Search Results

The Tacrolimus Assay Kit is used for quantitative determination of the tacrolimus concentration in human whole blood on the Beckman Coulter AU480. It is to be used as an aid in the management of liver and kidney allograft patients receiving tacrolimus therapy.

For In Vitro Diagnostic Use.

The Tacrolimus Assay Kit utilizes the latex-enhanced competitive immunoturbidimetry method for quantitative determination of the tacrolimus concentration in human whole blood. The assay consists of reagents, sample extract and calibrator.

The provided text describes the acceptance criteria and a study demonstrating the substantial equivalence of the "Tacrolimus Assay Kit" (candidate device) to a predicate device, the ARCHITECT Tacrolimus Assay.

Here's an analysis of the requested information:

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

The document does not explicitly list "acceptance criteria" in a structured table with direct performance targets. Instead, it states that "Analytical studies were performed to evaluate the precision, linearity, assay reportable range, recovery, specificity, and accuracy of the candidate device." The conclusion then states that these tests demonstrate "substantial equivalence." This implies that the performance in these areas met thresholds considered acceptable for substantial equivalence to the predicate device.

However, a key difference between the candidate and predicate device is the "Measuring Range." This could be considered a performance characteristic with an implicit acceptance criterion that the range should be clinically relevant and comparable to other devices.

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

The document does not provide details on the sample size used for the analytical studies (precision, linearity, etc.), nor does it specify the data provenance (country of origin, retrospective/prospective). It simply states that "Analytical studies were performed."

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 question is not applicable to this type of device (Tacrolimus Assay Kit). The "ground truth" for an in-vitro diagnostic test like this is established through reference methods or highly accurate analytical techniques, not through expert consensus on images or clinical assessments.

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

This question is not applicable. Adjudication methods like 2+1 or 3+1 are typically used for establishing ground truth in studies involving human interpretation (e.g., radiology studies). For an in-vitro diagnostic assay, the "adjudication" would involve rigorous laboratory protocols, quality control, and comparison to established reference materials or methods, not human adjudication between 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 question is not applicable. The device is a Tacrolimus Assay Kit, an in-vitro diagnostic test, not an AI-assisted diagnostic tool that would involve human readers interpreting images or data.

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

This question is not applicable in the context of "algorithm only" as typically understood for AI/CAD devices. However, the performance assessment described (precision, linearity, accuracy, etc.) is essentially "standalone" in the sense that it evaluates the kit's performance on its own, independent of human interpretation or intervention beyond standard laboratory procedures for running the assay. It's a laboratory test, not an AI algorithm.

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

For in-vitro diagnostic assays, "ground truth" is typically established by:

• Reference materials/standards: Samples with known concentrations of tacrolimus, often certified.
• Reference methods: Highly accurate and validated laboratory methods (e.g., mass spectrometry) used to determine the true concentration in patient samples.
• Split-sample comparison: Comparing results from the candidate device to a legally marketed predicate or other established method using the same patient samples.

The document implicitly refers to these by stating the studies evaluated "precision, linearity, assay reportable range, recovery, specificity, and accuracy." Accuracy, for instance, would be assessed against known values from reference methods or materials.

8. The sample size for the training set

This question is not applicable. The device is an in-vitro diagnostic assay based on a chemical/immunological reaction, not a machine learning model that requires a "training set" in the conventional sense.

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

This question is not applicable, as there is no "training set" for this type of device.

Ask a specific question about this device

Immunoassay for the in vitro quantitative determination of tacrolimus in EDTA human whole blood. The assay is used as an aid in the management of liver and kidney transplant patients receiving tacrolimus therapy.

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

The Elecsys Tacrolimus immunoassay uses the principle of electrochemiluminescence for detection and measurement. Before testing with the Elecsys Tacrolimus assay, the specimen, calibrators and controls are pretreated with the Elecsys ISD Pretreatment Reagent. The reagent lyses the cells, extracts Tacrolimus and precipitates virtually all of the blood proteins. The pretreated samples are centrifuged, and an aliquot of the resulting supernatant containing Tacrolimus is then assayed using the Elecsys Tacrolimus assay.

Results are determined via a calibration curve which is instrument-specifically generated by 2-point calibration and a master curve provided via the reagent barcode.

This document describes the Elecsys Tacrolimus immunoassay, an in vitro quantitative determination of tacrolimus in EDTA human whole blood. The assay is used as an aid in the management of liver and kidney transplant patients receiving tacrolimus therapy. It is intended for use on Elecsys and cobas e immunoassay analyzers.

Here's a breakdown of the acceptance criteria and study information:

