ADVIA CHEMISTRY LIPOPROTEIN(A) REAGENT ADVIA CHEMISTRY LIPOPROTEIN(A) CALIBRATOR

K123046 · Siemens Healthcare Diagnostics, Inc. · DFC · Dec 20, 2012 · Immunology

Device Facts

• Record ID: K123046
• Device Name: ADVIA CHEMISTRY LIPOPROTEIN(A) REAGENT ADVIA CHEMISTRY LIPOPROTEIN(A) CALIBRATOR
• Applicant: Siemens Healthcare Diagnostics, Inc.
• Product Code: DFC · Immunology
• Decision Date: Dec 20, 2012
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.5600
• Device Class: Class 2
• Attributes: AI/ML

Intended Use

The ADVIA® Chemistry Lipoprotein (a) assay is for in vitro diagnostic use in the quantitative measurement of lipoprotein(a) (Lp(a)) in human serum or plasma on the ADVIA Chemistry systems. Measurement of Lp(a) may aid in the diagnosis of disorders of lipid (fat) metabolism and assessing persons at risk for cardiovascular diseases when used in conjunction with clinical evaluation and other lipoprotein tests. The ADVIA Chemistry Lipoprotein (a) calibrator is for in vitro diagnostic use in the calibration of ADVIA® Chemistry systems for the ADVIA Chemistry Lipoprotein(a) (LPA) assay.

Device Story

Quantitative immunoturbidimetric assay for Lp(a) measurement in human serum or plasma. Uses ADVIA 1650 Chemistry system; reagents include glycine-EDTA buffer and latex particles coated with rabbit anti-human Lp(a) antibodies. Sample dilution followed by reagent mixing triggers antibody-antigen complex formation; resulting turbidity measured at 694 nm. Turbidity is directly proportional to Lp(a) concentration. Used in clinical laboratory settings by trained personnel. Output provides quantitative Lp(a) concentration (mg/dL) to assist clinicians in evaluating lipid metabolism and cardiovascular risk. Calibrators are lyophilized human serum-based products.

Clinical Evidence

Bench testing only. Precision evaluated per CLSI EP05-A2 (Total CV 1.1-1.6%). Linearity assessed across 7.75-102.30 mg/dL range. LoB=6.0 mg/dL, LoD=9.0 mg/dL, LoQ=10.0 mg/dL. Interference testing (hemoglobin, triglycerides, bilirubin) showed recovery within ±10%. Method comparison with predicate (n=68 serum, n=44 plasma) showed slope 1.01 and r=0.99.

Technological Characteristics

Latex-particle-enhanced immunoturbidimetric assay. Reagents: two-part liquid (R1 buffer, R2 antibody-coated latex). Calibrators: lyophilized human serum-based, 5 levels. Measurement: 694 nm absorbance. Instrument: ADVIA 1650 Chemistry system. Standards: CLSI EP07-A2 (interference), EP17-A (LoD/LoQ), EP05-A2 (precision).

Indications for Use

Indicated for the quantitative measurement of lipoprotein(a) in human serum or plasma to aid in diagnosing lipid metabolism disorders and assessing cardiovascular disease risk in patients, when used with clinical evaluation and other lipoprotein tests.

Regulatory Classification

Identification

A low-density lipoprotein immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the low-density lipoprotein in serum and other body fluids. Measurement of low-density lipoprotein in serum may aid in the diagnosis of disorders of lipid (fat) metabolism and help to identify young persons at risk from cardiovascular diseases.

Predicate Devices

• Randox Lipoprotein(a) assay (k011568)
• Randox Lipoprotein(a) Calibrator Series (k011568)

Submission Summary (Full Text)

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# DEC 2 0 2012

## 510(k) Summary of Safety and Effectiveness for the ADVIA® Chemistry Lipoprotein(a) Assay

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.

