(532 days)
For in vitro diagnostic use in the quantitative determination of human chorionic gonadotropin (hCG) in serum or plasma (EDTA or lithium heparin) using the ADVIA Centaur® XP system.
Human chorionic gonadotropin measurements are intended for use as an aid in the early detection of pregnancy.
The ADVIA Centaur® Total hCG assay reagents come in the following configurations:
5 ReadyPack primary reagent packs containing ADVIA Centaur Total hCG Lite Reagent and Solid Phase ADVIA Centaur and ADVIA Centaur CP Total hCG Master Curve card (250 Tests)
1 ReadyPack primary reagent pack containing ADVIA Centaur Total hCG Lite Reagent and Solid Phase ADVIA Centaur and ADVIA Centaur CP Total hCG Master Curve card (50 Tests)
The ReadyPack consists of the following:
ADVIA Centaur ThCG ReadyPack® primary reagent pack; Lite Reagent: 5.0 mL/reagent pack polyclonal goat anti-hCG antibody (~0.1 µg/mL) labeled with acridinium ester in buffered saline with sodium azide (0.1%) and preservatives
ADVIA Centaur ThCG ReadyPack primary reagent pack; Solid Phase Reagent: 22.5 mL/reagent pack monoclonal mouse anti-hCG antibody (~0.02 mg/mL) covalently coupled to paramagnetic particles in buffered saline with sodium azide (0.1%) and preservatives
ADVIA Centaur ThCG ReadyPack ancillary reagent pack; ThCG Diluent: 25.0 mL/reagent pack buffered heat-treated equine serum with EDTA, sodium azide (< 0.1%), and preservatives
ADVIA Centaur ThCG Diluent: 50.0 mL/vial buffered heat-treated equine serum with EDTA, sodium azide (< 0.1%), and preservatives
This document describes the validation of the ADVIA Centaur® Total hCG assay, primarily focusing on the addition of plasma (EDTA and lithium heparin) sample claims.
Here's an analysis of the acceptance criteria and the studies that demonstrate the device meets them:
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Characteristic | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|
| Detection Capability | LOQ (Limit of Quantification), LOD (Limit of Detection), LOB (Limit of Blank) within specified ranges. | LOQ: 4.0 mIU/mL (IU/L) LOD: 3.0 mIU/mL (IU/L) LOB: 2.0 mIU/mL (IU/L) |
| Precision | CV% within acceptable limits for various hCG concentrations (specified in CLSI EP05-A3). | Serum A (Mean 6.63 mIU/mL): Repeatability CV 4.4%, Between-Run CV 1.3%, Between-Day CV 3.6%, Within-Lab CV 5.8% Serum B (Mean 15.85 mIU/mL): Repeatability CV 3.3%, Between-Run CV 2.8%, Between-Day CV 2.0%, Within-Lab CV 4.8% Serum C (Mean 819.28 mIU/mL): Repeatability CV 2.5%, Between-Run CV 2.7%, Between-Day CV 1.5%, Within-Lab CV 4.0% Control 1 (Mean 7.43 mIU/mL): Repeatability CV 4.1%, Between-Run CV 2.0%, Between-Day CV 4.3%, Within-Lab CV 6.2% Control 2 (Mean 24.64 mIU/mL): Repeatability CV 2.5%, Between-Run CV 0.6%, Between-Day CV 2.3%, Within-Lab CV 3.5% Control 3 (Mean 164.66 mIU/mL): Repeatability CV 1.8%, Between-Run CV 0.5%, Between-Day CV 1.6%, Within-Lab CV 2.5% |
| Method Comparison (vs. Predicate) | High correlation (r value close to 1) and a slope and intercept indicating agreement (slope near 1, intercept near 0). | Equation: ADVIA Centaur Total hCG = 0.96 (Atellica IM ThCG assay) - 3.0 mIU/mL Correlation coefficient (r): 0.997 |
| Specimen Equivalence | Slope of 0.90–1.10 for alternate tube types versus serum, and high correlation coefficients. | Dipotassium EDTA plasma vs. Serum (N=53): Slope 0.99, Intercept 0.3, r 1.00 Lithium heparin plasma vs. Serum (N=51): Slope 1.01, Intercept -0.3, r 1.00 |
