(47 days)
Assay for the in vitro quantitative determination of folate in human serum. The visual "ECLIA" is intended for use on the Boehringer Mannheim Elecsys assay analyzers.
The Elecsys® test principle is based on the sandwich principle. Total duration of assay: 18 minutes.
● 1st Incubation (9 min.): By incubating the sample (15 µl) with the folate pretreatment 1 (15 µl) and pretreatment 2 (10 µl), bound folate is liberated into the serum.
● 2nd Incubation (9 min.): By incubating the pretreated sample with the Ruthenylated folate binding protein (80 µl), an FBP-folate complex is formed, the amount of which is dependent upon the analyte concentration in the sample.
● 3rd incubation (9 min.): after the addition of streptavidin-coated microparticles (30 µl) and folate labeled with biotin (50 µl), the unbound sites of the Ruthenylated folate binding protein become occupied, with formation of a Ruthenylated folate binding protein-folate biotin complex. The entire complex becomes bound to the solid phase via interaction of biotin and streptavidin.
The reaction mixture is aspirated into the measuring cell where the microparticles are magnetically captured onto the surface of the electrode. Unbound substances are then removed by washing with ProCell. Application of a voltage to the electrode then induces chemiluminescent emission which is measured by a photomultiplier (0.4 second read frame). Results are determined via a calibration curve which is instrument-specific generated by 2-point calibration and a master curve provided via the reagent bar code.
The Boehringer Mannheim Elecsys® FOLATE device is an electrochemiluminescent assay for the in vitro quantitative determination of folate in human serum. The study conducted to demonstrate its substantial equivalence focused on various performance aspects compared to a predicate device, the Bio-Rad Quantaphase II® B12/FOLATE Radioassay (K935286).
Here's a breakdown of the requested information:
Acceptance Criteria and Reported Device Performance
The provided 510(k) summary describes the types of studies performed but does not explicitly list numerical acceptance criteria or specific quantitative performance values for each criterion. It broadly states that studies were performed to evaluate precision, lower detection limit, linearity, correlation, and interference.
If this were a more detailed submission, the table below would contain specific targets (acceptance criteria) and the actual results from the Elecsys® FOLATE device. Based on the provided text, we can infer the categories of acceptance criteria that were likely in place, which would be met if the results were comparable or better than the predicate.
| Acceptance Criteria Category (Inferred) | Reported Device Performance (General Statement from 510(k)) |
|---|---|
| Precision (e.g., CV% within certain limits) | Evaluated according to NCCLS recommendations. |
| Lower Detection Limit (e.g., specific concentration) | Determined. |
| Linearity (e.g., R² value or range of linearity) | Demonstrated. |
| Correlation with Predicate Device (e.g., regression coefficient, R-value) | Correlation study performed with the predicate device. |
| Interference (e.g., % recovery with interferents) | Evaluation of the effect of various endogenous substances (biotin, triglyceride, lipemia, and rheumatoid factor) and commonly used pharmaceutical compounds. |
| Serum Sample Comparison | Performed. |
| Stability (e.g., shelf life, open-vial stability) | Studies performed. |
Study Information
The 510(k) summary provides limited detail on specific study parameters beyond the types of studies conducted.
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Sample sizes used for the test set and the data provenance: The document does not specify the sample sizes used for the various studies (precision, linearity, correlation, interference, stability). The provenance of the data (country of origin, retrospective or prospective) is also not explicitly stated. However, given it's an in vitro diagnostic device for use in human serum, it is highly likely that human serum samples were used, and such studies are typically performed prospectively or with carefully selected retrospective samples.
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Number of experts used to establish the ground truth for the test set and the qualifications of those experts: This device is an in vitro diagnostic for quantitative determination of a biomarker (folate). For such devices, the "ground truth" is typically established by reference assays or methods, often highly accurate laboratory methods, rather than clinical expert consensus on diagnostic images or patient presentations. Therefore, the concept of "experts establishing ground truth" in the way it applies to image recognition or clinical diagnosis by human interpretation is not directly applicable here. The "experts" would be laboratory scientists or technicians qualified to perform the reference assays. The document does not specify the number or qualifications of individuals involved in generating reference values.
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Adjudication method for the test set: Not applicable for this type of in vitro diagnostic device, as ground truth is established by laboratory measurement, not by human interpretation requiring adjudication.
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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: This is not applicable. The Elecsys® FOLATE device is an automated in vitro diagnostic assay, not an AI-assisted diagnostic tool that aids human readers in interpreting clinical cases.
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If a standalone (i.e. algorithm only without human-in-the-loop performance) was done: Yes, in essence, the Elecsys® FOLATE assay is a standalone algorithm/device in that it provides a quantitative result without direct human interpretation being part of the primary output. The device itself performs the electrochemical detection and provides a numerical folate concentration. The "performance" evaluated in the studies (precision, linearity, correlation) would represent this standalone performance.
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The type of ground truth used:
- For precision, lower detection limit, linearity, and stability, the "ground truth" is typically derived from internal laboratory standards, known concentrations, and repeated measurements to assess the device's inherent analytical performance.
- For correlation with the predicate device, the "ground truth" for the comparative performance would be the results obtained from the Bio-Rad Quantaphase II® B12/FOLATE Radioassay (K935286) when analyzing the same samples.
- For interference studies, the ground truth would be the expected result of the folate measurement in the absence of the interfering substance, or the recovery of a known amount of folate in the presence of the interferent.
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The sample size for the training set: The 510(k) summary does not provide information on a training set sample size. For in vitro diagnostic assays as described, the concept of a "training set" in the context of machine learning (where an algorithm learns from data) is not directly applicable. The device's operating characteristics (algorithms for signal processing, calibration curves) are typically established during development and validated through the performance studies mentioned, rather than 'training' on a dataset in the AI sense.
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How the ground truth for the training set was established: As the device doesn't involve a machine learning "training set" in the conventional sense, this question is not applicable. The analytical methods and parameters are developed and optimized by the manufacturer using internal validation processes.
§ 862.1810 Vitamin B
12 test system.(a)
Identification. A vitamin B12 test system is a device intended to measure vitamin B12 in serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of anemias of gastrointestinal malabsorption.(b)
Classification. Class II.