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The SPIFE A1AT kit is designed for the qualitative detection of the different phenotypes of Alpha-1 Antitypsin (Al AT). Phenotyping results in conjunction with clinical findings and other laboratory assays aid in the diagnosis of Alpha-1 Antitrypsin deficiency. The analysis is performed on human sera separated into electrophoretic patterns ready for qualitative analysis. The procedure includes isoelectrofocusing on agarose gel, performed on the semiautomatic SPIFE Touch system followed by immunofixation with anti-Alpha-1 Antiserum. For in vitro diagnostic use only.

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I apologize, but the provided text from the FDA 510(k) clearance letter for the SPIFE A1AT kit does not contain the detailed information necessary to answer your request about acceptance criteria and the study that proves the device meets those criteria.

The document is a clearance letter stating that the device is substantially equivalent to a predicate device and outlines general regulatory requirements. It does not include the specifics of the performance study, such as:

• A table of acceptance criteria and reported device performance.
• Sample sizes for test or training sets, or data provenance.
• Details about expert involvement in ground truth establishment or adjudication methods.
• Information on MRMC studies or effect sizes.
• Whether standalone performance was evaluated.
• The type of ground truth used.
• How ground truth was established for the training set.

To obtain this information, you would typically need to refer to the 510(k) summary or the full 510(k) submission for the device, which are often available through the FDA's public databases or directly from the manufacturer. The clearance letter itself only confirms the regulatory approval.

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The Progenika A1AT genotyping kit is a qualitative, polymerase chain reaction (PCR) and hybridization-based in vitro diagnostic test to be used with the Luminent (with xPONENT software) for the simultaneous detection and identification of 14 allelic variants and their associated alleles found in the Alpha-1 antitrypsin (AIAT) codifying gene SERPINA1. The test is intended for use with genomic DNA extracted from human whole blood samples collected as dry blood spots (DBS) or in K2-EDTA or from human saliva samples collected as buccal swabs using ORAcollect Dx OCD-100. The A1AT allelic variant genotypes and associated allele results, when used in conjunction with clinical findings and other laboratory tests, are intended as an aid in the diagnosis of individuals with A1AT deficiency (A1ATD). The kit is indicated for prescription use only.

Alpha 1 antitrypsin (A1AT) Genotyping Test utilizes Luminex xMAP technology. Genomic DNA is extracted from DBS, from human EDTA anticoagulated whole blood or from human saliva samples collected as buccal swabs using ORAcollect-Dx OCD-100. Extracted DNA is amplified and biotinylated by multiplex PCR and PCR products are denatured and hybridized to oligonucleotide probes coupled to color-coded beads. Hybridized DNA is labeled with a fluorescent conjugate and the resulting signal is detected with a Luminex® 200 system. Raw data obtained is processed with the A1AT Genotyping Test ANALYSIS SOFTWARE in order to obtain the final report. The A1AT Genotyping Test ANALYSIS SOFTWARE algorithm converts the allelic variant genotypes into associated alleles, based on the current literature.

The A1AT Genotyping Test Kit is composed of 4 reagent components (A1AT PCR Master Mix, A1AT Beads Master Mix, SAPE, SAPE Dilution Buffer) required to perform all the abovementioned processing steps. The A1AT Genotyping Test ANALYSIS SOFTWARE, instructions for use and other necessary files are uploaded on a Grifols website. Two kit configurations are available: for 48 or 192 tests (different amounts of the same reagent components are provided in each case).

The provided document describes the A1AT Genotyping Test. This 510(k) submission (K211115) is for a modified version of a previously cleared device (K192858), primarily involving a software update. Therefore, much of the performance data refers back to the original submissions (K192858 and K171868).

Here's a breakdown of the acceptance criteria and study information based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

2. Sample Sizes and Data Provenance

• Test Set Sample Size:
  • LoD: 20 replicates of nine DNA dilutions for a "Sample Panel" (total of 180 tests per lot, across two lots used).
  • Precision (Lot-to-Lot): Five DNA samples ("Sample Panel") tested in triplicate, with three different reagent lots, by two operators, on six non-consecutive days, alternating between two Luminex instruments (5 samples * 3 replicates * 3 lots * 2 operators * 6 days = 540 tests, plus additional factors for instruments).
  • Accuracy: For the predicate device, 147 samples were used. The document refers to K171868 and K192858 for specific method comparison data for the modified device, so the exact number for the modified device's accuracy testing isn't explicitly stated but would be similar to or larger than the predicate's 147.
• Data Provenance: Not explicitly stated as "country of origin for data" or "retrospective/prospective." However, the applicant is Progenika Biopharma S.A. based in Spain, suggesting the studies likely occurred in Spain or affiliated regions. The nature of the studies (analytical performance) implies laboratory-based testing, which can be seen as a form of controlled prospective data collection for the device's technical performance.

3. Number of Experts and Qualifications for Ground Truth (Test Set)

• The document does not mention the use of experts to establish ground truth for the test set for the analytical performance studies described (LoD, Precision). These studies focus on the device's ability to consistently and accurately detect specific genetic variants based on known DNA samples.
• For Accuracy (Method Comparison), the ground truth was established by Bi-directional Sanger sequencing. This is considered a gold standard in genetic sequencing, not typically requiring "experts" to interpret the sequence output, but rather highly skilled laboratory personnel and bioinformaticians.

