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The QMS® Everolimus Assay is intended for the quantitative determination of Everolimus in human whole blood on automated clinical chemistry analyzers. The results obtained are used as an aid in the management of kidney and liver transplant patients receiving Everolimus therapy. This in vitro diagnostic device is intended for clinical laboratory use only.

The QMS® Everolimus Assay consists of separately packaged reagents (R1, R2, and Precipitation Reagent) with the following contents and configurations.
R1 Antibody Reagent: <1.0% Anti-Everolimus polyclonal antibody (rabbit) in a buffer as stabilizer and <0.09% sodium azide as preservative. 1 x 22 mL
R2 Microparticle Reagent: <0.6% Everolimus-coated microparticles in buffer containing <0.05% sodium azide as preservative. 1 x 8 mL
Precipitation Reagent: Precipitating reagent, and <0.09% sodium azide as preservative. 1 x 8 mL
The reagents are supplied ready-to-use in liquid form in plastic HDPE bottles, for storage at 2 to 8°C. The reagent set is sufficient for 100 tests.

Here's an analysis of the acceptance criteria and study findings for the Thermo Scientific QMS® Everolimus Assay, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

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

• Test Set Sample Size: The document does not explicitly state the total number of samples used for the "Method Comparison" study or for other performance tests like precision and linearity. It mentions "Everolimus samples were tested for precision" and "Samples were tested in the QMS® Everolimus Assay and compared to LC/MS."
• Data Provenance: The document does not provide details on the country of origin of the data or whether the data was retrospective or prospective.

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

This section is not applicable as the device is an in-vitro diagnostic assay for quantitative determination of a drug in human whole blood. The "ground truth" for method comparison and analytical performance is established by comparison to a reference method (LC/MS) or by known concentrations of the analyte in manufactured samples (e.g., calibrators, controls). It does not involve human expert interpretation of images or clinical data.

4. Adjudication method for the test set

This is not applicable for this type of in-vitro diagnostic device. Analytical studies like method comparison and precision do not typically involve adjudication by experts.

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. This device is an automated in-vitro diagnostic (IVD) assay, not an AI-powered diagnostic tool requiring human interpretation or an MRMC study.

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

This is essentially how the device operates. The QMS® Everolimus Assay is an automated clinical chemistry assay that provides quantitative results. Its performance (analytical sensitivity, precision, method comparison) is evaluated in a standalone manner, meaning the assay itself generates the readings, which are then used by clinicians for patient management. There isn't a "human-in-the-loop" for the direct measurement process itself, although clinicians interpret the results.

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

The ground truth for the analytical performance studies appears to be:

• LC/MS (Liquid Chromatography/Mass Spectrometry): For the "Method Comparison" study, LC/MS served as the reference method for determining Everolimus concentrations.
• Known Concentrations: For studies like Analytical Sensitivity (LDD), Functional Sensitivity (LOQ), Precision, and Dilution Recovery, the ground truth would be based on precisely prepared samples with known concentrations of Everolimus (e.g., calibrators, controls, spiked samples).

8. The sample size for the training set

This information is not provided in the summary. For an IVD assay like this, there isn't a traditional "training set" in the sense of machine learning algorithms. Instead, assay development involves extensive testing and optimization using various formulations and spiked samples to establish performance characteristics, rather than a distinct training/test split of clinical data.

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

As noted above, a distinct "training set" with ground truth in the machine learning sense is not explicitly described or typically applicable for IVD assay development. The "ground truth" during development and optimization would involve using:

• Reference standards: Pure Everolimus used to create calibrators and controls with known concentrations.
• LC/MS analysis: As a highly accurate reference method to verify concentrations in samples during development.
• Spiked samples: Whole blood samples spiked with known amounts of Everolimus to assess recovery and other analytical parameters.

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The Dimension® Mycophenolic Acid Flex® reagent cartridge is an in vitro diagnostic test for the quantitative measurement of Mycophenolic acid (MPA) in human plasma on the Dimension® clinical chemistry system. Measurements of MPA are used as an aid in the management of mycophenolic acid therapy in renal, hepatic, and cardiac transplant patients.
The Dimension® Mycophenolic Acid Calibrator is an in vitro diagnostic product for the calibration of the Mycophenolic Acid method on the Dimension® clinical chemistry system.

The liquid reagents are configured in an eight well "Flex®"; the content of each Flex® well is described in the Instructions for Use.
The methodology for the Dimension® MPAT assay is based on a homogenous particle enhanced turbidimetric inhibition immunoassay (PETINIA) technique, which uses a latex particle mycophenolic acid conjugate (PR) and monoclonal mycophenolic acid specific antibody (Ab). Mycophenolic acid present in the sample competes with the mycophenolic acid on the particles for available antibody, thereby decreasing the rate of aggregation. Hence, the rate of aggregation is inversely proportional to the concentration of mycophenolic acid in the sample. The rate of aggregation is measured using bichromatic turbidimetric readings at 340 nm and 700 nm.
The Dimension MPAT Calibrator is used to calibrate the MPAT assay on the Dimension system. The calibrator is a five level aqueous BSA matrix product containing Mycophenolic acid. The typical calibration levels for levels 1 through 5 respectively, are 0.0, 0.7, 2.3, 6.7 and 30.0 µg/mL. Level 1 is a zero level, and can be used to dilute samples that exceed 30 µg/mL.

