FDA 510(k) Search - By Innolitics (SaMD and AI Experts)

The cobas pro integrated solutions is an IVD device used for the quantitation of clinical chemistry and Ion Selective Electrolyte parameters from various biological fluids.

Glucose HK Gen.3 is an in vitro test for the quantitative determination of glucose in human serum, plasma, urine and CSF on Roche/Hitachi cobas c systems. Glucose measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal hypoglycemia and pancreatic islet cell tumors.

The ISE indirect Na for Gen. 2 is intended for the quantitative determination of sodium in serum, plasma or urine using ion-selective electrodes. Sodium measurements are used in the diagnosis and treatment of aldosteronism (excessive secretion of the hormone aldosterone), diabetes insipidus (chronic excretion of dilute urine, accompanied by extreme thirst), adrenal hypertension, Addison's disease (caused by destruction of the adrenal glands), dehydration, inappropriate antidiuretic hormone secretion, or other diseases involving electrolyte imbalance.

Elecsys TSH immunoassay is intended for the in vitro quantitative determination of thyrotropin in human serum and plasma. Measurements of TSH are used in the diagnosis of thyroid and pituitary disorders. The electrochemiluminescence immunoassay "ECLIA" is intended for use on cobas e immunoassay analyzers.

Device Description

The cobas pro integrated solutions (cobas pro) is a fully automated, random-access, software controlled system intended for in vitro quantitative analysis of analytes in body fluids. It will typically be used in clinical laboratories with large workload. The system consolidates clinical chemistry, homogenous and heterogeneous immunoassays as well as electrolyte testing within one workplace. It consists of a high throughput sample distribution unit (core unit) and different analytical units for ISE (cobas pro ISE analytical unit), clinical chemistry (c 503 analytical unit) and immunoassay (e 801 analytical) testing. The system hardware is comprised of new or previously cleared members of the Roche/Hitachi cobas c or Elecsys families of analyzers. The instrument software is unique to the cobas pro and was developed from previous generations of Roche/Hitachi instrument systems.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the cobas pro integrated solutions device, specifically focusing on the Glucose HK Gen.3, ISE indirect Na for Gen.2, and Elecsys TSH assays.

Preamble: This document describes a Traditional 510(k) Premarket Notification for the cobas pro integrated solutions. The core purpose is to show that previously cleared Glucose, Sodium, and TSH assays, when run on the new cobas pro integrated solutions system, are substantially equivalent to their predicate devices. Therefore, the acceptance criteria and studies presented are largely comparative or validation studies demonstrating consistent performance with previously cleared devices and established analytical standards.

1. Table of Acceptance Criteria and Reported Device Performance

Given that this is a 510(k) submission demonstrating substantial equivalence to pre-existing predicate devices for assays and a new integrated system, the acceptance criteria are generally focused on meeting established performance claims or showing equivalence within acceptable statistical limits. The summary provided focuses on the reported device performance which is then implicitly compared to internal acceptance criteria (often relative to the predicate device or CLSI guidelines).

Note on Acceptance Criteria: The document explicitly states "All samples met the predetermined acceptance criterion" for precision studies. For LoQ, it states "LoQ determined at maximum allowable %TE (total error) of no more than 20% (Glucose and TSH) and 30% (Sodium)." For endogenous interference, it was "recovery of 100±10%". For exogenous interference (common drugs for Elecsys TSH), it was "± 10% of the reference value". For method comparisons, the slope, intercept, and correlation coefficients approaching 1 or 0 respectively, indicate strong agreement, satisfying the intent of substantial equivalence. Specific numerical acceptance criteria are not always stated outright but are implied by the study design and conclusion of meeting criteria.

Category	Acceptance Criteria (Explicit or Implied)	Reported Device Performance (Worst Case/Summary)
Precision	Samples met predefined acceptance criteria (based on CLSI EP05-A3 guidelines).	Glucose HK Gen.3 (N=84 per application):

