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The Atellica™ IM Ferritin (Fer) assay is for in vitro diagnostic use in the quantitative determination of ferritin in human serum and plasma (EDTA and lithium heparin) using the Atellica™ IM Analyzer. This assay can be used as an aid in the diagnosis of iron deficiency anemia and iron overload.

The Atellica Ferritin Assay kit includes the following components: Lite Reagent: 5.0 mL/reagent pack. Contains Goat polyclonal anti-ferritin antibody (~0.64 µg/mL) labeled with acridinium ester in HEPES buffer; protein stabilizers; sodium azide (< 0.1%); preservatives Solid Phase Reagent: 22.5 mL/reagent pack. Contains Mouse monoclonal anti-ferritin antibody (~32.2 µg/mL) covalently coupled to paramagnetic particles in sodium barbital buffer; protein stabilizers; sodium azide (< 0.1%); preservatives

Here's a breakdown of the acceptance criteria and study details for the Atellica IM Ferritin Assay, based on the provided document:

Acceptance Criteria and Reported Device Performance

Study Details

1. Sample sizes used for the test set and the data provenance:

   • Precision: 6 serum-based samples, plus calibrators and controls. 80 replicates per sample (20 days, 2 runs/day, duplicate).
   • Linearity/Assay Reportable Range: 11 samples. Tested in triplicates.
   • Detection Limit (LoB, LoD, LoQ):
     • LoB: 6 blank samples, 2 reagent lots, 2 replicates/day over 10 days (System 1) and 9 days (System 2).
     • LoD: 7 low-level human serum samples, 2 reagent lots, 10 days (System 1) and 9 days (System 2).
     • LoQ: 6 low human serum samples (System 1) and 5 low human serum samples (System 2), 2 reagent lots, 8 replicates/day over 5 days.
   • Interference:
     • Endogenous: 2 human serum pools (~20 ng/mL and ~200 ng/mL) spiked with interferent. Tested in replicates of 3.
     • Exogenous: 2 human serum pools (~20 ng/mL and ~200 ng/mL) spiked with interferent. Tested in replicates of 3.
   • Specificity (Cross-reactivity): 4 specimens with different endogenous ferritin levels. Replicates of 3.
   • Dilution Recovery: 3 human serum samples.
   • Spiking Recovery: 5 samples.
   • High-dose hook effect: 11 serial dilution samples from a high-concentration sample.
   • Method Comparison: 126 serum samples (107 included in final calculations).
   • Matrix Comparison: 56 paired sample sets (serum, K2 EDTA plasma, Lithium Heparin plasma).
   • Expected Values/Reference Range: 179 normal males, 275 normal females.

   Data Provenance: The document explicitly states "human serum" and "human serum-based samples". The reference ranges were established using "apparently healthy male and female subjects." The document does not specify the country of origin for the samples and does not explicitly state whether the data was retrospective or prospective, though the nature of laboratory performance studies usually implies prospective collection for the specific tests, but potentially using residual samples for some evaluations.

2. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

   • This device is an in vitro diagnostic assay for quantitative determination of ferritin. The "ground truth" here is the actual concentration of Ferritin in the samples, measured by a reference method or known by spiking/dilution. It is not typically established by human experts in the same way imaging or pathology devices are. The accuracy of the analytical measurements themselves are the ground truth for these types of studies.
   • For the "Expected Values/Reference Range" study, subjects selected had "normal liver function enzyme tests, bilirubin, and serum iron tests," which would imply medical expert evaluation of their health status, though no specific number or qualification of experts is mentioned for this selection.

3. Adjudication method for the test set:

   • Not applicable in the context of an in vitro diagnostic assay for quantitative measurement. The results are numerical values from the assay, and "adjudication" in the sense of expert consensus on a diagnosis is not relevant for establishing the assay's analytical performance.

4. 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 is an in vitro diagnostic assay, not an AI-powered diagnostic imaging or pathology system that assists human readers.

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

   • Yes, this entire submission describes the standalone performance of the Atellica IM Ferritin Assay (an in vitro diagnostic device). The performance characteristics are measured directly from the assay without human interpretation being part of the primary performance evaluation, beyond operating the instrument and interpreting the numerical output.

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

   • The ground truth for the analytical performance studies (precision, linearity, detection limit, interference, recovery) is either:
     • Known concentrations: Achieved through spiking or dilution with known amounts of ferritin.
     • Reference method comparison: For the method comparison study, the predicate device (ADVIA Centaur Ferritin Assay) serves as the comparative "truth" or reference.
     • Traceability to an international standard: The assay is traceable to the WHO 2nd International Standard (WHO 80/578).

7. The sample size for the training set:

   • For in vitro diagnostic assays of this type, a "training set" in the machine learning sense is not typically used for establishing the analytical performance characteristics. The assay is based on chemical reactions and optical detection, not a machine learning algorithm that learns from data.
   • However, if you consider the development process, there would have been internal R&D studies using various samples to optimize reagents and calibration, but these are not disclosed as formal "training sets" in the 510(k) submission.

8. How the ground truth for the training set was established:

   • As explained above, the concept of a "training set" and its associated ground truth in the context of machine learning does not directly apply to the analytical performance studies of this immunoassay. The validity comes from the known chemical properties of the reagents and the calibration against internationally recognized standards.

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The ADVIA Centaur® Insulin (IRI) Master Curve Material (MCM) is for in vitro diagnostic use in the verification of calibration and reportable range of the ADVIA Centaur® Insuin assay.

The ADVIA Centaur® Insulin (IRI) Calibrator is for in vitro diagnostic use in calibrating the ADVIA Centaur® systems Insulin assays.

ADVIA Centaur® Insulin (IRI) Master Curve Material is a set of ten vials of material containing various levels of insulin in buffered saline with casein, potassium thiocyanate (3.89%), sodium azide (<0.1%), and preservatives. Each set contains ten levels (MCM1-10); ready-to-use 1.0 mL per level. MCM1 contains no analyte. The IRI MCMs assigned values are lot-specific of target values: 0.0, 2.5, 4.5, 10.0, 20.0, 39.0, 79.0, 158, 225, and 330 mU/L.

ADVIA Centaur® Insulin (IRI) Calibrator is a set of four vials (two vials of low calibrator and two vials of high calibrator) comprised of buffered saline, with casein, potassium thiocyanate, sodium azide and preservative. Only the high calibrator contains insulin.

The provided text describes modifications to the "ADVIA Centaur® Insulin (IRI) Master Curve Material (MCM)" and "ADVIA Centaur® Insulin (IRI) Calibrator" and outlines the studies conducted to demonstrate their substantial equivalence to predicate devices.

Here's an analysis of the acceptance criteria and the study information, extracting what is available:

1. Table of Acceptance Criteria and Reported Device Performance:

The document doesn't explicitly state quantitative acceptance criteria in a table format with corresponding performance metrics for the modified devices. Instead, it states that "Verification testing was conducted and results show that the modified devices meet pre-determined acceptance criteria." and that a "method comparison study demonstrates that human clinical sample results are equivalent with both calibrators (modified and unmodified)."