| Linearity | Results spanning the entire assay range meet acceptance criteria. | Results met acceptance criteria, supporting an analytical measuring range from 4.0 mIU/mL to 1000 mIU/mL. |
| Dilution Recovery | % Recovery within an acceptable range (typically 90-110% or similar). | Mean % Recovery: 1:2 dilution (91%), 1:4 dilution (98%), 1:8 dilution (95%), 1:16 dilution (101%). Individual recovery values varied, but overall means were within typical acceptable ranges. |
| Interferences | % Bias from interfering substances within acceptable limits (typically ±10% or similar). | Human Serum Albumin: -0.3% to -0.2% bias Acetaminophen: -0.5% to 2.7% biasAcetylsalicylic acid: 0.4% to 2.7% biasHeparin: -8.2% to 1.6% biasIbuprofen: -1.4% to 0.3% biasEDTA: 1.8% to 4.1% biasEthanol: -1.1% to 2.7% biasAtropine: -1.5% to 0.0% biasCaffeine: 1.1% to 6.1% biasGentisic acid: -1.1% to 4.3% bias (All seem to meet typical ±10% bias acceptance criterion). |
| HIL Interference | % Bias from Hemolysis, Icterus, and Lipemia within acceptable limits. | Bilirubin (Conjugated): -1.0% to 3.3% bias Bilirubin (Unconjugated): -0.8% to 1.7% bias Hemoglobin: -0.5% to 1.3% bias Intralipid: -3.3% to -3.7% bias (All seem to meet typical ±10% bias acceptance criterion). |
| Expected Values (Reference Range) | Established reference intervals for non-pregnant and postmenopausal females. | Non-Pregnant Females (Age: ≤40, N=130): 0.03 – 0.6 mIU/mL Postmenopausal Females (Age: ≥41, N=150): 0.02 – 2.9 mIU/mL |
| Cross-Reactivity | Minimal interference from related hormones (FSH, TSH, LH, hGH, PRL). | Data provided for various hCG concentrations with and without cross-reactants. For example, for FSH at 500mIU/mL, hCG values without cross-reactant ranged from 0.5-493.1 mIU/mL, and with cross-reactant ranged from 1.6-475.4 mIU/mL. Similar data for TSH, LH, hGH, and PRL. (Implied acceptance is that the cross-reactants do not significantly alter the hCG measurement, which the provided data appears to support given the relative magnitudes). |
| Sample Handling/Stability | Stability for specified conditions (refrigeration, room temp, on-board, freeze/thaw cycles). | Storage refrigerated (2-8°C) for up to 48 hours. Storage at room temperature (25°C) for up to 8 hours. Kept on-board (30°C) for up to 8 hours. Frozen and thawed up to 1 time. |
2. Sample Sizes Used for the Test Set and Data Provenance
- Detection Capability: No specific sample size disclosed for LOB/LOD/LOQ determination in this summary.
- Precision: 320 total replicates for each of the 6 samples (3 serum, 3 control) over 20 days (e.g., 2 runs/day x 20 days x 2 replicates/run).
- Method Comparison: 117 samples (range 7.6 to 977.6 mIU/mL).
- Specimen Equivalence: 53 pairs for Dipotassium EDTA plasma vs. Serum; 51 pairs for Lithium heparin plasma vs. Serum.
- Linearity: Samples spanning the entire assay range. Specific number not provided.
- Dilution Recovery: Multiple samples tested across 4 dilution ratios (1:2, 1:4, 1:8, 1:16). Number of individual samples varies per dilution.
- Interferences (General, HIL): Not explicitly stated, but performed "used the paired-difference approach" at two analyte concentrations for each interferent.
- Expected Values (Reference Range): 130 non-pregnant females (≤40) and 150 postmenopausal females (≥41).
- Cross-Reactivity: Not explicitly stated, but multiple hCG values (low to high) tested against each cross-reactant.
