(94 days)
Tina-quant Transferrin ver.2 (urine application) assay is an in vitro test for the quantitative determination of transferrin in human urine on Roche/Hitachi cobas c systems.
A transferrin immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the transferrin (an iron-binding and transporting serum protein) in urine. Measurement of transferrin levels aids in the diagnosis of malnutrition, acute inflammation, infection, and red blood cell disorders, such as iron deficiency anemia.
The Tina-quant Transferrin ver.2 (urine application) assay is a two reagent assay for the in vitro quantitative determination of transferrin in human urine on automated clinical chemistry analyzers. It is an immunoturbidimetric assay in which human transferrin forms a precipitate with a specific antiserum which is determined turbidimetrically.
Engineering drawings, schematics, and figures are not pertinent to describe the device, as the device is a reagent.
The document provided is a 510(k) Premarket Notification for an in vitro diagnostic device, the "Tina-quant Transferrin ver.2 (urine application) assay." This type of submission focuses on demonstrating substantial equivalence to a legally marketed predicate device, rather than proving clinical effectiveness through extensive human studies often seen with novel medical devices. Therefore, the information regarding acceptance criteria and study design will be primarily focused on analytical performance validation rather than multi-reader multi-case clinical studies involving human interpretation of images, as this is a laboratory reagent.
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1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria for this device are largely implicit in the fact that "All data passed the predetermined acceptance criteria" for each analytical study. The performance is reported as the results of these studies.
| Performance Characteristic | Acceptance Criteria (Implicit: "All data passed the predetermined criteria") | Reported Device Performance |
|---|---|---|
| Precision | CV% and SD values within predefined limits. | Repeatability (within-run precision) |
| - PreciControl ClinChem Multi 1 | Not explicitly stated, but results passed. | Mean: 1.98 mg/dL, SD: 0.0140 mg/dL, CV: 0.7% |
| - PreciControl ClinChem Multi 2 | Not explicitly stated, but results passed. | Mean: 3.05 mg/dL, SD: 0.0242 mg/dL, CV: 0.8% |
| - Human Urine 1 | Not explicitly stated, but results passed. | Mean: 0.435 mg/dL, SD: 0.00979 mg/dL, CV: 2.3% |
| - Human Urine 2 | Not explicitly stated, but results passed. | Mean: 0.737 mg/dL, SD: 0.00920 mg/dL, CV: 1.2% |
| - Human Urine 3 | Not explicitly stated, but results passed. | Mean: 1.27 mg/dL, SD: 0.0107 mg/dL, CV: 0.8% |
| - Human Urine 4 | Not explicitly stated, but results passed. | Mean: 2.52 mg/dL, SD: 0.0184 mg/dL, CV: 0.7% |
| - Human Urine 5 | Not explicitly stated, but results passed. | Mean: 3.30 mg/dL, SD: 0.0252 mg/dL, CV: 0.8% |
| Intermediate Precision (within-lab precision) | Not explicitly stated, but results passed. | |
| - PreciControl ClinChem Multi 1 | Not explicitly stated, but results passed. | Mean: 1.98 mg/dL, SD: 0.0158 mg/dL, CV: 0.8% |
| - PreciControl ClinChem Multi 2 | Not explicitly stated, but results passed. | Mean: 3.05 mg/dL, SD: 0.0267 mg/dL, CV: 0.9% |
| - Human Urine 1 | Not explicitly stated, but results passed. | Mean: 0.435 mg/dL, SD: 0.0111 mg/dL, CV: 2.5% |
| - Human Urine 2 | Not explicitly stated, but results passed. | Mean: 0.737 mg/dL, SD: 0.0112 mg/dL, CV: 1.5% |
| - Human Urine 3 | Not explicitly stated, but results passed. | Mean: 1.23 mg/dL, SD: 0.0130 mg/dL, CV: 1.1% |
| - Human Urine 4 | Not explicitly stated, but results passed. | Mean: 2.52 mg/dL, SD: 0.0215 mg/dL, CV: 0.9% |
| - Human Urine 5 | Not explicitly stated, but results passed. | Mean: 3.30 mg/dL, SD: 0.0289 mg/dL, CV: 0.9% |
| Analytical Sensitivity | ||
