DIMENSION VISTA ALKALINE PHOSPHATASE (ALPI) FLEX REAGENT CARTRIDGE DIMENSION VISTA ALKALINE PHOSPHATASE CALIBRATOR (ALPI

K122323 · Siemens Healthcare Diagnostics · CJO · Aug 28, 2012 · Clinical Chemistry

Device Facts

• Record ID: K122323
• Device Name: DIMENSION VISTA ALKALINE PHOSPHATASE (ALPI) FLEX REAGENT CARTRIDGE DIMENSION VISTA ALKALINE PHOSPHATASE CALIBRATOR (ALPI
• Applicant: Siemens Healthcare Diagnostics
• Product Code: CJO · Clinical Chemistry
• Decision Date: Aug 28, 2012
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1050
• Device Class: Class 2

Intended Use

The ALPI method is an in vitro diagnostic test for the quantitative measurement of alkaline phosphatase in human serum and plasma on the Dimension Vista® System. Measurements of alkaline phosphatase or its isoenzymes are used in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases. ALPI CAL is an in vitro diagnostic product for the calibration of alkaline phosphatase (ALPI) method on the Dimension Vista® System.

Device Story

The ALPI method is an in vitro diagnostic assay for quantitative measurement of alkaline phosphatase (ALP) in human serum and plasma. The device uses a Flex® reagent cartridge on the automated Dimension Vista® System. Principle of operation: ALP catalyzes transphosphorylation of p-nitrophenylphosphate (p-NPP) to p-nitrophenol (p-NP) in the presence of 2-amino-2-methyl-1-propanol (AMP) buffer, magnesium, and zinc ions. The system measures the change in absorbance at 405 nm (bichromatic 405/510 nm rate technique), which is directly proportional to ALP activity. The ALPI CAL is a liquid, human serum albumin-based calibrator containing porcine kidney ALP used to calibrate the assay. The system is operated by laboratory personnel in clinical settings. Results are used by physicians to diagnose and monitor liver, bone, parathyroid, and intestinal conditions.

Clinical Evidence

Bench testing only. Method comparison study (n=116) against predicate showed correlation coefficient r=0.999, slope 1.05. Serum vs. plasma comparison (n=50) showed r=0.999, slope 1.02. Precision testing (n=80) per CLSI EP5-A2 showed within-lab CVs ranging from 1.8% to 4.1%. Linearity established from 10–1000 U/L. Interference testing per CLSI EP7-A2 showed bias <10% for hemoglobin, bilirubin, and lipemia (up to 400 mg/dL). LoB, LoD, and LoQ determined per CLSI EP17-A.

Technological Characteristics

Reagent: Flex® cartridge containing p-NPP, AMP buffer, Mg/Zn ions. Calibrator: Liquid, human serum albumin-based, porcine kidney ALP. Measurement: Bichromatic rate (405/510 nm). Connectivity: Automated clinical chemistry analyzer. Standards: CLSI EP5-A2, EP6-A, EP7-A2, EP9-A2, EP17-A, C28-A3.

Indications for Use

Indicated for quantitative measurement of alkaline phosphatase in human serum and plasma to aid diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases. For use on Dimension Vista® System.

Regulatory Classification

Identification

An alkaline phosphatase or isoenzymes test system is a device intended to measure alkaline phosphatase or its isoenzymes (a group of enzymes with similar biological activity) in serum or plasma. Measurements of alkaline phosphatase or its isoenzymes are used in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases.

Submission Summary (Full Text)

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### 510k Summarv

## Dimension Vista® Alkaline Phosphatase Flex® reagent cartridge (ALPI) Dimension Vista® Alkaline Phosphatase Calibrator (ALPI CAL)

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

### 1. 510(k) Number k122323

## 2. Applicant: Rose T. Marinelli Siemens Healthcare Diagnostics, Inc. P.O. Box 6101, Newark, DE 19714-6101 Office Number: 302-631-8805; Fax Number: 302-631-6299

3. Date: July 31, 2012

### 4. Proprietary and Established Names:

Dimension Vista® Alkaline Phosphatase Flex® reagent cartridge, (ALPI) Dimension Vista® Alkaline Phosphatase Calibrator (ALPI CAL)

