Atellica IM Total hCG (ThCG)

K172322 · Siemens Healthcare Diagnostics, Inc. · JHI · Mar 29, 2018 · Clinical Chemistry

Device Facts

• Record ID: K172322
• Device Name: Atellica IM Total hCG (ThCG)
• Applicant: Siemens Healthcare Diagnostics, Inc.
• Product Code: JHI · Clinical Chemistry
• Decision Date: Mar 29, 2018
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1155
• Device Class: Class 2

Intended Use

The Atellica IM Total hCG (ThCG) assay is for in vitro diagnostic use in the quantitative determination of human gonadotropin (hCG) in human serum using the Atellica IM Analyzer. The Atellica IM ThCG assay is intended as an aid in the early detection of pregnancy.

Device Story

The Atellica IM Total hCG (ThCG) assay is a quantitative chemiluminescent sandwich immunoassay performed on the Atellica IM Analyzer. It utilizes goat polyclonal anti-hCG antibodies labeled with acridinium ester and mouse monoclonal anti-hCG antibodies coupled to paramagnetic particles. The device measures hCG in human serum; the amount of hCG present is directly proportional to the relative light units (RLUs) detected by the analyzer. The assay is intended for use in clinical laboratory settings by trained personnel. Healthcare providers use the quantitative results to aid in the early detection of pregnancy. The device provides a standardized measurement of hCG, facilitating clinical assessment of pregnancy status.

Clinical Evidence

No clinical studies were performed. Evidence is based on analytical bench testing, including precision (n=320), linearity (n=11), dilution recovery, detection limits (LoB, LoD, LoQ), analytical specificity (cross-reactivity and interference), and a method comparison study (n=115) against the predicate device, yielding a correlation coefficient (R) of 0.999.

Technological Characteristics

Sandwich immunoassay; direct chemiluminescent detection. Reagents: goat polyclonal anti-hCG (acridinium ester) and mouse monoclonal anti-hCG (paramagnetic particles). Sample volume: 25 µL. Incubation: 8 minutes at 37°C. Standardized to WHO 4th IS 75/589. Automated platform (Atellica IM Analyzer).

Indications for Use

Indicated for the quantitative determination of hCG in human serum to aid in the early detection of pregnancy. No specific age or gender restrictions are provided, though reference ranges are established for non-pregnant women ages 17-54 and postmenopausal women aged ≥ 41.

Regulatory Classification

Identification

A human chorionic gonadotropin (HCG) test system is a device intended for the early detection of pregnancy is intended to measure HCG, a placental hormone, in plasma or urine. A human chorionic goadotropin (HCG) test system is a device intended for any uses other than early detection of pregnancy (such as an aid in the diagnosis, prognosis, and management of treatment of persons with certain tumors or carcinomas) is intended to measure HCG, a placental hormone, in plasma or urine.

Predicate Devices

• ADVIA Centaur® Total hCG assay (k925277)

Submission Summary (Full Text)

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March 29, 2018

Siemens Healthcare Diagnostics Inc. Anoop Joy Regulatory Clinical Affairs Specialist 511 Benedict Avenue Tarrytown, NY 10591

Re: k172322

Trade/Device Name: Atellica IM Total hCG (ThCG) Regulation Number: 21 CFR 862.1155 Regulation Name: Human chorionic gonadotropin (HCG) test system Regulatory Class: Class II Product Code: JHI Dated: February 20, 2018 Received: February 21, 2018

Dear Anoop Joy:

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 Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR

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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.

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.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email ([e-mail]) or phone [phone] or 301-796-7100).

> Sincerely, Kellie B. Kelm -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 | |
| <b>Indications for Use</b> | |
| Form Approved: OMB No. 0910-0120 | |
| Expiration Date: January 31, 2017 | |
| See PRA Statement below. | |

| 510(k) Number (if known) | k172322 |
|--------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Device Name | Atellica IM Total hCG (ThCG) |
| Indications for Use (Describe) | The Atellica IM Total hCG (ThCG) assay is for in vitro diagnostic use in the quantitative determination of human chorionic gonadotropin (hCG) in human serum using the Atellica IM Analyzer. The Atellica IM ThCG assay is intended for use as an aid in the early detection of pregnancy. |

| Type of Use (Select one or both, as applicable) | |
|--------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------|
| <div style="display:flex; align-items:center;"><input checked="" type="checkbox"/>Prescription Use (Part 21 CFR 801 Subpart D)</div> | <div style="display:flex; align-items:center;"><input type="checkbox"/>Over-The-Counter Use (21 CFR 801 Subpart C)</div> |

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# 510(k) Summary of Safety and Effectiveness

# Atellica IM Total hCG (ThCG)

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.

