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EliA M2 is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to M2 in human serum and plasma (Li-heparin, EDTA) to aid in the clinical diagnosis of primary biliary cirrhosis in conjunction with other laboratory and clinical findings. EliA M2 uses the EliA IgG method on the instrument Phadia 2500/5000.

The method-specific reagents are identical with K141375 (EliA M2 on Phadia 250), but are filled in containers specific for the Phadia 2500/5000 instrument. Each device consists of:

• Test Wells: -EliA M2 Wells are coated with native pyruvate dehydrogenase complex from mitochondria and recombinant M2-antigen - 4 carriers (12 wells each), ready to use:
• EliA Sample Diluent: PBS containing BSA, detergent and 0.095% (w/v) sodium azide - 6 bottles, 48 mL each, ready to use; or 6 bottles, 400 mL each, ready to use;
• EliA IgG Conjugate 50 or 200: ß-Galactosidase labeled anti-IgG (mouse monoclonal antibodies) in PBS containing BSA and 0.06% (w/v) sodium azide – 6 wedge shaped bottles, 5 mL each, ready to use; or 6 wedge shaped bottles, 19 mL each, ready to use
• EliA IgG Calibrator Strips: Human IgG (0, 4, 10, 20, 100, 600 µg/L) in PBS containing BSA, detergent and 0.095% (w/v) sodium azide - 5 strips, 6 singleuse vials per strip, 0.3 mL each, ready to use;
• -EliA IgG Curve Control Strips: Human IgG (20 ug/L) in PBS containing BSA, detergent and 0.095% (w/v) sodium azide - 5 strips, 6 single-use vials per strip, 0.3 mL each, ready to use;
• EliA IgG Calibrator Well: Coated with mouse monoclonal antibodies 4 carriers (12 wells each), ready to use.
  The Phadia EliA Immunodiagnostic System is an automated system for immunodiagnostic testing. The EliA reagents are available as modular packages, each purchased separately. All packages are required to carry out EliA M2 tests.

The provided text describes the 510(k) premarket notification for the EliA™ M2 Immunoassay, specifically focusing on its performance on new instrument platforms (Phadia® 2500/5000) compared to a previously cleared device (EliA M2 on Phadia 250 instrument, K141375).

This document is for an in vitro diagnostic (IVD) device, which measures IgG antibodies to M2 to aid in the clinical diagnosis of primary biliary cirrhosis. The "device" in this context is the immunoassay system, which includes the reagents and the instrument platforms.

Therefore, the acceptance criteria and study details discussed pertain to the analytical performance of this IVD device. The concepts of "human readers," "expert consensus for image interpretation," "MRMC," and "standalone algorithm performance" are not applicable here, as this is not an AI/ML imaging device or a device requiring human interpretation of complex visual data. The "ground truth" for an IVD diagnostic test is typically established through reference methods, established clinical diagnoses, or highly characterized samples.

Here's a breakdown of the acceptance criteria and study proof based on the provided text, focusing on the analytical performance of the immunoassay system.

Acceptance Criteria and Reported Device Performance

The core of the "acceptance criteria" for this 510(k) submission is demonstrating substantial equivalence to the predicate device. This is achieved by showing that the analytical performance characteristics of the EliA M2 immunoassay on the Phadia 2500/5000 instruments are comparable and acceptable. The document highlights various analytical performance parameters with their respective results.

1. Table of Acceptance Criteria and Reported Device Performance

Since this is an IVD device, the "acceptance criteria" aren't explicitly stated as pass/fail thresholds in a table, but rather implied by the data presented for substantial equivalence. The document presents the study results for various analytical performance metrics.

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

• Precision/Reproducibility:
  • Sample Size: Each sample was tested in four replicates/run, over 7 days, on 3 instruments. This totals 84 replicates per sample (4 replicates * 7 days * 3 instruments = 84 replicates). The document doesn't specify the number of distinct "samples" (control materials or patient samples) used to establish precision at different concentration levels, but it shows results for 5 different mean concentration levels (1.7, 4.0, 5.9, 74.8, 175.9 U/mL). Typically, these would be control materials or pooled patient samples.
  • Data Provenance: Not explicitly stated, but clinical studies for cut-off determination (K141375) and reference ranges mentioned a "Caucasian population obtained from a blood bank." For analytical studies like precision, standard reference materials or well-characterized internal controls are commonly used. The study was performed over 7 days.
• Linearity/Assay Reportable Range:
  • Sample Size: Four patient serum samples were diluted.
  • Data Provenance: Not explicitly stated regarding country of origin or retrospective/prospective nature for these specific samples.
• Detection Limit (LoB, LoD, LoQ):
  • Sample Size:
    • LoB: One blank sample, measured in twelve replicates in each of six runs (72 determinations total).
    • LoD: Five low-level samples, measured in twelve replicates in each of six runs (360 low level replicates total).
    • LoQ: 360 determinations.
  • Data Provenance: Not explicitly stated.
• Method Comparison (Instrument Comparison):
  • Sample Size: More than 100 samples.
  • Data Provenance: Not explicitly stated regarding country of origin or retrospective/prospective nature. Samples were run in "single replicates" on one Phadia 250 and one Phadia 2500/5000 instrument.

