ADVIA CENTAUR INACT PARATHYROID HORMONE (IPTH) ASSAY

K121981 · Siemens Healthcare Diagnostics · CEW · Mar 21, 2013 · Clinical Chemistry

Device Facts

• Record ID: K121981
• Device Name: ADVIA CENTAUR INACT PARATHYROID HORMONE (IPTH) ASSAY
• Applicant: Siemens Healthcare Diagnostics
• Product Code: CEW · Clinical Chemistry
• Decision Date: Mar 21, 2013
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1545
• Device Class: Class 2

Intended Use

The ADVIA Centaur iPTH assay is for in vitro diagnostic use in the quantitative determination of intact parathyroid hormone (iPTH) in EDTA plasma or serum using the ADVIA Centaur XP system. This assay is intended to be used to aid in the differential diagnosis of hyperparathyroidism and hypoparathyroidism.

Device Story

The ADVIA Centaur iPTH assay is a two-site sandwich immunoassay using direct chemiluminometric technology. It utilizes an automated system to process patient EDTA plasma or serum samples. The assay employs a polyclonal goat anti-human PTH (N-terminal 1-34) antibody labeled with acridinium ester and a biotinylated polyclonal goat anti-human PTH (39-84 region) antibody captured on streptavidin-coated paramagnetic latex particles. After washing, acid and base reagents are added to trigger a chemiluminescent reaction. The system detects relative light units (RLUs), which are directly proportional to the amount of iPTH in the sample. The output is a quantitative concentration of iPTH, used by clinicians to assist in the differential diagnosis of parathyroid disorders. The device is intended for use in clinical laboratory settings by trained laboratory personnel.

Clinical Evidence

Bench testing only. Precision evaluated per CLSI EP5-A2 (N=80 replicates per sample). Linearity evaluated per CLSI EP6-A (range 5.5-1900 pg/mL). LoB/LoD/LoQ determined per CLSI EP17-A (LoQ 5.55 pg/mL). Interference testing showed no significant interference from hemolysis, icterus, lipemia, or biotin. Cross-reactivity testing identified 51.4% cross-reactivity with PTH (7-84) fragment. Method comparison against predicate (N=177) yielded Y=1.03x-3.32, R=0.991. Reference range established using 180 healthy donor samples.

Technological Characteristics

Two-site sandwich immunoassay; direct chemiluminometric technology. Reagents: acridinium ester-labeled polyclonal goat anti-human PTH (1-34) and biotinylated polyclonal goat anti-human PTH (39-84) on streptavidin-coated paramagnetic latex particles. Automated system (ADVIA Centaur XP). Quantitative measurement. No specific material standards cited.

Indications for Use

Indicated for the quantitative determination of intact parathyroid hormone (iPTH) in EDTA plasma or serum to aid in the differential diagnosis of hyperparathyroidism and hypoparathyroidism in patients.

Regulatory Classification

Identification

A parathyroid hormone test system is a device intended to measure the levels of parathyroid hormone in serum and plasma. Measurements of parathyroid hormone levels are used in the differential diagnosis of hypercalcemia (abnormally high levels of calcium in the blood) and hypocalcemia (abnormally low levels of calcium in the blood) resulting from disorders of calcium metabolism.

Predicate Devices

• Abbott Architect Intact PTH Assay (k063232)

Submission Summary (Full Text)

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

#### 510(k) Summary of Safety and Effectiveness for the

#### ADVIA® Centaur Intact Parathyroid (iPTH) 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.

# A. 510(k) Number: K/2198)

B. Date of Preparation: March 8, 2013

#### C. Proprietary and Established Names:

ADVIA® Centaur Intact Parathyroid Hormone (iPTH) Assay

#### D. Applicant:

Siemens Healthcare Diagnostics Inc., 511 Benedict Ave, Tarrytown, NY 10591 Philip Liu, Senior Manager, Regulatory Affairs and Compliance Office: [phone] Fax: [phone]