Serum Repeatability CV: 0.4%-9.2%
Serum Intermediate Precision CV: 0.5%-10.0%
Urine Repeatability CV: 0.4%-8.3%
Urine Intermediate Precision CV: 0.7%-8.5%
CSF Repeatability CV: 0.4%-3.0%
CSF Intermediate Precision CV: 0.5%-3.5%
ISE indirect Na (N=84 per application):
Plasma Repeatability CV: 0.3%-0.6%
Plasma Intermediate Precision CV: 0.5%-1.5%
Serum Repeatability CV: 0.3%-0.5%
Serum Intermediate Precision CV: 0.5%-1.7%
Urine Repeatability CV: 0.3%-0.5%
Urine Intermediate Precision CV: 0.6%-4.8%
Elecsys TSH (N=84):
Repeatability CV: 1.6%-6.3%
Intermediate Precision CV: 2.4%-11.7% |
| Analytical Sensitivity | LoQ: Total error not more than 20% (Glucose, TSH), 30% (Na). | Glucose HK Gen.3: LoB: 0.2 mg/dL, LoD: 0.4 mg/dL, LoQ: 1.4 mg/dL.
Claimed: LoB: 2 mg/dL, LoD: 2 mg/dL, LoQ: 2 mg/dL.
ISE indirect Na: LoB: 3.50 mmol/L, LoD: 4.42-4.51 mmol/L, LoQ: 11.8-12.2 mmol/L.
Claimed: LoB: 3.5 mmol/L, LoD: 4.5 mmol/L, LoQ: 12.2 mmol/L.
Elecsys TSH: LoB: 0.0013-0.0015 µIU/mL, LoD: 0.00282-0.00348 µIU/mL, LoQ: 0.00386-0.00495 µIU/mL.
Claimed: LoB: 0.0025 µIU/mL, LoD: 0.005 µIU/mL, LoQ: 0.005 µIU/mL. |
| Linearity/Reportable Range | Deviations within predetermined acceptance criteria. | Glucose HK Gen.3: Serum (R2=0.9999), Urine (R2=0.9997), CSF (R2=0.9992) linear in claimed range (2.0-750 mg/dL).
ISE indirect Na: Plasma (R2=0.9998), Serum (R2=0.9998), Urine (R2=0.9999) linear in claimed range (80-180 mmol/L for S/P, 20-250 mmol/L for U).
Elecsys TSH: Serum (R2=0.9972) linear in range 0.004-118 uIU/mL. |
| High Dose Hook Effect | No hook effect observed up to a specified concentration. | Elecsys TSH: No hook effect up to 1466 uIU/mL TSH. |
| Endogenous Interference | Recovery of 100 ± 10%. | Glucose HK Gen.3: No interference from albumin, bilirubin, hemolysis, IgG, lipemia, etc. at specified high concentrations.
ISE indirect Na: No interference from bilirubin, hemolysis, lipemia at specified high concentrations.
Elecsys TSH: No interference from biotin, lipemia, hemoglobin, bilirubin, rheumatoid factor, immunoglobulins at specified high concentrations. |
| Exogenous Interference (Drugs) | ± 10% of the reference value in comparison to unspiked samples. | ISE indirect Na: No interference from various common and special drugs at specified concentrations.
Elecsys TSH: No interference from common and special drugs at specified concentrations. |
| Analytical Specificity/Cross-Reactivity | % cross-reactivity near zero. | Elecsys TSH: hGH, hCG, LH, FSH showed 0.000% cross-reactivity at high tested concentrations. |
| Method Comparison to Predicate | Strong correlation (slope ≈ 1, intercept ≈ 0, high R/tau values) indicating substantial equivalence to predicate device/reference method. | Glucose HK Gen.3: Slope close to 1.0, intercept close to 0, strong correlation (Pearson r/Kendall tau close to 1) comparing to cobas c 501.
ISE indirect Na: Slope close to 1.0, intercept close to 0, strong correlation (Pearson r close to 1) comparing to cobas c 501 ISE and Flame Photometer.
Elecsys TSH: Slope = 1.018 (LCL/UCL: 1.004/1.025), Intercept = -0.0018 µIU/mL (LCL/UCL: -0.0040/-0.0001), Pearson r = 0.999, Kendall tau = 0.977 when compared to predicate Elecsys TSH on cobas 8000. |
| Sample Matrix Comparison | Acceptable recovery of analyte values and strong correlation between different sample types (e.g., serum vs. various plasma anticoagulants). | Glucose HK Gen.3: Strong correlation (slope near 1, intercept near 0, r near 1) comparing serum to serum tube with separation gel, and various plasma anticoagulants (K2EDTA, Li-Heparin, NaF/K-Oxalate, NaF/Na2-EDTA, NaF/Citrate/Na2-EDTA, KF/Na2-EDTA).
ISE indirect Na: Strong correlation (Slope = 1.015, Intercept = -2.69, r = 0.998) between Serum and Li-Heparin Plasma.
Elecsys TSH: Strong correlation (slope near 1, intercept near 0, r near 1) comparing serum to Li-Heparin, K2-EDTA, and K3-EDTA plasma. |
| Stability | Stability data supports Roche Diagnostic's claims as reported in the package inserts. (Implied: device maintains performance over its claimed shelf life and in-use stability.) | Stability data for Glucose HK Gen.3, ISE indirect Na, and Elecsys TSH was provided in prior 510(k)s (K061048, K060373, and K190773 respectively) and supports the claims. |

