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The CELLTRACKS ANALYZER II® is a semi-automated fluorescence microscope used to enumerate fluorescently labeled cells that are immunomagnetically selected and aligned. This product is for in vitro diagnostic use when used in tandem with specimen preparation equipment and reagents that are legally marketed for in vitro diagnostic use with this device.

The CELLTRACKS ANALYZER II® is a semi-automated fluorescence microscope, consisting of the analyzer, a dedicated computer with CELLTRACKS® software, monitor, keyboard, mouse and uninterruptible power supply (UPS). The system also supports an optional Remote Review Workstation, which consists of a dedicated computer with CELLTRACKS® software, monitor, keyboard and mouse. Use of this product requires training and should be used under the supervision of laboratory management. The CELLTRACKS ANALYZER II® is for analysis of rare cells that are isolated from biological fluids including whole blood. It is used in conjunction with the CELLTRACKS® AUTOPREP® System, which automates and standardizes the sample preparation with specific reagent kits. The optional Remote Review Workstation provides the capability to review images and report results remotely.

The provided text does not contain detailed acceptance criteria or a specific study that demonstrates the device meets these criteria in the format requested. The document is a 510(k) summary for the CELLTRACKS ANALYZER II® System, focusing on establishing substantial equivalence to a predicate device.

However, based on the information provided, here's a breakdown of what can be inferred or explicitly stated, and what is not present:

1. Table of Acceptance Criteria and Reported Device Performance:

This information is not provided in the document. The submission states "The information presented in the premarket notification demonstrates that the performance of the CELLTRACKS ANALYZER II® System (modified) is substantially equivalent to the predicate device." but does not list specific performance metrics or their acceptable ranges.

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

This information is not explicitly provided in the document. The document mentions "Non-clinical testing for the CELLTRACKS ANALYZER II® System included: Unit/Integration/System Verification, System Level Validation, Stress Testing, Regression Testing, Control Cell/Sample Performance Validation Testing." but does not specify the sample sizes, data origin (country), or whether the data was retrospective or prospective for these tests.

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

This information is not provided in the document. The device is for "enumerating fluorescently labeled cells that are immunomagnetically selected and aligned," so human interpretation/adjudication might not be the primary ground truth establishment method. However, if any human review was involved in validation, it's not detailed.

4. Adjudication Method for the Test Set:

This information is not provided in the document.

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

This information is not provided in the document. Given the description of the device as a "semi-automated fluorescence microscope used to enumerate fluorescently labeled cells," it's unlikely a traditional MRMC study as commonly understood for image-based diagnostic interpretations was performed or would be relevant in the same way. The focus seems to be on the accuracy and consistency of the enumeration function itself.

6. Standalone (Algorithm Only) Performance:

The device is described as "semi-automated" and includes "CELLTRACKS® software." The primary study mentioned is "non-clinical functional testing" to demonstrate substantial equivalence. The document doesn't explicitly refer to "algorithm only" performance as a distinct study. However, the system's core function is automated cell enumeration, suggesting that its performance is essentially standalone in terms of the enumeration task. The "semi-automated" aspect likely refers to the overall workflow involving sample preparation and then the device's automated analysis.

7. Type of Ground Truth Used:

This information is not explicitly provided in the document. For a cell enumeration system, the ground truth would typically be established by a highly accurate (manual or another validated automated) counting method, or potentially by using spiked samples with a known number of cells. The document mentions "Control Cell/Sample Performance Validation Testing," which implies the use of samples with known characteristics, but the method for establishing that "known" is not detailed.

8. Sample Size for the Training Set:

This information is not provided in the document. The document refers to software modifications (version 2.6.0) but does not detail any machine learning algorithms or training processes that would require a separate training set. The term "algorithm" is not used in the context of learned models. It appears to be a rule-based or image processing system rather than a deep learning model.

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

This information is not provided and is likely not relevant as no machine learning training set is mentioned.

Summary of what is present:

• Device Name: CELLTRACKS ANALYZER II® System
• Predicate Device: CELLTRACKS ANALYZER II® (K113181)
• Modifications: Software update (version 2.6.0) and addition of an optional Remote Review Workstation.
• Basis for Equivalence: Non-clinical functional testing demonstrating performance is "substantially equivalent" to the predicate device.
• Testing Types Mentioned: Unit/Integration/System Verification, System Level Validation, Stress Testing, Regression Testing, Control Cell/Sample Performance Validation Testing.
• Intended Use/Indications: Enumerating fluorescently labeled cells that are immunomagnetically selected and aligned, for in vitro diagnostic use.

It's important to note that a 510(k) summary often provides a high-level overview. The detailed performance data, acceptance criteria, and study methodologies would be contained within the full 510(k) submission, which is not publicly available in this format.

