S TEST REAGENT CARTRIDGE CARBON DIOXIDE (CO2)

K140248 · Hitachi Chemical Diagnostics, Inc. · KHS · Mar 11, 2014 · Clinical Chemistry

Device Facts

• Record ID: K140248
• Device Name: S TEST REAGENT CARTRIDGE CARBON DIOXIDE (CO2)
• Applicant: Hitachi Chemical Diagnostics, Inc.
• Product Code: KHS · Clinical Chemistry
• Decision Date: Mar 11, 2014
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1160
• Device Class: Class 2

Intended Use

The S TEST Reagent Cartridge Carbon Dioxide (CO₂) is intended for the quantitative determination of carbon dioxide concentration in serum or lithium heparin plasma using the HITACHI Clinical Analyzer E40. Carbon dioxide measurements are used in the diagnosis and treatment of numerous potentially serious disorders associated with changes in body acid-base balance. The S TEST Reagent Cartridge Carbon Dioxide (CO₂) is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only.

Device Story

The S TEST Reagent Cartridge Carbon Dioxide (CO2) is a single-use plastic cartridge used with the Hitachi Clinical Analyzer E40, an automated bench-top wet chemistry system. The system is operated by laboratory personnel or clinicians in clinical or physician office laboratories. The cartridge contains two reagents (R1 and R2) and a reaction cell. The analyzer pipettes patient serum or lithium heparin plasma and reagents into the cell, mixes them, and uses a multi-wavelength photometer to measure absorbance at 405 nm/508 nm. The device uses an enzymatic reaction (PEPC and MDH) to convert bicarbonate to oxaloacetic acid, resulting in a change in absorbance proportional to CO2 concentration. Results are available in approximately 15 minutes. The analyzer displays results on an operations screen, which clinicians use to assess patient acid-base balance and guide clinical decision-making for serious disorders.

Clinical Evidence

Clinical performance was evaluated at three external physician office laboratory (POL) sites. Precision studies (n=30 replicates per sample level) showed total precision %CVs ranging from 1.9% to 6.0%. Method comparison studies (n=45-47 specimens per site) against a reference method demonstrated strong correlation (r=0.970 to 0.984) and Deming regression slopes between 0.91 and 0.92, confirming accuracy across the dynamic range of 5.1 to 36.8 mmol/L.

Technological Characteristics

Plastic reagent cartridge (13.5mm x 28mm x 20.2mm) with two reservoirs and a photometric cuvette. Uses enzymatic reaction (PEPC/MDH) monitored bichromatically at 405/508 nm. System is an automated bench-top wet chemistry analyzer. Calibration data is provided via a 2D dot code label on the cartridge. Shelf life is 6 months at 2-8°C.

Indications for Use

Indicated for quantitative determination of carbon dioxide in serum or lithium heparin plasma for patients requiring assessment of acid-base balance. Intended for use in clinical laboratories or physician office laboratories.

Regulatory Classification

Identification

A bicarbonate/carbon dioxide test system is a device intended to measure bicarbonate/carbon dioxide in plasma, serum, and whole blood. Bicarbonate/carbon dioxide measurements are used in the diagnosis and treatment of numerous potentially serious disorders associated with changes in body acid-base balance.

Predicate Devices

• Sekisui Diagnostics, PEI, Inc., Carbon Dioxide L3K Assay (k042362)

Submission Summary (Full Text)

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Image /page/0/Picture/0 description: The image shows the text "510(k) SUMMARY" in a bold, sans-serif font. The text is centered and appears to be the title or heading of a document. The letters are black against a white background, providing a clear contrast.