1. Table of Acceptance Criteria and Reported Device Performance

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

• Precision (Non-clinical):
  • Seven-member panel (four pooled patient and single donor spiked human whole blood samples, three controls).
  • Measured in single determination in four separate aliquots (divided in two runs per day) for 21 operating days. The number of samples for the test set is not explicitly stated as a single number but implies repeated measurements over time.
  • Data provenance: Not explicitly stated, but "pooled patient and single donor spiked human whole blood samples" suggests human biological samples.
• Limit of Blank (LoB):
  • Five analyte-free whole blood samples.
  • 30 measuring points collected per instrument, for a total of 60 measured values (across two instruments).
• Limit of Detection (LoD):
  • Five spiked human whole blood samples with low analyte.
  • 30 measuring points collected per instrument, for a total of 60 measured values (across two instruments).
• Limit of Quantitation (LoQ):
  • 14 spiked human whole blood samples each diluted to concentrations covering the range between LoB and 2x LoQ.
  • 84 measuring points collected per instrument, for a total of 168 measured values per lot (across two instruments and three reagent lots).
• Recovery (Accuracy):
  • ISD-free human blood spiked with tacrolimus.
  • Patient derived samples (from patients taking Tacrolimus) divided into at least four aliquots and spiked. The exact number of patient samples is not specified.
• Linearity:
  • Three dilution series prepared from three different spiked human whole blood samples.
  • Each dilution series included 22 dilutions.
• Dilution:
  • Three ISD-free human whole blood samples spiked separately.
  • Dilution series of nine respective dilutions.
• Analytical Specificity (Cross-reactivity):
  • Each cross-reactant compound spiked into two human whole blood samples (analyte-free and slightly elevated analyte level). Sample size for each cross-reactant is therefore 2 samples per compound.
• Endogenous Interferences:
  • Three spiked human whole blood samples (one low and one high concentration).
  • Dilution series of 10 dilutions.
• Exogenous Interferences (Drugs):
  • 16 common and 25 additional pharmaceutical compounds spiked into two spiked human tacrolimus containing human whole blood samples (single donor samples spiked with 3 ng/mL and 10 ng/mL tacrolimus). So, 2 samples per drug.
• Reagent Stability:
  • Study 1 & 2: Five human whole blood samples (pooled patient samples and single donor samples spiked with tacrolimus) and three controls.
  • Study 3: PreciControl ISD 1, 2, and 3.
• Sample Stability:
  • Not explicitly stated, but the studies mention "human EDTA blood" and "reference T0 (fresh sample) values."
• Reproducibility (Clinical):
  • Human sample pools (HSP 01-06) and PreciControl materials (PC ISD L1-L3).
  • N=90 for each sample type. Data provenance: Human samples.
• Method Comparison (Clinical):
  • Abbott ARCHITECT Tacrolimus vs. Elecsys Tacrolimus: Combined 553 samples (346 Kidney, 207 Liver).
  • Elecsys Tacrolimus vs. LC-MS/MS: Combined 554 samples (344 Kidney, 210 Liver).
  • Data provenance: Clinical test results for enrolled subjects. No country of origin is specified.

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

This document describes the validation of an in vitro diagnostic assay for quantitative determination of tacrolimus. There is no mention of human experts (e.g., radiologists) establishing ground truth. The ground truth is established by reference methods or gravimetric preparation of known concentrations.

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

Not applicable, as this is an in vitro diagnostic device and not a diagnostic imaging device requiring expert 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 is an in vitro diagnostic immunoassay, not an AI-driven imaging analysis system involving human readers.

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

The entire performance evaluation described is for the standalone device (Elecsys Tacrolimus immunoassay) without human-in-the-loop performance influencing the assay results. The device quantifies tacrolimus levels; human intervention is for sample preparation, loading, and interpretation of the quantitative result in a clinical context.

7. The Type of Ground Truth Used

The ground truth for the performance studies is established using:

• Gravimetrically prepared reference material: For spiking studies (recovery, linearity, dilution, exogenous/endogenous interferences).
• Reference Methods:
  • Abbott ARCHITECT Tacrolimus (a legally marketed predicate device) for method comparison studies.
  • LC-MS/MS (Liquid Chromatography-Mass Spectrometry/Mass Spectrometry) for method comparison studies, which is considered a gold standard for tacrolimus quantification.
• Assigned values for controls: For stability and reproducibility studies (e.g., PreciControl ISD).
• Analyte-free whole blood samples: For LoB determination.

8. The Sample Size for the Training Set

This document describes a premarket notification for an in vitro diagnostic device, not a machine learning or AI algorithm. Therefore, the concept of a "training set" in the context of AI models does not apply here. The document details studies designed to validate the assay's performance characteristics.

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 algorithm for this in vitro diagnostic device.

Ask a specific question about this device

The Dimension Tacrolimus Flex® Reagent Cartridge (TAC) is an in vitro diagnostic test for the quantitative measurement of tacrolimus in human whole blood on the Dimension® clinical chemistry system. Measurements of tacrolimus are used as an aid in the management of tacrolimus therapy in renal and hepatic transplant patients.

The Dimension Tacrolimus Callbrator (TAC CAL) is an in vitro diagnostic product for the Tacrolimus (TAC) method on the Dimension® clinical chemistry system.

The automated Dimension® TAC method uses an immunoassay technique in which free and tacrolimus-bound antibody-enzyme conjugate is separated using magnetic particles. The assay is performed using a method specific Flex® reagent cartridge. The Flex® cartridge contains a pretreatment reagent, antibody-ß-galactosidase conjugate, tacrolimus immobilized on chromium dioxide particles, chlorophenol red ß-d-galactopyranoside (CPRG) substrate, and diluent to hydrate the tablets.

Dimension® Tacrolimus (TAC) Calibrator is five level frozen liquid, whole blood hemolysate containing purified tacrolimus. The provided in 4.0 mL vials, 2 vials per level. There are five calibrator levels per kit which span the assay range for the Dimension® Tacrolimus (TAC) assay. Calibrators are filled with 1.0 mL per vial except for Level 1 calibrator which contains 2.0 mL per vial.