Data Provenance: The document does not explicitly state the country of origin for the clinical samples. It is a submission by Siemens Healthcare Diagnostics, Inc. based in Tarrytown, New York, USA, suggesting the work was likely conducted or overseen in the USA, but the origin of patient samples is not specified. The studies are retrospective, as they involve characterizing the performance of the assay with collected samples, rather than following patients prospectively as part of the study.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
For in vitro diagnostic assays like this, which measure an analyte (hCG), the "ground truth" is typically the concentration of the analyte itself, often established by a reference method or highly characterized reference materials for standardization, or by the clinical diagnosis. This is not a device where human experts (e.g., radiologists) interpret images or clinical data to establish a ground truth.
- Standardization: The ADVIA Centaur Total hCG assay is traceable to the World Health Organization (WHO) 5th IS 7/364 reference material. This material itself serves as the 'ground truth' for defining hCG concentration.
- Expected Values: The reference range study for Non-Pregnant and Postmenopausal Females established through a CLSI guideline, where the "ground truth" for non-pregnant status would be clinical assessment, and the hCG measurement would be the result to define the range.
Therefore, the concept of "number of experts used to establish ground truth" as it applies to image interpretation or clinical diagnosis is not directly applicable here. The ground truth is fundamentally analytical (traceability to reference standards) and clinical classification (e.g., non-pregnant status).
4. Adjudication Method for the Test Set
Not applicable for this type of in vitro diagnostic device study. Adjudication methods (like 2+1, 3+1) are typically used in clinical studies where individual expert opinions need to be reconciled for clinical endpoints or image interpretations. Here, the studies are analytical performance evaluations.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, If So, What Was the Effect Size of How Much Human Readers Improve with AI vs. Without AI Assistance
Not applicable. This device is an in vitro diagnostic assay, not an AI-assisted diagnostic imaging device or a system involving human readers interpreting outputs.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, the studies described are for the standalone analytical performance of the ADVIA Centaur® Total hCG assay. The device measures hCG quantitatively; its performance characteristics (precision, linearity, interference, etc.) are inherent to the assay and instrument system, independent of human interpretation of the measurement itself. The "without human-in-the-loop" concept applies.
7. The Type of Ground Truth Used (Expert Consensus, Pathology, Outcomes Data, etc.)
The ground truth depends on the specific performance characteristic:
- Analytical Ground Truth: For characteristics like method comparison, linearity, dilution recovery, interferences, and cross-reactivity, the ground truth is often defined by:
- Reference Methods: The predicate device (Atellica IM ThCG assay)
- Spiked Samples: Known concentrations of analyte or interfering substances added to samples.
- Traceability to International Standards: WHO 5th IS 7/364 reference material.
- Clinical Ground Truth: For the "Expected Values" study, the ground truth of "non-pregnant" or "postmenopausal" status would be established through clinical assessment of the individuals providing the samples.
8. The Sample Size for the Training Set
This document describes a 510(k) submission for an in vitro diagnostic (IVD) assay, not a machine learning or AI algorithm development. Therefore, the concept of a "training set" in the context of AI is not applicable. The assay's methods are based on established immunoassay principles, and the performance characteristics are determined through analytical validation studies.
9. How the Ground Truth for the Training Set Was Established
As explained in point 8, the concept of a training set for an AI/ML algorithm is not relevant for this traditional IVD assay validation. The assay is developed based on scientific and chemical principles, and its performance is validated against specific criteria using various types of samples.
{0}------------------------------------------------
Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
July 13, 2021
Siemens Healthcare Diagnostics, Inc. Mey Vasquez Regulatory Clinical Affairs Specialist 511 Benedict Ave. Tarrytown, New York 10591
Re: K200210
Trade/Device Name: ADVIA Centaur® Total hCG assay Regulation Number: 21 CFR 862.1155 Regulation Name: Human Chorionic Gonadotropin (HCG) Test System Regulatory Class: Class II Product Code: DHA Dated: October 16, 2020 Received: October 20, 2020
Dear Mey Vasquez:
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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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
{1}------------------------------------------------
801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; 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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
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/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). 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 (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Marianela Perez-Torres, Ph.D. Deputy Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
{2}------------------------------------------------
Indications for Use
510(k) Number (if known) K200210
Device Name ADVIA Centaur® Total hCG assay
Indications for Use (Describe)
For in vitro diagnostic use in the quantitative determination of human chorionic gonadotropin (hCG) in serum or plasma (EDTA or lithium heparin) using the ADVIA Centaur® XP system.