However, based on the context, the implicit acceptance criteria and reported performance would be:

2. Sample size used for the test set and the data provenance:

• Test set sample size: Not explicitly stated. The document mentions "human clinical sample results" were used in a method comparison study, but the number of samples is not provided.
• Data provenance: "human clinical sample results" are mentioned, suggesting human patient samples. The country of origin and whether the data is retrospective or prospective are not specified.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

This information is not provided. The study concerns assay calibrators and master curve materials, where "ground truth" would typically refer to the accurately assigned values of the analytes in the calibrators/controls, usually established through highly accurate reference methods or certified reference materials, not expert human interpretation.

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

Not applicable in this context. Adjudication methods like 2+1 or 3+1 are typically used for studies involving human interpretation of images or clinical data, where consensus among experts establishes ground truth. This is a study of in-vitro diagnostic device performance (calibrators and master curve materials), not human interpretation.

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 is not a study involving human readers or AI assistance.

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

The device is an in-vitro diagnostic calibrator/master curve material, not an algorithm. The performance evaluation is inherently "standalone" in the sense that the device itself is being tested for its ability to correctly verify calibration and calibrate assays. The study of "method comparison" compares the results obtained using the modified calibrators/materials versus the unmodified ones on human clinical samples, which is a standalone performance assessment of the materials.

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

The "ground truth" for the calibrator values and master curve material values is inherent in their design and manufacturing process, where specific concentrations of insulin are prepared and assigned. For the "method comparison study," the ground truth is implied to be the measurements obtained using the predicate (unmodified) calibrators/materials, with which the modified devices' performance is compared for equivalence. It's about demonstrating that measurements of "human clinical sample results" using the new materials are equivalent to those obtained using the established predicate materials.

8. The sample size for the training set:

Not applicable. This device is an in-vitro diagnostic calibrator/master curve material, not an AI/ML algorithm that requires a training set.

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

Not applicable, as there is no training set for this type of device.

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The ADVIA Centaur® Follicle Stimulating Hormone (FSH) Master Curve Material is for in vitro diagnostic use in the verification of calibration and reportable range of the ADVIA Centaur FSH assay.
The ADVIA Centaur® Free thyroxine (FT4) Master Curve Material is for in vitro diagnostic use in the verification of calibration and reportable range of the ADVIA Centaur FT4 assay.
The ADVIA Centaur® Thyroxine (T4) Master Curve Material is for in vitro diagnostic use in the verification of calibration and reportable range of the ADVIA Centaur T4 assay.
The ADVIA Centaur® Triiodothyronine (T3) Master Curve Material is for in vitro diagnostic use in the verification of calibration and reportable range of the ADVIA Centaur T3 assay.

ADVIA Centaur® FSH Master Curve Material is an in vitro diagnostic product containing various levels of follicle stimulating hormone spiked in lyophilized equine serum with sodium azide (0.1% after reconstitution) and preservatives. Each set contains eight levels (MCM1–8); with a reconstituted volume of 1.0 mL/vial per level. MCM1contains no analyte. The MCMs assigned values are lot-specific of target values: 0.00, 1.50, 4.50, 12.0, 30.0, 62.5, 130, 225 mIU/mL.
ADVIA Centaur® FT4 Master Curve Material is an in vitro diagnostic product containing various levels of thyroxine in human plasma with sodium azide. Each set contains seven levels; with a reconstituted volume of 1.0 mL/vial per level. MCM1 contains no analyte. The FT4 MCMs assigned values are lot-specific of target values: 0.00, 2.00, 5.00, 10.0, 15.0, 22.0, and 35.0 µg/dL which corresponds to FT4 values of 0.00, 0.42, 0.80, 1.70, 3.0, 5.6, and 13.5 ng/dL.
ADVIA Centaur® T4 Master Curve Material is an in vitro diagnostic product containing various levels of levothyroxine in human plasma with sodium azide and preservatives. Each set contains six levels; with a reconstituted volume of 1.0 mL/vial per level. MCM1 contains no analyte. The T4 MCMs assigned values are lot-specific of target values: 0.00, 2.50, 5.00, 10.0, 15.0. and 35.0 µg/dL.
ADVIA Centaur® T3 Master Curve Material is an in vitro diagnostic product containing various levels of liothyronine in human plasma with sodium azide and preservatives. Each se contains seven levels; with a reconstituted volume of 1.0 mL/vial per level. MCM1 contains no analyte. The T3 MCMs assigned values are lot-specific of target values: 0.00, 0.42, 0.69, 1.11, 1.65, 3.87, and 7.00 ng/mL.

The provided document describes the Siemens Healthcare Diagnostics ADVIA Centaur® Master Curve Materials (MCM) for Follicle Stimulating Hormone (FSH), Free Thyroxine (FT4), Thyroxine (T4), and Triiodothyronine (T3). These devices are quality control materials used for verification of calibration and reportable ranges of their respective ADVIA Centaur assays. The information is presented as a 510(k) Summary, which focuses on demonstrating substantial equivalence to predicate devices, rather than a detailed report of a clinical study for device performance against specific patient outcomes or diagnostic accuracy.

Here's a breakdown of the requested information based on the provided text, with an emphasis on its applicability to in vitro diagnostic quality control materials rather than typical diagnostic imaging AI studies, which often involve human readers and expert consensus.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for these devices are primarily related to stability (shelf-life, open vial, and on-board stability) and value assignment. The reported performance indicates that these criteria were met.

ADVIA Centaur® FSH Master Curve Material

ADVIA Centaur® FT4 Master Curve Material

ADVIA Centaur® T4 Master Curve Material

ADVIA Centaur® T3 Master Curve Material

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

The document describes several non-clinical performance tests, primarily stability studies and value assignment. These are prospective tests conducted by the sponsor (Siemens Healthcare Diagnostics Inc.).

• Stability Studies (Test Set):
  • Real Time/Shelf Life (Unopened): Each MCM (FSH, FT4, T4, T3) was stored unopened at 2-8°C and tested at T=0, 7 months, and 10 or 11 months. Ongoing studies were mentioned at further time points (e.g., 14, 18, 24, 25 months for FSH; 15, 19, 24, 30, 31 months for FT4, T4, T3). The comparison was made against -80°C reference MCMs. No specific number of replicate MCM vials tested at each time point is explicitly stated, other than 'test FSH MCMs were stored'.
  • In-Use Open Vial (Reconstituted): Each MCM (FSH, FT4, T3) was reconstituted, pooled, aliquoted, and stored at 2-8°C. They were tested in 5 replicates per level at T=0, 7, 14, 21, 28, and 29 days (for FSH, T3) or T=0, 7, 14, 21, 28, and 29 days (for FT4). T4 MCM summary did not include open vial stability data details.
  • On-Board Stability: Pooled aliquots of each MCM (FSH, FT4, T3) in sample cups were stored on the ADVIA Centaur system and measured at T=0, 2, 4, and 5 hours. T4 MCM summary did not include on-board stability data details.
• Value Assignment (Test Set):
  • For each new MCM lot, MCM1 (analyte-free) was run in 5 replicates on two separate runs.
  • Other MCM levels (MCM2-8 for FSH, MCM2-7 for FT4/T3, MCM2-6 for T4) were tested using a nested testing run protocol with alternating samples of reference and new MCM, totaling 20 replicates.
  • A performance verification run consisted of 6 replicates of each MCM level.
• Data Provenance: The studies were conducted by Siemens Healthcare Diagnostics Inc., likely in the USA. The data is prospective, generated specifically for this 510(k) submission.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

This type of in vitro diagnostic quality control material does not rely on "expert" interpretation in the same way as, for example, an imaging device. The "ground truth" for these materials is established through a process of:

• Traceability: Standardization to internationally recognized reference materials (e.g., WHO 2nd International Standard for human FSH) or internal standards traceable to official pharmacopeia (USP T4, T3 stock).
• Assigned Values: The values of the MCMs are assigned by the manufacturer based on these traceable standards and validated measurement procedures.
• Internal Protocols: The "sponsor's internal procedural specifications" and "qualified materials and measurement procedures" form the basis for establishing the expected values and ranges.

