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ACL TOP 970 CL: The ACL TOP 970 CL is a bench top, fully automated, random access analyzer designed specifically for in vitro diagnostic use by health care professionals in a clinical laboratory. The system provides results for both direct measurements and calculated parameters.
HemosIL CL Anti-Cardiolipin IgM: HemosIL CL Anti-Cardiolipin IgM is a fully automated chemiluminescent immunoassay for the semi-quantitative measurement of anti-cardiolipin (aCL) IgM antibodies in human 3.2% or 3.8% citrated plasma on the ACL TOP 970 CL in the laboratory setting by a healthcare professional, as an aid in the diagnosis of Antiphospholipid Syndrome (APS) when used in conjunction with other laboratory and clinical findings. For use with adult population. For prescription use only.
HemosIL CL Anti-ß2 Glycoprotein-I IgM: HemosIL CL Anti-B2 Glycoprotein-I IgM is a fully automated chemiluminescent immunoassay for the semi-quantitative measurement of anti-B2 Glycoprotein-I (anti-B2GPI) IgM antibodies in human 3.2% or 3.8% citrated plasma on the ACL TOP 970 CL in the laboratory setting by a healthcare professional, as an aid in the diagnosis of Antiphospholipid Syndrome (APS) when used in conjunction with other laboratory and clinical findings. For use with adult population. For prescription use only.

ACL TOP 970 CL Instrument: The ACL TOP 970 CL is an instrument that integrates new chemiluminescent test capability similar to the ACL AcuStar, K083518.
HemosIL CL Anti-Cardiolipin IgM: HemosIL CL Anti-Cardiolipin IgM is a chemiluminescent two-step immunoassay consisting of magnetic particles coated with cardiolipin and human purified ß2GPI, which capture, if present, the aCL antibodies from the sample. After incubation, magnetic separation, and a wash step, a tracer consisting of an isoluminol-labeled anti-human IgM antibody is added and may bind with the captured aCL IgM on the particles. After a second incubation, magnetic separation, and wash step, reagents that trigger the luminescent reaction are added, and the emitted light is measured as relative light units (RLU) by the ACL TOP 970 CL optical system. RLUs are directly proportional to the aCL IgM concentration in the sample.
HemosIL CL Anti-ß2 Glycoprotein-I IgM: HemosIL CL Anti-ß2 Glycoprotein-I IgM is a chemiluminescent two-step immunoassay consisting of magnetic particles coated with human purified ß2GPI, which capture, if present, the aß2GPI antibodies from the sample. After incubation, magnetic separation, and a wash step, a tracer consisting of an isoluminol-labeled anti-human IgM antibody is added and may bind with the captured aß2GPI IgM on the particles. After a second incubation, magnetic separation, and wash step, reagents that trigger the luminescent reaction are added, and the emitted light is measured as relative light units (RLUs) by the ACL TOP 970 CL optical system. RLUs are directly proportional to the aß2GPI IgM concentration in the sample.

The provided text describes the 510(k) summary for the ACL TOP 970 CL instrument and two associated immunoassays, HemosIL CL Anti-Cardiolipin IgM and HemosIL CL Anti-β2 Glycoprotein-I IgM. The studies presented focus on analytical performance and comparability to predicate devices, rather than AI model performance or human-in-the-loop studies. Therefore, many of the requested elements pertaining to AI-driven diagnostic devices (such as expert adjudication, MRMC studies, or training set details for AI) are not applicable or cannot be extracted from this document.

However, I can extract information related to the acceptance criteria for the analytical performance of the assays and how that performance was demonstrated.

Here's a breakdown of the available information:

1. Acceptance Criteria and Reported Device Performance

The acceptance criteria for these in vitro diagnostic devices are demonstrated through various analytical performance studies, focusing on precision, linearity, analytical sensitivity (LoD/LoQ), analytical specificity, and method comparison to predicate devices. The document does not explicitly state pre-defined acceptance thresholds for each parameter (e.g., minimum CV for precision, minimum slope for linearity). Instead, it presents the results of these studies, implying that the observed performance met internal or regulatory acceptance.

HemosIL CL Anti-Cardiolipin IgM

HemosIL CL Anti-β2 Glycoprotein-I IgM

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

• Precision Study (Test Set):
  • HemosIL CL Anti-Cardiolipin IgM & Anti-β2 Glycoprotein-I IgM: 5 plasma samples (3 positive, 2 negative) and 2 levels of controls. Each material was run in duplicate, twice per day over 20 days.
• Reproducibility Study (Test Set):
  • HemosIL CL Anti-Cardiolipin IgM & Anti-β2 Glycoprotein-I IgM: 4 plasma samples (3 positive, 1 negative for Anti-Cardiolipin IgM; 3 positive for Anti-β2 Glycoprotein-I IgM) and 2 levels of controls. Each material tested in triplicate, twice a day for 5 days, totaling 30 replicates per level.
• Analytical Sensitivity (LoD/LoQ):
  • Specific sample numbers for LoD/LoQ for new reagent lots are not detailed, but samples prepared by combining Ab-positive and normal donor plasma were used.
• Linearity:
  • For each assay, samples were prepared by diluting a high antibody plasma sample with a negative antibody plasma sample to create required concentrations. Each level was measured in seven replicates.
• Normal Reference Range:
  • 100 citrated plasma normal donor samples.
• Method Comparison:
  • HemosIL CL Anti-Cardiolipin IgM: N = 131 samples.
  • HemosIL CL Anti-β2 Glycoprotein-I IgM: N = 123 samples.
• APS Outcome Study (Diagnostic Performance):
  • HemosIL CL Anti-Cardiolipin IgM: N = 500 samples.
  • HemosIL CL Anti-β2 Glycoprotein-I IgM: N = 503 samples (indicated by the sum of Positive/Negative categories: 63+17+128+295=503).

Data Provenance: The document does not specify the country of origin for the data or whether the studies were retrospective or prospective, though typical clinical performance studies for diagnostic devices are usually prospective or utilize carefully curated samples. Reproducibility studies were conducted at "3 external sites."

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

This information is not provided. For these in vitro diagnostic immunoassays, the "ground truth" for the analytical performance studies (precision, linearity, etc.) is the quantitative measurement itself, validated against established laboratory methods or reference materials. For the "APS Outcome Study," the ground truth is "APS disease classification per 2006 International Consensus Statement from Miyakis et al." This classification is typically based on a combination of clinical and laboratory findings, interpreted by clinicians, but the specific number and qualifications of experts involved in this classification for the study samples are not detailed.

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

Not applicable, as this is an in vitro diagnostic device measuring analyte concentrations, not an imaging AI relying on expert interpretations or adjudications. The diagnostic performance (sensitivity/specificity) is compared against pre-defined clinical classification criteria (Miyakis et al. 2006).

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 document describes an in vitro diagnostic device (immunoassay and analyzer), not an AI-driven imaging diagnostic device. There is no mention of human readers or AI assistance in diagnostic interpretation.

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

The performance data provided (precision, linearity, sensitivity, specificity, method comparison) is the standalone performance of the device (instrument + assay). The device provides a semi-quantitative measurement of antibodies, which then aids in diagnosis when used "in conjunction with other laboratory and clinical findings." There is no "human-in-the-loop" component in the assay's direct operation or result generation as described beyond the healthcare professional performing the test.

7. The Type of Ground Truth Used

• Analytical Studies (Precision, Linearity, LoD/LoQ, Specificity): The ground truth is inherent to the nature of these highly controlled analytical tests. For example, for linearity, serially diluted samples with known concentrations are used. For interference, samples spiked with known interferents are used.
• Method Comparison: The ground truth is established by the measurements obtained from the predicate (reference) devices: HemosIL AcuStar Anti-Cardiolipin IgM (K092181) and HemosIL AcuStar Anti-β2 Glycoprotein-I IgM (K091556) on the ACL AcuStar (K083518).
• Normal Reference Range: Established by testing 100 samples from "normal donors."
• APS Outcome Study: "APS disease classification per 2006 International Consensus Statement from Miyakis et al." This is a consensus-based clinical classification criteria.

