HITACHI CLINICAL ANALYZER S TEST REAGENT CARTRIDGE CALCIUM (CA)

K130870 · Hitachi Chemical Diagnostics, Inc. · CIC · May 2, 2013 · Clinical Chemistry

Device Facts

• Record ID: K130870
• Device Name: HITACHI CLINICAL ANALYZER S TEST REAGENT CARTRIDGE CALCIUM (CA)
• Applicant: Hitachi Chemical Diagnostics, Inc.
• Product Code: CIC · Clinical Chemistry
• Decision Date: May 2, 2013
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1145
• Device Class: Class 2

Intended Use

The S TEST Reagent Cartridge Calcium (CA) is intended for the quantitative determination of calcium in serum, lithium heparinized plasma, and sodium citrate plasma using the HITACHI Clinical Analyzer E40. The S TEST Reagent Cartridge Calcium is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only. Calcium measurements are used in the diagnosis and treatment of parathyroid disease, a variety of bone diseases, chronic renal disease and tetany (intermittent muscular contractions or spasms).

Device Story

The Hitachi Clinical Analyzer is an automated, bench-top, wet chemistry system. It uses single-use plastic reagent cartridges containing two reservoirs (R1, R2) and a reaction cell. The system processes serum or plasma samples by pipetting sample and reagent into the reaction cell, mixing, and incubating. A multi-wavelength photometer measures the absorbance of the purple-red complex formed by calcium and o-cresolphthalein complexone (with 8-hydroxyquinoline to exclude magnesium interference). The analyzer calculates analyte concentration based on absorbance. Results are available in approximately 15 minutes. The device is operated by laboratory personnel or technicians in clinical or physician office laboratories. The output is a quantitative calcium concentration value, which assists clinicians in diagnosing and monitoring parathyroid, bone, and renal diseases.

Clinical Evidence

Bench testing included analytical sensitivity (LOD 0.19 mg/dL), linearity (0.4-17.1 mg/dL), 20-day precision (CVs 0.7-1.9%), and interference testing (bilirubin, lipemia, ascorbic acid, hemoglobin). Method comparison (n=97) showed r=0.976, slope 0.99. Matrix comparison (n=44) validated serum/plasma equivalence. Clinical performance was evaluated at three physician office laboratory (POL) sites (n=55-57 per site), demonstrating accuracy comparable to reference methods with r values ranging from 0.984 to 0.987 and slopes from 0.96 to 0.99.

Technological Characteristics

Bench-top automated wet chemistry analyzer. Reagent cartridges: plastic, 13.5mm x 28mm x 20.2mm. Sensing: multi-wavelength photometer (570/660 nm). Principle: colorimetric (o-cresolphthalein complexone). Connectivity: includes operations screen/printer. Software: embedded control for pipetting, incubation, and absorbance calculation.

Indications for Use

Indicated for quantitative determination of calcium in serum, lithium heparinized plasma, and sodium citrate plasma. Used in clinical/physician office labs for diagnosis/treatment of parathyroid disease, bone diseases, chronic renal disease, and tetany.

Regulatory Classification

Identification

A calcium test system is a device intended to measure the total calcium level in serum. Calcium measurements are used in the diagnosis and treatment of parathyroid disease, a variety of bone diseases, chronic renal disease and tetany (intermittent muscular contractions or spasms).

Submission Summary (Full Text)

{0}------------------------------------------------

## SECTION 8 510(k) SUMMARY

#### MAY 2 2013

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 K130870.

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

> Phone: [phone] [phone] FAX: Contact: Mr. Charles Tsou [e-mail]

> > and

| Name: | Ammirati Regulatory Consulting |
|----------|--------------------------------|
| Phone: | [phone] |
| FAX: | [phone] |
| Contact: | Ms. Erika Ammirati |
| | [e-mail] |

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

## Trade name:

Hitachi S TEST Reagent Cartridge Calcium (CA) .

Common Name: Routine chemistry analyzer for calcium

Regulation: 21 CFR § 862.1145 Calcium test system

Device Classification: Class 2

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

Cobas c systems Calcium (CA) (Roche Diagnostics, Inc., Indianapolis, IN)-K100853

## 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 Page 1 of 6

O Hitachi Chemical Dlagnostics, Inc.