Therefore, there are no "experts" (like radiologists) establishing ground truth in terms of diagnostic interpretation from patient data. The ground truth is analytical and based on metrological traceability and rigorous laboratory procedures.

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

Adjudication methods like 2+1 or 3+1 (where multiple experts independently assess and then resolve discrepancies) are not applicable here. These methods are used in scenarios involving subjective expert interpretation, often for imaging or clinical diagnosis. For these quality control materials, "ground truth" and performance are determined through quantitative analytical measurements against established reference values and statistical methods to ensure measurements fall within specified limits.

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

MRMC studies are typically performed for diagnostic imaging devices where human readers (e.g., radiologists) interpret cases, sometimes with AI assistance. This document describes in vitro diagnostic quality control materials, not a diagnostic AI device that involves human interpretation of cases. Therefore, no MRMC comparative effectiveness study was performed, and thus no effect size for human reader improvement with AI assistance is mentioned.

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

Yes, the studies described are standalone in the sense that they evaluate the performance of the quality control materials themselves (stability, value assignment) within the ADVIA Centaur assay system, without direct human cognitive input being part of the 'device's' analytical function during testing. The "algorithm" here is the underlying immunoassay technology, and the MCM's performance is tested analytically.

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

The ground truth used for these quality control materials is analytical traceability to recognized international standards (WHO) or national pharmacopeia (USP) for the respective analytes. It also includes reliance on the sponsor's "qualified materials and measurement procedures" and internal procedural specifications for value assignment. This is an objective, quantitative ground truth, not derived from expert consensus, pathology, or outcomes data.

8. The sample size for the training set

The concept of a "training set" is relevant for machine learning algorithms. These devices are chemical/biological reagents designed as quality control materials for immunoassays, not AI algorithms. Therefore, there is no "training set" as understood in machine learning. The manufacturing processes and associated testing are quality control steps, not a machine learning training phase.

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

As there is no "training set" in the machine learning sense for these devices, this question is not applicable. The establishment of ground truth for the performance evaluation (test set, as discussed in point 7) is through analytical traceability to standards.

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The ADVIA Centaur® IgE Master Curve Material is for in vitro diagnostic use in the verification of calibration and reportable range of the ADVIA Centaur Total IgE assay.

ADVIA Centaur® IgE Master Curve Material is an in vitro diagnostic product containing various levels of IgE spiked in lyophilized human plasma with sodium azide (0.1%) and preservatives. Each set contains seven levels (MCM1–7); with a reconstituted volume of 1.0 mL/vial per level. MCM1 contains no analyte. The MCMs assigned values are lot-specific of target values: 0.0, 12.5, 40.0, 270, 1000, 1700, and 3150 IU/mL.

This document describes the ADVIA Centaur® IgE Master Curve Material (MCM), a quality control material used for in vitro diagnostic verification of calibration and reportable range of the ADVIA Centaur Total IgE assay. It is not an AI/ML device, and therefore several of the requested sections (e.g., sample size for test/training sets, number/qualifications of experts, adjudication methods, MRMC studies, standalone algorithm performance, data provenance) are not applicable.

Here's a breakdown of the available information:

1. Table of Acceptance Criteria and Reported Device Performance

The device is a quality control material, not a diagnostic test with metrics like sensitivity or specificity. Its performance is measured by its stability and its ability to be correctly value-assigned.

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

This is not applicable as the device is a quality control material, not a diagnostic test evaluated with a patient test set. The "testing" refers to internal laboratory performance studies to validate the stability and value assignment of the quality control material itself.

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

Not applicable. Ground truth, in this context, relates to the accurate assignment of IgE values to the control materials, which is done through a standardized, traceable process rather than expert consensus on patient data.

4. Adjudication Method (e.g. 2+1, 3+1, none) for the Test Set

Not applicable.

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 is a quality control material, not an AI/ML diagnostic device for human reader assistance.

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

Not applicable. This is not an algorithm.

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

The "ground truth" for the ADVIA Centaur® IgE Master Curve Material is established through traceability to a recognized international standard: the World Health Organization (WHO) 75/502 reference material for IgE. This means the values assigned to the quality control material are linked to a globally accepted standard, ensuring consistency and accuracy.

8. The sample size for the training set

Not applicable. There is no "training set" as this is not an AI/ML model.

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

Not applicable.

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The ADVIA Centaur® Prolactin (PRL) Master Curve Material is for in vitro diagnostic use in the verification of calibration and reportable range of the ADVIA Centaur Prolactin assay.
The ADVIA Centaur® Cortisol (COR) Master Curve Material is for in vitro diagnostic use in the verification of calibration and reportable range of the ADVIA Centaur Cortisol assay.

ADVIA Centaur® Prolactin Master Curve Material is an in vitro diagnostic product containing various levels of prolactin spiked in lyophilized equine serum with sodium azide (0.1%) and preservatives including amphotericin B. Each set contains ten levels (MCM1–10); with a reconstituted volume of 1.0 mL per level. MCM1contains no analyte. The MCMs assigned values are lot-specific of target values: 0.00, 2.11, 4.61, 9.21, 26.0, 51.1, 82.9, 113, 161, and 218 ng/mL.
ADVIA Centaur® Cortisol Master Curve Materials is an in vitro diagnostic product containing various levels of cortisol in lyophilized human plasma with sodium azide. Each set contains seven lyophilized levels (MCM1-7); with a reconstituted volume of 1.0 mL each. MCM1 contains no analyte. The COR MCMs assigned values are lot-specific of target values: 0.00, 1.00, 2.00, 6.00, 12.0, 30.0, and 80.0 µg/dL.

The provided text describes the acceptance criteria and supporting studies for two Master Curve Materials (MCMs): ADVIA Centaur Prolactin (PRL) MCM and ADVIA Centaur Cortisol (COR) MCM. These materials are intended for in vitro diagnostic use in verifying the calibration and reportable range of their respective assays.