8. The Sample Size for the Training Set

Not applicable, as this is not an AI/machine learning device that requires a distinct training set. The "development" of the assays would involve internal R&D, but not a "training set" in the context of AI.

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

Not applicable, as there is no training set mentioned for an AI model. For the development/validation of the immunoassay itself, the "ground truth" for calibrators and controls would be established through careful analytical procedures, often traceable to international standards or reference materials, under strict quality control.

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HemosIL Liquid Anti-Xa is an automated chromogenic assay for in vitro diagnostic use by laboratory professionals in clinical laboratories. The assay provides quantitative results on 3.2% citrated human plasma for the following analytes based on the calibrators used:

· When used with HemosIL Heparin Calibrators:

Quantitative determination of unfractionated heparin (UFH) and low molecular weight heparin (LMWH) activity on the ACL TOP Family and ACL TOP Family 50 Series.

· When used with HemosIL Apixaban Calibrators:

Quantitative determination of apixaban on the ACL TOP Family 50 Series through measurement of factor Xa activity, which is inversely proportional to the apixaban level. With HemosIL Apixaban Calibrators, the assay is intended to measure apixaban concentrations in patients on apixaban therapy in the following situations where measurement of apixaban levels could be useful to have as additional information:

• Patients at risk for major bleeding

• Patients experiencing a bleeding episode

· When used with HemosIL Rivaroxaban Calibrators:

Quantitative determination of rivaroxaban on the ACL TOP Family and ACL TOP Family 50 Series through measurement of factor Xa activity, which is inversely proportional to the rivaroxaban level. With HemosL Rivaroxaban Calibrators, the assay is intended to measure rivaroxaban concentrations in patients on rivaroxaban therapy in the following situations where measurement of rivaroxaban levels could be useful to have as additional information:

• Patients at risk for major bleeding

• Patients experiencing a bleeding episode

The assay is not a stand-alone test and the results should be used in conjunction with other clinical and laboratory findings. For use in adult population. For prescription use only.

HemosIL Liquid Anti-Xa is a one stage chromogenic assay based on a synthetic chromogenic substrate and on Factor Xa inactivation. The assay provides quantitative rivaroxaban results on 3.2% citrated human plasma as follows: Rivaroxaban levels in patient plasma are measured automatically on ACL TOP Family and ACL TOP Family 50 Series when this assay is calibrated with HemosIL Rivaroxaban Calibrators. Rivaroxaban directly inhibits Factor Xa activity independent of the antithrombin present. The Factor Xa activity measured by the assay is exogenous. Factor Xa is neutralized directly by rivaroxaban. Residual Factor Xa is quantified with a synthetic chromogenic substrate. The paranitroaniline released is monitored kinetically at 405 nm and is inversely proportional to the rivaroxaban level in the sample.

HemosIL Liquid Anti-Xa is an automated chromogenic assay for in vitro diagnostic use by laboratory professionals in clinical laboratories. The assay provides quantitative results on 3.2% citrated human plasma for the following analytes based on the calibrators used:

When used with HemosIL Heparin Calibrators:
• Quantitative determination of unfractionated heparin (UFH) and low molecular weight heparin (LMWH) activity on the ACL TOP Family and ACL TOP Family 50 Series.

When used with HemosIL Apixaban Calibrators:
• Quantitative determination of apixaban on the ACL TOP Family and ACL TOP Family 50 Series through measurement of factor Xa activity, which is inversely proportional to the apixaban level. With HemosIL Apixaban Calibrators, the assay is intended to measure apixaban concentrations in patients on apixaban therapy in the following situations where measurement of apixaban levels could be useful to have as additional information:

• Patients at risk for major bleeding
• Patients experiencing a bleeding episode

When used with HemosIL Rivaroxaban Calibrators:
• Quantitative determination of rivaroxaban on the ACL TOP Family and ACL TOP Family 50 Series through measurement of factor Xa activity, which is inversely proportional to the rivaroxaban level. With HemosIL Rivaroxaban Calibrators, the assay is intended to measure rivaroxaban concentrations in patients on rivaroxaban therapy in the following situations where measurement of rivaroxaban levels could be useful to have as additional information:

• Patients at risk for major bleeding
• Patients experiencing a bleeding episode

The assay is not a stand-alone test and the results should be used in conjunction with other clinical and laboratory findings.

For use in adult population. For prescription use only.

This appears to be a 510(k) summary for a medical device called "HemosIL Liquid Anti-Xa," which is an in vitro diagnostic assay. The document details the device's technical specifications and performance studies to demonstrate substantial equivalence to a predicate device.

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

Important Note: The document focuses on demonstrating substantial equivalence for the HemosIL Liquid Anti-Xa assay for rivaroxaban measurement, comparing it to an existing HemosIL Liquid Anti-Xa device for apixaban measurement. Therefore, the "acceptance criteria" table below will reflect the performance characteristics the manufacturer is demonstrating for the new rivaroxaban application, and how its performance stacks up against those established for the predicate or against generally accepted analytical performance standards for such assays. It's not about a specific "AI" device as might be implied by some questions in the prompt, but rather a diagnostic assay.

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state "acceptance criteria" in a separate section with specific numerical targets. Instead, it presents various performance study results (Precision, Reproducibility, LoB/LoD/LoQ, Linearity, Interferences, Stability, Method Comparison) which collectively demonstrate the device's analytical performance. The acceptance is implied by the successful completion of these studies and the presented data.

Here's a table summarizing the reported device performance for the HemosIL Liquid Anti-Xa for rivaroxaban measurement. The implicit acceptance criteria are that these performance characteristics are adequate for the intended use and comparable to or better than the predicate device/industry standards.

2. Sample Sizes and Data Provenance

• Precision Study:
  • Sample Size: n=80 per instrument/lot for each sample level, tested over 20 days (2 runs/day, 2 replicates/run). 6 citrated plasma samples + Rivaroxaban Controls.
  • Data Provenance: Not explicitly stated (e.g., country of origin, prospective/retrospective). Implied to be internal laboratory studies.
• Reproducibility Study:
  • Sample Size: 270 replicates per level (Rivaroxaban Controls and 5 citrated plasma samples). Each material tested in triplicate, twice a day for 5 days.
  • Data Provenance: Conducted at 3 sites. No specific country of origin or retrospective/prospective status is given, but "multicenter" implies multiple distinct lab settings.
• LoB, LoD, LoQ Studies:
  • Sample Size: Not explicitly stated but implied to be sufficient to meet CLSI EP17-A2 guidelines.
  • Data Provenance: Not explicitly stated, implied to be internal laboratory studies.
• Linearity Studies:
  • Sample Size: Each rivaroxaban level tested in quadruplicate for Analytical Measuring Interval (13 concentrations) and Extended Measuring Interval (9 concentrations).
  • Data Provenance: Not explicitly stated, implied to be internal laboratory studies.
• Interference Studies:
  • Sample Size: Not explicitly stated but implied to be sufficient to meet CLSI EP07 guidelines.
  • Data Provenance: Not explicitly stated, implied to be internal laboratory studies.
• In-Use Stability and Shelf-life Studies:
  • Sample Size: Not explicitly stated.
  • Data Provenance: Not explicitly stated, implied to be internal laboratory studies.
• Method Comparison (HemosIL Liquid Anti-Xa vs. LC-MS/MS):
  • Sample Size: 337 samples.
  • Data Provenance: Multicenter study (3 laboratory sites). Samples were from patients treated with rivaroxaban, including 12 from bleeding patients and 261 from patients at risk of major bleeding. This indicates retrospective clinical samples where the rivaroxaban levels were already established or patients were undergoing treatment. No country of origin is specified.