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

| 11 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 | |
|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--|
| www.hcdiagnostics.com | |
| 1994 (1992) 1999-1999 (1992) 1992 (1992) 1992 1992 1992 1992 1994 1994 1994 1994 1994 1994 1994 1994 1994 1994 1994 1994 1994 1994 1994 1994 1994 1994 1994 1994 1994 1994 199 | |

{1}------------------------------------------------

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.

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 Calcium.

Chemistry reactions: Calcium in the sample combines with o-cresolphthalein complexone to form a purple-red complex. The concentration of calcium can be determined by measuring the absorbance of the resulting purple-red color. (With this method, the influence of magnesium is excluded by the addition of 8-hydroxyquinoline.)

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

The S TEST Reagent Cartridge Calcium (CA) is intended for the quantitative determination of calcium in serum, lithium heparinized plasma, and sodium citrate plasma using the HITACHI Clinical Analyzer E40. The S TEST Reagent Cartridge Calcium is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only.

Calcium measurements are used in the diagnosis and treatment of parathyroid disease, a variety of bone diseases, chronic renal disease and tetany (intermittent muscular contractions or spasms).

Page 2 of 6

#### O Hitachi Chemical Diagnostics, Inc. 630 Clyde Court, Mounlain View, CA 94043-2239 Tel: [phone]

www.hcdiagnostics.com

i.e. the set of all elements of either set or of both sets. Other set operations include set intersection (denoted ∩), set difference (denoted ), and set complement (denoted ′).

{2}------------------------------------------------

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

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

| Characteristic | Hitachi S TEST Systems | PREDICATE |
|-------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Instrument Platform | Hitachi Clinical Analyzer<br>(originally cleared under K111753) | Roche cobas c systems - K100853 |
| Calcium | K number- pending | Roche K number- K100853 |
| Device Class, Regulation Code | Class II, 21 CFR 862.1145 | Same |
| Classification Product Code | CIC | Same |
| Intended Use | Quantitative determination of CA | Same |
| Testing Environment | Physician office or clinical lab | Clinical lab |
| Test Principle | Calcium in the sample combines<br>with o-cresolphthalein complexone<br>to form a purple-red complex. The<br>concentration of calcium can be<br>determined by measuring the<br>absorbance of the resulting purple-<br>red color. (With this method, the<br>influence of magnesium is excluded<br>by the addition of 8-<br>hydroxyquinoline.) | Calcium ions react with o-<br>cresolphthalein complexone under<br>alkaline conditions to form a violet-<br>colored complex. The color intensity<br>of the formed complex is directly<br>proportional to the calcium<br>concentration and is measured<br>photometrically. The addition of 8-<br>hydroxyquinoline prevents<br>interference by magnesium and iron. |
| Specimen Type | Human serum or plasma | Same |
| Reportable Range | 0.5 to 15.0 mg/dL | 0.4 to 20.0 mg/dL |
| Detection Wavelength | 570/660 nm | 700/600 nm |
| Detection Limit | 0.4 mg/dL | 0.4 mg/dL |
| Linearity | 0.5 to 15.0 mg/dL | 0.4 to 20.0 mg/dL |
| Precision | %CVs range from 1.0% to 1.9% | %CVs range from 0.3% to 1.4%<br>(from product labeling) |

Page 3 of 6

ത്ര Hitachi Chemical Diagnostics, Inc.

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

| ком седантика се при седента се седения се седения представления се пристементации и пристементации продобразования продобразования продобразования продобразования продобразо |
|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| www.hcdiagnostics.com |
| ーーーーーーーーーーーーーーーーーーーーーーーーーーーーーーーーーーーーーーーーーーーーーーーーーーーーーーーーー<br>www.ba.us.often.org/lower/responses/articles/a-c-<br>a status and the contract and consisted on the commend of the program and the program and the many of the |

{3}------------------------------------------------

## 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 various plasma types.

### Analytical Sensitivity (Limits of Detection)- CA

The study followed CLSI EP17-A, and the limit of detection was found to be 0.19 mg/dL. The quantitation limit was found to be 0.4 mg/dL

#### Linearity- CA

The study followed CLSI EP-6A, and the range of linearity was 0.4 to 17.1 mg/dL. The reportable range is 0.5 to 15.0 mg/dL.