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92. The assigned 510(k) number is K140248.

| 807.92 (a)(1): Name: | Hitachi Chemical Diagnostics, Inc. |
|----------------------|--------------------------------------------|
| Address: | 630 Clyde Court<br>Mountain View, CA 94043 |
| Phone: | [phone] |
| FAX: | [phone] |
| Contact: | Mr. Charles Tsou |

Official Correspondent: Erika Ammirati Regulatory Consultant to Hitachi Chemical Diagnostics, Inc. Phone: [phone] FAX: [phone]

Date Prepared: February 19, 2014

# 807.92 (a)(2): Device name- trade name and common name, and classification

#### Trade name:

S TEST Reagent Cartridge Carbon Dioxide (CO2)

Common Name: Routine chemistry analyzer for carbon dioxide

Classification: 21 CFR § 862.1160- Bicarbonate/carbon dioxide test system, Class II, Product Code KHS

#### 807.92 (a)(3): Identification of the legally marketed predicate devices

Carbon Dioxide L.3K Assay, Sekisui Diagnostics, PEI, Inc., Canada- K042362

#### 807.92 (a)(4): Device Description

The Hitachi Clinical Analyzer is an automatic, bench-top, wet chemistry system intended for use in clinical laboratories or physician office laboratories. The instrument consists of a desktop analyzer unit, an operations screen that prompts the user for operation input and displays data, a printer, and a unit cover. The analyzer unit includes a single probe, an incubation rotor, carousels for sample cups and reagent cartridges, and a multi-wavelength photometer. The single-use reagent cartridges may be placed in any configuration on the carousel, allowing the user to develop any test panel where the reagent cartridges are available.

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Tal: 800 233 6278

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The S TEST reagent cartridges are made of plastic and include two small reservoirs capable of holding two separate reagents (R1 and R2), separated by a reaction cell/photometric cuvette. The cartridges also include a dot code label that contains all chemistry parameters, calibration factors, and other production-related information, e.g., expiration dating. The dimensions of the reagent cartridges are: 13.5 mm (W) × 28 mm (D) × 20.2 mm (H).

System operation: After the sample cup is placed into the carousel, the analyzer pipettes the sample, pipettes the reagent, and mixes (stirs) the sample and reagent together. After the sample and reagent react in the incubator bath, the analyzer measures the absorbance of the sample, and based on the absorbance of the reactions, it calculates the concentration of analyte in the sample. The test system can measure analytes in serum or plasma and results are available in approximately 15 minutes per test. This submission is for Reagent Cartridge Carbon Dioxide.

Chemistry reaction: The carbon dioxide (in the form of bicarbonate HCO2) in the sample reacts with phosphoenolpyruvate (PEP) in the presence of phosphoenolpyruvate carboxylase (PEPC) and magnesium to vield oxaloacetic acid (OAA) and phosphate. In the second reaction, and in the presence of malate dehydrogenase (MDH), the reduced cofactor is oxidized by OAA. The reduced cofactor absorbs strongly at 405 nm. whereas its oxidized form does not. The difference in absorbance between the final reading and the blank, monitored bichromatically at 405 nm/508 nm, is directly proportional to the total carbon dioxide concentration in the sample.

## 807.92 (a)(5): Intended Use

The S TEST Reagent Carbon Dioxide (CO2) is intended for the quantitative determination of carbon dioxide concentration in serum or lithium heparin plasma using the Hitachi Clinical Analyzer E40. Carbon dioxide measurements are used in the diagnosis and treatment of numerous potentially serious disorders associated with changes in body acidbase balance. The S TEST Reagent Cartridge Carbon Dioxide (CO2) is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only.

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CA 94043-2239 Tal: 800 233 6278 Fax: 850,989 2745

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# 807.92 (a)(6): Technological Similarities and Differences to the Predicate

The following chart describes similarities and differences between the carbon dioxide test systems.