Here's a summary of the acceptance criteria and study information for the Dimension Tacrolimus Flex® Reagent Cartridge (TAC) and Dimension Tacrolimus Calibrator (TAC CAL), based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state acceptance criteria in a quantitative format for most categories. Instead, it describes the type of testing performed and then indicates whether the device met certain expectations (e.g., "All samples met the acceptance criterion of ≤ 10% mean bias in recovery"). Where specific quantitative performance is given, it is included.

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

• Precision: No specific sample size for a single "test set" is provided, but reproducibility testing was conducted using different levels (1.8 to 27.4 ng/mL).

• Linearity: No specific sample size mentioned, but the study was performed by mixing a sample with a known high tacrolimus concentration (40.3 ng/mL) with a normal patient pool with no tacrolimus in various ratios.

• Specificity: No specific sample size mentioned for the interference or cross-reactivity studies, beyond stating "compounds tested" and "major tacrolimus metabolite... as well as minor metabolites."

• Recovery: No specific sample size mentioned, but "samples spiked with USP tacrolimus" were used.

• Method Comparison:

  • Versus LC-MS/MS: n = 315 patient samples.
  • Versus ARCHITECT Tacrolimus Assay: n = 308 patient samples.
  • Versus Dimension Tacrolimus (TACR) method: n = 213 patient samples.

• Data Provenance: The document states that method comparison studies, and some precision testing, were performed at two external evaluation sites in addition to internal testing. Patient samples for method comparison included a "nearly equal distribution of liver and kidney transplant patients." The country of origin is not specified but is implied to be within the scope of Siemens Healthcare Diagnostics operations, likely in the US given the FDA submission. The studies were retrospective in the sense that existing patient samples (whole blood) were used, though the testing itself was prospective for the device evaluation.

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

The concept of "experts" for ground truth (e.g., radiologists) is not applicable here as this is an in vitro diagnostic (IVD) assay. The ground truth for the method comparison studies was established using:

• LC-MS/MS reference method: This is an analytical "gold standard" for measuring tacrolimus concentrations.
• Predicate devices: ARCHITECT Tacrolimus Assay (K070820) and Dimension Tacrolimus (TACR) method (K060502), which are already legally marketed and accepted methods.

The experts involved would be the laboratory personnel performing these high-complexity reference and predicate assays, who are implicitly qualified to conduct such tests according to established laboratory practices. No specific number or qualifications (e.g., "10 years of experience") are provided for these individuals.

4. Adjudication Method for the Test Set

Not applicable. This is an IVD assay where quantitative measurements are obtained. Adjudication typically refers to resolving discrepancies between multiple human readers in image-based diagnostics. Here, the "truth" is established by a reference method or comparison to established predicate devices.

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

Not applicable. This is an in vitro diagnostic (IVD) assay and does not involve human readers interpreting images, nor does it involve AI assistance in the context of imaging diagnostics. The comparison is between the new device's analytical performance and established reference/predicate methods.

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

Yes, the studies reported are essentially standalone performance evaluations of the Dimension Tacrolimus Flex® Reagent Cartridge (TAC) system. The described testing (precision, linearity, specificity, recovery, method comparison) evaluates the analytical performance of the automated assay system itself. Human intervention is limited to standard laboratory procedures like sample preparation, loading, and result interpretation, not in an "AI-assisted reader" capacity.

7. The Type of Ground Truth Used

• Analytical Measuring Range (Linearity) & Recovery: "USP tacrolimus" (United States Pharmacopeia tacrolimus), which refers to highly pure, standardized tacrolimus used to spike samples to known concentrations.
• Method Comparison:
  • LC-MS/MS Assay for Tacrolimus: This is considered the analytical "reference method" and serves as a highly accurate ground truth.
  • Predicate Devices: ARCHITECT Tacrolimus Assay and Dimension Tacrolimus (TACR) method. While not a "ground truth" in the strictest sense of an absolute standard, they serve as the established clinical "truth" for comparison, demonstrating substantial equivalence.

8. The Sample Size for the Training Set

No explicit "training set" or sample size for it is mentioned. This is a chemical assay, not a machine learning algorithm in the typical sense that requires a separate training set for model development. The development of the assay reagents and protocols would involve internal optimization, but this is not typically referred to as a "training set" in the context of regulatory submissions for IVD devices.

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

Since there is no explicit "training set" or machine learning model, this question is not directly applicable. The development and optimization of the assay would rely on:

• Understanding of tacrolimus chemistry and pharmacology: To design reagents that specifically target tacrolimus.
• Standards and reference materials: Such as purified tacrolimus (used for calibrators and recovery studies) to ensure accurate concentration measurements.
• Internal validation and optimization studies: To fine-tune reagent concentrations, reaction conditions, and instrument parameters to achieve desired analytical performance characteristics.

Ask a specific question about this device

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

The QMS® Tacrolimus Calibrator set is intended for use in calibration of the QMS® Tacrolimus Immunoassay.

The QMS® Tacrolimus Immunoassay consists of separately packaged reagents (Reagent 1, Reagent 2 and Extraction Reagent) and calibrators (Calibrator A, B, C, D, E, and F).

Reagent 1 (Antibody Reagent):

Here's an analysis of the acceptance criteria and study information for the QMS® Tacrolimus Immunoassay, based on the provided 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance

Note: The document implies acceptance criteria based on standard laboratory practices for in vitro diagnostics. Specific numerical thresholds for "high correlation" or "acceptable level" for parameters like comparison studies and specificity are not explicitly stated as acceptance criteria but are inferred from the reported results being presented as evidence of performance.