Human chorionic gonadotropin measurements are intended for use as an aid in the early detection of pregnancy.
Type of Use (Select one or both, as applicable)
| Prescription Use (Part 21 CFR 801 Subpart D) |
|---|
| Over-The-Counter Use (21 CFR 801 Subpart C) |
CONTINUE ON A SEPARATE PAGE IF NEEDED.
This section applies only to requirements of the Paperwork Reduction Act of 1995.
DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.
The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:
Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."
{3}------------------------------------------------
Image /page/3/Picture/0 description: The image shows the Siemens Healthineers logo. The word "SIEMENS" is in teal, and the word "Healthineers" is in orange. To the right of the word "Healthineers" is a graphic of orange dots arranged in a circular pattern.
510(k) Summary of Safety and Effectiveness
Introduction: According to the requirements of SMDA 1990 and 21 CFR 807.92, the following information provides sufficient details to understand the basis for determination of substantial equivalence.
The assigned 510(k) Number: _
APPLICANT 1.
Siemens Healthcare Diagnostics Inc. 511 Benedict Avenue, Tarrytown, NY 10591 USA
| Contact: | Mey Vasquez |
|---|---|
| Regulatory Clinical Affairs Specialist | |
| Phone: | (201) 982-2455 |
| Fax: | (914) 524-3579 |
| E-mail: | mey.vasquez@siemens-healthineers.com |
Date Prepared: October 16, 2020
Regulatory Information 2.
Assay
| Trade Name | ADVIA Centaur® Total hCG assay |
|---|---|
| Device | system, test, human chorionic gonadotropin |
| Regulation Description | Human chorionic gonadotropin (HCG) test system |
| FDA Classification | Class II |
| Review Panel | Clinical Chemistry |
| Product Code | DHA |
| Regulation Number | 21 CFR 862.1155 |
{4}------------------------------------------------
Image /page/4/Picture/0 description: The image shows the logo for Siemens Healthineers. The word "SIEMENS" is written in teal, and the word "Healthineers" is written in orange below it. To the right of the word "Healthineers" is a cluster of orange dots.
3. PREDICATE DEVICE
Assay
Name of Device: Atellica IM Total hCG (ThCG)
510 (k): K172322
4. DEVICE DESCRIPTION
The ADVIA Centaur® Total hCG assay reagents come in the following configurations:
| Contents | Numberof Tests |
|---|---|
| 5 ReadyPack primary reagent packs containing ADVIA CentaurTotal hCG Lite Reagent and Solid Phase ADVIA Centaur andADVIA Centaur CP Total hCG Master Curve card | 250 |
| 1 ReadyPack primary reagent pack containing ADVIA Centaur TotalhCG Lite Reagent and Solid Phase ADVIA Centaur and ADVIACentaur CP Total hCG Master Curve card | 50 |
The ReadyPack consists of the following:
ADVIA Centaur ThCG ReadyPack® primary reagent pack; Lite Reagent
5.0 mL/reagent pack polyclonal goat anti-hCG antibody (~0.1 µg/mL) labeled with acridinium ester in buffered saline with sodium azide (0.1%) and preservatives
ADVIA Centaur ThCG ReadyPack primary reagent pack; Solid Phase Reagent
22.5 mL/reagent pack monoclonal mouse anti-hCG antibody (~0.02 mg/mL) covalently coupled to paramagnetic particles in buffered saline with sodium azide (0.1%) and preservatives
ADVIA Centaur ThCG ReadyPack ancillary reagent pack; ThCG Diluent
25.0 mL/reagent pack buffered heat-treated equine serum with EDTA, sodium azide (< 0.1%), and preservatives
ADVIA Centaur ThCG Diluent
50.0 mL/vial buffered heat-treated equine serum with EDTA, sodium azide (< 0.1%), and preservatives
{5}------------------------------------------------
Image /page/5/Picture/0 description: The image shows the logo for Siemens Healthineers. The word "SIEMENS" is written in teal, and the word "Healthineers" is written in orange below it. To the right of the word "Healthineers" is a cluster of orange dots.