4. Adjudication Method (Test Set)

• Not applicable as the ground truth for analytical performance studies is typically objective (e.g., known DNA concentrations, Sanger sequencing results). The results are compared directly to these objective standards.

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

• No, an MRMC comparative effectiveness study was not done. This device is an in vitro diagnostic (IVD) genetic test, which generates objective results (detection of allelic variants). The performance evaluation focuses on the analytical accuracy and precision of the device itself, rather than human interpretation of complex images or clinical scenarios that would necessitate an MRMC study.

6. Standalone Performance Study (Algorithm Only)

• Yes, a standalone performance study was done. The entire "Performance Data" section (H) describes the analytical studies to determine the device's capabilities (LoD, precision, stability, accuracy). These are evaluations of the algorithm and the assay itself, demonstrating its standalone performance from DNA input to reported genotype. The device includes "A1AT Genotyping Test ANALYSIS SOFTWARE" which processes raw data to obtain the final report, indicating its role as a standalone algorithm in the diagnostic process once the PCR and hybridization steps are completed.

7. Type of Ground Truth Used

• For LoD and Precision: Known DNA samples with established genotypes/concentrations were used.
• For Accuracy (Method Comparison): Bi-directional Sanger sequencing was used as the comparator (a gold standard laboratory method) to establish the ground truth for the samples tested.

8. Sample Size for the Training Set

• The document does not explicitly state the sample size used for the training set. This is a 510(k) submission for a device with a software update (v1.0.8.16 from v1.0.6.1). The software's algorithm for converting allelic variant genotypes into associated alleles is based on current literature. It's possible that the "training" for such an algorithm is not based on a 'training set' in the machine learning sense, but rather on established scientific knowledge and rules coded into the software. If any machine learning components were present, their training data is not disclosed here.

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

• Given that the document refers to the algorithm converting genotypes into alleles "based on the current literature," the ground truth for the "training" (or more accurately, the ruleset development) of the algorithm would be derived from published scientific literature and established genetic associations between allelic variants and their corresponding alleles for the SERPINA1 gene. There is no indication of a specific "training set" of patient samples with prospectively established ground truth for algorithm development in this context.

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The Progenika A1AT genotyping kit is a quantitative, polymerase chain reaction (PCR) and hybridization-based in vitro diagnostic test to be used with the Luminex 200 instrument (with xPONENT software) for the simultaneous detection and identification of 14 allelic variants and their associated alleles found in the Alpha-1 antitrypsin (A1AT) codifying gene SERPINA1. The test intended for use with genomic DNA extracted from human whole blood samples collected as dry blood spot (DBS) or in K2-EDTA or from human saliva samples collected as buccal swabs using ORAcollect Dx model OCD-100. The A1AT allelic variant genotypes and associated allele results, when used in conjunction with clinical findings and other laboratory tests, are intended as an aid in the diagnosis of individuals with A1AT deficiency (A1ATD). The kit is indicated for prescription use only.

Alpha 1 antitrypsin (A1AT) Genotyping Test utilizes Luminex xMAP technology. Genomic DNA is extracted from DBS or from human EDTA anticoagulated whole blood or from human saliva samples collected as buccal swabs using ORAcollect-Dx model OCD-100. Extracted DNA is amplified and biotinylated by multiplex PCR and PCR products are denatured and hybridized to oligonucleotide probes coupled to color-coded beads. Hybridized DNA is labeled with a fluorescent conjugate and the resulting signal is detected with a Luminex® 200 system. Raw data obtained is processed with the A1AT Genotyping Test ANALYSIS SOFTWARE in order to obtain the final report. The A1AT Genotyping Test ANALYSIS SOFTWARE algorithm converts the allelic variant genotypes into associated alleles, based on the current literature.

The A1AT Genotyping Test Kit is composed of 4 reagent components (A1AT PCR Master Mix, A1AT Beads Master Mix, SAPE, SAPE Dilution Buffer) required to perform all the above mentioned processing steps, and a CD containing the A1AT Genotyping Test ANALYSIS SOFTWARE and other necessary files. Two kit configurations are available: for 48 or for 192 tests (different amounts of the same reagent components are provided in each case).

Here’s a summary of the acceptance criteria and study details for the A1AT Genotyping Test, as extracted from the provided FDA 510(k) submission.

1. Table of Acceptance Criteria and Reported Device Performance

The submission does not explicitly list "acceptance criteria" in a separate section with specific numerical thresholds for each performance metric. Instead, the study aims to demonstrate "100% concordance" with bi-directional Sanger sequencing for accuracy. The "Performance specifications" section outlines the areas tested, and the "Comparison Data" section reports the accuracy.

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

• Sample Size for Accuracy Test Set: 147 DNA samples.
  • 140 archived left-over clinical genomic DNA samples obtained from human saliva (buccal swabs using ORAcollect Dx model OCD-100).
  • 3 genomic DNA samples extracted from cell lines.
  • 4 synthetic DNA samples.
• Data Provenance: The 140 clinical samples were "archived left-over clinical genomic DNA samples," suggesting a retrospective collection of samples from clinical practice. The country of origin for the clinical samples is not specified in the provided text.

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

Not applicable. The ground truth was established by bi-directional Sanger sequencing, which is a laboratory method, not human expert interpretation.

4. Adjudication Method for the Test Set

Not applicable, as the ground truth was based on a laboratory method (bi-directional Sanger sequencing) rather than expert review requiring adjudication.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

Not applicable. This device is a genotyping test, not an image-based AI-assisted diagnostic tool for human readers. It provides direct genetic results.