# The assigned 510(k) Number: k172322

#### . APPLICANT

Siemens Healthcare Diagnostics Inc. 511 Benedict Avenue, Tarrytown, NY 10591 USA

| Contact: | Anoop Joy |
|----------|----------------------------------------|
| | Regulatory Clinical Affairs Specialist |
| Phone: | [phone] |
| Fax: | [phone] |
| E-mail: | [e-mail] |

Date Prepared: March 28, 2018

#### Regulatory Information II.

# Assay

Name of Device: Atellica IM Total hCG (ThCG) Classification: Class II Regulation Section: 21 CFR § 862.1155 Product Code: JHI Panel: Clinical Chemistry

#### PREDICATE DEVICE .

# Assay

Name of Device: ADVIA Centaur® Total hCG assay 510 (k): k925277

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The Atellica IM ThCG Assay reagents come in the following configurations:

| Contents | Number<br>of Tests |
|----------------------------------------------------------------------------------------------------------------------------------------------------|--------------------|
| 1 ReadyPack primary reagent pack containing Atellica IM ThCG<br>Lite Reagent and Solid Phase<br>Atellica IM ThCG master curve and test definition | 90 |
| 5 ReadyPack primary reagent packs containing Atellica IM ThCG<br>Lite Reagent and Solid Phase<br>Atellica IM ThCG master curve and test definition | 450 |

The ReadyPack consists of the following:

#### Atellica IM ThCG ReadyPack® primary reagent pack Lite Reagent

5.0 ml/reagent pack Goat polyclonal anti-hCG antibody (~0.1 µg/mL) labeled with acridinium ester in buffered saline; sodium azide (0.1%); preservatives

#### Solid Phase

22.5 mL/reagent pack Mouse monoclonal anti-hCG antibody (~0.02 mg/mL) covalently coupled to paramagnetic particles in buffered saline; sodium azide (0.1%); preservatives.

# Atellica IM ThCG DIL ReadyPack ancillary reagent pack

25.0 mL/pack Buffered heat-treated equine serum; EDTA; sodium azide (< 0.1%); preservatives

#### Atellica IM ThCG DIL

50.0 mL/vial Buffered heat-treated equine serum; EDTA; sodium azide (< 0.1%); preservatives

#### INDICATIONS FOR USE >

The Atellica IM Total ß-hCG (ThCG) assay is for in vitro diagnostic use in the quantitative determination of human gonadotropin (hCG) in human serum using the Atellica IM Analyzer.

The Atellica IM ThCG assay is intended for use as an aid in the early detection of pregnancy.

#### INTENDED USE VI.

Same as Indications for Use

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#### COMPARISION OF TECHNOLOGICAL CHARACTERISTICS WITH THE VII PREDICATE DEVICE

The following table provides a comparison between the predicate and candidate device.

| Assay | | |
|-----------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Item | Predicate Device | Candidate Device |
| Intended Use | For in vitro diagnostic use in the<br>quantitative determination of<br>human chorionic gonadotropin<br>(hCG) in serum. The results<br>obtained from hCG specimens are<br>used as an aid in the assessment<br>of pregnancy status. This assay<br>detects the intact hCG molecule<br>and free beta-subunits of the hCG<br>molecule. | The Atellica IM Total β-hCG<br>(ThCG) assay is for in vitro<br>diagnostic use in the quantitative<br>determination of human<br>gonadotropin (hCG) in human<br>serum using the Atellica IM<br>Analyzer.<br>The Atellica IM ThCG assay is<br>intended for use as an aid in the<br>early detection of pregnancy. |
| Measurement | Quantitative | Same |
| Assay Range | 2.0–1000 mIU/mL (IU/L) | 2.6–1000 mIU/mL (IU/L) |
| Assay Principle | Sandwich immunoassay | Same |
| Technology | Direct chemiluminescent | Same |
| Sample Type | Serum | Same |
| Sample Volume | 50 µL | 25 µL |
| Reagent<br>Volume | 100 µL of Lite Reagent and 450 µL<br>of Solid Phase | 50 µL of Lite Reagent and 225 µL<br>of Solid Phase |
| Incubation<br>Time | 7.5 minutes at 37°C. | 8 minutes at 37°C |
| Standardization | Standardized against the World<br>Health Organization (WHO) 4th IS<br>75/589 reference material.<br>Assigned values for calibrators are<br>traceable to this<br>standardization. | Same |
| Calibration | 2-point | Same |
| Calibrators | ADVIA Centaur Calibrator B | Atellica IM CAL B |
| Number of<br>Calibrator<br>Levels | Two levels | Same |
| Controls | Commercial Controls | Same |
| Number of<br>Control Levels | 2 | Same |
| Detection<br>Antibody | Goat polyclonal anti-hCG antibody<br>labeled with acridinium ester | Same |
| Capture<br>Antibody | Mouse monoclonal anti-hCG<br>antibody<br>covalently coupled to paramagnetic | Same |
| | particles | |
| Expected<br>Values | 2–4 weeks 39.1–8388 (mIU/mL)<br>(IU/L)<br>5–6 weeks 861–88,769<br>6–8 weeks 8636–218,085<br>8–10 weeks 18,700–244,467<br>10–12 weeks 23,143–181,899<br>13–27 weeks 6303–97,171<br>28–40 weeks 4360–74,883 | The 2.5 and 97.5 percentiles of the<br>concentration values were<br>considered the expected value<br>range of the Atellica IM ThCG<br>assay. The expected value range of<br>non-pregnant females was 1.5—4.2<br>mIU/mL (IU/L) and the<br>postmenopausal female population<br>was 1.8–10.1 mIU/mL (IU/L) |