Here's an analysis of the provided text to extract the requested information:

Acceptance Criteria and Device Performance Study

The submission focuses on establishing substantial equivalence rather than defining explicit acceptance criteria for a new clinical performance study. The core of the evidence relies on a split-sample comparison to demonstrate agreement with existing, validated methods.

1. Table of Acceptance Criteria and Reported Device Performance

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

• Sample Size: 109 clinical samples
• Data Provenance: Clinical samples from kidney, heart, and liver transplant patients. The country of origin is not specified but is implied to be clinical data. The study is retrospective, as it involves a "split sample comparison" with existing methods, suggesting these samples were collected and then tested by both new and reference methods.

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

• This study does not involve "experts" in the traditional sense of clinicians or radiologists establishing ground truth. Instead, the ground truth is established by reference methods (HPLC/LC-MS assays). The qualifications of the personnel performing these reference assays are not detailed, but it's assumed they are trained laboratory professionals.

4. Adjudication Method for the Test Set

• There was no explicit "adjudication method" described as this was a quantitative comparison against established laboratory reference methods (HPLC/LC-MS). Discrepancies between the new device and the reference method would be analyzed through statistical comparison rather than a consensus process involving multiple human adjudicators.

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

• No, an MRMC comparative effectiveness study was not done. This device is an in vitro diagnostic (IVD) test system, not an imaging or diagnostic AI system that would typically involve human readers. The performance is assessed by comparing quantitative results to a gold standard, not by evaluating human reader performance with or without AI assistance.

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

• Yes, the performance described is effectively "standalone" for the device, meaning it's the performance of the automated assay itself. There is no human-in-the-loop component in the measurement of mycophenolic acid by the Dimension® MPAT system. The device produces a quantitative result without human interpretation of the assay's execution, though a human would interpret the clinical significance of the numerical result.

7. The Type of Ground Truth Used

• Reference Method Assays: The ground truth was established by HPLC/LC-MS assays. These are considered gold standard methods for quantitative measurement of analytes like mycophenolic acid in clinical chemistry.

8. The Sample Size for the Training Set

• The document does not provide information regarding a separate "training set" or its size. For an IVD assay like this, the development process likely involves extensive internal optimization and verification using various samples, but these are generally not described as a distinct "training set" in the context of a 510(k) submission for an immunoassay. The presented data is for the validation of the finalized device.

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

• Since a specific "training set" is not detailed, this information is not provided. If such a phase existed, the ground truth would similarly be established by robust reference methods or gravimetric preparation of known concentration samples.

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The QMS® Everolimus assay is intended for the quantitative determination of everolimus, the active ingredient of Zortress®, in human whole blood on automated clinical chemistry analyzers. The results obtained are used as an aid in the management of kidney transplant patients receiving Everolimus therapy. This in vitro diagnostic device is intended for clinical laboratory use only.

The QMS Everolimus Calibrators set is intended for use in calibration of the QMS Everolimus Assay.

The QMS® Everolimus Controls set is intended for use in quality control of the QMS® Everolimus Assay.

The QMS® Everolimus Assay system is a homogeneous assay utilizing particle agglutination technology and competitive binding principles.

The acceptance criteria and study proving device performance are detailed below:

1. Table of Acceptance Criteria and Reported Device Performance

2. Sample Size and Data Provenance

• Test Set Sample Size: The document does not explicitly state the specific number of samples used for each performance test (e.g., Functional Sensitivity, Precision, Method Comparison, Dilution Recovery, Stability). For Method Comparison, it mentions "Samples were tested in the Everolimus Assay and compared to LC/MS."
• Data Provenance: The document does not specify the country of origin of the data or whether the data was retrospective or prospective.

3. Number and Qualifications of Experts for Ground Truth

• This information is not provided. The ground truth for comparative studies (e.g., Method Comparison) was established using LC/MS, which is an analytical method rather than relying on human expert consensus.

4. Adjudication Method

• Not applicable as the ground truth for the Method Comparison was LC/MS, an analytical technique, not expert consensus requiring adjudication.

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

• No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not performed. This device is an in vitro diagnostic assay, and its performance is evaluated against reference analytical methods (like LC/MS) or established precision protocols, not against human reader performance.