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

The document does not explicitly state the specific number of samples used for the "test set" for each performance study. It mentions "samples were tested" implying internal validation.

• Functional Sensitivity (LOQ): Not specified.
• Precision: Not specified.
• Dilution Recovery: Not specified.
• Spike Recovery: Not specified.
• Method Comparison: Not specified. It indicates "samples were tested" and compared to LC-MS/MS and the predicate device.
• Specificity: Not specified. Indicated "studies were conducted for available major metabolites... medications routinely co-administered... and other over-the-counter drugs."
• Interfering Substances: Not specified. Indicated "endogenous substances... were tested."
• Reagent Stability: Not specified.
• Calibrator Stability: Not specified.

Data Provenance: The studies appear to be internal validation studies conducted by Thermo Fisher Scientific. The document does not specify country of origin for the data, nor does it explicitly state whether the data was retrospective or prospective, though it's typically prospective for performance validation.

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

This information is not applicable to this type of device (immunoassay). The "ground truth" for an immunoassay is established by reference methods or known concentrations, not by expert interpretation of images or other subjective data. For example:

• Method Comparison: The "ground truth" is provided by the LC-MS/MS method (a gold standard analytical technique for tacrolimus quantification). The predicate device also serves as a comparison.
• Dilution Recovery and Spike Recovery: The "ground truth" is the known concentration of tacrolimus added to the samples.
• Specificity: The "ground truth" for cross-reactivity is the known chemical structure and concentration of the potential interfering substances.

4. Adjudication Method for the Test Set

This is not applicable to this type of device. Adjudication methods (like 2+1, 3+1) are typically used in studies where multiple human readers independently assess data (e.g., medical images) and a consensus is needed to establish ground truth or resolve discrepancies. For this immunoassay, results
are quantitative measurements, not subjective interpretations.

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

No, an MRMC comparative effectiveness study was not done. This type of study assesses how human readers' performance changes with an AI aid. The QMS® Tacrolimus Immunoassay is an in vitro diagnostic device that quantifies a substance in whole blood through an automated process, not an AI system that assists human interpretation of complex medical cases.

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

Yes, the performance studies detailed in the summary (Functional Sensitivity, Precision, Dilution Recovery, Spike Recovery, Method Comparison, Specificity, Interfering Substances, and Stability) represent the standalone performance of the QMS® Tacrolimus Immunoassay. This device operates as an automated system to quantify tacrolimus, without direct human intervention in the interpretative process during testing. The results are generated by the algorithm/device itself.

7. The Type of Ground Truth Used

The ground truth used for validating the QMS® Tacrolimus Immunoassay stems from:

• Reference Method: For method comparison, the LC-MS/MS (Liquid Chromatography-Mass Spectrometry/Mass Spectrometry) method served as the primary reference standard. This is considered a highly sensitive and specific analytical technique for drug quantification.
• Known Concentrations: For studies like Functional Sensitivity, Dilution Recovery, Spike Recovery, Specificity, and Interfering Substances, the ground truth was based on samples with known, precisely prepared concentrations of tacrolimus, its metabolites, co-administered drugs, or endogenous interfering substances.
• Predicate Device Comparison: The previously cleared Abbott ARCHITECT® Tacrolimus Assay served as a comparative reference method for demonstrating substantial equivalence.

8. The Sample Size for the Training Set

The document does not specify a training set sample size. For an immunoassay, the concept of a "training set" in the context of machine learning (where algorithms learn from data) is not directly applicable in the same way. The immunoassays are developed and optimized through iterative processes using various reagents, controls, and calibration materials, rather than "training" an algorithm on a distinct dataset.

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

As noted above, a traditional "training set" with ground truth in the sense of machine learning is not described or applicable here. The development and optimization of an immunoassay rely on established chemical and biological principles, precise formulation of reagents, and validation against reference methods and known standards to ensure accuracy and reliability. The ground truth for such development is built upon fundamental analytical chemistry and knowledge of the analyte (tacrolimus).

Ask a specific question about this device

The ARCHITECT Tacrolimus assay is a chemiluminescent Microparticle immunoassay (CMIA) for the quantitative determination of tacrolimus in human whole blood on the ARCHITECT i System. The ARCHITECT Tacrolimus assay is to be used as an aid in the management of liver and kidney allograft patients receiving tacrolimus therapy.

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

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

The ARCHITECT Tacrolimus assay is a delayed one-step immunoassay for the quantitative determination of tacrolimus 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 and centrifyged. The supernatant is decanted into a Transplant Pretreatment Tube, which is placed onto the ARCHITECT i System.

Sample, assay diluent, and anti-tacrolimus coated paramagnetic microparticles are combined to create a reaction mixture. Tacrolimus present in the sample binds to the anti-tacrolimus coated microparticles. After a delay, tacrolimus acridinium-labeled conjugate is added to the reaction mixture. The tacrolimus on the acridinium-labeled conjugate competes for the available binding sites on the microparticles. Following an incubation, the microparticles are washed, and pretrigger 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 tacrolimus in the RLUs detected by the ARCHITECT i System optics.

Here's a summary of the acceptance criteria and the study details for the ARCHITECT Tacrolimus assay, based on the provided 510(k) summary:

Acceptance Criteria and Device Performance

This document primarily describes performance characteristics rather than explicit acceptance criteria with defined pass/fail thresholds against which the reported performance is compared. However, the reported performance values implicitly define the level of performance deemed acceptable by the manufacturer for substantial equivalence.