K123046 A. 510(k) Number:

B. Date of Preparation: 09/25/2012

### C. Proprietary and Established Names:

ADVIA® Chemistry Lipoprotein(a) (LPA) Assay ADVIA® Chemistry Lipoprotein(a) Calibrator

### D. Applicant

| Contact: | Neil Parker<br>Regulatory Affairs |
|----------|---------------------------------------------------------------------------------|
| Address: | Siemens Healthcare Diagnostics, Inc<br>511 Benedict Ave,<br>Tarrytown, NY 10591 |
| Phone: | [phone] |

## E. Regulatory Information:

Reagent

- 1. Regulation section: 21 CFR \$866.5600, LOW DENSITY LIPOROTEIN IMMUNOLOGICAL TEST SYSTEM
- 2. Classification: Class II
- 3. Product Code: DFC
- 4. Panel: Immunology
- Calibrator
- 1. Regulation section: 21 CFR §862.1150, Calibrator, secondary
- 2. Classification: Class II
- 3. Product Code: JIT
- 4. Panel:

Siemens Healthcare Diagnostics, Inc. ADVIA® Chemistry Lipoprotein(a) Assay Premarket Notification 510(k) - 510(k) Summary Page 1 of 7

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Clinical Chemistry

## F. Predicate Device:

Reagent

- 1. Device Name: Randox Lipoprotein (a) assay
- 2. Common Name: Randox Lipoprotein (a) assay
- 3. 510(k) Number: k011568
- 4. Manufacturer: Randox Laboratories, Ltd. Uk.

Calibrator

- 1. Device Name: Randox Lipoprotein(a) Calibrator Series
- 2. Common Name: Randox Lipoprotein(a) Calibrator Series
- 3. 510(k) Number: k011568
- 4. Manufacturer: Randox Laboratories, Ltd. UK.

## G. Intended Use:

The ADVIA® Chemistry Lipoprotein (a) assay is for in vitro diagnostic use in the quantitative measurement of lipoprotein(a) (Lp(a)) in human serum or plasma on the ADVIA Chemistry systems. Measurement of Lp(a) may aid in the diagnosis of disorders of lipid (fat) metabolism and assessing persons at risk for cardiovascular diseases when used in conjunction with clinical evaluation and other lipoprotein tests.

The ADVIA Chemistry Lipoprotein (a) calibrator is for in vitro diagnostic use in the calibration of ADVIA® Chemistry systems for the ADVIA Chemistry Lipoprotein(a) (LPA) assay.

## H. Device Description:

The Lipoprotein(a) reagents are ready-to-use liquid reagents packaged for use on the automated ADVIA 1650 Chemistry system. They are supplied as a 100 tests/wedge, 2 wedges/kit. ADVIA Chemistry Lipoprotein(a) calibrator is a single analyte, human serum based product containing human lipoprotein (a). The kit consists of 1 vial each of 5 calibrator levels which are lyophilized. The target concentrations of these calibrators are

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7.5, 15, 30, 65, and 95 mg/dL. The volume per vial (after reconstitution with deionized water) is 1.0 mL. Deionized water is recommended to be used as a zero calibrator.

### l. Test Principle:

In the ADVIA Chemistry Lipoprotein(a) assay, sample is diluted and then mixed with the R1 reagent (a buffer), followed by an addition of the R2 reagent (which contains latex particles coated with antibodies specific for Lipoprotein (a). The formation of the antibody-antigen complex during the reaction results in an increase in turbidity. This turbidity is measured at 694 nm. By constructing a standard curve from the absorbance of standards, Lipoprotein (a) concentration of a sample can be determined. Increasing Lipoprotein (a) results in increasing turbidity.

## J. Substantial Equivalence Information:

| Item | New Device:<br>ADVIA 1650 Chemistry<br>Lipoprotein(a) | Predicate Device:<br>Randox Lipoprotein(a) assay |
|-------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Analyte | lipoprotein (a) | Same |
| Intended<br>Use/Indications for Use | is for in vitro diagnostic use in<br>the quantitative measurement<br>of lipoprotein(a) (Lp(a)) in<br>human serum or plasma on<br>the ADVIA Chemistry<br>systems. Measurement of<br>Lp(a) may aid in the diagnosis<br>of disorders of lipid (fat)<br>metabolism and assessing<br>persons at risk for<br>cardiovascular diseases when<br>used in conjunction with<br>clinical evaluation and other<br>lipoprotein tests. | Same - Immunoturbidimetric<br>assay for the quantitative in<br>vitro determination of<br>Lipoprotein(a) in human<br>serum or plasma.<br>This product is suitable for<br>use on the Hitachi 717<br>analyser. |
| Measurement | quantitative | Same |
| Sample type | Serum<br>Lithium Heparin Plasma | Serum<br>Lithium Heparin, Sodium EDTA<br>plasma |
| Format | Liquid | Liquid |
| Use of Calibrators | Yes | Yes |
| Analytical measuring<br>interval | 10.00 mg/dL- 85.00 mg/dL | 2-90 mg/dL |
| Method Principle | latex-particle-enhanced immuno-<br>tubidimetric | latex-particle-enhanced immuno-<br>tubidimetric |
| Reagents | Two | Two |

