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The ADVIA Centaur® Anti-Müllerian Hormone (AMH) assay is for in vitro diagnostic use in the quantitative determination of anti-Müllerian hormone (AMH) in human serum and plasma (lithium heparin) using the ADVIA Centaur® XP system.

The measurement of AMH is used as an aid in the assessment of the ovarian reserve in women presenting to fertility clinics. This assay is intended to distinguish between women with AFC (antral follicle count) values > 15 (high ovarian reserve) and women with AFC values ≤ 15 (normal or diminished ovarian reserve).

This assay is intended to be used in conjunction with other clinical and laboratory findings, such as AFC, before starting fertility therapy. This assay is not intended to be used for monitoring women undergoing controlled ovarian stimulation in an Assisted Reproduction Technology program.

The ADVIA Centaur AMH assay is a sandwich immunoassay using direct acridinium ester-based chemiluminometric technology. Two monoclonal anti-AMH antibodies are employed in the assay. The first antibody in the Lite Reagent is a mouse monoclonal anti-AMH antibody labeled with acridinium ester. The second antibody is a biotinylated mouse monoclonal anti-AMH antibody coupled to streptavidin-coated magnetic particles in the Solid Phase.

A direct relationship exists between the amount of AMH present in the patient sample and the amount of relative light units detected by the system. Dose concentration results (ng/mL) are calculated based on a 2-point calibration from a pre-defined master curve.

Materials include:
ADVIA Centaur AMH ReadyPack® primary reagent pack: Solid Phase (Streptavidin-coated paramagnetic microparticles with biotinylated mouse monoclonal anti-human AMH antibody in buffer; sodium azide (

Here's the detailed breakdown of the acceptance criteria and study information for the ADVIA Centaur® Anti-Müllerian Hormone (AMH) assay, based on the provided FDA 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance

Plasma, lithium heparin vs. Serum:
Correlation coefficient (r) = 0.997
Regression Equation: y = 1.08x - 0.004 ng/mL (Slope: 1.08, Intercept: -0.004 ng/mL). Meets criteria. |
| Interferences (HIL) | Bias due to substances not to exceed 10% at specified AMH concentrations | Hemoglobin: No interference (1000 mg/dL).
Bilirubin, conjugated: No interference (66.0 mg/dL).
Bilirubin, unconjugated: No interference up to 39.0 mg/dL; however, >10% bias observed at ≥ 40 mg/dL (10.6% bias at 6.79 ng/mL AMH, 11.4% bias at 0.936 ng/mL AMH).
Lipemia (Intralipid): No interference (2000 mg/dL). |
| Interferences (Other Substances) | Bias due to substances not to exceed 10% at specified AMH concentrations | Acetaminophen, Acetylcysteine, Acetylsalicylic Acid, Ampicillin sodium, L-Ascorbic acid, Biotin, Cefoxitin sodium salt, Cholesterol, Cyclosporine, Doxycycline hyclate, Folic acid, Gonapeptyl, Heparin, Human IgA, Human IgG, Human IgM, Ibuprofen, Levodopa, Levothyroxine, Metformin hydrochloride, Methyldopa, Metronidazole, Phenylbutazone, Rheumatoid Factor, Rifampicin, Theophylline, Total Protein, Uric acid: All showed no interference (bias ≤ 10%) at tested concentrations. |
| Cross-Reactivity | Bias does not exceed 10% | Activin A, Activin B, Activin AB, Inhibin A, Inhibin B, TGF b-1: ≤ 0.1% cross-reactivity.
Follicle stimulating hormone (FSH) at 500 mIU/mL: Not Detectable, 0.2% bias.
Luteinizing hormone (LH) at 500 mIU/mL: Not Detectable, 2.9% bias. All considered insignificant. |
| Stability (On-board Reagents) | Reagents stable for 70 days | Determined to be 70 days. |
| Stability (Calibrators)| Calibrators stable at 2-8°C and ≤ -20°C for 90 days after reconstitution | Determined to be stable at 2-8°C and ≤ -20°C for 90 days after reconstitution. |
| High Dose Hook | (No explicit criterion given, but predicate states no hook effect up to 1000 ng/mL) | No hook effect observed up to 1151 ng/mL (8218 pmo/L). This exceeds the predicate. |
| Clinical Performance (Overall)| (Aid in distinguishing AFC > 15 vs ≤ 15 in fertility clinics) | Sensitivity: 90.5% (256/283) (95% CI: 86.47, 93.36)
Specificity: 52.0% (130/250) (95% CI: 45.82, 58.12)
PPV: 68.1% (256/376) (95% CI: 63.21, 72.59)
NPV: 82.8% (130/157) (95% CI: 76.13, 87.90) |
| **Clinical Performance (Age 15 vs ≤ 15 in fertility clinics for this age group) | Prevalence (AFC > 15): 67.4%
PPV: 73.6% (67.47, 78.88)
NPV: 65.1% (50.17, 77.58) |
| Clinical Performance (Age ≥ 35)| (Aid in distinguishing AFC > 15 vs ≤ 15 in fertility clinics for this age group) | Prevalence (AFC > 15): 38.4%
PPV: 59.7% (51.71, 67.27)
NPV: 89.5% (82.50, 93.88) |