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

N/A for this type of diagnostic assay. The "ground truth" for the method comparison study was established using a gold standard analytical method (LC-MS/MS), not by human experts interpreting images or clinical cases.

4. Adjudication Method for the Test Set

N/A. This is a quantitative diagnostic assay. The comparison is against a reference analytical method (LC-MS/MS), not subjective human interpretations requiring adjudication.

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

No, this is not applicable. An MRMC study is relevant for imaging or diagnostic tools where human interpretation is a primary component of the diagnostic process (e.g., radiologists reading scans). This device is an automated, chromogenic assay delivering quantitative results.

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

Yes, in essence, the entire performance evaluation (Precision, Reproducibility, LoB/LoD/LoQ, Linearity, Interferences, Stability) is a "standalone" evaluation of the assay's analytical performance. The method comparison study also evaluates the assay (algorithm + reagents + instrument) against a reference method. Human involvement is limited to performing the tests and interpreting the instrument's numerical output, not making a subjective diagnosis based on qualitative assay results.

7. The Type of Ground Truth Used

• For Analytical Performance Studies (Precision, Reproducibility, LoB/LoD/LoQ, Linearity, Interferences, Stability): The "ground truth" is established through carefully prepared samples with known concentrations (e.g., calibrators, controls, spiked samples) or by evaluating the assay's intrinsic performance characteristics against statistical and analytical chemistry standards (e.g., CLSI guidelines).
• For Method Comparison Study: The ground truth was established using LC-MS/MS (Liquid Chromatography–Mass Spectrometry/Mass Spectrometry), which is considered a highly accurate and precise reference method for drug concentration measurement in biological samples.

8. The Sample Size for the Training Set

N/A. This is an assay based on established chromogenic chemistry, not a machine learning or AI model that requires a "training set" in the computational sense. The device's calibration curves are established using calibrators with known concentrations, which are analogous to a very small "training set" in terms of how the system learns to relate absorbance to concentration, but it's not a large-scale data training as seen with AI.

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

N/A. As above, there is no "training set" in the AI/ML context. The assay's performance relies on its chemical and enzymatic principles, and its calibration is set using commercially supplied or manufactured calibrators with assigned values based on internal reference methods.

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Automated latex enhanced immunoassay for the quantitative determination of von Willebrand Factor Antigen (VWF:Ag) in human citrated plasma on IL Coagulation Systems.

The VWF:Ag kit is a latex particle enhanced immunoturbidimetric assay to quantify VWF:Ag in plasma. When a plasma containing VWF:Ag is mixed with the Latex Reagent and the Reaction Buffer included in the kit, the coated latex particles agglutinate. The degree of agglutination is directly proportional to the concentration of VWF:Ag in the sample and is determined by measuring the decrease of transmitted light caused by the aggregates.

The provided text describes a Special 510(k) submission for the HemosIL von Willebrand Factor Antigen assay. This submission focuses on a modification to the reagent's open vial stability claim, reducing it from 3 months to 14 days, rather than introducing a new AI/ML device or significant performance changes. Therefore, many of the requested categories related to AI/ML device performance, ground truth, and expert evaluation are not directly applicable.

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

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

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 specified in the provided text. The text only mentions "testing."
• Data Provenance: Not specified in the provided text.
• Retrospective or Prospective: Not specified.

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 applicable. This submission concerns a chemical reagent's stability, not an AI/ML device requiring expert ground truth for interpretation. The "ground truth" here is the chemical performance of the reagent over time.

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

Not applicable. Adjudication methods are relevant for subjective interpretations, typically in diagnostic imaging or similar fields. This study assesses objective chemical stability.

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/ML device or a diagnostic interpretation study involving human readers.

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

Not applicable. This is not an AI/ML diagnostic algorithm. The study assesses the standalone performance of the reagent's stability.

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

The "ground truth" for this study is the measured performance characteristics of the HemosIL von Willebrand Factor Antigen reagent (e.g., accuracy, precision, linearity) after being opened and stored for various durations up to 14 days, compared to its performance when fresh or within its original 3-month stability claim. The study aims to demonstrate that the reagent's performance remains acceptable throughout the 14-day open-vial period.

8. The sample size for the training set

Not applicable. There is no "training set" as this is not an AI/ML model being developed. The study is a stability test.

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

Not applicable. Refer to point 8.

Summary of the Study:

The study described is an open vial stability study for the HemosIL von Willebrand Factor Antigen reagent. The purpose was to provide data to support a change in the labeled open vial stability claim from 3 months to 14 days.

• Study Design: The study was likely a prospective laboratory study where the reagent was opened, stored at 2-8°C, and then tested at various time points (e.g., day 0, day 7, day 14) to assess its performance.
• Methodology: The testing was performed in accordance with the established CLSI EP25-A guideline, which provides guidance for evaluating reagent stability. This guideline would specify how to conduct the study, what performance parameters to measure (e.g., accuracy, precision, linearity), and acceptance criteria.
• Acceptance Criteria for the Study: While not explicitly listed in quantitative terms, the acceptance criteria would dictate the permissible deviation in performance (e.g., % bias, % CV) of the open and stored reagent compared to a freshly opened reagent or a reference measurement, over the 14-day period. The text states "Testing verified all acceptance criteria were met," implying these criteria were predefined and successfully achieved.
• Conclusion: The study demonstrated that the reagent maintained its defined performance specifications for 14 days after opening when stored at 2-8°C, thus supporting the modified insert claim.

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HemosIL Liquid Anti-Xa is an automated chromogenic assay for in vitro diagnostic use by laboratory professionals in clinical laboratories. The assay provides quantitative results on 3.2% citrated human plasma for the following analytes based on the calibrators used:

• · When used with HemosIL Heparin Calibrators: Quantitative determination of unfractionated heparin (UFH) and low molecular weight heparin (LMWH) activity on the ACL TOP Family and ACL TOP Family 50 Series.
• · When used with HemosIL Apixaban Calibrators:

Quantitative determination of apixaban on the ACL TOP Family 50 Series through measurement of Factor Xa activity, which is inversely proportional to the apixaban level. With HemosIL Apixaban Calibrators, the assay is intended to measure apixaban concentrations in patients on apixaban therapy in the following situations where measurement of apixaban levels could be useful to have as additional information:

• Patients at risk for major bleeding
• Patients experiencing a bleeding episode

The assay is not a stand-alone test and the results should be used in conjunction with other clinical and laboratory findings.

For use in adult population. For prescription use only.

HemosIL Liquid Anti-Xa is a one stage chromogenic assay based on a synthetic chromogenic substrate and on Factor Xa inactivation. The assay provides quantitative results on 3.2% citrated human plasma for the following analytes based on the calibrators used:

. When used with HemosIL Heparin Calibrators:

Heparin levels in patient plasma are measured automatically on ACL TOP Family and ACL TOP Family 50 Series when this assay is calibrated with HemosIL Heparin Calibrators.

Heparin is analyzed as a complex with antithrombin present in the sample. The concentration of this complex is dependent on the availability of the patient's endogenous antithrombin. When the heparinantithrombin complex is formed, two competing reactions take place.

• 1. Factor Xa is neutralized by heparin-antithrombin complex.
• 2. Residual Factor Xa is quantified with a synthetic chromogenic substrate. The paranitroaniline released is monitored kinetically at 405 nm and is inversely proportional to the heparin level in the sample.

In order to reduce the influence from heparin antagonists, such as platelet factor 4 (PF4), dextran sulfate is included in the reaction mixture.

When used with HemosIL Apixaban Calibrators: .

Apixaban levels in patient plasma are measured automatically on ACL TOP Family and ACL TOP Family 50 Series when this assay is calibrated with HemosIL Apixaban Calibrators.

