Elecsys TSH assay, cobas e 801 Immunoassay analyzer

K162606 · Roche Diagnostics · JLW · Jan 23, 2017 · Clinical Chemistry

Device Facts

• Record ID: K162606
• Device Name: Elecsys TSH assay, cobas e 801 Immunoassay analyzer
• Applicant: Roche Diagnostics
• Product Code: JLW · Clinical Chemistry
• Decision Date: Jan 23, 2017
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1690
• Device Class: Class 2

Intended Use

cobas e 801 immunoassay analyzer is intended for the in-vitro determination of analytes in body fluids. Elecsys TSH immunoassay is intended for the in vitro quantitative determination of thyrotropin in human serum and plasma. Measurements of TSH are used in diagnosis of thyroid or pituitary disorders. The Elecsys TSH immunoassay is an electrochemiluminescence immunoassay "ECLIA", which is in intended for use on the cobas e immunoassay analyzers.

Device Story

The cobas e 801 is a fully automated, modular immunoassay analyzer using electrochemiluminescence (ECLIA) technology. It processes human serum and plasma samples to quantify TSH levels. The system utilizes biotinylated monoclonal anti-TSH antibodies and ruthenium-labeled anti-TSH antibodies with streptavidin-coated microparticles. Samples are transported via universal racks to the analytical module; the system performs automated pipetting, incubation at 37°C, and signal detection via photomultiplier. The device provides quantitative results used by clinicians to diagnose thyroid and pituitary disorders. It features higher throughput (300 tests/hour/module) compared to the predicate, with electronic reagent management via RFID and cobas link. The system is intended for professional use in clinical laboratory settings.

Clinical Evidence

Bench testing only. Precision evaluated per CLSI EP05-A3 (CVs 1.3-11.3%). Linearity assessed per CLSI EP6-A (Pearson's r 0.9986-0.9994). Analytical sensitivity: LoB 0.0025 µIU/mL, LoD 0.005 µIU/mL, LoQ 0.005 µIU/mL. Interference testing confirmed no impact from common endogenous substances (lipids, biotin, bilirubin, hemoglobin, RF, IgG, IgM) or 16 common drugs. Method comparison with 130 samples showed high correlation (Passing/Bablok slope 0.936, Pearson's r 0.999).

Technological Characteristics

Electrochemiluminescence immunoassay (ECLIA) technology. Uses biotinylated monoclonal anti-TSH antibodies and ruthenium-labeled monoclonal anti-TSH antibodies with streptavidin-coated microparticles. Throughput: 300 tests/hour/module. Sample volume: 4-60 µL. Incubation: 37°C. Detection: Photomultiplier. Reagent ID: RFID. Connectivity: cobas link for electronic application transfer. Software: cobas 8000 modular system software.

Indications for Use

Indicated for the quantitative determination of thyrotropin (TSH) in human serum and plasma to aid in the diagnosis of thyroid or pituitary disorders. No specific age or gender restrictions are noted.

Regulatory Classification

Identification

A thyroid stimulating hormone test system is a device intended to measure thyroid stimulating hormone, also known as thyrotrophin and thyrotrophic hormone, in serum and plasma. Measurements of thyroid stimulating hormone produced by the anterior pituitary are used in the diagnosis of thyroid or pituitary disorders.

Predicate Devices

• Elecsys 2010/ Elecsys TSH (K961491)

Submission Summary (Full Text)

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Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized caduceus symbol, which is often associated with healthcare. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the caduceus.

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

January 23, 2017

ROCHE DIAGNOSTICS ANGELO PEREIRA REGULATORY AFFAIRS SENIOR PROGRAM MANAGER 9115 HAGUE ROAD INDIANAPOLIS, IN 46250 US

Re: K162606

Trade/Device Name: Elecsys TSH assay, Cobas e 801 immunoassay Analyzer Regulation Number: 21 CFR 862.1690 Regulation Name: Thyroid stimulating hormone test system Regulatory Class: Class II Product Code: JWL, JJE Dated: December 20, 2016 Received: December 21, 2016

Dear Angelo Pereira:

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

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electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), 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" (21CFR 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) k162606

Device Name cobas e 801 immunoassay Analyzer Elecsys TSH assay

### Indications for Use (Describe)

cobas e 801 immunoassay analyzer is intended for the in-vitro determination of analytes in body fluids.