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

• Detection Capability (LoB, LoD, LoQ): Not explicitly stated, but determined as described in CLSI protocol EP17-A2. These are typically derived from analytical studies involving numerous replicates of blank, low-concentration, and relevant samples.
• Precision and Reproducibility:
  • Precision: 480 measurements per sample/control (replicates of 2, 2 runs/day, 20-day protocol). This was across 2 instruments and 3 reagent lots.
  • Reproducibility: 90 measurements per sample/control (triplicate, 2 runs/day, 5 days) across 3 sites and 1 reagent lot.
• Assay Comparison: 120 samples (serum) vs. a commercial AMH assay.
• Specimen Equivalence: 88 samples for Gel-barrier tube (serum) vs. Serum, and 88 samples for Plasma (lithium heparin) vs. Serum.
• Interferences: The number of samples tested for each substance is not specified, but the testing was performed in accordance with CLSI Document EP07-ed3 and EP37-ed1.
• Cross-Reactivity: Number of samples not specified, performed in accordance with CLSI Document EP07-ed3.
• Stability: Not sample-based but rather experimental conditions and time points.
• Expected Values (Reference Intervals):
  • Females (18–25 years): 209 samples
  • Females (26–30 years): 122 samples
  • Females (31–35 years): 123 samples
  • Females (36–40 years): 126 samples
  • Females (41–45 years): 152 samples
  • Females (46–50 years): 121 samples
  • Females (51 years and older): 139 samples
• Clinical Sensitivity and Specificity: 533 women.
• Data Provenance:
  • Clinical Study: Prospectively collected from women presenting to fertility clinics for evaluation.
  • Country of Origin: 11 sites across the United States.
  • Expected Values: Samples were collected retrospectively or prospectively from "apparently healthy subjects," but the exact nature (retrospective/prospective) and location of collection is not explicitly detailed beyond "apparently healthy subjects". Given the clinical study provenance, it's likely linked, but not explicitly stated.

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

For the clinical performance study (Clinical Sensitivity and Specificity), the ground truth for ovarian reserve was established by Antral Follicle Count (AFC) values determined by transvaginal ultrasound.

• The document does not specify the number of experts (e.g., sonographers, radiologists) who performed or interpreted these ultrasounds.
• It also does not specify the individual qualifications (e.g., years of experience, board certification) of these experts. It only states that the AFC result was determined by transvaginal ultrasound.

4. Adjudication Method for the Test Set

The document does not explicitly describe an adjudication method (such as 2+1, 3+1) for establishing the ground truth (AFC values). The AFC results were simply stated as being "determined by transvaginal ultrasound." This suggests that the individual AFC measurements were taken as the singular truth, without a multi-reader review or adjudication process outlined to resolve discrepancies, if any.

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

No, an MRMC comparative effectiveness study involving human readers and AI assistance was not conducted. This device is an in vitro diagnostic (IVD) assay that quantitatively measures a biomarker (AMH) in serum/plasma. It does not involve interpretation of medical images or other data by human readers, and thus, AI assistance in the context of human reading is not applicable here.

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

Yes, the studies reported are essentially "standalone" performance evaluations of the ADVIA Centaur® Anti-Müllerian Hormone (AMH) assay itself. The clinical performance study evaluates the assay's ability to distinguish between high and normal/diminished ovarian reserve based on AMH measurements, against the ground truth of AFC. This is the performance of the device (the assay) as an algorithm or test method, independent of subsequent human interpretation enhancements.

