TOTAL PROTEIN URINE/CSF GEN.3

K141925 · Roche Diagnostics Operations (Rdo) · JIQ · Dec 9, 2014 · Clinical Chemistry

Device Facts

• Record ID: K141925
• Device Name: TOTAL PROTEIN URINE/CSF GEN.3
• Applicant: Roche Diagnostics Operations (Rdo)
• Product Code: JIQ · Clinical Chemistry
• Decision Date: Dec 9, 2014
• Decision: SESE
• Submission Type: Special
• Regulation: 21 CFR 862.1645
• Device Class: Class 1

Intended Use

The Total protein Urine/CSF Gen.3 is an in vitro test for the quantitative determination of total protein in human urine and cerebrospinal fluid (CSF) on Roche/Hitachi cobas c systems.

Device Story

TPUC3 Total Protein Urine/CSF Gen.3 is an in vitro diagnostic assay for quantitative protein measurement in human urine and CSF. Used on Roche COBAS Integra 400 plus analyzer; operates via turbidimetric method. Reagents (Sodium Hydroxide, EDTA-Na, Benzethonium chloride) react with protein samples to produce turbidity proportional to protein concentration. Analyzer measures turbidity; results provided to clinicians for diagnosis/treatment of renal, heart, thyroid, or CNS disorders. Modification adds interference limitations for radiopaque media (>6.4 g/L organically bound iodine) and homogentisic acid (>1.2 mmol/L). No high-dose hook effect up to 100 g/L. Benefits include accurate protein quantification to support clinical decision-making in disease management.

Clinical Evidence

Bench testing only. Verification and validation activities focused on interference testing for organically bound iodine, homogentisic acid, and hook effect to support updated labeling.

Technological Characteristics

Turbidimetric assay; reagents include Sodium Hydroxide (677 mmol/L), EDTA-Na (74 mmol/L), and Benzethonium chloride (32 mmol/L). Designed for use on COBAS Integra 400 plus analyzer. Measuring range 40-2000 mg/L. Standardized against NIST SRM-927. Connectivity via automated analyzer platform.

Indications for Use

Indicated for the quantitative determination of total protein in human urine and cerebrospinal fluid (CSF) for diagnostic purposes.

Regulatory Classification

Identification

A urinary protein or albumin (nonquantitative) test system is a device intended to identify proteins or albumin in urine. Identification of urinary protein or albumin (nonquantitative) is used in the diagnosis and treatment of disease conditions such as renal or heart diseases or thyroid disorders, which are characterized by proteinuria or albuminuria.

Predicate Devices

• Total protein Urine/CSF Gen.3 (K071239)

Submission Summary (Full Text)

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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

ROCHE DIAGNOSTICS OPERATIONS (RDO) PATRICK STIMART REGULATORY AFFAIRS CONSULTANT 9115 HAGUE ROAD INDIANAPOLIS IN 46250

December 9, 2014

Re: K141925

Trade/Device Name: TPUC3 Total Protein Urine/CSF Gen.3 Regulation Number: 21 CFR 862.1645 Regulation Name: Urinary protein or albumin (nonquantitative) test system Regulatory Class: I exempt, meets limitations of exemptions per 862.9 (c)(1)(4) Product Code: JIO Dated: November 7, 2014 Received: November 10, 2014

Dear Mr. Patrick Stimart:

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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. 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); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number [phone] or [phone] or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled. "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number [phone] or [phone] or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

# Katherine Serrano -S

For : Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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#### Indications for Use

510(k) Number (if known) k141925

Device Name Total Protein Urine/CSF Gen.3

#### Indications for Use (Describe)

In vitro test for the quantitative determination of the total protein concentration in urine and cerebral spinal fluid.

Protein measurements in urine are used in the diagnosis and treatment of disease conditions such as renal or heart diseases, or thyroid disorders.

CSF protein measurements are used in the diagnosis and treatment of conditions such as meningitis, brain tumors, and infections of the central nervous systems.

| Type of Use (Select one or both, as applicable) | |
|---------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------|
| <div> <span> Prescription Use (Part 21 CFR 801 Subpart D) </span> </div> | <div> <span> Over-The-Counter Use (21 CFR 801 Subpart C) </span> </div> |