5. INDICATIONS FOR USE
For in vitro diagnostic use in the quantitative determination of human chorionic gonadotropin (hCG) in serum or plasma (EDTA or lithium heparin) using the ADVIA Centaur® XP system.
Human chorionic gonadotropin measurements are intended for use as an aid in the early detection of pregnancy.
INTENDED USE 6.
Same as Indications for Use
7. Purpose of the Submission
The purpose of this submission is for the addition of plasma (EDTA and lithium heparin) sample claim for the ADVIA Centaur® Total hCG assay.
8. COMPARISION OF TECHNOLOGICAL CHARACTERISTICS WITH THE PREDICATE DEVICE
The following table demonstrates substantial equivalence between the ADVIA Centaur® Total hCG assay (Candidate Device) that has modified Instructions for Use (Package Inserts) with the addition of the plasma (EDTA and lithium) sample claim and the currently marketed Atellica IM® Total hCG (ThCG) (Predicate Device) that was cleared under 510(k) K172322.
{6}------------------------------------------------
Image /page/6/Picture/0 description: The image shows the logo for Siemens Healthineers. The word "SIEMENS" is written in teal, and the word "Healthineers" is written in orange below it. To the right of the word "Healthineers" is a graphic of orange circles.
| Assay | ||
|---|---|---|
| Item | Predicate Device | Candidate Device |
| Atellica IM® Total hCG (ThCG) | ADVIA Centaur® Total hCG assay | |
| Intended Use | The Atellica® IM Total hCG (ThCG) assay is for invitro diagnostic use in the quantitativedetermination of human chorionic gonadotropin(hCG) in human serum or plasma (EDTA orlithium heparin) using the Atellica® IM Analyzer.The Atellica IM ThCG assay is intended for use asan aid in the early detection of pregnancy. | For in vitro diagnostic use in the quantitative determination ofhuman chorionic gonadotropin(hCG) in serum or plasma (EDTA or lithium heparin) usingthe ADVIA Centaur® XP systems.Human chorionic gonadotropin measurements are intendedfor use as an aid in the early detection of pregnancy. |
| Measurement | Quantitative | Same |
| Assay Range | 2.6-1000 mIU/mL (IU/L) | 4.0-1000 mIU/mL (IU/L) |
| Assay Principle | 2-site Sandwich immunoassay | Same |
| Technology | Direct chemiluminescent | Same |
| Sample Type | Serum, EDTA Plasma, lithium heparin plasma | Serum or plasma (EDTA orlithium heparin) |
| Sample Volume | 25 µL | 50 µL |
| ReagentVolume | 50 µL of Lite Reagent and 255 µL of Solid Phase | 100 µL of Lite Reagent and 450 µL of Solid Phase |
| IncubationTime | 8 minutes at 37°C. | 7.5 minutes at 37°C. |
| Standardization | The Atellica IM ThCG assay standardization istraceable to the World Health Organization(WHO) 4th IS 75/589 reference material. Assignedvalues for calibrators are traceable to thisstandardization. | The ADVIA Centaur Total hCG assay is traceable to theWorld Health Organization (WHO) 5th IS 7/364 referencematerial. |
| Calibration | 2 point | 2 point |
Table 1: Substantial Equivalence Comparison
4
{7}------------------------------------------------
Image /page/7/Picture/0 description: The image shows the logo for Siemens Healthineers. The word "SIEMENS" is in teal, and the word "Healthineers" is in orange. To the right of the word "Healthineers" is an orange graphic of several circles.
PERFORMANCE CHARACTERISTICS DATA 9.