6. Standalone Performance Study

• Yes, a standalone performance study was done for the algorithm (assay). The performance metrics like Functional Sensitivity, Precision, Method Comparison, Dilution Recovery, and Stability are all assessments of the device's standalone analytical performance.

7. Type of Ground Truth Used

• For the Method Comparison study, the ground truth was LC/MS (Liquid Chromatography/Mass Spectrometry), which is a gold standard analytical method for quantifying Everolimus in biological samples.

8. Sample Size for the Training Set

• This information is not provided. The document describes an assay system, not a machine learning algorithm that requires a separate "training set" in the conventional sense. The "calibration" of the assay refers to establishing a standard curve with known concentrations, but the sample size for developing this calibration is not specified.

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

• For the assay's calibration (which can be considered analogous to training in a general sense for an analytical device), the QMS® Everolimus Assay's calibrators are "Traceable to calibration based on minimization of bias between the QMS assay and an LCMSMS assay for a specified adult renal transplant sample set." This means the ground truth for these calibrators was established by comparing them to results from an LC/MS/MS assay using a specific set of clinical samples.

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The Emit® 2000 Sirolimus Assay is for the in vitro quantitative analysis of sirolimus in human whole blood as an aid in the management of sirolimus therapy in kidney transplant patients.

The Emit® 2000 Siro/Tacro Sample Pretreatment Reagent is an accessory reagent for use with the Emit® 2000 Sirolimus Assay and/or the Emit® 2000 Tacrolimus Assay.

The Emit® 2000 Sirolimus Calibrators are intended for use in the calibration of the Emit® 2000 Sirolimus Assay.

The Emit® 2000 Sirolimus Assay is for in vitro diagnostic use for the quantitative analysis of sirolimus in human whole blood as an aid in the management of sirolimus therapy in kidney transplant patients. The Emit® 2000 Sirolimus Assay is comprised of an antibody reagent, a buffer reagent and an enzyme reagent. This assay contains mouse monoclonal antibodies with a high specificity for sirolimus.

The Emit® 2000 Siro/Tacro Sample Pretreatment Reagent is an accessory reagent for use with the Emit® 2000 Sirolimus Assay. The Emit® 2000 Siro/Tacro Sample Pretreatment Reagent is used to pretreat the whole blood samples, calibrators, and controls prior to testing with the Emit® 2000 Sirolimus Assay. The pretreatment process lyses the cells, extracts the sirolimus, and precipitates most of the blood proteins. The pretreated samples are centrifuged, and an aliquot of the resulting supernatant containing sirolimus is then assayed using the Emit® 2000 Sirolimus Assay.

The Emit® 2000 Sirolimus Calibrators are frozen material containing sirolimus in preserved whole blood hemolysate. There are six (6) calibrator levels containing 0, 3, 6, 12, 24 and 36 ng/mL.

Here's a breakdown of the acceptance criteria and study information for the Emit® 2000 Sirolimus Assay, Emit® 2000 Siro/Tacro Sample Pretreatment Reagent, and Emit® 2000 Sirolimus Calibrator, based on the provided text:

1. Acceptance Criteria and Reported Device Performance

Note: The document does not explicitly state pre-defined acceptance criteria values for slope, intercept, or correlation coefficient. However, the reported values are presented as the "result" of the study, implying they met the internal criteria for substantial equivalence to the predicate device and the reference method (LC/MS/MS).

2. Sample Size and Data Provenance

• Test Set Sample Size: 128 samples
• Data Provenance: Samples were from kidney transplant patients and were collected from two external sites. The document does not specify the country of origin, but it implies a clinical setting.
• Retrospective or Prospective: The document does not explicitly state whether the study was retrospective or prospective. Given that samples from kidney transplant patients were used and compared against LC/MS/MS, it is likely a retrospective analysis of existing patient samples where Sirolimus levels were measured by both methods, or a prospective collection for the purpose of the study.

3. Number of Experts and Qualifications for Ground Truth

The concept of "experts" to establish ground truth in the context of diagnostic assay comparison is typically applied when the ground truth is subjective (e.g., image interpretation). For this device, which measures a quantitative analyte (Sirolimus), the ground truth is established by a reference method (LC/MS/MS), not by human experts interpreting results. Therefore, this section is not directly applicable in the way it would be for, say, a radiology AI device.

4. Adjudication Method for the Test Set

Not applicable. As described above, the ground truth was established by LC/MS/MS, a laboratory reference method, not by human interpretation requiring adjudication.

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

No, an MRMC comparative effectiveness study was not conducted or described. This type of study focuses on comparing the diagnostic performance of human readers, with and without AI assistance, on multiple cases. The Emit® 2000 Sirolimus Assay is a standalone in vitro diagnostic device, not an AI-assisted interpretation system for human readers.