2. Sample Size Used for the Test Set and Data Provenance

Glucose HK Gen.3 (Precision):
- Sample Size: 84 measurements for each control level (PreciControl ClinChem Multi 1 and 2) and 5 human serum samples per application (serum, urine, CSF). So, for repeatability and intermediate precision, 84 measurements for 2 controls + 5 samples, across serum, urine, and CSF applications.
- Data Provenance: Human serum, plasma, urine, and CSF samples. These were "native, single donors as well as pools." The study was conducted in-house by Roche Diagnostics (implied by the submission).
ISE indirect Na (Precision):
- Sample Size: 84 measurements for each control level (PreciControl ClinChem Multi 1 and 2, Liquichek 1 and 2) and 5 human plasma, serum, and urine samples per application. So, for repeatability and intermediate precision, 84 measurements for controls + 5 samples, across Li-Heparin Plasma, Serum, and Urine.
- Data Provenance: Human Li-Heparin plasma, serum, and urine samples. These were "native, single donors as well as pools." Conducted in-house by Roche Diagnostics.
Elecsys TSH (Precision):
- Sample Size: 84 measurements for each control level (PreciControl Universal, PC Thyro Sensitive) and 5 human serum samples.
- Data Provenance: Human serum samples. These were "native, single donors as well as pools." Conducted in-house by Roche Diagnostics.
Analytical Sensitivity (LoB, LoD, LoQ) for all assays:
- Sample Size:
  - LoB: ≥ 60 measurements of analyte-free samples.
  - LoD: 60 measurements (5 low-analyte concentration samples, measured in duplicate over 6 runs, 3 days).
  - LoQ: ≥ 60 measurements per sample type (samples with low analyte concentration measured over 3 to 5 days).
- Data Provenance: Not explicitly stated for specific blanks or low-concentration samples beyond "analyte-free" or "low-analyte concentration". Conducted in-house by Roche Diagnostics.
Linearity/Assay Reportable Range:
- Glucose HK Gen.3: Three high analyte human serum, urine, and CSF samples diluted to 12 levels.
- ISE indirect Na: Three high analyte human serum, urine, and CSF samples diluted to multiple aliquot concentrations.
- Elecsys TSH: Three high analyte human serum samples diluted to concentrations covering the measuring range.
- Data Provenance: Human serum, urine, CSF samples. Conducted in-house by Roche Diagnostics.
Endogenous Interference:
- Glucose HK Gen.3: Plasma and urine samples, glucose levels ~79.5 mg/dL and ~116.3 mg/dL.
- ISE indirect Na: Human plasma, serum, and urine samples. Low (~124 mmol/L) and high (~151 mmol/L) for S/P; low (26.3 mmol/L) and high (188 mmol/L) for urine.
- Elecsys TSH: Human serum samples with TSH concentrations ~0.462 uIU/mL, ~3.95 µIU/mL, and ~7.54 µIU/mL.
- Data Provenance: Human samples. Conducted in-house by Roche Diagnostics.
Exogenous Interference (Drugs):
- ISE indirect Na: Two sample pools (low and high concentration ISE indirect Na).
- Elecsys TSH: Two human serum samples (~0.5 uIU/mL and ~8 uIU/mL TSH).
- Data Provenance: Human samples. Conducted in-house by Roche Diagnostics.
Analytical Specificity/Cross-Reactivity (Elecsys TSH):
- Sample Size: Native human serum sample pool.
- Data Provenance: Human serum samples. Conducted in-house by Roche Diagnostics.
Method Comparison to Predicate:
- Glucose HK Gen.3: 74 native human serum samples, 67 native human urine samples, 75 native CSF samples.
- ISE indirect Na: 120 human Lithium heparin plasma samples (vs cobas c 501 ISE), 118 human Lithium heparin plasma (vs Flame Photometer), 120 human serum (vs cobas c 501 ISE), 120 human serum (vs Flame Photometer), 120 human urine (vs cobas c 501 ISE/Flame Photometer).
- Elecsys TSH: 138 samples (129 native human serum, 9 diluted human serum samples; single donors and pools).
- Data Provenance: Native human samples (serum, plasma, urine, CSF), some diluted. Conducted in-house by Roche Diagnostics.
Sample Matrix Comparison:
- Glucose HK Gen.3: At least 39 serum/plasma pairs for each anticoagulant type (K2-EDTA, Li-Heparin, NaF/K-Oxalate, NaF/Na2-EDTA, NaF/Citrate/Na2-EDTA, KF/Na2-EDTA plasma tubes) + serum vs. serum tube with separation gel.
- ISE indirect Na: 50 serum/Li-Heparin plasma pairs.
- Elecsys TSH: Minimum of 56 serum/plasma pairs for Li-Heparin, K2-EDTA, K3-EDTA plasma tubes. Serum separation tubes from 3 manufacturers, blood from five donors were used.
- Data Provenance: Native human samples. Conducted in-house by Roche Diagnostics.