Here's a breakdown of the requested information:

ADVIA Centaur Prolactin (PRL) Master Curve Material

1. Table of acceptance criteria and reported device performance:

2. Sample size used for the test set and the data provenance:

• Real Time/Shelf Life (unopened): Test PRL MCMs stored unopened. Tested at T=0, 12 months, and 30 months. The sample size for each time point is not explicitly stated in terms of number of individual units, but it's implied that multiple samples were tested to establish dose recovery.
• In-Use Open Vial (reconstituted): Reconstituted PRL MCMs, each level pooled, aliquotted, and stored at 2-8°C. Tested in 5 replicates per level at T=0, 7, 14, 21, 28, and 29 days. (10 levels * 5 replicates * 6 time points = 300 measurements total, minimum).
• On-Board Stability: Pooled aliquots of test PRL MCMs in sample cups. Measured at T=0, 2, 4, and 5 hours. Sample size not explicitly stated for number of individual units, but likely multiple measurements per time point.
• Value Assignment Test Set: For a new PRL MCM lot, MCM1 is run in 5 replicates on two separate runs. MCM2-MCM10 were tested on 20 replicates in total (one run and four sample cups run in 5 replicates). Performance verification run used 6 replicates of each MCM level.
• Data Provenance: The studies were conducted by Siemens Healthcare Diagnostics, Inc. The data is retrospective for the purpose of demonstrating the device's performance for this 510(k) submission. Country of origin not explicitly stated, but the manufacturer is based in the USA.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
Not applicable. These are in vitro diagnostic materials used for calibration verification, not for making clinical diagnoses based on subjective expert review. The "ground truth" for the MCMs is established by their formulation (analyte-free for MCM1, spiked levels for others) and traceability to recognized standards (WHO 3rd IRP for Prolactin 84/500) and internal reference materials.

4. Adjudication method for the test set:
Not applicable for this type of device and study. Performance is assessed against quantitative, pre-defined acceptance criteria, not through expert adjudication of results.

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 is an in vitro diagnostic (IVD) material, not an AI-powered diagnostic device, and therefore no MRMC study was performed.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
Not applicable. This is an IVD material, not an algorithm. Its performance is evaluated intrinsically through stability and value assignment studies on an automated analyzer (ADVIA Centaur system).

7. The type of ground truth used:
The ground truth for the PRL MCMs is primarily based on:

• Traceability to International Standards: Specifically, the World Health Organization (WHO) 3rd International Reference Preparation (IRP) for human Prolactin 84/500.
• Analytical Procedures: MCMs are manufactured using qualified materials and measurement procedures, and for MCMs 2-10, known concentrations of prolactin are spiked into a matrix. MCM1 is analyte-free basepool.
• Value Assignment: Reference calibrators are prepared using Prolactin stock traceable to the WHO standard. The MCMs are value assigned against these reference calibrators using a nested testing run protocol to account for system and run variation.

8. The sample size for the training set:
Not applicable. This is an IVD material, not an AI model that requires a training set.

9. How the ground truth for the training set was established:
Not applicable.

ADVIA Centaur Cortisol (COR) Master Curve Material

1. Table of acceptance criteria and reported device performance:

2. Sample size used for the test set and the data provenance:

• Real Time/Shelf Life (unopened): Test COR MCMs stored unopened. Tested at T=0, 12 months, 18 months, and 23 months. The sample size for each time point is not explicitly stated in terms of number of individual units, but it's implied that multiple samples were tested to establish dose recovery.
• In-Use Open Vial (reconstituted): Reconstituted COR MCMs, each level pooled, aliquotted, and stored at 2-8°C. Tested in 5 replicates per level at T=0, 2, 4, 7, 11, 14, and 15 days. (7 levels * 5 replicates * 7 time points = 245 measurements total, minimum).
• On-Board Stability: Pooled aliquots of test COR MCMs in sample cups. Measured at T=0, 2, 4, and 5 hours. Sample size not explicitly stated for number of individual units, but likely multiple measurements per time point.
• Value Assignment Test Set: For a new COR MCM lot, MCM1 is run in 5 replicates on two separate runs. MCM2-MCM7 were tested on 20 replicates in total (one run and four sample cups run in 5 replicates). Performance verification run used 6 replicates of each MCM level.
• Data Provenance: The studies were conducted by Siemens Healthcare Diagnostics, Inc. The data is retrospective for the purpose of demonstrating the device's performance for this 510(k) submission. Country of origin not explicitly stated, but the manufacturer is based in the USA.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
Not applicable. These are in vitro diagnostic materials used for calibration verification, not for making clinical diagnoses based on subjective expert review. The "ground truth" for the MCMs is established by their formulation (analyte-free for MCM1, spiked levels for others) and traceability to recognized standards (GCMS) and internal reference materials.

4. Adjudication method for the test set:
Not applicable for this type of device and study. Performance is assessed against quantitative, pre-defined acceptance criteria, not through expert adjudication of results.

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 is an in vitro diagnostic (IVD) material, not an AI-powered diagnostic device, and therefore no MRMC study was performed.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
Not applicable. This is an IVD material, not an algorithm. Its performance is evaluated intrinsically through stability and value assignment studies on an automated analyzer (ADVIA Centaur system).

7. The type of ground truth used:
The ground truth for the COR MCMs is primarily based on:

• Traceability to Reference Methods: Specifically, gas chromatography-mass spectroscopy (GCMS) through analytically prepared internal standards.
• Analytical Procedures: MCMs are manufactured using qualified materials and measurement procedures, and for MCMs 2-7, known concentrations of cortisol are spiked into a matrix. MCM1 is analyte-free basepool.
• Value Assignment: Reference calibrators are prepared using cortisol stock traceable to GCMS. The MCMs are value assigned against these reference calibrators using a nested testing run protocol to account for system and run variation.

8. The sample size for the training set:
Not applicable. This is an IVD material, not an AI model that requires a training set.

9. How the ground truth for the training set was established:
Not applicable.

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The ADVIA Centaur® C-peptide (CpS) Master Curve Material is for in vitro diagnostic use in the verification of calibration and reportable range of the ADVIA Centaur C-peptide assay.

The ADVIA Centaur® Insulin (IRI) Master Curve Material is for in vitro diagnostic use in the verification of calibration and reportable range of the ADVIA Centaur Insulin assay.

ADVIA Centaur® C-peptide Master Curve Material is an in vitro diagnostic product containing various levels of C-peptide spiked in citric acid buffer with casein and preservatives. Each set contains ten levels (MCM1–10); ready-to-use 1.0 mL per level. MCM1 contains no analyte. The MCMs assigned values are lot-specific of target values 0.0 0.14, 0.25, 0.55, 1.05, 2.05, 4.00, 8.00, 16.0, 32.5 ng/mL.

ADVIA Centaur® Insulin Master Curve Materials is an in vitro diagnostic product containing various levels of insulin in buffered saline with casein, potassium thiocyanate (3.89%), sodium azide (<0.1%), and preservatives. Each set contains ten levels (MCM1-10); ready-to-use 1.0 mL per level. MCM1 contains no analyte. The IRI MCMs assigned values are lotspecific of target values: 0.0, 2.5, 4.5, 10.0, 20.0, 39.0, 79.0, 158, 225, and 300 mU/L.

The provided document describes the Siemens ADVIA Centaur C-peptide (CpS) Master Curve Material (MCM) and ADVIA Centaur Insulin (IRI) Master Curve Material (MCM). These devices are described as in vitro diagnostic products for the verification of calibration and reportable range of their respective assays. The document focuses on establishing substantial equivalence to predicate devices and describes relevant performance characteristics, primarily stability and value assignment.