7. The Type of Ground Truth Used

• Analytical Studies (Detection Capability, Precision, Linearity, Interference, Cross-reactivity, Stability, Hook Effect): The ground truth for these studies is typically derived from highly characterized reference materials, spiked samples with known concentrations, or established analytical methods.
• Expected Values (Reference Intervals): Established by collecting samples from "apparently healthy subjects" and calculating statistical percentiles (90th and 95th reference intervals). The ground truth here is the statistical distribution of AMH levels in a healthy population defined by age.
• Clinical Sensitivity and Specificity: The ground truth for ovarian reserve was Antral Follicle Count (AFC) values, as measured by transvaginal ultrasound. This is a clinical measure widely accepted in fertility assessment.

8. The Sample Size for the Training Set

The document does not specify a separate "training set" in the context of a machine learning or AI algorithm development. This is an in vitro diagnostic assay, where performance is typically established through analytical validation and clinical correlation studies, not through AI model training. The data used for most performance characteristics are considered validation data.

• The "Expected Values" data set (totaling 209+122+123+126+152+121+139 = 992 samples) could be seen as reference data used to establish norms, but not a "training set" for an algorithm in the AI sense.
• The "Clinical Sensitivity and Specificity" study of 533 women served as a clinical validation dataset.

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

As no "training set" in the AI sense is explicitly mentioned for algorithm development, there's no described method for establishing ground truth for such a set. For the validation data described:

• Clinical Study Ground Truth: The ground truth was Antral Follicle Count (AFC) values, determined by transvaginal ultrasound by unspecified qualified personnel at 11 sites across the US.
• Expected Values Ground Truth: These are based on AMH measurements from "apparently healthy subjects," where their health status (absence of relevant pathologies) constitutes the ground truth for establishing normal ranges.

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The Access AMH assay is a paramagnetic particle chemiluminescent immunoassay for the quantitative determination of anti-Müllerian hormone (AMH) levels in human serum and lithium heparin plasma using the Access Immunoassay Systems as an aid in the assessment of ovarian reserve in women presenting to fertility clinics. This system is intended to distinguish between women presenting with AFC (antral follicle count) values > 15 (high ovarian reserve) and women with AFC values ≤ 15 (normal or diminished ovarian reserve). The Access AMH is intended to be used in conjunction with other clinical and laboratory findings such as antral follicle count, before starting therapy. The Access AMH is not intended to be used for monitoring of women undergoing controlled ovarian stimulation in an Assisted Reproduction Technology program.

The Access Anti-Mullerian Hormone Assay, Access Anti-Mullerian Hormone Calibrators, and the Access Immunoassay analyzers comprise the Dxl 9000 Access Immunoassay System for the quantitative determination of Anti-Mullerian Hormone levels in human serum and lithium heparin plasma using the Dxl 9000 Access Immunoassay system.

The provided text describes the performance of the Access AMH assay on the Dxl 9000 Access Immunoassay Analyzer, comparing it to a predicate device (Access AMH assay on Access 2 Immunoassay System).

Here's an analysis of the acceptance criteria and study data:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly present a single table outlining acceptance criteria for all aspects, but rather describes them within the "Summary of Studies" section. Based on the text, here's a reconstructed table:

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

• Method Comparison:
  • Sample Size: N = 126
  • Data Provenance: Not specified (e.g., country of origin, retrospective/prospective). The "Concentration Range" is specified as "Access 2 values," suggesting that these are samples previously run on the predicate device.
• Imprecision:
  • Sample Size: 88 for each of the 9 samples tested (total 9 x 88 = 792 individual measurements).
  • Data Provenance: Not specified.
• Linearity, LoB, LoD, LoQ, Reproducibility:
  • Sample Size: Not explicitly stated for these individual studies, beyond the "N" values in the imprecision table.
  • Data Provenance: Not specified.

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

The document describes performance characteristics of an in vitro diagnostic (IVD) assay quantifying AMH levels. Ground truth in this context typically refers to the true concentration of AMH in a sample, often established by a reference method or highly accurate assay.

