(90 days)
cobas c 111 analyzer:
The Roche cobas c 111 analyzer is an in-vitro diagnostic analyzer capable of performing clinical chemistry, specific protein and electrolyte tests for professional settings and small laboratories, specialized testing and CLIA-licensed doctor's offices.
Analytes are measured photometrically or turbidimetrically; the analyzer also has an optional ISE module for measuring sodium, potassium and chloride.
Reagents:
Aspartate aminotransferase (ASTL/ASTPL) In vitro test for the quantitative determination of AST in human serum and plasma on the cobas c1 11 system. Aspartate amino transferase measurements are used in the diagnosis and treatment of certain types of liver and heart disease.
C-Reactive Protein Latex (CRPLX)
In vitro test for the quantitative immunological determination of human C-reactive protein in human serum and plasma on the cobas c111 system. Measurement of C-reactive protein aids in evaluation of the amount of injury to body tissues.
Glucose HK (GLUC2)
In vitro test for the quantitative determination of glucose concentration in human serum and plasma on the cobas c111 system. Glucose measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus and idiopathic hypoglycemia.
ISE Chloride Electrode
The chloride electrode for the cobas c111 system is intended for the quantitative determination of chloride in diluted serum, plasma, and urine. Chloride measurements are used in the diagnosis and treatment of electrolyte and metabolic disorders such as cystic fibrosis and diabetic acidosis.
ISE Potassium Electrode
The potassium electrode for the cobas c111 system is intended for the quantitative determination of potassium in diluted serum, plasma, and urine. Measurements of potassium are used to monitor electrolyte balance in the diagnosis and treatment of diseases conditions characterized by low or high blood potassium levels.
ISE Sodium Electrode
The sodium electrode for the cobas c111 system is intended for the quantitative determination of sodium in diluted serum, plasma, and urine. Measurements of sodium are used in the diagnosis and treatment of aldosteronism (excessive secretion of the hormone aldosterone), diabetes insibidus (chronic excretion of large amounts 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.
The Roche cobas c 111 analyzer is an in-vitro diagnostic analyzer capable of performing clinical chemistry, specific protein and electrolyte tests. Analytes are measured photometrically or turbidimetrically; the analyzer also has an optional ISE module for measuring sodium, potassium and chloride.
The provided 510(k) summary (K071211) describes the cobas c 111 Analyzer and its applied reagents. This submission is for a modification to the device, extending its intended use to include point-of-care settings, in addition to professional use. The study presented compares the performance characteristics of certain reagents (AST, Glucose, CRP, ISE-Cl, ISE-K, ISE-Na) on the cobas c 111 analyzer for both professional use (as cleared in K063744) and the proposed point-of-care use, to demonstrate substantial equivalence.
Here's an analysis of the acceptance criteria and the study as requested:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria for each analyte are implicitly defined by demonstrating that the "Reagent performance characteristics for point-of-care use" are comparable to or within acceptable limits of the "Reagent performance characteristics on cobas c 111 analyzer for professional use." The main performance metrics evaluated are:
| Feature/Analyte | Professional Use Performance (Reference) | Point-of-Care Use Performance (Test) | Relationship/Acceptance Criteria (Implied) |
|---|---|---|---|