Here's an analysis of the acceptance criteria and supporting studies based on the provided text:

Device Type: In vitro diagnostic Master Curve Material (MCM) - these are control materials used to verify the calibration and reportable range of an assay, not a diagnostic device that produces patient-specific results. Therefore, the questions related to clinical performance (e.g., diagnostic accuracy metrics like sensitivity, specificity, PPV, NPV), multi-reader multi-case studies, human reader improvement with AI, and specific ground truth types like pathology or outcomes data are not applicable in the context of this device and the provided documentation. The "performance" here refers to the stability and accurate value assignment of the control material itself.

1. Acceptance Criteria and Reported Device Performance

For ADVIA Centaur C-peptide (CpS) Master Curve Material (MCM):

For ADVIA Centaur Insulin (IRI) Master Curve Material (MCM):

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

The document does not explicitly define a "test set" in the context of clinical or diagnostic performance, as the device is a control material. Instead, testing involves stability studies and value assignment.

• Sample Size for Stability Studies:
  • C-peptide MCM: For each MCM level, 3 replicates were run at each time point (T=0, 3, 9, 12, 13 months for real-time; T=0, 2, 4, 5 hours for on-board).
  • Insulin MCM: For each MCM level, 3 replicates were run at each time point (T=0, 3, 7, 9, 12 months for real-time; T=0, 2, 4, 6, 8, 9 hours for on-board).
• Sample Size for Value Assignment:
  • C-peptide MCM: MCM1-10 are run in 3 replicates across two ADVIA Centaur instruments using two reagent kit lots, run twice on each instrument. This totals 24 replicates per MCM level (3 replicates * 2 instruments * 2 reagent lots * 2 runs). Additionally, MCM9 is run diluted 1:2 using MCM1. Three levels of commercially available controls and two levels of in-house controls are used.
  • Insulin MCM: MCM1-10 are run in replicates of three across two ADVIA Centaur instruments using two reagent kit lots, run twice on each instrument. This totals 24 replicates per MCM level. MCM10 is also run diluted 1:2 using MCM1. Two lots of commercially available controls (3 levels each) are used.
• Data Provenance: The document does not specify the country of origin for the data or whether it is retrospective or prospective. Given the nature of stability and value assignment studies for an in-house manufactured control material, it is highly likely that these studies were conducted prospectively by the manufacturer (Siemens Healthcare Diagnostics Inc., based in Tarrytown, NY, USA).

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

This information is not applicable as the devices are control materials for assay calibration verification. The "ground truth" here is the assigned value of the control material, which is established through a standardized value assignment process rather than expert interpretation of clinical data.

4. Adjudication Method for the Test Set

This is not applicable as there is no "test set" in the sense of a collection of cases requiring interpretation or adjudication. The studies involve objective measurements of analyte concentration in control materials.

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 device is a control material, not an AI-powered diagnostic system or an imaging device designed for human reader interpretation. No human-in-the-loop performance is being evaluated.

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

This is not applicable. The device is a physical control material used in conjunction with an immunoassay analyzer. It does not involve an algorithm working in "standalone" mode.

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

For both the C-peptide and Insulin MCMs, the "ground truth" (or reference value) is established through traceability to World Health Organization (WHO) international reference materials.

• C-peptide MCM: Traceable to WHO IS 84/510 reference material.
• Insulin MCM: Traceable to WHO 1st IRP 66/304 reference material.

The assigned values for master curve standards, calibrators, and MCMs are directly traceable to these international standards.

8. The Sample Size for the Training Set

This is not applicable. As a control material, there is no "training set" in the machine learning sense. The devices are manufactured according to specifications and their performance (stability and assigned values) is evaluated. The "value assignment" process could be considered analogous to establishing the expected values for the controls, but it's not a training phase for an algorithm.

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

This is not applicable for the reasons outlined in point 8. The ground truth for the value assignment of the MCMs themselves is established through traceability to WHO international reference materials, as described in point 7.

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The ADVIA Centaur® Vitamin B12 (VB12) Master Curve Material is for in the verification of calibration and reportable range of the ADVIA Centaur VB12 assay.

The ADVIA Centaur® Total hCG (ThCG) Master Curve Material is for in the verification of calibration and reportable range of the ADVIA Centaur ThCG assay.

The ADVIA Centaur® Testosterone (TSTO) Master Curve Material is for in the verification of calibration and reportable range of the ADVIA Centaur Testosterone assay.

ADVIA Centaur® Vitamin B12 Master Curve Material is an in vitro diagnostic product containing various levels of vitamin B12 in buffered human serum albumin with sodium azide (0.2%) and preservatives. Each set contains six levels (MCM1-6); with a fill volume of 1.0 mL per level. VB12 MCMs are ready-to-use liquid products. MCM1 contains no analyte. The MCMs assigned values are lot-specific of target values: 0.00, 100, 250, 500, 1000, and 2200 pg/mL.

ADVIA Centaur® ThCG Master Curve Materials is an in vitro diagnostic product containing various levels of ThCG in lyophilized equine serum with preservatives including amphotericin B. Each set contains ten lyophilized levels (MCM1-10); with a reconstituted volume of 1.0 mL each. MCM1 contains no analyte. The ThCG MCMs assigned values are lot specific of target values: 0.0, 5.00, 10.0, 25.0, 50.0, 100, 250, 500, 750, and 1400 mIU/mL.

ADVIA Centaur® TSTO Master Curve Materials is an in vitro diagnostic product containing various levels of testosterone spiked in lyophilized human plasma with sodium azide and preservatives. Each set contains seven lyophilized levels (MCM1-7); with a reconstituted volume of 1.0 mL each. MCMI contains no analyte. The TSTO MCMs assigned values are lot specific of target values 0.00, 50.0, 100, 500, 750, 1000, and 1600 ng/dL.

Acceptance Criteria and Study for ADVIA Centaur® VB12 Master Curve Material

The document describes three separate Master Curve Materials (MCMs): VB12, ThCG, and TSTO. This analysis focuses specifically on the ADVIA Centaur® Vitamin B12 (VB12) Master Curve Material.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for the ADVIA Centaur® VB12 MCMs primarily relate to their stability. The study demonstrated that the device met these criteria.

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

• Test Set Description: The test set for stability studies consisted of "Test VB12 MCMs" which were individual levels of the Master Curve Material (MCM1-6).
• Sample Size:
  • Real Time/Shelf Life: Not explicitly stated as a number of individual samples, but likely involved multiple aliquots of each MCM level (MCM1-6) stored and tested at T=0, 6 months, 12 months, and 15 months. The exact number of replicates per time point is not specified but implied to be sufficient for a robust assessment.
  • On-Board Stability: Not explicitly stated as a number of individual samples, but "Pooled aliquots of test VB12 MCMs in sample cups" were used and measured at T=0, 2, 4, and 5 hours. The exact number of replicates per time point is not specified.
• Data Provenance: Not explicitly stated in the provided text (e.g., country of origin). The studies appear to be prospective as they involved controlled storage and testing over defined time intervals to assess stability.

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

This device is a Quality Control (QC) material, not a diagnostic device requiring human interpretation of clinical images or data. Therefore, the concept of "experts" establishing ground truth in the traditional sense (e.g., radiologists) does not apply. The "ground truth" for the performance of this QC material is established by analytical testing against defined reference materials and specifications.