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

• Not applicable. This is an in vitro diagnostic (IVD) immunoassay system, not an AI/ML imaging device that requires human expert interpretation of visual data. The "ground truth" for IVD laboratory tests is typically established by:
  • Quantitative values: Directly measured by reference methods or highly characterized (e.g., gravimetric, spectrophotometric) standards traceability.
  • Qualitative results (positive/negative): Defined by cut-off values derived from clinical studies, often comparing against a gold standard diagnostic method (e.g., biopsy, established clinical diagnosis of PBC).

4. Adjudication Method for the Test Set

• Not applicable. This concept (e.g., 2+1, 3+1) relates to consensus reading in imaging studies. For an IVD assay, results are quantitative values or interpreted based on pre-defined cut-offs.

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 IVD immunoassay device, not an AI-assisted diagnostic imaging system. There are no "human readers" in the context of image interpretation improving with AI assistance. The device directly measures antibody levels.

6. If a Standalone (i.e. Algorithm Only Without Human-in-the Loop Performance) Was Done

• Partially applicable, but in a different sense. The device itself performs the measurement and provides a quantitative result. The "performance" demonstrated (precision, linearity, LoD, method comparison) is inherently "standalone" in that it's the instrument and reagents producing the values. The "human-in-the-loop" would be the clinician interpreting the numerical result in conjunction with other clinical findings for diagnosis. There isn't an "algorithm" making a diagnostic call independently like in an imaging AI; rather, it's a measurement system.

7. The Type of Ground Truth Used

• Analytical Performance:
  • Reference materials and statistical methods: For precision, linearity, and detection limit, the ground truth is based on highly characterized control materials, serial dilutions, and established statistical methodologies (e.g., CLSI guidelines EP05-A3, EP06-A, EP17-A).
• Clinical Performance (Cut-off determination and comparison):
  • Clinical diagnosis and predicate device comparison: The clinical cut-off values for "Negative," "Equivocal," and "Positive" were "derived from the clinical studies (s. K141375)." This implies that the cut-offs were established using patient samples with confirmed clinical diagnoses of primary biliary cirrhosis (or healthy controls) as the ground truth in the predicate device's original studies.
  • For the current submission, the "ground truth" for the method comparison study (comparing Phadia 2500/5000 to Phadia 250) is the result generated by the predicate device (EliA M2 on Phadia 250 instrument). The goal is to show the new instrument produces substantially equivalent results to the established predicate.

8. The Sample Size for the Training Set

• Not applicable in the AI/ML sense. This is an immunoassay system; it does not have a "training set" in the context of machine learning model development. The development process would involve formulation optimization, reagent stability testing, and calibration studies, but not "training data" for an algorithm that learns patterns. The calibration curve is established using calibrators provided with the kit.

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

• Not applicable. See point 8. For IVDs, the "ground truth" for establishing a calibration curve (which is somewhat analogous to "training" the system to interpret raw signals into quantitative units) is defined by the known concentrations of the calibrator materials provided in the kit. These calibrators are rigorously manufactured and assigned values traceable to reference standards.

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QUANTA Flash M2 (MIT3) is a chemiluminescent immunoassay for the semi-quantitative determination of IgG antimitochondrial antibodies in human serum. The presence of antibodies, in conjunction with clinical findings and other laboratory tests, is an aid in the diagnosis of primary biliary cholangitis.

QUANTA Flash M2 (MIT3) Calibrators are intended for use with the QUANTA Flash M2 (MIT3) chemiluminescent immunoassay for the determination of IgG anti-mitochondrial antibodies in human serum. Each calibrator establishes a point of reference for the working curve that is used to calculate unit values.

QUANTA Flash M2 (MIT3) Controls are intended for use with the QUANTA Flash M2 (MIT3) chemiluminescent immunoassay for quality control in the determination of IgG anti-mitochondrial antibodies in human serum.