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

A standalone performance study was done for the device, where its results were compared directly against bi-directional Sanger sequencing (the ground truth). The A1AT Genotyping Test ANALYSIS SOFTWARE algorithm processes raw data to obtain the final report, effectively representing the "algorithm only" performance against the comparator.

7. The Type of Ground Truth Used

The ground truth used for the accuracy study was bi-directional Sanger sequencing.

8. The Sample Size for the Training Set

The document does not explicitly mention a "training set" for the device itself in the context of an AI/ML algorithm. This device is a PCR and hybridization-based assay with associated analysis software. The performance data presented refers to the evaluation of this assay. If the "ANALYSIS SOFTWARE" incorporates machine learning, the training set details are not provided. However, given the nature of the device (genotyping test), it is unlikely to involve a dynamic machine learning model in the typical sense that would require a separate, distinct training set in the context of this submission. The software's algorithm converts allelic variants into associated alleles based on existing literature.

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

Not applicable, as a distinct training set (in the context of AI/ML) and its ground truth establishment are not discussed in the provided text. The "analysis software algorithm" is described as converting genotypes into alleles "based on the current literature," implying established scientific knowledge rather than a learned model from a specific training dataset.

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The Progenika A1AT genotyping kit is a qualitative, polymerase chain reaction (PCR) and hybridization-based in vitro diagnostic test to be used with the Luminex 200TM instrument (with xPONENT® software) for the simultaneous detection and identification of 14 allelic variants and their associated alleles found in the Alpha-1 antitypsin (A1AT) codifying gene SERPINA1. The test is intended for use with genomic DNA extracted from human whole blood samples collected as dry blood spots (DBS) or in K2-EDTA. The A1AT allelic variant genotypes and associated allele results, when used in conjunction with clinical findings and other laboratory tests, are intended as an aid in the diagnosis of individuals with A1AT deficiency (A1ATD).

The kit is indicated for prescription use only.

Alpha 1 antitrypsin (A1AT) Genotyping Test utilizes Luminex xMAP technology. Genomic DNA is extracted from DBS or from human K2-EDTA anticoaqulated whole blood. Extracted DNA is amplified and biotinylated by multiplex PCR and PCR products are denatured and hybridized to oligonucleotide probes coupled to color-coded beads. Hybridized DNA is labeled with a fluorescent conjugate and the resulting signal is detected with a Luminex® 200 system. Raw data obtained is processed with the A1AT Genotyping Test ANALYSIS SOFTWARE in order to obtain the final report. The A1AT Genotyping Test ANALYSIS SOFTWARE algorithm converts the allelic variant genotypes into associated alleles, based on the current literature.

The A1AT Genotyping Test Kit is composed of 4 reagent components (A1AT PCR Master Mix, A1AT Beads Master Mix, SAPE, SAPE Dilution Buffer) required to perform all the above mentioned processing steps, and a CD containing the A1AT Genotyping Test ANALYSIS SOFTWARE and other necessary files. Two kit configurations are available: for 48 or for 192 tests (different amounts of the same reagent components are provided in each case).

Here's a breakdown of the acceptance criteria and study information for the A1AT Genotyping Test, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The FDA summary does not explicitly list "acceptance criteria" but rather presents the results of various performance studies. The reported performance implies the acceptance criteria were met for each category.

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

The "test set" for the primary method comparison study consisted of 116 DNA samples.

• Data Provenance:
  • Clinical Samples: 66 samples, type not specified (retrospective/prospective, country of origin not specified).
  • Genomic DNAs from Cell Lines: 46 samples, type not specified.
  • Synthetic DNA Samples: 4 samples, type not specified.

For the External Reproducibility study, 17 samples were used (5 collected in DBS, 11 archived genomic DNA samples, and 1 synthetic sample). These were tested at external sites in the USA (LifeShare Blood Center and Progenika Inc.) and Italy (University of Pavia). This suggests a mix of prospective and retrospective data, depending on the nature of the archived samples.

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

The ground truth for the test set in the Method Comparison study was established by bi-directional Sanger sequencing. This is a laboratory-based method of genetic sequencing and does not involve human experts in the interpretation of the results to establish ground truth in the same way clinical image or pathology interpretation would. Therefore, the concept of "number of experts" or their "qualifications" is not directly applicable in this context.

4. Adjudication Method for the Test Set

Not applicable. The ground truth was established by bi-directional Sanger sequencing, which is an objective laboratory method, not subject to adjudication by multiple human readers.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, If So, What Was the Effect Size of How Much Human Readers Improve with AI vs without AI Assistance

No, an MRMC comparative effectiveness study was not done. This device is a diagnostic test for genetic variants, not an AI-assisted interpretation tool for human readers. Its performance is evaluated fundamentally as a standalone test against an established gold standard (Sanger sequencing).

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

Yes, a standalone performance study was done. The entire performance data presented (analytical and method comparison) reflects the performance of the A1AT Genotyping Test system (including the assay and its associated software) as a standalone diagnostic tool. The A1AT Genotyping Test ANALYSIS SOFTWARE algorithm converts the allelic variant genotypes into associated alleles.

7. The Type of Ground Truth Used

The primary ground truth used for the method comparison study was bi-directional Sanger sequencing, a molecular biology technique considered a gold standard for genetic sequence verification.

