(80 days)
The cassette Roche COBAS INTEGRA Carbon Dioxide (CO2-S) contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of the carbon dioxide concentration in serum and plasma. Determination of carbon dioxide concentration in blood is most commonly performed as an initial test in the cvaluation of the body's ability to control blood pH by appropriate removal of metabolism byproducts via the lung and kidneys.
The cassette Roche COBAS INTEGRA Glucose HK Liquid contains an in vitro diagnostic reagent system intended for use on the COBAS INTEGRA for the quantitative determination of the glucose concentration in serum, plasma, urine and cerebrospinal fluid (CSF). In addition, an optional glucose "fast application" for serum and plasma is available. Glucose measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus and idiopathic hypoglycemia.
The COBAS INTEGRA test applications contained in this submission are intended for use with the COBAS INTEGRA Analyzer. The COBAS INTEGRA Analyzer and COBAS INTEGRA Reagent cassettes together provide an integrated system for in vitro diagnostic testing. The COBAS INTEGRA Analyzer utilizes three measuring principles, i.e., absorbance, fluorescence polarization and ion-selective electrodes. The analyzer has a throughput of up to 600 tests per hour with STAT samples prioritized and tested immediately. Random sample access, robotics and a user interface optimize time management and streamline workflow. The COBAS INTEGRA can store up to 68 COBAS INTEGRA Reagent Cassettes on board, 24 hours a day at 2-8℃. The COBAS INTEGRA Reagent Cassettes are compact and preparation-free with the added convenience of long term on-board stability. Barcode readers are used to identify newly loaded reagent cassettes, samples for patient identification, and rack inserts and to read calibration and control data from the cassette label. COBAS INTEGRA tests include chemistry, drugs of abuse, immunology, ion selective electrodes, therapeutic drug monitoring, and hematology reagents.
The provided text describes two devices, COBAS INTEGRA Carbon Dioxide (CO2-S) and COBAS INTEGRA Glucose HK Liquid (GLULF), in a 510(k) submission. Here's an analysis of the acceptance criteria and supporting studies for each:
Device 1: COBAS INTEGRA Carbon Dioxide (CO2-S)
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state "acceptance criteria." However, substantial equivalence is determined by comparing the performance characteristics of the proposed device against a legally marketed predicate device. The values presented for the proposed device imply the performance achieved for each characteristic, and the aim is to demonstrate that these are equivalent to or better than the predicate.
| Performance Characteristic | Acceptance Criteria (Predicate) | Reported Device Performance (CO2-S) |
|---|---|---|
| Assay Range | 0 - 40 mmol/L | 0 - 50 mmol/L |
| Sensitivity | $5.2 \times 10^{-2} \Delta A$ per mmol/L | $1.5 \times 10^{-2} \Delta A$ per mmol/L |
| Precision: | ||
| Level 1 Mean (mmol/L) | 18.9 | 19.5 |
| Level 2 Mean (mmol/L) | 33.0 | 33.8 |
| % CV (within-run) | Level 1: 1.2; Level 2: 1.1 | Level 1: 1.1; Level 2: 1.2 |
| % CV (total) | Level 1: 2.5; Level 2: 1.9 | Level 1: 3.1; Level 2: 2.5 |
| Accuracy: | ||
| Sample size (n) | 200 | 220 |
| Corr. Coefficient (r) | 0.997 | 0.999 |
| Linear Regression | 1.04x + 0.4 mmol/L | 1.01x - 0.8 mmol/L |
Note: The reported sensitivity for the proposed device (1.5 x 10^-2 ΔA per mmol/L) is lower than the predicate (5.2 x 10^-2 ΔA per mmol/L). In immunoassay terms, a lower ΔA indicates lower sensitivity, which could be a point of divergence. However, the FDA's clearance implies that the overall performance was deemed substantially equivalent, often considering the clinical impact and other strong performance metrics like accuracy and precision. The assay range of the proposed device is wider, which is generally an improvement. The precision and accuracy metrics are comparable or slightly better in some aspects for the proposed device.
2. Sample size used for the test set and the data provenance
- Sample size for accuracy test set (n): 220
- Data provenance: Not explicitly stated (e.g., country of origin, retrospective or prospective). The document uses generic terms like "clinical and nonclinical studies." Given the context of a 510(k) submission to the US FDA, it's highly probable the data was collected under controlled conditions to support regulatory approval, likely in a prospective manner, but this is not explicitly confirmed.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
Not applicable. This is an in vitro diagnostic device measuring a quantitative analyte. The "ground truth" (or reference values) for comparison are established by a reference method or legally marketed predicate device, not by expert interpretation of images or other qualitative data. Therefore, no experts were used in this manner.
4. Adjudication method for the test set
Not applicable for this type of in vitro diagnostic device. Adjudication methods like 2+1 or 3+1 are typically used for qualitative assessments, often in imaging studies where multiple readers interpret results and discrepancies need resolution. For quantitative measurements, comparisons are made against established reference methods or predicate devices.
