COBAS INTEGRA C 111

K063744 · Rochdiag · CIG · Jan 17, 2007 · Clinical Chemistry

Device Facts

• Record ID: K063744
• Device Name: COBAS INTEGRA C 111
• Applicant: Rochdiag
• Product Code: CIG · Clinical Chemistry
• Decision Date: Jan 17, 2007
• Decision: SESE
• Submission Type: Special
• Regulation: 21 CFR 862.1110
• Device Class: Class 2

Intended Use

In vitro test for the quantitative determination of total bilirubin in human serum and plasma on the cobas c 111 system. Measurements of the levels of bilirubin and organic compound formed during normal and abnormal destruction of red cells, is used in the diagnosis of liver, hemolytic hematological and metabolic disorders, including hepatitis and gall bladder block.

Device Story

Total Bilirubin Special is an in vitro diagnostic reagent used on the cobas c 111 analyzer. The system accepts human serum or plasma samples. The analyzer uses photometric analysis to measure bilirubin levels via a diazo-based chemical reaction. The cobas c 111 is a benchtop, random-access analyzer operated by professional laboratory staff in clinical environments. The device transforms optical absorbance data into quantitative concentration results through automated calculation against a calibration curve. Healthcare providers use these results to diagnose liver, hemolytic, hematological, and metabolic conditions. The device benefits patients by providing rapid, automated clinical chemistry testing to support timely medical decision-making.

Clinical Evidence

Bench testing only; design control activities and risk analysis performed to verify/validate modifications against predetermined acceptance criteria.

Technological Characteristics

Photometric chemistry analyzer; uses diazo reagent chemistry. Reagents: Sodium acetate buffer, sulfamic acid, hydrochloric acid, diazonium ion. Sensing: Absorbance photometry (tungsten/halogen lamp, 20W). Form factor: Benchtop. Connectivity: RS232C host interface. Software: Embedded Linux/vxWorks. Sterilization: N/A (reagent).

Indications for Use

Indicated for the quantitative determination of total bilirubin in human serum and plasma to aid in the diagnosis of liver, hemolytic, hematological, and metabolic disorders (e.g., hepatitis, gall bladder block).

Regulatory Classification

Identification

A bilirubin (total or direct) test system is a device intended to measure the levels of bilirubin (total or direct) in plasma or serum. Measurements of the levels of bilirubin, an organic compound formed during the normal and abnormal distruction of red blood cells, if used in the diagnosis and treatment of liver, hemolytic hematological, and metabolic disorders, including hepatitis and gall bladder block.

Predicate Devices

• K951595

Submission Summary (Full Text)

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K063744

JAN 1 7 2007

## Special 510(k) Summary

Purpose for Submission

Roche Diagnostics hereby submits this Special 510(k) to provide notification of modification to our Total Bilirubin Special test system. The reagent was originally cleared for use as:

- . COBAS INTEGRA Total Bilirubin Special K981632/A001
And modified as COBAS INTEGRA Total Bilirubin Special K063543 ● Modifications to the test systems include:

- Reagent application to the cobas c 111 analyzer .
- Other editorial labeling changes .

A full description of the differences and similarities between performance of Total Bilirubin Special on the COBAS INTEGRA 400 plus and cobas c 111 is described bclow.

The cobas c 111 analyzer is a new member of the COBAS INTEGRA® family of analyzers and will use reagents and calibrators identical to those of other INTEGRA analyzers. The cobas c 111 is a device modification of the current COBAS INTEGRA® 400 plus analyzer, cleared in a letter to file K951595. A full description of the differences and similarities between the two analyzers, software modifications and a summary of the design validation and verification activities for the modified software is included in this submission as part of the modifications to the Total Bilirubin Special test system.

In accordance with the FDA policy, new applications of previously cleared reagents to the cobas c 111 analyzer were completed, along with new labeling in the form of cobas c 111 package inserts. For all subsequent applications of previously cleared reagents, Roche Diagnostics is following the FDA guidance, Replacement Reagent and Instrument Family Policy - Dec 11, 2003, to demonstrate equivalence to the original reagent/instrument performance. Data will be available for FDA review upon request.

The additional labeling provided in this submission is for purposes of CLIA categorization.