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The CELLTRACKS® AUTOPREP® System is a laboratory instrument used with immunomagnetic reagents that capture and enrich target cells, and labeling reagents that differentiate cells in whole blood. The CELLTRACKS ANALYZER II® may be used for cell identification and enumeration. The system is for in vitro diagnostic use.

The CELLTRACKS® AUTOPREP® System is a general purpose laboratory instrument used with immunomagnetic reagents that capture and enrich target cells, and labeling reagents that differentiate cells in whole blood. The CELLTRACKS® AUTOPREP® System processes up to 8 samples in a batch, performing all required process steps, including red cell detection, plasma aspiration and final transfer to the analysis cartridge. The user is prompted to perform various pre-processing operations such as dilution and centrifugation. Cell analyzers such as the CELLTRACKS ANALYZER II® may be used for cell identification and enumeration following processing. The CELLTRACKS® AUTOPREP® system uses a series of immunomagnetic separation procedures to isolate the cells of interest and to stain the cells with fluorescence-labeled monoclonal antibodies.

This is a 510(k) summary for the CELLTRACKS® AUTOPREP® System, a medical device for in vitro diagnostic use. The purpose of this submission is to demonstrate substantial equivalence to a predicate device (CELLTRACKS® AUTOPREP® System (current - K110406)). The only change is a modification to the pipetting probe to reduce potential carryover and a corresponding label change.

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

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

The provided 510(k) summary does not explicitly state numerical acceptance criteria for carryover. Instead, it focuses on demonstrating equivalence to the predicate device and characterization of the new probe's performance regarding carryover.

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

The document does not explicitly state the sample size used for the test set in terms of the number of patient samples. It mentions "up to 8 samples in a batch" for processing but this refers to the operational capacity of the instrument, not the sample size of the study for performance validation.

• Test Set Sample Size: Not explicitly stated for each test, but "up to 8 samples in a batch" is mentioned for processing.
• Data Provenance: Not explicitly stated (e.g., country of origin, retrospective/prospective). The testing is described as "Non-clinical functional testing," implying laboratory-based testing rather than patient data collection in a clinical setting.

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

Not applicable. This device is an automated instrument for processing and enriching cells. The evaluation appears to be based on analytical performance metrics (e.g., carryover levels, assay performance equivalence) rather than expert interpretation of images or patient data. Therefore, there's no mention of experts establishing ground truth for the test set in this context.

4. Adjudication method for the test set

Not applicable, as there are no human interpretations or classifications that would require adjudication. The testing is focused on the device's functional performance.

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

Not applicable. This is not an AI-assisted diagnostic device that involves human readers. It's an automated sample preparation system.

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

This refers to a standalone product. The CELLTRACKS® AUTOPREP® System is a standalone instrument for sample preparation. The performance evaluation described is of the instrument's functional characteristics (e.g., pipetting, carryover), which is inherently "standalone" in its operation relative to the manual methods it automates. The "algorithm" in this context would be the automated processing steps of the instrument.

7. The type of ground truth used

The "ground truth" for this device would be defined by the expected analytical performance. For example:

• Known Cell Spikes: For CTC spike level characterization, a known number of tumor cells would be "spiked" into samples, and the device's ability to recover them, and the level of carryover from these known spikes, would be measured.
• Control Cells: For control cell carryover, known control cells would be used.
• Reference Methods: The "new reagent probe versus current reagent probe assay performance equivalence" would imply comparison to assays run with the predicate device's probe, where the "truth" is the established performance of the predicate.
• Engineering Specifications: Reliability/Life testing would be against pre-defined engineering specifications for durability and performance over time.

Therefore, the ground truth is based on analytical standards, known input concentrations (e.g., spiked cells), and comparison to a well-characterized predicate device's performance.

8. The sample size for the training set

Not applicable. This device is not an AI/ML algorithm that requires a "training set." It's an automated instrument where the "learning" is incorporated during its design and engineering phases, not through a data-driven training process.

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

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

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The CellTracks® AutoPrep® System is a general purpose laboratory instrument used with immunomagnetic reagents that capture and enrich target cells, and labeling reagents that differentiate cells in whole blood. Cell analyzers such as the CellTracks Analyzer II®, flow cytometers or microscopes may be used for cell identification and enumeration. The system is for in vitro diagnostic use.

The CellTracks® AutoPrep® System is a general purpose laboratory instrument used with immunomagnetic reagents that capture and enrich target cells, and labeling reagents that differentiate cells in whole blood.

This document is a FDA 510(k) clearance letter and does not contain the detailed information required to answer the prompt. Specifically, it does not describe the acceptance criteria, the study details, sample sizes, expert qualifications, or ground truth establishment. It merely states that the device, CellTracks® AutoPrep® System, is substantially equivalent to a legally marketed predicate device for its indicated use.