Detection Capability
| Detection Capabilities | Package InsertClaims(mIU/mL) |
|---|---|
| LOQ | 4.0 |
| LOD | 3.0 |
| LOB | 2.0 |
Precision
Precision was determined in accordance with CLSI Document EP05-A3. Samples were assayed in duplicate in 2 runs per day for 20 days. The following results are representative of the performance of the assay:
| Repeatability | Between-Run | Between-Day | Within-Lab | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Sample Type | N | MeanmIU/mL(IU/L) | SDmIU/mL(IU/L) | CV(%) | SDmIU/mL(IU/L) | CV(%) | SDmIU/mL(IU/L) | CV(%) | SDmIU/mL(IU/L) | CV(%) | |
| Serum A | 320 | 6.63 | 0.29 | 4.4% | 0.09 | 1.3% | 0.24 | 3.6% | 0.39 | 5.8% | |
| Serum B | 320 | 15.85 | 0.53 | 3.3% | 0.45 | 2.8% | 0.31 | 2.0% | 0.76 | 4.8% | |
| Serum C | 320 | 819.28 | 20.25 | 2.5% | 22.47 | 2.7% | 12.09 | 1.5% | 32.58 | 4.0% | |
| Control 1 | 320 | 7.43 | 0.30 | 4.1% | 0.15 | 2.0% | 0.32 | 4.3% | 0.46 | 6.2% | |
| Control 2 | 320 | 24.64 | 0.61 | 2.5% | 0.14 | 0.6% | 0.58 | 2.3% | 0.85 | 3.5% | |
| Control 3 | 320 | 164.66 | 2.96 | 1.8% | 0.79 | 0.5% | 2.71 | 1.6% | 4.09 | 2.5% |
{8}------------------------------------------------
Image /page/8/Picture/0 description: The image shows the logo for Siemens Healthineers. The word "SIEMENS" is written in teal, and the word "Healthineers" is written in orange below it. To the right of the words is a graphic of orange dots arranged in a circular pattern.
Method Comparison
Method comparison studies were conducted according to CLSI EP09-A3: Measurement Procedure Comparison and Bias Estimation Using Patient Samples; Approved Guideline-Third Edition. The following results were obtained:
For 117 samples in the range of 7.6 to 977.6 mIU/mL (IU/L), the relationship between the ADVIA Centaur Total hCG assay and the Atellica IM ThCG assay is described by the equation:
ADVIA Centaur Total hCG = 0.96 (Atellica IM ThCG assay) - 3.0 mIU/mL
Correlation coefficient (r) = 0.997
Specimen Equivalence
Serum/plasma (K2 EDTA and lithium heparin) sample equivalence was evaluated by method comparison studies of matched-sample sets. The studies were conducted in accordance to CLSI EP09-A3: Method Comparison and Bias Estimation using Patient Samples. The following results were obtained:
| Tube (y) vs. Serum (x) | Na | Sample Interval | Slope | Intercept | rb |
|---|---|---|---|---|---|
| Dipotassium EDTA plasma | 53 | 4.7 – 948.9 mIU/mL (IU/L) | 0.99 | 0.3 | 1.00 |
| Lithium heparin plasma | 51 | 4.7 – 975.7 mIU/mL (IU/L) | 1.01 | - 0.3 | 1.00 |
a Number of samples tested.
b Correlation coefficient.
The assay is designed to have a slope of 0.90–1.10 for alternate tube types versus serum.
Agreement of the specimen types may vary depending on the study design and sample population used. Assay results obtained at individual laboratories may vary from the data presented.
Linearity
Linearity of the ADVIA Centaur Total hCG assay was performed in accordance to CLSI EP6-A: Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach. The following results were obtained:
The linearity study included samples spanning the entire assay range. Results met acceptance criteria. Therefore, the results from the linearity study support an analytical measuring range from 4.0 mlU/mL to 1000 mlU/mL.
{9}------------------------------------------------
Image /page/9/Picture/0 description: The image shows the logo for Siemens Healthineers. The word "SIEMENS" is written in teal, and the word "Healthineers" is written in orange below it. To the right of the word "Healthineers" is a graphic of orange dots.