Ask a specific question about this device

The Waters MassTrak Immunosuppressants Kit is indicated for the quantification of the immunosuppressive drug Tacrolimus (FK506; Prograf) in liver and kidney transplant patient whole blood samples for the purposes of monitoring drug levels to direct subsequent patient dosing.

The MassTrak Immunosuppressants Kit for Tacrolimus is an in vitro medical device intended to facilitate quantitative determination of Tacrolimus in human whole blood as an aid in the management of kidney and liver transplant patients receiving Tacrolimus drug therapy. The components of the kit are intended for use with an LC/MS/MS system. The kit materials - calibrators, quality control materials, internal standards, and neat solutions, as well as a MassTrakTM 2.1 x 10 mm C18 cartridge column - have been optimized for use with the Waters Quattro micro and Alliance 2795 System, but can be used with any LC/MS/MS configuration optimized for quantification.

The provided text describes the Waters MassTrak™ Immunosuppressants Kit, an in vitro diagnostic device used for quantifying Tacrolimus in human whole blood. The submission outlines performance data and comparison studies to establish substantial equivalence to predicate devices.

Here's a breakdown of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance

The document describes various performance studies and their acceptance criteria. The table below synthesizes this information for the MassTrak™ Immunosuppressants Kit.

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

• Sample Size for Test Set:
  • Precision/Reproducibility: Not explicitly stated beyond "three levels of spiked whole blood pools," with "Specimens at each level were analyzed in duplicate twice per day for 20 days." This implies a total of (3 levels * 2 duplicates * 2 runs/day * 20 days) = 240 measurements.
  • Linearity: "nine test samples."
  • Sample Dilution: "A minimum of ten patient samples."
  • Accuracy: "series of 44 samples provided by the Tacrolimus International Proficiency Testing Scheme."
  • Method Comparison: "A minimum of 50 samples for each transplant type were compared at each site." The types mentioned are kidney and liver, so at least 100 samples across the two types if only one site, or more if multiple sites were used.
• Data Provenance:
  • The studies were conducted "at the clinical sites using Alliance HT 2795 High Performance Liquid Chromatography Systems coupled to Quattro micro triple quadrupole mass spectrometers." This suggests a clinical laboratory setting.
  • Specific country of origin is not directly stated, but the reference to the "Tacrolimus International Proficiency Testing Scheme (www.bioanalytics.co.uk)" implies international data sources for accuracy and potentially method comparison (UK-based scheme).
  • The linearity, sample dilution, and method comparison studies used "patient specimens" or "patient samples," indicating the data is from relevant patient populations.
  • The nature of "proficiency testing scheme" samples means they represent retrospective, collected samples used for external quality assessment.
  • The precision, stability, spike & recovery, and interference studies utilized "spiked whole blood pools" or "drug-free whole blood," which are laboratory-prepared samples.

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

• The concept of "ground truth" established by experts, as typically understood in AI/ML contexts for image interpretation or diagnosis, does not directly apply to this device. This device is an analytical instrument for quantitative determination of a drug concentration.
• For Accuracy and Method Comparison: The "ground truth" or reference values for accuracy and method comparison are derived from established reference methods or proficiency testing schemes.
  • For the Accuracy study, the reference was "the Tacrolimus International Proficiency Testing Scheme (www.bioanalytics.co.uk)." The acceptable range was defined as "±3 SD of method mean," indicating a consensus or calculated mean from multiple laboratories/methods participating in the scheme, rather than a single expert.
  • For Method Comparison, the "ground truth" was implied by the "test laboratory's current methodology (the 'Comparative Method')" which the device was compared against. This comparative method would be a previously validated analytical technique for Tacrolimus quantification.
  • No information is provided about individual "experts" establishing a single ground truth; rather, it hinges on established analytical reference systems or comparative methods.

4. Adjudication Method for the Test Set

• Adjudication methods (like 2+1, 3+1) are typically used in studies where human readers independently assess data and then resolve discrepancies, often in image interpretation.
• This is an in vitro diagnostic device for quantitative drug measurement. The "adjudication" (if one can call it that) is inherent in the analytical process:
  • Measurements are performed in replicate (e.g., "duplicate twice per day for 20 days" for precision, "replicate determinations" for linearity, "triplicate determinations" for spike & recovery).
  • Statistical methods (e.g., %CV, 95% confidence level, Deming Regression, t-test, ±3 SD of method mean) are used to assess the agreement, consistency, and accuracy of these quantitative measurements against predefined criteria or reference values.
  • Thus, there is no human adjudication process described in the conventional sense.

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

• No, an MRMC comparative effectiveness study involving human readers and AI assistance was not done.
• This device is an in vitro diagnostic (IVD) kit for quantifying drug levels, not an AI-powered diagnostic tool for interpretation by human readers. Its primary function is to provide a quantitative measurement.

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

• Yes, this entire submission describes the standalone performance of the analytical device (MassTrak™ Immunosuppressants Kit) without human-in-the-loop performance in the sense of interpretative AI systems.
• The device itself, an LC/MS/MS system with specialized reagents, performs the quantification. While a human operates the instrument and interprets the numerical output, the "performance" described relates to the accuracy, precision, linearity, etc., of the instrument and reagents in generating those numbers.
• The acceptance criteria and reported performances directly reflect the standalone analytical capabilities of the kit.

