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.

Device Description

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.

AI/ML Overview

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 plasmaGlucose: serum and plasmaCRP: serum and plasmaISE-Cl: serum, plasma and urineISE-K: serum, plasma and urineISE-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, εGlucose: standardized against ID/MSCRP: 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/LGlucose: 0.11-40 mmol/LCRP: 1-200 mg/LISE-Cl: 20-250 mmol/LISE-K: 1-100 mmol/LISE-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/LGlucose: 0.11 mmol/LCRP: 1.0 mg/LISE-Cl: slope range -25 to -56 mV/decISE-K: slope range 45 to 63 mV/decISE-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/LGlucose: 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/dLCRP: 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/dLISE-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/LGlucose: 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/LCRP: 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/dLISE-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/LGlucose: 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/dLCRP: 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/dLISE-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/LGlucose: 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/LCRP: 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/dLISE-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 = 82Glucose: y = 1.02x - 0.009 mmol/L, $\tau$ = 0.983, n = 80CRP: y = 0.995x + 1.334 mg/L, $\tau$ = 0.970, n = 63ISE-Cl: y = 1.014x - 3.236 mmol/L, r = 0.982, n = 51ISE-K: y = 0.984x - 0.003 mmol/L, r = 1.000, n = 51ISE-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 = 333Glucose: y = 0.997x + 2.069 mg/dL, $\tau$ = 0.9217, n = 333CRP: y = 1.058x + 0.022 mg/L, $\tau$ = 0.9789, n = 326ISE-Cl: y = 1.011x - 0.51 mmol/L, $\tau$ = 0.7532, n = 280ISE-K: y = 0.943x + 0.189 mmol/L, $\tau$ = 0.8835, n = 280ISE-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 proceduresISE-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.

Summary

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K071211

JUL 3 0 2007

510(k) Summary

Introduction	According to the requirements of 21 CFR 807.92, the following information provides sufficient detail to understand the basis for a determination of substantial equivalence.
Submitter name, address, contact	Roche Diagnostics Operations9115 Hague RoadIndianapolis, IN 46250317-521-3831Contact Person: Corina HarperDate Prepared: April 2007
Device name	Proprietary name: cobas c 111 AnalyzerCommon name: Analyzer, Chemistry (Photometric, Discrete), for clinical useClassification name: Discrete photometric chemistry analyzer for clinical use
Establishment information	The establishment registration number for Roche Diagnostics Ltd. is 3003795116.The establishment registration number for Roche Diagnostics GmbH is 9610126.The establishment registration number for Roche Diagnostics Corporation is 1823260.
Classification	The FDA has classified a discrete photometric analyzer in Class I.
	Panel	Classification Number	Classification Name	Regulation Citation
	75 Clinical Chemistry	1	Discrete photometric chemistry analyzer for clinical use	21 CFR 862.2160

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Performancestandards	To date, no performance standards that affect this device have been finalizedunder Section 514 of the Act.
Submissionhistory	The cobas c111 analyzer is a member of the COBAS INTEGRA® family ofanalyzers cleared in the Total Bilirubin reagent submission as K063744. Thereagents applied to this analyzer are cleared reagents for the COBAS INTEGRAfamily of analyzers and were successfully applied to the cobas c 111 analyzerusing the Replacement Reagent and Instrument Family Policy - Dec 11, 2003, todemonstrate equivalence to the original reagent/instrument performance.
Devicemodification -Additionalindication forcobas c 111analyzer	The table below compares the additional intended use for the device, cobas c111 analyzer to the current device, cobas c 111 for professional use.

Performancestandards

To date, no performance standards that affect this device have been finalizedunder Section 514 of the Act.

Submissionhistory

The cobas c111 analyzer is a member of the COBAS INTEGRA® family ofanalyzers cleared in the Total Bilirubin reagent submission as K063744. Thereagents applied to this analyzer are cleared reagents for the COBAS INTEGRAfamily of analyzers and were successfully applied to the cobas c 111 analyzerusing the Replacement Reagent and Instrument Family Policy - Dec 11, 2003, todemonstrate equivalence to the original reagent/instrument performance.