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The CELLTRACKS ANALYZER II® is a semi-automated fluorescence microscope used to enumerate fluorescently labeled cells that are immunomagnetically selected and aligned. This product is for in vitro diagnostic use when used in tandem with specimen preparation equipment and reagents that are legally marketed for in vitro diagnostic use with this device.

The CELLTRACKS ANALYZER II® is a semi-automated fluorescence microscope, consisting of the analyzer, a dedicated computer with CELLTRACKS® software, monitor, keyboard, mouse and uninterruptible power supply (UPS). Use of this product requires training and should be used under the supervision of laboratory management. The CELLTRACKS ANALYZER II® is for analysis of rare cells that are isolated from biological fluids including whole blood. It is used in conjunction with the CELLTRACKS® AUTOPREP® System, which automates and standardizes the sample preparation with specific reagent kits.

Here's an analysis of the provided text regarding the CellTracks Analyzer II® device's acceptance criteria and studies:

Based on the provided 510(k) summary, the device under review (CellTracks Analyzer II®) is an upgrade to an existing predicate device (CellTracks Analyzer II® K060110). This submission primarily focuses on software verification and validation, rather than a new standalone clinical study with specific acceptance criteria in terms of diagnostic performance metrics like accuracy, sensitivity, or specificity against a clinical ground truth.

The document does not explicitly state specific acceptance criteria in terms of diagnostic performance metrics for the device. Instead, the acceptance criterion appears to be demonstrating substantial equivalence to the predicate device through software verification and validation.

The "study" that proves the device meets the acceptance criteria is the software verification and validation activities. The summary states: "Equivalence was demonstrated through software verification and validation." This implies that the software changes (upgrade from version 2.4 to 2.5.0, operating system update, anomaly solutions, new features) were thoroughly tested to ensure they did not negatively impact the device's function and continued to perform as expected, consistent with the predicate device.

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

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria (Implied by the 510(k) Summary):

• Maintain substantial equivalence to the predicate device (CellTracks Analyzer II® K060110).
• Ensure the software upgrade (from version 2.4 to 2.5.0) does not introduce new safety or effectiveness issues.
• The software performs its intended functions (image acquisition, analysis, cell selection, review, reporting, archiving, logic and interface to PC) consistently with the predicate.

Reported Device Performance (from the 510(k) Summary):

• The performance of the CellTracks Analyzer II® (modified) is demonstrated to be substantially equivalent to the predicate device.
• No new issues of safety or effectiveness have been raised.
• Changes made include an upgraded operating system, solutions to software anomalies, new features for customer satisfaction, and software text string translations.

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

The 510(k) summary does not explicitly mention a "test set" in the context of clinical cases or patient samples for diagnostic performance evaluation or sample sizes for such tests. Given that the submission is for a software upgrade to an already cleared device and demonstrates equivalence through software verification and validation, it's highly probable that testing involved internal software validation datasets and possibly samples used in regression testing, but no specific number of patient samples or studies on human data are described as part of this submission for establishing substantial equivalence. The data provenance is not specified.

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

This information is not provided in the summary. Since the submission focuses on software changes and substantial equivalence through software verification/validation rather than a new clinical performance study, there's no mention of experts establishing ground truth for a test set of patient data.

4. Adjudication Method for the Test Set

Since no clinical "test set" with expert assessment is mentioned, no adjudication method is described.

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 according to this 510(k) summary. The submission focuses on software verification and validation to demonstrate equivalence to a predicate device, not on assessing human reader improvement with or without AI assistance. The device itself is a "semi-automated fluorescence microscope" for enumeration, implying technical functionality rather than direct AI assistance to human diagnostic interpretation in the typical MRMC study context.

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

The 510(k) summary does not explicitly describe a standalone performance study of the algorithms. However, the device description states it is a "semi-automated fluorescence microscope" and explicitly mentions that "All of the algorithms associated with image acquisition, analysis, cell selection, review, reporting and archiving and the logic and interface to the PC remain the same" as the predicate. This suggests the algorithms have a standalone function within the semi-automated enumeration process, but formal standalone performance metrics (e.g., accuracy, precision of enumeration against a 'true' count) for the upgraded software version are not presented as part of this summary to demonstrate acceptance criteria. The verification and validation activities would have confirmed that these algorithms continue to perform their intended function.

7. The Type of Ground Truth Used

Given the nature of the device (immunomagnetic cell selection and enumeration) and the focus on software updates for an existing device, the "ground truth" during software verification and validation would likely involve:

• Reference data/simulated data: To test algorithm changes and ensure correct processing.
• Known sample counts/calibrated controls: For enumeration accuracy testing.
• Comparison to the predicate device's output: To ensure consistent results post-update.

However, the specific type of ground truth (e.g., pathology, outcomes data, expert consensus on images) is not detailed in this summary. It's more likely related to internal technical validation against established benchmarks for cell enumeration and image processing.