| - Limit of Blank (LoB) | LoB Claim: 0.10 mg/dL (highest measurement for blank sample with stated prob.) | Lot #1: 0.0150 mg/dL, Lot #2: 0.0130 mg/dL, Lot #3: 0.0150 mg/dL |
| - Limit of Detection (LoD) | LoD Claim: 0.15 mg/dL (lowest detectable analyte concentration with 95% prob.) | Lot #1: 0.0382 mg/dL, Lot #2: 0.0331 mg/dL, Lot #3: 0.0353 mg/dL |
| - Limit of Quantitation (LoQ) | LoQ Claim: 0.22 mg/dL with 20% CV (lowest quantifiable concentration) | Lot #1: 0.124 mg/dL, Lot #2: 0.137 mg/dL, Lot #3: 0.143 mg/dL |
| Linearity/Assay Reportable Range | Linear relationship across the measuring range. | |
| - Measuring Range Claim | 0.22 to 3.5 mg/dL. | Confirmed. |
| - Pearson Correlation Coefficient (r) | Close to 1. | Lot 1: 0.9999, Lot 2: 0.9999, Lot 3: 0.9997 |
| Endogenous Interferences | No interference at specified concentrations. | |
| - Albumin | No interference ≤ 5000 mg/L. | Passed (tested at 5 g/L). |
| - Calcium | No interference ≤ 8 mmol/L. | Passed (tested up to 9.92/9.80 mmol/L). |
| - Citrate | No interference ≤ 10 mmol/L. | Passed (tested up to 11 mmol/L). |
| - Creatinine | No interference ≤ 44 mmol/L. | Passed (tested up to 88 mmol/L). |
| - Glucose | No interference ≤ 111 mmol/L. | Passed (tested up to 388 mmol/L). |
| - Hemoglobin | No significant interference up to 100 mg/dL. | Passed (tested up to 146/149 mg/dL). |
| - Immunoglobulin (IgG) | No interference ≤ 500 mg/L. | Passed (tested up to 1.1 g/L). |
| - Magnesium | No interference ≤ 75 mmol/L. | Passed (tested up to 75 mmol/L). |
| - Oxalate | No interference ≤ 2.2 mmol/L. | Passed (tested up to 3.75 mmol/L). |
| - Phosphate | No interference ≤ 40 mmol/L. | Passed (tested up to 130 mmol/L). |
| - Urea | No interference ≤ 1000 mmol/L. | Passed (tested up to 1500/1800 mmol/L). |
| - Uric Acid | No interference ≤ 6 mmol/L. | Passed (tested up to 6 mmol/L). |
| - Urobilinogen | No interference ≤ 15 mg/dL. | Passed (tested up to 15 mg/dL). |
| Exogenous Interferences – Drugs | No interference at therapeutic concentrations (except noted). | |
| - Acetaminophen | Not explicitly stated, but results passed up to 3000 mg/L. | No interference up to 3000 mg/L. |
| - Ascorbic acid | Not explicitly stated, but results passed up to 4000 mg/L. | No interference up to 4000 mg/L. |
| - Cefoxitin | Not explicitly stated, but results passed up to 12000 mg/L. | No interference up to 12000 mg/L. |
| - Gentamicin sulfate | Not explicitly stated, but results passed up to 400 mg/L. | No interference up to 400 mg/L. |
| - Ibuprofen | Not explicitly stated, but results passed up to 500 mg/L. | No interference up to 500 mg/L. |
| - Levodopa | Not explicitly stated, but results passed up to 1000 mg/L. | No interference up to 1000 mg/L. |
| - Methyldopa | Not explicitly stated, but results passed up to 2000 mg/L. | No interference up to 2000 mg/L. |
| - N-Acetylcysteine | Not explicitly stated, but results passed up to 10 mg/L. | No interference up to 10 mg/L. |
| - Ofloxacine | No interference. | Interference observed (artificially high results). Claim adjusted. |
| - Phenazopyridine | Not explicitly stated, but results passed up to 50 mg/L. | No interference up to 50 mg/L. |
| - Salicyluric acid | Not explicitly stated, but results passed up to 100 mg/L. | No interference up to 100 mg/L. |
| - Tetracycline | Not explicitly stated, but results passed up to 300 mg/L. | No interference up to 300 mg/L. |
| Method Comparison to Predicate | Predetermined acceptance criteria met. (e.g. slope near 1, intercept near 0, high r) | y = 1.007x + 0.0052, r = 0.995 (Passing Bablok Regression) |
2. Sample Size Used for the Test Set and Data Provenance
- Precision and Analytical Sensitivity (LoB, LoD, LoQ):
- Precision (Repeatability and Intermediate Precision): 5 human urine sample pools and 2 control samples. Tested for 21 days, 1 run/day, with 2 aliquots per sample in singlicate per part. This setup generates a large number of individual measurements over time to assess variability.