## 20-day In-house Precision- CA

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:

### Calcium- Low, Level 1, Summary

| Calcium | Within-Run | Total |
|--------------|------------|-------|
| Mean (mg/dL) | 5.21 | 5.21 |
| SD (mg/dL) | 0.07 | 0.10 |
| %CV | 1.3% | 1.9% |

## Calcium- Middle, Level 2, Summary

| Calcium | Within-Run | Total |
|--------------|------------|-------|
| Mean (mg/dL) | 10.06 | 10.06 |
| SD (mg/dL) | 0.11 | 0.14 |
| %CV | 1.1% | 1.4% |

## Calcium- High, Level 3, Summary

| Calcium | Within-Run | Total |
|--------------|------------|-------|
| Mean (mg/dL) | 13.03 | 13.03 |
| SD (mg/dL) | 0.09 | 0.14 |
| %CV | 0.7% | 1.0% |

Page 4 of 6

#### O Hitachl Chemical Diagnostics, Inc.

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

| Controller controller controllation of the management construction of the manufacturer in the consistence in the may and | |
|--------------------------------------------------------------------------------------------------------------------------|--|
| www.hcdiaanostics.com | |
| Con all controllection of the comments of any of any of any of any of any of the final of the final of the final | |

{4}------------------------------------------------

## Interference Testing (per CLSI EP7-A2)

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

Unconiugated bilirubin: no interference up to 50 mg/dL Lipemia: no interference up to 500 mg/dL Ascorbic acid: no interference up to 50 mg/dL Hemoglobin: no interference up to 500 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 4 and 11 mg/dL calcium.

## Method Comparison

A total of 97 clinical specimens spanning the dynamic range (1.2 to 14.8 mg/dL), 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 linear 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 |
|----|-------|------------------------|--------------------------|-----------|-----------|
| 97 | 0.976 | 0.99<br>(0.94 to 1.03) | -0.25<br>(-0.68 to 0.18) | 9.4 mg/dL | 9.0 mg/dL |

## Matrices Comparisons

A study was performed to validate the use of two plasma types as an alternative to serum for the Hitachi Clinical Analyzer with S TEST Reagent Cartridge Calcium. The plasma types were sodium citrate and lithium heparin. Forty-four (44) matched serum/plasma samples that spanned the dynamic range (0.9 to 14.7 mg/dL) were assayed in singleton and the results were compared using linear regression (plasma = y-axis, each type). The performance characteristics were as follows.

N = 44

Range (serum) = 0.9 to 14.7 mg/dL calcium

| | Na Citrate Plasma | Heparinized Plasma |
|-----------------------|-----------------------|-----------------------|
| Slope (95% CIs) | 0.98 (0.95 to 1.02) | 0.96 (0.91 to 1.00) |
| y-intercept (95% CIs) | -0.14 (-0.48 to 0.19) | -0.02 (-0.44 to 0.41) |
| r | 0.993 | 0.988 |

## 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 Calcium in one of its targeted intended use environments, the physician's office laboratory.

Page 5 of 6

#### O Hitachi Chemical Dlagnostics, Inc.

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

| | 1. Partil Pro Pro Production Comments of Children Program Program Program Program Program Program Program Programment Programment Programment Programment Programment Programm | |
|--|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--|
| | www.hcdiaonostics.com | |
| | 1 (2011) 11:12 PM (2017) 11:12 PM (2017) 11:11) 11:11 PM (2019) 11:10 PM (2017) 11:11 PM (2016) 11:10 PM (2016) 11:10 PM (2014) 11:11 | |
| | | |

