(266 days)
Binding assay for the in vitro quantitative determination of folate in erythrocytes (red blood cells, RBC). Folate measurements are used in the diagnosis and treatment of anemia. The electrochemiluminescence immunoassay "ECLIA" is intended for use on cobas e immunoassay analyzers.
Elecsys Folate III is a binding assay that makes use of a competitive test principle using a ruthenium labeled folate-binding assay.
Elecsys Folate III is a binding assay for the in vitro quantitative determination of folate in erythrocytes (red blood cells, RBC). Folate measurements are used in the diagnosis and treatment of anemia. The electrochemiluminescence immunoassay "ECLIA" is intended for use on cobas e immunoassay analyzers.
Whole blood treated with anticoagulants (heparin or EDTA) is mixed with ascorbic acid solution and incubated for approximately 90 minutes at 20-25 °C. Lysis of the erythrocytes takes place, with liberation and stabilization of the intracellular folate. The resulting hemolysate sample is then used for subsequent measurement.
Results are determined via a calibration curve, which is instrument-specifically generated by 2point calibration, and a master curve provided via the cobas link.
Here's a summary of the acceptance criteria and study details for the Elecsys Folate III device, based on the provided FDA 510(k) summary:
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Metric | Acceptance Criteria (Implied / Stated) | Reported Device Performance |
|---|---|---|
| Precision | "All predefined acceptance criteria was met for the precision experiments." (Specific numerical criteria not explicitly stated in this document but implied to be within acceptable limits as per CLSI guideline EP05-A3.) | Repeatability (within-run precision) & Intermediate Precision (within-laboratory precision) (cobas e 801 analyzer) |
| Sample | Mean (ng/mL) | Repeatability SD (ng/mL) |
| --------------- | -------------- | -------------------------- |
| Hemolysate 1 | 152 | 5.73 |
| Hemolysate 2 | 206 | 6.14 |
| Hemolysate 3 | 252 | 6.70 |
| Hemolysate 4 | 363 | 8.01 |
| Hemolysate 5 | 605 | 10.7 |
| Lot-to-lot Reproducibility: "All predefined acceptance criteria was met for the lot-to-lot reproducibility experiment." (Specific data not provided, but confirmed to meet criteria.) | ||
| Analytical Sensitivity | Based on CLSI EP17-A2 guidelines for Limit of Blank (LoB), Limit of Detection (LoD), and Limit of Quantitation (LoQ). | LoB: 45 ng/mL |
| LoD: 70 ng/mL | ||
| LoQ: 120 ng/mL | ||
| Linearity | Measurements across the claimed measuring range (120 - 620 ng/mL) must be linear as assessed per CLSI EP06-Ed2. | Linearity confirmed to support the measuring range of 120 - 620 ng/mL. |
| Dilution | Data must support instruction for use for samples diluted 1:2. | Data supports instruction for use. |
| Endogenous Interferences | "All predefined acceptance criteria were met" for various endogenous substances including Bilirubin, Intralipid, Biotin, Rheumatoid factors, IgG, IgA, IgM, at specified concentrations, confirming no significant interference. (Specific thresholds for non-interference not provided in text, but implied to be within acceptable limits). | No significant interference for: |
| Bilirubin: ≤ 29 mg/dL | ||
| Intralipid: ≤ 1500 mg/dL | ||
| Biotin: ≤ 1200 ng/mL | ||
| Rheumatoid factors: ≤ 1000 IU/mL | ||
| IgG: ≤ 1.6 g/dL | ||
| IgA: ≤ 0.4 g/dL | ||
| IgM: ≤ 1 g/dL | ||
| Analytical Specificity/Cross-Reactivity | Expected low cross-reactivity with specified compounds. (Specific thresholds for cross-reactivity not provided in text, but implied to be within acceptable limits). | Low cross-reactivity: |
| Amethopterin: (750 ng/mL) 1.7% | ||
| Aminopterin: (750 ng/mL) 2.0% | ||
| Folinic acid: (750 ng/mL) 2.6% | ||
| Exogenous Interferences | No interference from 17 commonly used pharmaceuticals and erythropoietin. (Specific thresholds for non-interference not provided in text, but implied to be within acceptable limits). | No interference found from 17 commonly and 1 specially used pharmaceutical (erythropoietin) compounds. |
| Sample Matrix Comparison | Results within specification, supporting the use of hemolysate prepared from whole blood treated with Na-heparin or K3-EDTA. | Results were within specification and support the use of hemolysate prepared from whole blood and treated with Na-heparin or K3-EDTA. |
| Method Comparison to Predicate | High correlation and agreement with the predicate device (Elecsys Folate RBC). | Number of samples: 119 (concentrations 132-618 ng/mL) |
| Passing/Bablok: y = 1.04x - 14.6, τ = 0.913 | ||
| Linear regression: y = 1.03x - 11.0, r = 0.991 | ||
| Reagent Stability (On-board) | Reagent kits can be stored on-board for up to 16 weeks. | Tested on one cobas e 801 analyzer; Elecsys Folate III reagent kits can be stored on-board for up to 16 weeks. (Note: The product comparison table states "2 weeks" for predicate; this indicates an improvement for the candidate device.) |
| Calibration Stability (Lot) | Calibration for a lot is recommended every 12 weeks; during this period, fresh kits of same lot can be used without re-calibration using the day 0 curve. | Tested on one cobas e 801 analyzer. Calibration of an Elecsys Folate III reagent lot is recommended every 12 weeks. |
| Calibration Stability (On-board) | Reagent epacks can be stored on-board for up to 28 days without a new calibration. | Tested on one cobas e 801 analyzer. Elecsys Folate III epacks can be stored on board of the analyzers for up to 28 days without a new calibration. |
2. Sample Sizes and Data Provenance
- Precision (Repeatability & Intermediate Precision): Not explicitly stated, but typically involves multiple replicates over several days/runs with multiple instruments. Specific sample types are "Hemolysate 1" to "Hemolysate 5".