8. The Sample Size for the Training Set

The document does not specify a training set size. As a diagnostic test that relies on PCR and hybridization, it is unlikely to have a "training set" in the machine learning sense. The device's underlying chemistry and software algorithm are likely developed and validated using a different process than data-driven AI models.

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

Not applicable, as a "training set" in the context of machine learning for an AI algorithm is not explicitly mentioned or implied for this device. The development of the assay and its software would involve standard molecular biology and software engineering validation processes.

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The Human α1-antitrypsin Kit for use on SPAPLUs is designed for the quantitative in vitro determination of a1-antitrypsin in human serum using the SPAPLus turbidimetric analyzer. The measurement of a1- antitrypsin aids in the diagnosis of several conditions including adult cirrhosis of the liver. In addition, a1- antitrypsin deficiency has been associated with pulmonary emphysema. This test should be used in conjunction with other laboratory and clinical findings.

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The provided document is a 510(k) clearance letter from the FDA for the "Human alpha-1 Antitrypsin Kit for use on SPAPLUS". It states that the device is substantially equivalent to a predicate device. However, it does not contain any information about the acceptance criteria, study details, performance data, sample sizes, ground truth establishment, or expert involvement as requested in the prompt.

Therefore, I cannot provide the requested information based on the input document.

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The HYDRAGEL 18 A1AT ISOFOCUSING kit is designed for the qualitative detection and identification of the different phenotypes of Alpha-1 antitrypsin (A1AT). Phenotyping results in conjunction with clinical findings and other laboratory assays aid in the diagnosis of Alpha-1 antitrypsin deficiency The analysis is performed on human sera separated into electrophoretic patterns ready for qualitative analysis. The procedure includes isoelectrofocusing on agarose gel, performed on the semi-automatic HYDRASYS system, followed by immunofixation with anti-Alpha-1 antitrypsin antiserum. The use of enzyme labeled anti-Alpha-1 antiserum enhanced the detection and identification of the different phenotypes.

The configurations of the HYDRAGEL 18 A1AT ISOFOCUSING kit consist of the components summarized in Tables I and II in main 510(k) submission. Each kit is supplied with Package Insert which contains instruction for use and all the necessary information on the reagents needed to run the tests that are sold separately. Each Package Insert also contains information on storage conditions, shelf-life and signs of deterioration of the kit components and the reagents sold separately, and on interpretation of the results.

The provided 510(k) summary for the SEBIA HYDRAGEL 18 A1AT ISOFOCUSING kit describes a traditional IVD device, not an AI/ML device. Therefore, the concepts of acceptance criteria for AI algorithms, sample sizes for test/training sets, expert ground truth establishment, MRMC studies, or standalone algorithm performance are not applicable in their usual sense.

The submission focuses on demonstrating substantial equivalence to a predicate device for the qualitative detection and identification of Alpha-1 antitrypsin (A1AT) phenotypes. The "acceptance criteria" here relate to the device showing comparable performance to the predicate method.

Here's an interpretation based on the given information, adapted for an IVD device submission:

1. Table of Acceptance Criteria and Reported Device Performance

The submission does not explicitly state quantitative acceptance criteria in the typical sense of sensitivity/specificity/accuracy thresholds that an AI/ML algorithm might have. Instead, the acceptance criterion implicitly is "substantial equivalence" to the predicate device. The performance is demonstrated through concordance and reproducibility studies.

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

The exact sample size for the concordance study (which would act as the "test set" for equivalence) is not explicitly stated in the provided text. The document mentions "Performance study and comparisons of the HYDRAGEL 18 A1AT ISOFOCUSING KITS with polyacrylamide gels isoelectric focusing and comassie blue staining was done." and "Data are presented documenting substantial equivalency...".

• Sample Size for Test Set: Not explicitly provided.
• Data Provenance: Not explicitly stated, though the comparative predicate technique is described as "currently used in clinical diagnostic laboratories in the United States." This suggests the comparison data would likely derive from similar clinical settings. The nature of the study (comparison to an existing method) suggests it would be retrospective as it's comparing against previously characterized samples or existing results.

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

Since this is a laboratory assay where the "ground truth" is established by a predicate analytical method (polyacrylamide gel isoelectric focusing with Coomassie Blue staining), the concept of "experts" establishing ground truth in the traditional sense of clinical opinion is not directly applicable. The "ground truth" here is the result obtained from the well-established predicate method. The reading and interpretation of the gels would likely be performed by trained laboratory personnel, but no specific number or qualification of "experts" is provided for this purpose.

4. Adjudication Method for the Test Set

As the "ground truth" is based on a laboratory analytical predicate method, an adjudication method (like 2+1, 3+1 typically used for discordant expert opinions) is not applicable. The comparison is between the new device's output and the predicate device's output. Any discrepancies would be investigated as part of the validation, not adjudicated through consensus of human readers.

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

No, an MRMC comparative effectiveness study was not done, as this is an IVD device and not an AI/ML diagnostic system requiring human interpretation as the primary endpoint. The device performs a laboratory test resulting in an electrophoretic pattern. The evaluation is on the accuracy of this pattern generation and its agreement with a predicate method, not on how human readers' diagnostic accuracy improves with or without an AI assist.

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

Yes, in a sense, a standalone performance was done. The device itself (HYDRAGEL 18 A1AT ISOFOCUSING kit on the HYDRASYS system) produces the electrophoretic patterns, which are then "evaluated visually." The core performance assessment is on the kit's ability to accurately produce these patterns, independent of human interpretation variability. The concordance study compares the patterns generated by the new device to those from the predicate device. While visual evaluation by a human is involved in reading the gels, the primary focus of the performance assessment is on the analytical capability of the device to produce patterns that are substantially equivalent to the predicate.