Apixaban directly inhibits Factor Xa activity independent of the antithrombin present. The Factor Xa activity measured by the assay is exogenous. Factor Xa is neutralized directly by apixaban.

Residual Factor Xa is quantified with a synthetic chromogenic substrate. The paranitroaniline released is monitored kinetically at 405 nm and is inversely proportional to the apixaban level in the sample.

Measurement of apixaban concentration is recommended by the International Society of Thrombosis and Hemostasis Subcommittee on Control of Anticoagulation in certain clinical scenarios including bleeding episodes, perioperative management, and suspicion of overdose.

The provided document is a 510(k) summary for a medical device (HemosIL Liquid Anti-Xa), primarily focused on a specific change: modifying the labeled on-board instrument stability claim from 7 days to 4 days and removing claims for a particular instrument family (ACL Elite/Elite Pro). This type of submission (Special 510(k)) indicates that the core device and its fundamental performance characteristics are already established and the submission is for a minor modification.

Therefore, the document does not contain the information typically found in a clinical study report that would establish the initial acceptance criteria and prove the device meets them from scratch. It refers to a guideline (CLSI EP25-A) for the testing conducted for the stability claim change, but doesn't detail the acceptance criteria for the entire device's performance (e.g., accuracy, precision, linearity, etc., across its full analytical range).

The information requested in the prompt (sample size for test set, data provenance, number/qualifications of experts, adjudication method, MRMC study, standalone performance, ground truth establishment for training and test sets) is characteristic of studies for diagnostic devices, particularly AI/software-as-a-medical-device (SaMD) products, where performance is often evaluated against human expert consensus or clinical outcomes. The HemosIL Liquid Anti-Xa is an in vitro diagnostic (IVD) assay, not an AI/SaMD product that requires human expert review of images or signals for ground truth. Its performance validation relies on analytical studies (e.g., accuracy against reference methods, precision, linearity, interference studies).

Based on the provided document, I cannot fulfill most of the requested information because it is not contained within this 510(k) summary.

Specifically, the document:

• Does not provide a full table of acceptance criteria for the device's overall performance (only discusses a change in stability claim).
• Does not discuss aspects like sample size for test sets in the context of clinical performance evaluation against a human-established ground truth, data provenance for such sets, expert numbers/qualifications, or adjudication methods, as these are typically not relevant for an IVD reagent's analytical performance assessment in the same way they are for image-based AI diagnostics.
• Does not mention any multi-reader multi-case (MRMC) comparative effectiveness study, as it's not an AI-assisted diagnostic tool.
• Does not discuss standalone algorithm performance, as it's a reagent for an automated instrument.
• Does not specify the type of ground truth used in the context of human expert review. For an IVD, "ground truth" would typically refer to reference method results or clinical diagnosis established through established laboratory and clinical procedures.
• Does not provide information on training set sample size or how ground truth was established for a training set, as it is not an AI/machine learning device that undergoes a training phase in the typical sense.

The only relevant information that can be extracted regarding a "study" is for the change being submitted:

1. Acceptance Criteria and Device Performance (for On-Board Stability Change):

The document states the study was conducted "based on testing to the current CLSI EP25-A guideline" to support the change in on-board stability from 7 days to 4 days. While it doesn't explicitly list the numerical acceptance criteria for this specific study, the implication is that the data collected over 4 days met the performance specifications (e.g., accuracy, precision) as defined by the CLSI EP25-A guideline for reagent stability. The reported performance is that the device meets the 4-day stability claim, leading to the regulatory approval.

2. Sample Size and Data Provenance for Stability Test: While the specific sample size for the stability study is not detailed, it would involve multiple replicates of control and/or patient samples measured over the 4-day period on the specified instruments (ACL TOP Family and ACL TOP Family 50 Series) stored at 15-25°C. Data provenance would be from internal laboratory studies of Instrumentation Laboratory Co. (the manufacturer). This would be a prospective analytical study designed to assess reagent stability under defined conditions.

3. Number of Experts and Qualifications / Adjudication Method / MRMC Study / Standalone Performance: Not applicable for this type of IVD reagent validation. There are no human experts involved in establishing ground truth for analytical performance, nor is there a multi-reader study or standalone algorithm.

4. Type of Ground Truth Used: For analytical performance like stability, the "ground truth" would be the initial performance of the freshly prepared reagent or its performance compared to a reference method, against which subsequent measurements over time are compared to assess degradation. This is an analytical ground truth, not a clinical ground truth established by human experts.

5. Training Set Sample Size and Ground Truth Establishment: Not applicable. This is an IVD reagent and not an AI/ML device that requires a "training set" in the sense of machine learning. The design and parameters of the assay are established through chemical and biological research and development, not data-driven machine learning.

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HemosIL ReadiPlasTin is an in vitro diagnostic thromboplastin reagent, based on recombinant human tissue factor, for the quantitative determination, in human citrated plasma, of Prothrombin Time (PT) and Fibrinogen, on the ACL TOP Family and ACL TOP Family 50 Series of analyzers. The product is intended to be used for the extrinsic coagulation pathway and the monitoring of Oral Vitamin K Antagonist Therapy.

The thromboplastin reagent included in the ReadiPlasTin kit, after mixing with the ReadiPlasTin Diluent, is a liposomal preparation that contains recombinant human tissue factor (RTF), re-lipidated in a synthetic phospholipid blend. In the PT test, the addition of the tissue thromboplastin (ReadiPlasTin reagent) to the patient plasma in the presence of calcium ions initiates the activation of the extrinsic pathway. This results ultimately in the conversion of fibrin, with formation of a solid gel. The fibrinogen is quantitated (PT-based method) by relating the absorbance or light-scatter during clotting to a calibrator.

The provided text is a 510(k) Summary for a medical device called "HemosIL ReadiPlasTin." This document doesn't describe an AI/ML-based device, but rather an in vitro diagnostic (IVD) reagent used for Prothrombin Time (PT) and Fibrinogen determination. Therefore, many of the requested categories related to AI/ML device testing (e.g., number of experts for ground truth, adjudication method, MRMC study, training set information) are not applicable to this type of submission.

However, I can extract the relevant information regarding acceptance criteria and performance studies for this IVD device.

Here's a breakdown of the requested information, adapted for an IVD reagent:

Device: HemosIL ReadiPlasTin (In vitro diagnostic thromboplastin reagent)
Purpose: Quantitative determination of Prothrombin Time (PT) and Fibrinogen in human citrated plasma.
Reason for Submission (K213426): Reformulation of the existing HemosIL ReadiPlasTin by adding EDTA as a stabilizer and removing unnecessary fillers.

1. Table of Acceptance Criteria and Reported Device Performance

For this IVD, "acceptance criteria" are typically defined by the method validation standards (e.g., CLSI guidelines) and the equivalence to the predicate device. The performance data presented are the results of meeting these criteria.

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

• Precision:

  • Sample Size: 80 measurements per instrument per lot (n=80/instrument/lot) for PT (controls + 6 native patient samples) and Fibrinogen (controls + 6 fibrinogen sample pools at 3 levels). Tested across 3 lots and representative members of both ACL TOP Family and ACL TOP Family 50 Series.
  • Data Provenance: Not explicitly stated, but "native (unadulterated) patient samples" and "fibrinogen sample pools" suggest human biological samples. Typically, these studies are conducted in a controlled laboratory setting (Likely within the manufacturer's R&D facilities or a contract research organization). The document is submitted to the US FDA, implying relevance to the US market. The retrospective/prospective nature is generally prospective for these types of validation studies.

• Interference:

  • Sample Size: Two clinical sample levels each for PT (normal pooled plasma and a high INR clinical sample) and Fibrinogen (normal pooled plasma and a low fibrinogen sample). Specific "n" per concentration/sample type is not given, but refers to CLSI EP07, 3rd Ed and CLSI EP37, 1st Ed which define the study design.
  • Data Provenance: Not explicitly stated, but "clinical sample levels" implies human biological samples.