6. Standalone Performance Study

Yes, a standalone performance study was done. The method comparison study directly evaluated the performance of the Emit® 2000 Sirolimus Assay against the LC/MS/MS reference method. This assesses the algorithm's (assay's) performance without human-in-the-loop interaction for result generation, although human operators perform the assay.

7. Type of Ground Truth Used

The type of ground truth used was comparison to a reference method: Liquid Chromatography/Mass Spectrometry/Mass Spectrometry (LC/MS/MS). LC/MS/MS is considered a "gold standard" or highly accurate method for quantifying Sirolimus in biological samples.

8. Sample Size for the Training Set

The document does not mention a training set or its sample size. This is a common characteristic of traditional in vitro diagnostic assays, which are developed and validated through analytical studies and method comparisons, rather than "trained" in the machine learning sense. The assay relies on specific reagents (antibodies, enzymes) designed for Sirolimus detection.

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

Not applicable, as no distinct "training set" in the machine learning context is mentioned or implied for this device. The development and optimization of such assays typically involve extensive analytical studies using characterized samples, but these are not referred to as a "training set" with ground truth established in the same manner as for AI/ML algorithms.

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The CEDIA Mycophenolic Acid Assay is an in vitro diagnostic medical device intended for the quantitative measurement of mycophenolic acid in human plasma using automated clinical chemistry analyzers as an aid in the management of mycophenolic acid therapy in renal and cardiac transplant patients.

The CEDIA Mycophenolic Acid Calibrators are intended for use in the calibration of the CEDIA MPA Assay.

The MAS Mycophenolic Acid Controls are intended for use as assayed quality control material for validation of MPA assays.

The CEDIA Mycophenolic Acid Assay is a homogeneous assay based on the enzyme ()-galactosidase, which has been genetically engineered into two inactive fragments termed enzyme donor (ED) and enzyme acceptor (EA). These fragments spontaneously re-associate to form fully active enzymes that, in assay format, cleave a substrate, generating a color change that can be measured spectrophotometrically.

The assay consists of a set of four reagents: Enzyme Acceptor Buffer, Enzyme Acceptor Reagent, Enzyme Donor Buffer, and Enzyme Donor Reagent. A two-level (Low and High) set of calibrators is used to calibrate the assay. A three-level set of controls (1 through 3) is used for quality control of the assay.

Here's an analysis of the provided text regarding the acceptance criteria and study for the CEDIA Mycophenolic Acid Assay:

This submission is a 510(k) premarket notification for a new in vitro diagnostic (IVD) device, the CEDIA® Mycophenolic Acid Assay. The primary purpose of a 510(k) is to demonstrate that the new device is "substantially equivalent" to a legally marketed predicate device. Therefore, the "acceptance criteria" for this submission are not expressed as specific performance thresholds for sensitivity, specificity, etc., as one might find in an AI/software device submission for an imaging modality. Instead, the acceptance criteria are implicitly that the device performs comparably to the predicate device across various technological characteristics. The study presented is a "performance testing" to verify that the device functions as intended and that design specifications have been satisfied, in comparison to the predicate.

Here's the information as requested, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

Given that this is a 510(k) for an in vitro diagnostic device seeking substantial equivalence to a predicate, the "acceptance criteria" are the functional and performance characteristics of the predicate device that the new device aims to match or be comparable to. The reported "device performance" is how the new device measures up against those characteristics. The document doesn't provide specific quantitative acceptance ranges for parameters like analytical sensitivity or precision, but rather a direct comparison of the characteristics.

Conclusion on Acceptance: The document explicitly states: "As summarized, the CEDIA Mycophenolic Acid Assay is substantially equivalent to the Roche Total Mycophenolic Acid assay. Substantial equivalence has been demonstrated through performance testing to verify that the device functions as intended and that design specifications have been satisfied." This indicates that the device met the implicit acceptance criteria of being comparable to the predicate for the purpose of a 510(k) clearance.

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

The provided text does not explicitly state the sample size used for the performance testing (test set) or the data provenance (e.g., country of origin, retrospective or prospective). For IVD devices, such studies would typically involve a certain number of patient samples, but this detail is not present in the summary.

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

This information is not applicable and therefore not provided in the document. For an IVD assay measuring a chemical compound (mycophenolic acid), the "ground truth" is typically established by reference methods (e.g., mass spectrometry, HPLC) or by the performance of the predicate device itself, not by expert human graders or clinicians evaluating images.

4. Adjudication Method for the Test Set

This information is not applicable and therefore not provided in the document. Adjudication methods like 2+1 or 3+1 are relevant for tasks involving subjective human interpretation (e.g., radiology reads), which is not the case for a quantitative chemical assay.

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

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study is relevant for imaging devices where multiple human readers interpret cases. For an IVD assay, the comparison is directly between the new assay's quantitative results and those of a predicate device or reference method.