Devicemodification -Additionalindication forcobas c 111analyzer

The table below compares the additional intended use for the device, cobas c111 analyzer to the current device, cobas c 111 for professional use.

Topic	cobas c 111 Analyzerprofessional use(K063744)	cobas c 111 Analyzerwith extended intendeduse
Analyzer Description
IntendedUse/Indications of 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

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Device modifications reagents comparison

The following table compares the panel of six assays performance characteristics on cobas c 111 analyzer for professional use with the point-ofcare use.

Feature	Reagent performancecharacteristics on cobas c 111analyzer for professional use	Reagentperformancecharacteristicsfor point-of-care use
Intended Use forrepresentativereagents	AST:In vitro test for the quantitative determinationof aspartate aminotransferase (AST) in humanserum and plasma on the cobas c 111 system.Glucose:In vitro test for the quantitative determinationof glucose in human serum and plasma on thecobas c 111 system.CRP:In vitro test for the quantitative determinationof C-reactive protein in human serum andplasma on the cobas c 111 system.ISE-C1:The chloride electrode for the cobas c 111system is intended for the quantitativedetermination of chloride in diluted serum,plasma and urine.ISE-K:The potassium electrode for the cobas c 111system is intended for the quantitativedetermination of chioride in diluted serum,plasma and urine.ISE-Na:The sodium electrode for the cobas c 111system is intended for the quantitativedetermination of chloride in diluted serum,plasma and urine.	Same
Instrument	cobas c 111 analyzer	Same
Operator	Professional setting	Point-of-caresetting
Sample type	AST: serum and plasmaGlucose: serum and plasmaCRP: serum and plasmaISE-Cl: serum, plasma and urineISE-K: serum, plasma and urineISE-Na: serum, plasma and urine	Same
Feature	Reagent performancecharacteristics on cobas c 111analyzer for professional use	Reagentperformancecharacteristicsfor point-of-careuse
Traceability/Standardization	AST: standardized against the originalIFCC formulation using calibrated pipettestogether with manual photometer providingabsolute values and the substrate-specific absorptivity, $ε$Glucose: standardized against ID/MSCRP: standardized against the referencepreparation of the IRMM - BCR470/CRM470 (RPPHS - Reference Preparationfor Proteins in Human Serum)ISE-Cl/K/Na: standardized against primarycalibrators prepared gravimetrically frompurified salts	Same
Measuring range	AST: 2-700 U/LGlucose: 0.11-40 mmol/LCRP: 1-200 mg/LISE-Cl: 20-250 mmol/LISE-K: 1-100 mmol/LISE-Na: 20-250 mmol/L	Same
Analyticalsensitivity(LDL)	AST: 2 U/LGlucose: 0.11 mmol/LCRP: 1.0 mg/LISE-Cl: slope range -25 to -56 mV/decISE-K: slope range 45 to 63 mV/decISE-Na: slope range 45 to 63 mV/dec	Same

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Device modifications – reagents comparison (continued)

Continued on next page

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Feature	Reagent performance characteristics on cobas c 111 analyzer for professional use	Reagent performance characteristics for point-of-care use
PrecisionWithin run(CV%/SD)	ASTHuman Sera :SD 0.37 at 26.2 U/L0.5% at 221 U/LControls:1.1% at 39.7 U/L0.4% at 123 U/L	Human sera:SD 0.78 at 18.98 U/L2.07% at 46.92 U/LControls:1.99% at 41.05 U/L0.63% at 137.93 U/L
	GlucoseHuman Sera:SD 0.5 at 40.9 mg/dL0.8% at 180 mg/dLControls:1.0% at 90.6 mg/dL0.5% at 252 mg/dL	Human sera:0.56% at 89.14 mg/L0.63% at 168.29 mg/LControls:0.63% at 96.11 mg/L0.66% at 255.47 mg/L
	CRPHuman Sera:SD 0.01 at 0.42 mg/dL1.3% at 23.4 mg/dLControls:0.8% at 1.83 mg/dL0.6% at 3.77 mg/dL	Human sera:SD 0.072 at 0.356 mg/dL1.15%-- 0t 0.554 mg/dL1.23% at 2.385 mg/dLControls:0.68% at 0.842 mg/dL0.41% at 4.792 mg/dL
	ISE – ClHuman Sera:0.30% at 97 mmol/L0.24% at 1.27 mmol/LPlasma:0.29% at 93 mmol/L	Human sera:0.72% at 109.03 mmol/L0.72% at 98.55 mmol/LControls:SD 0.43 at 86.22 mmol/L