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

| Type of Use (Select one or both, as applicable) | |
|-----------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------|
| <span> <span style="font-size: 16px;">☑</span> Prescription Use (Part 21 CFR 801 Subpart D) </span> | <span> <span style="font-size: 16px;">☐</span> Over-The-Counter Use (21 CFR 801 Subpart C) </span> |

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# Cobas e 801analyzer —Elecsys TSH

# 510(k) Summary

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR 807.92.

| Submitter Name | Roche Diagnostics |
|----------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Address | 9115 Hague Road<br>P.O. Box 50416<br>Indianapolis, IN 46250-0416 |
| Contact | Angelo Pereira<br>Phone: [phone]<br>FAX: [phone]<br>Email: [e-mail] |
| Date Prepared | January 23, 2017 |
| Proprietary Name | cobas e 801 Immunoassay analyzer;<br>Elecsys TSH assay |
| Common Name | Immunoassay analyzer;<br>Thyroid-stimulating hormone test system |
| Classifications | 21CFR862.2160, Chemistry analyzer; Class I<br>21CFR862.1690, Thyroid-stimulating hormone test system Class II |
| Product Codes | JJE<br>JLW |
| Predicate Devices | Elecsys 2010/ Elecsys TSH K961491 |
| Establishment Registration | For cobas e 801 and Elecsys TSH, the establishment registration number for<br>Roche Diagnostics GmbH in Mannheim, Germany is 9610126, and for Penzberg,<br>Germany, 9610529. The establishment registration number for Roche<br>Diagnostics in the United States is 1823260. |

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#### DEVICE DESCRIPTION 1.

The cobas e 801 immunoassay analyzer is a fully automated, software controlled analyzer system for in vitro determination of analytes in human body fluids. It is part of the cobas 8000 modular analyzer series cleared under K100853. It uses electrochemiluminescent technology for signal generation and measurement.

#### INTENDED USE 2.

cobas e 801 immunoassay analyzer is intended for the in vitro determination of analytes in body fluids.

Elecsys TSH is an immunoassay for the in vitro quantitative determination of thyroid stimulating hormone in human serum and plasma. Measurement of thyroid stimulating hormone produced by the anterior pituitary are used in the diagnosis of thyroid and pituitary disorders. The electrochemiluminescence immunoassay 'ECLIA' is intended for use on the cobas e

immunoassay analyzers.

#### DEVICE TO WHICH EQUIVALENCE IS CLAIMED 3.

The cobas e 801 analyzer module is a modified version of the predicate device, the Elecsys 2010 with Elecsys TSH as the representative quantitative assay, cleared under K961491.

A comparison of the significant features of the cobas e 801 and the Elecsys 2010 is provided in the table below.

| Topic | Predicate device: Elecsys 2010 analyzer | Candidate device:cobas e801 analyzer<br>module |
|-----------------------|------------------------------------------------------------------------|------------------------------------------------|
| Basic Features | | |
| Intended Use | Intended for the in vitro determination of<br>analytes in body fluids. | Same |
| Measurement principle | Electrochemiluminescence immunoassay<br>method (ECLIA) | Same |
| Workflow principle | Batch or random access | Same |
| Throughput | 86 tests/hour | 300 tests/hour/module |

| | | Table 1: Similarities and differences between the cobas e 801 and Elecsys 2010 analyzers | | | | |
|--|--|------------------------------------------------------------------------------------------|--|--|--|--|
| | | | | | | |

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| Topic | Predicate device: Elecsys 2010 analyzer | Candidate device:cobas e801 analyzer module |
|------------------------------------------------|-----------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------|
| Sample Handling | | |
| Typical sample volumes | 10-50μL | 4-60 µL |
| Sample types | Serum, plasma, urine, saliva | Same |
| Sample handling system | Via sample disk or racks | Input and transport of samples using universal sample racks, modular sample buffer input, core/transportation unit and STAT port. |
| Sample capacity on board | Disc: 30; rack:75 | 300 |
| Sample identification | Positive id-yes | Same |
| Reagent Handling | | |
| Reagent volume | 10-190 μL | 6-60 µL |
| Onboard storage temperature | 18-22°C | 5-10°C |
| Reagent bottle/Cassette identification | 2-d barcode | RFID |
| Application information transfer to instrument | Via barcode on reagent pack | Electronic transfer via cobas link |
| Test Reaction Chamber | | |
| Temp. control | Incubation at 37°C. | Same |
| Detection | | |
| Measuring unit | 1 | 2 |
| Detection unit | ECL unit with sipper, measuring cell and photomultiplier | Design of the sipper changed to shorten the detection cycle time; measuring cell and photomultiplier are the same |
| Detection time | 1.2 seconds | Same |
| Detection cycle time | 42 sec | 24 sec |
| Software | | |
| Software | Elecsys 2010 Software | cobas 8000 modular System Software |
| Configuration | Stand alone | One PC and one core in combination with several e-modules or c analytical modules |
| Analytical Unit(s) functions | Control of analytic processes (pipetting, incubation, detection) and Primary Signal processing | Same |
| Result calculation | Automated measuring of ECL signal and automated calculation of concentrations via calibration curve | Same |