7. The Type of Ground Truth Used

The ground truth used is the results obtained from a legally marketed predicate device/method: polyacrylamide gel isoelectric focusing followed by Coomassie Blue staining, which is described as a "technique currently used in clinical diagnostic laboratories." This is essentially a "predicate analytical method" ground truth.

8. The Sample Size for the Training Set

The concept of a "training set" is not applicable for this type of conventional IVD submission. The device is a chemical reagent kit for a laboratory procedure, not an algorithm that learns from data.

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

As there is no "training set" for this conventional IVD device, this question is not applicable.

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Dimension Vista™ A1AT Flex® reagent cartridge:
The A1AT method is an in vitro diagnostic test for the quantitative determination of a - antitrypsin in human serum, heparinized plasma or EDTA plasma on the Dimension Vista® System. Measurements of a-antitrypsin aid in the diagnosis of cirrhosis of the liver and pulmonary emphysema.

Dimension Vista™ Protein 1 Calibrator
PROT1 CAL is an in vitro diagnostic product for the calibration of the a1antitrypsin (A1AT), C3 Complement (C3), C4 Complement (C4), Immunoglobulin A (IGA), Immunoglobulin G (IGG), Immunoglobulin M (IGM), and Prealbumin (PREALB) methods on the Dimension Vista® System.

Dimension Vista™ Protein 1 Control L. M and H
PROT1 CON L, M and H are assayed intralaboratory quality controls for assessment of precision and analytical bias in the determination of α1-antitrypsin (A1AT), C3 Complement (C3), C4 Complement (C4), immunoglobulin A (IGA), immunoglobulin G (IGG), immunoglobulin M (IGM), and prealbumin (PREALB) on the Dimension Vista® System.

Dimension Vista" A1AT Flex® reagent cartridge
Proteins contained in human body fluids form immune complexes in an immunochemical reaction with specific antibodies. These complexes scatter a beam of light passed through the sample. The intensity of the scattered light is proportional to the concentration of the respective protein in the sample. The result is evaluated by comparison with a standard of known concentration.

Dimension Vista™ Protein 1 Calibrator
Protein 1 Calibrator is a multi-analyte, liquid, human serum based product containing a1antitrypsin (A1AT). C3 complement, C4 complement, immunoglobulin A (IGA). immunoglobulin G (IGG), immunoglobulin M (IGM) and prealbumin (PREALB).

Dimension Vista" Protein 1 Control L. M and H
Protein 1 Control L, M and H are multi-analyte, liguid, human serum based products containing a1-antitrypsin (A1AT), C3 complement, C4 complement, immunoglobulin A (IGA), immunoglobulin G (IGG), immunoglobulin M (IGM) and prealbumin (PREALB).

Here's an analysis of the provided text regarding the acceptance criteria and study for the Dimension Vista" A1AT Flex® reagent cartridge:

Acceptance Criteria and Device Performance Study

The submission focuses on establishing substantial equivalence for the Dimension Vista™ A1AT Flex® reagent cartridge by comparing its performance to a legally marketed predicate device, the Dade Behring N Antisera to Human α1-Antitrypsin assay on the BN ProSpec® System. The primary method used to demonstrate this is a method comparison study.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for substantial equivalence in this context are typically demonstrated through strong correlation and agreement between the new device and the predicate device. While explicit numerical acceptance criteria (e.g., minimum correlation coefficient, maximum allowable bias) are not directly stated as "acceptance criteria" in the provided document, they are implied by the reported results and the conclusion of equivalence.

For the purpose of this analysis, I will infer the performance metrics from the Method Comparison Study as the "reported device performance," which implicitly met the internal or regulatory acceptance thresholds for demonstrating equivalence.

Conclusion from document: "These studies demonstrate correlation and equivalent performance between the Dade Behring N Antisera to Human α-Antitrypsin assay and the Dimension Vista™ A1AT assay."

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

• Test Set Sample Size: 139 samples.
• Data Provenance: The document does not explicitly state the country of origin or whether the data was retrospective or prospective. It only mentions "evaluating serum and plasma samples." Given the nature of a 510(k) submission for an in vitro diagnostic, these samples would typically come from human subjects, either collected retrospectively or prospectively for the purpose of the study. Without further information, we cannot definitively classify the provenance.

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

This type of submission for an in vitro diagnostic (IVD) assay typically relies on a "predicate device" as the gold standard or reference for comparison, rather than expert consensus on individual cases. The "ground truth" for the test set is established by the results obtained from the predicate device (Dade Behring N Antisera to Human α1-Antitrypsin assay on the BN ProSpec® System). Therefore, there were no human "experts" establishing a ground truth in the traditional sense of clinical diagnosis or interpretation for this specific method comparison.

4. Adjudication Method

As the "ground truth" or reference method is another automated IVD assay, there is no adjudication method described or necessary in the sense of resolving discrepancies between human readers or interpretations. The comparison is between two quantitative analytical measurements.

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

No, an MRMC comparative effectiveness study was not done. This type of study (MRMC) is relevant for diagnostic imaging devices or other tests that involve human interpretation and reader variability. For an automated in vitro diagnostic assay like the Dimension Vista™ A1AT Flex® reagent cartridge, the performance is assessed by analytical comparison to a predicate method, not by comparing human reader performance with and without AI assistance.