Device modifications – reagents comparison (continued)

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Feature	Reagent performancecharacteristics on cobas c111 analyzer forprofessional use	Reagent performancecharacteristics for point-of-care use
PrecisionWithin run(CV%)	ISE - KHuman Sera:0.49% at 2.1 mmol/L0.40% at 5.7 mmol/LPlasma:0.41% at 2.0 mmol/L0.32% at 60. mmol/L	Human sera:0.79% at 4.65 mmol/L0.71% at 4.69 mmol/LControls:0.47% at 3.465 mmol/LSD 0.040 at 6.621 mmol/L
	ISE - NaHuman Sera:0.32% at 130 mmol/L0.31% at 156 mmol/LPlasma0.31% at 127 mmol/L0.30% at 151 mmol/L	Human sera:0.59% at 144.69 mmol/L0.61% at 133.70 mmol/LControls:0.39% at 126.66 mmol/L0.41% at 150.50 mmol/L
PrecisionTotal(CV%/SD unit)	ASTHuman Sera:SD 0.64 at 19.5 U/L1.0% at 306 U/LControls:2.4% at 38.6 U/L0.9% at 126 U/L	Human sera:SD 1.2 at 16.4 U/L3.7% at 48.7 U/LControls:3.3% at 40.24 U/L2.2% at 137.04 U/L
	GlucoseHuman Sera:SD 0.2 at 45.4 mg/dL0.6% at 178 mg/dLControls:0.7% at 92.3 mg/dL0.5% at 254 mg/dL	Human sera:2.6% at 97.5 mg/L2.8% at 130.7 mg/LControls:2.5% at 93.03 mg/L2.5% at 247.08 mg/L

Device modifications - reagents comparison (continued)

