ADVIA CHEMISTRY TRIGLYCERIDES_2 (TRIG_2) REAGENT

K133067 · Siemens Healthcare Diagnostics, Inc. · CDT · Nov 22, 2013 · Clinical Chemistry

Device Facts

• Record ID: K133067
• Device Name: ADVIA CHEMISTRY TRIGLYCERIDES_2 (TRIG_2) REAGENT
• Applicant: Siemens Healthcare Diagnostics, Inc.
• Product Code: CDT · Clinical Chemistry
• Decision Date: Nov 22, 2013
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1705
• Device Class: Class 1

Intended Use

The ADVIA® Chemistry Triglycerides 2 assay (TRIG 2) is intended for in vitro diagnostic use in the quantitative measurement triglycerides in human serum and plasma on the ADVIA® Chemistry systems. Measurements of triglycerides are used in the diagnosis and treatment of patients with diabetes mellitus, nephrosis, liver obstruction, other diseases involving lipid metabolism, or various endocrine disorders.

Device Story

ADVIA Chemistry Triglycerides 2 (TRIG 2) is a ready-to-use liquid reagent for automated clinical chemistry analyzers (ADVIA 1800). Input: human serum or plasma samples. Principle: Fossati three-step enzymatic reaction; lipase converts triglycerides to glycerol and fatty acids; glycerol kinase and glycerol-3-phosphate-oxidase produce hydrogen peroxide; peroxidase catalyzes formation of colored complex with 4-aminophenazone and 4-chlorophenol. Output: absorbance measured at 505/694 nm, proportional to triglyceride concentration. Used in clinical laboratories by trained personnel. Results assist physicians in diagnosing and monitoring lipid metabolism, diabetes, and endocrine disorders.

Clinical Evidence

Bench testing only. Precision established per CLSI EP5-A2 (N=80 per sample, total CV 0.4-1.0%). Linearity assessed across 10-550 mg/dL range (R²=0.9998). LoB/LoD/LoQ determined per CLSI EP17-A2 (LoQ=10 mg/dL). Method comparison with predicate (N=101) yielded slope 0.94, intercept 4.4 mg/dL. Matrix comparison (N=60) performed for Lithium Heparin and K-EDTA plasma. Interference testing evaluated bilirubin, hemolysis, and ascorbic acid; bias >10% defined as significant interference.

Technological Characteristics

Liquid enzymatic reagent; Fossati three-step method (lipase, glycerol kinase, glycerol-3-phosphate-oxidase, peroxidase). Endpoint measurement at 505/694 nm. Traceable to NIST SRM909c. Packaged in 40 mL wedges. Compatible with ADVIA 1800 Chemistry system. Calibrated using Siemens Set-Point Chemistry calibrator (k030169).

Indications for Use

Indicated for quantitative measurement of triglycerides in human serum and plasma to aid in diagnosis and treatment of patients with diabetes mellitus, nephrosis, liver obstruction, lipid metabolism disorders, or endocrine disorders.

Regulatory Classification

Identification

A triglyceride test system is a device intended to measure triglyceride (neutral fat) in serum and plasma. Measurements obtained by this device are used in the diagnosis and treatment of patients with diabetes mellitus, nephrosis, liver obstruction, other diseases involving lipid metabolism, or various endocrine disorders.

Submission Summary (Full Text)

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KB3067

# 510(k) Summary of Safety and Effectiveness ADVIA® 1800 Chemistry Triglycerides 2 Reagents (TRIG 2)

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.

2. 510(k) Number:

- 2. Applicant:

| Contact: | Kira Gordon, PhD<br>Sr. Regulatory Affairs Specialist |
|----------|---------------------------------------------------------------------------------|
| Address: | Siemens Healthcare Diagnostics, Inc<br>511 Benedict Ave,<br>Tarrytown, NY 10591 |
| Phone: | [phone]<br>[phone] (FAX) |

- September 26. 2013 3. Date:
#### 4. Proprietary and Established Names: ADVIA® Chemistry Triglycerides 2 Assay (TRIG 2)

#### 5. Regulatory Information:

Regulation section: 21 CFR §862.1705, Triglyceride test system Classification: Class I, Reserved Product Code: CDT Panel: Clinical Chemistry

#### 6. Predicate Device:

Device Name: Dimension Clinical Chemistry Triglycerides FLEX reagent cartridge Common Name: Dimension Clinical Chemistry Triglycerides reagent 510(k) Number: k010871 Panel: Clinical Chemistry Manufacturer Siemens Healthcare Diagnostics, Inc.

