Elecsys HCG STAT

K203227 · Roche Diagnostics · DHA · Aug 18, 2021 · Clinical Chemistry

Device Facts

• Record ID: K203227
• Device Name: Elecsys HCG STAT
• Applicant: Roche Diagnostics
• Product Code: DHA · Clinical Chemistry
• Decision Date: Aug 18, 2021
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1155
• Device Class: Class 2

Indications for Use

For the in vitro quantitative determination of human chorionic gonadotropin (hCG) in human serum and plasma. The Elecsys HCG STAT immunoassay is intended for use in the early detection of pregnancy. The electrochemiluminescence immunoassay "ECLIA" is intended for use on the cobas e 601 immunoassay analyzer.

Device Story

Elecsys HCG STAT is an in vitro diagnostic immunoassay for quantitative hCG measurement in human serum and plasma. It utilizes a sandwich immunoassay principle with monoclonal antibodies directed against hCG; antibodies are labeled with a ruthenium complex and biotin. The device operates on the cobas e 601 analyzer using electrochemiluminescence (ECLIA) technology. It is intended for use by laboratory professionals in clinical settings. The analyzer processes samples, and the resulting hCG concentration is used by clinicians for the early detection of pregnancy. The device provides quantitative results to aid in clinical decision-making regarding pregnancy status.

Clinical Evidence

No clinical data. Performance established via bench testing including precision (CLSI EP05-A3), limit of detection/quantitation (CLSI EP17-A2), linearity (CLSI EP6-A), and interference studies (hemoglobin, intralipid, bilirubin, rheumatoid factor, biotin, and common drugs). Method comparison against the predicate (n=131) showed high correlation (Passing/Bablok y=1.012x-0.970, r=1.000).

Technological Characteristics

Sandwich immunoassay; electrochemiluminescence detection. Reagents: Streptavidin-coated microparticles (0.72 mg/mL), biotinylated monoclonal anti-hCG antibody (2.3 mg/L), ruthenium-labeled monoclonal anti-hCG antibody (6.0 mg/L). Instrument: cobas e 601 analyzer. Measuring range: 1.0-10000 mIU/mL. Standardized against NIBSC 75/589. Connectivity: Integrated with cobas e 601 system.

Indications for Use

Indicated for the in vitro quantitative determination of human chorionic gonadotropin (hCG) in human serum and plasma for the early detection of pregnancy. For prescription use only.

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

• Elecsys HCG Test System (K002148)

Submission Summary (Full Text)

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FDA U.S. FOOD & DRUG ADMINISTRATION

# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

ASSAY ONLY

## I Background Information:

A 510(k) Number

K203227

B Applicant

Roche Diagnostics

C Proprietary and Established Names

Elecsys HCG STAT

D Regulatory Information

| Product Code(s) | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| DHA | Class II | 21 CFR 862.1155 - Human Chorionic Gonadotropin (HCG) Test System | CH - Clinical Chemistry |

## II Submission/Device Overview:

A Purpose for Submission:

Modification of a previously cleared assay (k002148) to decrease interference to biotin.

B Measurand:

Human Chorionic Gonadotropin (hCG)

C Type of Test:

Quantitative immunoassay

Food and Drug Administration

10903 New Hampshire Avenue

Silver Spring, MD 20993-0002

www.fda.gov

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# III Intended Use/Indications for Use:

## A Intended Use(s):
See Indications for Use below.

## B Indication(s) for Use:
For the in vitro quantitative determination of human chorionic gonadotropin (hCG) in human serum and plasma. The Elecsys HCG STAT immunoassay is intended for use in the early detection of pregnancy.