• Method Comparison:

  • Sample Size:
    • PT (INR): 160 samples (normal and abnormal) for both ACL TOP Family and ACL TOP Family 50 Series.
    • Fibrinogen (mg/dL): 135 samples for ACL TOP Family, 134 samples for ACL TOP Family 50 Series.
  • Data Provenance: Not explicitly stated, but "normal and abnormal samples" implies human biological samples. The study was "in-house."

• Open Vial and On-board Instrument Stability:

  • Sample Size: For PT, controls and four native (unadulterated) patient samples were tested in eight replicates at each time interval. For Fibrinogen, controls and six fibrinogen sample pools at three levels were tested in eight replicates at each time interval.
  • Data Provenance: Not explicitly stated, but "native (unadulterated) patient samples" and "fibrinogen sample pools" imply human biological samples.

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

This is not applicable for this type of IVD device. The ground truth for chemical assays like PT and Fibrinogen is established through precise measurement methods and reference materials, not through expert consensus of visual or diagnostic interpretations. The "truth" is the quantitative value derived from the reference method or calibrator.

4. Adjudication Method for the Test Set

Not applicable, as this is an IVD reagent and not an AI/ML-based diagnostic system requiring human interpretation or 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, as this is an IVD reagent and not an AI/ML-based diagnostic system involving human interpretation.

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

Not applicable, as this is an IVD reagent. Its performance is inherent to the chemical reaction and the analytical instrument it is used with.

7. The Type of Ground Truth Used

The "ground truth" for this IVD is established by:

• Reference Methods/Materials: For PT and Fibrinogen, this would rely on internationally recognized standards and calibrators, and the values obtained from a validated reference method (or the predicate device in method comparison studies).
• Known Concentrations: For linearity and interference studies, samples are often spiked with known concentrations of analytes or interfering substances.
• Validated Predicate Device: In the method comparison study, the predicate device (HemosIL RecombiPlasTin 2G) serves as the comparator for verifying the new formulation's performance.

8. The Sample Size for the Training Set

Not applicable. This is an IVD reagent, not an AI/ML model that requires a "training set." The development of the reagent involves chemical formulation and optimization, not data-driven machine learning.

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

Not applicable, as there is no "training set" for an IVD reagent.

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The GEM Premier 5000 is a portable critical care system for use by health care professionals to rapidly analyze heparinized whole blood samples at the point of health care delivery in a clinical setting and in a central laboratory. The instrument provides quantitative measurements of pH, pCO2, pO2, sodium, chloride, ionized calcium, glucose, lactate, hematocrit, total bilirubin and CO-Oximetry (tHb, O2Hb, COHb, MHb, sO2*) parameters from arterial, venous or capillary heparinized whole blood. These parameters, along with derived parameters, aid in the diagnosis of a patient's acid/base status, electrolyte and metabolite balance and oxygen delivery capacity.

*sO2 = ratio between the concentration of oxyhemoglobin plus deoxyhemoglobin plus deoxyhemoglobin.

· pH, pCO2, and pO2 measurements in whole blood are used in the diagnosis and treatment of life-threatening acid-base disturbances.

· Electrolytes in the human body have multiple roles. Nearly all metabolic processes depend on or vary with electrolytes:

· Sodium (Na+) measurements are used in the diagnosis and treatment of aldosteronism, diabetes insipidus, adrenal hypertension, Addison's disease, dehydration, inappropriate antidiuretic secretion, or other diseases involving electrolyte imbalance.

· Potassium (K+) measurements are used to monitor electrolyte balance in the diagnosis and treatment of disease conditions characterized by low or high blood potassium levels.

· Ionized calcium (Ca++) measurements are used in the diagnosis and treatment of parathyroid disease, a variety of bone diseases, chronic renal disease and tetany.

· Chloride (Cl-) measurements are used in the diagnosis and treatment of electrolyte and metabolic disorders, such as cystic fibrosis and diabetic acidosis.

· Hematocrit (Hct) measurements in whole blood of the packed red cell volume of a blood sample are used to distinguish normal from abnormal states, such as anemia and erythrocytosis (an increase in the number of red cells).

· Glucose (Glu) measurement is used in the diagnosis, monitoring and treatment of carbohydrate metabolism disturbances including diabetes mellitus, neonatal hypoglycemia, idiopathic hypoglycemia, and pancreatic islet cell carcinoma.

• · Lactate (Lac) measurement is used:
• · to evaluate the acid-base status of patients suspected of having lactic acidosis;
• · to monitor tissue hypoxia and strenuous physical exertion;
• in the diagnosis of hyperlactatemia.

· Total Bilirubin (tBili) measurement is used to aid in assessing the risk of kernicterus and hyperbilirubinemia in neonates.

· CO-Oximetry (tHb, COHb, MetHb, O2Hb. HHb, and sO2) evaluates the ability of the blood to carry oxygen by measuring total hemoglobin and determining the percentage of functional hemoglobin species.

• Total Hemoglobin (tHb): Total hemoglobin measurements are used to measure the hemoglobin content of whole blood for the detection of anemia.

· COHb: Carboxyhemoglobin measurements are used to determine the carboxyhemoglobin content of human blood as an aid in the diagnosis of carbon monoxide poisoning.

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· MetHb: Methemoglobin measurements are used to determine different conditions of methemoglobinemia.

· HHb: Deoxyhemoglobin, as a fraction of total hemoglobin, is used in combination with oxyhemoglobin to measure oxygen status.

· O2Hb: Oxyhemoglobin, as a fraction of total hemoglobin, is used in combination with deoxyhemoglobin to measure oxygen status.

• sO2: Oxygen saturation, more specifically the ratio between the concentration of oxyhemoglobin and oxyhemoglobin plus deoxyhemoglobin, is used to measure oxygen status.

The GEM Premier 5000 system provides fast, accurate, quantitative measurements of heparinized whole blood pH, pCO2, pO2, Na+, K+, Cl-, Ca++, glucose, lactate, Hct, total bilirubin and CO-Oximetry (tHb, O2Hb, COHb, MetHb, HHb, sO2) from arterial, venous or capillary samples.

The provided text is a 510(k) summary for the GEM Premier 5000 device, detailing an operating system upgrade. This document is a regulatory submission for a device change and does not contain the information requested regarding acceptance criteria, device performance tables, study specifics (sample size, data provenance, expert qualifications, adjudication methods, MRMC studies, standalone performance), or ground truth establishment.

The submission is a Special 510(k), which indicates a modification to an already cleared device, not a de novo clearance requiring extensive clinical performance studies. The core of this submission is a software update (operating system change from Fedora 17 Linux to WindRiver LTS 18 Linux) with the stated reason to "accommodate long-term support of resolutions for common vulnerability exposures."

The document explicitly states:

• "Performance data is limited to Software Verification as the scope of this Special 510(k) is specific to an operating system upgrade..."
• "The changes in this submission do not introduce: Changes to indications for use or intended use, Changes to the fundamental scientific technology, Changes to operating principle, Changes to labeled performance claims."

Therefore, the requested information, which typically pertains to the establishment of initial clinical performance and effectiveness, is not present in this regulatory document for this specific submission. The focus here is on ensuring the device continues to meet its previously established performance claims after a technical software upgrade, rather than demonstrating new performance capabilities.

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HemosIL Liquid Anti-Xa is an automated chromogenic assay for in vitro diagnostic use by laboratory professionals in clinical laboratories. The assay provides quantitative results on 3.2% citrated human plasma for the following analytes based on the calibrators used:

. When used with HemosIL Heparin Calibrators:

Quantitative determination of unfractionated heparin (UFH) and low molecular weight heparin (LMWH) activity on the ACL TOP Family, ACL TOP Family 50 Series, and ACL Elite/Elite Pro.