8. The Sample Size for the Training Set

The 510(k) summary does not mention a training set in the context of machine learning. The device described appears to use established algorithms for image analysis and cell enumeration rather than a machine learning model that requires a "training set" in the modern sense. Therefore, this question is not applicable based on the provided document.

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

As no training set is mentioned (see point 8), this information is not applicable.

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The CellSearch® Circulating Tumor Cell Kit is intended for the enumeration of circulating tumor cells (CTC) of epithelial origin (CD45-, EpCAM+, and cytokeratins 8, 18+, and/or 19+) in whole blood. The presence of CTC in the peripheral blood, as detected by the CellSearch® Circulating Tumor Cell Kit, is associated with decreased progression free survival and decreased overall survival in patients treated for metastatic breast, colorectal or prostate* cancer. The test is to be used as an aid in the monitoring of patients with metastatic breast, colorectal or prostate cancer. Serial testing for CTC should be used in conjunction with other clinical methods for monitoring metastatic breast, colorectal and prostate cancer. Evaluation of CTC at any time during the course of disease allows assessment of patient prognosis and is predictive of progression free survival and overall survival.

*Metastatic prostate cancer patients in this study were defined as having two consecutive increases in the serum marker PSA above a reference level, despite standard hormonal management. These patients are commonly described as having androgen-independent, hormone-resistant, or castration-resistant prostate cancer.

The CellSearch® Circulating Tumor Cell Kit contains a ferrofluid-based capture reagent and immunofluorescent reagents. The ferrofluid reagent consists of small particles with a magnetic core surrounded by a polymeric layer coated with antibodies targeting the EpCAM antigen for capturing CTC. After immunomagnetic capture and enrichment, fluorescent reagents are added for identification and enumeration of CTC. The fluorescent reagents include the following: anti-CK-Phycoerythrin (PE) specific for the intracellular protein cytokeratin (characteristic of epithelial cells), DAPI, which stains the cell nucleus, and anti-CD45-Allophycocyanin (APC) specific for leukocytes.

The reagent/sample mixture is dispensed by the CellTracks® AutoPrep® System into a cartridge that is inserted into a MagNest® cell presentation device. The strong magnetic field of the MagNest® device attracts the magnetically labeled epithelial cells to the surface of the cartridge. The CellTracks Analyzer II® or CellSpotter® Analyzer automatically scans the entire surface of the cartridge, acquires images and displays any event to the user where CK-PE and DAPI fluorescence are co-located. Images are presented to the user in a gallery format for final classification. An event is classified as a tumor cell when its morphological features are consistent with that of a tumor cell and it exhibits the phenotype EpCAM+, CK+, DAPI+ and CD45-.

The provided document (K103502) describes a 510(k) submission for a modified CellSearch® Circulating Tumor Cell Kit. However, it does not contain a study with acceptance criteria and a detailed report of device performance against those criteria in the way typically expected for a new or significantly modified device efficacy trial.

Instead, this 510(k) is a Special 510(k), which is submitted when there are minor changes to a legally marketed device that do not affect the intended use, fundamental scientific technology, mode of operation, or specimen type. In this particular case, the changes were labeling changes to assist the operator.

Therefore, the submission demonstrates equivalence to the predicate device (K073338) through verification of labeling specifications for the modified device and labeling process validation, rather than through a new clinical study with performance metrics against acceptance criteria.

Due to the nature of this particular 510(k) submission, many of the requested details about a clinical study, such as sample size, ground truth establishment for test and training sets, expert adjudication, and MRMC studies, are not present in the provided text.

Here's a breakdown of the available information:

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

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

• Not applicable / Not provided. The submission focused on equivalence based on labeling and process validation, not a new clinical performance study.

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

• Not applicable / Not provided. No new clinical test set requiring expert ground truth was described.

4. Adjudication method for the test set:

• Not applicable / Not provided.

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. This device is for circulating tumor cell enumeration, not an imaging device requiring human reader interpretation in the context of an MRMC study comparing AI assistance. The CellTracks Analyzer II® or CellSpotter® Analyzer presents images to the user for final classification, but the 510(k) does not detail MRMC studies for this specific change.

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

• Not explicitly stated as a new study for this 510(k). The device involves an automated process for capture, enrichment, and initial scanning, with a user performing final classification. The submission focuses on the impact of labeling changes, not on a standalone algorithm performance study.

7. The type of ground truth used:

• Not applicable / Not provided for this specific 510(k). For the original predicate device, the "ground truth" for CTC identification would likely be based on the biological markers detected (EpCAM+, CK+, DAPI+, CD45-) and morphological features recognized by trained operators. However, this 510(k) does not present new performance data.

8. The sample size for the training set:

• Not applicable / Not provided. No new algorithm training was described for this submission.

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

• Not applicable / Not provided.