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

The device itself is a standalone algorithm/assay in the context of its function, meaning it directly measures mycophenolic acid concentration. The performance testing outlined in the 510(k) (though not detailed here) would be analogous to a "standalone" evaluation of the assay's accuracy, precision, linearity, and other analytical performance characteristics against established laboratory standards or the predicate device. There is no human "in-the-loop" for the measurement process itself, although clinicians use the results in patient management.

7. The Type of Ground Truth Used

The "ground truth" for this type of IVD device is generally established by:

• Comparison to a legally marketed predicate device: The new device's results are compared to the predicate device's results using patient samples.
• Analytical performance studies: This involves assessing parameters like accuracy (recovery), precision (reproducibility), linearity, limit of detection, and interference studies against known standards or reference materials.
• In some cases for quantitative assays, reference methods (e.g., mass spectrometry, HPLC) are considered the "gold standard" for establishing true values.

The provided summary emphasizes substantial equivalence to the predicate device based on "performance testing," suggesting the predicate's results served as a primary reference for comparison.

8. The Sample Size for the Training Set

The provided text does not state the sample size for any "training set." For a traditional IVD assay like this, there isn't typically a "training set" in the machine learning sense. The assay is developed and optimized, and then its performance is validated in studies. If any statistical models or thresholds were optimized during development, those would involve internal R&D data, not a formally defined "training set" as understood in AI/ML contexts.

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

As there's no explicitly defined "training set" in the AI/ML sense, this information is not applicable and not provided. The development of the assay would have involved standard chemical and biochemical experimentation with known concentrations of mycophenolic acid and other substances to optimize the reagent formulations and reaction conditions.

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The SIRO method is an in vitro diagnostic test for the quantitative measurement of Sirolimus in human whole blood on the Dimension® clinical chemistry system. Measurements of Sirolimus are used as an aid in the management of sirolimus therapy in renal transplant patients.
The Sirolimus Calibrator is an in vitro diagnostic product for the calibration of Sirolimus (SIRO) on the Dimension® clinical chemistry system.

The automated Dimension® SIRO method uses an immunoassay technique in which free and sirolimus-bound antibody-enzyme conjugates are separated using magnetic particles. The assay is performed using a method specific Flex® reagent cartridge. The Flex® cartridge contains a pretreatment reagent, antibody-B-galactosidase conjugate, sirolimus immobilized on chromium dioxide particles, chlorophenol red ß-d-galactopyranoside (CPRG) substrate, and diluent to hydrate the tablets.
To perform the SIRO assay, a sample cup (or SSC) containing the whole blood sample to be analyzed and a SIRO Flex® reagent cartridge are placed appropriately on the Dimension® system. The Dimension® system mixes and lyses the whole blood sample. The lysed sample is then mixed with the antibody enzyme conjugate. The sirolimus present in the sample is bound by the sirolimus antibody conjugate reagent. Magnetic particles coated with sirolimus are added to bind free (unbound) antibody-enzyme conjugate. The reaction mixture is then separated magnetically. Following separation, the supernatant containing the sirolimus-antibody-enzyme complex is transferred to another cuvette and mixed with the substrate. B-galactosidase catalyzes the hydrolysis of CPRG (chlorophenol red ß-d-galactopyranoside) to produce CPR (chlorophenol red) that absorbs light maximally at 577 nm. The change in absorbance at 577 nm due to the formation of CPR is directly proportional to the amount of sirolimus in the patient's sample and is measured using a bichromatic (577, 700 nm) rate technique.
The Dimension® Sirolimus Calibrator (DC306) is an in-vitro diagnostic product intended to be used to calibrate the Dimension® Sirolimus method. It is a frozon liquid product packaged as a single vial for each of five levels. The matrix is human whole blood hemolysate with preservatives. Levels 2, 3, 4, and 5 contain sirolimus drug at target values of 5, 10, 20, and 31.5 ng/mL, respectively. Level 1 is a human whole blood hemolysate that does not contain sirolimus drug.

Here's a summary of the acceptance criteria and study details for the Dimension SIRO Flex® reagent cartridge, based on the provided 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance

The 510(k) summary focuses on demonstrating substantial equivalence to a predicate device (Abbott IMx Sirolimus) and uses specific performance characteristics as evidence. While explicit "acceptance criteria" for each performance metric are not strictly defined as numerical thresholds in the provided text beyond the predicate device's performance, the goal is to show comparable or improved performance.

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

• Method Comparison (Test Set for demonstrating agreement with reference method):
  • Sample Size: n = 119 patient samples.
  • Data Provenance: The text states "A split patient sample (EDTA whole blood) method comparison." It does not explicitly state the country of origin or if it was retrospective or prospective, but "split patient sample" implies prospective collection from a patient population specifically for this comparison.
• Reproducibility (Test Set for precision):
  • Sample Size: Not explicitly stated as a single "test set" size. However, for each test level (3 whole blood pools and 2 QC levels), a single test from two independent cups was analyzed twice per day over an unspecified number of days/runs. This is repeated across one internal and two external locations.
  • Data Provenance: Not explicitly stated, though the mention of "one internal and two external locations" suggests it likely involved multiple sites, potentially geographically diverse (though specific countries are not mentioned). It's a prospective study designed to assess precision.