The QUANTA Flash M2 (MIT3) assay is designed to run on the BIO-FLASH® instrument. This platform is a fully automated closed system with continuous load and random access capabilities that automatically processes the samples, runs the assay and reports the results. It includes liquid handling hardware, luminometer and computer with software-user interface. The QUANTA Flash M2 (MIT3) assay utilizes a reagent cartridge format, which is compatible with the BIO-FLASH instrument.

Recombinant MIT3 antigen is coated onto paramagnetic beads. The bead suspension is lyophilized and stored in the bead tube. Prior to use in the BIO-FLASH system, the sealed reagent tubes are pierced with the reagent cartridge lid and the beads are rehydrated and resuspension buffer by pipetting up and down with a transfer pipette. The reagent cartridge is then loaded onto the BIO-FLASH instrument. Samples are also loaded onto the instrument in samples are diluted by the BIO-FLASH with system rinse in a small disposable plastic cuvette. Small amounts of the diluted patient serum, the beads, and assay buffer are combined into a second cuvette, and mixed. This cuvette is then incubated at 37°C. The beads are magnetized and washed several times. Isoluminol conjugated anti-human IgG antibodies are then added to the cuvette, and again incubated at 37°C. The beads are magnetized and washed repeatedly. The isoluminol conjugate is oxidized when Trigger 1 (Fe(II)coproporphyrin in sodium hydroxide solution) and Trigger 2 (urea-hydrogen peroxide in sodium chloride solution) are added to the cuvette, and the flash of light produced from this reaction is measured as Relative Light Units (RLU) by the BIO-FLASH optical system. The RLU are proportional to the amount of isoluminol conjugate that is bound to the human IgG, which is in turn proportional to the amount of anti-M2 (MIT3) antibodies bound to the corresponding beads.

For quantitation, the QUANTA Flash M2 (MIT3) assay utilizes a predefined lot specific Master Curve that is uploaded onto the instrument through the reagent cartridge barcode. Every new lot number of reagent cartridge must be calibrated before first use, with the QUANTA Flash M2 (MIT3) Calibrators. Based on the results obtained with the three Calibrators included in the Calibrator Set (sold separately), an instrument specific Working Curve is created, which is used to calculate chemiluminescent units (CU) from the instrument signal (RLU) obtained for each sample.

The QUANTA Flash M2 (MIT3) kit contains the following materials:

One (1) QUANTA Flash M2 (MIT3) Reagent Cartridge One (1) vial of Resuspension buffer One (1) Transfer pipette

The QUANTA Flash M2 (MIT3) reagent cartridge contains the following reagents for 50 determinations:

• M2 (MIT3) coated paramagnetic beads, lyophilized. a.
• b. Assay buffer - colored pink, containing Tris-buffered saline, Tween 20, protein stabilizers and preservatives.
• Tracer IgG Isoluminol labeled anti-human IgG antibodies in buffer, containing protein C. stabilizers and preservative.

The QUANTA Flash M2 (MIT3) Calibrators kit contains two vials each of Calibrator 2, and Calibrator 3:

QUANTA Flash M2 (MIT3) Calibrators:

• QUANTA Flash M2 (MIT3) Calibrator 1: Two (2) barcode labeled tubes containing 0.3 mL prediluted, ready to use reagent. Calibrators contain human anti-mitochondrial antibodies in stabilizer and preservative.
• -QUANTA Flash M2 (MIT3) Calibrator 2: Two (2) barcode labeled tubes containing 0.3 mL prediluted, ready to use reagent. Calibrators contain human anti-mitochondrial antibodies in stabilizer and preservative.
• -QUANTA Flash M2 (MIT3) Calibrator 3: Two (2) barcode labeled tubes containing 0.3 mL prediluted, ready to use reagent. Calibrators contain human anti-mitochondrial antibodies in stabilizer and preservative.

The QUANTA Flash M2 (MIT3) Controls kit contains two vials of Negative Control and two vials of Positive Control:

QUANTA Flash M2 (MIT3) Controls:

• QUANTA Flash M2 (MIT3) Negative Control: Two (2) barcode labeled tubes containing 0.5 mL, ready to use reagent. Controls contain human anti-mitochondrial antibodies in stabilizer and preservative.
• QUANTA Flash M2 (MIT3) Positive Control: Two (2) barcode labeled tubes containing 0.5 mL, ready to use reagent. Controls contain human anti-mitochondrial antibodies in stabilizer and preservative.

Here's a breakdown of the acceptance criteria and study information for the QUANTA Flash M2 (MIT3) device:

1. Table of Acceptance Criteria and Reported Device Performance

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An enzyme linked immunosorbent assay (ELISA) for the qualitative detection of anti-mitochondria antibodies (AMA) in human serum to aid in the diagnosis of primary biliary cirrhosis (PBC) in conjunction with other laboratory tests and clinical findings.