• The text does not mention the use of human experts (e.g., radiologists) or their qualifications to establish ground truth for the analytical performance studies (method comparison, imprecision, linearity, LoB, LoD, LoQ, reproducibility).
• For these types of IVD studies, the "ground truth" is often established by comparing the device's results to a recognized reference method or the established predicate device, or by using validated calibrators and controls with known analyte concentrations.

4. Adjudication Method for the Test Set

Given that this is an in vitro diagnostic device assessing analytical performance rather than diagnostic imaging interpretation, an adjudication method (like 2+1 or 3+1) is not applicable and therefore not mentioned. The evaluation relies on quantitative measurements against analytical criteria or a comparative method.

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

• No, an MRMC comparative effectiveness study was not done.
• This device is an in vitro diagnostic test for Anti-Müllerian hormone (AMH) levels, not an AI-assisted diagnostic imaging or interpretation tool for human readers. Therefore, the concept of improving human reader performance with AI assistance is not relevant to this submission.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done

• Yes, the provided studies describe standalone performance of the assay.
• The Access AMH assay is an automated chemiluminescent immunoassay run on an analyzer (Dxl 9000 Access Immunoassay Analyzer). The performance metrics (method comparison, imprecision, linearity, LoB, LoD, LoQ, reproducibility) are inherently standalone, reflecting the analytical capabilities of the device itself without direct human interaction in the measurement process (beyond operating the instrument and collecting/inputting samples).

7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)

• For the analytical performance studies (method comparison, imprecision, linearity, LoB, LoD, LoQ, reproducibility), the ground truth is implicitly defined by:
  • Reference method/Predicate device comparison: For the method comparison study, the "Access 2 values" (from the predicate device) serve as the reference point for comparison.
  • Known concentrations: For imprecision, linearity, LoB, LoD, LoQ studies, ground truth is established using samples (e.g., controls, calibrators, spiked samples) with known or carefully characterized AMH concentrations. This is a common practice in IVD analytical validation.
• It is not based on expert consensus, pathology, or outcomes data, as these are typically used for clinical diagnostic accuracy studies or imaging interpretation.

8. The Sample Size for the Training Set

The document describes performance validation studies, not development studies involving a training set in the context of machine learning.

• Therefore, the concept of a "training set" in this context is not applicable as this is an immunoassay, not an AI/ML algorithm that requires training data.

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

As mentioned above, the concept of a "training set" is not applicable. Therefore, there is no discussion of how ground truth for a training set was established.

Ask a specific question about this device

Elecsys AMH is intended for the in vitro quantitative determination of anti-Müllerian hormone (AMH) in human serum and lithium heparin plasma. The determination of AMH is used for the ovarian reserve in women presenting to fertility clinics. This immunoassay is intended to distinguish between women presenting with AFC (antral follicle count) values > 15 (high ovarian reserve) and women with AFC values ≤ 15 (normal or diminished ovarian reserve). This immunoassay is intended to be used for assessing the ovarian reserve in conjunction with other clinical and laboratory findings before starting any fertility therapy. Elecsys AMH is not intended to be used for monitoring of women undergoing controlled ovarian stimulation in an Assisted Reproduction Technology program.

The electrochemiluminescence immunoassay "ECLIA" is intended for use on cobas e immunoassay analyzers.

The Elecsys AMH immunoassay makes use of a sandwich test principle using a biotinylated monoclonal AMH-specific antibody and a monoclonal AMH-specific antibody labeled with a ruthenium complex. The Elecsys AMH immunoassay is intended for the quantitative determination of anti-Müllerian hormone (AMH) in human serum and lithium heparin plasma. It is intended for use on the cobas e immunoassay analyzers.

Results are determined via a calibration curve which is instrument-specifically generated by a two-point calibration and a master curve provided via the reagent barcode.

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-AMH-Ab~biotin (gray cap), 1 bottle, 8 mL: Biotinylated monoclonal anti-AMH antibody (mouse) 1.0 mg/L, phosphate buffer 50 mmol/L, pH 7.5; preservative.

• Anti-AMH-Ab~Ru(bpy) (black cap), 1 bottle, 8 mL: Monoclonal anti-AMH antibody (mouse) labeled with ruthenium complex 1.0 mg/L, biotin scavenger antibody 1 mg/mL, phosphate buffer 50 mmol/L, pH 7.5; preservative.