- Lot-to-lot Reproducibility: "three reagent lots" were used.
- Analytical Sensitivity (LoB, LoD, LoQ): Not explicitly stated, but determined according to CLSI EP17-A2, which involves specific numbers of blank and low-concentration samples.
- Linearity and Dilution: "At least seven concentrations using hemolysate samples" for linearity. Dilution study used "high concentration hemolysate samples".
- Endogenous Interferences: Not explicitly stated, but "various endogenous substances" were evaluated.
- Analytical Specificity/Cross-Reactivity: Not explicitly stated.
- Exogenous Interferences: "17 commonly and 1 specially used pharmaceutical" compounds.
- Sample Matrix Comparison: "Whole blood samples were drawn into Na-Heparin and K3-EDTA tubes." (Number not specified).
- Method Comparison to Predicate: 119 samples with concentrations between 132 and 618 ng/mL.
- Reagent Stability (On-board), Lot Calibration Stability, On-board Calibration Stability: Tested on "one cobas e 801 analyzer".
Data Provenance: The document states "NON-CLINICAL PERFORMANCE EVALUATION" and refers to CLSI (Clinical and Laboratory Standards Institute) guidelines, which are standard for in-vitro diagnostic device performance studies. The data is internal to Roche Diagnostics, a company with global operations. The specific country of origin for the studies is not stated, but given the submission is to the U.S. FDA, the studies are expected to meet international and U.S. regulatory standards. These are retrospective studies in the context of device development and validation.
3. Number of Experts and Qualifications for Ground Truth (Test Set)
This device is an in-vitro diagnostic (IVD) assay that produces quantitative measurements of folate. It does not involve human interpretation of images or other subjective data. Therefore, the "ground truth" for its performance is established by reference methods, calibrated standards, and accurate measurement principles, rather than human expert consensus. No human experts were used to establish ground truth in the way one would for an AI imaging device.
4. Adjudication Method (Test Set)
Not applicable, as this is an IVD device producing quantitative results, not an AI imaging device requiring expert adjudication.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
Not applicable. This is an in-vitro diagnostic device, not an AI device assisting human readers with interpreting cases.
6. Standalone (Algorithm Only) Performance
Yes, the studies described are standalone performance evaluations of the Elecsys Folate III assay (the "algorithm" in a broad sense for an IVD) without human intervention in the measurement process. The device performs the quantitative determination of folate using its defined binding assay and electrochemiluminescence immunoassay (ECLIA) method.
7. Type of Ground Truth Used
The ground truth for evaluating the Elecsys Folate III's performance is established through:
- Reference materials/standards: For analytical sensitivity (LoB, LoD, LoQ) and linearity, where known concentrations are used.
- Performance against a predicate method: For method comparison, the results are compared to a previously cleared, established method (Elecsys Folate RBC).
- CLSI guidelines: Adherence to established scientific and statistical methodologies for validating assay performance, implying well-defined benchmarks for accuracy, precision, and interference.
8. Sample Size for the Training Set
Not explicitly stated. For an IVD like the Elecsys Folate III, a traditional "training set" as understood in machine learning is not directly applicable. The "training" for such a system would involve the development and optimization of the reagent formulations, assay parameters, and calibration curve algorithms, using various samples and experiments during the research and development phase. However, a specific training set size with corresponding ground truths is not documented in the same way as an AI algorithm.
9. How the Ground Truth for the Training Set was Established
As above, a formal "training set ground truth" isn't directly applicable in the machine learning sense. The "ground truth" during the development and optimization (analogous to training) would have been established through:
- Known concentrations: Using purified folate standards or spiked samples.
- Reference methods: Comparing early-stage assay performance against established, often more labor-intensive or gold-standard methods for folate determination.
- Clinical correlation: (Though "clinical testing" is marked Not Applicable for this 510(k), early development might involve correlation with clinical status or outcomes).
- Statistical optimization: Adjusting reagent ratios, incubation times, and instrument settings to achieve optimal analytical performance characteristics (sensitivity, specificity, precision, linearity) based on these known values and reference method comparisons.
§ 862.1295 Folic acid test system.
(a)
Identification. A folic acid test system is a device intended to measure the vitamin folic acid in plasma and serum. Folic acid measurements are used in the diagnosis and treatment of megaloblastic anemia, which is characterized by the presence of megaloblasts (an abnormal red blood cell series) in the bone marrow.(b)
Classification. Class II.