## C Special Conditions for Use Statement(s):
For Prescription Use Only

## D Special Instrument Requirements:
Cobas e 601 immunoassay analyzer.

# IV Device/System Characteristics:

## A Device Description:
The Elecsys HCG STAT is an immunoassay that uses antibodies labeled with ruthenium complex consist of a chimeric construct from human and mouse specific components. The reagent working solutions include:
Rack Pack (kit placed on the analyzer).
- M Streptavidin-coated microparticles (transparent cap), 1 bottle, 6.5 mL: Streptavidin-coated microparticles 0.72 mg/mL; preservative.
- R1 Anti-hCG-Ab~biotin (gray cap), 1 bottle, 9 mL: Biotinylated monoclonal anti-hCG antibody (mouse) 2.3 mg/L; phosphate buffer 40 mmol/L, pH 7.5; preservative.
- R2 Anti-hCG-Ab~Ru(bpy)23+ (black cap), 1 bottle, 10 mL: Monoclonal anti-hCG antibody (mouse) labeled with ruthenium complex 6.0 mg/L; phosphate buffer 40 mmol/L, pH 6.5; preservative.

## B Principle of Operation:
The Elecsys HCG STAT immunoassay uses sandwich test principle using monoclonal antibodies specifically directed against Human Chorionic Gonadotropin (HCG). During a 9-minute incubation, hCG present in the sample reacts with biotinylated monoclonal hCG-specific antibody and streptavidin-coated microparticles to form a sandwich immune complex, which is bound to the solid phase. The reaction mixture is aspirated into a measuring cell where the microparticles are magnetically captured onto the surface of the electrode. Unbound substances are then removed. Application of a voltage to the electrode induces chemiluminescent emission which is measured by a photomultiplier. Results are determined via a calibration curve.

# V Substantial Equivalence Information:

## A Predicate Device Name(s):
Elecsys HCG Test System

## B Predicate 510(k) Number(s):
K002148

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C Comparison with Predicate(s):

| Device & Predicate Device(s): | K203227 | K002148 |
| --- | --- | --- |
| Device Trade Name | Elecsys HCG STAT | Elecsys HCG Test System |
| General Device Characteristic Similarities | | |
| Intended Use/Indications For Use | Immunoassay for the in vitro quantitative determination of human chorionic gonadotropin in human serum and plasma. Elecsys HCG STAT is intended for use especially in the diagnosis and monitoring of pregnancy. | Same |
| Assay Method | Electrochemiluminescence immunoassay | Same |
| Sample type | Serum and Plasma (Lithium heparin, K2-EDTA, and K3-EDTA) | Same |
| Test time | 9 minutes | Same |
| General Device Characteristic Differences | | |
| Measuring range | 1.0-10,000 mIU/mL | 0.500-10,000 mIU/mL |
| Biotin Interference | This assay is unaffected by biotin concentrations up to 3600 ng/mL | This assay is unaffected by biotin concentrations up to 40 ng/mL |

VI Standards/Guidance Documents Referenced:

Clinical and Laboratory Standards Institute (CLSI) EP05-A3 Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline—Third Edition.

CLSI EP06-A Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline.

CLSI EP07 Interference Testing in Clinical Chemistry; Approved Guideline —Third Edition.

CLSI EP17-A2 Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline—Second Edition.

VII Performance Characteristics (if/when applicable):

A Analytical Performance:

1. Precision/Reproducibility:

The sponsor provided three (3) precision studies: a 21-day precision study, a 5-day precision study and a multiple-site precision study. Please see below for details.

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# 21 Day Precision Study

Precision was evaluated on one cobas e 601 analyzer according to CLSI guideline EP05-A3. The protocol consisted of testing two replicates of each control (PC1-PC2) and human serum samples (HS1-HS5) per run, in two runs per day for 21 days with one reagent lot. The results of the study are shown below.