### 5. Regulatory Information:

Alkaline Phosphatase (ALPI) Flex® reagent cartridge

Regulation section: 21 CFR 862.1050 Alkaline phosphatase or isoenzymes test system Classification: Class II Product Code: CJO Panel: Clinical Chemistry

Alkaline Phosphatase Calibrator (ALPI CAL)

Regulation section: 21 CFR 862.1150 Calibrator, Secondary . Classification: Class II Product Code: JIT Panel: Clinical Chemistry

### 6. Predicate Devices:

The predicate device used to demonstrate substantial equivalence to the Dimension® Alkaline Phosphatase (ALPI) Flex® reagent cartridge is the ADVIA® Chemistry Alkaline Phosphatase AMP Method previously cleared under k991576.

The predicate device used to demonstrate substantial equivalence to the Dimension Vista® Alkaline Phosphatase Calibrator (ALPI CAL) is the Dimension Vista® Alkaline Phosphatase Calibrator previously cleared under k061818.

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## 7. Device Description:

The ALPI method employs alkaline phosphatase that catalyzes the transphosphorylation of pnitrophenylphosphate (p-NPP) to p-nitrophenol (p-NP) in the presence of the transphosphorylating buffer, 2 amino-2-methyl-1-propanol (AMP). The reaction is enhanced through the use of magnesium and zinc ions. The change in absorbance at 405 nm due to the formation of p-NP is directly proportional to the ALP activity, since other reactants are present in non-rate limiting quantities and is measured using a bichromatic (405, 510 nm) rate technique.

$$\text{p-NPP} + \text{AMP} \qquad \xrightarrow[\begin{array}{c} \text{pH} \ 10.25\\ \text{p-NP} \ \text{10.25} \\ \text{Mg/Zn} \end{array}} \qquad \text{p-NP} + \text{AMP} + \text{PO}_4$$

The ALPI CAL is a one (1) level, liquid calibrator. It is packaged as a kit of three vials of Calibrator A (Level 2) with 1.0 mL per vial. The product matrix is a human serum albumin based product containing alkaline phosphatase from porcine kidney. Level 1 is a zero level (system water). Level 2 contains alkaline phosphatase at 1000 U/L.

This product is sold separately from the Flex® reagent cartridge. Values are assigned to new lots from a Masterpool that is from an International Federation of Clinical Chemistry (IFCC) reference.

### 8. Intended Use:

The ALPI method is an in vitro diagnostic test for the quantitative measurement of alkaline phosphatase in human serum and plasma on the Dimension Vista® System. Measurements of alkaline phosphatase or its isoenzymes are used in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases.

ALPI CAL is an in vitro diagnostic product for the calibration of alkaline phosphatase (ALPI) method on the Dimension Vista® System.

### 9. Indication(s) for Use:

Same as Intended Use

### 10. Substantial Equivalence Information:

Both the Dimension Vista® Alkaline Phosphatase Flex® reagent cartridge (ALPI) assay and the predicate ADVIA® Chemistry Alkaline Phosphatase AMP assay employ prepackaged reagents for use on an automated clinical chemistry test systems. A comparison of the similarities and differences between the devices is provided in the following tables:

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# Similarities for Dimension Vista® ALPI assay:

| Feature | Dimension Vista® Alkaline Phosphatase Flex® reagent cartridge<br>Predicate: ADVIA® Chemistry Alkaline Phosphatase AMP k991576 |
|--------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | The ALPI method is an <i>in vitro</i> diagnostic test for the quantitative measurement of alkaline phosphatase in human serum and plasma on the Dimension Vista® System. Measurements of alkaline phosphatase or its isoenzymes are used in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases.<br>For <i>in vitro</i> diagnostic use in the quantitative determination of alkaline phosphatase in human serum and plasma on the ADVIA® Chemistry systems. Such measurements are used in the diagnosis and treatment of hepatobiliary and bone disease. |
| Sample Type | Serum and Lithium Heparin Plasma |
| Measurement | Bichromatic rate<br>Rate (RRA) |