7. The Type of Ground Truth Used (Expert Consensus, Pathology, Outcomes Data, etc.)

For this quantitative diagnostic device, the "ground truth" is established by:

• Reference Methods/Materials: For accuracy testing, the Tacrolimus International Proficiency Testing Scheme provides reference values (implied consensus/method mean). For method comparison, another established and validated laboratory methodology serves as the comparator.
• Calculated or Spiked Concentrations: For studies like linearity, precision, spike & recovery, and interference, the "ground truth" concentrations are known either because they were precisely spiked into a matrix or calculated from known mixtures.
• Statistical Definitions: Acceptance criteria often define "ground truth" in terms of statistical acceptability (e.g., %CV ≤ 10%, bias ≤ 10%, p ≥ 0.05).

8. The Sample Size for the Training Set

• The concept of "training set" is not directly applicable in the context of this 510(k) submission for a non-AI-based IVD device.
• This device is an analytical chemistry kit, not a machine learning algorithm that is "trained" on a dataset.
• The manufacturer would have performed internal R&D, method development, and optimization studies, which could be considered analogous to "training," but these activities do not typically involve a formally defined "training set" with established ground truth in the same way an AI model does.

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

• As stated above, a formal "training set" as understood in AI/ML is not applicable.
• The "ground truth" during method development would have been established through a combination of:
  • Reference standards: Using highly pure Tacrolimus standards at known concentrations to calibrate and verify the analytical method.
  • Internal validation: Running samples with known "spiked-in" concentrations or comparing with existing, well-established (often more laborious) reference methods to optimize the LC/MS/MS parameters, reagent formulations, and analytical protocols.
  • Iterative refinement: Adjusting parameters until desired performance characteristics (e.g., sensitivity, specificity, linearity) are achieved.

Ask a specific question about this device

The Dimension® TACR Flex® reagent cartridge is an in vitro diagnostic test intended to quantitatively measure tacrolimus in human whole blood on the Dimension® clinical chemistry system. Measurements of tacrolimus are used as an aid in the management of tacrolimus therapy in kidney and liver transplant patients.

The Dimension® TACR Flex® reagent cartridge is an in vitro diagnostic device that consists of prepackaged reagents in a plastic eight-well cartridge for use on the Dade Behring Dimension® clinical chemistry system.

The provided text describes a 510(k) premarket notification for the Dimension® TACR Flex® reagent cartridge, an in vitro diagnostic device used to measure tacrolimus in human whole blood. The submission aims to demonstrate substantial equivalence to a predicate device, the Abbott IMx® Tacrolimus II Assay.

Here's an analysis of the acceptance criteria and study information based on your request:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state acceptance criteria in terms of pre-defined thresholds for slope, intercept, or correlation coefficient. Instead, it presents the results of method comparison studies and implies that these results are considered acceptable for demonstrating substantial equivalence. The predicate device's assay range (1.5-30 ng/mL) is a point of comparison for the new device's range (1.2-30 ng/mL).

However, based on the provided comparative method tables, we can deduce what was measured:

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

• Sample Size for Test Set:
  • Vs. LC/MS/MS: 184 samples (103 kidney, 81 liver)
  • Vs. Abbott IMx® Tacrolimus II Assay: 175 samples (97 kidney, 78 liver)
• Data Provenance:
  • Country of Origin: Not explicitly stated, but the studies were conducted at "two external sites." This usually implies clinical sites within the country where regulatory approval is sought (e.g., USA for FDA submission) unless specified otherwise.
  • Retrospective or Prospective: Not explicitly stated. However, "samples from 2 transplant patient groups (liver and kidney) were included in the studies" suggests these were patient samples collected for the purpose of the study, making it likely a prospective or retrospectively collected cohort specifically for this validation. Given the date of submission (2006), it's more probable that these were prospectively collected samples from transplant patients.

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

This information is not applicable to this type of device. For in vitro diagnostic assays measuring a quantitative analyte like tacrolimus, the "ground truth" is typically established by a highly sensitive and specific reference method (like LC/MS/MS) or a well-established, legally marketed comparative method (like the Abbott IMx® assay). There are no human experts involved in "scoring" or "interpreting" the results to establish ground truth in the way there would be for image-based diagnostic AI.

4. Adjudication Method for the Test Set

This is not applicable. Adjudication methods (like 2+1, 3+1) are used to resolve discrepancies in human expert interpretations, especially in studies involving subjective assessments (e.g., image-based diagnostics). For quantitative chemical assays, the agreement is determined mathematically by statistical methods (e.g., Passing Bablok regression) between the test device and the reference/predicate method.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size of Human Improvement with AI vs. Without AI Assistance

This information is not applicable. This device is an in vitro diagnostic reagent cartridge for laboratory testing, not an AI-assisted diagnostic tool that aids human readers (e.g., radiologists interpreting images). Therefore, no MRMC study or AI assistance effect size is relevant.

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

Yes, the studies presented are essentially standalone performance studies of the Dimension® TACR Flex® reagent cartridge. The device provides a quantitative measurement of tacrolimus. Its performance is evaluated directly against established methods (LC/MS/MS and the Abbott IMx® Tacrolimus II Assay) without human intervention in the result generation itself. The results (slope, intercept, r-value) characterize the algorithm/device's performance.

