(142 days)
(1) Elecsys Folate RBC Assay: Binding assay for the in vitro quantitative determination of folate erythrocytes (red blood cells, RBCs). The binding assay is intended for use on Elecsys and cobas e immunoassay analyzers. Measurements obtained by this assay are used in the diagnosis and treatment of anemias.
(2) Elecsys Folate RBC CalSet: The Elecsys Folate RBC CalSet is used for calibrating the quantitative Elecsys Folate RBC assay on the Elecsys and cobas e immunoassay analyzers.
(3) Elecsys Folate RBC CalCheck: Elecsys Folate RBC CalCheck is used for the verification of the calibration established by the Elecsys Folate RBC reagent on the indicated Elecsys and cobas e immunoassay analyzers. For in vitro diagnostic use.
(1) The Elecsys Folate RBC assay employs a competitive test principle using natural folate binding protein specific for folate. Manually prepared hemolysate samples are used with this assay. Folate in the sample competes with the added folate (labeled with biotin) for the binding sites on folate binding protein (labeled with ruthenium complex). Results are determined via a calibration curve which is instrument-specifically generated by 2-point calibration and a master curve provided via the reagent barcode encoded on the reagent packaging.
(2) The Elecsys Folate RBC CalSet is a lyophilized product consisting of human serum with folate in two concentration ranges. During manufacture, the analyte is spiked into the matrix. This calibrator is used to calibrate the Elecsys Folate RBC assay.
(3) The Elecsys Folate RBC CalCheck is a lyophilized product consisting of a hemolysate with folic acid. During manufacture, the analyte is spiked into the matrix. This solution is used to verify the calibration established with the Elecsys Folate RBC CalSet.
The provided text describes the Elecsys Folate RBC Test System, but it is a device for in vitro quantitative determination of folate in red blood cells and not an AI or imaging device. Therefore, many of the requested categories related to AI performance, such as MRMC studies, ground truth establishment by experts for image data, or training/test set sample sizes for AI models, are not applicable.
However, I can extract information related to the device's analytical performance and the studies conducted to demonstrate its substantial equivalence to a predicate device, focusing on the available information.
Here's the breakdown based on the provided text, adapted for a non-AI diagnostic device:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are not explicitly stated as distinct pass/fail thresholds in a table format. Instead, the submission demonstrates substantial equivalence by comparing the performance characteristics of the new Elecsys Folate RBC Assay to the predicate device (Elecsys RBC Folate III Assay) in a feature-by-feature comparison. The reported performance of the new device is shown alongside the predicate's performance. The "acceptance criteria" here are implicitly the predicate device's performance, as the goal is to show substantial equivalence.
| Feature | Acceptance Criteria (Predicate Device Performance) | Reported Device Performance (Elecsys Folate RBC Assay) |
|---|---|---|
| Measuring Range | 46.5 - 620 ng/mL | 120 ng/mL - 620 ng/mL |
| Analytical Sensitivity (LoB) | ≤ 19.84 ng/mL | ≤ 20 ng/mL |
| Analytical Sensitivity (LoD) | ≤ 46.5 ng/mL | ≤ 46.5 ng/mL |
| Analytical Sensitivity (LoQ) | ≤ 62.0 ng/mL | ≤ 120.0 ng/mL |
| Dilution (Min. diluted conc.) | The concentration of the diluted sample must be > 310 ng/mL. | The concentration of the diluted sample must be >265 ng/mL. |
| Precision (Repeatability, Elecsys 2010/cobas e411, Sample 1/Hemolysate 2) | Mean 229 ng/mL: SD 12.2 ng/mL; CV 5.3% | Hemolysate 2, mean 155 ng/mL: SD 7.73 ng/mL; CV 5.0% |
| Precision (Repeatability, Elecsys 2010/cobas e411, Sample 2/Hemolysate 3) | Mean 350 ng/mL: SD 17.0 ng/mL; CV 4.9% | Hemolysate 3, mean 272 ng/mL: SD 11.2 ng/mL; CV 4.1% |
| Precision (Repeatability, Elecsys 2010/cobas e411, Sample 3/Hemolysate 4) | Mean 481 ng/mL: SD 25.7 ng/mL; CV 5.3% | Hemolysate 4, mean 527 ng/mL: SD 17.1 ng/mL; CV 3.3% |
| Precision (Repeatability, Elecsys Modular E170/cobas e 601/602, Hemolysate 2) | Not applicable (predicate not tested on these platforms) | Hemolysate 2, mean 191 ng/mL: SD 11.5 ng/mL; CV 6.0% |
| Precision (Repeatability, Elecsys Modular E170/cobas e 601/602, Hemolysate 3) | Not applicable | Hemolysate 3, mean 258 ng/mL: SD 14.1 ng/mL; CV 5.5% |
| Precision (Repeatability, Elecsys Modular E170/cobas e 601/602, Hemolysate 4) | Not applicable | Hemolysate 4, mean 580 ng/mL: SD 12.8 ng/mL; CV 2.2% |
| Precision (Intermediate Precision, Elecsys 2010/cobas e411, Sample 1/Hemolysate 2) | Mean 229 ng/mL: SD 16.1 ng/mL; CV 7.0% | Hemolysate 2, mean 155 ng/mL: SD 12.2 ng/mL; CV 7.9% |
| Precision (Intermediate Precision, Elecsys 2010/cobas e411, Sample 2/Hemolysate 3) | Mean 350 ng/mL: SD 25.2 ng/mL; CV 7.2% | Hemolysate 3, mean 272 ng/mL: SD 16.9 ng/mL; CV 6.2% |
| Precision (Intermediate Precision, Elecsys 2010/cobas e411, Sample 3/Hemolysate 4) | Mean 481 ng/mL: SD 34.6 ng/mL; CV 7.2% | Hemolysate 4, mean 527 ng/mL: SD 24.8 ng/mL; CV 4.7% |
| Precision (Intermediate Precision, Elecsys Modular E170/cobas e 601/602, Hemolysate 2) | Not applicable | Hemolysate 2, mean 191 ng/mL: SD 12.5 ng/mL; CV 6.5% |
| Precision (Intermediate Precision, Elecsys Modular E170/cobas e 601/602, Hemolysate 3) | Not applicable | Hemolysate 3, mean 258 ng/mL: SD 15.1 ng/mL; CV 5.9% |
| Precision (Intermediate Precision, Elecsys Modular E170/cobas e 601/602, Hemolysate 4) | Not applicable | Hemolysate 4, mean 580 ng/mL: SD 19.7 ng/mL; CV 3.4% |