#### E. Regulatory Information:

- 1. Regulation section: 21 CFR § 862.1545
- 2. Classification: Class II
- 3. Product Code: CEW, Parathyroid Hormone Test System
- 4. Panel: Clinical Chemistry

#### F. Predicate Device:

The ADVIA® Centaur iPTH Assay is substantially equivalent to the Abbott Architect Intact PTH Assay cleared under 510(k) k063232

#### G. Device Description:

The ADVIA Centaur iPTH assay is a two-site sandwich immunoassay using direct chemiluminometric technology, which uses constant amounts of an antihuman PTH antibody in the Lite Reagent and an antihuman PTH antibody in the Solid Phase Reagent. The first antibody is a polyclonal goat antihuman PTH (N-terminal 1-34) antibody labeled with acridinium ester. The second antibody is a biotinylated polyclonal goat antihuman PTH (39-84 region) antibody that is preformed to streptavidin coated paramagnetic latex particles in the Solid Phase reagent.

The ADVIA Centaur iPTH reagent kit contains the following:

- . ReadyPack® primary reagent pack containing ADVIA Centaur Lite and Solid Phase Reagent)
- ADVIA Centaur iPTH Master Curve card .

Siemens Healthcare Diagnostics ADVIA Centaur iPTH Premarket Notification 510(k) March, 2013

1

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

#### Materials Required but Not Provided

- iPTH Calibrator .
#### Optional Reagents

- ADVIA Centaur Multi-Diluent 11 .
- iPTH 1, 2, 3 quality control material .
- iPTH Master Curve Material .

#### H. Intended Use / Indications for Use:

The ADVIA Centaur iPTH assay is for in vitro diagnostic use in the quantitative determination of intact parathyroid hormone (iPTH) in EDTA plasma or serum using the ADVIA Centaur XP system. This assay is intended to be used to aid in the differential diagnosis of hyperparathyroidism and hypoparathyroidism.

#### l. Substantial Equivalence Information:

Both the ADVIA Centaur iPTH assay (New Device) and Abbott Architect Intact PTH assay (Predicate Device cleared under k063232) employ prepackaged reagents for use on automated test systems. A comparison of the important similarities and differences of these assays is shown in the following tables:

#### Similarities:

| Item | New Device:<br>ADVIA Centaur Intact PTH<br>Assay | Predicate Device:<br>Abbott Architect Intact PTH Assay |
|------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | For in vitro diagnostic use in the<br>quantitative determination of<br>intact parathyroid hormone (iPTH)<br>in EDTA plasma or serum using<br>the ADVIA Centaur systems | For in vitro chemiluminescent<br>microparticle immunoassay (CMIA) for<br>the quantitative determination of<br>intact parathyroid hormone (PTH) in<br>human serum and plasma on the<br>ARCHITECT i System |
| Indications for<br>Use | This assay is intended to be used<br>to aid in the differential diagnosis<br>of hyperparathyroidism and<br>hypoparathyroidism. | In conjunction with serum calcium levels,<br>this assay may be used as an aid in the<br>differential diagnosis of hypercalcemia,<br>hypocalcemia, or parathyroid disorders. |
| Sample type | EDTA Plasma, Serum | Serum and Plasma |
| Measurement | Quantitative | Same |
| Operating<br>Principle | Sandwich immunoassay | Same |
| Technology | Chemiluminescence | Same |
| Detection<br>Antibody | Goat polyclonal antibody<br>conjugated to Acridium Ester | Goat polyclonal antibody conjugated to<br>Acridium |
| Capture<br>Antibody | Goat polyclonal antibody<br>conjugated to biotin directly<br>coupled to streptavidin magnetic<br>particles | Goat polyclonal antibody coated to<br>microparticles |
| Interference | No significant interference by<br>hemolysis, icterus (bilirubin) | No significant interference from<br>hemoglobin, bilirubin, triglycerides or |