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

• For Method Comparison:
  • The ground truth was established by HPLC/MS (High-Performance Liquid Chromatography/Mass Spectrometry), which is referred to as "the reference method." This is an analytical laboratory technique, not an expert human assessment.
• For Reproducibility:
  • The "ground truth" here is the expected value of the control materials (e.g., "Level 1 Whole Blood Pool" mean 4.41 ng/mL). These values are typically established through extensive testing by the manufacturer using validated methods, not by a panel of experts.

4. Adjudication Method for the Test Set

• For Method Comparison: No adjudication method involving human experts is applicable as the comparison is against an instrumental reference method (HPLC/MS).
• For Reproducibility: No adjudication method is applicable. The data is statistical analysis of repeated measurements of control materials.

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

• This device is an in-vitro diagnostic (IVD) test for measuring a drug concentration (Sirolimus) in whole blood. It is an automated clinical chemistry system.
• Therefore, an MRMC comparative effectiveness study where human "readers" (e.g., clinicians interpreting images or patient data) improve with "AI assistance" is not applicable to this type of device. There is no human interpretation of complex data that the device is intended to assist. The device provides a quantitative numerical result.

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

• Yes, this is a standalone device. The performance data (method comparison, reproducibility) directly reflects the algorithm (the immunoassay technique and automated system) without human intervention in the result generation process. The device performs the measurement and outputs a quantitative value. Clinical interpretation of that value by a physician occurs after the device provides its result, but the device's performance itself is standalone.

7. The Type of Ground Truth Used

• For Method Comparison: Analytical reference method (HPLC/MS).
• For Reproducibility: Established mean values of control materials (whole blood pools and QC materials) through internal validation processes.

8. The Sample Size for the Training Set

• The 510(k) summary does not provide details on a separate "training set" sample size. For IVD devices like this, the development process involves extensive internal testing and optimization of reagents and methods which could be considered "training data" in a broad sense, but it is not typically disclosed with sample sizes in the same way as machine learning models. The data presented here are for the validation of the final device.

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

• As mentioned above, specific "training set" details are not provided. However, generally, for the development of such an immunoassay, the "ground truth" during development would be established similarly to the validation:
  • Reference methods (like HPLC/MS) for accurate quantification of sirolimus.
  • Known concentrations of sirolimus in prepared samples.
  • Patient samples with clinically relevant sirolimus levels.
  • The goal during development (training) would be to optimize reagent concentrations, reaction conditions, and calibration algorithms to achieve accurate and precise measurements against these known or reference values.

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The ARCHITECT Sirolimus assay is a chemiluminescent microparticle immunoassay (CMIA) for the quantitative determination of sirolimus in human whole blood on the ARCHITECT i System. The ARCHITECT Sirolimus assay is to be used as an aid in the management of renal transplant patients receiving sirolimus therapy.

The ARCHITECT Sirolimus Calibrators are for the calibration of the ARCHITECT i System when used for the quantitative determination of sirolimus in human whole blood.

The ARCHITECT Sirolimus Whole Blood Precipitation Reagent is for the extraction of sirolimus from samples (human whole blood patient specimens, controls, and ARCHITECT Sirolimus Calibrators) to be tested on the ARCHITECT i System.

The ARCHITECT Sirolimus assay is a delayed one-step immunoassay for the quantitative determination of sirolimus in human whole blood using CMIA technology with flexible assay protocols, referred to as Chemiflex.

Prior to the initiation of the automated ARCHITECT sequence, a manual pretreatment step is performed in which the whole blood sample is extracted with a precipitation reagent, heated, and centrifuged. The supernatant is decanted into a Transplant Pretreatment Tube, which is placedonto the ARCHITECT i System.

Sample, assay diluent, and anti-sirolimus coated paramagnetic microparticles are combined to create a reaction mixture. Sirolimus present in the sample binds to the anti-sirolimus coated microparticles. After a delay, sirolimus acridinium-labeled conjugate is added to the reaction mixture. The sirolimus acridinium-labeled conjucate competes for the available binding sites on the anti-sirolimus coated paramagnetic microparticles. Following an incubation, the microparticles are washed, and pre-trigger and trigger solutions are added to the reaction mixture. The resulting chemiluminescent reaction is measured as relative light units (RLUs),

An indirect relationship exists between the amount of sirolimus in the RLUs detected by the ARCHITECT i System optics.

The provided document describes the ARCHITECT Sirolimus Assay and its performance characteristics, primarily focusing on demonstrating substantial equivalence to a predicate device (ABBOTT IMx® Sirolimus Microparticle Enzyme Immunoassay) and LC/MS/MS as a reference method.