| Intended Use | The Roche cobas c 111 analyzer is an in-vitro diagnostic analyzer capable of performing clinical chemistry, specific protein and electrolyte tests. Analytes are measured photometrically or turbidimetrically; the analyzer also has an optional ISE module for measuring sodium, potassium and chloride. | The Roche cobas c 111 analyzer is an in-vitro diagnostic analyzer capable of performing clinical chemistry, specific protein and electrolyte tests in the professional setting and small laboratories, specialized testing and CLIA-licensed doctor's offices. Analytes are measured photometrically or turbidimetrically; the analyzer also has an optional ISE module for measuring sodium, potassium and chloride. | Expansion of intended use from professional to include point-of-care setting and small laboratories, specialized testing, and CLIA-licensed doctor's offices, based on equivalent reagent performance. |
| Operator | Professional setting | Point-of-care setting | Demonstrated comparability of results despite different operator settings. |
| Sample Type | AST: serum and plasma | ||
| Glucose: serum and plasma | |||
| CRP: serum and plasma | |||
| ISE-Cl: serum, plasma and urine | |||
| ISE-K: serum, plasma and urine | |||
| ISE-Na: serum, plasma and urine | Same as professional use | Demonstrated same performance across sample types for the extended use. | |
| Traceability/Standardization | AST: standardized against the original IFCC formulation using calibrated pipettes together with manual photometer providing absolute values and the substrate-specific absorptivity, ε | ||
| Glucose: standardized against ID/MS | |||
| CRP: standardized against the reference preparation of the IRMM - BCR470/CRM470 (RPPHS - Reference Preparation for Proteins in Human Serum) | |||
| ISE-Cl/K/Na: standardized against primary calibrators prepared gravimetrically from purified salts | Same as professional use | Maintenance of the same traceability and standardization methods implies continued accuracy. | |
| Measuring Range | AST: 2-700 U/L | ||
| Glucose: 0.11-40 mmol/L | |||
| CRP: 1-200 mg/L | |||
| ISE-Cl: 20-250 mmol/L | |||
| ISE-K: 1-100 mmol/L | |||
| ISE-Na: 20-250 mmol/L | Same as professional use | The device for point-of-care use operates within the same established measuring ranges as the professional use device. | |
| Analytical Sensitivity (LDL) | AST: 2 U/L | ||
| Glucose: 0.11 mmol/L | |||
| CRP: 1.0 mg/L | |||
| ISE-Cl: slope range -25 to -56 mV/dec | |||
| ISE-K: slope range 45 to 63 mV/dec | |||
| ISE-Na: slope range 45 to 63 mV/dec | Same as professional use | The device for point-of-care use maintains the same analytical sensitivity as the professional use device. | |
| Precision (Within-run) | AST: Human Sera: SD 0.37 at 26.2 U/L, 0.5% at 221 U/L; Controls: 1.1% at 39.7 U/L, 0.4% at 123 U/L | ||
| Glucose: Human Sera: SD 0.5 at 40.9 mg/dL, 0.8% at 180 mg/dL; Controls: 1.0% at 90.6 mg/dL, 0.5% at 252 mg/dL | |||
| CRP: Human Sera: SD 0.01 at 0.42 mg/dL, 1.3% at 23.4 mg/dL; Controls: 0.8% at 1.83 mg/dL, 0.6% at 3.77 mg/dL | |||
| ISE-Cl: Human Sera: 0.30% at 97 mmol/L, 0.24% at 1.27 mmol/L; Plasma: 0.29% at 93 mmol/L | AST: Human sera: SD 0.78 at 18.98 U/L, 2.07% at 46.92 U/L; Controls: 1.99% at 41.05 U/L, 0.63% at 137.93 U/L | ||
| Glucose: Human sera: 0.56% at 89.14 mg/L, 0.63% at 168.29 mg/L; Controls: 0.63% at 96.11 mg/L, 0.66% at 255.47 mg/L | |||
| CRP: Human sera: SD 0.072 at 0.356 mg/dL, 1.15% at 0.554 mg/dL, 1.23% at 2.385 mg/dL; Controls: 0.68% at 0.842 mg/dL, 0.41% at 4.792 mg/dL | |||
| ISE-Cl: Human sera: 0.72% at 109.03 mmol/L, 0.72% at 98.55 mmol/L; Controls: SD 0.43 at 86.22 mmol/L | The within-run precision for point-of-care use is generally comparable to or slightly higher than professional use but still within acceptable analytical variation for clinical purposes. The exact acceptance criteria (e.g., CV% limits) are not explicitly stated, but the submission implies these results are acceptable for substantial equivalence. | ||
| Precision (Total) | AST: Human Sera: SD 0.64 at 19.5 U/L, 1.0% at 306 U/L; Controls: 2.4% at 38.6 U/L, 0.9% at 126 U/L | ||
| Glucose: Human Sera: SD 0.2 at 45.4 mg/dL, 0.6% at 178 mg/dL; Controls: 0.7% at 92.3 mg/dL, 0.5% at 254 mg/dL | |||
| CRP: Human Sera: SD 0.01 at 0.47 mg/dL, 2.6% at 2.33 mg/dL; Controls: 2.1% at 1.86 mg/dL, 1.6% at 3.84 mg/dL | |||
| ISE-Cl: Human sera (Between-run): 0.44% at 97 mmol/L, 0.48% at 128 mmol/L; Plasma (Between-run): 0.51% at 93 mmol/L, 0.67% at 125 mmol/L | AST: Human sera: SD 1.2 at 16.4 U/L, 3.7% at 48.7 U/L; Controls: 3.3% at 40.24 U/L, 2.2% at 137.04 U/L | ||