Table 1: Substantial Equivalence Comparison

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#### PERFORMANCE CHARACTERISTICS DATA VIII.

# Detection Capability

Detection capability was determined in accordance with CLSI Document EP17-A2.

The LoB corresponds to the highest measurement result that is likely to be observed for a blank sample. The LoB of the Atellica IM ThCG assay is 1.5 mIU/mL (IU/L).

The LoD corresponds to the lowest concentration of hCG that can be detected with a probability of 95%. The LoD for the Atellica IM ThCG assay is 1.7 mlU/mL (IU/L), and was determined using 601 determinations, with 300 blank and 301 low-level replicates, and an LoB of 1.5 mIU/mL (IU/L).

The LoQ corresponds to the lowest amount of hCG in a sample at which the percent total error is 30%. The LoQ of the Atellica IM ThCG assay is 2.6 mIU/mL (IU/L), and was determined using multiple samples prepared from the World Health Organization (WHO) human chorionic gonadotropin reference material (NIBSC code: 99/688) in the interval 1.9–6.7 mIU/mL (IU/L). All samples were assayed in replicates of 5 in each of 2 runs per day using 2 reagent lots, over a period of 5 days

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# Precision

Precision was determined in accordance with CLSI Document EP05-A3. Samples were assayed in duplicate in 2 runs per day for 20 days using two reagent lots on each of two Atellica IM analyzers. The following results were obtained:

| Sample | Na | Mean<br>mIU/mL<br>(IU/L) | Repeatability | | Between Run | | Between Day | | Within-Lab | |
|-----------|-----|--------------------------|-------------------------|------|------------------------|------|-------------------------|------|-------------------------|------|
| | | | SDb<br>mIU/mL<br>(IU/L) | %CVc | SD<br>mIU/mL<br>(IU/L) | %CVc | SDb<br>mIU/mL<br>(IU/L) | %CVc | SDb<br>mIU/mL<br>(IU/L) | %CVc |
| Serum 1 | 320 | 2.4 | 0.2 | 8.8 | 0.1 | 3.3 | 0.1 | 4.7 | 0.3 | 10.5 |
| Serum 2 | 320 | 12.6 | 0.4 | 2.8 | 0.2 | 1.6 | 0.1 | 1.0 | 0.4 | 3.4 |
| Serum 3 | 320 | 782.0 | 14.0 | 1.8 | 6.9 | 0.9 | 6.7 | 0.9 | 17.0 | 2.2 |
| Control 1 | 320 | 6.8 | 0.3 | 4.5 | 0.0 | 0.3 | 0.2 | 3.0 | 0.4 | 5.5 |
| Control 2 | 320 | 23.4 | 0.6 | 2.6 | 0.4 | 1.7 | 0.4 | 1.6 | 0.8 | 3.5 |
| Control 3 | 320 | 202.1 | 3.6 | 1.8 | 2.4 | 1.2 | 3.4 | 1.7 | 5.5 | 2.7 |

Number of samples tested. a

മ Standard deviation.

- Coefficient of variation. ು
# Method Comparison

The Atellica IM ThCG assay is designed to have a correlation coefficient of ≥ 0.95 and a slope of 1.0 ±0.10 compared to the ADVIA Centaur Total hCG assay. Assay comparison was determined using the weighted Deming regression model in accordance with CLSI Document EP09-A3. The following results were obtained:

| Specimen | Comparative Assay (x) | Regression Equation | Sample Interval | Nᵃ | rᵇ |
|----------|-------------------------|----------------------------------|-------------------------|-----|------|
| Serum | ADVIA Centaur Total hCG | $y = 0.94x + 0.23 mIU/mL (IU/L)$ | 2.4-947.7 mIU/mL (IU/L) | 115 | 1.00 |

a Number of samples tested.

b Correlation coefficient.