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Feature	Reagent performance characteristics on cobas c111 analyzer forprofessional use	Reagent performance characteristics forpoint-of-care use
PrecisionTotal(CV%/SD unit)	CRPHuman Sera:SD 0.01 at 0.47 mg/dL2.6% at 2.33 mg/dLControls:2.1% at 1.86 mg/dL1.6% at 3.84 mg/dL	Human sera:3.7% at 4.044 mg/dL3.2% at 4.670 mg/LControls:2.6% at 0.835 mg/dL2.9% at 4.764 mg/dL
	ISE – Cl (Between-run)Human sera:0.44% at 97 mmol/L0.48% at 128 mmol/LPlasma (Between-run):0.51% at 93 mmol/L0.67% at 125 mmol/L	Human sera:1.4% at 104.7 mmol/L1.6% at 104.6 mmol/LControls:SD 2.0 at 87.16 mmol/L2.0% at 119.97 mmol/L
	ISE – K (Between –run)Human Sera:0.45% at 2.1 mmol/L0.30% at 5.7 mmol/LPlasma (Between-run)0.78% at 2.0 mmol/L0.72% at 6.0 mmol/L	Human sera:1.4% at 4.465 mmol/L1.6% at 4.540 mmol/LControls:1.8% at 3.466 mmol/LSD 1.8 at 6.646 mmol/L
	ISE – Na (Between-run)Human Sera:0.42% at 130 mmol/L0.48% at 155 mmol/LPlasma:0.80% at 128 mmol/L0.75% at 151 mmol/L	Human sera:1.6% at 139.9 mmol/L1.6% at 131.6 mmol/LControls:1.8% at 126.48 mmol/L1.7% at 151.0 mmol/L
Feature	Reagent performancecharacteristics on cobas c111 analyzer for professionaluse	Reagent performancecharacteristics forpoint-of-care use
Limitations -interferences	AST:Bilirubin- no interference up to Iindex of 67 (conjugated) and Iindex of 65 (unconjugated)Hemolysis: elevated results withcontamination of erythrocytesLipemia: interferencesAnticoagulants: citrate andfluoride interfereGlucose:Bilirubin– no interference up to Iindex of 67 (conjugated orunconjugated)Hemolysis: no interference up to Hindex of 1046Lipemia: no interference up to Lindex of 2126CRP:Bilirubin– no interference up to Iindex of 60 (conjugated orunconjugated)Hemolysis: no interference up to Hindex of 700Lipemia: no interference up to Lindex of 700Rheumatoid factors up to 1200IU/mL do not interfereNo high dose hook-effect is seen upto a CRP concentration of 3100mg/L	Same
Feature	Reagent performancecharacteristics on cobas c111 analyzer for professionaluse	Reagent performancecharacteristics forpoint-of-care use
Limitations -interferences	ISE-Cl:Serum/Plasma:Hemolysis: Avoid hemolyzedsamples. No significantinterferences up to ahemoglobin level of 10 g/LBilirubin/Lipemia: Nosignificant interferences	Same
	ISE-K:Serum/Plasma:Hemolysis: Avoid hemolyzedsamples. No significantinterferences up to ahemoglobin level of 1 g/L.Potassium centration inerythrocytes is 25 times higherthan in normal plasma. Thelevel of interference may bevariable depending on theexcat content of erythrocytes.Bilirubin/Lipemia: Nosignificant interferences
	ISE-Na:Serum/Plasma:Hemolysis: Avoid hemolyzedsamples. No significantinterferences up to ahemoglobin level of 10 g/LBilirubin/Lipemia: Nosignificant interferences
Feature	Reagent performancecharacteristics on cobas c111 analyzer for professionaluse	Reagent performancecharacteristics forpoint-of-care use
Endogenousinterferences	AST:No interferences found usingcommon drug panel, except:Doxycycline HCl causes artificiallylow resultsGlucose:No interferences found usingcommon drug panel.CRP:No interferences found usingcommon drug panel.ISE-Cl:Serum/Plasma:Panel of drugs tested causes nosignificant interferencesSalicylic acid in concentration of 5mmol/L causes artificially elevatedresultsUrine:Panel of drugs tested causes nosignificant interferences, except:Salicylic acid, Ca-dobesilate and Na-cefoxitin which causes artificiallyelevated Cl concentrationsISE-K:Serum/Plasma:	Same
	Panel of drugs tested causes nosignificant interferences up to theindicated concentration.Urine:Panel of drugs tested causes nosignificant interferences up to theindicated concentration.
Feature	Reagent performancecharacteristics on cobas c111 analyzer for professionaluse	Reagent performancecharacteristics forpoint-of-care use
Endogenousinterferences	ISE-Na:Serum/Plasma:Panel of drugs tested causes nosignificant interferences up tothe indicated concentration.Urine:Panel of drugs tested causes nosignificant interferences up tothe indicated concentration.pH – Acidified urines can givefalse results.	Same
Calibrationfrequency	AST/Glucose/CRP:Each lot and as requiredfollowing quality controlproceduresISE-CI/K/Na:24 hours (main calibration)After ISE cleaning andmaintenance, changing reagentbottles, replacing electrodes	Same
Feature	Reagent performancecharacteristics oncobas c 111 analyzerfor professional use	Reagent performancecharacteristics forpoint-of-care use
Method ComparisonProfessional usey = cobas c 111x = Integra 400	AST:Passing Bablok:y = 0.989x + 1.869 U/L$\tau$ = 0.981n = 82	AST:Passing Bablok:y = 0.989x + 1.276 U/L$\tau$ = 0.8316n = 333
Point-of-care use:y = cobas c 111x = Integra 400	Glucose:y = 1.02x - 0.009mmol/L$\tau$ = 0.983n = 80	Glucose:y = 0.997x + 2.069 mg/dL$\tau$ = 0.9217n = 333
	CRP:y = 0.995x + 1.334 mg/L$\tau$ = 0.970n = 63	CRP:y = 1.058x + 0.022 mg/L$\tau$ = 0.9789n = 326
	ISE-Cl:y = 1.014x - 3.236mmol/Lr = 0.982n = 51	ISE-Cl:y = 1.011x - 0.51 mmol/L$\tau$ = 0.7532n = 280
	ISE-K:y = 0.984x - 0.003mmol/Lr = 1.000n = 51	y = 0.943x + 0.189 mmol/L$\tau$ = 0.8835n = 280
	ISE-Na:y = 0.986x - 0.364mmol/L$\tau$ = 0.983n = 51	ISE-Na:y = 1.064x - 9.818 mmol/L$\tau$ = 0.6920n = 280
Feature	Reagent performance characteristics on cobas c 111 analyzer for professional use	Reagent performance characteristics for point-of-care use
Expected values(from reference)(also please reference methodsheet)	AST:Female: up to 32 U/LMales: up to 38 U/LGlucose:Plasma fasting: 3.88-6.38 mmol/LSerum/Plasma Adults: 4.11-5.89 mmol/LCRP:Adults: less than 5 mg/LISE-C1:Serum/Plasma (adults): 98-107 mmol/LUrine (24h, adults): 110-250 mmol/LISE-K:Serum (adults): 3.5-5.1 mmol/LPlasma (adults): 3.4-4.5 mmol/LUrine (24h, adults) 25-125 mmol/LISE-Na:Serum (adults): 136-145 mmol/LPlasma (adults): 136-145 mmol/LUrine (24h, adults): 40-220 mmol/L	Same