Device Name Proprietary name: Total Bilirubin Special

Common name: Bilirubin total

Classification name: Bilirubin (total or direct) test system

Continued on next page

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| Establishment<br>Registration | The establishment registration number for Roche Diagnostics Gmbh Penzberg<br>is 9610529. | | | |
|-------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------|--------------------------------------------|------------------------|
| | The establishment registration number for Roche Diagnostics Corporation is<br>1823260. | | | |
| | The establishment registration number for Roche instrument Center (RIC) is<br>3003795116. | | | |
| Classification | The FDA has classified a discrete photometric chemistry analyzer in Class I. | | | |
| | Panel | Classification<br>Number | Classification<br>Name | Regulation<br>Citation |
| | 75 Clinical<br>Chemistry | CIG | Bilirubin (total or<br>direct) test system | 21 CFR 862.111<br>0 |
| Device<br>Description | The Total Bilirubin Special reagent is intended for use on the cobas c 111<br>analyzer for the quantitative determination of total or direct bilirubin in serum<br>and plasma.<br><br>The cobas c 111 analyzer is a partially automated, <i>in-vitro</i> diagnostic<br>analyzer capable of performing clinical chemistry, specific protein and<br>electrolyte tests. Analytes are measured photometrically or turbidimetrically;<br>the analyzer also has an optional ISE module for measuring sodium,<br>potassium and chloride.<br><br>The cobas c 111 instrument is a random access analyzer designed to be<br>operated on a bench top in the professional environment using a combination<br>of a photometric analysis unit and an optional ion selective electrodes (ISE). | | | |
| Performance<br>Standards | To date, no performance standards that affect this device have been finalized<br>under Section 514 of the Act. | | | |
| Intended use | In vitro test for the quantitative determination of total bilirubin in human<br>serum and plasma on the cobas c 111 system. | | | |
| Predicate<br>device | We claim substantial equivalence to the Total Bilirubin Special reagent<br>cleared as K063543. | | | |

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## Substantial equivalency-Similarities

The table below indicates the similarities and differences between the modified Bilirubin total reagent and its predicate device.