In summary: K103502 is a Special 510(k) for minor labeling changes to an already cleared device. It establishes substantial equivalence by demonstrating that these changes do not affect the device's fundamental performance, rather than by presenting new clinical performance data from a dedicated study with specific acceptance criteria and detailed methodologies for establishing ground truth, sample sizes, or reader studies. The "study" proving the device meets acceptance criteria in this context is the verification of labeling specifications and validation of the labeling process, demonstrating that the modified device remains functionally identical to the predicate.

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The CellTracks® AutoPrep® System is a general purpose laboratory instrument used with immunomagnetic reagents that capture and enrich target cells, and labeling reagents that differentiate cells in whole blood. Cell analyzers such as the CellTracks Analyzer II®, CellSpotter® System, flow cytometers or microscopes may be used for cell identification and enumeration. The system is for in vitro diagnostic use.

The CellTracks® AutoPrep® System is a general purpose laboratory instrument used with immunomagnetic reagents that capture and enrich target cells, and labeling reagents that differentiate cells in whole blood. The CellTracks® AutoPrep® System processes up to 8 samples in a batch, performing all required process steps, including red cell detection, plasma aspiration and final transfer to the analysis cartridge. The user is prompted to perform various pre-processing operations such as dilution and centrifugation. Cell analyzers such as the CellTracks Analyzer II®, CellSpotter® System, flow cytometers or microscopes may be used for cell identification and enumeration following processing.

The AutoPrep® system uses a series of immunomagnetic separation procedures to isolate the cells of interest and to stain the cells with fluorescence-labeled monoclonal antibodies.

The provided text describes a 510(k) premarket notification for the CellTracks® AutoPrep® System. This is a general purpose laboratory instrument for automated blood cell preparation, not an AI/ML powered diagnostic device. Therefore, much of the requested information (such as AI performance metrics, expert adjudication, MRMC studies, and training/test set details) is not applicable or cannot be extracted from this document.

However, I can extract the acceptance criteria related to its substantial equivalence to the predicate device and the study that demonstrates this.

1. Table of Acceptance Criteria and Reported Device Performance

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

The document does not specify a distinct "test set" in the context of AI/ML. The evaluation was based on "functional testing of the bulk fluid module" and "performance testing using quality control samples." The specifics of these samples (e.g., number, type, origin) are not detailed.

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

Not applicable. Ground truth as typically defined for AI/ML validation (e.g., expert consensus on images or pathology) is not relevant for this device's evaluation as it is a laboratory instrument, not an interpretive diagnostic.

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

Not applicable. This concept is typically associated with expert review of diagnostic outputs, which is not described for this device.

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

Not applicable. This device is a pre-analytic instrument, not an AI-powered diagnostic that assists human readers.

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

This refers to the performance of the instrument itself. The study mentioned "functional testing of the bulk fluid module" and "performance testing using quality control samples," which represents the standalone performance of the modified device.

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

The "ground truth" for this device would be the expected functional output and performance metrics based on established laboratory standards and comparisons to the predicate device. This is indicated by "functional testing" and "performance testing using quality control samples." The specific methodology for establishing these performance benchmarks is not detailed beyond these general terms.

8. The sample size for the training set

Not applicable. This device is an instrument, not an AI/ML model that requires a training set.

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

Not applicable.

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The CellSearch™ Circulating Tumor Cell Kit is intended for the enumeration of circulating tumor cells (CTC) of epithelial origin (CD45-, EpCAM+, and cytokeratins 8, 18+, and/or 19+) in whole blood.

The presence of CTC in the peripheral blood, as detected by the CellSearch™ Circulating Tumor Cell Kit, is associated with decreased progression free survival and decreased overall survival in patients treated for metastatic breast, colorectal or prostate* cancer. The test is to be used as an aid in the monitoring of patients with metastatic breast, colorectal or prostate cancer. Serial testing for CTC should be used in conjunction with other clinical methods for monitoring metastatic breast, colorectal and prostate cancer. Evaluation of CTC at any time during the course of disease allows assessment of patient prognosis and is predictive of progression free survival and overall survival.

*Metastatic prostate cancer patients in this study were defined as having two consecutive increases in the serum marker PSA above a reference level, despite standard hormonal management. These patients are commonly described as having androgen-independent, hormone-resistant, or castration-resistant prostate cancer.

The CellSearch" Circulating Tumor Cell Kit contains a ferrofluid-based capture reagent and immunofluorescent reagents. The ferrofluid reagent consists of nanoparticles with a magnetic core surrounded by a polymeric layer coated with antibodies targeting the EpCAM antigen for capturing CTC. After immunomagnetic capture and enrichment, fluorescent reagents are added for identification and enumeration of CTC. The fluorescent reagents include the following: anti-CK-Phycoerythrin (PE) specific for the intracellular protein cytokeratin (characteristic of epithelial cells), DAPI which stains the cell nucleus, and anti-CD45-Allophycocyanin (APC) specific for leukocytes.