The provided text describes the Elecsys AMH device, an immunoassay used for the quantitative determination of anti-Müllerian hormone (AMH) in human serum and lithium heparin plasma. It is intended to assess ovarian reserve in women presenting to fertility clinics by distinguishing between women with high ovarian reserve (AFC > 15) and those with normal or diminished ovarian reserve (AFC ≤ 15). The submission is a Traditional 510(k) Premarket Notification for an updated version of the Elecsys AMH assay designed to mitigate biotin interference.

Here's a breakdown of the requested information based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document lists various performance criteria and states that "All samples met the predetermined acceptance criteria" or "All lots met the predetermined acceptance criterion" for each. Specific numerical acceptance criteria are generally not explicitly stated, but the reported performance values are provided for some.

2. Sample size used for the test set and the data provenance (e.g., country of origin of the data, retrospective or prospective)

The text provides some details on sample sizes for specific tests:

• Precision and Reproducibility: "two replicates per run, 2 runs per day for 21 days" for precision; "three sites with three reagent lots for five days using native human serum pools" for reproducibility.
• LoB: "Five analyte-free samples were measured in two-fold determinations in six runs, distributed over 6 days using native human serum samples and serum pools."
• LoD: "Five native samples with low-analyte concentration were measured in 2-fold determination in 6 runs, distributed over 6 days, on one analyzer."
• LoQ: "Ten low-level human serum samples (HS) were measured in five-fold determinations with one run per day over 5 days."
• Linearity: "one human serum sample with high analyte content... The dilution series contained 15 steps (dilutions)."
• HAMA: "two-fold determination... A serum pool with a high-HAMA concentration and a serum pool without HAMA... diluted in 11 steps."
• Biotin Interference: "Three human serum samples (containing low, mid, and high concentrations of AMH) were tested in duplicate with three reagent lots."
• Endogenous Interfering Substances: "For each potential interferent, three human serum samples (containing low, mid, and high concentrations of AMH) were tested in duplicate with one reagent lot."
• Specificity (Cross-reactants): "a native human serum pool without analyte content... Samples were measured in the presence and absence of the potential cross-reactants."
• Pharmaceutical Compounds: "Sixteen pharmaceutical compounds and four special pharmaceutical compounds were spiked into two human serum sample pools (low-AMH concentration and high-AMH concentration)."
• Sample Type Equivalence: "human samples drawn into Serum and Li Heparin plasma primary tubes."

Data Provenance: The data provenance (e.g., country of origin of the data, retrospective or prospective) is not explicitly stated in the provided text. The samples are described as "native human serum" or "human serum samples," but their origin is not specified.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g., radiologist with 10 years of experience)

This device is an in vitro diagnostic (IVD) immunoassay, not an imaging device that would typically rely on expert human interpretation for ground truth. The "ground truth" here is based on analytical measurements against established laboratory standards and control materials. Therefore, the concept of "experts establishing ground truth for the test set" in the context of radiologists or similar clinical experts is not applicable to this type of device. The ground truth is inherent to the chemical and biological properties being measured and assessed through the analytical methods described (e.g., CLSI guidelines).

4. Adjudication method (e.g., 2+1, 3+1, none) for the test set

Adjudication methods like 2+1 or 3+1 typically refer to the process of resolving discrepancies among multiple expert readers in diagnostic imaging. As this is an in vitro diagnostic immunoassay, such adjudication methods are not applicable. Quality control and analytical performance are verified through statistical methods and adherence to CLSI guidelines.

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

An MRMC comparative effectiveness study is designed for evaluating the impact of AI on human readers, typically in imaging diagnostics. The Elecsys AMH is an automated immunoassay for quantitative measurement of a biomarker. It does not involve human readers interpreting images or otherwise making diagnostic decisions that would be augmented by AI. Therefore, an MRMC study and effect size of human improvement with AI assistance are not applicable to this device.