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

| Item | New Device:<br>ADVIA Centaur Intact PTH Assay | Predicate Device:<br>Abbott Architect Intact PTH Assay |
|--------------------------|----------------------------------------------------------|--------------------------------------------------------|
| | triglycerides, or biotin at tested<br>levels | protein at tested levels |
| Expected Values | 13.8 - 85.0 pg/mL (plasma)<br>12.4 - 76.8 pg/mL (serum) | 8.7 - 77.1 pg/mL |
| Calibration | 2 Point | 6 Point |
| Calibrators | Siemens iPTH Calibrators | ARCHITECT Intact PTH Calibrators |
| Number of<br>calibrators | Two (2) levels | Six (6) levels |
| Use of Controls | Yes (recommended) | Same |
| Number of<br>controls | Three levels | Same |
| Detection<br>Antibody | Goat polyclonal antibody<br>conjugated to Acridium Ester | Same |

#### Differences:

| Item | New Device:<br>ADVIA Centaur Intact PTH<br>Assay | Predicate Device:<br>Abbott Architect Intact PTH Assay |
|--------------------------|--------------------------------------------------|--------------------------------------------------------|
| Assay Range | 5.5 – 1900 pg/mL | 3.0 – 3000 pg/mL (Routine)<br>4.0 – 2500 pg/mL (STAT) |
| Sample Volume | 200 μL | 150 μL |
| Calibrators | Siemens iPTH Calibrators | ARCHITECT Intact PTH Calibrators |
| Calibration | 2 Point | 6 Point |
| Number of<br>calibrators | Two (2) levels | Six (6) levels |

#### J. Test Principle

The ADVIA Centaur Intact PTH assay is a two-site sandwich immunoassay using direct chemiluminometric technology. PTH in the sample reacts with the first antibody which is a polyclonal goat anti-human PTH (N-terminal 1-34) antibody labeled with acridinium ester. This complex is then captured by the solid phase (a second antibody which is a biotinylated polyclonal goat anti-human PTH (39-84 region) antibody that is preformed to streptavidin coated paramagnetic latex particles). Unbound materials are then removed by washing. Acid Reagent and Base Reagent are then added to initiate the chemiluminescent reaction. A direct relationship exists between the amount of PTH present in the patient sample and the amount of relative light units (RLUs) detected by the system.

Siemens Healthcare Diagnostics ADVIA Centaur iPTH Premarket Notification 510(k) March, 2013

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

#### K. Performance Characteristics

Substantial equivalence was demonstrated by testing several performance characteristics including imprecision, interfering and cross-reacting substances, and method comparison.

#### a. Precision

Precision estimates were computed according to CLSI document EP05-A2, Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline. Within run and total imprecision were evaluated by testing one EDTA plasma (patient) pool, five (5) Medical Decision Pools (iPTH spiked into human EDTA plasma pools), two levels of calibrators, and 3 levels of commercial control materials. Each sample was assayed in 2 replicates per run, 2 runs per day for 20 days for a total of 80 replicates.

| | | | Within Run | | Total | |
|-------------------------|---------------|------|------------|------|-------|--|
| Sample | MEAN<br>pg/mL | SD | %CV | SD | %CV | |
| Patient Pool | 16.7 | 0.8 | 4.6 | 1.5 | 9.2 | |
| Low Calibrator | 33.0 | 2.0 | 6.0 | 2.3 | 6.9 | |
| Control 1 | 45.2 | 2.0 | 4.4 | 3.2 | 7.0 | |
| Medical Decision Pool 1 | 47.3 | 1.4 | 2.9 | 2.3 | 4.8 | |
| Medical Decision Pool 2 | 97.3 | 2.8 | 2.9 | 3.9 | 4.0 | |
| Medical Decision Pool 3 | 175.6 | 4.8 | 2.7 | 10.5 | 6.0 | |
| Control 2 | 196.6 | 6.8 | 3.5 | 8.3 | 4.2 | |
| Control 3 | 691.0 | 17.8 | 2.6 | 24.5 | 3.5 | |
| Medical Decision Pool 4 | 699.8 | 20.1 | 2.9 | 24.4 | 3.5 | |
| High Calibrator | 807.7 | 23.1 | 2.9 | 37.7 | 4.7 | |
| Medical Decision Pool 5 | 1802.9 | 46.7 | 2.6 | 57.7 | 3.2 | |