An enzyme linked immunoassay (ELISA) for the qualitative or semi-quantitative detection of anti-mitochondria IgG antibodies in human serum to aid in the diary cirrhosis (PBC) in conjunction with other laboratory tests and clinical findings.

This test is performed as a solid phase immunoassy. Microwells are coated with recombinant Mitochondrial antigen. Controls, calibrators and patient sera are incubated in the antibodies present in the serum to bind to the Mitochondria antigen. Bound antibodies are detected by adding an enzyme labeled anti-human IgG or IgA/JgG/JgM conjugate. Specific enzyme substrate (TMB) is then added and the presence of antibodies is detected by a color change that is read by a spectrophotometer at 450 nm. Results are expressed in ELISA units per milliliter (EU/ml) and reported as positive or negative.

This test is performed as a solid phase immunoassy. Microwells are coated with recombinant mitochondrial antigen. Controls, calibrators and patient sera are incubated in the antigen coated wells to allow specific antibodies present in the serum to bind to the Mitochondria antigen. Bound antibodies are detected by adding an enzyme labeled anti-human IgG or IgA/gG/lgM conjugate. Specific enzyme substrate (TMB) is then added and the presence of antibodies is detected by a color change that is read by a spectrophotometer at 450 nm. Results are expressed in ELISA units per milliliter (EU/ml) and reported as positive or negative.

Here's a breakdown of the acceptance criteria and the study that proves the device meets them, based on the provided text.

Note: The document describes two devices:

1. ImmuLisa Enhanced™ Anti-Mitochondria IgG Antibody (AMA) ELISA (referred to as "AMA IgG ELISA")
2. ImmuLisa Enhanced™ Anti-Mitochondria IgA/IgG/IgM Antibody (AMA) ELISA (referred to as "AMA IgA/IgG/IgM ELISA")

Since the structure of the provided text details similar studies for both, I will present the information for both devices where available, clearly distinguishing between them. The acceptance criteria themselves are implied from the "Clinical Study" results where clinical sensitivity and specificity are reported.

1. Table of Acceptance Criteria and Reported Device Performance

For ImmuLisa™ Enhanced Anti-Mitochondria IgG Antibody (AMA) ELISA:

For ImmuLisa™ Enhanced Anti-Mitochondria IgA/IgG/IgM Antibody (AMA) ELISA:

Note on Acceptance Criteria: The document does not explicitly state pre-defined acceptance criteria values (e.g., "Sensitivity must be >= 80%"). Instead, it presents the results of the clinical study, implying that these achieved performance metrics are acceptable for regulatory clearance.

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

The document describes "Clinical Study" results, which serve as the test set performance.

For both AMA IgG ELISA and AMA IgA/IgG/IgM ELISA:

• Sample Size for Test Set:
  • 193 primary biliary cirrhosis (PBC) subjects.
  • 898 autoimmune and infectious disease controls.
  • Total: 1091 samples.
• Data Provenance: Not explicitly stated (e.g., country of origin). The study states "Sets of clinical samples were tested," suggesting they are human clinical samples. It does not specify if these were retrospective or prospective, but based on the overall context of a 510(k) summary, they are typically retrospective or collected for the purpose of the study.

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

• The document states that the samples were "well-characterized primary biliary cirrhosis subjects and disease controls." This implies that the diagnosis of PBC and the control conditions were established by medical professionals.
• Number of Experts: Not specified.
• Qualifications of Experts: Not specified. However, the nature of diagnosing primary biliary cirrhosis and various autoimmune/infectious diseases requires specialized medical expertise, likely from clinicians, hepatologists, or infectious disease specialists.

4. Adjudication Method

• Adjudication Method: Not explicitly stated. The phrase "well-characterized" suggests a established diagnosis rather than a specific adjudication process for the study.

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

• No, an MRMC comparative effectiveness study was not done. The studies presented are "standalone" performance evaluations of the device against established clinical diagnoses.

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

• Yes, standalone performance studies were done. The clinical sensitivity and specificity results are for the device (ELISA kit) itself, used as a diagnostic aid. Human interpretation is involved in reading the spectrophotometer results and applying the cutoff values, but it's not a human-in-the-loop AI system in the typical sense where AI provides an initial read for human verification/modification. The device provides a quantitative or qualitative result (EU/ml, positive/negative) that aids clinical findings.

7. Type of Ground Truth Used

• Type of Ground Truth: The ground truth used was based on clinical diagnosis of primary biliary cirrhosis (PBC) and various autoimmune/infectious diseases for the control group. This is implied by the term "well-characterized primary biliary cirrhosis subjects and disease controls." "Indeterminate samples for these studies were considered positive."

