Dimension Vista MMB Assay

K143720 · Siemens Healthcare Diagnostics · JHY · Sep 18, 2015 · Clinical Chemistry

Device Facts

• Record ID: K143720
• Device Name: Dimension Vista MMB Assay
• Applicant: Siemens Healthcare Diagnostics
• Product Code: JHY · Clinical Chemistry
• Decision Date: Sep 18, 2015
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1215
• Device Class: Class 2

Intended Use

The MMB method is an in vitro diagnostic test for the quantitative measurement of mass creatine kinase MB isoenzyme (EC 2.7.3.2) in human serum and plasma on the Dimension Vista® System for confirmation of acute myocardial infarction.

Device Story

The Dimension Vista MMB Assay is a homogeneous sandwich chemiluminescent immunoassay using LOCI technology; it measures mass creatine kinase MB isoenzyme in human serum and plasma. The assay utilizes two synthetic bead reagents: Sensibeads (streptavidin-coated, photosensitive dye) and Chemibeads (anti-mass CK-MB monoclonal antibody, chemiluminescent dye). Sample incubation with biotinylated antibody and Chemibeads forms a sandwich; Sensibeads bind to biotin to create bead-pair immunocomplexes. Illumination at 680 nm triggers singlet oxygen diffusion from Sensibeads to Chemibeads, inducing chemiluminescence measured at 612 nm. The signal intensity is proportional to CK-MB concentration. The assay runs on the Dimension Vista 1500 System, a fully automated, microprocessor-controlled floor instrument. The system performs pipetting, mixing, and spectral intensity measurement. Healthcare providers use the quantitative output to confirm acute myocardial infarction. The device is intended for clinical laboratory use.

Clinical Evidence

Bench testing only. Precision/reproducibility evaluated per CLSI EP5-A2 (20 days, 3 instruments, 5 levels); within-lab CVs ranged 1.80%–5.99%. Linearity confirmed per CLSI EP6-A (1–300 ng/mL, r=0.999). Detection limits (LOB 0.4 ng/mL, LOD 0.8 ng/mL, LOQ 1.0 ng/mL) established per CLSI EP17-A2. Method comparison (n=111) against predicate system showed Passing Bablok slope 0.99 and intercept -0.16 ng/mL. No clinical studies performed.

Technological Characteristics

LOCI (Luminescent Oxygen Channeling Immunoassay) technology. Reagents: biotinylated monoclonal antibody, Chemibeads, Streptavidin Sensibeads. Detection: Photomultiplier tube (PMT) with multiple dynodes. System: fully automated, microprocessor-controlled, floor-model analyzer. Connectivity: integrated, non-wireless. Sterilization: N/A (reagents). Software: embedded firmware for instrument control and signal processing.

Indications for Use

Indicated for quantitative measurement of mass creatine kinase MB isoenzyme in human serum and plasma for confirmation of acute myocardial infarction. For prescription use only.

Regulatory Classification

Identification

A creatine phosphokinase/creatine kinase or isoenzymes test system is a device intended to measure the activity of the enzyme creatine phosphokinase or its isoenzymes (a group of enzymes with similar biological activity) in plasma and serum. Measurements of creatine phosphokinase and its isoenzymes are used in the diagnosis and treatment of myocardial infarction and muscle diseases such as progressive, Duchenne-type muscular dystrophy.

Predicate Devices

• Dimension Vista® MMB (Mass creatine kinase MB isoenzyme) (K970343)
• Dimension Vista® 1500 Integrated System (K051087)

Submission Summary (Full Text)

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Image /page/0/Picture/1 description: The image is a black and white logo for the U.S. Department of Health & Human Services. The logo features a stylized image of three human profiles facing right, with flowing lines suggesting hair or movement. The profiles are stacked slightly on top of each other. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular fashion around the image.

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

September 18, 2015

SIEMENS HEALTHCARE DIAGNOSTICS KATHLEEN DRAY-LYONS REGULATORY AND CLINICAL AFFAIRS SPECIALIST 500 GBC DRIVE, P.O. BOX 6101 NEWARK, DE 19714

Re: K143720

Trade/Device Name: Dimension Vista MMB Assay, Dimension Vista 1500 System Regulation Number: 21 CFR 862.1215 Regulation Name: Creatine phosphokinase/creatine kinase or isoenzymes test system Regulatory Class: Class II Product Code: JHY, JJE Dated: July 31, 2015 Received: August 3, 2015

Dear Ms. Kathleen Dray-Lyons:

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/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 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.

Sincerelv vours.