6. Standalone Performance Study

Yes, a standalone performance study was implicitly done. The "Method Comparison Study" directly evaluates the performance of the Dimension Vista™ A1AT assay (the new device, effectively "standalone" in its measurement capability) against a predicate device. The reported slope, intercept, and correlation coefficient are standard metrics for evaluating the analytical performance of an IVD assay by itself when compared to a reference method, without human intervention in the measurement process itself.

7. Type of Ground Truth Used

The ground truth used for the comparison was the results obtained from a legally marketed predicate in vitro diagnostic assay (Dade Behring N Antisera to Human α1-Antitrypsin assay on the BN ProSpec® System). This is a common and accepted method for establishing equivalence for new IVD assays.

8. Sample Size for the Training Set

This information is not provided. The document describes a "Method Comparison Study" for the new device against a predicate. For IVD assays, there wasn't a separate "training set" in the context of machine learning, and the study doesn't mention how the assay itself (e.g., reagent formulation, instrument parameters) was developed or optimized. The 139 samples were used for the performance evaluation, not to "train" an algorithm.

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

As there is no mention of a "training set" or a machine learning component for this traditional IVD reagent cartridge, this question is not applicable in the context of the provided document. The assay's analytical principles are based on known immunochemical reactions, and its calibration would be established using calibrators with known concentrations (as mentioned for the Dimension Vista™ Protein 1 Calibrator), not through a "training set" and ground truth in the AI sense.

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In vitro diagnostic reagents for the quantitative determination of a -antitrypsin in human serum, heparinized and EDTA plasma by means of immunonephelometery on the BN™ Systems. The measurement of a-antitrypsin aids in the diagnosis of several conditions including adult cirrhosis of the liver. In addition, a r-antitrypsin deficiency has been associated with pulmonary emphysema in conjunction with other laboratory and clinical findings.

Proteins contained in human body fluids form immune complexes in an immunochemical reaction with specific antibodies. These complexes statter a beam of light passed through the sample. The intensity of the scattered light is proportional to the concentration of the relevant protein in the sample. The result is evaluated by comparison with a standard of known concentration.

This document describes the N Antisera to Human α-Antitrypsin Assay, an in vitro diagnostic reagent for the quantitative determination of alpha-1-antitrypsin (α1-AT) in human serum, heparinized, and EDTA plasma using immunonephelometry on the BN™ Systems.

1. Acceptance Criteria and Reported Device Performance:

The document does not explicitly state pre-defined acceptance criteria in terms of numerical thresholds for a specific performance metric. Instead, the "device performance characteristics" section in the K053072 summary focuses on demonstrating equivalence in measurement between different sample types (serum, heparinized plasma, and EDTA plasma) and to a legally marketed predicate device.

The reported device performance is based on method comparison studies:

Study Proving Acceptance Criteria:

The study proving the device meets its implied acceptance criteria of equivalence was a method comparison study.

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

• Sample Size: The document does not specify the exact sample size for the test set used in the method comparison studies. It only states that "method comparisons were performed."
• Data Provenance: The document does not explicitly state the country of origin of the data or whether the study was retrospective or prospective. Given that the manufacturer is based in Germany (Dade Behring Marburg GmbH) and the contact information for regulatory submission is in the US (Dade Behring Inc.), the data could be from various global sites.

3. Number of Experts Used to Establish Ground Truth and Qualifications:

Not applicable. This device is an in vitro diagnostic reagent for quantitative measurement of a biomarker. The "ground truth" for method comparison studies would typically be the results obtained from a reference method or the established predicate device, not expert consensus on qualitative interpretation.

4. Adjudication Method:

Not applicable. As described above, this is a quantitative measurement, and adjudication by experts is not a relevant component of its validation.

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

Not applicable. An MRMC study is relevant for devices that involve human interpretation of images or other qualitative data, particularly in the context of diagnostic accuracy. This device is an automated quantitative reagent.

6. Standalone Performance Study:

Yes, a standalone performance study was conducted in the sense that the device's analytical performance (specifically, its ability to yield comparable quantitative results across different sample matrices) was evaluated intrinsically. The method comparison studies demonstrated the performance of the algorithm/reagent by itself in generating the quantitative alpha-1-antitrypsin values. This means the analytical performance of the device without human interpretation was assessed.

7. Type of Ground Truth Used:

The "ground truth" for the method comparison studies would be the quantitative results obtained from:

• Measurements using the predicate device (N Antisera to Human α-Antitrypsin, K860894), for establishing substantial equivalence.
• Measurements from serum samples when comparing performance with heparinized and EDTA plasma. This implies that serum is considered the primary, well-established matrix for α1-AT determination against which other matrices are compared.

8. Sample Size for the Training Set:

Not applicable. This device is a reagent for an immunonephelometry system. It is not an AI/ML algorithm that requires a "training set" in the conventional sense of machine learning. The "training" of such a system would involve calibration curves and reagent optimization, which are part of the manufacturing and method development process, not a distinct training set for an algorithm.

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

Not applicable, as there is no "training set" in the context of an AI/ML algorithm. The calibration and optimization of the reagent and system would follow established laboratory practices for IVD assays, using certified reference materials or well-characterized control sera with known α1-AT concentrations to establish calibration curves. This is an analytical validation process, not a ground truth establishment for a training set.