8. Sample Size for the Training Set

• The document does not explicitly mention a separate training set or its sample size. The studies described appear to be validation studies of the finished device. For an ELISA kit, development and optimization (analogous to training) are typically part of the manufacturing and design control process, not usually reported as a separate "training set" in the same way as machine learning algorithms. The "Method Comparison" and "Cross Reactivity" sections utilize larger sample sizes, but these are for testing characteristics rather than training.

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

• Since a separate "training set" is not explicitly detailed in the provided text in the context of machine learning, the method for establishing its ground truth is also not described. Device development typically involves internal validation using reference materials and clinically characterized samples, which would serve a similar purpose to a training set for optimizing assay parameters.

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EliA M2 is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to M2 in human serum and plasma (heparin, EDTA) to aid in the clinical diagnosis of primary biliary cirrhosis in conjunction with other laboratory and clinical findings. EliA M2 uses the EliA IgG method on the instruments Phadia 100 and Phadia 250.

EliA M2 Positive Control 100 is intended for laboratory use in monitoring the performance of in vitro measurement of M2 antibodies with Phadia 100 using the EliA IgG method.

EliA M2 Positive Control 250 is intended for laboratory use in monitoring the performance of in vitro measurement of M2 antibodies with Phadia 250 using the EliA IgG method.

The new device belongs to a fully integrated and automated system for immunodiagnostic testing. It comprises a Fluorescence-Immunoassay test system using EliA single wells as the solid phase and is intended to be performed on the instruments Phadia 100 and Phadia 250.

The conjugate for the EliA IgG method is mouse anti-human IgG beta-galactosidase, which uses 4-Methylumbelliferyl-ßD-Galactoside as substrate.

The total IgG calibration is based on a set of six WHO-standardized IgG Calibrators derived from human serum. They are used to establish an initial calibration curve, which may be used for up to 28 days on additional assays and can be stored by the instrument. Each additional assay includes calibrator (curve) controls that have to recover in defined ranges to ensure that the stored calibration curve is still valid. The Fluorescence-Immunoassay test system includes test-, method-specific and general reagents that are packaged as separate units.

The provided text describes a submission for an in vitro diagnostic device, not an AI/ML-based medical device. Therefore, many of the requested categories related to AI/ML device studies (such as MRMC studies, training set size, expert adjudication, etc.) are not applicable and cannot be extracted from this document.

However, I can extract information regarding acceptance criteria and device performance from the provided text, focusing on the clinical study that supports its intended use.

Here's the information based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state numerical acceptance criteria in the form of a table. However, it implies that the device's performance needs to be comparable to the predicate device and show appropriate results with clinically defined sera and normal populations.

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

• Sample Size: The document does not explicitly state the specific number of samples for the test set used in the comparison study, clinically defined sera, or normal population. It mentions "a data set including results obtained within a comparison study," "results obtained for clinically defined sera," and "results obtained for samples from apparently healthy subjects (normal population)."
• Data Provenance: Not specified in terms of country of origin. The study appears to be retrospective, using existing "clinically defined sera" and "samples from apparently healthy subjects."

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

Not applicable. This is an immunoassay, not an AI/ML device requiring expert interpretation of images or other complex data for ground truth establishment. The "ground truth" for this type of device would typically be the clinical diagnosis of primary biliary cirrhosis, likely established by standard clinical criteria, not by individual experts assessing the samples themselves for ground truth.

4. Adjudication method for the test set

Not applicable. This is an immunoassay. The concept of adjudication for a test set typically applies to areas where human interpretation or labeling is involved, such as image analysis.

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 immunoassay, not an AI/ML device, and no human reader interpretation is described.

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

This refers to the performance of the immunoassay device itself. The study described focuses on the comparison of the new immunoassay device (EliA M2) to a predicate device (Quanta Lite M2 EP (MIT3), INOVA K052262), and its performance with clinically defined sera and healthy subjects. The entire system (reagents, instrument Phadia 100/250, and software for evaluation) constitutes the "standalone" performance of the diagnostic test.

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

The ground truth for the "clinically defined sera" and "samples from apparently healthy subjects" would be based on the established clinical diagnosis of Primary Biliary Cirrhosis (PBC) for positive cases and the absence of PBC for healthy subjects, determined through a combination of clinical findings and other laboratory tests. The document implies a clinical diagnosis.

8. The sample size for the training set

Not applicable. This is an immunoassay, not an AI/ML device that requires a training set in the conventional sense. The "training" of the device is inherent in its design and calibration, not through data learning.