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# Differences for Dimension Vista® ALPI assay:

| Feature | Dimension Vista® Alkaline<br>Phosphatase Flex® reagent cartridge | Predicate: ADVIA® Chemistry<br>Alkaline Phosphatase AMP Method<br>k991576 |
|--------------------|------------------------------------------------------------------|---------------------------------------------------------------------------|
| Measuring<br>Range | 10 - 1000 U/L | 0 - 1100 U/L |
| Sample Size | 3.48 µL | 3 µL |

# Similarities for Dimension Vista® ALPI Calibrator

| Feature | Dimension Vista® Alkaline<br>Phosphatase Calibrator ALPI CAL | Predicate: Dimension Vista®<br>Alkaline Phosphatase Calibrator<br>ALP CAL k061818 |
|--------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | ALPI CAL is an in vitro diagnostic<br>product for the calibration of<br>alkaline phosphatase (ALPI) method<br>on the Dimension Vista® System. | The ALP CAL is an in vitro<br>diagnostic product for the<br>calibration of Alkaline Phosphatase<br>(ALP) method on the Dimension<br>Vista® System. |
| Preparation | Liquid:<br>Provided ready to use. | Liquid:<br>Provided ready to use. |
| Storage | 2 – 8 °C | 2 – 8 °C |
| Target<br>Concentrations | Level 2 (CAL A): 1000 U/L<br>Note: Level 1 is System Water | Level 2: (CAL A) 1000 U/L<br>Note: Level 1 is System Water |

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Differences for Dimension Vista® ALPI CAL

| Feature | Dimension Vista® Alkaline<br>Phosphatase Calibrator ALPI CAL | Predicate: Dimension Vista®<br>Alkaline Phosphatase Calibrator<br>ALP CAL k061818 |
|--------------|--------------------------------------------------------------|-----------------------------------------------------------------------------------|
| Matrix | Human serum albumin based | Bovine protein based |
| Traceability | IFCC reference method | Masterpool values |

## 11. Standard/Guidance Document Reference:

- · Evaluation of Precision Performance of Quantitative Measurement in Methods; Approved Guideline (EP5-A2)
- · Evaluation of the Linearity of Quantitative Measurement Procedures; A Statistical Approach; Approved Guideline (EP6-A)
- · Interference Testing in Clinical Chemistry; Approved Guideline (EP7-A2)
- · Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline (EP9-A2)
- · Protocols for Determination of Limits of Detection and Quantitation; Approved Guideline (EP17-A)
- · Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory; Approved Guideline (C28-A3)

## 12. Performance Characteristics

The following data represent typical performance for the Dimension Vista® System and were collected on a Dimension Vista® 500.

## Method Comparison

Split sample comparison between the Dimension Vista® Alkaline Phosphatase assay and the ADVIA® Chemistry Alkaline Phosphatase AMP assay gave the following correlation statistics, when tested with patient samples:

| Dimension<br>Vista® | Predicate | Slope | Intercept U/L | Correlation<br>Coefficient (r) | n |
|---------------------|------------------|-------|---------------|--------------------------------|-----|
| ALPI | ADVIA®<br>ALPAMP | 1.05 | -0.4 | 0.999 | 116 |

Dimension® Alkaline Phosphatase (ALPI) vs. Predicate

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## Serum/Plasma Comparison

To demonstrate equivalency between serum and lithium heparin plasma for Dimension Vista® ALPI, comparison testing of 50 matched serum and lithium heparin plasma samples were tested on the Dimension Vista® System and gave the following linear regression statistics:

| Serum vs. | Slope | Intercept U/L | Correlation<br>Coefficient (r) | n |
|------------------------------|-------|---------------|--------------------------------|----|
| Lithium<br>Heparin<br>Plasma | 1.02 | -7.7 | 0.999 | 50 |

Serum vs. Plasma Comparison Data

## Reference Interval (Expected Values)

Samples were collected from 133 healthy adults and analyzed with the Dimension® ALPI method. The reference interval was calculated non-parametrically and represents the central 95% of results determined from the population.