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/imaging device. It is an in vitro diagnostic reagent system for quantitative determination of a chemical analyte.
6. If a standalone (i.e. algorithm only without human-in-the loop performance) was done
Yes, the performance characteristics provided (assay range, sensitivity, precision, accuracy) represent the standalone performance of the COBAS INTEGRA Carbon Dioxide (CO2-S) reagent on the COBAS INTEGRA Analyzer. This is typical for in vitro diagnostic devices where the analytical performance of the assay itself is validated.
7. The type of ground truth used
The ground truth for the analytical accuracy (correlation and linear regression) is based on comparison against a reference method or a predicate device. The linearity and correlation coefficients indicate how well the proposed device's measurements align with these established methods. The predicate device "COBAS INTEGRA Carbon Dioxide (CO2)" (K954992) serves as the primary comparator.
8. The sample size for the training set
Not provided. For in vitro diagnostic devices like this, there isn't typically a "training set" in the machine learning sense. Method development and optimization (which might be analogous to training) would involve various samples, but the specific number is not disclosed in the 510(k) summary, which focuses on validation/test data.
9. How the ground truth for the training set was established
Not applicable as there is no explicitly defined "training set" with ground truth in the traditional sense for this type of device in the provided document. Method development and optimization would use samples with known CO2 concentrations, but the specific process for establishing these values for internal development is not detailed.
Device 2: COBAS INTEGRA Glucose HK Liquid (GLULF) (fast application)
1. Table of Acceptance Criteria and Reported Device Performance
Similar to CO2-S, the document presents performance characteristics for the proposed GLULF "fast application" in comparison to its predicate (standard application).
| Performance Characteristic | Acceptance Criteria (Predicate) | Reported Device Performance (GLULF - fast application) |
|---|---|---|
| Assay Range | 0 - 40 mmol/L | 0 - 30 mmol/L |
| Sensitivity | $5.4 \times 10^2 \Delta A$ per mmol/L | $5.4 \times 10^2 \Delta A$ per mmol/L |
| Precision: | ||
| Level 1 Mean (mmol/L) | 5.3 | 4.7 |
| Level 2 Mean (mmol/L) | 33.2 | 27.7 |
| % CV (within-run) | Level 1: 1.7; Level 2: 0.72 | Level 1: 1.4; Level 2: 0.5 |
| % CV (total) | Level 1: 2.6; Level 2: 1.5 | Level 1: 2.4; Level 2: 1.2 |
| Accuracy: | ||
| Sample size (n) | 220 | 216 |
| Corr. Coefficient (r) | 0.999 | 0.999 |
| Linear Regression | 1.05x - 0.2 mmol/L | 0.99x + 0.01 mmol/L |
Note: The reported assay range for the "fast application" is narrower (0-30 mmol/L) compared to the standard application (0-40 mmol/L). However, precision for the fast application appears slightly better (lower %CVs), and the sensitivity is identical. The accuracy metrics (correlation coefficient and linear regression) are highly comparable, indicating substantial equivalence in performance for the intended use and specified range.
2. Sample size used for the test set and the data provenance
- Sample size for accuracy test set (n): 216
- Data provenance: Not explicitly stated (e.g., country of origin, retrospective or prospective). Similar to CO2-S, the data would likely be from controlled studies, presumably prospective, but this is not explicitly confirmed.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
Not applicable. This is an in vitro diagnostic device measuring a quantitative analyte. The "ground truth" for comparison is established by a reference method or legally marketed predicate device.
4. Adjudication method for the test set
Not applicable for this type of in vitro diagnostic device.
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/imaging device.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, the performance characteristics provided represent the standalone analytical performance of the COBAS INTEGRA Glucose HK Liquid (GLULF) fast application reagent on the COBAS INTEGRA Analyzer.
7. The type of ground truth used
The ground truth for the analytical accuracy is based on comparison against a reference method (enzymatic reference method with hexokinase) or a predicate device (COBAS INTEGRA Glucose HK Liquid - standard application, K972250).
8. The sample size for the training set
Not provided. Similar to CO2-S, "training set" in the machine learning sense is not applicable or detailed in the document.
9. How the ground truth for the training set was established
Not applicable as there is no explicitly defined "training set" with ground truth in the traditional sense for this type of device in the provided document. Method development and optimization would use samples with known glucose concentrations, but the specific process for establishing these values for internal development is not detailed.
§ 862.1160 Bicarbonate/carbon dioxide test system.
(a)
Identification. A bicarbonate/carbon dioxide test system is a device intended to measure bicarbonate/carbon dioxide in plasma, serum, and whole blood. Bicarbonate/carbon dioxide measurements are used in the diagnosis and treatment of numerous potentially serious disorders associated with changes in body acid-base balance.(b)
Classification. Class II.