### 7. Intended Use:

The ADVIA® Chemistry Triglycerides 2 assay (TRIG 2) is intended for in vitro diagnostic use in the quantitative measurement triglycerides in human serum and plasma on the ADVIA® Chemistry systems. Measurements of triglycerides are used in the diagnosis and treatment of patients with diabetes mellitus, nephrosis, liver obstruction, other diseases involving lipid metabolism, or various endocrine disorders.

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# 8. Indications for Use:

Same as Intended Use

# 9. Device Description:

The Triglyceride 2 reagent is a ready-to-use liquid reagent packaged for use on the automated ADVIA 1800 Chemistry system. It is supplied as a 358 tests/wedge. 4 wedges/Kit with a 38 mL fill in a 40 mL wedge size.

Existing Siemens Set-Point Chemistry calibrator (classified under CFR 862.1150 - calibrator, multi-analyte mixture, product code JIX), cleared under 510k k030169, is used to calibrate the assay on the ADVIA Chemistry systems.

# 10. Test Principle:

The Triglycerides method is based on the Fossati three-step enzymatic reaction with a Trinder endpoint. The single-reagent procedure measures the concentrations of the total triglycerides including mono and diglycerides and the free glycerol fractions. The triglycerides are converted to glycerol and free fatty acids by lipase. The glycerol is then converted to glycerol-3-phosphate by glycerol kinase followed by its conversion by glycerol-3-phosphate-oxidase to hydrogen peroxide. A colored complex is formed from hydrogen peroxide, 4-aminophenazone and 4-chlorophenol under the catalytic influence of peroxidase. The absorbance of the complex is measured as an endpoint reaction at 505/694 nm.

# 11. Substantial Equivalence Information:

| Predicate device name: | Dimension Clinical Chemistry Triglycerides FLEX Reagent<br>cartridge |
|------------------------|----------------------------------------------------------------------|
| Predicate K number: | k010871 |

| Item | New Device:<br>ADVIA 1650 Chemistry<br>Triglyceride (TRIG_2) Assay | Predicate Device:<br>Dimension Clinical Chemistry<br>Triglycerides FLEX Reagent<br>cartridge (TGL) |
|--------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------|
| Analyte | Triglycerides | Same |
| Intended Use | For <i>in vitro</i> diagnostic use in the<br>quantitative measurement of<br>triglycerides. | Same |
| Indications for Use | Measurements obtained by this<br>device are used in the diagnosis<br>and treatment of patients with<br>diabetes mellitus, nephrosis, liver<br>obstruction, other diseases<br>involving lipid metabolism, or<br>various endocrine disorders | Same |
| Instrument to be<br>used | ADVIA 1800 Chemistry System | Dimension Clinical Chemistry<br>system (XPand) |
| Measurement | quantitative | Same |
| Sample type | Serum, Plasma | Same |

# Comparison with Predicate:

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| Reference interval | Normal: < 150 mg/dL<br>Borderline high: 150-199 mg/dL<br>High 200-499 mg/dL<br>Very high > 500 mg/dL | Same |
|----------------------------------|------------------------------------------------------------------------------------------------------|-----------------|
| Format | Liquid | Same |
| Use of Calibrators | Yes | Same |
| Analytical<br>measuring interval | 10 - 550 mg/dL | 15 - 1000 mg/dL |
| Method Principle | enzymatic | Same |
| Reagents | One Reagent | Same |

# 12. Standard/Guidance Document Reference

- · Interference Testing in Clinical Chemistry; Approved Guideline Second Edition (CLSI EP7-A2)
- · Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline - Second Edition (CLSI EP17-A2)
- · Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline-Second Edition (CLSI EP5-A2)

# 13. Performance Characteristics

The following data represent typical performance of the ADVIA Chemistry Triglycerides 2 assay and were collected on ADVIA 1800 Chemistry system. Substantial equivalence was demonstrated by testing several performance characteristics including imprecision, method comparison, interfering substances and analytical range. All of the evaluation studies gave acceptable results when compared to the predicate device. These studies support that the ADVIA® Chemistry Triglycerides 2 assay on ADVIA® 1800 Chemistry system is substantially equivalent to the predicate device.

# 1. Precision

..............................................................................................................................................................................