4. Adjudication Method for the Test Set

The concept of an adjudication method (like 2+1, 3+1) is not applicable here. The performance is assessed by comparing dose recovery results to pre-defined numerical acceptance criteria for stability.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, an MRMC comparative effectiveness study was not done. This type of study is relevant for diagnostic devices where human readers interpret clinical cases, often with and without AI assistance. This device is a quality control material for an in-vitro diagnostic assay.

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

The performance study (stability) is inherently "standalone" in the sense that it evaluates the material's integrity over time without human-in-the-loop performance, as it's a quality control product. The assay itself for which this MCM is used is automated.

7. The Type of Ground Truth Used

The ground truth for the VB12 MCM is established through:

• Traceability to a recognized standard: The assigned reference calibrators are prepared using USP (United States Pharmacopeia) VB12 stock and are traceable to USP internal material.
• Defined analytical specifications: The dose recovery acceptance criteria (e.g., ≤ 45 pg/mL, % recovery ranges) serve as the "ground truth" for determining if the material remains stable and performs as expected.
• Manufacturing procedures: MCMs are manufactured using "qualified materials and measurement procedures."

8. The Sample Size for the Training Set

This device is a physical Master Curve Material (MCM), not a machine learning model that requires a "training set" in the conventional sense. The "value assignment" process could be considered analogous to establishing its baseline characteristics.

For value assignment of a new VB12 MCM lot:

• MCM1: Run in 5 replicates on two separate runs using one reagent kit lot.
• MCM2-MCM6: Tested on 20 replicates in total, comprised of one run and four sample cups run in 5 replicates on one system and one reagent kit lot.

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

As noted above, there isn't a "training set" in the machine learning context. However, the process by which the "ground truth" or assigned values for the MCMs are established is described as follows:

• Reference Calibrators: The ADVIA Centaur VB12 MCMs are value assigned using assigned reference calibrators. These calibrators are prepared using USP (United States Pharmacopeia) VB12 stock and are traceable to USP internal material.
• Value Assignment Process:
  • MCM1's target is 0.0 dose, and its quality control specifications ensure it measures at or below the assay sensitivity limit.
  • A nested testing run protocol is used for MCM2-MCM6, involving running alternating samples of the reference and new MCM level in the same run to remove system and run variation.
  • Resulting MCM dose values are generated using a two-point calibration.
  • The new MCM dose is calculated based on the relationship between the observed reference MCM dose and its assigned value.
• Performance Verification: A performance verification run with 6 replicates of each MCM level (using one instrument, one reagent kit lot, and Bio-Rad controls) is conducted. The mean MCM doses of the new lot must fall within customer range specifications.

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The ADVIA Centaur® TnI-Ultra® Master Curve Material is for in vitro diagnostic use in the verification of calibration and reportable range of the ADVIA Centaur TnI-Ultra assay.
The ADVIA Centaur® Digoxin Master Curve Material is for in vitro diagnostic use in the verification of calibration and reportable range of the ADVIA Centaur Digoxin assay.

ADVIA Centaur® TnI-Ultra® Master Curve Material is an in vitro diagnostic product containing various levels of bovine cardiac troponin I in a goat serum matrix with preservatives. Each set contains five lyophilized levels (MCM1-5); with a reconstituted volume of 1.0 ml each. MCM1 contains no analyte. The Tnl-Ultra MCMs assigned values are lot-specific of target values 0.00, 1.00, 3.50, 14.0 and 40.0 ng/mL.
ADVIA Centaur® Digoxin Master Curve Materials is an in vitro diagnostic product containing various levels of digoxin in defibrinated human plasma with sodium azide (0.1% after reconstitution) and preservatives. Each set contains six lyophilized levels (MCM1-6); with a reconstituted volume of 1.0 mL each. MCM1 contains no analyte. The Digoxin MCMs assigned values are lot specific of target values 0.0, 0.50, 1.00, 2.00, 3.00, 5.50 ng/mL.

The provided text describes two separate devices: ADVIA Centaur® TnI-Ultra® Master Curve Material (MCM) and ADVIA Centaur® Digoxin Master Curve Material (MCM). Both are quality control materials. I will detail the acceptance criteria and study information for each device independently.

ADVIA Centaur® TnI-Ultra® Master Curve Material (MCM)

1. Table of Acceptance Criteria and Reported Device Performance

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

• Real Time/Shelf Life (Unopened): Samples were tested at T=0, 3 months, and 10 months. The number of replicates per time point is not explicitly stated, but the study "supports a shelf-life claim of 9 months." Data provenance is assumed to be internal laboratory data, prospective (as it's a real-time study). No country of origin is specified beyond general Siemens Healthcare Diagnostics Inc. information.
• In Use (Open Vial) @ 2-8°C (Reconstituted): Each level tested in 5 replicates per level at T=0, 2, 4, 6, 8, 9, 24, and 25 hours.
• In Use (Open Vial) @ -20°C (Reconstituted): Each level tested in 5 replicates per level at Day=0, 14, 28, 35, 45, 60, and 63 days.
• On-Board Stability: Each level tested at T=0, 2, 4, and 5 hours. The number of replicates per level is not explicitly stated.
• Value Assignment:
  • MCM1: 5 replicates on two separate runs.
  • MCM2-MCM5: 20 replicates in total (one run, four sample cups run in 5 replicates).
  • Performance Verification Run: 6 replicates of each MCM level.

Data provenance for all these studies is internal Siemens laboratory data, prospective in nature as they are performance characteristic studies for the device.

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

Not applicable. This device is a quality control material intended for verification of calibration and reportable range for an assay. Its performance is assessed against defined analytical criteria, not against clinical expert interpretations of patient data. The "ground truth" here is the result from reference calibrators and defined analytical specifications, not expert consensus on patient conditions.

4. Adjudication Method for the Test Set

Not applicable, as no expert adjudication of clinical cases is involved. Performance is based on predefined analytical acceptance criteria compared to measured values.

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

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This type of study is not relevant for a quality control material.

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

Yes, the performance studies described are essentially "standalone" in that they evaluate the analytical performance of the Master Curve Material itself, independent of human interpretation of clinical outcomes. The device is a reagent, and its performance is measured directly by an automated system (ADVIA Centaur system).

7. The Type of Ground Truth Used

The ground truth used for performance evaluation is based on:

• Pre-defined analytical specifications and acceptance criteria for dose recovery and stability.
• Comparison against T=0 dose recovery results for stability studies.
• Comparison against freshly reconstituted -80°C stored MCM average dose results for "in use" stability.
• Traceability to NIST SRM 2921 and highly purified internal materials for value assignment.
• The "target for MCM1 is assigned a 0.0 dose" without a statistical method, and its range is less than 3 times the limit of sensitivity.

8. The Sample Size for the Training Set

Not applicable. This device is a quality control material and does not involve an "algorithm" in the sense of machine learning that requires a training set. The "training" for such a product would be its manufacturing and validation process to meet specifications.

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

Not applicable, as there is no training set for this type of device.