#### b. Interfering Substances

Interference by hemoglobin, triglycerides (Intralipids), bilirubin, and biotin was evaluated in the ADVIA Centaur iPTH assay at three levels of PTH. There was no indication of interference (< 10% effect) up to the interferent levels claimed.

| Interferent | [Interf]<br>mg/dL | Patient 1<br>Dose<br>(pg/mL) | Patient 1<br>Bias (%) | Patient 2<br>Dose<br>(pg/mL) | Patient 2<br>Bias (%) | Patient 3<br>Dose<br>(pg/mL) | Patient 3<br>Bias (%) |
|-----------------------------|-------------------|------------------------------|-----------------------|------------------------------|-----------------------|------------------------------|-----------------------|
| Hemoglobin | 500 | 11.16 | -3.19% | 52.35 | -0.22% | 182.15 | -9.59% |
| | 250 | 10.58 | -8.26% | 51.41 | -2.03% | 191.19 | -5.10% |
| | 0 | 11.53 | | 52.47 | | 201.48 | |
| Bilirubin<br>(unconjugated) | 40 | 27.26 | 6.33% | 64.48 | -3.78% | 126.70 | -2.27% |
| | 20 | 26.09 | 1.76% | 64.64 | -3.55% | 122.52 | -5.49% |
| | 0 | 25.64 | | 67.02 | | 129.64 | |
| Bilirubin<br>(conjugated) | 40 | 25.29 | -7.19% | 64.49 | -2.85% | 116.18 | -3.72% |
| | 20 | 26.35 | -3.32% | 62.57 | -5.75% | 116.28 | -3.64% |
| | 0 | 27.25 | | 66.38 | | 120.67 | |

4

Siemens Healthcare Diagnostics ADVIA Centaur iPTH

Premarket Notification 510(k) March, 2013

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

| Interferent | [Interf] :<br>mg/dL | Patient 1<br>Dose<br>(pg/mL) | Patient 1<br>Bias (%) | Patient 2<br>Dose<br>(pg/mL) | Patient 2<br>Bias (%) | Patient 3<br>Dose<br>(pg/mL) | Patient 3<br>Blas (%) |
|---------------|---------------------|------------------------------|-----------------------|------------------------------|-----------------------|------------------------------|-----------------------|
| Triglycerides | 3000 | 23.70 | 2.50% | 80.56 | 7.14% | 115.71 | 6.11% |
| | 1500 | 22.34 | -3.38% | 72.37 | -3.75% | 111.29 | 2.06% |
| | 0 | 23.13 | | 75.19 | | 109.05 | |
| Biotin | 0.10 | 25.29 | 3.35% | 85.09 | 7.54% | 120.45 | -1.45% |
| | 0.05 | 24.77 | 1.24% | 78.16 | -1.22% | 118.13 | -3.35% |
| | 0.00 | 24.47 | | 79.12 | | 122.23 | |

#### c. Cross-reactivity

Cross reactivity was evaluated in the ADVIA Centaur iPTH immunoassay using a normal EDTA plasma sample and an assay specific Multi-diluent 11 (buffered goat serum with no analyte). No cross reactivity was observed at the highest levels tested with the exception of the PTH 7 - 84 fragment (~ 51%) - this will be reported in the Labeling.

