry principles: Designing the competitive immunoassay with specific antibodies and detection systems.
- Biochemical characterization: Ensuring the specificity of T4-specific antibodies.
- Manufacturing controls: Producing reagents with consistent quality and concentration.
- Calibration curve development: Establishing the relationship between signal (electrochemiluminescence) and analyte concentration using a predefined set of calibrators with known concentrations that are traceable to reference methods (e.g., equilibrium dialysis).
§ 862.1695 Free thyroxine test system.
(a)
Identification. A free thyroxine test system is a device intended to measure free (not protein bound) thyroxine (thyroid hormone) in serum or plasma. Levels of free thyroxine in plasma are thought to reflect the amount of thyroxine hormone available to the cells and may therefore determine the clinical metabolic status of thyroxine. Measurements obtained by this device are used in the diagnosis and treatment of thyroid diseases.(b)
Classification. Class II.