# 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) K143720

#### Device Name

· Dimension Vista® MMB (Mass creatine kinase MB isoenzyme) Assay

- · Dimension Vista® 1500 System
#### Indications for Use (Describe)

Dimension Vista® MMB Assay:

The MMB method is an in vitro diagnostic test for the quantitative measurement of mass

creatine kinase MB isoenzyme in human serum and plasma on the Dimension Vista® System for confirmation of acute myocardial infarction.

Dimension Vista® 1500 System:

The Siemens Healthcare Diagnostics Dimension Vista® 1500 System is an in vitro diagnostic device intended to duplicate manual analytical procedures such as pipetting, mixing, and measuring spectral intensities to determine a variety of analytes in human body fluids. Dimension Vista® chemical and immunochemical applications use photometric, turbidimetric, chemiluminescence, nephelometric and integrated ion-selective multisensor technology for clinical use.

X Prescription Use (Part 21 CFR 801 Subpart D)

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

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Siemens Healthcare Diagnostics
Dimension® Vista MMB Assay on the Dimension® Vista 1500 System 510(k) Premarket Notification

## 510(k) Summary

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

The assigned 510(k) number is: K143720

- 1. Manufacturer's Name, Address, Telephone, and Contact Person, Date of Preparation

| Manufacturer: | Siemens Healthcare Diagnostics Inc.<br>500 GBC Drive<br>Newark, DE 19714 |
|----------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Contact Information: | Siemens Healthcare Diagnostics Inc.<br>P.O. Box 6101<br>Newark, DE 19714<br>Attn: Kathleen Dray-Lyons<br>Tel: [phone]<br>Email: [e-mail] |
| Date of Preparation: | September 15, 2015 |

#### 2. Device Names:

- o Dimension Vista® MMB (Mass creatine kinase MB isoenzyme)
- Dimension Vista® 1500 System o

## Classifications:

- 21 CFR §862.1215; Creatine phosphokinase/creatine kinase or o isoenzymes test system, Class II
- 21 CFR §862.2160; Analyzer, chemistry (photometric, discrete), For o Clinical Use, Class I

## Product Codes:

- o JHY
- o JJE

#### Panels:

- o Chemistry
#### 3. Identification of the Predicate Devices:

Dimension Vista® MMB (Mass creatine kinase MB isoenzyme) - K970343 Dimension Vista® 1500 Integrated System - K051087

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Siemens Healthcare Diagnostics
Dimension® Vista MMB Assay on the Dimension® Vista 1500 System 510(k) Premarket Notification

#### Device Description: 4.

## Dimension Vista® MMB Assay:

The MMB method is a homogeneous sandwich chemiluminescent immunoassay based on LOCI® technology. LOC10 reagents include two synthetic bead reagents and a biotinylated antimass creatine kinase MB isoenzvme monoclonal antibody fragment. The first bead reagent (Sensibeads) is coated with streptavidin and contains photosensitive dye. The second bead reagent (Chemibeads) is coated with a second anti-mass creatine kinase MB isoenzyme monoclonal antibody and contains chemiluminescent dye. Sample is incubated with Chemibeads and biotinylated antibody to form a beadmass creatine kinase MB isoenzyme-biotinylated antibody sandwich. Sensibeads are added and bind to the biotin to form bead-pair immunocomplexes. Illumination of the complex by light at 680 nm generates singlet oxygen from Sensibeads which diffuses into the Chemibeads, triggering a chemiluminescent reaction. The resulting signal is measured at 612 nm and is a direct function of the mass creatine kinase MB isoenzyme concentration in the sample.

#### The Dimension Vista® 1500 System:

The Dimension Vista® 1500 System is a floor model, fully automated, microprocessor-controlled, integrated instrument system that uses prepackaged Flex reagent test cartridges to measure a variety of analytes in human body fluids. The system is a multi-functional analytical tool that processes chemical and immunochemical methodologies, utilizing photometric, turbidimetric, chemiluminescence, nephelometric, and integrated ion selective multisensor detection technologies for clinical use. The Dimension Vista® 1500 System can analyze up to 1500 tests/hour (typical, depending on the method mix) using a variety of analytical detection capabilities. Dimension Vista® 1500 System detection technologies are: Photometric, Turbidimetric, Chemiluminescent, Nephelometric, Multisensor, ion selective technology

#### 5. Device Intended Use:

## Dimension Vista® MMB Assay:

The MMB method is an in vitro diagnostic test for the quantitative measurement of mass creatine kinase MB isoenzyme (EC 2.7.3.2) in human serum and plasma on the Dimension Vista® System for confirmation of acute myocardial infarction.