| 21-Day Precision | | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Sample | Mean hCG conc. (mIU/mL) | Repeatability | | Between Run | | Between Day | | Intermediate precision | |
| | | SD | CV% | SD | CV% | SD | CV% | SD | CV % |
| HS1 | 5.01 | 0.117 | 2.3 | 0.0673 | 1.3 | 0.272 | 5.4 | 0.304 | 6.1 |
| HS2 | 8.38 | 0.211 | 2.5 | 0.010 | 0.1 | 0.419 | 5.0 | 0.469 | 5.6 |
| HS3 | 3211 | 38.3 | 1.2 | 61.9 | 1.9 | 93.2 | 2.9 | 118 | 3.7 |
| HS4 | 6305 | 89.1 | 1.4 | 83.5 | 1.3 | 291 | 4.6 | 315 | 5.0 |
| HS5 | 9691 | 139 | 1.4 | 181 | 1.9 | 232 | 2.4 | 325 | 3.4 |
| PC1 | 5.50 | 0.105 | 1.9 | 0.093 | 1.7 | 0.110 | 2.0 | 0.178 | 3.2 |
| PC2 | 47.3 | 1.31 | 2.8 | 0.412 | 0.9 | 0.875 | 1.8 | 1.63 | 3.4 |

# 5 Day Precision Study

Precision was evaluated on one cobas e 601 analyzer according to CLSI guideline EP05-A3. The protocol consisted of testing 5 replicates of each control (PC1-PC2) and human serum samples (HS1-HS5) per run, one run per day for five days with three reagent lots. The results of from a representative lot are shown below.

| 5-Day Precision | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| Sample | Mean hCG conc. (mIU/mL) | Repeatability | | Between Day | | Intermediate precision | |
| | | SD | CV% | SD | CV% | SD | CV % |
| HS1 | 4.05 | 0.034 | 0.8 | 0.058 | 1.4 | 0.067 | 1.7 |
| HS2 | 5.04 | 0.082 | 1.6 | 0.074 | 1.5 | 0.111 | 2.2 |
| HS3 | 3434 | 43.0 | 1.3 | 36.7 | 1.1 | 56.5 | 1.6 |
| HS4 | 5664 | 114 | 2.0 | 0.000 | 0.0 | 114 | 2.0 |
| HS5 | 9591 | 150 | 1.6 | 77.5 | 0.8 | 169 | 1.8 |
| PC1 | 5.66 | 0.123 | 2.2 | 0.069 | 1.2 | 0.141 | 2.5 |
| PC2 | 46.0 | 0.761 | 1.7 | 0.411 | 0.9 | 0.865 | 1.9 |

# Multiple Sites (Reproducibility) Study

The Reproducibility study was performed for a total of one run per day with five replicates of each human serum sample (HSP 1-6) and each control (CTR 1-2) per run, one run per day. The study was performed in two external laboratories and one internal laboratory. The samples were run in randomized order on the analyzers. Human serum pools (HSP 1-4) and diluted single donor samples (HSP 5-6) were used to calculate Repeatability and Intermediate precision according to CLSI EP05-A3. The results of the study are shown below.