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

Not applicable for the same reasons as point 8.

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The EUROIMMUN Anti-M2-3E ELISA (IgG) test kit is intended for the qualitative or semi-quantitative determination of IgG class autoantibodies against the mitochondrial antigens M2 in human serum and plasma. It is used as an aid in the diagnosis of primary billary cirrhosis (PBC), in conjunction with other laboratory and clinical findings.

The EUROIMMUN Anti-M2-3E ELISA (IgG) consists of a microwell ELISA plate coated with M2-3E antigen, 3 calibrators, positive and negative control, peroxidase-labelled anti-human IgG conjugate, sample buffer, wash buffer concentrate, TMB chromogen/substrate solution and stop solution.

The provided text describes the performance characteristics of the EUROIMMUN Anti-M2-3E ELISA (IgG) test kit and its comparison to a predicate device and clinical studies. However, it does not explicitly define "acceptance criteria" in a separate section with specific numerical thresholds for each performance metric before presenting the study results. Instead, the "Performance Characteristics" section M presents the study results for analytical and clinical performance.

Based on the information provided, I will infer what constitutes "acceptance criteria" from the reported performance, especially for the "Method comparison with predicate device" and "Clinical studies" sections, where the device needs to show substantial equivalence or good diagnostic accuracy.

1. Table of Acceptance Criteria and Reported Device Performance

Inferred Acceptance Criteria:

• Precision/Reproducibility: Intra-assay and Inter-assay CVs 90%
• Clinical Sensitivity (for PBC): High sensitivity (e.g., >90%).
• Clinical Specificity: High specificity (e.g., >90%) across various control groups.

Reported Device Performance:

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

• Precision/Reproducibility:
  • Intra-assay: 12 unique samples, each tested 20 times.
  • Inter-assay: 12 unique samples, each tested 4 times over 6 days (total 24 determinations per sample).
  • Lot to Lot: 8 unique samples, each tested across 3 different lots and 2 runs (total 6 determinations per sample).
• Linearity: 5 patient sera, each serially diluted up to 1/32, with single determinations.
• Analytical Specificity (Cross-reactivity): 29 sera (10 PCA, 10 GBM, 9 LKM positive).
• Interference: 5 different specimens at varying Anti-M2-3E concentrations, spiked with potential interfering substances.
• Method Comparison with Predicate Device: 127 clinically characterized samples (39 AIH, 49 PBC, 32 AIH/PBC overlap, and 7 created "borderline" samples by mixing) collected at EUROIMMUN UK Ltd. This data appears to be retrospective as samples were already "clinically characterized."
• Matrix Comparison: 21 sample pairs of serum and corresponding plasma.
• Clinical Studies: 1180 clinically characterized samples (251 from PBC patients and 929 from control groups). The text mentions "performed in cooperation with several university hospitals," suggesting retrospective collection of already diagnosed patient samples.

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

The document does not specify the number of experts used to establish the ground truth, nor their qualifications for any of the studies (method comparison or clinical studies). It states samples were "clinically characterized" for the method comparison and "clinically characterized" for the clinical study, but does not detail the process or who performed it.

4. Adjudication method for the test set

The document does not describe any adjudication method for establishing the ground truth for either the method comparison or the clinical studies. Ground truth appears to be based on "clinical characterization" which typically implies diagnosis based on multiple clinical and laboratory findings, but the specific process for confirming these diagnoses is not elaborated.

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 to the provided document. The device is an in vitro diagnostic ELISA test kit, not an AI-assisted diagnostic tool that would involve human readers interpreting images or data with and without AI assistance. The performance is based on the assay's ability to detect autoantibodies.

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

Yes, the studies presented are all standalone performance evaluations of the EUROIMMUN Anti-M2-3E ELISA (IgG) test kit. The performance characteristics (analytical and clinical) measure the device's ability to detect specific autoantibodies directly, without human interpretation of the assay's output other than reading the optical density and interpreting the result against the established cutoff.

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

The ground truth for the clinical studies appears to be based on clinical diagnosis of Primary Biliary Cirrhosis (PBC) and various control conditions. The phrase "clinically characterized samples" implies that these diagnoses were established through a combination of clinical findings, patient history, other laboratory tests, and possibly biopsy/pathology results, as part of routine medical practice at the "several university hospitals." However, specific details like "expert consensus" or "pathology" are not explicitly mentioned as the sole or primary ground truth source.

8. The sample size for the training set

The document does not mention a distinct "training set" in the context of machine learning or algorithm development. The ELISA test kit is a biochemical assay. The "calibrators" are used to establish a calibration curve for quantitative or semi-quantitative results, and "controls" are used for quality assurance, but these are not a "training set" in the AI/ML sense. The product development would involve internal validation and optimization, but specific "training set sizes" are not provided.