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For in vitro diagnostic use only. VITROS Chemistry Products AAT Reagent is used to quantitatively measure α₁-antitrypsin concentration in human serum. The measurement of α₁-antitrypsin in serum aids in the diagnosis of cirrhosis of the liver and pulmonary emphysema.

For in vitro diagnostic use only. VITROS Chemistry Products Calibrator Kit 99 is used to calibrate VITROS 5,1 FS Chemistry Systems for the quantitative measurement of α₁-antitrypsin (AAT).

For in vitro diagnostic use only. VITROS Chemistry Products AAT Performance Verifiers are assayed controls used to monitor performance of VITROS AAT Reagents on VITROS 5,1 FS Chemistry Systems.

The VITROS Chemistry Products AAT Reagent is used in conjunction with the VITROS Chemistry Products Calibrator Kit 99 and VITROS Chemistry Products FS Diluent Pack 2 (BSA/Saline) on VITROS 5,1 FS Chemistry Systems for the quantitative measurement of α₁-antitrypsin (AAT) in human serum.

The VITROS AAT Reagent is a dual chambered package containing ready-to-use liquid reagents. Samples, calibrators and controls are automatically diluted in saline from VITROS FS Diluent Pack 2 and mixed with Reagent 1 containing a polymer. Addition of antisera specific for human α₁-antitrypsin (Reagent 2) produces an immunochemical reaction yielding antigen/antibody complexes. The light scattering properties of the antigen/antibody complexes increase solution turbidity proportional to α₁-antitrypsin concentration in the sample. The turbidity is measured spectrophotometrically at 340 nm. Once a calibration has been performed for each reagent lot, the a1-antitrypsin concentration in each unknown sample can be determined using the stored calibration curve and the measured absorbance obtained in the assay of the sample.

The VITROS Chemistry Products Calibrator Kit 99 are prepared from processed human serum to which inorganic salts, buffers, and preservatives have been added. These standards are used to calibrate VITROS 5,1 FS Chemistry Systems for the quantitative measurement of α₁-antitrypsin (AAT).

The VITROS Chemistry Products FS Diluent Pack 2 (BSA/Saline) is a common reagent that is used by multiple assays on the VITROS 5,1 FS System. This is a dual chambered package containing two ready-to-use liquid diluents. Diluent 1 is prepared from processed water to which inorganic salt has been added. Diluent 2 is prepared from processed water to which bovine serum albumin, inorganic salts and preservatives have been added.

The VITROS 5,1 FS Chemistry System is a clinical chemistry instrument that provides automated use of the VITROS Chemistry Products MicroTip® and MicroSlides® range of products. The VITROS 5,1 FS System was cleared for market by 510(k) premarket notification (K031924).

The VITROS Chemistry Products AAT Performance Verifiers I, II and III are prepared from processed human serum to which inorganic salts, buffers, and preservatives have been added. These are assayed controls used to monitor performance of VITROS AAT Reagent on VITROS 5,1 FS Chemistry Systems.

Here's an analysis of the acceptance criteria and supporting studies for the VITROS Chemistry Products AAT Reagent, Calibrator Kit 99, and Performance Verifiers, based on the provided text.

Note: This document describes an in vitro diagnostic device, not an AI/ML-driven medical device for image analysis as might be typical for some of these questions. Therefore, some of the requested categories (e.g., number of experts for ground truth, adjudication method, MRMC study, sample size for training set) are not directly applicable or are not explicitly detailed in the provided text for this type of device. I will address the relevant sections and note when information is not present or applicable.

1. Table of Acceptance Criteria and Reported Device Performance

The provided 510(k) summary focuses on demonstrating substantial equivalence to a predicate device rather than setting explicit, quantifiable acceptance criteria with specific performance targets (like sensitivity/specificity for clinical decisions). Instead, performance is shown through correlation and comparison to the predicate.

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

• Test Set Sample Size: The document mentions that equivalence was demonstrated "using a commercially available assay along with patient samples." However, the exact number of patient samples used in the correlation studies (test set) is not specified in the provided text.
• Data Provenance: The data provenance is stated as "patient samples," but the country of origin or whether it was retrospective or prospective data is not specified.

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

This question is not applicable in the context of this in vitro diagnostic device. The "ground truth" for an AAT assay would typically be established by comparing its results to a well-established reference method or a predicate device on patient samples, based on quantitative measurements rather than expert interpretation of images or clinical cases.

4. Adjudication Method for the Test Set

This question is not applicable for this in vitro diagnostic device. Adjudication methods like 2+1 or 3+1 are typically used for subjective assessments (e.g., image interpretation where experts disagree), not for quantitative chemical measurements.

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. MRMC studies are typically used for diagnostic imaging devices where human readers interpret cases, and performance with/without AI assistance is evaluated. This document describes a chemical assay, not an imaging device with human readers.

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

Yes, a standalone performance study was done. The entire submission describes the performance of the VITROS AAT assay system (reagent, calibrator, verifiers, and instrument) as a standalone device to measure α₁-antitrypsin concentration in human serum. Its performance is compared to a predicate device and validated through various bench tests (specificity, expected values, limit of detection, dilution, specimen matrix). The "algorithm" in this context is the immunoturbidimetric chemical reaction and the spectrophotometric measurement by the VITROS 5,1 FS Chemistry System.