7. The Type of Ground Truth Used

The ground truth used was:

• Reference Method: Liquid Chromatography / Tandem Mass Spectrometry (LC/MS/MS)
• Comparative Method: Abbott IMx® Tacrolimus II Assay (a predicate device)

8. The Sample Size for the Training Set

The document does not explicitly mention a separate training set for this device. For in vitro diagnostic assays like this, it is common that:

• The assay's formulation and optimization would occur during development using a variety of samples and calibrators, which could be considered an internal "training" phase for the assay itself.
• The statistical analysis (Passing Bablok regression) is performed on the entire test set against the reference or predicate method.

If the device involved a machine learning algorithm, a dedicated training set would be described. Since it's an immunoassay, the "training" analogous to ML would be the assay development and calibration process. The document only describes the validation (test set) data.

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

As no specific "training set" for an explicit algorithm is mentioned, this question is not directly applicable. For the development and calibration of the immunoassay, the "ground truth" would be established using:

• Highly purified tacrolimus standards.
• Reference methods like LC/MS/MS to assign values to calibrator materials.
• Internal validation and quality control procedures.

Ask a specific question about this device

The Emit® 2000 Tacrolimus Assay is for in vitro quantitative analysis of tacrolimus and metabolite in human whole blood as an aid in the management of tacrolimus therapy in liver and kidney transplant patients.

The Emit® 2000 Tacrolimus Sample Pretreatment Reagent is an accessory reagent for use with the Emit® 2000 Tacrolimus Assay.

The Emit® 2000 Tacrolimus Assay is for in vitro diagnostic use for the quantitative analysis of tacrolimus and metabolite in human whole blood as an aid in the management of tacrolimus therapy in liver and kidney transplant patients. The Emit® 2000 Tacrolimus 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 tacrolimus.

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

The provided document K060385 describes the Emit® 2000 Tacrolimus Assay and its associated Sample Pretreatment Reagent. The study presented compares the performance of this new assay against two established methods: Liquid Chromatography/Mass Spectrometry (LC/MS) and the Abbott IMx® Tacrolimus II Assay.

Here's an analysis of the acceptance criteria and the study that proves the device meets those criteria:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria (e.g., a specific minimum slope and correlation coefficient). Instead, it presents the results of method comparison studies and implies that these results demonstrate substantial equivalence to the predicate devices. The "reported device performance" refers to the results obtained from these comparison studies.

Note: Since explicit acceptance criteria are not provided, the "acceptance criteria" column is implicitly an expectation of strong correlation and a slope/intercept close to 1 and 0 respectively for substantial equivalence, which the reported performance aims to demonstrate.

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

• Sample Size for Test Set:
  • For comparison against LC/MS/MS: 197 samples (All samples)
  • For comparison against Abbott IMx® Tacrolimus II Assay: 192 samples (All samples)
• Data Provenance: The samples were from "2 transplant groups (liver and kidney)". The studies were "conducted at two external sites". This indicates the data is prospective or at least gathered specifically for this study, and likely from a clinical setting. The country of origin is not explicitly stated, but given the manufacturer (Dade Behring Inc., US-based) and the FDA submission, it is likely the data was collected in the United States.

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

This information is not provided in the document. For methods like LC/MS/MS, the "ground truth" is typically defined by the analytical method itself rather than human expert interpretation of results, as it is considered a highly accurate and precise reference method.

4. Adjudication Method for the Test Set

This information is not applicable/provided. Adjudication methods are typically relevant for studies where human interpretation of data (e.g., images) forms the ground truth or is being evaluated for consistency. In this case, the comparisons are against established quantitative analytical methods (LC/MS/MS and a predicate immunoassay), where the result is a numerical value directly from the instrument.

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 evaluating the impact of an AI system on human interpretation of medical images or other data. The Emit® 2000 Tacrolimus Assay is an in vitro diagnostic test that provides a quantitative result directly, not a system designed for human-in-the-loop assistance for interpretation.

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

Yes, a standalone performance evaluation was done. The entire study focuses on the "algorithm only" (the Emit® 2000 Tacrolimus Assay) performance by comparing its quantitative output to other analytical methods. The device provides a direct numerical result without human interpretation being part of its core function or an evaluated human-in-the-loop workflow.

7. The Type of Ground Truth Used

The ground truth used for comparison was established by:

• Liquid Chromatography/Mass Spectrometry (LC/MS/MS): This is a highly accurate and precise analytical method often considered the gold standard for quantitative measurements of tacrolimus.
• Abbott IMx® Tacrolimus II Assay: This is a legally marketed predicate device, recognized as an established method for tacrolimus testing.

8. The Sample Size for the Training Set

The document does not provide information regarding a "training set" or its sample size. Immunoassays like the Emit® 2000 Tacrolimus Assay are developed through chemical and biological engineering, not typically 'trained' in the same way machine learning algorithms are. The provided data represents validation against existing methods.

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

As no training set is mentioned for this type of IVD device, this information is not applicable/provided. The ground truth for validation was established by LC/MS/MS and the predicate device.

Ask a specific question about this device

The CEDIA® Tacrolimus Assay is an in vitro diagnostic medical device intended for the quantitative determination of tacrolimus in human whole blood using automated clinical chemistry analyzers as an aid in the management of kidney and liver transplant recipients receiving tacrolimus therapy.

CEDIA® Tacrolimus Calibrators are intended for calibration of the CEDIA® Tacrolimus Assay in whole blood.