{5}------------------------------------------------

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 calcium. 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 (U/L) | %CV | SD (U/L) | %CV |
| 1 | A | 5.3 | 0.07 | 1.3 | 0.11 | 2.1 |
| 2 | A | 5.4 | 0.06 | 1.2 | 0.22 | 4.1 |
| 3 | A | 5.1 | 0.22 | 4.4 | 0.29 | 5.6 |
| 1 | B | 9.2 | 0.11 | 1.2 | 0.14 | 1.5 |
| 2 | B | 9.4 | 0.09 | 1.0 | 0.26 | 2.7 |
| 3 | B | 8.7 | 0.25 | 2.8 | 0.41 | 4.7 |
| 1 | C | 12.3 | 0.11 | 0.9 | 0.18 | 1.4 |
| 2 | C | 12.6 | 0.14 | 1.1 | 0.25 | 2.0 |
| 3 | C | 11.6 | 0.45 | 3.9 | 0.84 | 7.2 |

CA (mg/dL) n = 30 replicates per sample per site

For the external method comparison studies, a series of approximately 55 serum specimens with calcium values ranging from 1.3 to 14.6 mg/dL, were assayed on the Hitachi E40 Clinical Analyzer at three sites using S TEST Reagent Cartridge Calcium (y) and a comparative method as the reference method (x). Linear regression analyses (least squares) yielded the following results:

| Site # | n | Range<br>(mg/dL) | Regression<br>Equation | "r" | SE<br>(mg/dL) | CI*<br>Slope | CI Intercept |
|--------|----|------------------|------------------------|-------|---------------|--------------|--------------|
| 1 | 57 | 1.3 to 14.6 | y = 0.96x -0.2 | 0.986 | 0.4 | 0.91 to 1.00 | -0.5 to 0.3 |
| 2 | 55 | 1.4 to 14.0 | y = 0.97x -0.1 | 0.984 | 0.5 | 0.91 to 1.03 | -0.6 to 0.5 |
| 3 | 55 | 1.3 to 13.6 | y = 0.99x -0.1 | 0.987 | 0.4 | 0.95 to 1.04 | -0.6 to 0.3 |

## POL ACCURACY DATA SUMMARY- CA (mg/dL)

*95% Confidence Interval

## 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 Calcium. The test system was shown to be safe and effective for its intended use.

Page 6 of 6

#### O Hitachi Chemical Dlagnostics, Inc.

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

www.hcdiagnostics.com"

{6}------------------------------------------------

Image /page/6/Picture/1 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo consists of a stylized eagle with three stripes representing the agency's mission to protect the health of all Americans and provide essential human services. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular fashion around the eagle.

Public Health Service

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

May 2, 2013

Hitachi Chemical Diagnostics, Inc. C/O Ms. Erika Ammirati Ammirati Regulatory Consulting 575 Shirlynn Court LOS ALTOS CA 94022

Re: K130870

Trade/Device Name: S TEST Reagent Cartridge Calcium Regulation Number: 21 CFR 862.1145 Regulation Name: Calcium test system

- Regulatory Class: II Product Code: CIC Dated: March 28, 2013 Received: March 29, 2013
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 Part 801); 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.

{7}------------------------------------------------

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please go to http://www.fda.gov/AboutFDA/CentersOffices/CDRH/CDRHOffices/ucm115809.htm for the Center for Devices and Radiological Health's (CDRH's) Office of Compliance. 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/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Carol G. Benson -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

{8}------------------------------------------------

# INDICATIONS FOR USE

#### k130870 510(k) Number (if Known):

## Device Name:

S TEST Reagent Cartridge Calcium

## Indications for Use:

The S TEST Reagent Cartridge Calcium (CA) is intended for the quantitative determination of calcium in serum, lithium heparinized plasma, and sodium citrate plasma using the HITACHI Clinical Analyzer E40. The S TEST Reagent Cartridge Calcium is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only.

Calcium measurements are used in the diagnosis and treatment of parathyroid disease, a variety of bone diseases, chronic renal disease and tetany (intermittent muscular contractions or spasms).

Prescription Use X (21 CFR Part 801 Subpart D) And/Or

Over the Counter Use _________________________________________________________________________________________________________________________________________________________ (21 CFR Part 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostics and Radiological Health (OIR)

# Yung MD Chan -S

Division Sign-Off "Office of In Vitro Diagnostics and Radiological Health (OIR)

510(k) k130870

Page 1 of 1