HITACHI CLINICAL ANALYZER S TEST REGENT CARTRIDGE C-REACTIVE PROTEIN (CRP)

K113809 · Hitachi Chemical Diagnostics, Inc. · DCN · Aug 17, 2012 · Immunology

Device Facts

• Record ID: K113809
• Device Name: HITACHI CLINICAL ANALYZER S TEST REGENT CARTRIDGE C-REACTIVE PROTEIN (CRP)
• Applicant: Hitachi Chemical Diagnostics, Inc.
• Product Code: DCN · Immunology
• Decision Date: Aug 17, 2012
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.5270
• Device Class: Class 2

Intended Use

The Hitachi Clinical Analyzer S TEST reagent cartridge CRP is intended for the quantitative measurement of C-reactive protein in serum, lithium heparin plasma, K3-EDTA plasma, and sodium citrate plasma. The test system is intended for use in clinical laboratories or physician office laboratories. CRP measurements aid in the evaluation of injury to body tissues, and infection and inflammatory disorders. For in vitro diagnostic use only.

Device Story

The Hitachi Clinical Analyzer is an automated, bench-top, wet chemistry system for clinical laboratories or physician offices. It utilizes single-use plastic reagent cartridges containing two reservoirs (R1, R2) and a reaction cell. The device accepts serum or plasma samples. Operation involves automated pipetting of sample and reagent into the reaction cell, mixing, and incubation. The system uses latex agglutination turbidimetric immunoassay; CRP in the sample reacts with goat anti-human CRP antibody-coated latex to induce agglutination. A multi-wavelength photometer measures absorbance changes to calculate analyte concentration. Results are available in approximately 15 minutes. The system includes an operations screen for user input and data display. Healthcare providers use the quantitative CRP results to assist in the clinical evaluation of tissue injury, infection, and inflammatory disorders.

Clinical Evidence

Clinical performance was evaluated at three physician office laboratory (POL) sites. Precision studies (n=30 replicates per sample per site) showed total precision %CVs ranging from 2.9% to 14.1% across low, middle, and high CRP concentrations. Method comparison studies (n=55-56 specimens per site) against a reference method demonstrated strong correlation (r=0.998-0.999) with slopes ranging from 1.02 to 1.06, confirming accuracy across the 1-130 mg/L range.

Technological Characteristics

Plastic reagent cartridge with two reservoirs and integrated photometric cuvette. Detection via latex agglutination turbidimetry at 570/800 nm. Calibration via lot-specific barcode. Traceable to IRMM ERM-DA472. Designed for use on Hitachi Clinical Analyzer. Sterilization not specified.

Indications for Use

Indicated for quantitative measurement of C-reactive protein (CRP) in serum, lithium heparin plasma, K3-EDTA plasma, and sodium citrate plasma to aid in evaluating tissue injury, infection, and inflammatory disorders in patients.

Regulatory Classification

Identification

A C-reactive protein immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the C-reactive protein in serum and other body fluids. Measurement of C-reactive protein aids in evaluation of the amount of injury to body tissues.

Predicate Devices

• Roche C-Reactive Protein Latex (CRPLX) (k073277)

Submission Summary (Full Text)

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K113809

# SECTION 8 510(k) SUMMARY

AUG 1 7 2012

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 K113809.

807.92 (a)(1): Name: Address: Hitachi Chemical Diagnostics 630 Clyde Court Mountain View, CA 94043

Phone: FAX: Contact: [phone] [phone] Mr. Bunichiro Nakajima

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

#### Trade name:

Hitachi Clinical Analyzer S TEST Reagent Cartridge C-Reactive Protein (CRP)

Common Name: Routine chemistry analyzer for C-Reactive Protein (CRP)

Classifications: 21 CFR § 866.5270- C-reactive protein immunological test system (CRP)

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

#### Reagent Test:

Roche C-Reactive Protein Latex (CRPLX)- k073277

#### Instrument Platform:

Roche Cobas 8000 Modular Series Analyzer - k100853 Alfa Wasserman Diagnostic Technologies S40 Clinical Analyzer - k091413

#### 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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Hitachi Chemical Diagnostics, Inc.

Tal: 800 233 8278

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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) x 28 mm (D) x 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 test systems for CRP.

#### Chemistry reactions:

CRP in samples causes an antigen-antibody reaction with latex sensitizes with Goat antihuman C-Reactive Protein antibody to induce agglutination. The concentration of CRP can be determined by measuring this agglutination as the amount of change in absorbance.

CRP + Goat anti-human C-reactive protein antibody coated latex -> Agglutination due to antigen-antibody reaction

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

The Hitachi Clinical Analyzer S TEST reagent cartridge CRP is intended for the quantitative measurement of C-reactive protein in serum, lithium heparin plasma, K3 EDTA plasma, and sodium citrate plasma. The test system is intended for use in clinical laboratories or physician office laboratories. CRP measurements aid in the evaluation of injury to body tissues, and infection and inflammatory disorders. For in vitro diagnostic use only.