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

1. Table of Acceptance Criteria and Reported Device Performance:

The document doesn't explicitly state numerical acceptance criteria in a dedicated section with pre-defined thresholds. Instead, it presents the results of equivalence studies against a predicate device and a reference method, implying that the observed performance was deemed acceptable for demonstrating substantial equivalence. For performance characteristics like precision, linearity, and sensitivity, the results are presented, and implicit acceptance is given by stating the achieved values (e.g., "less than or equal to 10%").

Here's a table summarizing the reported device performance from the provided text:

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

• Sample Size for Equivalence Studies:
  • ARCHITECT Sirolimus vs. IMx Sirolimus: 168 observations (specimens).
  • ARCHITECT Sirolimus vs. LC/MS/MS: 167 observations (specimens).
• Data Provenance: "human whole blood specimens from renal transplant patients receiving sirolimus therapy." The country of origin is not specified, but the context of an FDA 510(k) submission typically implies US-based or internationally accepted clinical study protocols. The data is retrospective in the sense that the patients were already receiving therapy and specimens were collected. It's not explicitly stated if it was a prospective collection for this specific study, but it's patient data.

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

This information is not provided in the document. For an immunoassay device like this, ground truth is typically established by comparing against a reference method (like LC/MS/MS) or a previously validated predicate device. Human expert interpretation of results is not usually the primary ground truth for quantitative laboratory assays.

4. Adjudication Method for the Test Set:

This information is not applicable and therefore not provided in the document. Adjudication methods (like 2+1, 3+1) are typically used in studies involving subjective human interpretation of images or clinical events, where multiple readers' assessments need to be reconciled to form a ground truth. For quantitative assays like the Sirolimus assay, the ground truth is based on the chemical measurement itself, often against a gold standard method.

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

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study focuses on the impact of a device on human readers' performance (e.g., radiologists interpreting images using an AI tool). The ARCHITECT Sirolimus Assay is a standalone, quantitative in vitro diagnostic device, not one that assists human readers in making interpretations.

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

Yes, the studies presented are standalone performance studies. The ARCHITECT Sirolimus Assay, as an immunoassay, works as an "algorithm only" (the automated measurement process produces a quantitative result) without human input during the core measurement process. The results reported (equivalence, precision, linearity, sensitivity, interference, specificity) directly reflect the performance of the device itself.

7. Type of Ground Truth Used:

• Predicate Device Comparison: The ABBOTT IMx® Sirolimus Microparticle Enzyme Immunoassay (K042411) was used as a reference for comparison. While not a "ground truth" in the strictest sense, it's a legally marketed and accepted assay that served as a benchmark for substantial equivalence.
• Reference Method Comparison: LC/MS/MS (Liquid Chromatography-Mass Spectrometry/Mass Spectrometry) was used as a more definitive "ground truth" or reference method for validating the assay's accuracy against a highly sensitive and specific analytical technique.

8. Sample Size for the Training Set:

The document does not provide specific information on the sample size used for the training set. Immunoassays are often developed and optimized using a variety of samples and reagents during the R&D phase, but a distinct "training set" in the machine learning sense is not typically explicitly defined or reported for this type of device in a 510(k) summary. The development process would involve iterative testing and refinement.

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

As the document doesn't detail a specific "training set" or its ground truth, this information is not provided. For immunoassay development, ground truth for initial optimization would similarly be based on established reference methods (like LC/MS/MS) or careful spiking/dilution experiments with known concentrations of the analyte.

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The IMx Sirolimus assay is an in vitro reagent system for the quantitative determination of sirolimus in human whole blood as an aid in the management of renal transplant patients receiving sirolimus therapy.

The IMx® Sirolimus Calibrators are for the calibration of the IMx Analyser when used for the quantitative determination of sirolimus in human whole blood.

The IMx® Sirolimus MODE 1 Calibrator is for the adjustment of the stored calibration of the IMx Analyser when used for the quantitative determination of sirolimus in human whole blood.

The IMx® Sirolimus Controls are for the verification of the calibration of the IMx Analyser when used for the quantitative determination of sirolimus in human whole blood.

The IMx Sirolimus Whole Blood Precipitation Reagent is for the extraction of sirolimus from samples (whole blood patient specimens, IMx® Sirolimus Calibrators and Controls) to be tested on the IMx® Sirolimus assay.

Microparticle Enzyme Immunoassay (MEIA) for use on Abbott IMx® system.

Assay procedure:

• Incubate the sample with the anti-sirolimus antibody-coated microparticles.
• Add sirolimus alkaline phosphatase conjugate and incubate.
• Transfer to matrix cell.
• Wash to remove unbound substances.
• Add substrate.
• Measure fluorescent product.