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/13/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle with three stripes forming its body and wings. The eagle is positioned inside a circle, and the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is written around the circle's perimeter. The text is in all capital letters.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Roche Diagnostics Corporation c/o Corina Harper, Regulatory Affairs Consultant 9115 Hague Road Indianapolis, IN 46250

JUL 3 0 2007

Re: K071211 Trade/Device Name: cobas c 111 analyzer and applied reagents Regulation Number: 21 CFR 862.1100 Regulation Name: Aspartate amino transferase (AST/SGO) test system Regulatory Class: Class II Product Code: CIT, CFR, DCN, CEM, CGZ, JGS, JJE Dated: April 30, 2007 Received: May 1, 2007

Dear Ms. Harper:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food. Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA), You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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Page 2 --

This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific information about the application of labeling requirements to your device. or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240) 276-0490. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (240) 276-3150 or at its Internet address at http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours.

Jean M. Cooper, M.S., D.V.M.

Yean M. Cooper, M.S., D.V.M. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known):

Device Name: cobas c 111 analyzer and applied reagents

Indications For Use:

cobas c 111 analyzer:

Analytes are measured photometrically or turbidimetrically; the analyzer also has an optional ISE module for measuring sodium, potassium and chloride.

Reagents:

Prescription Use XXXX (Part 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use (21 CFR 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

CarolC. Benam

Sign-O

്ffice of In Vitro Diagnostic Device Evaluation and Safety

K071211

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Indications for Use

510(k) Number (if known): _ K071211

Device Name: cobas c 111 analyzer and reagents

Indications For Use:

C-Reactive Protein Latex (CRPLX)

Glucose HK (GLUC2)

ISE Chloride Electrode

Prescription Use XXXX (Part 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use (21 CFR 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Carol C. Benson
on Sign-Off

Page 2 of 3

ice of In Vitro Diagnostic Device Juation and Safety

K071211

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Indications for Use

510(k) Number (if known):

Device Name: cobas c 111 analyzer and reagents

Indications For Use:

ISE Potassium Electrode

ISE Sodium Electrode

Prescription Use XXXX (Part 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use (21 CFR 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Page 3 of 3

Sign-Off

be of In Vitro Diagnostic Device uation and Safety

4071211

Regulation Number and Section

§ 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.