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**www.hcdiagnostics.com**

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

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

| Characteristic | Hitachi S TEST Systems | PREDICATE(S) |
|-------------------------------|--------------------------------------------------------------------|-----------------------------------------------------------------|
| Instrument Platform | Hitachi Clinical Analyzer | Roche cobas 8000 - K100853<br>also, Alfa Wasserman S40- K091413 |
| C-Reactive Protein (CRP) | K number- K113809 | Roche C-Reactive Protein Latex<br>(CRPLX)<br>K073277 |
| Device Class, Regulation Code | Class II, 21 CFR 866.5270 | Same |
| Classification Product Code | DCN | Same |
| Intended Use | Quantitative determination of CRP | Same |
| Testing Environment | Physician office or clinical lab | Clinical lab- Roche cobas<br>POL/Clin Lab - Alfa Wasserman |
| Test Principle | Latex agglutination turbidimetric<br>immunoassay | Particle-enhanced<br>immunoturbidimetric assay |
| Specimen Type | Human serum or plasma | Same |
| Reportable Range | 1 to 150 mg/L | 1 to 250 mg/L |
| Detection Wavelength | 570/800 nm | -/546 nm |
| Detection Limit | 1 mg/L | Same |
| Linearity | 1 to 154 mg/L | 1 to 250 mg/L |
| Precision | %CVs range from 7.7% (mean 15.6<br>mg/L) to 2.8% (mean 122.1 mg/L) | %CVs range from 0.9% to 2.5%<br>(from product labeling) |

### 807.92 (b)(1): Brief Description of Nonclinical Data

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

# Analytical Sensitivity (Limits of Detection)

The study followed CLSI EP17-A, and the sensitivity was found to be 0.7 mg/L.

#### Linearity

The study followed CLSI EP-6A , and the range of linearity was 1 to 154 mg/L.

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![]()Hitachi Chemical Diagnostics, Inc.

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

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#### 20-day In-house Precision

The studies followed CLSI EP5-A2, where three levels of samples were each tested in two runs, twice a day, for 20 days. The results were as follows:

#### Precision Summary:

#### CRP- Low, Level 1, Summary

| CRP | Within-Run | Total |
|-------------|------------|-------|
| Mean (mg/L) | 6.0 | 6.0 |
| SD (mg/L) | 0.34 | 0.44 |
| % CV | 5.7% | 7.3% |

#### CRP- Middle, Level 2, Summary

| CRP | Within-Run | Total . |
|--------------|------------|---------|
| Mean (mg/dL) | 15.6 | 15.6 |
| SD (mg/dL) | 1.16 | 1.20 |
| %CV | 7.4% | 7.7% |

#### CRP - High, Level 3, Summary

| CRP | Within-Run | Total |
|-------------|------------|-------|
| Mean (mg/L) | 122.1 | 122.1 |
| SD (mg/L) | 3.01 | 3.41 |
| % CV | 2.5% | 2.8% |

## Interference Testing (per CLSI EP7-A2)

The data demonstrated that the C-reactive protein test system was not affected by high levels of the following substances at the levels noted:

Hemoglobin: no interference up to 1000 mg/dL Unconjugated bilirubin: no interference up to 50 mg/dL Lipemia: no interference up to 2000 mg/dL Ascorbic acid: no interference up to 50 mg/dL

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 12 mg/L and 80 mg/L C-reactive protein.

#### Method Comparison (per CLSI EP9-A2)

A total of 88 clinical specimens, spanning the dynamic range (1 to 125 mg/L), were assayed in singleton and in a blinded fashion by both the Hitachi system and a standard laboratory system. Regression statistics are based on the balance of the paired results, and the data were as follows:

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#### CRP Regression Statistics:

| n | r | Slope<br>(95% CI) | y-intercept<br>(95% CI) | X mean | Y mean |
|----|-------|------------------------|-------------------------|---------|---------|
| 88 | 0.994 | 0.99<br>(0.96 to 1.01) | 0.14<br>(-0.64 to 0.92) | 15 mg/L | 15 mg/L |

#### Matrices Comparisons

A study was performed to validate the use of various plasma types, as an alternative to serum, for the Hitachi Clinical Analyzer with S TEST reagent cartridge for C-Reactive Protein. The plasma types were sodium citrate, lithium heparin, and K3 EDTA. Forty-five (45) matched serum/plasma samples that spanned the dynamic range (1 to 123 mg/L) were assayed in singleton and the results were compared using least squares liner regression (plasma = y-axis, each type). The performance characteristics were as follows.