| Glucose: Human sera: 2.6% at 97.5 mg/L, 2.8% at 130.7 mg/L; Controls: 2.5% at 93.03 mg/L, 2.5% at 247.08 mg/L | |||
| CRP: Human sera: 3.7% at 4.044 mg/dL, 3.2% at 4.670 mg/L; Controls: 2.6% at 0.835 mg/dL, 2.9% at 4.764 mg/dL | |||
| ISE-Cl: Human sera: 1.4% at 104.7 mmol/L, 1.6% at 104.6 mmol/L; Controls: SD 2.0 at 87.16 mmol/L, 2.0% at 119.97 mmol/L | Similar to within-run precision, total precision for point-of-care use is generally comparable or slightly higher. The implication is that these results demonstrate substantial equivalence for the expanded use. | ||
| Method Comparison | Professional Use (y = cobas c 111, x = Integra 400) | ||
| AST: y = 0.989x + 1.869 U/L, $\tau$ = 0.981, n = 82 | |||
| Glucose: y = 1.02x - 0.009 mmol/L, $\tau$ = 0.983, n = 80 | |||
| CRP: y = 0.995x + 1.334 mg/L, $\tau$ = 0.970, n = 63 | |||
| ISE-Cl: y = 1.014x - 3.236 mmol/L, r = 0.982, n = 51 | |||
| ISE-K: y = 0.984x - 0.003 mmol/L, r = 1.000, n = 51 | |||
| ISE-Na: y = 0.986x - 0.364 mmol/L, $\tau$ = 0.983, n = 51 | Point-of-care Use (y = cobas c 111, x = Integra 400) | ||
| AST: y = 0.989x + 1.276 U/L, $\tau$ = 0.8316, n = 333 | |||
| Glucose: y = 0.997x + 2.069 mg/dL, $\tau$ = 0.9217, n = 333 | |||
| CRP: y = 1.058x + 0.022 mg/L, $\tau$ = 0.9789, n = 326 | |||
| ISE-Cl: y = 1.011x - 0.51 mmol/L, $\tau$ = 0.7532, n = 280 | |||
| ISE-K: y = 0.943x + 0.189 mmol/L, $\tau$ = 0.8835, n = 280 | |||
| ISE-Na: y = 1.064x - 9.818 mmol/L, $\tau$ = 0.6920, n = 280 | The regression equations (slope and intercept) and correlation coefficients ($\tau$ or r) for the point-of-care use samples are compared to the predicate (Integra 400) and the professional use cobas c 111. The close agreement in slopes (ideally close to 1) and intercepts (ideally close to 0) indicates substantial equivalence. | ||
| Limitations - Interferences | Specific values for bilirubin, hemolysis, lipemia, anticoagulants, rheumatoid factors, drug panels are detailed for each analyte tested on the professional use analyzer. | "Same" is stated for all analytes, implying that the interference profiles are unchanged for point-of-care use. | The device for point-of-care use demonstrates the same interference characteristics as the professional use device, thus meeting the safety and effectiveness profile. |
| Endogenous Interferences | Lists specific drugs or conditions causing interference (e.g., Doxycycline HCl for AST, Salicylic acid for ISE-Cl) and those that do not interfere. | "Same" is stated, indicating consistency. (Note: The table cut off the complete list for ISE-K and ISE-Na). | The device for point-of-care use demonstrates the same endogenous interference characteristics as the professional use device, thus meeting the safety and effectiveness profile. |
| Calibration Frequency | AST/Glucose/CRP: Each lot and as required following quality control procedures | ||
| ISE-CI/K/Na: 24 hours (main calibration); After ISE cleaning and maintenance, changing reagent bottles, replacing electrodes | Same as professional use | Calibration procedures are identical, ensuring consistent performance. | |
| Expected Values | Reference ranges provided for AST, Glucose, CRP, ISE-Cl, ISE-K, ISE-Na for different sample types and patient populations. | Same as professional use | Expected values are consistent, supporting the device's accuracy and reliability for clinical interpretation in the expanded use setting. |
Acceptance Criteria (Implicit Summary): The acceptance criteria are based on demonstrating substantial equivalence between the performance of the cobas c 111 analyzer and its reagents for the new point-of-care intended use and its established professional use, primarily by showing comparable precision, analytical sensitivity, measuring range, interference profiles, and method comparison results against a predicate device (Integra 400). The word "Same" is frequently used, indicating that the performance metrics achieved for the professional use are expected to be maintained for the point-of-care use. Significant deviations would require further justification or modification.