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

As there is no "training set" in the context of an algorithm, this question is not applicable. For the calibrators and controls included in the kit, their "ground truth" (i.e., their known concentration or reactivity level) is established during the manufacturing and quality control processes of the diagnostic kit.

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The QUANTA Lite™ M2 EP (MIT3) ELISA is an enzyme-linked immunosorbent assay (ELISA) for the semi-quantitative detection of mitochondrial antibodies in human serum. The presence of mitochondrial antibodies can be used in conjunction with clinical findings to aid in the diagnosis of primary biliary cirrhosis.

The QUANTA Lite™ M2 EP (MIT3) ELISA is an enzyme-linked immunosorbent assay (ELISA)

The provided document is a 510(k) premarket notification letter from the FDA regarding the QUANTA Lite™ M2 EP (MIT3) ELISA device. While it states that the device is substantially equivalent to a predicate device, it does not contain the detailed study information needed to answer the questions about acceptance criteria and device performance.

Specifically, the document only provides:

• Device Name: QUANTA Lite™ M2 EP (MIT3) ELISA
• Intended Use: Semi-quantitative detection of mitochondrial antibodies in human serum to aid in the diagnosis of primary biliary cirrhosis.
• Regulatory Classification: Class II, Product Code DBM.

The document does NOT include any information on:

1. A table of acceptance criteria and reported device performance.
2. Sample size used for the test set or data provenance.
3. Number of experts and their qualifications used to establish ground truth.
4. Adjudication method for the test set.
5. Multi-reader multi-case (MRMC) comparative effectiveness study results.
6. Standalone (algorithm-only) performance.
7. Type of ground truth used.
8. Sample size for the training set.
9. How ground truth for the training set was established.

To obtain this information, one would typically need to review the full 510(k) submission (not just the FDA's decision letter), which includes the detailed analytical and clinical performance studies conducted by the manufacturer.

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The MESACUP-2 TEST Mitochondria M2 is semi-quantitative enzyme-linked immunosorbent assay (ELISA) for the detection of anti-Mitochondrial antibodies in human serum as an aid in the diagnosis of primary biliary cirrhosis.

The MESACUP-2 Test Mitochondria M2 is an enzyme-linked immunosorbent assay (ELISA), utilizing the 96-microwell plate format, similar to the predicate device. Diluted serum samples, calibrator sera, and controls are incubated in microwells coated with mitochondria M2 antigens. Incubation allows the antimitochondria M2 antibodies present in the samples to react with the immobilized antigen. After the removal of unbound serum proteins by washing, antibodies specific for human immunoglobulins (IgG, IgM and IgA), labeled with horseradish peroxidase (HRP), are added forming complexes with the mitochondria M2 bound antibodies. Following another washing step, the bound enzyme-antibody conjugate is assayed by the addition of a single solution containing tetramethlybenzidine (TMB) and hydrogen peroxide (H3O2) as the chromogenic substrate. The intensity of the color generated is proportional to the serum concentration of anti-mitochondria M2 antibodies. Optical density is read spectrophotometrically at 450mm. The total incubation time (at room temperature) of the assay is 150 minutes. The assay makes use of two calibrators to measure the amount of anti-mitochondria M2 antibodies in patient samples.

Here's a breakdown of the acceptance criteria and study information for the MESACUP-2 Test Mitochondria M2 device, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance:

The document doesn't explicitly state "acceptance criteria" in a tabular format, but rather compares the performance of the MESACUP-2 Test to a legally marketed predicate device (Quanta Lite Mitochondria M2 ELISA) and implies that comparable performance is the measure of acceptance. The key performance metrics are clinical specificity and sensitivity.

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

• Sample Size: Not explicitly stated as a numerical value for each group. The text mentions "a healthy donor serum population" and "a primary biliary cirrhosis population."
• Data Provenance: The studies were "In-house studies," suggesting they were conducted by RhiGene, Inc. The country of origin of the data is not specified but implied to be the US given the submission to the FDA. The studies were likely retrospective as they involve patient populations already categorized.

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. The text does not elaborate on how the classification of "healthy donor serum population" or "primary biliary cirrhosis population" was established.

4. Adjudication Method for the Test Set:

This information is not provided in the document.

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 an ELISA assay for detecting antibodies, not an AI-assisted diagnostic imaging or interpretation tool that involves human readers.