Expected Values: 45-117 U/L [0.75 – 1.95 µkat/L]

### Precision

Precision testing was performed in accordance with CLSI EP5-A2 Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline – Second Edition. Samples consisted of three levels of Bio-Rad® Multiqual Assayed Quality Controls and two serum pools. Testing was performed over 20 days, two separate runs with two test samples for each test material. Analysis of variance (ANOVA) was used to evaluate the data consistent with the recommendations of EP5-A2. The data are summarized in the following Dimension Vista® Alkaline Phosphatase (ALPI) Summary Table:

| | Mean (U/L) | Repeatability | | Within-Lab | |
|------------------------------|------------|---------------|-----|-------------|--------|
| Sample n=80 | | SD (U/L) | %CV | SD<br>(U/L) | %CV |
| BioRad® Multiqual Assayed QC | | | | | |
| Level l | 34 | 1.0 | 2.9 | 1.4 | 4.1 |
| Level 2 | । રેર | 1.9 | 1.2 | 3.1 | 2.0 |
| Level 3 | 301 | 4.0 | 1.3 | 4.6 | ાં 'રે |
| Pools | | | | | |
| Serum Pool 1 | 78 | 1.3 | 1.7 | 1.5 | 1.9 |
| Serum Pool 2 | 833 | । 3.6 | 1.6 | 15.0 | 1.8 |

Linearity

The linear range was determined according to CLSI EP-6A, Evaluation of the Linearity of Quantitative Measurement Procedures; A Statistical Approved Guideline. Based on the results of this

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testing and the Limit of Detection testing on the Dimension Vista® System, the analytical measurement range was determined to be 10 – 1000 U/L.

Image /page/5/Figure/1 description: The image shows a graph titled "Vista ALPI Linearity Assessment with High Serum Pool". The x-axis is labeled "Expected ALPI Concentration (U/L)" and ranges from 0 to 1200. The y-axis is labeled "Observed ALPI Concentration (U/L)" and ranges from 0 to 1200. A line of best fit is plotted on the graph, and the equation of the line is y = 1.010x + 3.461, with an R-squared value of 0.999.

# Analytical Specificity/Interferences

The ALPI method was evaluated for interference according to CLSI EP7-A2 Interference Testing in The Ferrance The over as over wed Guideline - Second Edition. Bias is the difference in the results between the control sample (without the interferent) and the test sample (contains the interferent) expressed in percent. Bias exceeding 10% is considered interference.

| Substance Tested | Substance Concentration | Alkaline Phosphatase<br>U/L [µkat/L] | Bias<br>% |
|-----------------------------|--------------------------|--------------------------------------|------------|
| Hemoglobin<br>(hemolysate) | 1000 mg/dL [0.62 mmol/L] | 278 [4.641]<br>787 [13.14] | <10<br><10 |
| Bilirubin<br>(unconjugated) | 60 mg/dL [1026 µmol/L] | 269 [4.49]<br>804 [13.43] | <10<br><10 |
| Bilirubin<br>(conjugated) | 60 mg/dL [1026 µmol/L] | 268[4.48]<br>799 [13.34] | <10<br><10 |
| Lipemia<br>(Intralipid®) | 400 mg/dL [4 g/L] | 298 [4.98]<br>849 [14.18] | <10<br><10 |
| | 500 mg/dL [5 g/L] | 299 [4.99]<br>850 [14.20] | j<br>j |

j. Lipemia (Intralipid") at 500 mg/dL [5 g/L] and above tripped a test report message; interference could not be determined.

Studies were also performed following CLSI EP7-A2 for Interference Testing of exogenous substances at an alkaline phosphatase concentration of 286 U/L and 799 U/L and were found not to interfere with the

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ALPI method when present in serum and plasma. Inaccuracies (biases) were all less than 10%. See Dimension Vista® ALPI Instructions for Use for a full list of substances tested.

## Limit of Blank, Limit of Determination and Limit of Quantitation

The Limit of Blank (LoB), Limit of Detection (LoD) and Limit of Quantitation (LoQ) was evaluated in accordance with CLSI EP17-A Protocols for Determination of Limits of Detection and Limits of Quantitation; Approved Guideline. Studies were performed on the Dimension® clinical chemistry analyzer with the following results:

| Dimension® Alkaline Phosphatase (ALPI) | | |
|----------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------|----------|
| Limit | Protocol | Value |
| LoB | 5 samples of Enzyme Diluent<br>(zero level) were tested for 3<br>days, one run per day, 2<br>replicates per run, 2 reagent lots,<br>1 instrument | -0.2 U/L |
| LoD | 5 low level samples were tested<br>for 3 days, one run per day, 2<br>replicates per run, 2 reagent lots,<br>1 instrument | 1U/L |
| LoQ | 3 low level samples diluted with<br>enzyme diluent were tested for 3<br>days, one run per day, 3<br>replicates per run, 2 reagent lots,<br>1 instrument | 8 U/L |