6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done

Yes, the studies described are essentially standalone performance evaluations of the algorithm (the immunoassay) without human-in-the-loop diagnostic performance being assessed. The device itself (on the cobas e immunoassay analyzers) performs the quantitative determination of AMH. The studies assess the analytical performance of this automated system, such as precision, accuracy, limits of detection, and interference, demonstrating its capability independent of human interpretation of the primary result.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

The ground truth for this type of IVD device is primarily based on analytical standards, reference materials, and established laboratory methods. For example:

• Known concentrations of AMH in spiked samples for linearity, accuracy, and interference studies.
• Analyte-free samples for LoB.
• Low-concentration samples with known, very low AMH levels for LoD and LoQ.
• Comparison to predicate device measurements in method comparison studies as an established "truth" for substantial equivalence.
• Verification against CLSI guidelines which represent standardized and accepted analytical performance criteria.

It's about the chemical and biological accuracy of the measurement, not a clinical ground truth like pathology or patient outcomes, although the results are used in a clinical context.

8. The sample size for the training set

The text does not provide information regarding a specific "training set" for the Elecsys AMH. As an immunoassay, its development would involve optimizing reagents and assay conditions, calibration curve generation, and extensive analytical validation. This is different from machine learning algorithms that typically have distinct training and test sets. The calibration curve is instrument-specifically generated by a two-point calibration and a master curve provided via the reagent barcode. This "master curve" could be considered analogous to some form of "training" for the instrument to interpret signals, but the raw data it was derived from is not detailed here.

9. How the ground truth for the training set was established

Since a "training set" in the context of machine learning is not explicitly mentioned or directly applicable to this immunoassay in the way it's described, the method for establishing its "ground truth" is not provided. Essentially, the assay is developed and optimized to accurately measure AMH concentrations, and its calibration (using known calibrators) serves a similar function to establishing a ground truth reference for its measurements. The master curve is provided with the reagent, implying it's based on extensive characterization with reference materials.

Ask a specific question about this device

The Access AMH assay is a paramagnetic particle chemiluminescent immunoassay for the quantitative determination of anti-Müllerian hormone (AMH) levels in human serum and lithium heparin plasma using the Access Immunoassay Systems as an aid in the assessment of ovarian reserve in women presenting to fertility clinics. This system is intended to distinguish between women presenting with AFC (antral follicle count) values > 15 (high ovarian reserve) and women with AFC values ≤ 15 (normal or diminished ovarian reserve). The Access AMH is intended to be used in conjunction with other clinical and laboratory findings such as antral follicle count, before starting fertility therapy. The Access AMH is not intended to be used for monitoring of women undergoing controlled ovarian stimulation in an Assisted Reproduction Technology program.

The Access AMH assay, Access AMH Calibrators, Access AMH QC, along with the Access 2 Immunoassay System analyzer comprise the Access Immunoassay System for the quantitative determination of anti-Müllerian hormone (AMH) levels in human serum and plasma.

This document describes the Beckman Coulter Access AMH assay, a paramagnetic particle chemiluminescent immunoassay for the quantitative determination of anti-Müllerian hormone (AMH) levels. It is intended as an aid in assessing ovarian reserve in women presenting to fertility clinics to distinguish between women with AFC (antral follicle count) values > 15 (high ovarian reserve) and women with AFC values ≤ 15 (normal or diminished ovarian reserve). The document outlines various analytical and clinical studies to demonstrate the device's performance.

Here's an analysis of the provided information, structured according to your request:

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state "acceptance criteria" for each parameter, but it implies performance goals based on its design and comparisons. I will present the stated design goals/expectations as acceptance criteria and the reported performance.

2. Sample sizes used for the test set and the data provenance

• Clinical Study Test Set:
  • Sample Size: 164 women.
  • Data Provenance: Prospective, multi-center, conducted at 13 geographically diverse sites in the US.
  • Inclusion Criteria: ≥ 21 and

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Elecsys AMH system, consisting of the Elecsys AMH CalSet, PreciControl AMH, and AMH CalCheck 5, is intended for use in the in vitro quantitative determination of anti-Müllerian hormone (AMH) in human serum and lithium heparin plasma. The determination of AMH is used for the assessment of ovarian reserve in women presenting to fertility clinics. This system is intended to distinguish between women presenting with AFC (antral follicle count) values >15 (high ovarian reserve) and women with AFC values ≤15 (normal or diminished ovarian reserve). This system is intended to be used for assessing the ovarian reserve in conjunction with other clinical and laboratory findings before starting any fertility therapy. The Elecsys AMH system is not intended to be used for monitoring of women undergoing controlled ovarian stimulation in an Assisted Reproduction Technology program.

