(146 days)
In vitro test for the quantitative determination of the total protein concentration in urine and cerebral spinal fluid.
Protein measurements in urine are used in the diagnosis and treatment of disease conditions such as renal or heart diseases, or thyroid disorders.
CSF protein measurements are used in the diagnosis and treatment of conditions such as meningitis, brain tumors, and infections of the central nervous systems.
The Total Protein Urine/CSF assay provides quantitative measurement of total protein that is present in human urine and cerebral spinal fluid (CSF). Measurement is accomplished using a turbidimetric method.
Reagents for the COBAS Integra 400 plus analyzer are packaged in a cobas c pack with two bottles labeled with their instrument positioning, Reagent R1 in position B and Reagent SR in position C.
R1 contains Sodium Hydroxide: 677 mmol/L; EDTA-Na: 74 mmol/L
SR contains Benzethonium chloride: 32 mmol/L
Here's an analysis of the acceptance criteria and study findings for the TPUC3 Total Protein Urine/CSF Gen.3 device, based on the provided document:
1. Table of Acceptance Criteria and Reported Device Performance
| Test | Acceptance Criterion | Reported Device Performance |
|---|---|---|
| Interference by Radiopaque Media | Deviation ≤ ± 10% | At 6.4 g/L organically bound Iodine: |
- Deviation = 5.6% at level 1 (92.5 mg/L total protein)
- Deviation = 9.7% at level 2 (961 mg/L total protein)
Meets criterion. |
| Interference by Homogentisic Acid | Deviation ≤ ± 10% | At 1.2 mmol/L homogentisic acid: - Deviation = 6.8% at level 1 (107 mg/L total protein)
- Deviation = 6.9% at level 2 (1180 mg/L total protein)
Meets criterion. |
| High Dose Hook Effect | No false result reported up to a protein concentration of 100 g/L. All samples above the measuring range are flagged. | No false result reported up to a protein concentration of 100 g/L.
All samples above the measuring range are flagged as either being above the measuring range or above the absorbance limit.
Meets criterion. |
2. Sample Sizes Used for the Test Set and Data Provenance
- Interference by Radiopaque Media: The test used pooled human urine samples at two different total protein levels. Each level was spiked with 10 dilution steps of Hexabrix and tested in triplicate. The specific number of distinct pooled samples is not stated, but at least two unique pooled samples were used (referred to as "level 1" and "level 2").
- Interference by Homogentisic Acid: The test used the same protocol as for radiopaque media, meaning pooled human urine samples at two different total protein levels, spiked with homogentisic acid, and tested in triplicate at 10 dilution steps.
- High Dose Hook Effect: The test used one pooled human urine sample which was spiked with human Albumin up to 100 g/L, and a dilution series was prepared from this spiked sample. The samples were tested in triplicate.
Data Provenance: The document explicitly states "pooled human urine samples." While it doesn't specify the country of origin, the FDA submission context usually implies data relevant to the US regulatory environment. The studies appear to be prospective as they were specifically designed and conducted to evaluate the device's performance against the defined acceptance criteria.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications of those Experts
This document describes performance studies for an in vitro diagnostic (IVD) device that quantifies total protein. The ground truth for such devices is typically established by:
- Reference methods/materials (e.g., traceable calibrators like NIST SRM-927 mentioned in the similarities section for calibration traceability)
- Known concentrations of interference substances (e.g., Hexabrix, homogentisic acid)
- Known concentrations of the analyte itself (e.g., human Albumin for the hook effect).
Therefore, the ground truth is based on analytical standards and precise spiking of known concentrations, not interpretation by medical experts. No human experts (like radiologists) were involved in establishing the ground truth for these specific performance tests.
4. Adjudication Method for the Test Set
Not applicable. The tests involve quantitative measurements against known spiked concentrations or defined analytical limits. There is no subjective interpretation requiring adjudication.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No. This document describes the performance of an IVD analyzer for quantitative protein measurement. MRMC studies are typically performed for diagnostic imaging devices where human readers interpret medical images. This is a standalone device performance study.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes. The entire study described focuses on the standalone performance of the TPUC3 Total Protein Urine/CSF Gen.3 assay on the Roche COBAS Integra 400 plus analyzer. It evaluates the device's accuracy in the presence of specific interferents and its response to high analyte concentrations, without any human interpretation of the results being part of the performance evaluation.
7. The Type of Ground Truth Used
The ground truth used for these studies is based on:
- Known (spiked) concentrations of interferents (organically bound iodine from Radiopaque media, homogentisic acid) in pooled human urine.
- Known (spiked) concentrations of the analyte (human Albumin) to assess the high dose hook effect.
- The concentrations of these substances were precisely controlled and quantified.
8. The Sample Size for the Training Set
The document does not provide information on the training set size. This submission is for modifications to an existing device (TPUC3 Total Protein Urine/CSF Gen.3). The described studies are validation/verification tests for these specific modifications related to interference claims and hook effect, not for initial model development or training. IVD devices like this are typically developed through iterative analytical and clinical studies, but information about the "training set" for the underlying chemistry/method is not detailed here.
9. How the Ground Truth for the Training Set Was Established
As no training set information is provided, there is no information on how its ground truth was established. For IVD devices, the initial ground truth for method development (analogous to a training set) would generally involve:
- Certified reference materials.
- Patient samples characterized by established reference methods.
- Spiking studies with known concentrations of analytes and interferents.
§ 862.1645 Urinary protein or albumin (nonquantitative) test system.
(a)
Identification. A urinary protein or albumin (nonquantitative) test system is a device intended to identify proteins or albumin in urine. Identification of urinary protein or albumin (nonquantitative) is used in the diagnosis and treatment of disease conditions such as renal or heart diseases or thyroid disorders, which are characterized by proteinuria or albuminuria.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 862.9.