| Analytical Specificity / Cross-Reactivity | Aminopterin 2.7%, Folinic acid 2.3%, Amethopterin 2.3% | Same (Implies similar or acceptable cross-reactivities, though specific percentages are not re-listed for the new device) |
| Interferences | Unaffected by icterus, lipemia, biotin (up to 86.1 nmol/L or 21 ng/mL), IgG, IgA. No interference from rheumatoid factors up to 1000 IU/mL. No interference from 18 common pharmaceuticals or human erythropoietin. | Similar interference study reported ("Same") with an added precautionary statement for high protein samples causing protein gel. Specific interference limits are not re-listed but implied to be similar or improved. |
| Expected Values (Whole Blood Folate) | American Journal of Clinical Nutrition Expected = 4.6 - 34.8 ng/mL (all ages & male/female) | Expected = 209-640 (2.5th - 97.5th percentile) (from hemolysate sample) |
| Expected Values (RBC Folate) | Not separately specified for predicate in this section | Expected = 499-1504 ng/mL (2.5th - 97.5th percentile) (folate in erythrocyte fraction) |
Study Proving Device Meets Acceptance Criteria:
The study proving the device meets the acceptance criteria is a substantial equivalence comparison study against a legally marketed predicate device, the Elecsys RBC Folate III Test System (K082340). This type of study demonstrates that the new device is as safe and effective as the predicate device by showing that it has similar technological characteristics and performance.
2. Sample Size Used for the Test Set and Data Provenance
The document does not explicitly state a single "test set" sample size in the way an AI model validation might. Instead, it details various analytical performance studies with different "samples" for each attribute:
- Precision (Repeatability & Intermediate Precision): Tested on multiple "Hemolysate" or "Sample" controls at different concentration levels. For each level, measurements were taken to determine SD and CV. The exact number of replicates or runs is not specified in the summary but is typically substantial for precision studies (e.g., multiple runs over several days).
- Analytical Sensitivity (LoB, LoD, LoQ): Determined using analytical methods, likely involving dilutions of folate-containing samples. The specific sample count for these determinations is not provided.
- Interferences: Tested using various interfering substances and pharmaceuticals. The number of samples/donors tested for each interference is not specified, but typically involves spiking known concentrations into samples and assessing recovery.
- Expected Values: Determined from a "Whole Blood Folate (from hemolysate sample)" study and an "RBC Folate (folate in erythrocyte fraction)" study. The sample size for these population studies is not provided in the summary.
Data Provenance: The document does not explicitly state the country of origin or whether the data was retrospective or prospective. For in vitro diagnostic device submissions, such data is typically generated in a controlled laboratory setting (prospective) and may involve samples from different geographical regions, but this is not specified here.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of those Experts
Not applicable. This is not an AI/imaging device where expert consensus is used to establish ground truth for a test set. This device quantifies a biomarker (folate in RBCs). The "ground truth" for its analytical performance is established through reference methods and internal validation procedures, not human interpretation or adjudication by experts.
4. Adjudication Method for the Test Set
Not applicable. As this device measures a quantitative biomarker, there is no "adjudication" in the sense of resolving discrepancies in human interpretation or labeling. Analytical performance is typically verified against established laboratory standards and reference methods.
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 an AI device used for interpretation or diagnosis by human readers, so an MRMC study is irrelevant.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
This is a standalone device performance study. The Elecsys Folate RBC Test System performs the quantitative measurement of folate in RBCs automatically on immunoassay analyzers (Elecsys and cobas e platforms) without human-in-the-loop interpretative performance. The performance metrics (measuring range, sensitivity, precision, interference) are all measures of the algorithm and system's analytical capability.
7. The Type of Ground Truth Used
The "ground truth" for this device's performance relies on analytical reference methods and established laboratory principles. For example:
- For analytical sensitivity (LoB, LoD, LoQ): Determined using standard statistical methods and known concentrations of analyte.
- For precision: Assessed by running replicate measurements on control samples.
- For accuracy/comparison to predicate: The predicate device itself (Elecsys RBC Folate III Assay) serves as the "reference" for demonstrating substantial equivalence. The traceability of the new device is stated as "Reference method is Folate III (Application on the E2010)", meaning its measurements are compared to the predicate's measurements. The predicate's traceability is to the "Elecsys Folate II assay."
8. The Sample Size for the Training Set
Not applicable. This is not an AI/machine learning device that requires a "training set." The system's underlying principles are based on known biochemistry (competitive binding assay using folate binding protein) and not data-driven learning from a training set.
9. How the Ground Truth for the Training Set was Established
Not applicable, as there is no training set for this type of in vitro diagnostic device.
§ 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.