- LoB: One analyte-free sample, measured 10-fold per run across 6 runs (over 4 days) on 3 reagent lots, resulting in 60 measurements per lot.
- LoD: Five human urine samples with low-analyte concentration, measured 2-fold per run across 6 runs (over 4 days) on 3 reagent lots, resulting in 60 measurements per lot.
- LoQ: A low-level sample set prepared by diluting 5 human urine samples, tested in 5 replicates per sample on 4 days, 1 run per day.
- Linearity/Assay Reportable Range: Dilution series prepared using human urine sample pools (number of pools not specified, but likely at least one concentrated pool), with 13 concentrations measured on 3 lots in triplicate.
- Endogenous Interferences: Two human urine pools (at two transferrin concentrations) were used for each interferent. Each pool was divided into two aliquots (spiked with interferent vs. solvent control). A dilution series of 11 steps was prepared and 3 aliquots per level were tested.
- Exogenous Interferences – Drugs: Two human urine sample pools (spiked with approximately 0.433 and 2.48 mg/dL transferrin concentrations) were used for each drug. Each pool was divided into two aliquots (drug spiked vs. solvent control), measured in triplicate.
- Method Comparison to Predicate: One hundred and seven (107) routine fresh, never-frozen human urine samples. Two samples were excluded (pH >8, value outside measuring range), so 107 samples were truly used in the comparison.
- Data Provenance: The document explicitly states "human urine samples" or "human urine sample pools." For the method comparison, samples were "routine fresh, never-frozen human urine samples." There is no specific mention of the country of origin, but Roche Diagnostics Operations (RDO) is located in Indianapolis, Indiana, USA, and Roche Diagnostics GmbH, Mannheim, Germany is also mentioned as having the establishment registration. The studies are prospective analytical validation studies conducted with collected samples, not retrospective analysis of clinical patient data in the typical sense for imaging.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications of Those Experts
This type of in vitro diagnostic device (IVD) aims for quantitative measurement of a biomarker. Therefore, the "ground truth" is established through analytical reference methods, certified reference materials, or highly rigorous internal validation processes tied to metrological traceability, rather than human expert consensus on subjective findings (as would be the case for an imaging AI).
- The ground truth for the test set is established by the analytical measurement on the reference method (for method comparison study), and by the known concentrations/dilutions of samples prepared for analytical studies (e.g., linearity, sensitivity, interference).
- No "experts" in the sense of radiologists interpreting images were involved in establishing the ground truth for these analytical performance studies. The accuracy of measurements is verified against the reference standard or predetermined analytical values.
4. Adjudication Method for the Test Set
Not applicable for this type of analytical performance study. Adjudication methods (e.g., 2+1, 3+1) are common in clinical studies where multiple human readers independently assess data (like images) and then a consensus or tie-breaking mechanism is needed to establish ground truth or assess agreement. For an IVD, the "truth" is typically defined by the analytical method itself or a reference method.
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 device is a quantitative laboratory assay (a reagent for measuring transferrin in urine), not an AI imaging algorithm that assists human readers. No MRMC study was performed as it is irrelevant to the device's function.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, the analytical performance studies (Precision, Analytical Sensitivity, Linearity, Interference, Method Comparison) represent the "standalone" performance of the assay itself (the reagent/instrument system) without human intervention in the result generation beyond operating the analyzer according to instructions. This is the primary form of performance evaluation for an IVD.
7. The Type of Ground Truth Used
- For Precision, Analytical Sensitivity, Linearity, and Interference studies: The ground truth is effectively derived from known concentrations in prepared samples (e.g., analyte-free samples, low-concentration samples, dilution series, spiked samples) or reference materials/controls with established values.
- For Method Comparison: The ground truth is the measurement obtained from the predicate device, the "N Antisera to Human Transferrin (Siemens) on the BN ProSpec analyzer." This establishes substantial equivalence to an already legally marketed device.
8. The Sample Size for the Training Set
Not applicable. This is not an AI/machine learning device that requires "training data" in the conventional sense. It's a chemical reagent for an established analytical method (immunoturbidimetry). The development process would have involved formulation and optimization, but not "training" on a data set in the way an AI model would be.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no "training set" for this type of IVD, which relies on chemical and immunological principles rather than machine learning from data.
§ 866.5880 Transferrin immunological test system.
(a)
Identification. A transferrin immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the transferrin (an iron-binding and transporting serum protein) in serum, plasma, and other body fluids. Measurement of transferrin levels aids in the diagnosis of malnutrition, acute inflammation, infection, and red blood cell disorders, such as iron deficiency anemia.(b)
Classification. Class II (performance standards).