#### N = 45

#### Range (serum) = 1 to 123 mg/L

| | Lithium Heparin<br>Plasma | K3 EDTA Plasma | Na Citrate Plasma |
|-----------------------|---------------------------|----------------------|-----------------------|
| Slope (95% CIs) | 1.00 (0.98 to 1.01) | 0.99 (0.97 to 1.00) | 1.00 (0.99 to 1.01) |
| y-intercept (95% CIs) | -0.12 (-0.75 to 0.52) | 0.06 (-0.55 to 0.67) | -0.26 (-0.82 to 0.30) |
| r | 0.999 | 0.999 | 0.999 |

#### 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 Clinical Analyzer with S TEST reagent cartridges for CRP 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 CRP. Each sample was assayed six times per day for five days, reporting 30 results per level per analyte. Precision estimates for total precision were as follows:

® **Hitachi Chemical Diagnostics, Inc.**

cdiagnostics.com

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

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| Site | Sample | Mean | Within-run Precision | | Total Precision | |
|--------|--------|------|----------------------|-------|-----------------|-------|
| | | | SD (mg/L) | % CV | SD (mg/L) | % CV |
| Site 1 | A | 3.9 | 0.2 | 5.9% | 0.3 | 6.6% |
| Site 2 | A | 3.6 | 0.4 | 12.4% | 0.5 | 14.1% |
| Site 3 | A | 3.9 | 0.4 | 11.6% | 0.4 | 11.2% |
| Site 1 | B | 49.7 | 1.9 | 3.8% | 1.7 | 3.5% |
| Site 2 | B | 52.3 | 1.5 | 2.8% | 1.5 | 2.9% |
| Site 3 | B | 54.1 | 1.2 | 2.3% | 2.1 | 3.9% |
| Site 1 | C | 95.5 | 5.1 | 5.3% | 5.3 | 5.6% |
| Site 2 | C | 92.3 | 4.0 | 4.3% | 6.5 | 7.1% |
| Site 3 | C | 94.0 | 3.5 | 3.7% | 4.0 | 4.2% |

# CRP (mg/L) n = 30 replicates per sample per site

A series of approximately 55 serum specimens with C-Reactive Protein values ranging from 1 mg/L to 130 mg/L were assayed on the HITACHI Clinical Analyzer at three sites using S TEST CRP (y) and a comparative method as the reference method (x). Linear regression analysis (least squares) yielded the following results:

DATA SUMMARY- C-reactive protein mg/L

| Site # | n | Range | Regression Equation | "r" | CI* Slope | CI* Intercept |
|--------|----|----------|---------------------|-------|--------------|---------------|
| 1 | 56 | 1 to 122 | y = 1.02x + 0.1 | 0.998 | 1.00 to 1.04 | -0.5 to 0.6 |
| 2 | 56 | 1 to 130 | y = 1.06x - 0.2 | 0.999 | 1.05 to 1.08 | -0.6 to 0.2 |
| 3 | 55 | 1 to 125 | y = 1.03x + 0.2 | 0.998 | 1.01 to 1.05 | -0.4 to 0.8 |

*95% Confidential Interval

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

Nonclinical and clinical testing was performed for the Hitachi Clinical Analyzer with reagent cartridges for CRP. The test system was shown to be safe and effective for its intended use.

Hitachi Chemical Diagnostics, Inc. 830 Clyde Court, Mountain Vlew, CA 94043-2239 Tal· 800 233 6278

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Image /page/6/Picture/12 description: The image shows the seal of the Department of Health & Human Services (HHS) of the United States. The seal features the department's name encircling a stylized emblem. The emblem consists of a stylized caduceus, a symbol often associated with medicine and healthcare, with three figures representing health, services, and humanity.

10903 New Hampshire Avenue Silver Spring, MD 20993

Hitachi Chemical Diagnostics, Inc. c/o Ms. Erika B. Ammirati Managing Director 575 Shirlynn Court Los Altos, CA 94022

AUG 1 7 2012

Re: k113809

Trade/Device Name: Hitachi Clinical Analyzer S TEST Reagent Cartridge CRP Regulation Number: 21 CFR §866.5270 Regulation Name: C-reactive protein immunological test system Regulatory Class: Class II Product Code: DCN Dated: August 10, 2012 Received: August 14, 2012

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.

If your device is classified (see above) into class II (Special Controls), 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); medical device reporting (reporting of

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# Page 2 - Ms. Ammirati

medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). 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 advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at [phone]. 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 Small Manufacturers, International and Consumer Assistance at its toll-free number [phone] or [phone] or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

roge

Reena Philip

Maria M. Chan, Ph.D. Director Division of Immunology and Hematology Devices 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): k113809

Device Name: Hitachi Clinical Analyzer S TEST Reagent Cartridge CRP

### Indications For Use:

The Hitachi Clinical Analyzer S TEST reagent cartridge CRP is intended for the quantitative measurement of C-reactive protein in serum, lithium heparin plasma, K3 EDTA plasma, and sodium citrate plasma. The test system is intended for use in clinical laboratories or physician office laboratories. CRP measurements aid in the evaluation of injury to body tissues, and infection and inflammatory disorders. For in vitro diagnostic use only.

Prescription Use × AND/OR

Over-The-Counter Use

(Part 21 CFR 801 Subpart D)

(21 CFR 807 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)

Division Sign-Off

Division Sign-Off

Office of In Vitro Diagnos Device Evaluation a

510K K113869

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