| Characteristic | Hitachi S TEST Systems | PREDICATE |
|-------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------|
| Instrument Platform | Hitachi Clinical Analyzer<br>(originally cleared under K111753) | Olympus/Beckman AU400<br>(originally cleared under K981743) |
| Carbon Dioxide | K140248 | Sekisui K number- K042362 |
| Device Class, Regulation Code | Class II, 21 CFR 862.1160 | Same |
| Classification Product Code | KHS | Same |
| Intended Use | Quantitative determination of<br>carbon dioxide | Same |
| Testing Environment | Physician office or clinical lab | Clinical lab |
| Test Principle | Carbon dioxide (in the form of<br>bicarbonate HCO3-) reacts with<br>phosphoenolpyruvate in the presence<br>of phosphoenolpyruvate carboxylase<br>(and magnesium) to yield<br>oxaloacetic acid (OAA). In the<br>presence of malate dehydrogenase,<br>reduced cofactor is oxidized by<br>OAA. The decrease in the<br>concentration of reduced cofactor is<br>monitored, and is proportional to the<br>carbon dioxide concentration in the<br>sample. | Same |
| Specimen Type | Human serum or lithium heparin<br>plasma | Same |
| Reportable Range | 5.0 to 40.0 mmol/L | 2.9 to 50.0 mmol/L |
| Detection Wavelength | 405/508 nm | 405/415 nm |
| Detection Limit (LoQ) | 1.3 mmol/L | 2.9 mmol/L |
| Linearity | 1.4 to 44.0 mmol/L | 2.9 to 50.0 mmol/L |
| Precision | %CVs range from 1.9% to 6.0%<br>(POL testing) | %CVs range from 1.1% to 1.7%<br>(from product labeling) |

# 807.92 (b)(1): Brief Description of Nonclinica! Data

A series of studies were performed that evaluated the following nonclinical performance characteristics: analytical sensitivity (limits of detection), linearity, 20-day in-house precision, interference testing, in-house method comparison, and matrix s comparison between serum and lithium heparin plasma.

C Hitachi Chemical Diagnostics, Inc. 630 Cryde Court, Mountain View, CA 94043-2239 Tel: [phone] Fax: [phone]

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# Analytical Sensitivity (Limit of Detection)

The study followed CLSI EP17-A2 where 60 replicates of the reagent blank and 60 replicates of three low samples were tested. The following results were reported: limit of blank = 0.7 mmol/L; limit of detection = 0.9 mmol/L; the limit of quantitation (LoQ) study evaluated three low level specimens in six runs with three instruments over three days. The LoQ was found to be approximately 4 mmol/L, with %CVs less than 11%.

#### Linearity

The study followed CLSI EP-6A where 10 serial dilutions, plus the zero standard (n = 11), were assayed in duplicate and the results were averaged. The expected values (x-axis) were compared to the observed values (y-axis). The data showed the following linear regression equation: y = 0.918x + 0.091; r2-0.9988. The range of linearity was 1.4 mmol/L to 44.0 mmol/L. The reportable range is 5 to 40 mmol/L.

#### 20-dav In-house Precision

The studies followed CLSI EPS-A2, where three levels of serum-based commercial controls were each tested in two runs, twice a day, for 20 days. The results were as follows:

| Carbon Dioxide- Low Summary | | |
|-----------------------------|------------|-------|
| Carbon Dioxide | Within-Run | Total |
| Mean (mmol/L) | 10.11 | 10.11 |
| SD (mmol/L) | 0.13 | 0.45 |
| %CV | 1.3% | 4.4% |

#### Precision Summaries:

#### Carbon Dioxide- Middle Summary

| Carbon Dioxide | Within-Run | Total |
|----------------|------------|-------|
| Mean (mmol/L) | 19.41 | 19.41 |
| SD (mmol/L) | 0.25 | 0.72 |
| %CV | 1.3% | 3.7% |

#### Carbon Dioxide- High Summary

| Carbon Dioxide | Within-Run | Total |
|----------------|------------|-------|
| Mean (mmol/L) | 33.06 | 33.06 |
| SD (mmol/L) | 0.40 | 1.22 |
| %CV | 1.2% | 3.7% |

Interference Testing (per CLSI EP7-A2)

The data demonstrated that the carbon dioxide test system was not affected by high levels of the following substances at the levels noted:

Lipemia: no interference up to 1,000 mg/dL Intralipid

Ascorbic acid: no interference up to 50 mg/dL

Hemoglobin: no interference up to 1,000 mg/dL

Unconjugated bilirubin: no interference up to 19.1 mg/dL

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® Hitachi Chemical Diagnostics, Inc.