Dilution Recovery
The dilution recovery study was carried out following the dilution ratios: 1:2, 1:4, 1:8 and 1:16. The following results were obtained:
| Dilution | Observed mIU/mL(IU/L) | Expected mIU/mL(IU/L) | % Recovery |
|---|---|---|---|
| 1:2 | 609.5 | 672.4 | 91% |
| 794.8 | 877.1 | 91% | |
| 893.3 | 966.9 | 92% | |
| Mean | 91% | ||
| 1:4 | 315.5 | 336.2 | 94% |
| 430.9 | 438.6 | 98% | |
| 487.5 | 483.5 | 101% | |
| 520.3 | 533.5 | 98% | |
| 581.1 | 611.5 | 95% | |
| 961.8 | 932.2 | 103% | |
| Mean | 98% | ||
| 1:8 | 156.8 | 168.1 | 93% |
| 213.4 | 219.3 | 97% | |
| 235.2 | 241.7 | 97% | |
| 259.7 | 266.8 | 97% | |
| 295.7 | 305.8 | 97% | |
| 486.5 | 466.1 | 104% | |
| 836.6 | 1010.8 | 83% | |
| Mean | 95% | ||
| 1:16 | 87.9 | 84.1 | 105% |
| 109.8 | 109.6 | 100% | |
| Dilution | Observed mIU/mL(IU/L) | Expected mIU/mL(IU/L) | % Recovery |
| 120.1 | 120.9 | 99% | |
| 129.1 | 133.4 | 97% | |
| 149.6 | 152.9 | 98% | |
| 258.3 | 233.0 | 111% | |
| 454.1 | 505.4 | 90% | |
| 985.3 | 896.4 | 110% | |
| Mean | 101% |
{10}------------------------------------------------
Image /page/10/Picture/0 description: The image contains the logos for Siemens and Healthineers. The Siemens logo is in teal, and the Healthineers logo is in orange. The Healthineers logo also has a series of orange dots to the right of the word.
Interferences
Interference testing was conducted in accordance with CLSI EP07:Ed3: Interference Testing in Clinical Chemistry; Approved Guideline —Third Edition. This study was carried out used the paired-difference approach.
| Substance | SubstanceTestConcentration | AnalyteConcentrationmIU/mL (IU/L) | % Bias |
|---|---|---|---|
| Human SerumAlbumin | 6 g/dL | 7.0 | -0.3% |
| 494.4 | -0.2% | ||
| Acetaminophen | 20 mg/dL | 7.3 | 2.7% |
| 498.5 | -0.5% | ||
| Acetylsalicylic acid | 65 mg/dL | 7.5 | 2.7% |
| 500.4 | 0.4% | ||
| Heparin | 7200 IU/dL | 7.3 | -8.2% |
| 502.7 | 1.6% | ||
| Ibuprofen | 50 mg/dL | 7.3 | -1.4% |
| 502.8 | 0.3% | ||
| EDTA | 3.4 $ μ $ mol/L | 7.4 | 4.1% |
| 473.4 | 1.8% | ||
| Ethanol | 600 mg /dL | 7.3 | 2.7% |
| 500.0 | -1.1% | ||
| Atropine | 20 mg/dL | 6.6 | 0.0% |
{11}------------------------------------------------
Image /page/11/Picture/0 description: The image contains the logo for Siemens Healthineers. The word "SIEMENS" is written in teal, and the word "Healthineers" is written in orange. To the right of the word "Healthineers" is a graphic of orange dots.
| Substance | SubstanceTestConcentration | AnalyteConcentrationmIU/mL (IU/L) | % Bias | |
|---|---|---|---|---|
| 499.0 | -1.5% | |||
| Caffeine | 556 um/L | 6.6 | 6.1%1.1% | |
| 485.2 | ||||
| Gentisic acid | 7.0 | 4.3% | ||
| 117 µmol/L | 500.3 | -1.1% |
Hemolysis, Icterus, and Lipemia (HIL)
| Substance | SubstanceTestConcentration | AnalyteConcentrationmIU/mL (IU/L) | % Bias |
|---|---|---|---|
| Bilirubin(Conjugated) | 40 mg/dL | 5.9 | 3.3% |
| 508.3 | -1.0% | ||
| Bilirubin(Unconjugated) | 40 mg/dL | 6.4 | -0.8% |
| 489.5 | 1.7% | ||
| Hemoglobin | 1000 mg/dL | 6.4 | 1.3% |
| 478.4 | -0.5% | ||
| Intralipid | 3000 mg/dL | 6.5 | -3.7% |
| 442.9 | -3.3% |
{12}------------------------------------------------
Image /page/12/Picture/0 description: The image shows the Siemens Healthineers logo. The word "SIEMENS" is in teal, and the word "Healthineers" is in orange. To the right of the word "Healthineers" is a cluster of orange dots.