| Feature | Modified Device:<br>Total Bilirubin Special | Predicate device:<br>COBAS INTEGRA Total Bilirubin<br>Special, K063543 |
|----------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| General<br>Intended Use/<br>Indications for<br>Use | In vitro test for the quantitative<br>determination of total bilirubin in<br>human serum and plasma on the<br>cobas c 111 system. | The COBAS INTEGRA Total<br>Bilirubin Special (BILTS) cassette<br>contains an in vitro diagnostic<br>reagent system intended for use on<br>COBAS INTEGRA systems for the<br>quantitative determination of total<br>bilirubin in serum and plasma of<br>adults and neonates (test BILTS, 0-<br>985). |
| Specimen | serum and plasma | serum and plasma |
| Test Principle | | |
| Reference<br>method | Same | Diazo method |
| Reagent information | | |
| Reagent<br>composition | Same | R1: Sodium acetate buffer 85<br>mmol/L, Sulfamic acid 110 mmol/L<br>R2: Hydrochloric acid 100 mmol/L,<br>Diazonium ion 3 mmol/L |
| Stability - shelf<br>life and on-<br>board | 2-8 °C until expiration date<br>On-board 4 weeks | 2-8 °C until expiration date<br>COBAS INTEGRA 400/400 plus:<br>On-board at 10-15 °C 5 weeks<br>COBAS INTEGRA 700/800:<br>On-board at 8 °C 5 weeks |
| Calibrator | Same | Calibrator f.a.s. |
| Quality control | Same | Precinorm U, Precipath U<br>Precinorm U plus, Precipath U plus |
| Traccability | Same | Standardized against the Doumas<br>reference method |
| Performance characteristics | | |
| Precision | Within-run<br>1.79% @ 21.7 µmol/L<br>0.64% @ 64.2 µmol/L<br>2.94% @ 15.2 µmol/L<br>0.77% @ 60.0 µmol/L<br>Total<br>2.32% @ 21.6 µmol/L<br>0.71% @ 67.4 µmol/L<br>3.10% @ 16.2 µmol/L<br>0.79% @ 83.0 µmol/L | Within run:<br>2.44% @ 15.80 µmol/L<br>1.39% @ 54.00 µmol/L<br>Between day:<br>4.13% @ 14.7 µmol/L<br>2.15% @ 47.20 µmol/L |
| Measuring | 0.1-25.2 mg/dL | 0-25 mg/dL |
| Measuring range | 0.1-101 mg/dL (with postdilution) | 0-250 mg/dL (with postdilution) |
| Lower detection<br>limit | 0.1 mg/dL | 0.063 mg/dL |
| Expected values<br>(literature<br>reference) | Same | Adults and children: up to 1.0<br>mg/dL<br>Neonates:<br>Age of newborn Premature<br>24hrs: 1.0-6.0 mg/dL<br>48hrs: 6.0-8.0 mg/dL<br>3-5 days: 10.0-15.0 mg/dL<br>Age of newborn Full Term<br>24hrs: 2.0-6.0 mg/dL<br>48hrs: 6.0-7.0 mg/dL |
| Endogenous | Same | 3-5 days: 4.0-12.0 mg/dL<br>Hemolysis: No significant |
| interferences | | interference up to 1000 mg/dL<br>Lipemia: No significant interference<br>up to 1400 mg/dL as Intralipid |
| Exogenous<br>interferences | Same | Ascorbic acid at 30 mg/dL causes<br>artificially decreased total bilirubin<br>values |
| | | Analyzer |
| Topic | cobas c 111 Analyzer<br>(Modified Device) | COBAS INTEGRA® 400 plus<br>with ISE<br>(K951595) |
| | | Analyzer Description |
| Intended Use | The Roche cobas c 111 analyzer is<br>an in-vitro diagnostic analyzer<br>capable of performing clinical<br>chemistry, specific protein and<br>electrolyte tests. Analytes are<br>measured photometrically or<br>turbidimetrically; the analyzer also<br>has an optional ISE module for<br>measuring sodium, potassium and<br>chloride. | The Roche COBAS INTEGRA 400<br>plus is an automated in vitro<br>diagnostic analyzer capable of<br>performing general chemistry,<br>specific protein, electrolyte tests,<br>therapeutic drug, drug of abuse and<br>thyroid analyses. It is equipped with<br>modules for absorption photometry,<br>fluorescence polarization<br>photometry and potentiometry (ISE)<br>and works in conjunction with in<br>vitro diagnostic reagents. |
| Analyzer Description (continued) | | |
| Measurement<br>principle | • Absorbance Photometry<br>(enzymes, substrates,<br>proteins)<br>• ISE Potentiometry<br>(electrolytes) | • Absorbance Photometry<br>(enzymes, substrates,<br>proteins, DAT)<br>• Fluorescence Photometry<br>(TDM)<br>• ISE Potentiometry<br>(electrolytes) |
| Reaction<br>modes | Same | Endpoint, kinetic, potentiometric |
| Software SIMILARITIES | | |
| Software | cobas c 111 analyzer software | Cobas Integra® 400 plus Analyzer<br>Software |
| Configuration | Integrated bench top analyzer<br>(including Absorbance Photometer)<br>with optional ISE unit | Integrated benchtop analyzer (incl.<br>Abs, FP-Photometer & ISE module) |
| Functions<br>performed | Same | Data input, sample processing, result<br>calculation, result reporting, quality<br>control |
| Computer | Data management & user interaction | Data management & user interaction |
| Infrastructure | on cmbedded CPU with Linux | on PC based computer with |
| | operating analyzer | Windows XP operating analyzer |
| | Instrument management and real- | Instrument management and real- |
| | time control on cmbedded CPU with | time control on embedded CPU with |
| | vxWorks operating analyzer | vxWorks operating analyzer |
| Analytical | Same | Control of analytical processes |
| Functions | | (pipetting, incubation, detection), |
| | | primary signal processing |
| Data storage | Same but no patient demographies | Storage of analyzer and application |
| | are stored (due to less storage<br>capacity). | parameters, calibration data, QC |
| | | data, sample results, alarms, patient |
| | | demographics, service actions and |
| Result | Same | status information |
| calculation | | Automated measuring of signal for<br>kinetic and endpoint methods |
| | | according to cycle time and |
| | | automated calculation of |
| | | concentration via calibration curve |
| User | Same | User ID and password |
| management | | |
| Flagging of | Same | Available |
| errors | | |
| | | |
| Software DIFFFRENCES | | |
| Initial cassette | Not applicable: | |
| volume check | | Available |
| (ICVC) for | Instead of cassettes single bottles | |
| reagent | with liquid level detection are used | |
| pipetting | | |
| Data concept | Applications via barcode | |
| (Application | | Applications via diskette |
| parameter | | |
| transfer) | | |
| Data concept | Automatic QC when QC samples | Automatic QC with on board QC |
| (Cal/QC | are placed manually | samples |
| assigned values) | | |
| Analyzer Features | | |
| Throughput | Max 100 tests per hour | Max 400 tests per hour |
| Analyzer Size | Same but smaller | Integrated benchtop analyzer |
| Sample Handling | | |
| Typical sample | Typically 2 - 10 µL per test (same) | Typically 2 - 10 µL per test |
| volumes | ISE (serum, plasma): | ISE (serum, plasma): |
| | 25 µL (indirect mode) | 20 uL (indirect mode) |
| | ISE (urine): | 97 uL (direct mode) |
| | 25 µL (indirect mode): | ISE (urine):<br>20 µL (indirect mode): |
| Sample Types | Same, but not CSF | Serum, plasma, urine, CSF; whole blood and hemolysate for HbAlc |
| Sample<br>Handling<br>Analyzer | Sample area for samples, calibrators and controls. | Rack analyzer for samples, calibrators and controls. |
| Sample capacity<br>on board | 8 places for cups / tubes. | Up to six racks with max. 15 sample cups/tubes per rack on board. |
| Sample<br>identification | Same | ID- Barcode |
| Reagent Handling | | |
| Reagent<br>Volume | Same | 20 – 150 μL |
| Reagent<br>Container | Unisys 20mL bottle | Integra cassette / cobas c pack |
| Reagent<br>Container<br>(Electrolytes) | Same…