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

The device itself is a standalone in vitro diagnostic (IVD) test. It's an "algorithm only" in the sense that it provides a semi-quantitative result based on a chemical reaction and optical density reading, without direct human interpretation of complex patterns in the way an imaging AI would. The performance metrics (specificity and sensitivity) are derived from the device's output.

7. The Type of Ground Truth Used:

The ground truth used was clinical diagnosis/status. The populations were defined as "healthy donor serum population" and "primary biliary cirrhosis population." It's assumed that this classification was based on established clinical diagnostic criteria (e.g., patient history, physical examination, other laboratory tests, biopsies if applicable for PBC).

8. The Sample Size for the Training Set:

This information is not provided. The document describes a comparison study, implying that the MESACUP-2 Test has already been developed. There is no mention of a separate "training set" for the device itself, as it's a biochemical assay rather than a machine learning algorithm that requires explicit training data in the modern sense.

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

This information is not provided and is largely not applicable in the context of a traditional ELISA assay development, which focuses on chemical and biological validation rather than algorithmic training with ground truth labels in the same way an AI model would be.

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This assay is intended for the in-vitro measurement of specific IgG, IgA and IgM autoantibodies against mitochondria present in human serum as an aid in the diagnosis of primary biliary cirrhosis (PBC) when used in conjunction with other clinical observations.

BINDAZYME® Anti-Mitochondria M2 IgGAM EIA Kit

The provided text describes a 510(k) premarket notification for the "BINDAZYME® Anti-Mitochondria M2 IgGAM EIA Kit." This document is a regulatory letter from the FDA determining substantial equivalence, and it does not contain the detailed study results, acceptance criteria, or performance data typically found in a clinical study report.

Therefore, I cannot extract the specific information requested about acceptance criteria, device performance, sample sizes, expert qualifications, adjudication methods, MRMC studies, standalone performance, or ground truth establishment.

The document primarily states:

• Device Name: BINDAZYME® Anti-Mitochondria M2 IgGAM EIA Kit
• Intended Use: "This assay is intended for the in-vitro measurement of specific IgG, IgA and IgM autoantibodies against mitochondria present in human serum as an aid in the diagnosis of primary biliary cirrhosis (PBC) when used in conjunction with other clinical observations."
• Regulatory Status: Substantially equivalent to a legally marketed predicate device.
• Product Code: DBM (Anti-mitochondrial antibody immunological test system)
• Regulatory Class: Class II

To provide the information you requested, access to the actual 510(k) submission document or a clinical study report would be necessary.

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Intended for the in vitro determination of mitochondrial (M2) antibody in human serum. Anti-M2 assays are used as an aid in the diagnosis of Primary Biliary Cirrhosis - CFR 866.5090

Not Found

The provided text is a 510(k) approval letter from the FDA for a device called "TRACE Enzymatic Mitochondria (M2) Antibody Reagent." This document does not contain the detailed information required to answer your questions about acceptance criteria and the study proving device performance.

Specifically, the letter is a regulatory filing indicating substantial equivalence to a previously marketed device, allowing it to be sold. It does not include:

• Details of a performance study.
• Acceptance criteria for such a study.
• Sample sizes for test or training sets.
• Information on expert ground truth, adjudication methods, or MRMC studies.

Therefore, I cannot provide the requested table or answer the specific questions based on the input text.

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This enzyme-linked immunosorbent assay (ELISA) is indicated for the detection and measurement of antimitochondrial antibodies in human serum. The presence of mitochondrial antibodies, in combination with clinical observations and other serological tests, can aid in the diagnosis of primary biliary cirrhosis(PBC)

An enzyme-linked immunosorbent assay (ELISA) designed for the detection and measurement of antibodies to mitochondrial antigen in human serum. The ELISA methodology is commonly used for serum antibody evaluations. Purified mitochondrial antigen has been attached to the inner surfaces of the microwell plate. During the initial incubation step, antibodies in patient serum bind specifically to the immobilized antigen and remain in place after a wash step. A second antibody which is conjugated to horseradish peroxidase (HRP) is used to recognize the "heavy + light" chain regions of the patient's antibodies remaining after the wash step. In the wells where the second antibody remains bound, the conjugated HRP catalyzes a color change in the substrate, tetramethyl benzidine (TMB). After the reaction is stopped, the color is read in an EIA Plate reader.

The provided document describes the VIRGO® AMA ELISA KIT, an enzyme-linked immunosorbent assay designed for the detection and measurement of antimitochondrial antibodies in human serum. This device is intended to aid in the diagnosis of primary biliary cirrhosis (PBC) when used in combination with clinical observations and other serological tests.

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria with numerical targets. However, based on the comparative testing and precision studies, the implied criteria are:

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