630 Clyde Court, Mountain View, CA 94043-2239 Tel: [phone] Fax: [phone]

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Lack of interference was defined as recoveries between 90% and 110% of the neat value, and assay performance claims were established on the HITACHI Clinical Analyzer by testing two serum pools containing approximately 17 and 30 mmol/L carbon dioxide.

## Method Comparison

A total of 96 clinical specimens (including 3 spiked and 3 diluted samples) spanning the dynamic range (5.0 to 40.0 mmol/L) were assayed in singleton and in a blinded fashion by both the Hitachi E40 system and a standard laboratory system. The comparative data were analyzed by Deming regression and are shown below. (CI = confidence interval).

# Regression Statistics:

| n | r | Slope<br>(95% CI) | y-intercept<br>(95% CI) | X mean | Y mean |
|----|-------|------------------------|-------------------------|--------------|--------------|
| 96 | 0.981 | 1.03<br>(0.97 to 1.08) | 0.98<br>(-0.17 to 2.12) | 22.54 mmol/L | 24.07 mmol/L |

# Matrix Comparison

A study was performed to validate the use of lithium heparin plasma as an alternative to serum for the Hitachi Clinical Analyzer with S TEST Reagent Cartridge Carbon Dioxide. Fifty (50) matched serum/plasma samples (including 2 spiked and 4 diluted samples) that spanned the dynamic range (5.0 to 40.0 mmol/L, serum) were assayed in singleton and the results were compared using linear regression (plasma = y-axis). The performance characteristics were as follows.

N = 50 Range (serum) = 5 4 to 38 6 mmol/L. carbon dioxide

| | Lithium Heparinized Plasma |
|-----------------------|----------------------------|
| Slope (95% CIs) | 1.00 (0.94 to 1.05) |
| y-intercept (95% CIs) | -0.34 (-1.97 to 1.30) |
| r | 0.980 |

## Reference Range

Reference range: 22 - 29 mmol/L 1

1. Tietz, Fundamentals of Clinical Chemistry, 4th Edition, WB Saunders Company, (1996)

# Traceability/Calibration

Each lot of S TEST Reagent Cartridge Carbon Dioxide (CO2) is calibrated by the manufacturer prior to shipment using material referenced to a standard which is traceable to American Chemical Society (ACS) reagent grade sodium carbonate alkalimetric standard. The 2D code printed on each cartridge provides the analyzer with lot-specific calibration data.

# Stabilitv

Real time stability testing is ongoing. Stability testing has been performed to support a shelf life of 6 months at 2-8°C.

Hitachi Chemical Diagnostics, Inc.

330 Clyde Court, Mountain View, CA 94043-2239 Tel: [phone] Fax: [phone]

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# 807.92 (b)(2): Brief Description of Clinical Data

Studies for precision and method comparison (accuracy) were performed at three external POL-type sites to evaluate the Hitachi E40 Clinical Analyzer with S TEST Reagent Cartridge Carbon Dioxide in one of its targeted intended use environments, the physician's office laboratory.

For the external site precision study, each site received three blinded serum samples (the Precision Panel, labeled A, B, and C) that were chosen to represent low, middle, and high concentrations of carbon dioxide. Each sample was assayed six times per day for five days, reporting 30 results per level. Precision estimates for total precision were as follows:

| Site | Sample | Mean | Within-run Precision | | Total Precision | |
|------|--------|-------|----------------------|-----|-----------------|-----|
| | | | SD (mmol/L) | %CV | SD (mmol/L) | %CV |
| 1 | A | 8.75 | 0.16 | 1.8 | 0.36 | 4.1 |
| 2 | A | 7.29 | 0.33 | 4.6 | 0.44 | 6.0 |
| 3 | A | 8.06 | 0.23 | 2.9 | 0.25 | 3.1 |
| 1 | B | 15.27 | 0.35 | 2.3 | 0.74 | 4.8 |
| 2 | B | 15.01 | 0.23 | 1.5 | 0.67 | 4.4 |
| 3 | B | 16.25 | 0.27 | 1.7 | 0.30 | 1.9 |
| 1 | C | 29.46 | 0.51 | 1.7 | 0.94 | 3.2 |
| 2 | C | 29.47 | 0.81 | 2.7 | 1.08 | 3.7 |
| 3 | C | 31.01 | 0.58 | 1.9 | 1.16 | 3.7 |