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Elecsys TSH was used as the representative assay for this submission. Comparative data for the Elecsys TSH assay run on the cobas e 801 and the Elecsys 2010 is provided in the table below.

| Feature | Predicate Device: Elecsys TSH on Elecsys<br>2010 analyzer (K961491) | Candidate Device: Elecsys TSH on<br>cobas e801 analyzer module |
|-----------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------|
| Intended Use | Immunoassay for the in vitro quantitative<br>determination of thyroid stimulating hormone in<br>human serum and plasma | Same |
| Instrument Platform | Elecsys immunoassay analyzer | Elecsys immunoassay analyzer, part of the<br>cobas 8000 modular analyzer series<br>(K100853) |
| Measurement principle | Electrochemiluminescence immunoassay<br>(ECLIA) method | Same |
| Antibody/ Reagents | Biotinylated monoclonal anti-TSH antibody<br>(mouse)<br>Monoclonal anti-TSH antibody<br>(mouse/human) labeled with ruthenium<br>complex<br>Streptavidin -coated microparticles | Same |
| Sample size | 50 µL of sample | 30µL of sample |
| Measuring Range | 0.005-100 µIU/mL | Same |
| Sample Types | Serum, serum with separating gel, Li-heparin,<br>K₂EDTA, K₃EDTA<br>Also, Sodium citrate and NaF/K oxalate | Serum, serum with separating gel, Li-<br>heparin, K₂EDTA and K₃EDTA. |

Table 2: Similarities and Differences for Elecsys TSH on cobas e 801 versus Elecsys 2010

#### PERFORMANCE CHARACTERISTICS 4.

#### Repeatability and Intermediate Precision 4.1.

Precision of the Elecsys TSH assay was evaluated on one cobas e 801 analyzer according to CLSI EP05-A3. One reagent lot was evaluated.

The protocol consisted of testing 2 replicates of each control (PC Universal and PreciControl TS) and human sera (HS) per run, 2 runs per day for 21 days. The samples were run in randomized order on the analyzer. Pooled serum samples were used (Human serum 1-5, 11) and pooled spiked sera (Human serum 6-10).

The results of the precision studies are given in the table below:

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| | | Repeatability | | Intermediate precision | |
|-----------------|------------------|--------------------------------|----------------------|--------------------------------|----------------------|
| Sample | Mean<br>(µIU/mL) | SD<br>(µIU/mL)<br>(SD 95% UCL) | CV (%)<br>(UCL* 95%) | SD<br>(µIU/mL)<br>(SD 95% UCL) | CV (%)<br>(UCL* 95%) |
| Human serum 1 | 0.00851 | 0.000600<br>(0.000734) | 7.1 (8.6) | 0.000962<br>(0.00118) | 11.3 (13.8) |
| Human serum 2 | 0.209 | 0.00338<br>(0.00412) | 1.6 (2.0) | 0.00520<br>(0.00624) | 2.5 (3.0) |
| Human serum 3 | 1.88 | 0.0264<br>(0.0322) | 1.4 (1.7) | 0.0432<br>(0.0533) | 2.3 (2.8) |
| Human serum 4 | 51.8 | 0.653<br>(0.797) | 1.3 (1.5) | 1.05<br>(1.26) | 2.0 (2.4) |
| Human serum 5 | 90.0 | 1.24<br>(1.52) | 1.4 (1.7) | 1.75<br>(2.07) | 1.9 (2.3) |
| PC Universal 1 | 1.41 | 0.0197<br>(0.0240) | 1.4 (1.7) | 0.0301<br>(0.0362) | 2.1 (2.6) |
| PC Universal 2 | 8.18 | 0.132<br>(0.161) | 1.6 (2.0) | 0.207<br>(0.250) | 2.5 (3.1) |
| PreciControl TS | 0.184 | 0.00325<br>(0.00397) | 1.8 (2.2) | 0.00417<br>(0.00495) | 2.3 (2.7) |

#### Linearity 4.2.

Linearity of the Elecsys TSH assay was assessed on the cobas e 801 Immunoassay Analyzer according to CLSI EP6-A. Three high analyte serum samples were diluted with Diluent MultiAssay. 12 concentrations (dilutions) throughout the measuring range were prepared. Samples were assayed in 3-fold determination within a single run. The linearity data were analyzed with regards to linear, quadratic and cubic polynomials according to CLSI EP6-A. A summary of the linearity data is presented below:

Serum 1: intercept = -0.00155, slope = 0.963, Pearson's r = 0.9994

Serum 2 intercept = -0.00193, slope = 0.958, Pearson's r = 0.9992

Serum 3 intercept = -0.00272, slope = 0.952, Pearson's r = 0.9986

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#### Analytical sensitivity 4.3.