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| Introduction | The following information provides sufficient detail to understand the basis for a<br>determination of substantial equivalence according to the requirements of 21 CFR<br>807.92.<br>Note: There were no prior submissions for this device for which FDA provided<br>feedback related to the data or information needed to support substantial<br>equivalence. | | | |
|---------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------|--|--|
| Applicant | This Special 510(k) premarket notification was prepared by Patrick Stimart from<br>Roche Professional Diagnostics Regulatory Affairs and submitted on July 15, 2014. | | | |
| | Roche Diagnostics Operations<br>c/o Patrick Stimart, Regulatory Affairs<br>PO Box 50416<br>Indianapolis IN 46250-0416 | | | |
| | Phone: [phone]<br>Fax: [phone]<br>e-mail: patrick.stimart(@roche.com | | | |
| Candidate<br>device | Proprietary name: TPUC3 Total Protein Urine/CSF Gen.3<br>Common name: Total Protein Urine/CSF | | | |
| Measurand | Total Protein | | | |
| Predicate<br>device | The candidate device is a modification of the predicate device. The device name,<br>TPUC3 Total Protein Urine/CSF Gen.3, is unchanged from how it was cleared in<br>510(k) K071239. | | | |
| Regulatory | Table 1: Regulatory Classification of Candidate Device | | | |
| classification of | Device Classification Name | Urinary protein or albumin test system | | |
| device | Produce Code | JIQ | | |
| | Device Class | ]* | | |
| | Regulation | 862.1645 | | |
| | Panel | Clinical Chemistry | | |
| | | | | |

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| Regulatory<br>classification of<br>device<br>(Continued) | * Although the regulation for this assay lists it as Class I, exempt from 510(k)<br>requirements, a 510(k) submission is required because the Total Protein Urine/CSF<br>Gen.3 assay meets the limitations for exemption found in 21 CFR 862.9 (c) 1 and 4. |
|----------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Device<br>description | The Total Protein Urine/CSF assay provides quantitative measurement of total<br>protein that is present in human urine and cerebral spinal fluid (CSF). Measurement<br>is accomplished using a turbidimetric method.<br>Reagents for the COBAS Integra 400 plus analyzer are packaged in a cobas c pack<br>with two bottles labeled with their instrument positioning, Reagent R1 in position B<br>and Reagent SR in position C.<br>R1 contains Sodium Hydroxide: 677 mmol/L; EDTA-Na: 74 mmol/L<br>SR contains Benzethonium chloride: 32 mmol/L |
| Intended<br>use/indications<br>for use | In vitro test for the quantitative determination of the total protein concentration in<br>urine and cerebral spinal fluid.<br>Protein measurements in urine are used in the diagnosis and treatment of disease<br>conditions such as renal or heart diseases, or thyroid disorders.<br>CSF protein measurements are used in the diagnosis and treatment of conditions<br>such as meningitis, brain tumors and infections of the central nervous systems.<br>Note: The intended use of the modified device, as described in its labeling, has not<br>changed as a result of the modification. |
| Special<br>conditions for<br>use | For prescription use only |
| Special<br>instruments<br>required | For use on the Roche COBAS Integra 400 plus analyzer |
| | Continued on next page |

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| Device<br>modification | The candidate device, Total Protein Urine/CSF Gen.3, has been modified from the<br>predicate device with the addition of the following information to the Limitations-<br>interferences section of the labeling:<br>Patient samples containing greater than 6.4 g/L of organically bound iodine<br>from Radiopaque media (e.g. Hexabrix) may have falsely elevated results. High levels of homogentisic acid can be found in the urine of patients with<br>the rare genetic disorder Alkaptonuria10. Homogentisic acid in urine<br>samples at concentration greater than 1.2 mmol/L can cause falsely elevated<br>results. There is no high dose hook effect at protein concentrations up to 100 g/L. |
|------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
|------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|