The reagent/sample mixture is dispensed by the CellTracks® AutoPrep® System into a cartridge that is inserted into a MagNest® cell presentation device. The strong magnetic field of the MagNest® device attracts the magnetically labeled epithelial cells to the surface of the cartridge. The CellTracks Analyzer II or CellSpotter® Analyzer automatically scans the entire surface of the cartridge, acquires images and displays any event to the user where CK-PE and DAPI fluorescence are co-located. Images are presented to the user in a gallery format for final classification. An event is classified as a tumor cell when its morphological features are consistent with that of a tumor cell and it exhibits the phenotype EpCAM+, CK+, DAPI+ and CD45 -.

Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:

Device: CellSearch™ Circulating Tumor Cell Kit (expanded indications for use in Metastatic Prostate Cancer)

1. Table of Acceptance Criteria and Reported Device Performance:

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The CellSearch™ Circulating Tumor Cell Kit is intended for the enumeration of circulating tumor cells (CTC) of epithelial origin (CD45-, EpCAM+, and cytokeratins 8, 18+, and/or 19+) in whole blood.

The presence of CTC in the peripheral blood, as detected by the CellSearch™ Circulating Tumor Cell Kit, is associated with decreased progression free survival and decreased overall survival in patients treated for metastatic breast or metastatic colorectal cancer. The test is to be used as an aid in the monitoring of patients with metastatic breast or metastatic colorectal cancer. Serial testing for CTC should be used in conjunction with other clinical methods for monitoring breast and colorectal cancer. Evaluation of CTC at any time during the course of disease allows assessment of patient prognosis and is predictive of progression free survival and overall survival.

The CellSearch" Circulating Tumor Cell Kit contains a ferrofluid-based capture reagent and immunofluorescent reagents. The ferrofluid reagent consists of nanoparticles with a magnetic core surrounded by a polymeric layer coated with antibodies targeting the EpCAM antigen for capturing CTC. After immunomagnetic capture and enrichment, fluorescent reagents are added for identification and enumeration of CTC. The fluorescent reagents include the following: anti-CK-Phycoerythrin (PE) specific for the intracellular protein cytokeratin (characteristic of epithelial cells), DAPI which stains the cell nucleus, and anti-CD45-Allophycocyanin (APC) specific for leukocytes.

The reagent/sample mixture is dispensed by the CellTracks® AutoPrep® System into a cartridge that is inserted into a MagNest® cell presentation device. The strong magnetic field of the MagNest® device attracts the magnetically labeled epithelial cells to the surface of the cartridge. The CellTracks® Analyzer II or CellSpotter® Analyzer automatically scans the entire surface of the cartridge, acquires images and displays any event to the user where CK-PE and DAPI fluorescence are co-located. Images are presented to the user in a gallery format for final classification. An event is classified as a tumor cell when its morphological features are consistent with that of a tumor cell and it exhibits the phenotype EpCAM+, CK+, DAPI+ and CD45 -.

Here's a breakdown of the acceptance criteria and the study details for the CellSearch™ Circulating Tumor Cell Kit, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document describes several performance characteristics without explicitly stating "acceptance criteria" for each. However, the study results clearly demonstrate the device's performance in these areas.

• 1300 expected: 1215 mean observed (91-95% range)
• 325 expected: 308 mean observed (82-101% range)
• 81 expected: 85 mean observed (80-136% range)
• 20 expected: 22 mean observed (95-140% range)
• 5 expected: 7 mean observed (120-200% range)
  Linear regression: Y=0.93x + 3.87, R=0.999. |
  | Linearity/Reportable Range | Detection of CTCs should be linear over the reportable range. | Linear detection over the reportable range of 0 to 1238 tumor cells. After factoring out percent recovery, regression of observed vs. expected tumor cells yielded a slope of 1.007, an intercept of 3.0, and an R² = 0.990 (R = 0.995). |
  | Limit of Detection (LoD) | Ability to detect a low number of CTCs. | 1 CTC per 7.5 mL can be detected by the CellTracks® Analyzer II. The 7% loss in recovery does not reduce this LoD. |
  | System Reproducibility (Control) | Consistent results for control samples. | Low Control (N=99): Mean cell count 48, Total Precision Standard Deviation (% CV) 18%.
  High Control (N=99): Mean cell count 969, Total Precision Standard Deviation (% CV) 5%. |
  | System Reproducibility (Patient Samples - MBC) | Consistent results for duplicate patient samples for MBC. | MBC (N=163 duplicate samples): Regression equation Y=0.98x + 0.67, R=0.99. |
  | System Reproducibility (Patient Samples - MCRC) | Consistent results for duplicate patient samples for MCRC. | MCRC (N=1627 duplicate samples): Regression equation Y=0.98x + 0.18, R²=0.96. |
  | PFS Prediction (MCRC) | Ability to differentiate patient groups with significantly different Progression Free Survival based on CTC levels. | Baseline CTC: Median PFS significantly longer in

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The CellSearch™ Circulating Tumor Cell Kit is intended for the enumeration of circulating tumor cells (CTC) of epithelial origin (CD45-, EpCAM+, and cytokeratins 8, 18+, and/or 19+) in whole blood.

