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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 or plasma (EDTA or lithium heparin) using the Atellica® IM Analyzer.

Human chorionic gonadotropin measurements are intended for use as an aid in the early detection of pregnancy.

Device Description

The Atellica® IM Total hCG (ThCG) Assay reagents come in the following configurations:
1 ReadyPack primary reagent pack containing Atellica IM ThCG Lite Reagent and Solid Phase Atellica IM ThCG master curve and test definition (90 Tests)
5 ReadyPack primary reagent packs containing Atellica IM ThCG Lite Reagent and Solid Phase Atellica IM ThCG master curve and test definition (450 Tests)

The ReadyPack consists of the following:
Atellica IM ThCG ReadyPack primary reagent pack Lite Reagent: 4.5 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: 20.3 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 (

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the Atellica® IM Total hCG (ThCG) device, based on the provided FDA 510(k) summary:

The purpose of this submission (K192790) is to add a plasma (EDTA and lithium heparin) sample claim for the Atellica® IM Total hCG (ThCG) assay, which was previously cleared for serum samples under K172322. Therefore, the acceptance criteria and supporting studies specifically address the performance of the device with these new sample types.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for the new plasma sample types are implicitly derived from the established performance of the predicate device with serum and are demonstrated through equivalency studies. The key performance indicator for this submission is the agreement between plasma and serum samples.

Acceptance Criteria Category	Specific Criteria (Implicit for equivalency to serum)	Reported Device Performance (Plasma vs. Serum)	Comments
Specimen Equivalence	Slope: 0.90 – 1.10	Dipotassium EDTA plasma (y) vs. Serum (x):
Slope = 1.02, Intercept = -1.4 mIU/mL	Meets the acceptance criteria for slope.
	Intercept: Close to 0		Intercept is low relative to the assay range.
	Correlation Coefficient (r): Close to 1.00	Correlation Coefficient (r) = 1.00	Excellent correlation.
		Lithium heparin plasma (y) vs. Serum (x):
Slope = 1.05, Intercept = 0.2 mIU/mL	Meets the acceptance criteria for slope.
			Intercept is very low, indicating good agreement.
		Correlation Coefficient (r) = 1.00	Excellent correlation.
Interference	Bias %: No significant bias	Dipotassium EDTA (9.0 mg/mL):
1.5% (at 21.1 mIU/mL), 0.7% (at 626.4 mIU/mL)	Low bias, indicating no significant interference.
		Heparin (75 U/mL):
1.8% (at 25.4 mIU/mL), 0.7% (at 668.9 mIU/mL)	Low bias, indicating no significant interference.

2. Sample Size Used for the Test Set and Data Provenance

Sample Size for Specimen Equivalence (Test Set):
- Dipotassium EDTA plasma: 116 samples
- Lithium heparin plasma: 134 samples
Sample Interval: 3.8 - 959.2 mIU/mL (IU/L) for both plasma types.
Data Provenance: The document does not explicitly state the country of origin or whether the samples were retrospective or prospective.
Sample Size for Interference (Test Set): Not explicitly stated, however, the results show bias at two analyte concentrations for each interferent, suggesting a controlled experimental setup, likely with replicates for each condition.

3. Number of Experts Used to Establish Ground Truth for the Test Set and Their Qualifications

This type of immunoassay (quantitative determination of hCG) typically does not involve human experts establishing a subjective "ground truth" for individual test samples, as the analyte concentration is an objective biochemical measurement. The ground truth, in this context, is the measured hCG concentration in the serum samples, which essentially serves as the reference for comparison against plasma samples. The accuracy of these serum measurements would be ensured by laboratory quality controls and standardization against international reference materials (WHO 4th IS 75/589 reference material), as mentioned in the "Standardization" section. Therefore, no "experts" in the sense of clinical reviewers are used to establish ground truth for this type of quantitative assay performance study.

4. Adjudication Method for the Test Set

Not applicable. For a quantitative assay comparing different sample matrices, adjudication methods like N+1 consensus are not used. The comparison is statistical, based on linear regression and bias analysis between the results from the plasma samples and the reference serum samples.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done

No, an MRMC comparative effectiveness study was not done. This device is an in vitro diagnostic assay that quantitatively measures a biomarker (hCG). MRMC studies are typically performed for imaging devices or other diagnostic tools where human interpretation plays a role, to assess the impact of AI assistance on human reader performance. This submission focuses on the analytical performance of the assay itself with different sample types.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) was done

Yes, the performance studies described are standalone. The "device" in question is the Atellica® IM Total hCG (ThCG) assay, which is an automated in vitro diagnostic system. The performance data presented (specimen equivalence and interference) directly reflects the analytical performance of the assay when run on the Atellica® IM Analyzer, without human intervention in the measurement process itself, beyond standard laboratory procedures for sample handling and instrument operation.