Expected Values
The reference range study was performed in accordance CLSI EP28-A3c: Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory, 3rd Edition. The following results were obtained:
| Sample Category | Na | Median(mIU/mL) (IU/L) | Reference IntervalmIU/mL) (IU/L)2.5-97.5 Percentile |
|---|---|---|---|
| Non-Pregnant Females(Age: ≤40) | 130 | 0.03 | 0.03 - 0.6 |
| PostmenopausalFemales(Age: ≥41) | 150 | 0.02 | 0.02 – 2.9 |
ª Number of samples.
Standardization:
The ADVIA Centaur Total hCG assay is traceable to the World Health Organization WHO 5th IS 7/364 reference material.
Cross-Reactivity
| Cross-reactant | hCG Value withoutCross-reactant (mIU/mL)(IU/L) | hCG Value withCross-reactant (mIU/mL)(IU/L) |
|---|---|---|
| FSH 500mIU/mL | 0.5 | 1.6 |
| 7.7 | 8.0 | |
| 54.9 | 54.4 | |
| 493.1 | 475.4 | |
| TSH 1000ulU/mL | 1.3 | 1.4 |
| 7.6 | 7.4 | |
| 54.2 | 51.6 | |
| 499.9 | 462.9 | |
| LH 500mIU/mL | 0.9 | 1.1 |
| 7.8 | 7.0 | |
| 56.2 | 47.7 | |
| 487.9 | 428.5 | |
| hGH 500 ng/mL | 0.8 | 0.9 |
| 7.3 | 7.2 | |
| 53.0 | 52.9 | |
| 482.3 | 487.7 | |
| PRL 1000 ng/mL | 0.8 | 0.6 |
| 7.9 | 7.5 |
{13}------------------------------------------------
Image /page/13/Picture/0 description: The image shows the logo for Siemens Healthineers. The word "SIEMENS" is in teal, and the word "Healthineers" is in orange. To the right of the words is a graphic of several orange dots arranged in a circular pattern.
| Cross-reactant | hCG Value withoutCross-reactant (mIU/mL)(IU/L) | hCG Value withCross-reactant (mIU/mL)(IU/L) |
|---|---|---|
| 54.6 | 54.6 | |
| 490.5 | 494.2 |
Sample Handling Studies:
The sample handling and stability study show acceptable data to support the labeling claims for serum and plasma samples outlined below.
- -Samples can be stored refrigerated (2-8°C) for up to 48 hours.
- Samples can be stored at room temperature (25°C) for up to 8 hours. -
- Samples can be kept on-board (30°C) for up to 8 hours. -
- -Samples can be frozen and thawed up to 1 time.
CONCLUSION X.
Comparative testing of the ADVIA Centaur® Total hCG assay is substantially equivalent in principle and performance to the Predicate Device – Atellica IM ThCG assay cleared under 510(k) K172322.
§ 862.1155 Human chorionic gonadotropin (HCG) test system.
(a)
Human chorionic gonadotropin (HCG) test system intended for the early detection of pregnancy —(1)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.(2)
Classification. Class II.(b)
Human chorionic gonadotropin (HCG) test system intended for any uses other than early detection of pregnancy —(1)Identification. 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.(2)
Classification. Class III.(3)
Date PMA or notice of completion of a PDP is required. As of the enactment date of the amendments, May 28, 1976, an approval under section 515 of the act is required before the device described in paragraph (b)(1) may be commercially distributed. See § 862.3.