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Interference testing was performed in accordance with CLSI Document EP07-A2 using the Atellica IM Analyzer.

The following substances were added to serum samples containing different concentrations of hCG. Bias is the difference in the results between the control sample (does not contain the interferent) and the test sample (contains the interferent) expressed in percent. Analyte results should not be corrected based on the bias.

| Substance | Substance Test Concentration | Analyte Concentration<br>mIU/mL (IU/L) | Bias (%) |
|----------------------|------------------------------|----------------------------------------|----------|
| Acetaminophen | 20 mg/dL | 5.7 | 0.9 |
| | 20 mg/dL | 495.3 | 2.9 |
| Acetylsalicylic acid | 65 mg/dL | 5.4 | 7.3 |
| | 65 mg/dL | 502.1 | -0.8 |
| Atropine | 20 mg/dL | 5.7 | -4.7 |
| | 20 mg/dL | 503.6 | -0.9 |
| Caffeine | 308 $ µmol/L $ | 5.6 | 5.4 |
| | 308 $ µmol/L $ | 511.9 | -1.8 |
| EDTA | 3.4 $ µmol/L $ | 5.5 | 5.9 |
| | 3.4 $ µmol/L $ | 508.9 | -2.2 |
| Ethanol | 100 mg/dL | 6.0 | -6.6 |
| | 100 mg/dL | 506.2 | 2.0 |
| Gentisic acid | 117 $ µmol/L $ | 6.2 | -5.8 |
| | 117 $ µmol/L $ | 507.1 | -2.7 |
| Heparin | 7200 IU/dL | 5.5 | -2.3 |
| | 7200 IU/dL | 491.3 | 1.1 |
| Human Serum Albumin | 6 g/dL | 6.0 | -0.3 |
| | 6 g/dL | 511.8 | 1.3 |
| Ibuprofen | 50 mg/dL | 5.5 | 6.5 |
| | 50 mg/dL | 490.1 | -2.7 |

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Hemolysis, Icterus, and Lipemia (HIL): The Atellica IM ThCG assay is designed to have ≤ 10% interference from hemoglobin, bilirubin, and lipemia. Interfering substances were tested at the levels indicated in the table below. Bias is the difference in the results between the control sample (does not contain the interferent) and the test sample (contains the interferent) expressed in percent.

| Substance | Substance Test Concentration | Analyte Concentration<br>mIU/mL (IU/L) | Bias (%) |
|-------------------------|------------------------------|----------------------------------------|----------|
| Hemoglobin | 1000 mg/dL (0.62 mmol/L) | 5.6 | 8.9 |
| | 1000 mg/dL (0.62 mmol/L) | 501.7 | -1.2 |
| Bilirubin, conjugated | 40 mg/dL (681 $\mu$ mol/L) | 6.1 | -0.3 |
| | 40 mg/dL (681 $\mu$ mol/L) | 530.3 | -1.8 |
| Bilirubin, unconjugated | 40 mg/dL (681 $\mu$ mol/L) | 6.0 | 0.3 |
| | 40 mg/dL (681 $\mu$ mol/L) | 520.8 | -1.8 |
| Lipemia (Intralipid®) | 3000 mg/dL (34 mmol/L) | 6.1 | 2.0 |
| | 3000 mg/dL (34 mmol/L) | 458.8 | 2.4 |

# Expected Values

Data were obtained on 366 serum samples from 192 apparently healthy non-pregnant females and 174 apparently healthy postmenopausal females. The expected value range of non-pregnant females was 1.5—4.2 mIU/mL (IU/L) and the postmenopausal female population was 1.8–10.1 mIU/mL (IU/L), as shown in the table below.

| Sample Category | Na | Median<br>mIU/mL (IU/L) | Reference Interval<br>mIU/mL (IU/L)<br>2.5-97.5 Percentile |
|--------------------------------------|-----|-------------------------|------------------------------------------------------------|
| Non-Pregnant Females<br>(Age: 17-54) | 192 | 2.0 | 1.5-4.2 |
| Postmenopausal Females<br>Age: ≥ 41 | 174 | 3.9 | 1.8-10.1 |

a Number of samples.

#### CONCLUSION x

Comparative testing of the Atellica IM ThCG Assay is substantially equivalent in principle and performance to the Predicate Device - ADVIA Centaur® Total hCG assay cleared under 510(k) K925277.