The Elecsys AMH system is intended for use on cobas e 411 analyzer.

AMH CalSet is used for calibrating the quantitative Elecsys AMH assay.

PreciControl AMH is used for quality control of the Elecsys AMH assay.

AMH CalCheck 5 is an assayed control for use in calibration verification and for use in the verification of the assay range established for the Elecsys AMH assay.

The Elecsys AMH reagent working solutions are packed in Rack Pack (kit placed on analyzer), which include:

• Streptavidin-coated microparticles (transparent cap). 1 bottle. 6.5 mL: Streptavidin-. coated microparticles 0.72 mg/mL; preservative.
• . Reagent 1: Anti-AMH-Ab~biotin (gray cap), 1 bottle, 8 mL: Biotinylated monoclonal anti-AMH antibody (mouse) 1.0 mg/L, phosphate buffer 50 mmol/L, pH 7.5: preservative.
• Reagent 2: Anti-AMH-Ab~Ru(bpy)32+ (black cap), 1 bottle, 8 mL: Monoclonal . anti-AMH antibody (mouse) labeled with ruthenium complex 1.0 mg/L, phosphate buffer 50 mmol/L, pH 7.5; preservative.

The AMH CalSet is a lyophilized equine serum matrix with endogenous AMH (Cal 1) and a lyophilized equine serum matrix with added bovine AMH (Cal 2). The CalSet includes:

• AMH Cal 1: approximately 0.04 ng/mL endogenous AMH in an equine serum matrix, . preservative.
• . AMH Cal 2: approximately 8 ng/mL bovine AMH in an equine serum matrix, preservative.

PreciControl AMH is a lyophilized equine serum matrix with added bovine AMH (male fetal bovine serum) in two concentration ranges. The controls are used for monitoring the accuracy and precision of the Elecsys AMH assay. PreciControl AMH includes:

• . PC AMH 1: approximately 1 ng/mL bovine AMH in an equine serum matrix, preservative.
• PC AMH 2: approximately 5 ng/mL bovine AMH in an equine serum matrix, ● preservative.

AMH CalCheck 5 is a (b) (4) (b) (4) (b) (4)

Here's an analysis of the acceptance criteria and study details for the Elecsys AMH system, based on the provided text:

Acceptance Criteria and Reported Device Performance

• Control 1 (1.14 ng/mL): Repeatability 1.4% CV, Intermediate Precision 1.6% CV
• Control 2 (5.61 ng/mL): Repeatability 1.6% CV, Intermediate Precision 1.8% CV
• Human Serum 1 (0.055 ng/mL): Repeatability 1.6% CV, Intermediate Precision 2.3% CV
• Human Serum 2 (1.05 ng/mL): Repeatability 1.3% CV, Intermediate Precision 1.8% CV
• Human Serum 3 (3.56 ng/mL): Repeatability 1.5% CV, Intermediate Precision 1.6% CV
• Human Serum 4 (11.7 ng/mL): Repeatability 1.0% CV, Intermediate Precision 1.2% CV
• Human Serum 5 (19.0 ng/mL): Repeatability 1.4% CV, Intermediate Precision 1.5% CV

Reproducibility (External Sites):