The CEDIA® Tacrolimus Assay uses recombinant DNA technology (US Patent No. 4708929) to produce a unique homogeneous enzyme immunoassay system. The assay is based on the bacterial enzyme ß-galactosidase, which has been genetically engineered into two inactive fragments i.e., enzyme acceptor (EA) and enzyme donor (ED). These fragments spontaneously reassociate to form fully active enzyme that, in the assay format, cleaves a substrate, generating a color change that can be measured spectrophotometrically.

In the assay, analyte in the sample competes with analyte conjugated to one inactive fragment (ED) of ß-galactosidase for antibody binding site. If analyte is present in the sample, it binds to antibody, leaving the inactive enzyme fragments free to form active enzyme. If analyte is not present in the sample, antibody binds to analyte conjugated on the inactive fragment, inhibiting the reassociation of inactive ß-galactosidase fragments, and no active enzyme is formed. The amount of active enzyme formed and resultant absorbance change are directly proportional to the amount of analyte present in the sample.

The provided text describes the 510(k) summary for the CEDIA® Tacrolimus Assay, primarily focusing on its substantial equivalence to a predicate device rather than detailing specific acceptance criteria and a dedicated study proving its fulfillment. Therefore, some information, particularly regarding specific performance metrics and a standalone study to meet predefined acceptance criteria, is not explicitly present.

However, based on the context of a 510(k) submission and the information provided, we can infer and construct a response.

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

Acceptance Criteria and Device Performance Study

The document states that the CEDIA® Tacrolimus Assay is substantially equivalent to the IMx® Tacrolimus II (MEIA). This equivalence is demonstrated by comparing device characteristics and, implicitly, performance, although specific performance acceptance criteria and direct comparative performance data against these criteria are not explicitly detailed in the provided summary. The guidance document "Class II Special Controls Guidance Document: Cyclosporine and Tacrolimus Assays; Guidance for Industry and FDA", dated September 16, 2002, was followed to demonstrate this equivalence.

Given the nature of diagnostic assays, "acceptance criteria" generally involve analytical performance characteristics like precision, accuracy, linearity, lower limit of detection (LoD), upper limit of quantification (LoQ), and potential interferences. While these specific criteria and the detailed results against them are not provided, the claim of "substantial equivalence" implies that these were assessed and found comparable to the predicate device.

1. Table of Acceptance Criteria and Reported Device Performance

As specific numerical acceptance criteria and direct performance metrics against them are not explicitly stated in the provided text, the table below will reflect the comparison made for "substantial equivalence" based on device characteristics. For a diagnostic assay, typical performance criteria would involve analytical accuracy, precision, and agreement with the predicate.

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

The document does not specify the sample size used for the test set or the data provenance (e.g., country of origin, retrospective or prospective). It broadly mentions that "Data and results provided in this premarket notification were collected and prepared, respectively, in accordance with the established guideline, 'Class II Special Controls Guidance Document: Cyclosporine and Tacrolimus Assays; Guidance for Industry and FDA'". This guideline is likely to define the requirements for such studies, but the specific details are absent from this summary.

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

This information is not applicable and hence not provided. For an in vitro diagnostic (IVD) quantitative assay like the CEDIA® Tacrolimus Assay, ground truth is typically established through reference methods, certified calibrators, or established analytical techniques directly measuring tacrolimus concentration, rather than human expert interpretation of images or clinical assessments.

4. Adjudication method for the test set

This information is not applicable and hence not provided for a quantitative IVD assay. Adjudication methods like "2+1" or "3+1" are relevant for subjective interpretations, often in imaging or pathology, where human experts might disagree.

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

This information is not applicable. The CEDIA® Tacrolimus Assay is an in vitro diagnostic (IVD) device for quantitative biochemical analysis, not an AI-assisted diagnostic tool that aids human readers (e.g., radiologists interpreting images). Therefore, an MRMC study with human readers and AI assistance is not relevant to this device.

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

Yes, a standalone performance assessment was implicitly done. The CEDIA® Tacrolimus Assay is an automated enzyme immunoassay system. Its performance evaluation would have been conducted as an "algorithm only" (or assay-only) study to determine its analytical characteristics (accuracy, precision, linearity) and compare them to the predicate device. The claim of "substantial equivalence" is based on the standalone performance of the assay. The summary does not detail the specifics of this standalone study, but it is integral to the submission.

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

For this type of quantitative diagnostic assay, the "ground truth" would be established by:

• Reference materials/calibrators: Tacrolimus concentrations would be measured against highly pure, certified reference standards.
• Comparison to a legally marketed predicate device: The submitted study directly aims to show substantial equivalence to the IMx® Tacrolimus II, implying the predicate device's results serve as a comparative standard or "ground truth" for evaluating the novel assay's performance.

8. The sample size for the training set

The document does not provide details on a "training set." The development of an IVD assay typically involves internal development and validation, which might use various samples (clinical, spiked, controls) for optimization and preliminary testing. However, the term "training set" is more commonly used in machine learning and AI contexts. For an immunoassay, the samples used for validating performance are usually referred to as "validation sets" or "test sets" as outlined in question 2.

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

As there is no explicit mention of a "training set" in the context of machine learning for this IVD device, this question is not directly applicable in the sense of establishing ground truth for AI model training. The ground truth for assay development and validation (if considered broadly analogous to "training/validation" in an AI sense) would be established as described in point 7 (reference materials/calibrators, comparison to predicate).

Ask a specific question about this device