ADVIA Centaur® Digoxin Master Curve Material (MCM)

1. Table of Acceptance Criteria and Reported Device Performance

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

• Real Time/Shelf Life (Unopened): Samples were tested at T=0, 12 months, 18 months, and 33 months. The number of replicates per time point is not explicitly stated. Data provenance is assumed to be internal laboratory data, prospective.
• In Use (Open Vial) @ 2-8°C (Reconstituted): Each level tested in 5 replicates per level at T=0, 7, 14, 21, 28, and 29 days.
• On-Board Stability: Each level tested at T=0, 2, 4, and 5 hours. The number of replicates per level is not explicitly stated.
• Value Assignment:
  • MCM1: 5 replicates on two separate runs.
  • MCM2-MCM6: 20 replicates in total (one run, four sample cups run in 5 replicates).
  • Performance Verification Run: 6 replicates of each MCM level.

Data provenance for all these studies is internal Siemens laboratory data, prospective in nature.

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

Not applicable. This device is a quality control material, and its performance is assessed against defined analytical criteria, not against clinical expert interpretations of patient data. The "ground truth" here is the result from reference calibrators and defined analytical specifications.

4. Adjudication Method for the Test Set

Not applicable, as no expert adjudication of clinical cases is involved. Performance is based on predefined analytical acceptance criteria compared to measured values.

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

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This type of study is not relevant for a quality control material.

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

Yes, the performance studies described are essentially "standalone" in that they evaluate the analytical performance of the Master Curve Material itself, independent of human interpretation of clinical outcomes. The device is a reagent, and its performance is measured directly by an automated system (ADVIA Centaur system).

7. The Type of Ground Truth Used

The ground truth used for performance evaluation is based on:

• Pre-defined analytical specifications and acceptance criteria for dose recovery and stability.
• Comparison against T=0 dose recovery results for stability studies.
• Comparison against -80°C stored MCM average dose results for "in use" stability.
• Traceability to USP (United States Pharmacopeia) Digoxin stock and USP internal material for value assignment.
• The "target for MCM1 is assigned a 0.0 dose" without a statistical method, and its range is less than 3 times the limit of sensitivity.

8. The Sample Size for the Training Set

Not applicable. This device is a quality control material and does not involve an "algorithm" in the sense of machine learning that requires a training set.

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

Not applicable, as there is no training set for this type of device.

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The ADVIA® Chemistry Myoglobin assay is for in vitro diagnostic use in the quantitative measurement of myoglobin in human serum or plasma on the ADVIA® Chemistry systems. Measurement of myoglobin aids in the rapid diagnosis of heart or renal disease.

The ADVIA Chemistry Myoglobin calibrator is for in vitro diagnostic use in the calibration of ADVIA® Chemistry system for Myoglobin assay.

The Myoglobin reagents are ready-to-use liquid reagents packaged for use on the automated ADVIA 1650 Chemistry system. They are supplied as a 100 tests/wedge, 2 wedges/kit. ADVIA Chemistry Myoglobin calibrator is a single analyte, human serum based product containing myoglobin derived from human heart source. The kit consists of 1 vial each of 4 calibrator levels which are lyophilized. The target concentrations of these calibrators are 50, 100, 200, and 720 ng/mL. The volume per vial (after reconstitution with deionized water) is 1.0 mL. Deionized water is recommended to be used as a zero calibrator.

Here's a breakdown of the acceptance criteria and study information based on the provided 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance:

The document describes several performance characteristics and the results obtained for the ADVIA® 1650 Chemistry Myoglobin Assay. Since this is a submission for substantial equivalence to a predicate device, the "acceptance criteria" are implicitly the performance levels of the predicate device or generally accepted clinical laboratory standards as guided by CLSI documents. The reported performance of the new device is compared to these.

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

• Precision:
  • Serum Pool 1: 40 replicates (assayed over 5 days)
  • Control 1, Control 2, Control 3: 80 replicates each (assayed over 20 days)
  • Serum Pool 2, Serum Pool 3, Serum Pool 4: 80 replicates each (assayed over 20 days)
  • Data Provenance: Not explicitly stated, but typically these types of studies are prospective lab studies conducted internally or by contract research organizations (CROs) for the manufacturer. The document doesn't mention country of origin or if samples were from specific patient populations, implying a general laboratory setting for assay validation.
• Linearity/Assay Reportable Range: Nine intermediate levels were created from low and high serum pools, plus two additional low levels. The total number of samples is not explicitly given but would be at least 11.
  • Data Provenance: Not explicitly stated, but likely laboratory-prepared serum pools.
• Limit of Blank, Limit of Detection, Limit of Quantitation:
  • LoB: 160 replicates of "zero" serum pool.
  • LoD/LoQ: Several serum pools with myoglobin concentration up to 4 x LOD level. (Exact number not specified for these pools).
  • Data Provenance: Not explicitly stated, likely laboratory-prepared or confirmed serum pools.
• Method Comparison (Serum): 71 serum samples. One sample was removed.
  • Data Provenance: Not explicitly stated, but typically these are human patient samples. The country of origin is not specified, and it's not stated whether they were retrospective or prospectively collected for the study, but typically for method comparison, they would be prospectively selected from a relevant patient population.
• Matrix Comparison (Plasma): 64 plasma samples.
  • Data Provenance: Similar to serum comparison, likely human patient samples. Country/retrospective/prospective not specified.
• Analytical Specificity (Interference): Test samples at specific myoglobin concentrations (50, 100, 400 ng/mL) were spiked with various interferents. The number of samples for each interferent type and concentration is not explicitly given but implies multiple measurements.
  • Data Provenance: Not explicitly stated, likely laboratory-prepared spiked samples using various concentrations of human physiological interferents.

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

• This device is a quantitative immunological test system for measuring myoglobin. The "ground truth" for the test set is established by the predicate device (ADVIA Centaur Myoglobin Assay), which is itself a legally marketed device. There is no explicit mention of human experts establishing a "ground truth" for individual patient samples in the way it might be done for an imaging device (e.g., radiologists). The performance is assessed against an established analytical reference method (the predicate).

4. Adjudication Method:

• Not applicable in the typical sense for a diagnostic imaging or clinical decision support device where human experts adjudicate. For analytical assays, the "adjudication" is inherent in the analytical method comparison and statistical analysis against the predicate device.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:

• No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study is relevant for diagnostic imaging or interpretation systems where human readers are making diagnoses. This device is an in vitro diagnostic (IVD) assay that provides a quantitative measurement, not an interpretation by a human reader.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study:

• Yes, the entire performance evaluation described (precision, linearity, LoB/LoD/LoQ, method comparison, interference) is a standalone (algorithm only) performance study. The ADVIA® 1650 Chemistry Myoglobin assay is an automated system that performs the measurement without direct human interaction in the analytical process after sample loading.

7. Type of Ground Truth Used:

• The primary "ground truth" used for evaluating the new device's performance is the results obtained from the predicate device (ADVIA Centaur Myoglobin Assay) and, for basic analytical characteristics like LoB/LoD/LoQ, established analytical methodologies and industry standards (CLSI guidelines). For interference, the ground truth is the absence of interfering substances, and deviations are measured against that.

8. Sample Size for the Training Set:

• This 510(k) summary is for an in vitro diagnostic (IVD) assay, not a machine learning or AI model in the typical sense that requires explicit "training data" in the submission. The methods (e.g., latex-particle-enhanced immunoturbidimetric) are based on established chemical and immunological principles. Therefore, there is no specific "training set" sample size mentioned or generally applicable in the context of such an IVD submission. The assay's parameters would have been optimized during its development phase, but these aren't typically documented as a "training set" in a 510(k).