Carbon Dioxide (mmol/L) n = 30 replicates per sample per site

For the external method comparison studies, a series of 47 serum specimens (including three spiked and four diluted samples) with carbon dioxide values ranging from 5.1 to 36.8 mmol/L, were assayed on the Hitachi E40 Clinical Analyzer at three sites using S TEST Reagent Cartridge Carbon Dioxide (y) and a comparative method as the reference method (x). Deming regression vielded the following results:

| Site # | n | Range<br>(mmol/L) | Regression<br>Equation | "r" | CI**<br>Slope | CI Intercept |
|--------|-----|-------------------|------------------------|-------|---------------|---------------|
| 1 | 47 | 6.6 to 36.8 | y = 0.91x + 1.49 | 0.984 | 0.87 to 0.95 | 0.67 to 2.32 |
| 2 | 45* | 5.5 to 34.4 | y = 0.92x + 0.56 | 0.970 | 0.80 to 1.04 | -2.31 to 3.43 |
| 3 | 47 | 5.1 to 35.5 | y = 0.92x + 0.79 | 0.982 | 0.87 to 0.97 | -0.43 to 2.01 |

POL ACCURACY DATA SUMMARY- Carbon Dioxide (mmol/L)

* 2 samples at Site 2 quantitated below to dynamic range (<5 mmol/L) and were excluded from data analysis. **95% Confidence Interval

## Expected Range

22 -- 29 mmol/L (Tietz, Fundamentals of Clinical Chemistry, 40 Edition, WB Saunders Company, (1996))

# 807.92 (b)(3): Conclusions from Nonclinical and Clinical Testing

Nonclinical and clinical testing was performed for the Hitachi Clinical Analyzer E40 with Reagent Cartridge Carbon Dioxide. The test system was shown to be safe and effective for its intended use.

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#### DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

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

March 11, 2014

HITACHI CHEMICAL DIAGNOSTICS, INC. c/o ERIKA AMMIRATI AMMIRATI REGULATORY CONSULTING 575 SHIRLYNN COURT LOS ALTOS. CA 94022

Re: K140248

Trade/Device Name: S TEST Reagent Cartridge Carbon Dioxide (CO2) Regulation Number: 21 CFR 862.1160 Regulation Name: Bicarbonate/carbon dioxide test system Regulatory Class: II Product Code: KHS Dated: January 29, 2014 Received: January 30, 2014

Dear Ms. Ammirati:

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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Page 2-Ms. Ammirati

If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number [phone] or [phone] or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/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 Small Manufacturers. International and Consumer Assistance at its toll-free number [phone] or [phone] or at its Internet address http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm.

Sincerely yours,

# Courtney H. Lias -S

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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#### DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

# Indications for Use

Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement on last page.

510(k) Number (if known) k140248

#### Device Name

S TEST Reagent Cartridge Carbon Dioxide (CO2)

Indications for Use (Describe)

The S TEST Reagent Cartridge Carbon Dioxide (CO2) is intended for the quantitative determination of carbon dioxide concentration in serum or lithium heparin plasma using the HITACHI Clinical Analyzer E40. Carbon dioxide measurements are used in the diagnosis and treament of numerous potentially serious disorders associated with changes in body acid-base balance. The S TEST Reagent Cartridge Carbon Dioxide (CO2) is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only.

Type of Use (Select one or both, as applicable)

2 Prescription Use (Part 21 CFR 801 Subpart D)

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

## PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON A SEPARATE PAGE IF NEEDED.

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