The limit of Blank (LoB) determines the highest observed measurement values for samples free of analyte. It was determined for three reagent lots using 60 replicates (one cobas e 801 instrument, six days, one run per day, one blank sample with ten replicates per run). LoB is 0.0025 µIU/mL

The Limit of Detection (LoD) was determined as the lowest amount of analyte in a sample that can be detected with 95% probability. It was determined for three reagent lots using 60 replicates (one cobas e 801 instrument, six days, one run per day, two replicates per sample per run and five low-level human serum samples). LoD is 0.005 µIU/mL.

The Limit of Quantitation (LoQ) is defined as the mean value of that sample which is the first that fulfills the specification for the intermediate precision and for which no sample with higher concentration exists that exceeds this specification. It was determined for three reagent lots using 10 low level TSH samples tested on one instrument, for five days, one run per day and five replicates per sample. The mean value and the intermediate precision as coefficient of variation (CV) and standard deviation (SD) for each LoQ sample were then calculated. The LoQ is 0.005 µIU/mL at a CV≤ 20 %.

#### Endogenous interferences 4.4.

The effect on quantitation of analyte in the presence of endogenous interfering substances using the Elecsys TSH was determined on the cobas e 801 Immunoassay analyzer using human serum samples. No interference was observed up to the levels indicated:

| Interferent | No interference seen up to | |
|----------------------|----------------------------|-------|
| Intralipid (Lipemia) | 2000 | mg/dL |
| Biotin | 56.0 | ng/mL |
| Bilirubin | 66.0 | mg/dL |
| Hemoglobin | 1000 | mg/dL |
| Rheumatic Factor | 1500 | IU/mL |
| human IgG | 2.80 | g/dL |
| human IgM | 0.500 | g/dL |

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#### 4.5. Exogenous interferences- anticoaqulants

The effect on quantitation of analyte in the presence of anticoagulants with the Elecsys TSH Immunoassay was determined by comparing values obtained from samples (single donors, native as well as spiked) drawn into Serum, Li-Heparin, K2-EDTA and K3-EDTA plasma tubes. Anticoagulants: A minimum of 40 serum/plasma pairs per sample material were tested in singleton with one reagent lot on one cobas e 801 Immunoassay Analyzer. Data were evaluated using a regression analysis according to Passing/Bablok and supported the above sample types.

#### Exogenous interferences- drugs 4.6.

In vitro tests were performed on 16 commonly used drugs. No interference with the assay was found. In addition the following special drugs were tested. No interference with the assay was found to the levels tested:

| Drug | Concentration tested (mg/L) |
|------------------|-----------------------------|
| Amiodarone | 200 |
| Carbimazole | 30 |
| Fluocortolone | 100 |
| Hydrocortisone | 200 |
| Iodide | 0.2 |
| Levotyroxine | 0.25 |
| Liothyronine | 0.015 |
| Methimazole | 80 |
| Octreotide | 0.3 |
| Prednisolone | 100 |
| Propanolol | 240 |
| Propylthiouracil | 60 |
| Perchlorate | 2000 |

#### 4.7. Method comparison

A method comparison was performed between the cobas e 801 and the predicate Elecsys 2010. A total of 130 human serum samples (single donors and serum pools; native, spiked as well as diluted) were measured with the Elecsys TSH immunoassay on analyzers in singlicate covering

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the entire measuring range. Sample concentrations were between 0.008 - 92.6 µIU/mL. The summary of the analysis is presented in the table below:

| | Passing/Bablok | Linear regression |
|-------------------------|----------------|-------------------|
| N | 130 | |
| Slope | 0.936 | 0.958 |
| Intercept | -0.003 | -0.052 |
| Correlation coefficient | | |
| Pearson (r) Kendall | - | 0.999 |
| ( $\u03c4$ ) | 0.989 | - |

#### Expected Values 4.8.

0.27-4.20 µIU/mL

These values correspond to the 2.5th and 97.5th percentiles of results obtained from a total of 516 healthy test subjects examined.

# CONCLUSION

The Elecsys TSH assay applied to the cobas e 801 analyzer is substantially equivalent to the predicate device based on the intended use, principle and performance characteristics described above.