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| Sample Material | Mean [mIU/mL] | Repeatability (Within-run Precision) | | Intermediate Precision | |
| --- | --- | --- | --- | --- | --- |
| | | SD [mIU/mL] | CV [%] | SD [mIU/mL] | CV [%] |
| Site 1 | | | | | |
| HSP1 | 4.25 | 0.103 | 2.4 | 0.120 | 2.8 |
| HSP2 | 7.30 | 0.129 | 1.8 | 0.165 | 2.3 |
| HSP3 | 2969 | 44.9 | 1.5 | 44.9 | 1.5 |
| HSP4 | 5783 | 63.2 | 1.1 | 77.8 | 1.3 |
| HSP5 | 9093 | 127 | 1.4 | 132 | 1.5 |
| HSP6 | 9303 | 147 | 1.6 | 149 | 1.6 |
| CTR1 | 4.82 | 0.0912 | 1.9 | 0.105 | 2.2 |
| CTR2 | 43.8 | 0.558 | 1.3 | 0.820 | 1.9 |
| Site 2 | | | | | |
| HSP1 | 4.84 | 0.0865 | 1.8 | 0.126 | 2.6 |
| HSP2 | 7.98 | 0.137 | 1.7 | 0.157 | 2.0 |
| HSP3 | 3030 | 30.1 | 1.0 | 51.2 | 1.7 |
| HSP4 | 5895 | 62.1 | 1.1 | 70.5 | 1.2 |
| HSP5 | 9242 | 156 | 1.7 | 170 | 1.8 |
| HSP6 | 9501 | 108 | 1.1 | 111 | 1.2 |
| CTR1 | 5.41 | 0.106 | 2.0 | 0.1228 | 2.3 |
| CTR2 | 45.4 | 0.415 | 0.9 | 0.5668 | 1.2 |
| Site 3 | | | | | |
| HSP1 | 4.66 | 0.164 | 3.5 | 0.187 | 4.0 |
| HSP2 | 7.85 | 0.0988 | 1.3 | 0.127 | 1.6 |
| HSP3 | 3040 | 21.1 | 0.7 | 37.6 | 1.2 |
| HSP4 | 5940 | 34.9 | 0.6 | 71.7 | 1.2 |
| HSP5 | 9420 | 68.6 | 0.7 | 266 | 2.8 |
| HSP6 | 9590 | 91.7 | 0.9 | 285 | 2.9 |
| CTR1 | 5.28 | 0.127 | 2.4 | 0.161 | 3.0 |
| CTR2 | 47 | 0.614 | 1.3 | 0.748 | 1.6 |

2. Linearity:

Linearity testing was performed with one reagent lot tested on one cobas e 601 analyzer with one run. One human serum sample with high analyte content above the measuring range was diluted to the lower end of the measuring range with various amounts of human serum sample without analyte content. The dilution series contained 21 steps and included concentrations between 0.25 and 11,411 mIU/mL. Samples were assayed in three replicates.

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Linear, quadratic and cubic regression analyses were performed. The results of the linear regression analysis are provided below.

$$
y = 0.997 * x - 0.492, r^2: 0.9977
$$

The results support the claimed analytical measurement range of 1.0 to 10,000 mIU/mL.

**Auto Dilution:**

Verification studies were performed to determine the sample dilution recovery of the Elecsys HCG STAT immunoassay. HCG free human serum was spiked with WHO HCG standard material (6th standard). These samples were automatically diluted (1:100) by the instrument, the obtained value was multiplied by 100 and the ratio of the theoretical value and the obtained value multiplied by 100 was generated.

The results are summarized in the tables below.

| Sample number | Target concentration | Measured concentration | Recovery [%] |
| --- | --- | --- | --- |
| 1 | 50000 | 49109 | 98% |
| 2 | 100000 | 98039 | 98% |
| 3 | 200000 | 204455 | 102% |
| 4 | 300000 | 306419 | 102% |
| 5 | 400000 | 399352 | 100% |
| 6 | 500000 | 504148 | 101% |
| 7 | 600000 | 643585 | 107% |
| 8 | 700000 | 733311 | 105% |
| 9 | 800000 | 872342 | 109% |
| 10 | 900000 | 940542 | 105% |
| 11 | 950000 | 996460 | 105% |
| 12 | 1000000 | 1096419 | 110% |

These results support the extended measuring range of the assay.

3. Analytical Specificity/Interference:

**High Dose Hook Effect**

The high-dose hook effect of the Elecsys HCG STAT assay was assessed with one reagent lot on one cobas e 601 analyzer in one-fold determination. Three (3) human serum samples were spiked with analyte (HCG) to achieve high HCG concentrations. No Hook effect was observed up to ≥ 500,000 mIU/mL of HCG.

**Endogenous interference**

Native human serum sample pools at three (~4, ~3000, and 9000 mIU/mL) concentrations of hCG were tested using one reagent lot. Test samples spiked with endogenous substance and control samples with no endogenous substance were measured and compared. There was no significant interference (< ± 10% bias between test sample and control sample) up to the concentrations shown in the table below.