Within run and Total Precision were established by assaving serum sample pools and serum based controls. Each sample was assayed 2 replicates per run, 2 runs per day, for at least 20 days. Precision estimates were computed according to CLSI document EP5-A2, Evaluation of Precision Performance of Quantitative Measurement Methods: Approved Guideline,

| | | MEAN | | Within Run | | Between Run | | Between Day | Total | |
|---------------|----|-------|------|------------|------|-------------|------|-------------|-------|-----|
| Product | N | mg/dL | SD | CV | SD | CV | SD | CV | SD | CV |
| Serum Control | 80 | 183 | 1.60 | 0.9 | 0.42 | 0.2 | 0.64 | 0.3 | 1.77 | 1.0 |
| Serum Control | 80 | 92 | 0.28 | 0.3 | 0.31 | 0.3 | 0.71 | 0.8 | 0.82 | 0.9 |
| Serum Pool | 80 | 254 | 0.86 | 0.3 | 1.31 | 0.5 | 1.31 | 0.5 | 2.04 | 0.8 |
| Serum Pool | 80 | 503 | 1.16 | 0.2 | 0.89 | 0.2 | 1.37 | 0.3 | 2.00 | 0.4 |

# 2. Linearity/assay reportable range

A linearity study across the entire assay measuring range was assessed on ADVIA 1800 Chemistry system using low and high serum pools. The low and high pools were mixed to make nine (9) intermediate levels and additional 3 levels at the low end of the assay. All

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samples were tested on the ADVIA 1800 Chemistry analyzer and the observed values were compared to the expected values. Linear/measuring range of the assay is 10 to 550 mg/dL with a deviation from linearity of ≤ 5%. The low end of the assay range is calculated based on the Limit of Quantitation. The high end of the assay range is based on the linearity calculations.

Image /page/3/Figure/1 description: The image shows a graph titled "ADVIA TRIG_2 Linearity" and "ADVIA 1800 Chemistry system". The graph plots "Observed TRIG_2 values (ng/mL)" on the y-axis against "Expected TRIG_2 values (ng/mL)" on the x-axis. A linear trendline is plotted on the graph, and the equation of the line is y = 1.005x + 2.4645, with an R-squared value of 0.9998.

..............................................................................................................................................................................

# 3. Limit of Blank, Limit of Detection, Limit of Quantitation

The estimations of the Limit of Blank (LoB), Limit of Detection (LoD) and Limit of Quantitation (LoQ) were performed according to CLSI guideline EP17-A2, Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures. The LoB for the ADVIA Chemistry TRIG 2 assay on ADVIA 1800 Chemistry system is 5 mg/dL. The Limit of Detection (LoD) is the smallest amount that this assay can reliably detect to determine presence or absence of an analyte. The LoD for ADVIA Chemistry TRIG 2 assay on ADVIA 1800 Chemistry system is 8 mg/dL. LoB and LoD values are determined with proportions of false positives (a) less than 5% and false negatives (8) less than 5%, based on 320 determinations with 160 blank and 160 low-level sample replicates. Limit of Quantitation (LoQ) is 10 mg/dL

## 4. Method comparison with predicate device

The performance of the ADVIA Chemistry Triglycerides 2 assay (v) for serum samples on ADVIA 1800 Chemistry system was compared with the performance of the predicate device. One hundred and one (101) serum samples with triglycerides concentrations throughout the range of the assay were tested. The results calculated using least squares linear regression (188 replicate) are as follows:

ADVIA Chemistry TRIG 2 on ADVIA 1800 Chemistry system = 0.94 (predicate device) + 4.4 mg/dL

Slope 95%CI: 0.93 to 0.95 Intercept 95% CI: 2.88 to 5.85 Sample range: 20 - 540 mg/dL

Siemens Healthcare Diagnostics, Inc. ADVIA® Chemistry TRIG_2 510(k) Premarket Notification September 2013

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# 5. Matrix comparison with predicate device

The performance of the ADVIA Chemistry Triglycerides 2 assay (y) for plasma samples on ADVIA 1800 Chemistry systems was compared with the performance of the predicate device. Sixty plasma samples (Lithium Heparin and Potassium EDTA) with triglycerides concentrations throughout the range of the assay were tested in parallel on ADVIA 1800 Chemistry system and the predicate device. The results calculated using linear regression (15th replicate) are as follows:

ADVIA Chemistry TRIG 2 on ADVIA 1800 Chemistry system Plasma (Lithium Heparin) = 1.01 (predicate device) - 2.6 mg/dL Slope 95% CI: 0.99 to 1.3 Intercept 95% CI: -5.95 to 0.73 Sample range: 34 - 509 mg/dL

ADVIA Chemistry TRIG 2 on ADVIA 1800 Chemistry system Plasma (Potassium EDTA) = 1.02 (predicate device) - 7.5 g/dL Slope 95% CI: 1.00 to 1.03 Intercept 95% Cl: -10.18 to -4.76 Sample range: 34 - 509 mg/dL

## 6. Analytical specificity

Interferences from icterus, hemolysis, ascorbic acid were evaluated in the ADVIA Chemistry TRIG 2 assay on ADVIA Chemistry 1800 system using a significance criterion of >10% bias. 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.