| Protein | Interfi<br>pg/mL | Multi-Dil 11<br>iPTH Dose<br>(pg/mL) | %Cross<br>React. | Plasma<br>Sample<br>iPTH Dose<br>(pg/mL) | %Cross<br>React |
|-----------------|------------------|--------------------------------------|------------------|------------------------------------------|-----------------|
| PTH 1-34 | 300 | 0.00 | 0.00% | 45.17 | 0.09% |
| PTH 39-68 | 100,000 | 0.00 | 0.00% | 32.25 | -0.01% |
| PTH 39-84 | 100,000 | 0.42 | 0.00% | 26.23 | -0.02% |
| PTH 44-68 | 100,000 | 0.00 | 0.00% | 34.52 | -0.01% |
| PTH 53-84 | 100,000 | 1.32 | 0.00% | 29.61 | -0.02% |
| Calcitonin | 100,000 | 0.00 | 0.00% | 43.56 | 0.00% |
| PTH 7-84 | 300 | 152.21 | 50.74% | 203.70 | 51.39% |
| Beta-Cross Laps | 1000 | 0.00 | 0.00% | 33.44 | 0.17% |
| Osteocalcin | 50,000 | 0.00 | 0.00% | 32.67 | 0.00% |

#### d. Method Comparison

Method Comparison studies were done with EDTA plasma samples to demonstrate equivalence to the Predicate (Abbott Architect Intact PTH assay). The ADVIA Centaur iPTH assay shows good correlation in sample results compared to the Predicate.

| System (y) | N | Regression<br>Equation* | R** | Mean<br>(Median)<br>Bias (%) | Sample Range<br>(pg/mL) |
|-------------------------------------|-----|-------------------------|-------|------------------------------|-------------------------|
| ADVIA Centaur iPTH<br>(EDTA Plasma) | 177 | y = 1.03x - 3.32 | 0.991 | -2.0<br>(-1.5) | 10.5 - 1882 |

x =Predicate (Abbott Architect Intact PTH assay)

* Passing & Bablok

** Least Squares Linear regression

#### e. Serum Plasma Matrix Equivalency

EDTA plasma and serum samples were compared in the ADVIA Centaur iPTH assay. Correlation results for EDTA plasma and serum demonstrate that the matrices are equivalent using the ADVIA Centaur iPTH assay.

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

| | N | Regression<br>Equation* | R | Sample Range<br>(pg/mL) |
|--------------------|----|-------------------------|-------|-------------------------|
| ADVIA Centaur iPTH | 79 | 0.98x + 3.72 | 0.992 | 11.1 - 1791 |

x = EDTA plasma, y = Serum

* Weighted Linear regression

### f. Expected Values

Matched serum and plasma samples from apparently healthy donors were tested with the ADVIA Centaur iPTH to confirm that the Expected Values or reference range is comparable to the Predicate Device. The Expected Results (from 95% of the values) are:

For plasma: 13.8 to 85.0 pg/mL (1.46 to 9.01 pmol/L) For serum: 12.4 to 76.8 pg/mL (1.31 to 8.14 pmol/L)

#### L. Conclusions

Comparative testing of the ADVIA Centaur iPTH assay is substantially equivalent in principle and performance to the Predicate Device, Architect Intact PTH assay, cleared under 510(k) k063232.

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

#### DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/6/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an abstract image of an eagle.

#### Public Health Service

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

#### March 21, 2013

Siemens Healthcare Diagnostics c/o Philip Liu, Ph.D. 511 Benedict Avenue Tarrytown, New York 10591

Re: k121981

Trade/Device Name: ADVIA® Centaur Intact Parathyroid (iPTH) Assay Regulation Number: 21 CFR 862.1545 Regulation Name: Parathyroid Hormone Test System Regulatory Class: Class II Product Code: CEW Dated: February 14, 2013 Received: February 15, 2013

Dear Dr. Liu:

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. Ilsting 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 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}------------------------------------------------

Page 2 - Philip Liu

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 -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

510(k) Number (if known): k121981

Device Name:

ADVIA® Centaur Intact Parathyroid (iPTH) Assay

Indications for Use:

The ADVIA® Centaur Intact Parathyroid (iPTH) assay is for in vitro diagnostic use in the quantitative determination of intact parathyroid hormone (iPTH) in EDTA plasma or serum using the ADVIA Centaur XP system. This assay is intended to be used to aid in the differential diagnosis of hyperparathyroidism and hypoparathyroidism.

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)

Ruth A. Chesleis-S

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

k121981 510(k)