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| Potential Interferent | Highest concentration tested without significant interference |
| --- | --- |
| Intralipid (Lipemia) | ≤ 2600 mg/dL |
| Bilirubin | ≤ 66 mg/dL |
| Hemoglobin | ≤ 1600 mg/dL |
| Rheumatoid Factor | ≤ 1200 IU/mL |

## Cross-reactivity

Cross-reactivity of the Elecsys HCG STAT assay was determined with one reagent lot on one cobas e 601 analyzer using a human serum sample with ~4.7 mIU/mL hCG. Samples were spiked with the following potential cross-reactants: luteinizing hormone (LH), follicle stimulating hormone (FSH), or thyroid stimulating hormone (TSH). Samples with and without the potential cross-reactants were measured and cross reactivity was calculated. No cross-reactivity was observed for TSH up to 2,000 mIU/mL and FSH up to 4,000 mIU/mL. Cross reactivity for LH in the presence of hCG was found to be dependent upon LH concentration, as shown in the table below:

| | Measured hCG concentration (mIU/mL) | | |
| --- | --- | --- | --- |
| LH [mIU/mL] | Without LH | With LH | Cross reactivity |
| 4000 | 5.05 | 32.4 | 0.69% |
| 500 | 5.19 | 8.37 | 0.64% |
| 450 | 4.75 | 5.70 | 0.21% |
| 400 | 4.73 | 5.55 | 0.21% |
| 350 | 4.78 | 5.48 | 0.20% |
| 300 | 4.83 | 5.45 | 0.21% |
| 250 | 4.79 | 5.36 | 0.23% |
| 200 | 4.76 | 5.25 | 0.25% |
| 150 | 4.87 | 5.21 | 0.23% |
| 100 | 4.98 | 4.99 | 0.01% |

## Biotin Interference

Biotin interference was tested using the Elecsys HCG STAT on a cobas e 601 analyzer and three serum samples containing hCG (4.5 mIU/mL, 3,000 mIU/mL, and 10,000 mIU/mL). Test samples spiked with biotin up to 3600 ng/mL and control samples with no biotin were measured and compared. There was no significant interference (≤ ± 10% bias between test sample and control sample) observed for biotin concentrations up to 3600 ng/mL.

## Common drugs interference

Potential interference from drugs was determined by comparing values obtained from serum samples containing hCG concentrations near 5 mIU/mL and near 50 mIU/mL. Test samples spiked with each of 17 common pharmaceutical compounds were measured and compared with the control sample (no interferent). There was no significant interference (≤ ± 10% bias between the test sample and the control sample) up to the concentrations illustrated below.

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| Potential Interferent | Highest concentration tested without significant interference (mg/dL) |
| --- | --- |
| Acetylcysteine | 15 |
| Acetylsalicylic acid | 3.0 |
| Ampicillin - Na | 7.5 |
| Ascorbic acid | 5.25 |
| Cefoxitin | 75.0 |
| Doxycycline | 1.8 |
| Heparin | 330 IU/dL |
| Levodopa | 0.75 |
| Methyldopa +1.5 | 2.25 |
| Metronidazole | 12.3 |
| Rifampicin | 4.8 |
| Acetaminophen | 15.6 |
| Cyclosporine | 0.18 |
| Ibuprofen | 21.9 |
| Theophylline | 6.0 |
| Phenylbutazone | 32.1 |
| Itraconazole | 3.0 |

4. Assay Reportable Range:

The reportable range is 1.0 -10,000 mIU/mL.

5. Traceability, Stability, Expected Values (Controls, Calibrators, or Methods):

This assay has been standardized against the World Health Organization (WHO) 4th International Standard Chorionic Gonadotropin, Human, National Institute for Biological Standards and Control (NIBSC), code 75/589.