3. Number of Experts and Qualifications for Ground Truth

This submission concerns in vitro diagnostic (IVD) devices for quantitative measurements of analytes. For such devices, "ground truth" is typically established by:

Reference methods (e.g., flame photometry for Sodium reference),
Previously cleared and validated predicate devices,
Known concentrations in control materials or spiked samples, or
The inherent chemical/physical measurement by the device itself (for analytical performance criteria like precision, linearity).
No human "experts" (like radiologists interpreting images) were used to establish ground truth in the context of these analytical performance studies. The "ground truth" is analytical, derived from established chemical/instrumental methods and reference standards.

4. Adjudication Method for the Test Set

Since this is an IVD device for quantitative measurements and the studies are analytical performance evaluations based on instrumental precision, accuracy, and comparison to established methods or predicate devices, there is no adjudication method (e.g., 2+1, 3+1) involving human experts as would be seen in diagnostic imaging studies. The data points are quantitative measurements from the instruments themselves or reference methods. Statistical analysis (e.g., regression, CVs, SDs) is used to assess performance against pre-defined criteria.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No MRMC comparative effectiveness study was done. This type of study, involving multiple human readers interpreting cases with and without AI assistance, is relevant for diagnostic imaging AI algorithms where human interpretation is part of the clinical pathway. This submission is for an in vitro diagnostic (IVD) measurement system, not an AI-powered diagnostic imaging tool that assists human readers. The comparative studies involved comparing the new system's analytical performance against predicate IVD systems or reference methods, not human readers.

6. Standalone Performance Study (Algorithm Only)

The entire non-clinical performance evaluation could be considered analogous to a "standalone" performance study, as it describes the analytical performance of the device itself (the integrated system with its assays) without human intervention in the measurement process. The device provides quantitative results, and these results are directly evaluated for precision, linearity, sensitivity, interference, and agreement with predicate devices or reference methods. There is no "human-in-the-loop" aspect to the core measurement and output of these IVD assays.

7. Type of Ground Truth Used

The ground truth used for these analytical studies consists of:

Known concentrations: For studies like linearity, analytical sensitivity (LoB, LoD, LoQ), and interference, samples prepared with known concentrations of analytes or interferents serve as the ground truth.
Reference methods: For method comparison studies, well-established and often independently validated reference methods (e.g., flame photometry for sodium measurement) serve as the ground truth or gold standard for comparison.
Predicate device results: For demonstrating substantial equivalence, the results obtained from a legally marketed predicate device (which itself has established ground truth capabilities) serve as the comparative ground truth.
Internal statistical controls: For precision studies, consistent and stable control materials are used, where the expected range or value is the "ground truth" against which repeatability and intermediate precision are measured.

8. Sample Size for the Training Set

This document describes the non-clinical performance evaluation for a 510(k) submission, primarily for demonstrating analytical performance and substantial equivalence. It does not describe the development or training of an AI algorithm based on machine learning, so there is no specific "training set" in the context of AI/ML models. The data presented here are validation data for the analytical performance of the assay and integrated system.

For a traditional IVD device, method development involves internal studies and optimization, but this is distinct from "training data" for a machine learning model. The various studies (precision, linearity, etc.) use samples/replicates as described in point 2.

9. How the Ground Truth for the Training Set Was Established

As noted in point 8, there isn't a "training set" in the machine learning sense described in this document. If this were to refer to the developmental studies for the underlying assays (Glucose HK Gen.3, ISE indirect Na, Elecsys TSH, which are previously cleared), their ground truth would have been established during their initial development and validation process using:

Reference materials: Certified reference materials (CRMs) with known analyte concentrations.
Clinical samples: Patients samples characterized by confirmed diagnoses or clinical outcomes for intended use populations.
Comparison to established methods: Correlation with existing, approved methods, often considered the "gold standard."
Spiking and dilution experiments: Preparing samples with known added amounts of analyte.

These are standard practices in IVD assay development, ensuring the analytical and clinical performance of the individual assays before they are integrated into a new system like the cobas pro integrated solutions.

Summary

Regulation Number and Section

§ 862.1345 Glucose test system.

(a)
Identification. A glucose test system is a device intended to measure glucose quantitatively in blood and other body fluids. Glucose measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal hypoglycemia, and idiopathic hypoglycemia, and of pancreatic islet cell carcinoma.(b)
Classification. Class II (special controls). The device, when it is solely intended for use as a drink to test glucose tolerance, is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.