Reagent

Siemens Healthcare Diagnostics, Inc. ADVIA® Chemistry Lipoprotein(a) Assay Premarket Notification 510(k) - 510(k) Summary

Page 3 of 7

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| | R1 and R2 | R1 and R2 |
|-----------------------|----------------------|----------------------|
| Instrument to be used | ADVIA 1650 Chemistry | Hitachi 717 Analyzer |

Calibrator

| Item | New Device:<br>ADVIA Chemistry Lipoprotein(a)<br>calibrator | Predicate Device:<br>Randox Lipoprotein(a)<br>Calibrator Series |
|---------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------|
| Intended Use | For <i>in vitro</i> diagnostic use in the<br>calibration of ADVIA® Chemistry<br>systems for the ADVIA Chemistry<br>Lipoprotein(a) (LPA) assay. | Same - For use in the<br>calibration of Lipoprotein(a)<br>assays |
| Measured Analytes<br>(value assigned) | lipoprotein (a) | Same |
| Form | Lyophilized | Same |
| Matrix | Human serum | Same |
| Analyte source | Derived from human source | Same |
| Number of levels | Six (the lowest level is a zero-<br>level, not included) | Same |
| Fill Volume | 1.0 mL each vial | Same |
| Shelf Life Stability | 36 months at 2-8°C | Same |
| Open Vial stability | 14 days at 2-8°C | Same |

## K. Standard/Guidance Document Reference

- Interference Testing in Clinical Chemistry; Approved Guideline Second Edition . (CLSI EP07-A2)
- Protocols for Determination of Limits of Detection and Limits of Quantitation; . Approved Guideline (CLSI EP17-A)
- . Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline-Second Edition (CLSI EP05-A2)

## L. Performance Characteristics

All studies were performed using the ADVIA 1650 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 Lipoprotein(a) assay is substantially equivalent to the predicate device.

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#### Precision -

Within run and Total Precision were established by assaying 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 EP05-A2, Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline.

| | | | | | Within Run | | Between Run | | Between Day | | Total | |
|---------------|----------|----------|----------|-------|------------|-----|-------------|-----|-------------|-----|-------|-----|
| Sample | #<br>Day | #<br>Run | #<br>Rep | MEAN | SD | CV | SD | CV | SD | CV | SD | CV |
| Serum Control | 20 | 40 | 80 | 14.17 | 0.12 | 0.9 | 0.12 | 0.8 | 0.08 | 0.5 | 0.19 | 1.3 |
| Serum Control | 20 | 40 | 80 | 18.44 | 0.14 | 0.7 | 0.12 | 0.6 | 0.07 | 0.4 | 0.20 | 1.1 |
| Serum Pool 1 | 20 | 40 | 80 | 49.75 | 0.40 | 0.8 | 0.43 | 0.9 | 0.30 | 0.6 | 0.66 | 1.3 |
| Serum Pool 2 | 20 | 40 | 80 | 83.67 | 1.03 | 1.2 | 0.85 | 1.0 | 0.00 | 0.0 | 1.34 | 1.6 |

#### II. Linearity/assay reportable range

A linearity study across the entire measuring range was assessed using nine diluted samples prepared from high and low serum pools by dilution. All samples were tested on the ADVIA Chemistry analyzer. The range of samples tested was from 7.75 -102.30 mg/dL. The observed values were compared to the expected values. Linear/measuring range of the assay is 10 to 85.0 mg/dL. 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 calculation.

#### III. 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-A, Protocols for Determination of Limits of Detection and Limits of Quantitation, by running 160 replicates of "zero" serum pool and several serum pools with Lipoprotein (a) concentration up to 4 x LOD level. Data (LoB = 5.35 mg/dL, LoD = 8.90 mg/dL and LoQ = 9.02 mg/dL) support the following claims LoB = 6.0 mg/dL, LoD = 9.0 mg/dL and LoQ = 10.0 mg/dL.