6. Detection Limit:

Limit of Blank (LoB)

For determination of LoB five analyte free samples were measured in two-fold determinations in 6 runs, distributed over $\geq 3$ days, with two (2) different lots on one (1) cobas e 601 analyzer. In total 60 measured values of analyte free samples were obtained per lot. The results provided support LoB of $0.5\mathrm{mIU/mL}$

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Limit of Detection (LoD)

For determination of LoD five samples with low-analyte concentration (from 0.5 mIU/mL up to 1.9 mIU/mL) were measured in 2-fold determination in 6 runs, distributed over ≥ 3 days, with 2 different lots on one cobas e 601 analyzer. In total 60 measured values of samples with low analyte concentrations were obtained per lot. The results provided support LoD of 1 mIU/mL.

Limit of Quantitation (LoQ)

For the determination of LoQ, 2 lots were evaluated, each with 5 human serum samples covering the range between 0.57 and 1.8 mIU/mL. Each sample was measured in 5 replicates with one run per day over 5 days on one cobas e 601 analyzer. The results support the claimed LoQ of 1 mIU/mL.

7. Assay Cut-Off:

Not Applicable.

B Comparison Studies:

1. Method Comparison with Predicate Device:

A method comparison study between the candidate Elecsys HCG STAT assay and the predicate device, Elecsys HCG STAT assay (k002148), was conducted internally using both the predicate and candidate assays on the cobas e 601 analyzer. One hundred thirty-one (131) samples spanning the range between 1.32 mIU/mL and 9848 mIU/mL were tested with one run per sample. Passing-Bablok regression analysis of the results is provided below.

| | Passing/Bablok regression analysis |
| --- | --- |
| N | 131 |
| Range Tested (predicate) | 1.32 – 9848 mIU/mL |
| Slope | 1.012 (95% CI: 1.010, 1.014) |
| Intercept | -0.970 mIU/mL (95% CI: -2.69, -0.2) |
| Correlation coefficient r | 1.000 |

2. Matrix Comparison:

A matrix comparison study was performed to evaluate matrices suitable for use with the Elecsys HCG STAT assay. Native human serum samples drawn into serum primary tubes (reference) were compared to matched Li-Heparin, K2-EDTA or K3-EDTA plasma samples. The samples were run on the cobas e 601 analyzer. The results were assessed using Passing/Bablok regression analysis.

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Serum/Li-Heparin Plasma Summary Results

| | Passing/Bablok regression analysis |
| --- | --- |
| N | 56 |
| Range | 1.63 – 9975 mIU/mL |
| Slope | 0.982 (LCL 95%: 0.978 and UCL 95%: 0.990) |
| Intercept | 0.001 mIU/mL (LCL 95%: -1.85 and UCL 95%: 0.989) |
| Correlation coefficient r | 1.00 |

Serum/K2-EDTA Plasma Summary Results

| | Passing/Bablok regression analysis |
| --- | --- |
| N | 60 |
| Range | 2.24 – 9463 mIU/mL |
| Slope | 0.983 (LCL 95%: 0.976 and UCL 95%: 0.990) |
| Intercept | 0.058 mIU/mL (LCL 95%: -1.63 and UCL 95%: 4.00) |
| Correlation coefficient r | 0.998 |

Serum/K3-EDTA Plasma Summary Results

| | Passing/Bablok regression analysis |
| --- | --- |
| N | 45 |
| Range | 1.33 – 9436 mIU/mL |
| Slope | 0.973 (LCL 95%: 0.963 and UCL 95%: 1.002) |
| Intercept | -1.76 mIU/mL (LCL 95%: -18.7 and UCL 95%: 0.036) |
| Correlation coefficient r | 0.997 |

B Clinical Studies:

1. Clinical Sensitivity:
Not Applicable.

2. Clinical Specificity:
Not Applicable.

3. Other Clinical Supportive Data (When 1. and 2. Are Not Applicable):
Not Applicable.

C Clinical Cut-Off:
Not Applicable.

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D Expected Values/Reference Range:

The reference range was established in K002148.

VIII Proposed Labeling:

The labeling supports the finding of substantial equivalence for this device.

IX Conclusion:

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

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