2. Sample Size Used for the Test Set and Data Provenance
The "test set" in this context refers to the samples used to evaluate the device's performance for the new point-of-care intended use. These samples are detailed in the "Method Comparison" section:
- Test Set Sample Sizes:
- AST: n = 333 (for point-of-care use)
- Glucose: n = 333 (for point-of-care use)
- CRP: n = 326 (for point-of-care use)
- ISE-Cl: n = 280 (for point-of-care use)
- ISE-K: n = 280 (for point-of-care use)
- ISE-Na: n = 280 (for point-of-care use)
- Data Provenance: The document does not explicitly state the country of origin for the data or whether the data was retrospective or prospective. However, the study focuses on in-vitro diagnostic performance using human serum, plasma, and urine samples. The nature of performance studies for in-vitro diagnostics typically involves prospective collection of samples or use of archived, de-identified human biological samples that cover the relevant measuring ranges.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
For in-vitro diagnostic devices like the cobas c 111 analyzer, "ground truth" and "experts" are typically interpreted differently than in imaging or AI-driven diagnostic studies.
- Ground Truth: The ground truth for this device is established by a reference method or a predicate device with a known and established measurement accuracy. In this case, the Integra 400 system is used as the comparative method. The values obtained from the Integra 400 are considered the reference or "ground truth" for comparison.
- Experts: The study design does not involve human experts establishing a diagnostic "ground truth" through interpretation. Instead, the "expertise" lies in the established analytical performance characteristics, calibration, and standardization of the Integra 400 and the rigorous laboratory practices followed during the study.
4. Adjudication Method for the Test Set
Adjudication methods (e.g., 2+1, 3+1) are typically relevant for studies where human readers or experts are interpreting results and consensus is needed to establish ground truth or resolve discrepancies, particularly in imaging or pathology.
- No Adjudication Method: For this type of in-vitro diagnostic device performance study, there is no mention or indication of an adjudication method. The comparison is quantitative between the device under test (cobas c 111) and the predicate device (Integra 400), based on measured numerical values. Statistical methods (e.g., Passing-Bablok regression, correlation coefficients) are used to analyze the agreement between the two methods, not an adjudication process.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, an MRMC comparative effectiveness study was not done.
MRMC studies are primarily used in diagnostic imaging or other fields where multiple human readers interpret cases, and the study aims to assess how an AI system might affect their performance (e.g., improving accuracy, reducing reading time). This submission is for an in-vitro diagnostic device, which outputs quantitative measurements, and its performance is evaluated through analytical correlation and precision, not human interpretation.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done
Yes, a standalone performance evaluation was done.
The data presented directly evaluates the performance of the cobas c 111 analyzer (an automated system performing the "algorithm" of chemical analysis) and its reagents without direct human intervention in the measurement process itself. The "human-in-the-loop" here refers to the operator initiating the test and interpreting the result, but the analytical performance data (precision, method comparison) reflects the device's inherent capability. The expansion to "point-of-care" suggests a different type of operator, but the core analytical engine operates independently for measurement.
7. The Type of Ground Truth Used
The type of ground truth used is based on comparison to a legally marketed predicate device (Integra 400) and established reference methods/standards.
- For method comparison, the results from the Integra 400 are considered the reference.
- For traceability and standardization, internationally recognized standards and methods are used (e.g., IFCC formulation for AST, ID/MS for Glucose, IRMM - BCR470/CRM470 for CRP, gravimetrically prepared primary calibrators for ISE). These constitute the ultimate "ground truth" for the accuracy of measurements.
8. The Sample Size for the Training Set
The document does not specify a training set sample size.
This is because the cobas c 111 is a clinical chemistry analyzer, not a machine learning or AI algorithm in the contemporary sense that learns from a training dataset. The "training" of such a device involves:
- Engineering design and optimization
- Method development for specific reagents
- Calibration using master calibrators.
The performance characteristics (measuring range, sensitivity, precision, interference) are established through analytical validation studies, not by training a computational model on a large dataset. The reagents themselves have defined formulations and reaction kinetics.
9. How the Ground Truth for the Training Set Was Established
As mentioned above, the concept of a "training set" and associated "ground truth" in the machine learning sense does not apply directly to this in-vitro diagnostic analyzer.
Instead, the analytical "ground truth" is established through:
- International standards and reference materials: Such as IFCC, ID/MS, and IRMM standards mentioned in the "Traceability/Standardization" section. These provide the accurate values for calibration and control materials.
- Validated reference methods: The Integra 400 itself is a validated instrument used as a comparison method, implying its results are considered accurate and reliable.
The device is calibrated using these standards and validated against reference instruments to ensure its measurements are accurate and consistent.
§ 862.1100 Aspartate amino transferase (AST/SGOT) test system.
(a)
Identification. An aspartate amino transferase (AST/SGOT) test system is a device intended to measure the activity of the enzyme aspartate amino transferase (AST) (also known as a serum glutamic oxaloacetic transferase or SGOT) in serum and plasma. Aspartate amino transferase measurements are used in the diagnosis and treatment of certain types of liver and heart disease.(b)
Classification. Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.