7. The Type of Ground Truth Used

For the specimen equivalence study, the ground truth for comparison was the hCG concentration determined in human serum samples using the Atellica® IM Total hCG (ThCG) assay (the predicate device). The new sample types (EDTA plasma and lithium heparin plasma) were then tested on the same device and compared against these serum results.

For interference testing, the "ground truth" would be the expected hCG concentration in the samples without the interferent, or a known spiked concentration.

8. The Sample Size for the Training Set

The document does not explicitly mention a "training set" in the context of this 510(k) submission. This is typical for in vitro diagnostic assays based on established immunoassay principles, where the assay design, calibration, and optimization (which can be analogous to "training" in AI/ML) would have been performed during the initial development and clearance of the predicate device (K172322). This submission is an extension of that device for new sample types, relying on the already established assay method.

9. How the Ground Truth for the Training Set was Established

As noted above, a distinct "training set" in the AI/ML sense is not directly applicable here. The "ground truth" for the development and establishment of the assay's performance would have involved:

Standardization: Against the World Health Organization (WHO) 4th IS 75/589 reference material for hCG. This provides the fundamental "ground truth" reference for hCG concentration.
Calibration: Assigned values for calibrators are traceable to this WHO standard.
Analytical Performance Studies: Initial studies (precision, linearity, detection capability) performed for the predicate device (K172322) would have established the assay's performance characteristics against these standardized references and known concentrations.

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K Number

K172322

Device Name

Atellica IM Total hCG (ThCG)

Manufacturer

Siemens Healthcare Diagnostics Inc.

Date Cleared

2018-03-29

(240 days)

Product Code

JHI

Regulation Number

862.1155

Type

Traditional

Panel

Clinical Chemistry (CH)

Reference & Predicate Devices

k925277

Intended Use

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.

Device Description

The Atellica IM Total hCG (ThCG) assay is an in vitro diagnostic assay for the quantitative determination of human chorionic gonadotropin (hCG) in human serum using the Atellica IM Analyzer. The assay utilizes a sandwich immunoassay principle with direct chemiluminescent technology. The reagents include a Lite Reagent containing goat polyclonal anti-hCG antibody labeled with acridinium ester and a Solid Phase containing mouse monoclonal anti-hCG antibody covalently coupled to paramagnetic particles. Ancillary reagents like Atellica IM ThCG DIL are also part of the system.

AI/ML Overview

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

Here's an analysis of its acceptance criteria and the study that proves its performance:

1. Table of Acceptance Criteria and Reported Device Performance:

The provided document outlines several performance characteristics, including detection capability, precision, and method comparison, against a predicate device (ADVIA Centaur Total hCG assay).

Performance Characteristic	Acceptance Criteria (Implicit)	Reported Device Performance
Detection Capability
Limit of Blank (LoB)	Not explicitly stated as acceptance criteria, but lowest measurement result for a blank sample expected to be below LoD/LoQ.	1.5 mIU/mL (IU/L)
Limit of Detection (LoD)	Probability of 95% detection for the lowest concentration.	1.7 mIU/mL (IU/L) (determined using 601 determinations, with 300 blank and 301 low-level replicates, and an LoB of 1.5 mIU/mL (IU/L)).
Limit of Quantitation (LoQ)	Lowest amount of hCG with a percent total error of 30%.	2.6 mIU/mL (IU/L) (determined using multiple samples prepared from WHO 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).
Precision	Not explicitly stated as numerical acceptance criteria, but typical expectations are low %CV for various levels.	Repeatability (Within-run): Serum 1 (2.4 mIU/mL): 8.8% CV; Serum 2 (12.6 mIU/mL): 2.8% CV; Serum 3 (782.0 mIU/mL): 1.8% CV. Control 1 (6.8 mIU/mL): 4.5% CV; Control 2 (23.4 mIU/mL): 2.6% CV; Control 3 (202.1 mIU/mL): 1.8% CV.
Within-Lab: Serum 1 (2.4 mIU/mL): 10.5% CV; Serum 2 (12.6 mIU/mL): 3.4% CV; Serum 3 (782.0 mIU/mL): 2.2% CV. Control 1 (6.8 mIU/mL): 5.5% CV; Control 2 (23.4 mIU/mL): 3.5% CV; Control 3 (202.1 mIU/mL): 2.7% CV.
Method Comparison	Correlation coefficient (r) ≥ 0.95 and a slope of 1.0 ± 0.10 compared to the ADVIA Centaur Total hCG assay.	r = 1.00 (for serum samples, n=115, in the range 2.4-947.7 mIU/mL (IU/L)).
Regression Equation: $y = 0.94x + 0.23 mIU/mL (IU/L)$. The slope (0.94) is within the 1.0 ± 0.10 criterion. The intercept (0.23) indicates a small constant bias.
Interference	Not explicitly stated as acceptance criteria, but generally a bias of ≤ 10% is considered acceptable for common interfering substances.	Most reported bias values for various substances (Acetaminophen, Acetylsalicylic acid, Atropine, Caffeine, EDTA, Ethanol, Gentisic acid, Heparin, Human Serum Albumin, Ibuprofen) are well within the typical ±10% range. For HIL (Hemoglobin, Bilirubin, Lipemia), the assay is designed to have ≤ 10% interference, and reported values are generally within this range (highest reported is 8.9% for Hemoglobin at 5.6 mIU/mL).