## Dimension Vista® 1500 System:

The Siemens Healthcare Diagnostics Dimension Vista® 1500 System is an in vitro diagnostic device intended to duplicate manual analytical procedures such as pipetting, mixing, heating, and measuring spectral intensities to determine a variety of analytes in human body fluids. Dimension Vista® 1500 System chemical and immunochemical applications use photometric, turbidimetric, chemiluminescence, nephelometric and integrated ion-selective multisensor technology for clinical use.

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#### 6. Medical device to which equivalence is claimed:

The modified Dimension Vista® MMB test system for use on the Dimension Vista® 1500 System with the new photomultiplier tube (PMT) is substantially equivalent to the currently marketed Dimension Vista®MMB assay (K970343) on the Dimension Vista® 1500 Integrated System (K051087).

A comparison of the similarities and differences between the devices is provided in the following tables:

| Feature | Predicate<br>Dimension Vista® MMB Flex®<br>reagent cartridge | Proposed<br>Dimension Vista® MMB Flex®<br>reagent cartridge |
|--------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------|
| Intended Use | Dimension Vista®MMB Assay:<br>The MMB method is an <i>in vitro</i><br>diagnostic test for the<br>quantitative measurement of<br>mass creatine kinase MB<br>isoenzyme (EC 2.7.3.2) in<br>human serum and plasma on<br>the Dimension Vista® System for<br>confirmation of acute myocardial<br>infarction. | Same |
| Assay Range | 0.5–300 ng/mL | 1.0 – 300 ng/mL |
| Sample Type | Human serum and plasma | Same |
| Technology | LOCI® technology | Same |
| Sample size | 5 µL | Same |
| Reagents and<br>antibody | Biotinylated monoclonal<br>antibody, mass creatine kinase<br>MB isoenzyme Chemibeads,<br>Streptavidin Sensibeads, assay<br>buffer | Same |

## Dimension Vista® MMB Assay Similarities and Differences

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| | Predicate | Propose Device |
|-------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------|
| Feature | Dimension Vista® 1500<br>Integrated System<br>(Current) | Dimension Vista® 1500 System<br>(Modified with new PMT) |
| | Dimension Vista® 1500 Integrated<br>System | |
| Intended Use | The Siemens Healthcare<br>Diagnostics Dimension Vista®<br>Integrated System is an <i>in vitro</i><br>diagnostic device intended to<br>duplicate manual analytical<br>procedures such as pipetting,<br>mixing, heating, and measuring<br>spectral intensities to determine a<br>variety of analytes in human body<br>fluids. Dimension Vista® chemical<br>and immunochemical applications<br>use photometric, turbidimetric,<br>chemiluminescence, nephelometric<br>and integrated ion-selective<br>multisensor technology for clinical<br>use. | Same |
| System Control | Fully automated and controlled by<br>microprocessors | Same |
| User Interface | Contains graphical user interface<br>screens | Same |
| Detection<br>Technologies | Contains a photometer and a<br>multisensor electrode for<br>performing photometric tests, and<br>electrolyte tests. It also has a<br>LOCI® module for immunoassay<br>tests. | Same |
| Reagents | Uses pre-packaged Flex® reagent<br>cartridges. Reagents are hydrated<br>and stored on-board the instrument | Same |
| Temperature | Reagents are stored at 2 - 8°C.<br>Reactions are controlled at 37°C. | Same |
| Operating System | Windows Operating System | Same |
| Photomultiplier tube<br>used to count the<br>signal in the<br>chemiluminescent<br>methods | Contains a faceplate<br>❖ Contains a photocathode<br>❖ Contains an anode at end | Same |

# Similarities between the predicate Dimension Vista® 1500 System and the

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Siemens Healthcare Diagnostics
Dimension® Vista MMB Assay on
the Dimension® Vista 1500 System 510(k) Premarket Notification

## Differences between the predicate Dimension Vista® 1500 System and the Modified Dimension Vista® 1500 Integrated System with new PMT:

| Feature | Predicate<br>Dimension Vista® 1500<br>Integrated System (Current) | Propose Device<br>Dimension Vista® 1500<br>(Modified with new PMT) |
|-------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------|--------------------------------------------------------------------|
| Photomultiplier tube<br>used to count the<br>signal in the<br>chemiluminescent<br>methods | Vendor: Excelitas<br>Multiplier channel: Enhanced Glass<br>Single Surface Tube | Vendor: Hamamatsu<br>Multiplier channel: multiple dynodes |
| Component Area<br>Network (CAN<br>Board) | Included in current Dimension<br>Vista® 1500 Integrated System | Updated to also be compatible with<br>new PMT |