· When used with HemosIL Apixaban Calibrators:

Quantitative determination of apixaban on the ACL TOP Family and ACL TOP Family 50 Series through measurement of Factor Xa activity, which is inversely proportional to the apixaban level. With HemosIL Apixaban Calibrators, the assay is intended to measure apixaban concentrations in patients on apixaban therapy in the following situations where measurement of apixaban levels could be useful to have as additional information:

• Patients at risk for major bleeding
• Patients experiencing a bleeding episode

The assay is not a stand-alone test and the results should be used in conjunction with other clinical and laboratory findings.

For use in adult population. For prescription use only.

HemosIL Liquid Heparin and HemosIL Liquid Anti-Xa are one stage chromogenic assays based on a synthetic chromogenic substrate and on Factor Xa inactivation. The assay provides quantitative apixaban results on 3.2% citrated human plasma when used with HemosIL Heparin Calibrators and/or HemosIL Apixaban Calibrators.

The assay contains:

• Factor Xa reagent purified bovine Factor Xa, Tris-Buffer, EDTA, dextran sulfate, . sodium chloride, and bovine serum albumin
• Chromogenic substrate liquid chromogenic substrate S-2732 and bulking agent .

The assay requires the following components which are not included in the assay kit:

• HemosIL Apixaban Calibrators two levels ( and ( ( ng/mL) of lyophilized calibrators . prepared from human citrated plasma containing apixaban, buffers, and stabilizers.
• HemosIL Apixaban Controls two levels (1) and (1) of lyophilized controls . prepared from human citrated plasma containing apixaban, buffers, and stabilizers,
• HemosIL Heparin Calibrator three levels (0, 0.8 and 2.0 IU/mL) of lyophilized . calibrators prepared from human citrated plasma containing heparin, buffer and stablizers.
• HemosIL LMW Heparin Controls two levels (low and high) of lyophilized controls . prepared from human citrated plasma containing low molecular weight (LMW) heparin, buffers and stabilizers. Each lot of LMW Heparin Controls is traceable to the 3rd International WHO Standadrd 11/176 for LMW heparin.
• Hemos IL UF Heparin Controls two levels (low and high) of lyophilized controls . prepared from human citrated plasma containing unfractionated (UF) heparin, buffers and stabilizers. Each lot of UF Heparin Controls is traceable to the 6th International WHO standard 07/328 for UF heparin.
• Cleaning solution .
• Cleaning agent .
• Factor diluent .

The HemosIL Liquid Anti-Xa assay is an automated chromogenic assay designed for in vitro diagnostic use to quantitatively determine unfractionated heparin (UFH), low molecular weight heparin (LMWH) activity, and apixaban levels in citrated human plasma.

Here's an analysis of its acceptance criteria and the study that proves its performance:

1. Table of Acceptance Criteria and Reported Device Performance

The document primarily focuses on analytical performance for apixaban, as heparin performance was previously reported. The key performance criteria evaluated for apixaban are precision, linearity/reportable range, traceability, stability, detection limits, and analytical specificity.

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

• Precision Studies (Test Set):
  • Study 1: 240 determinations (80 per reagent lot).
  • Study 2: Total number of determinations not fully specified, but involved multiple instrument models and reagent lots.
  • Study 3: No specific number of determinations given, states "prodeterminations".
  • Study 4: 270 determinations (multisite).
  • Study 5: 270 determinations (multisite).
• Linearity Studies (Test Set): Normal pooled plasma (NPP) spiked with known concentrations of apixaban, tested in four replicates.
• Detection Limit Studies (Test Set):
  • LoB: n=60 determinations per reagent lot per instrument model (using four citrated plasma pools).
  • LoD: n=60 determinations per reagent lot per instrument model (using four citrated plasma pools).
  • LoQ: n=40 determinations per reagent lot per instrument model (using four citrated plasma pools).
• Analytical Specificity/Interference Studies (Test Set): Test samples (spiked with apixaban) and control samples, tested in a minimum of four replicates.
• Clinical Accuracy (Method Comparison Study Test Set): 367 clinical samples collected from patients receiving apixaban.
• Data Provenance: The method comparison study involved clinical samples collected from three different U.S. clinical sites. This indicates the data is prospective or retrospective clinical data, collected in a real-world setting.
  • For the analytical studies (precision, linearity, detection limits, interference), these were laboratory-controlled studies using spiked or pooled plasma samples.

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

For the clinical accuracy study, the ground truth was established by a validated apixaban LC-MS/MS method. The document does not specify the number or qualifications of experts involved in running or validating this LC-MS/MS method, as LC-MS/MS is a highly sensitive and precise analytical technique typically performed by trained laboratory personnel.

4. Adjudication Method for the Test Set

Not applicable. The ground truth for the clinical accuracy study was established by a quantitative instrumental method (LC-MS/MS), not through expert consensus requiring adjudication.

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 device is an automated in vitro diagnostic assay, not an imaging or diagnostic interpretation device that would typically involve human readers. Therefore, the concept of human readers improving with AI vs. without AI assistance does not apply.

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

Yes, the studies reported are standalone performance evaluations of the HemosIL Liquid Anti-Xa assay (an automated algorithm/instrument system). The performance characteristics presented are for the device itself, generating quantitative results. While the device results are intended to be used by laboratory professionals and clinicians, the performance of the device is measured directly, not in conjunction with human interpretation for accuracy.

7. The Type of Ground Truth Used

• Analytical Performance Studies (Precision, Linearity, Detection Limits): Ground truth was established by known concentrations of apixaban used to spike samples, or intrinsic properties of control materials and pooled plasma.
• Clinical Accuracy (Method Comparison Study): Ground truth was established by a validated apixaban Liquid Chromatography - tandem Mass Spectrometry (LC-MS/MS) method. LC-MS/MS is considered a gold standard for drug quantification.

8. The Sample Size for the Training Set

The document does not explicitly mention a "training set" in the context of machine learning. The HemosIL Liquid Anti-Xa is a chromogenic assay based on biochemical reactions and factor Xa inactivation, not a machine learning algorithm that requires specific training data in the traditional sense. The development of such assays involves extensive R&D, reagent optimization, and calibration curve generation, which could be seen as analogous to "training" but is not reported with a distinct sample size for "training set" in this context.

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

As noted above, a traditional "training set" as understood in machine learning is not applicable here. The assay relies on established biochemical principles and calibration against known standards.

• Calibration: For apixaban, calibrator value assignments are traceable to apixaban supplied by the manufacturer and quantitated in plasma assayed by LC-MS/MS. This process ensures the assay accurately measures apixaban concentrations.

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Automated latex enhanced immunoassay for the quantitative determination of von Willebrand Factor Antigen (VWF:Ag) in human citrated plasma on IL Coagulation Systems.

The VWF:Ag kit is a latex particle enhanced immunoturbidimetric assay to quantify VWF:Ag in plasma. When a plasma containing VWF:Ag is mixed with the Latex Reagent and the Reaction Buffer included in the kit, the coated latex particles agglutinate. The degree of agglutination is directly proportional to the concentration of VWF:Ag in the sample and is determined by measuring the decrease of transmitted light caused by the aggregates.

The provided document is a 510(k) Summary for the HemosIL von Willebrand Factor Antigen device. It describes a Special 510(k) submission rather than a traditional premarket notification that would typically include substantial new performance data. The core of this submission is a modification to a limitation/interference claim regarding Rheumatoid Factor (RF) rather than a broader study proving overall device performance against new acceptance criteria.

Therefore, the requested information, particularly regarding a comprehensive study with a test set, expert adjudication, MRMC studies, and standalone performance for an AI/algorithm-based device, is not present in this document. This submission pertains to an in-vitro diagnostic (IVD) assay that measures a biological marker, not an AI-powered diagnostic device.