Calibrator Stability and Value Assignment:

- For opened products, once the cap is removed, assigned values are stable for 7 days stored on the . Dimension Vista® System.
- Once cap is removed, assigned values are stable for 30 days when recapped immediately after use . and stored at 2-8℃. Do not use this vial on board the instrument.

The shelf life of the Dimension Vista® Alkaline Phosphatase Calibrator (ALPI CAL) is 12 months. For unopened product, see the expiration date on the calibrator carton.

Calibrator value assignments for anchor pools were assigned by a reference laboratory using the IFCC reference method. Masterpools are assigned in-house from anchor pools and commercial lots are assigned from the Masterpools using Dimension Vista® System.

13. Conclusion: The Dimension Vista® Alkaline Phosphatase (ALPI) Flex® reagent cartridge with the associated Dimension Vista® Alkaline Phosphatase Calibrator (ALPI CAL) are substantially equivalent in principle and performance to the ADVIA® Chemistry Alkaline Phosphatase AMP assay and Dimension Vista® Alkaline Phosphatase (ALP) calibrator respectively.

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Food and Drug Administration

10903 New Hampshire Avenue Silver Spring, MD 20993

Siemens Healthcare Diagnostics, Inc c/o Rose T. Marinelli 500 GBC Drive, MS 514 Newark, DE 19702

AUG 2 8 2012

k122323 Re:

Trade Name: Dimension Vista® Alkaline Phosphatase Flex®reagent cartridge, (ALPI) Dimension Vista® Alkaline Phosphatase Calibrator (ALPI CAL) Regulation Number: 21 CFR §862.1050 Regulation Name: Alkaline phosphatase or isoenzymes Test System Regulatory Class: Class II Product Codes: CJO, JIT Dated: July 31, 2012 Received: August 1, 2012

Dear Ms Marinelli::

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 approvisions 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 either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting (1 wr 1), it is a 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 modified in any Federal statutes and regulations administered by other Federal agencies. of mo recordly 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 and nismig (21 % 10 % 10 % = 10 % = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please If you desire specific advice 10. your as . Device Evaluation and Safety at [phone]. Also, comact the other of in Vitro Diaghosing by reference to premarket notification" (21 please note the regulation chance, "Minner," while and surveillance, please contact CDRH301 CI'K Fall 607.77). For questions regarding postmarket Surveillance at (301)
Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at (301) Office of Surveinance and Diolineare a (Oorting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/Medical

CI K Fall 803), picaso go to impliw will 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 Tou may other only 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,

.

Couriney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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# Indications for Use Form

510(k) Number (if known): _ K 122323

Device Name: Dimension Vista® Alkaline Phosphatase Flex® reagent cartridge (ALPI)

Indications for Use:

The ALPI method is an in vitro diagnostic test for the quantitative measurement of alkalinc phosphatase in human serum and plasma on the Dimension Vista® System. Measurements of alkaline phosphatase or its isoenzymes are used in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases.

Prescription Use X (Part 21 CFR 801 Subpart D)

AND/OR

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

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE OF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostics Devices (OIVD)

Division Sign-Off

Office of In Vitro Diagnostic Device

Evaluation and Safety

510(k) K122323

Page 1 of

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# Indications for Use Form

510(k) Number (if known): __ K 122323

Device Name: Dimension Vista® Alkaline Phosphatase Calibrator (ALPI CAL)

Indications for Use:

ALPI CAL is an in vitro diagnostic product for the calibration of alkaline phosphatase (ALPI) method on the Dimension Vista@ System.

Prescription Use ਮ (Part 21 CFR 801 Subpart D)

AND/OR

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

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE OF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostics Devices (OIVD)

Yung Chan

Division Sign-Off

Office of In Vitro Diagnostic Device

Evaluation and Safety

sio(k) k122323

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