2. Sample Size Used for the Test Set and Data Provenance:

Detection Capability (LoD): 601 determinations, with 300 blank and 301 low-level replicates. The document doesn't specify data provenance (country of origin or retrospective/prospective).
Detection Capability (LoQ): Multiple samples prepared from the World Health Organization (WHO) human chorionic gonadotropin reference material (NIBSC code: 99/688). No specific sample count is given for the test set, but it implies a study on prepared samples. Data provenance is implied to be laboratory-based and controlled using a recognized international standard.
Precision: Not a "test set" from patients, but rather control materials and serum pools. Samples were assayed in duplicate in 2 runs per day for 20 days using two reagent lots on each of two Atellica IM analyzers, leading to 320 data points for each serum pool and control (2 duplicates * 2 runs/day * 20 days * 2 analyzers * 1 sample type / 2 for reagent lots = 320 for each condition)
Method Comparison: 115 serum specimens. The data provenance (country of origin, retrospective or prospective) is not specified.
Interference: "Serum samples" used, concentrations given, but no specific number of unique patient samples mentioned.
Expected Values: 366 serum samples from 192 apparently healthy non-pregnant females and 174 apparently healthy postmenopausal females. The provenance is not specified. This appears to be a prospective collection for establishing reference ranges.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:

This information is not applicable as the Atellica IM Total hCG assay is a quantitative diagnostic test for a biomarker (hCG) in serum. The 'ground truth' for such assays is typically established by:

Reference Methods: Highly accurate and precise laboratory methods.
Certified Reference Materials: Materials with an assigned value from an authoritative source (like the WHO reference material mentioned for LoQ).
Clinical Diagnosis: For outcomes like pregnancy, a clinical diagnosis confirms the state, and the device then quantifies the biomarker associated with that state.

There is no mention of human experts establishing a 'ground truth' in the context of image interpretation or subjective diagnosis for this device.

4. Adjudication Method for the Test Set:

This is not applicable as the Atellica IM Total hCG assay is an automated quantitative assay. There is no subjective interpretation or need for adjudication by experts as would be found in image-based diagnostic systems.

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:

This is not applicable. The Atellica IM Total hCG assay is an automated in vitro diagnostic device, not an AI-assisted diagnostic tool that involves human readers interpreting cases. Therefore, an MRMC study related to human reader improvement with AI assistance is not relevant.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done:

The performance studies described (detection capability, precision, method comparison, interference, expected values) represent the standalone performance of the Atellica IM Total hCG assay. This device is designed to provide quantitative results directly from serum samples through an automated analyzer, without direct human-in-the-loop interpretation that would alter the result. The device performance itself is evaluated.

7. The Type of Ground Truth Used:

Detection Capability (LoD, LoQ): Determined using prepared samples traceable to the World Health Organization (WHO) 4th International Standard (NIBSC code: 99/688) for human chorionic gonadotropin. This is a form of certified reference material ground truth.
Precision: Internal serum pools and commercial controls with known concentrations served as the basis for evaluating reproducibility.
Method Comparison: The ADVIA Centaur Total hCG assay (predicate device) served as the comparative reference, implying that its established measurements were the 'ground truth' for comparison, to show substantial equivalence.
Interference: Spiked serum samples (serum with known amounts of hCG and interferents added) were used.
Expected Values: Clinical classification of "non-pregnant females" and "postmenopausal females" served as the basis for establishing reference intervals. This aligns with clinical outcome/classification ground truth.

8. The Sample Size for the Training Set:

The document does not explicitly describe a "training set" in the context of machine learning or AI, as this is an immunoassay device. The studies described are performance validation studies. The calibration of the device (using Atellica IM CAL B) and the determination of its "master curve" can be thought of as akin to a training process for an assay, but no sample size for this is provided.

9. How the Ground Truth for the Training Set Was Established:

As mentioned, there isn't a "training set" in the AI/ML sense. The "ground truth" for the assay's operational parameters (like calibration and standardization) is established through:

Standardization against the World Health Organization (WHO) 4th IS 75/589 reference material. This is a universally recognized standard, meaning calibrator values are traceable to this international reference.
Two-point calibration using specific calibrators (Atellica IM CAL B) which themselves are assigned values traceable to the WHO standard.

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