The presence of CTC in the peripheral blood, as detected by the CellSearch™ Circulating Tumor Cell Kit, is associated with decreased progression free survival and decreased overall survival in patients treated for metastatic breast cancer. The test is to be used as an aid in the monitoring of patients with metastatic breast cancer. Serial testing for CTC should be used in conjunction with other clinical methods for monitoring breast cancer. A CTC count of 5 or more per 7.5 mL of blood at any time during the course of the disease is predictive of shorter progression free survival and overall survival.

The CellSearch™ Circulating Tumor Cell Kit contains a ferrofluid-based capture reagent and immunofluorescent reagents. The ferrofluid reagent consists of nanoparticles with a magnetic core surrounded by a polymeric layer coated with antibodies targeting the EpCAM antigen for capturing CTC. After immunomagnetic capture and enrichment, fluorescent reagents are added for identification and cnumeration of CTC. The fluorescent reagents include the following: anti-CK-Phycoerythrin (PE) specific for the intracellular protein cytokeratin (characteristic of epithelial cells), DAPI which stains the cell nucleus, and anti-CD45-Allophycocyanin (APC) specific for leukocytes.

The reagent/sample mixture is dispensed by the CellTracks AutoPrep® System into a cartridge that is inserted into a MagNest® cell presentation device. The strong magnetic field of the MagNest® device attracts the magnetically labeled epithelial cells to the surface of the cartridge. The CellTracks® Analyzer II or CellSpotter® Analyzer automatically scans the entire surface of the cartridge, acquires images and displays any event to the user where CK-PE and DAPI fluorescence are co-located. Images are presented to the user in a gallery format for final classification. An event is classified as a tumor cell when its morphological features are consistent with that of a tumor cell and it exhibits the phenotype EpCAM+, CK+, DAPI+ and CD45-.

The CellSearch™_Circulating Tumor Cell Kit is intended for the enumeration of circulating tumor cells (CTC) of epithelial origin (CD45-, EpCAM+, and cytokeratins 8, 18+, and/or 19+) in whole blood. The presence of CTC in the peripheral blood, as detected by the CellSearch™_Circulating Tumor Cell Kit, is associated with decreased progression free survival and decreased overall survival in patients treated for metastatic breast cancer. The test is to be used as an aid in the monitoring of patients with metastatic breast cancer. Serial testing for CTC should be used in conjunction with other clinical methods for monitoring breast cancer. A CTC count of 5 or more per 7.5 mL of blood at any time during the course of the disease is predictive of shorter progression free survival and overall survival.

ACCECPTANCE CRITERIA

STUDY DETAILS

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

   • Recovery and Linearity: 30 samples from 5 healthy donors. Spiked with cultured breast cancer cells (SK-BR-3).
   • Reproducibility (Patient Samples): 163 duplicate samples from 47 patients.
   • Expected Values (Control Subjects): 345 total samples (145 healthy volunteers, 101 women with non-malignant breast disease, 99 women with other non-malignant diseases).
   • Clinical Study (Metastatic Breast Cancer): 177 patients with metastatic breast cancer. Follow-up analyses had varying sample sizes at different time points (e.g., 126 at 3-5 weeks, 138 for imaging comparison).
   • Data Provenance: Retrospective for recovery, linearity, and reproducibility. Prospective, multi-center clinical trial for metastatic breast cancer patients. Country of origin not specified, but the applicant is Veridex, LLC, located in Warren, NJ, USA.

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

   • Clinical Study (Imaging Ground Truth): Two expert radiologists initially, blinded to clinical information. A third independent radiologist adjudicated disagreements. Qualifications are not specified beyond "expert radiologists."

3. Adjudication method for the test set:

   • Imaging Ground Truth:
     • If one radiologist categorized as Indeterminate (I) and the other as Stable Disease (S), Partial Response (PR), or Progressive Disease (PD), the latter radiologist's classification was used (n=11).
     • If both radiologists categorized as Indeterminate (I), the data was not used (n=3).
     • A third independent radiologist adjudicated disagreements between the two primary readers regarding PD and NPD (n=27). If the third radiologist rendered "Indeterminate (I)", the data was not used (n=2).

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

   • The study did not describe an MRMC comparative effectiveness study involving AI or human readers being assisted by AI. The comparison was betweenCTC measurements and radiological assessments, primarily on their prognostic value and variability. The device is not an AI-assisted diagnostic tool for human readers but rather an automated system for CTC enumeration.