#### 7. Performance Characteristics

#### Method Comparison:

A split sample method comparison between the Dimension Vista® MMB assay (K970343) on the modified Dimension Vista® 1500 System with the new PMT and the predicate Dimension Vista® 1500 Integrated System (K051087), was performed with 111 native de-identified human serum and plasma samples across the assay range (1.0 to 300 ng/mL). Analysis of the results yielded the following:

| Method | Predicate<br>Sample<br>Range<br>(ng/mL) | Slope<br>(95% CI) | Intercept ng/dL<br>(95% CI) | Correlation<br>Coefficient<br>(std linear<br>regression) | n |
|-------------------------------|-----------------------------------------|-----------------------|-----------------------------|----------------------------------------------------------|-----|
| MMB<br>(Passing<br>Bablok) | 1.0 - 274.0 | 0.99<br>(0.98 - 0.99) | -0.16<br>(-0.20 - -0.10) | Not<br>applicable | 111 |
| MMB<br>(linear<br>regression) | 1.0 - 274.0 | 0.97 | 0.64 | 0.999 | 111 |

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## Precision:

Reproducibility testing was conducted in accordance with the CLSI/NCCLS Approved Guideline for User Evaluation of Precision Performance of Clinical Chemistry Devices EP5-A2. For each test level, a single test from two independent cups was analyzed twice per day for 20 days. The repeatability and within-lab standard deviations were calculated by the analysis of variance method.

Typical precision observed on the modified Dimension Vista® 1500 System is summarized below:

| Material | Mean<br>ng/mL | Repeatability | | Within-Lab Precision | |
|-----------------------------------------------------------------|---------------|---------------|------|----------------------|------|
| | | SD | %CV | SD | %CV |
| Thermo Cardiolmmune XL Liquid<br>Assayed Cardiac Marker Control | | | | | |
| QC1 | 8.66 | 0.15 | 1.72 | 0.22 | 2.59 |
| QC2 | 24.13 | 0.36 | 1.50 | 0.56 | 2.30 |
| QC3 | 70.73 | 0.91 | 1.28 | 1.27 | 1.80 |
| Plasma<br>Pool 1 | 3.26 | 0.15 | 4.71 | 0.19 | 5.99 |
| Plasma<br>Pool 2 | 6.15 | 0.15 | 2.45 | 0.21 | 3.40 |

## Modified Dimension Vista® 1500 System (new PMT)

# Linearity

Linearity across the assay range (1.0 to 300 ng/mL) was confirmed according to CLSI EP6-A. Evaluation of the Linearity of Quantitative Measurement, by testing a sample with a high concentration of MMB. This sample was serially diluted with a low concentration sample producing ten test samples ranging from 0 to 313.5 ng/mL. Each dilution was assayed in replicates of five. Data were analyzed using linear regression analysis [x-axis: theoretical concentration versus y-axis: measured concentration]. 200 - and 3rd -order polynomial regressions of the mean observed analyte values vs. expected concentrations were generated. A summary of the linearity data is presented below.

| Range of<br>Samples | Slope | Intercept | Correlation<br>Coefficient. | N |
|---------------------|-------|-----------|-----------------------------|----|
| 0 – 313.5 ng/mL | 1.004 | 0.170 | 0.999 | 10 |

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## LoB, LoD and LoQ

The Limit of Blank (LoB) was calculated to be 0.4 ng/mL [0.4 µg/L]. LoD is the lowest concentration of analyte that can be detected reliably, while LoB is the highest concentration that is likely to be observed for a blank sample. The Limit of Detection (LoD) was determined to be 0.8 ng/mL [0.8 µg/L]. The proportions of false positives (α) was less than 5% and false negatives (β) less than 5%, based on 260 determinations, with 60 blank replicates and 200 low level replicates.

The limit of quantitation (LoQ) corresponds to a within-laboratory imprecision coefficient of variation (CV) of ≤ 20% at a mass creatine kinase MB isoenzyme concentration ≤ 1.0 ng/mL [1.0 µg/L]. Refer to Attachment 1 and 2 for a copy of the LOB, LOD and LOQ protocol and line data respectively.

## Specificity

Specificity studies were not performed, because specificity is antibody dependent and there were no changes to the MMB assay antibody or concentration of the antibody conjuqates. In addition, the Dimension Vista® 1500 System new photomultiplier tube, which is used to count the signal, would not impact assay specificity. Refer to the original 510(k) clearance, k970343 for the specificity data.

#### 8. Conclusion:

The proposed modified Dimension Vista® MMB test system for use on the Dimension Vista® 1500 System is substantially equivalent to the current legally marketed device based on intended use, principle and the performance characteristics above.