| Interferent | Interferent Level | Triglycerides<br>Sample<br>Concentration | Interference |
|-----------------------------|-------------------|------------------------------------------|--------------|
| Bilirubin<br>(conjugated) | 15 mg/dL | 148.0 mg/dL | NSI* |
| | 22.5 mg/dL | 148.0 mg/dL | -12.0% |
| | 30.0 mg/dL | 505.0 mg/dL | NSI* |
| Bilirubin<br>(unconjugated) | 7.5 mg/dL | 148.0 mg/dL | NSI* |
| | 15.0 mg/dL | 148.0 mg/dL | +12.4% |
| | 30.0 mg/dL | 506.0 mg/dL | NSI* |
| Hemolysis<br>(hemoglobin) | 500.0 mg/dL | 138.0 mg/dL | NSI* |
| | 750.0 mg/dL | 138.0 mg/dL | +11.9% |
| | 1000.0 mg/dL | 473.0 mg/dL | NSI* |
| Ascorbic Acid | 3.0 mg/dL | 144.0 mg/dL | NSI* |
| | 6.0 mg/dL | 144.0 mg/dL | -13.1% |
| | 12.0 mg/dL | 492.0 mg/dL | NSI* |

· NSI = No Significant Interference. A percentage effect of ≥ 10% is considered a significant interference.

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# 7. Reference Interval (Expected Values*) Normal: < 150 mg/dL Borderline high: 150 - 199 mg/dL High: 200 - 499 mg/dL Very High: > 500 mg/dL * - Wu AHB. Tietz Clinical Guide to Laboratory Tests, 4th ed., Saunders Elsevier, St. Louis, MO. 2006:1074.

Siemens provides this information for reference. As with all in vitro diagnostic assays each laboratory should determine its normal range.

# 8. Stability:

..............................................................................................................................................................................

Reagent: for opened products, once placed on the system reagents are stable for 60 days. The shelf life of the ADVIA Chemistry Albumin Triglycerides 2 Reagents is 12 months at 2-8°C. For unopened product, see the expiration date on the calibrator carton.

# 9. Traceability

The assay is traceable to the reference material SRM909c from the National Institute of Standards and Technology (NIST). Assigned values of the Siemens Chemistry Calibrator are traceable to this standardization

# 14. Clinical Studies

Not applicable.

# 15. Clinical cut-off

Not applicable

# 16. Conclusion

The ADVIA Chemistry Triglycerides 2 Assay (TRIG 2) is substantially equivalent in principle and performance to the Siemens Healthcare Diagnostics Dimension Triglycerides FLEX reagent cartridge cleared under k010871.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/6/Picture/1 description: The image shows the logo for the Department of Health & Human Services USA. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" around the perimeter. In the center of the seal is an abstract symbol that resembles an eagle or bird-like figure. The symbol is composed of three curved lines that form the body and wings of the bird.

Public Health Service

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

November 22, 2013

SIEMENS HEALTHCARE DIAGNOSTICS, INC. KIRA GORDON, PH.D. SR. REGULATORY AFFAIRS SPECIALIST 511 BENEDICT AVE TARRYTOWN NY 10591

Re: K133067

Trade/Device Name: ADVIA Chemistry Triglycerides_2 (TRIG_2) Reagent Regulation Number: 21 CFR 862.1705 Regulation Name: Triglyceride test system Regulatory Class: I, meets limitations of exemptions, 21 CFR 862.9(c)(4) Product Code: CDT Dated: September 26, 2013 Received: September 27, 2013

Dear Dr. Gordon:

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. Drue, 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. Iisting 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 (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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Page 2-Dr. Gordon

If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Small Manufacturers, International (1) Consumer Assistance at its toll-free number [phone] or [phone] or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, plaase noce the regulation entitled, "Misbranding by reference to premarket notification" (21CFF) 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/MedicalDcvices/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 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

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

# Indications for Use

510(k) Number (if known) k133067

#### Device Name

:

ADVIA® Chemistry Triglycerides_2 (TRIG_2) Reagent

#### Indications for Use (Describe)

For in vitro diagnostic use in the quantitative measurement triglycerides in human serum or the ADVIA® Chenistry systems. Measurements obtained by this device are used in the diagnosis with diabetes mellitus, nephosis, liver obstruction, other diseases involving lipid metabolism, or various endocrine disorders.

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

2 Prescription Use (Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR 807 Subpart C)

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

#### FOR FDA USE ONLY

Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)

FORM FDA 3881 (6/13)

, '

Form Approved: OMB No. 0910-0120 Expiration Date: December 31, 2013 See PRA Statement on last page.