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

• As there is no "training set" specified in the context of an AI/ML model for this IVD assay, this question is not applicable. The "ground truth" for developing and optimizing such an assay would be based on fundamental chemical/immunological principles and experiments to ensure accurate and precise measurement of myoglobin concentrations.

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The B12 Flex® reagent cartridge is an in vitro diagnostic test for the quantitative measurement of Vitamin B12 in human serum and plasma on the Dimension Vista® system. Measurements obtained by this device are used in the diagnosis and treatment of gastrointestinal malabsorption.

The FOL Flex® reagent cartridge is an in vitro diagnostic test for the quantitative measurement of folate in human serum and plasma on the Dimension Vista® system. Measurements obtained by this device are used in the diagnosis and treatment of megaloblastic anemia.

The LOCI 4 Calibrator is an in vitro diagnostic product for the calibration of Ferritin (FERR), Vitamin B12 (B12), and Folate (FOL) methods on the Dimension Vista® system.

B12: The Dimension Vista® Vitamin B12 method is a homogeneous, competitive chemiluminescent immunoassay based on LOCTM technology. LOCT™ reagents include two synthetic bead reagents and biotinylated intrinsic factor (IF). The first bead reagent (Chemibeads) is coated with a B12 derivative and contains a chemiluminescent dye. The second bead reagent (Sensibeads) is coated with streptavidin and contains photosensitive dye. The patient sample is pretreated with NaOH to release the serum B12 from its carrier proteins. Potassium cyanide (KCN) is added to convert all the forms of B12 into a single, cyanocobalamin form, and dicyanocobinamide is added to keep the B12 from rebinding with the carrier proteins. After the sample pretreatment, the biotinylated IF and Chemibead reagents are added sequentially to the reaction vessel. Vitamin B12 from the sample competes with the B12-Chemibead for a limited amount of biotinylated IF. Sensibeads are then added and bind to the biotin to form bead pair immunocomplexes. Illumination of the complex at 680 nm generates singlet oxygen from the Sensibeads which diffuses to the Chemibeads triggering a chemiluminescent reaction. The resulting signal is measured at 612 nm and is an inverse function of the concentration of vitamin B12 in the sample.

FOL: The Dimension Vista® Folate method is a homogenous, competitive chemiluminescent immunoassay based on LOCT™ technology. LOCT™ reagents include two synthetic bead reagents and labeled folate binding protein (FBP). The first bead reagent (Chemibeads) is coated with a folic acid derivative and contains a chemiluminescent dye. The second bead reagent (Sensibeads) is coated with streptavidin and contains photosensitive dye. Before the immunological portion of the reaction is initiated, the patient sample is pretreated with NaOH and DTT to release serum folate from endogenous folate binding protein and to maintain 5-methyl tetrahydrofolate in its reduced form. After the sample pretreatment, Chemibeads and labeled folate binding reagent are added sequentially to the reaction vessel. Folate from the patient sample competes with the folate-Chemibead for a limited amount of labeled FBP. Sensibeads are then added and bind to the biotinylated portion of the labeled FBP to form bead pair immunocomplexes. Illumination of the complex by light at 680 nm generates singlet oxygen from the Sensibeads which diffuses to the Chemibeads triggering a chemiluminescent reaction. The resulting signal is measured at 612 nm and is an inverse function of the concentration of folate in the sample.

Calibrator: The Dimension Vista® LOCI 4 Calibrator is a five level, liquid calibrator. It is packaged as a kit of 10 vials, two vials each of five levels. The product matrix is 6% bovine serum albumin with buffer, stabilizer and preservatives. Level A is zero. Levels B through E contain Ferritin, Vitamin B12, and Folate at the following target concentrations: Level A: Ferritin 0 ng/mL, B12 0 pg/mL, Folate 0.0 ng/mL; Level B: Ferritin 26 ng/mL, B12 200 pg/mL, Folate 2.5 ng/mL; Level C: Ferritin 210 ng/mL, B12 500 pg/mL, Folate 5.0 ng/mL; Level D: Ferritin 1050 ng/mL, B12 1000 pg/mL, Folate 10.0 ng/mL; Level E: Ferritin 2000 ng/mL, B12 2100 pg/mL, Folate 21.0 ng/mL. Values are assigned to new lots from a masterpool that is referenced to the WHO standard for FERR, 3 14 IS 94/572 and United States Pharmacopoeia materials for B12 and Folate.

This document describes the regulatory submission for three in-vitro diagnostic products: Dimension Vista® Vitamin B12 Flex® reagent cartridge (B12), Dimension Vista® Folate Flex® reagent cartridge (FOL), and Dimension Vista® LOCI 4 Calibrator. The submission aims to demonstrate substantial equivalence to previously cleared predicate devices.

1. Table of Acceptance Criteria and Reported Device Performance

For the Dimension Vista® B12 and FOL Flex® reagent cartridge assays, the acceptance criteria are implicitly based on demonstrating comparable performance (correlation, slope, and intercept) to their respective predicate devices. The reported performance is based on a split-sample comparison study.

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

The test set consisted of clinical patient samples.

• B12: 124 clinical patient samples
• FOL: 110 clinical patient samples

The data provenance is not explicitly stated in terms of country of origin but is referred to as "clinical patient samples," implying retrospective. The study type is a "split sample comparison" study, which means portions of the same patient sample were tested on both the new device and the predicate device.

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

This information is not provided in the document. For in-vitro diagnostic comparative studies like this, the "ground truth" for individual patient samples is usually established by the predicate device's measurement, which is considered the established method. There is no mention of independent expert review of results or a separate ground truth determination method by experts.

4. Adjudication Method for the Test Set

This information is not applicable/provided as the study design is a direct comparison to a predicate device, not a classification task requiring adjudication of expert opinions.

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 information is not applicable. The device is an in-vitro diagnostic assay for measuring biomarkers (Vitamin B12 and Folate) and a calibrator. It is not an imaging or diagnostic aid that would involve human "readers" or AI assistance in interpretation.

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

The performance data presented is for the standalone performance of the Dimension Vista® B12 and FOL Flex® reagent cartridge assays, as they are fully automated in-vitro diagnostic tests. There is no human interpretation component in the measurement itself, only in the clinical application of the results.

7. The Type of Ground Truth Used

The ground truth for the performance study (comparison to predicate) was established by the measurements obtained from the legally marketed predicate devices (VB12 and FOL assays on the ADVIA Centaur® System). This is a common approach for demonstrating substantial equivalence for in-vitro diagnostic devices.

8. The Sample Size for the Training Set

This information is not provided. As an in-vitro diagnostic reagent and calibrator kit, these devices do not typically have an "algorithm" in the sense of machine learning that requires a separate training set. Their development involves R&D and validation steps, but not a distinct "training set" like an AI product would.

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

This information is not provided and is generally not applicable in the context of these types of IVD reagent kits and calibrators. The development and manufacturing of these products involve rigorous quality control and calibration processes, often referenced to international standards, but not a "ground truth for a training set" in the common AI/machine learning sense.

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