## IV. Method and matrix comparison with predicate device

The performance of the ADVIA Chemistry Lipoprotein(a) assay (y) for serum samples was compared with the performance of Randox Lipoprotein(a) assay on the Hitachi 717 (x). sixty-eight serum samples were tested. The sample results ranged from 11.00 -81.60 mg/dL lipoprotein (a) (x), and gave a correlation coefficient of 0.99. The results calculated using least squares linear regression (18 replicate) are as follows:

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ADVIA Chemistry Lipoprotein (a) = 1.01 (predicate device) - 1.02 mg/dL Slope 95%C1: 1.00 - 1.02 Intercept 95% CI: - 1.47 - - 0.57

#### V. Matrix comparison with predicate device

The performance of the ADVIA Chemistry Lipoprotein(a) assay (y) for plasma samples on ADVIA Chemistry was compared with the performance of Randox Lipoprotein(a) assay on the Hitachi 717 (x). Forty-four plasma samples were tested; the sample results ranged from 12.0 - 80.1 mg/dL Lipoprotein(a) (x), and gave a correlation coefficient of 0.99. The results calculated using linear regression (188 replicate) are as follows:

ADVIA Chemistry 1650 Lipoprotein(a) = 1.01 (predicate device) - 0.98 mg/dL Slope 95%CI: 0.99 - 1.02 Intercept 95% CI: -1.49 - - 0.47

#### VI. Analytical specificity

Interferences from icterus, lipemia and hemolysis were evaluated in the ADVIA Chemistry Lipoprotein (a) assay using a significance criterion of >10% variance from the control. No significant interference was found at unconjugated bilirubin levels from 0-60 mg/dL in 14, 28, and 47 mg/dL lipoprotein (a) samples. No significant interference was found at conjugated bilirubin levels from 0-60 mg/dL in 14, 28, and 46 mg/dL lipoprotein (a) samples. No significant lipemia interference was found at Intralipid levels from 0-1000 mg/dL in 13, 26, and 44 mg/dL lipoprotein (a) samples. No significant hemoglobin interference was found at hemoglobin levels from 0-1000 mg/dL in 18, 31, and 46 mg/dL lipoprotein (a) samples.

VII. Clinical Studies

Not applicable.

VIII. Clinical cut-off

Not applicable

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## L. Conclusion

The ADVIA Chemistry Lipoprotein(a) assay is substantially equivalent in principle and performance to other products in commercial distribution intended for similar use. Most notably, it is substantially equivalent to the currently marketed Randox Lipoprotein(a) Assay (k011568).

The ADVIA Chemistry Lipoprotein(a) calibrator is substantially equivalent in principle and performance to other products in commercial distribution intended for similar use. Most notably, it is substantially equivalent to the currently marketed Randox Lipoprotein(a) Calibrator Series (k011568).

Siemens Healthcare Diagnostics, Inc. ADVIA® Chemistry Lipoprotein(a) Assay Premarket Notification 510(k) - 510(k) Summary

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Image /page/7/Picture/0 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized depiction of an eagle or bird-like figure with three curved lines forming its body and wings. The logo is surrounded by text that reads "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" in a circular arrangement.

### DEPARTMENT OF HEALTH & HUM AN SERVICES

Public Health Service

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-002

December 20, 2012

Siemens Healthcare Diagnostics, Inc. c/o Neil Parker 511 Benedict Ave. Tarrytown, NY 10591

Re: k123046

Trade/Device Name: ADVIA Chemistry Lipoprotein(a) Assay

ADVIA Chemistry Lipoprotein(a) Calibrator

Regulation Number: 21 CFR 866.5600

Regulation Name: Low Density Lipoprotein Immunological Test System Regulatory Class: Class II Product Code: DFC, JIT Dated: September 25, 2012 Received: September 28, 2012

Dear Mr. Parker:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into 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

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Page 2 – Neil Parker

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.

If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostics and Radiological Health at [phone]. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office

of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number [phone] or [phone] or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

#### Carol C.'Benson 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): k123046

Device Name:

ADVIA® Chemistry Lipoprotein(a) Assay ADVIA® Chemistry Lipoprotein(a) Calibrator

Indications for Use:

For in vitro diagnostic use in the quantitative measurement of lipoprotein(a) (Lp(a)) in human serum or plasma on the ADVIA Chemistry systems. Measurement of Lp(a) may aid in the diagnosis of disorders of lipid (fat) metabolism and assessing persons at risk for cardiovascular diseases when used in conjunction with clinical evaluation and other lipoprotein tests.

The ADVIA® Chemistry Lipoprotein(a) calibrators is intended for use in the calibration of ADVIA® Chemistry systems for the ADVIA Chemistry Lipoprotein(a) (LPA) assay.

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)

Bute Chealer

Division Sign-Off Office of In Vitro Diagnostics and Radiological Health

510(k) k12304.6