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| Feature | Predicate Device | Candidate Device | |
|---------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------|
| | Total Protein Urine/CSF<br>Gen.3 | Total Protein Urine/CSF<br>Gen.3 | |
| | In vitro test for the<br>quantitative determination of<br>the total protein concentration<br>in urine and cerebrospinal<br>fluid on COBAS INTEGRA<br>systems. | same | |
| Intended<br>use/indications for<br>use | Protein measurements in<br>urine are used in the<br>diagnosis and treatment of<br>disease conditions such as<br>renal or heart diseases, or<br>thyroid disorders, which are<br>characterized by proteinuria<br>or albuminuria.<br>CSF protein measurements<br>are used in the diagnosis and<br>treatment of conditions such<br>as meningitis, brain tumors<br>and infections of the central<br>nervous systems. | same | |
| Test principle | Turbidimetric method | same | |
| Sample volume | 10 µL | same | |
| Sample types | Urine and cerebral spinal<br>fluid (CSF) | same | |
| Reagents | R1: Sodium hydroxide 677<br>mmol/L; EDTA-Na 74<br>mmol/L<br>SR: Benzethonium chloride<br>32 mmol/L | same | |
| Similarities,<br>continued | Feature | Predicate Device | Candidate Device |
| Table 4: Similarities between Predicate and Candidate Devices | | | |
| | Total Protein Urine/CSF<br>Gen.3 | Total Protein Urine/CSF<br>Gen.3 | |
| | Calibration<br>interval | COBAS INTEGRA 400 plus<br>system:<br>• each cobas c pack<br>• every 43 days<br>• as required following<br>quality control<br>procedures | same |
| | Traceability | Traceability: This method has<br>been standardized against the<br>National Bureau of Standards<br>Reference Material SRM-927<br>using the biuret method for<br>the quantitation of protein. | same |
| | Reagent stability | Shelf life at 15-25 °C<br>See expiration date on cobas<br>c pack label<br>COBAS INTEGRA 400 plus<br>system<br>On-board in use at 10-15 °C<br>12 weeks | same |
| | Measuring range | 40-2000 mg/L (4-200mg/dL) | same |
| | Lower detection<br>limit | 40 mg/L (4 mg/dL) | same |
| | Expected values | Urine: 24h: < 150 mg/24 h<br>CSF: 150-450 mg/L<br>(15-45 mg/dL)<br>Each laboratory should<br>investigate the transferability<br>of the expected values to its<br>own patient population and if<br>necessary determine its own<br>reference ranges. | same |
| Feature | Predicate Device | Candidate Device | |
| | Total Protein Urine/CSF<br>Gen.3 | Total Protein Urine/CSF<br>Gen.3 | |
| Instrument<br>platform | COBAS Integra<br>400/400+/700/800 | COBAS Integra 400+ | |
| Calibrator | C.f.a.s. TPUC 200 | C.f.a.s. PUC | |
| Controls | Use commercially available<br>urine and CSF protein<br>controls or other suitable<br>control material.<br>See predicate method sheet | Precinorm PUC, Precipath<br>PUC<br>In addition, other suitable<br>control material can be used. | |
| Limitations –<br>interference | | Same as predicate except for<br>the following additions:<br>Patient samples containing<br>greater than 6.4 g/L of<br>organically bound iodine<br>from Radiopaque media (e.g.<br>Hexabrix) may have falsely<br>elevated results.<br>High levels of homogentisic<br>acid can be found in the urine<br>of patients with the rare<br>genetic disorder<br>Alkaptonuria10.<br>Homogentisic acid in urine<br>samples at concentration<br>greater than 1.2 mmol/L can<br>cause falsely elevated results.<br>There is no high dose hook<br>effect at protein<br>concentrations up to 100 g/L. | |

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#### Differences

#### Table 5: Differences between Predicate and Candidate Devices

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| Summary of<br>performance<br>data | Based on the risk analysis, the modifications to the Total Protein Urine/CSF Gen.3<br>did not introduce any new risks to the performance of the assay.<br>To address the modifications, performance data from verification and validation<br>testing demonstrated that all of the acceptance criteria were met. |
|-------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Testing of<br>interference by<br>radiopaque<br>media | Testing is performed in pooled human urine samples at two different total protein<br>levels on the Integra 400 plus analyzer. Each level is spiked with varying levels of<br>the radiopaque media Hexabrix containing organically bound iodine (10 dilution<br>steps per level) which were tested in triplicate and the median value was used to<br>calculate % deviation from expected concentration. |
| | Acceptance criterion: Deviation $≤ ± 10 %$ |
| | Results: At an organically bound Iodine concentration of 6.4 g/L;<br>Deviation = 5.6 % at level 1 (92.5 mg/L total protein)<br>Deviation = 9.7 % at level 2 (961 mg/L total protein) |
| | The results meet the criterion of $≤ ± 10 %$ deviation at all concentrations tested up to<br>and including 6.4 g/L of organically bound iodine, and thus support the claim of no<br>interference up to 6.4 g/L of organically bound iodine from Radiopaque media. |
| Testing of<br>interference by<br>Homogentisic<br>acid | The same protocol as described for radiopaque media above except that human urine<br>samples were spiked with homogentisic acid instead of Hexabrix.<br>Acceptance criterion: Deviation $≤ ± 10 %$ |
| | Results: At a homogentisic acid concentration of 1.2 mmol/L;<br>Deviation = 6.8 % at level 1 (107 mg/L total protein)<br>Deviation = 6.9 % at level 2 (1180 mg/L total protein) |
| | The results meet the criterion of $≤± 10 %$ deviation at all concentrations tested up to<br>and including 1.2 mmol/L of homogentisic acid, and thus support the claim of no<br>interference up to 1.2 mmol/L of homogentisic acid. |

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| Testing for high<br>dose hook effect | A pooled human urine sample was spiked with human Albumin up to a total protein<br>concentration of 100 g/L. A dilution series was prepared by diluting the sample with<br>un-spiked pooled human urine sample. The samples were tested in triplicate. The<br>median was calculated. |
|--------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | Acceptance criterion:<br>No false result reported up to a protein concentration 100 g/L.<br>All samples above the measuring range are flagged. |
| | Results: No false result reported up to a protein concentration up to 100 g/L.<br>All samples above the measuring range are flagged as either being above the<br>measuring range or above the absorbance limit. |
| | The results meet the criterion of no false result reported up to a protein concentration<br>100 g/L, and thus support the claim that there is no high dose hook effect at protein<br>concentrations up to 100 g/L. |
| Conclusion | The submitted information in this premarket notification supports a substantial<br>equivalence decision. The differences between predicate and candidate do not<br>impact the indications for use or technological characteristics. |