This document describes the performance characteristics and acceptance criteria for the Abbott IMx® Sirolimus Microparticle Enzyme Immunoassay (MEIA) test.

Here's the breakdown of the information requested:

1. Table of Acceptance Criteria and Reported Device Performance

Study Proving Device Meets Acceptance Criteria:

The document describes a 510(k) Pre-market Notification for the IMx® Sirolimus Microparticle Enzyme Immunoassay. This submission aims to demonstrate substantial equivalence to a legally marketed predicate device, the Microgenics CEDIA® Sirolimus Assay (K034069), and also includes a comparison to the current accepted reference method for sirolimus measurement, High Performance Liquid Chromatography-tandem Mass Spectrometry (HPLC/MS/MS).

The "acceptance criteria" are implied by the comparison to the predicate device's performance characteristics, and the IMx® Sirolimus MEIA Test reports its own performance to show it is comparable or superior. The comparison to HPLC/MS/MS provides further evidence of the device's accuracy.

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

• Comparison to HPLC/MS/MS Method (Analytical Test Set):

  • Sample Size: 221 samples ("n").
  • Data Provenance: Not explicitly stated, but the study involved "All Sites," suggesting a multi-center study. The document is from Axis-Shield Diagnostics Ltd. in Scotland, UK, but the origin of the patient samples is not specified as domestic or international, nor if they were retrospective or prospective. It is likely that these were prospective samples collected specifically for method comparison, but this is an inference.

• Performance Characteristics Comparison (IMx vs. CEDIA):

  • The sample sizes for individual performance parameters (Precision, Recovery, Linearity, etc.) for the IMx® Sirolimus MEIA Test are not explicitly stated in the provided text. The results are reported as summary statistics (e.g., "Total imprecision of ≤ 15%", "Mean recovery across samples").
  • Data Provenance: Not explicitly stated for these individual studies, but presumably conducted by Axis-Shield Diagnostics Ltd.

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

• For the HPLC/MS/MS comparison: The ground truth is established by the HPLC/MS/MS method itself, which is described as the "current Device accepted reference method for sirolimus measurement." This is an instrumental method, not based on human expert consensus. Therefore, the concept of "experts used to establish ground truth" does not apply in the traditional sense for this part of the study.
• For other performance characteristics: The ground truth for determining precision, recovery, linearity, sensitivity, specificity, and interference in laboratory assays is typically established by the inherent properties of the reference materials and methods used in the testing, not by expert consensus.

4. Adjudication Method for the Test Set

• Not applicable. This study is for an in vitro diagnostic (IVD) quantitative assay. Adjudication methods (like 2+1 or 3+1) are typically used in imaging studies or clinical trials where human interpretation of data is subjective and requires consensus. For an IVD assay, performance is quantitatively measured against a reference method or known values, not adjudicated by experts in the same way.

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

• No. This is an in vitro diagnostic (IVD) device, not an imaging or interpretive device that would typically involve a multi-reader multi-case study with human readers. The device provides a quantitative measurement, not an interpretation of a complex input that human readers would evaluate.

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

• Yes, this is a standalone performance study. The document describes the performance of the IMx® Sirolimus Microparticle Enzyme Immunoassay (MEIA) test itself, as an automated system on the Abbott IMx® analyser. The results reported are directly from the device's measurement. While a human operates the device and interprets the numerical output in a clinical context, the performance characteristics detailed here (precision, sensitivity, comparison to HPLC/MS/MS) are inherent to the assay and instrument itself, without "human-in-the-loop" influencing the reported measurement accuracy or precision for these specific studies.

7. The Type of Ground Truth Used

• Instrumental Reference Method: For the direct comparison study, the ground truth was the High Performance Liquid Chromatography-tandem Mass Spectrometry (HPLC/MS/MS) method, described as the "current Device accepted reference method for sirolimus measurement."
• Known Reference Values/Spiked Samples: For parameters like Precision, Recovery, Dilution Linearity, Analytical Sensitivity, Specificity, and Interference, the ground truth is established using samples with known concentrations of sirolimus, its metabolites, or interfering substances. These known values act as the "ground truth" against which the device's measurements are compared.

8. The Sample Size for the Training Set

• The document describes a 510(k) submission for a finished IVD product, not a deep learning or AI model that typically has a separate "training set." The IMx® Sirolimus assay is an established technology (Microparticle Enzyme Immunoassay - MEIA).
• Therefore, the concept of a "training set" in the context of machine learning is not applicable to this type of device. The development and optimization of such an assay would involve internal R&D studies, but these are not referred to as "training sets" in the same way.

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

• Not applicable. As explained above, there is no "training set" in the machine learning sense for this device. The development process would have involved rigorous analytical testing using reference materials and calibrated instruments to establish assay parameters, but not a "ground truth for a training set" as it would be understood for an AI algorithm.

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