• Total %CV ranged from 3.45% (Serum 3, 3.55 ng/mL) to 5.24% (Control 1, 0.93 ng/mL)
• Repeatability %CV ranged from 1.41% (Serum 3) to 1.89% (Control 2) |
  | Linearity/Reportable Range | Evaluation according to CLSI EP6-A; linear regression with high correlation (r) to support claimed measuring range. | Three sample sets showed slopes close to 1 (1.0091, 1.0054, 1.0063) and correlation coefficients (r) of 0.999. Supports claimed measuring range of 0.03 ng/mL - 23 ng/mL. |
  | Dilution | Demonstrated ability to dilute samples with AMH concentrations above the measuring range, both manually and automatically, with Diluent Universal 2 (1:2 ratio). | Data supports dilution with Diluent Universal 2 (1:2 ratio) for samples > 10 ng/mL, with automatic adjustment by cobas e software or manual multiplication. |
  | Traceability | Adequate traceability plan to minimize the risk of drift; traceability to manufacturer's internal reference standards. Target values for Calibrators. | AMH CalSet traceable to manufacturer's internal reference standards (Master Calibrators). Target values for Calibrator 1 ( 15)** | Prospective clinical study demonstrating clinical performance; adequate clinical performance relative to a well-accepted comparator (AFC). AFC cutoff (15) correlated with AMH cutoff (1.77 ng/mL). PPV, NPV, Sensitivity, Specificity reported with 95% CI. | A multicenter, prospective, non-interventional study (N=856 women) correlated AMH values with AFC. Used an AMH cutoff of 1.77 ng/mL for predicting AFC > 15. Results: PPV 75.2% (71.3-78.8%), NPV 84.3% (80.0-88.1%), Sensitivity 88.3% (85.0-91.2%), Specificity 68.3% (63.6-72.8%). |
  | Matrix Equivalence | Demonstration that Li-Heparin plasma samples perform equivalently to serum samples. | 75 matched serum/Li-Heparin plasma samples tested. Passing/Bablok regression analysis yielded a slope of 1.017, intercept of -0.00186, and correlation coefficient (r) of 0.999, demonstrating equivalence. |
  | Reference Intervals | Reference intervals generated by testing an adequate number of samples from apparently healthy normal individuals in the intended use population. | Age-dependent reference ranges established in 718 healthy females (20-44 years). Detailed percentile values (2.5%, 5%, Median, 95%, 97.5%) with 95% CIs provided for 5-year age groups. |
  | Labeling | Sufficient and satisfies 21 CFR Parts 801 and 809 and special controls, including warning statement about use in conjunction with other clinical and laboratory findings and AFC. | Labeling deemed sufficient. Includes requirements for use in conjunction with other clinical/laboratory findings and AFC before fertility therapy. |

Study Details for Clinical Performance (Prediction of AFC > 15)

1. Test Set Sample Size: N = 856 women
2. Data Provenance:
   • Country of Origin: United States (samples collected at 13 geographically diverse sites).
   • Retrospective or Prospective: Prospective, non-interventional study.
3. Number of Experts and Qualifications for Ground Truth: The document does not specify the number of experts or their qualifications for determining the Antral Follicle Count (AFC) which served as the ground truth. It states that "AFC was determined by transvaginal ultrasonography (TVUS)". It's implied that trained medical professionals (e.g., sonographers, gynecologists, reproductive endocrinologists) performed the TVUS, but specific numbers and experience levels are not provided.
4. Adjudication Method: Not specified. It only states that AFC was determined by TVUS.
5. Multi Reader Multi Case (MRMC) Comparative Effectiveness Study (AI vs. without AI assistance): Not applicable. This device is an immunoassay system, not an AI-assisted diagnostic imaging or interpretation tool for human readers. It provides a quantitative AMH value.
6. Standalone Performance (Algorithm only without human-in-the-loop): Yes, the study evaluates the standalone performance of the Elecsys AMH system. The AMH values determined by the system are correlated directly with the AFC values, operating without a human interpretation loop of the AMH value itself (though the AFC ground truth is human-derived). The reported Sensitivity, Specificity, PPV, and NPV are for the device's ability to predict AFC > 15 at a given cutoff.
7. Type of Ground Truth: "Antral Follicle Count (AFCS)" determined by transvaginal ultrasonography (TVUS).
8. Training Set Sample Size: The document does not explicitly mention a separate "training set" for the AMH assay itself in the context of predicting AFC. The N=856 women study is referred to as the "Clinical Studies" and the results from this study are presented as the device's clinical performance. Immunoassay development typically involves extensive analytical validation (precision, linearity, specificity, etc.) and calibration, which would use dedicated sample sets, but these are not explicitly labeled as "training sets" in the AI sense. The cut-off of 1.77 ng/mL for predicting AFC > 15 would have been established during the development and optimization phase of the assay, likely using a dataset from which this clinical study was drawn or informed.
9. How Ground Truth for Training Set was Established: Not explicitly detailed in the provided text for a specific "training set." For the purpose of establishing the AMH cutoff (1.77 ng/mL) which aligns with AFC > 15, it would have involved analyzing AMH levels and corresponding AFC values from a cohort of patients. The AFC ground truth would have been established via transvaginal ultrasonography, similar to the method used in the main clinical study, guided by a clinical definition of antral follicles (2-10 mm).

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