However, I can extract the relevant information from the document regarding the acceptance criteria related to the modified claim and the "study" (which in this context refers to the basis for the change, here being a literature reference and internal design control activities rather than a new clinical trial).

Here's an attempt to answer based on the provided document, while clarifying what information is missing due to the nature of this particular 510(k) submission:

Acceptance Criteria and Device Performance for HemosIL von Willebrand Factor Antigen (K200033) - Modifed Rheumatoid Factor Interference Claim

This 510(k) submission is a Special 510(k), indicating a minor change to an already cleared device. The "acceptance criteria" and "study" are specifically focused on the modified claim regarding Rheumatoid Factor interference, rather than a broad re-evaluation of the device's overall performance. No new clinical study was conducted for this specific submission to prove general device performance. Instead, the modification is based on internal design control activities and a literature reference.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criterion for this specific modification is the non-interference within a certain concentration range of Rheumatoid Factor (RF). The "reported device performance" reflects a change in the claimed non-interference level.

Note on "Acceptance Criteria" for a Special 510(k): For this type of submission, the primary acceptance criterion is that the modified device remains substantially equivalent to the predicate device and that the change does not introduce new questions of safety or effectiveness. For the specific change (RF interference), the acceptance is based on the rationale provided (literature reference). No specific quantitative performance metric (e.g., accuracy, sensitivity, specificity) for the RF non-interference claim is explicitly stated, other than the new 50 IU/mL threshold being deemed acceptable.

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

• Test Set Sample Size: Not applicable. The document explicitly states: "Performance data are unnecessary since the current Rheumatoid Factor claim in the HemosIL von Willebrand Factor Antigen insert is being replaced with a limitation and a supporting literature reference." This indicates that a dedicated new test set for this specific change was not used for performance validation.
• Data Provenance: Not explicitly stated as new data was not generated. The basis for the change is a "supporting literature reference."

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

• Not applicable. There was no new test set requiring expert ground truth establishment for this specific change.

4. Adjudication Method for the Test Set

• Not applicable. No new test set requiring adjudication was used.

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

• Not applicable. This device is an in-vitro diagnostic assay, not an AI-assisted diagnostic tool that would typically involve human readers.

6. Standalone Performance Study (Algorithm Only)

• Not applicable. This device is an in-vitro diagnostic assay. The concept of "standalone performance" typically applies to AI algorithms operating independently of human interpretation.

7. Type of Ground Truth Used

• For the modified RF interference claim: The "ground truth" for the new claim (non-interference up to 50 IU/mL) is based on a "supporting literature reference" combined with internal design control activities and possibly previous knowledge/studies that led to the revised understanding of RF interference. No new direct "ground truth" (e.g., from pathology, clinical outcomes, or expert consensus on new data) was established for this specific special 510(k).

8. Sample Size for the Training Set

• Not applicable. This is an IVD assay, not an AI/machine learning algorithm that requires a training set.

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

• Not applicable. No training set was used.

Summary of Key Takeaway from the Document:

This 510(k) submission (K200033) is a Special 510(k) for the HemosIL von Willebrand Factor Antigen. The purpose is to modify the product insert's "Limitations/Interfering substances" section concerning Rheumatoid Factor interference. The submission states that no new performance data was generated or deemed necessary for this change because it relies on existing knowledge and a literature reference. Therefore, the detailed requirements for a study proving device performance (especially for an AI/algorithm) are not met by this particular regulatory filing, as it pertains to a different type of device and a very specific, limited modification.

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The GEM Premier ChemSTAT is a portable critical care system for use by health care professionals to rapidly analyze lithium heparinized whole blood samples at the point of health care delivery in a clinical setting and in a central laboratory. The instrument provides quantitative measurements of Glucose (Glu), Lactate (Lac), Hematocrit (Hct), pH and partial pressure of carbon dioxide (pCO2) from arterial and venous heparinized whole blood. These parameters, along with derived parameters, aid in the diagnosis of a patient's acid/base status and metabolite balance.

• · Glucose (Glu) measurement is used in the diagnosis, monitoring and treatment of carbohydrate metabolism disturbances including diabetes mellitus, neonatal hypoglycemia, idiopathic hypoglycemia, and of pancreatic islet cell carcinoma.
• · Lactate (Lac) measurement is used to evaluate the acid-base status of patients suspected of having lacidosis, to monitor tissue hypoxia and strenuous physical exertion, and in the diagnosis of hyperlactatemia.
• Hematocrit (Hct) measurements in whole blood of the packed red cell volume of a blood sample are used to distinguish normal from abnormal states, such as anemia and erythrocytosis (an increase in the number of ed cells).
• · DH and pCO2 measurements in whole blood are used in the diagnosis and treatment of life-threatening acid-base disturbances.

The GEM Premier ChemSTAT is a portable system that analyzes arterial and venous lithium heparinized whole blood at the point of health care delivery in a clinical setting and in a central laboratory for Glu, Lac, Hct, pH, and pCO2. All tests are included in a single self-contained, disposable GEM Premier ChemSTAT PAK (cartridge).

Key Components:
Analyzer: The GEM Premier ChemSTAT analyzer has the internal logic and processing power necessary to perform analysis. It employs a unique touch-sensitive color screen and a simple set of menus and buttons for user interaction. The analyzer guides operators through the sampling process with simple, clear messages and prompts.
PAK (Cartridge): The disposable, multi-use GEM Premier ChemSTAT PAK is a completely closed cartridge that houses all components necessary to operate the instrument once the GEM PAK is validated. These components include the sensors, Process Control (PC) Solutions, sampler, and waste bag. The values of all PC Solutions are read from the GEM PAK Electronically Erasable Programmable Read Only Memory (EEPROM) chip. The components and processes used to manufacture the PC Solutions in the GEM PAK are traceable to National Institute of Standards and Technology (NIST) standards, Clinical & Laboratory Standards Institute (CLSI) procedures or other internal standards, where available and appropriate. The GEM Premier ChemSTAT PAK has flexible menus to assist facilities in maximizing efficiency. As part of this program, GEM ChemSTAT CVP (Calibration Valuation Products) are external solutions intended to complete the calibration process and final accuracy assessment of the iQM cartridge calibration following warm-up.
Intelligent Quality Management (iQM): Intelligent Quality Management (iQM) is used as the quality control and assessment system for the GEM Premier ChemSTAT system. iQM is an active quality process control program designed to provide continuous monitoring of the analytical process before and after sample measurement with real-time, automatic error detection, automatic correction and automatic documentation of all corrective actions. iQM performs 4 types of continuous, quality checks to monitor the performance of the GEM PAK, sensors, and reagents throughout the cartridge use-life. These checks include System, Sensor, Pattern Recognition (PR) and Stability Checks.

The provided text describes a 510(k) premarket notification for the GEM Premier ChemSTAT device, a portable system for analyzing whole blood samples. The document focuses on demonstrating substantial equivalence to a predicate device (GEM Premier 4000) through various performance studies.

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

Acceptance Criteria and Reported Device Performance

The acceptance criteria are not explicitly stated as distinct numerical targets in a single table, but rather implied through the successful completion of various performance studies and the conclusion that "All results were within specification." The reported device performance is presented in several tables detailing precision, linearity, and method comparison.