7. The Type of Ground Truth Used

The ground truth for validating the VITROS Chemistry Products AAT assay was established through comparison to a predicate device (IMMAGE® Immunochemistry Systems AAT assay) using patient samples, and through bench testing for various analytical performance characteristics (specificity, limit of detection, etc.). For a quantitative chemical assay, the "ground truth" is typically a known, well-characterized value or the result obtained from a recognized reference method.

8. The Sample Size for the Training Set

The document does not explicitly mention a "training set" in the context of an AI/ML algorithm. For an IVD assay like this, product development involves a series of experiments and optimizations to establish reagent formulations, calibration curves, and analytical procedures. The phrase "training set" doesn't directly apply in the same way it would for AI model development. The development data used to optimize the assay would implicitly serve this purpose, but its sample size is not specified.

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

As noted above, the concept of a "training set" ground truth as applied to AI/ML isn't directly applicable here. The development of the assay would involve establishing the expected concentrations of AAT in various samples, using reference methods or characterized materials, to ensure the assay accurately measures the analyte. The specific methodology or exact sample sizes for this developmental phase are not provided in the summary.

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The Quantia A1-AT is intended for the in vitro quantitative determination of alpha-1-antitrypsin concentration in human serum or plasma (heparin with or without gel separator, EDTA) on the AEROSET® system as an aid in the diagnosis of juvenile and adult cirrhosis of the liver and pulmonary emphysema.

Quantia PROTEINS Control is intended for use in monitoring the quality control of results obtained with the Quantia A1-AT reagents by turbidimetry. (NOTE: This control has been also FDA 510(k) submitted for use with Quantia Beta-2 Microglobulin). For in vitro diagnostic use.

Quantia PROTEINS standard is intended for use in establishing the calibration curve for the Quantia A1-AT reagents by turbidimetry. For in vitro diagnostic use.

The Quantia A1-AT is intended for the in vitro quantitative determination of alpha-1-antityypsin concentration in human serum or plasma (heparin with or without gel separator, EDTA) on the AEROSET® system as an aid in the diagnosis of juvenile and adult cirrhosis of the liver and pulmonary emphysema.

Quantia PROTEINS Control is intended for use in monitoring the quality control of results obtained with the Quantia A1-AT reagents by turbidimetry. (NOTE: This control has been also FDA 510(k) submitted for use with Quantia Beta-2 Microglobulin). For in vitro diagnostic use.

Quantia PROTEINS standard is intended for use in establishing the calibration curve for the Quantia A1-AT reagents by turbidimetry. For in vitro diagnostic use.

Here's an analysis of the provided text regarding the Quantia A1-AT device, structured to answer your questions about acceptance criteria and the supporting study:

Acceptance Criteria and Device Performance

1. A table of acceptance criteria and the reported device performance

Note on Acceptance Criteria: The document primarily focuses on demonstrating "substantial equivalence" to a predicate device. For in-vitro diagnostic devices like this, substantial equivalence means demonstrating that the new device is as safe and effective as a legally marketed predicate device. This typically involves showing comparable performance across key metrics. The specific numerical acceptance criteria (e.g., minimum 'r' value, maximum CV%) are not explicitly stated in the summary but are implied by the successful demonstration of substantial equivalence and the comparison to the predicate. The provided performance data (slope, correlation, precision) would have met the FDA's unstated, but understood, thresholds for equivalence.

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

• Sample Size (Test Set): 111 samples
• Data Provenance: Not explicitly stated. The submitting company (Biokit S.A.) is located in Barcelona, Spain. It's not clear from this summary if the samples themselves were from Spain, generated in specific clinical settings, or their origin. It is also not specified if the study was retrospective or prospective.

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

• This device is an in-vitro diagnostic test for quantitative determination of alpha-1-antitrypsin concentration. The "ground truth" in this context is established by the predicate device's measurement and the assigned values of control materials, not by expert human interpretation of images or other subjective assessments.
• Therefore, the concept of "experts" to establish ground truth as described in the prompt (e.g., radiologists) is not applicable here. The comparison is made against the performance of an established, legally marketed device (N Antisera to Human alpha-1-Antitrypsin) and standardized control materials with known A1-AT levels.

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

• Not applicable. This is not a study involving human interpretation or adjudication of cases. The comparison is between the quantitative results of two different assay methods (the new device vs. the predicate device).

5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

• No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This device is an automated in-vitro diagnostic test, not an AI-assisted diagnostic tool that would involve human readers.

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

• Yes, the performance study effectively represents a "standalone" assessment of the device's accuracy and precision. The "method comparison study" directly compares the results of the Quantia A1-AT system (algorithm/reagents only) to the predicate device's results. The precision studies also evaluate the device in isolation, without human-in-the-loop performance influencing the measurement itself.

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

• The "ground truth" for the method comparison study was the results obtained from the predicate device (N Antisera to Human alpha-1-Antitrypsin). For the precision studies, the ground truth was the known, assigned values of the control materials (Low Control, Control (I + II), High Control).

8. The sample size for the training set

• The document does not mention a separate "training set." For an in-vitro diagnostic device like this, the development process (which would include internal validation and optimization) would involve various samples, but a distinct "training set" in the machine learning sense is not typically described in 510(k) summaries for such devices unless AI/ML is a core component, which is not the case here. The 111 samples described were for the performance evaluation (test set) to demonstrate equivalence.

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

• Not applicable, as a distinct "training set" in the context of an AI/ML system with its associated ground truth establishment is not mentioned or relevant for this type of device. The device's calibration and performance would be based on established reference materials and comparison to a predicate, rather than a "training set" with expert-derived ground truth.

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