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

   • Yes, the performance of the CellSearch™ system, which includes automated scanning and image acquisition (CellTracks® Analyzer II or CellSpotter® Analyzer) with user classification of events, was evaluated. The "user classification" aspect suggests a human-in-the-loop for final interpretation of events presented by the system, but the core processing and initial identification are automated. The recovery, linearity, limits of detection, and reproducibility studies assess the standalone performance of the system for enumerating CTCs.

6. The type of ground truth used:

   • Recovery & Linearity: Expected cell counts from spiked cultured breast cancer cells.
   • Reproducibility: Comparison of duplicate samples processed by the system.
   • Clinical Study:
     • Prognosis (PFS/OS): Clinical outcomes data (progression-free survival and overall survival) based on CT scans, clinical signs and symptoms, and time to death.
     • Imaging Comparison: Expert consensus of radiologists based on World Health Organization (WHO) bi-dimensional criteria for disease assessment (NPD vs. PD).

7. The sample size for the training set:

   • The document does not explicitly describe a separate "training set" for the device's development or a machine learning algorithm. The studies detailed are primarily validation studies of the device's technical performance and clinical utility.

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

   • Not applicable as no specific training set for a machine learning algorithm is described. The device operates based on immunomagnetic capture and fluorescent labeling with rule-based classification principles, followed by user classification, rather than being a trained AI model in the modern sense.

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The CellSearch™ Circulating Tumor Cell Kit is intended for the enumeration of circulating tumor cells (CTC) of epithelial origin (CD45-, EpCAM+ and cytokeratin 8 & 18+, and/or cytokeratin 19+) in whole blood in conjunction with the CellTracks® AutoPrep System, the CellSpotter® Analyzer or CellTracks® Analyzer II, and the CellSearch™ Circulating Tumor Cell Control Kit.

The presence of CTC in the peripheral blood, as detected by the CellSearch™ Circulating Tumor Cell Kit, is associated with decreased progression free survival and decreased overall survival in patients treated for metastatic breast cancer. A CTC count of 5 or more per 7.5 mL of blood generally is predictive of shorter progression free survival and shorter overall survival.

Not Found

This document is a 510(k) clearance letter for the CellSearch™ Circulating Tumor Cell Kit, not a study report. Therefore, it does not contain the detailed acceptance criteria and study results in the format requested. The letter confirms that the FDA has found the device to be substantially equivalent to legally marketed predicate devices.

However, I can extract what is present related to device function and some context of a study that would have been submitted to the FDA for this clearance.

Missing Information: Most of the requested information regarding detailed acceptance criteria, sample sizes, ground truth establishment, expert qualifications, adjudication methods, and MRMC study details are not available within this document. This information would typically be found in the 510(k) submission itself, which is a much larger technical dossier.

Here's what can be gathered, with the understanding that key details are absent:

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

• Acceptance Criteria: Not explicitly stated in the document. The clearance letter only states that the device is "substantially equivalent" to predicate devices for its intended use. This implies the device met certain performance criteria compared to the predicate, but these criteria are not itemized here.
• Reported Device Performance: The document provides the intended use and clinical significance of the device's measurements, rather than raw performance metrics.

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

• Sample Size: Not available in this document.
• Data Provenance: Not available in this document.

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)

• Not available in this document. Since this is an assay for enumerating circulating tumor cells using technology like immunomagnetic separation and image analysis, the "ground truth" would likely involve methods beyond just human expert review, potentially including independent staining and manual counting by trained laboratory personnel.

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

• Not available in this document.

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

• This device is for automated enumeration of circulating tumor cells using an analyzer (CellSpotter® Analyzer or CellTracks® Analyzer II). While there's a human element in initiating the test and interpreting the clinical significance, it's primarily an automated system. An "MRMC study" in the traditional sense (improving human reader performance with AI) is unlikely to be directly applicable as the primary claim is the enumeration by the device. The "AI" would be embedded in the CellSpotter® Analyzer's image analysis algorithms. The document does not provide details on such a study or effect sizes.

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

• Yes, the core claim is for the "CellSearch™ Circulating Tumor Cell Kit" used in conjunction with the "CellTracks® AutoPrep System, the CellSpotter® Analyzer or CellTracks® Analyzer II". This implies a standalone performance component of the automated system in enumerating CTCs. However, the exact performance metrics of this standalone component are not provided in this clearance letter. The indications for use describe the kit's function with the automated analyzers.

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

• The "Indications for Use" mentions the device "is associated with decreased progression free survival and decreased overall survival in patients treated for metastatic breast cancer." This suggests that clinical outcomes data (progression-free survival and overall survival) were used to establish the clinical utility and significance of the CTC counts provided by the device. The "ground truth" for enumerating CTCs would typically involve orthogonal methods like manual microscopy counts by trained cytotechnologists or other validated cell counting methods, though this is not explicitly stated.

8. The sample size for the training set

• Not available in this document.

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

• Not available in this document.

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