Here's a compilation of the reported device performance, which implies the acceptance criteria were met if these results were deemed "within specification":

Table of Reported Device Performance (Implied Acceptance Criteria)

Study Details:

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

   • Internal Precision Study – Whole Blood: 5 concentrations of whole blood per analyte, run on 3 analyzers for 5 days, 8 replicates per run per level (N=120 per level/analyte).
   • Reproducibility Study with Aqueous Controls – Point-of-Care (POC) Setting: 7 levels (Glucose, Lactate) or 6 levels (Hct, pH, pCO2) of quality control material, run in triplicate, twice a day for 5 days (30 replicates per level). Pooled N=90 across 3 sites for each control level for each analyte.
   • External Precision – Whole Blood: Various N values per analyte and POC site, ranging from 3 to 198 (pooled). The text states "Less than 10% of samples included in the study were contrived." This indicates the majority are real patient samples.
   • LoB, LoD, and LoQ: Not specified how many physical samples, but performed using three (3) lots of GEM Premier ChemSTAT PAKs (cartridges).
   • Linearity: Minimum of 9 levels per analyte (whole blood spiked or diluted). Each blood level analyzed in triplicate on six (6) GEM Premier ChemSTAT test analyzers (except pH and pCO2, which were tested on 3 analyzers). N per level: 18 for Glucose, Lactate, Hematocrit; 9 for pH, pCO2.
   • Analytical Specificity: Not explicitly stated N, but various test substances were screened at specified concentrations.
   • Clinical Testing (Method Comparison):
     • Glucose: N=432
     • Lactate: N=432
     • Hematocrit: N=431
     • pH: N=552
     • pCO2: N=559
     • Provenance: Lithium heparinized whole blood patient samples from the intended use population. Samples from three (3) external point-of-care (POC) sites and an internal Customer Simulation Laboratory (CSL). Less than 10% of samples were contrived. This implies the data is a mix of prospective (patient samples from POC sites) and potentially some retrospective (if sourced from a biobank, though "patient samples" often implies prospective collection for the study) and/or controlled spiked samples. The specific country of origin is not stated but "external point-of-care (POC) sites" and "internal Customer Simulation Laboratory (CSL) at IL" (Instrumentation Laboratory Co., Bedford, MA) suggest US-based data.

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

   • This document describes in vitro diagnostic (IVD) device performance against established analytical methods and a predicate device, not an AI/ML device relying on human expert interpretation of images. Therefore, the concept of "experts establishing ground truth" in the sense of radiologists or pathologists for an AI model's output does not directly apply here.
   • The "ground truth" for the test set values (sample concentrations) for analytes like Glucose, Lactate, Hct, pH, and pCO2 would typically be established by a reference method or the established predicate device (GEM Premier 4000) itself, which is considered the "truth" for comparison in the method comparison study. The laboratory professionals operating these devices and following standard protocols implicitly ensure the accuracy of these reference values.
   • For the reproducibility study, "nine (9) different operators" were involved at "three (3) external clinical point-of-care (POC) sites". These would be healthcare professionals (e.g., nurses, lab technicians) trained to use the device. Their qualifications are not specified beyond being "health care professionals."

3. Adjudication Method for the Test Set:

   • Adjudication methods (like 2+1, 3+1) are typically used in studies involving subjective human interpretation of data, often for diagnostic image analysis where disagreement among readers needs resolution.
   • For an IVD device measuring quantitative analytes, the "ground truth" is typically the result from a reference standard instrument or method. Discrepancies are usually investigated through analytical means (re-testing, troubleshooting) rather than human adjudication of interpretive differences. The document does not mention any such adjudication process.

4. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done, and Effect Size:

   • No, an MRMC study was not done. MRMC studies are specifically designed for evaluating diagnostic tools where human readers interpret cases, often with and without AI assistance (e.g., radiology AI).
   • This submission is for an IVD device for quantitative measurements of analytes, not an AI/ML-driven diagnostic imaging device. Therefore, the concept of "human readers improve with AI vs without AI assistance" is not relevant here.

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

   • This device is an IVD instrument, not an algorithm/software in the typical AI sense. Its performance (accuracy, precision, linearity) is inherently "standalone" in how it processes a blood sample to produce a result, without needing human "in-the-loop" interpretation of the measurement itself.
   • Clinical testing (method comparison) directly assesses the device's standalone performance against a predicate device.

6. The Type of Ground Truth Used:

   • The ground truth for the analytical studies (precision, linearity, LoB/D/Q, specificity) is based on analytical standards, control materials with known concentrations, and comparison to a legally marketed predicate device (GEM Premier 4000).
   • For the clinical testing/method comparison, the predicate device (GEM Premier 4000) provides the comparative "ground truth" for patient samples, ensuring the new device yields comparable results within acceptable ranges. This is a common approach for IVD substantial equivalence.

7. The Sample Size for the Training Set:

   • This document describes a conventional IVD device, not an AI/ML device that requires a "training set" in the machine learning sense. The device is based on established electrochemical and conductivity principles (Amperometry, Potentiometry, Conductivity), not on learning from a large dataset.
   • Therefore, there is no explicit "training set" size or process described. The "training" of such a device involves its initial design, calibration protocols, and quality control procedures during manufacturing, which are validated through the performance studies presented.

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

   • As there is no "training set" in the AI/ML context, this question is not applicable to the GEM Premier ChemSTAT device as described. The "ground truth" for calibrating and setting up an IVD device's internal algorithms (e.g., sensor response curves, temperature compensation) would be established using traceable reference materials and industry-standard analytical methods during the device's development and manufacturing.

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The GEM Premier ChemSTAT is a portable critical care system for use by health care professionals to rapidly analyze lithium heparinized whole blood samples at the point of health care delivery in a clinical setting and in a central laboratory. The instrument provides quantitative measurements of Sodium (Na+), Ionized Calcium (Ca++) and Chloride (C1-) from arterial and venous heparinized whole blood. These parameters. along with derived parameters, aid in the diagnosis of a patient's electrolyte balance.

Electrolytes in the human body have multiple roles. Nearly all metabolic processes depend on or vary with electrolytes:

• · Sodium (Na+) measurements are used in the diagnosis and treatment of aldosteronism, diabetes insipidus, adrenal hypertension, Addison's disease, dehydration, inappropriate antidiuretic secretion, or other diseases involving electrolyte imbalance.
• · Potassium (K+) measurements are used to monitor electrolyte balance in the diagnosis and treatment of disease conditions characterized by low or high blood potassium levels.
• Ionized calcium (Ca++) measurements are used in the diagnosis and treatment of parathyroid disease, a variety of bone diseases, chronic renal disease and tetany.
• · Chloride (Cl-) measurements are used in the diagnosis and metabolic and metabolic disorders, such as, cystic fibrosis and diabetic acidosis.

The GEM Premier ChemSTAT is a portable system that analyzes arterial and venous lithium heparinized whole blood at the point of health care delivery in a clinical setting and in a central laboratory for Na*, K*, Ca** and Cl . All tests are included in a single self-contained, disposable GEM Premier ChemSTAT PAK (cartridge).

Key Components:
Analyzer: The GEM Premier ChemSTAT analyzer has the internal logic and processing power necessary to perform analysis. It employs a unique touch-sensitive color screen and a simple set of menus and buttons for user interaction. The analyzer guides operators through the sampling process with simple, clear messages and prompts.
PAK (Cartridge): The disposable, multi-use GEM Premier ChemSTAT PAK is a completely closed cartridge that houses all components necessary to operate the instrument once the GEM PAK is validated. These components include the sensors, Process Control (PC) Solutions, sampler, and waste bag. The values of all PC Solutions are read from the GEM PAK Electronically Erasable Programmable Read Only Memory (EEPROM) chip. The components and processes used to manufacture the PC Solutions in the GEM PAK are traceable to National Institute of Standards and Technology (NIST) standards, Clinical & Laboratory Standards Institute (CLSI) procedures or other internal standards, where available and appropriate. The GEM Premier ChemSTAT PAK has flexible menus to assist facilities in maximizing efficiency. As part of this program, GEM ChemSTAT CVP (Calibration Valuation Products) are external solutions intended to complete the calibration process and final accuracy assessment of the iQM cartridge calibration following warm-up.
Intelligent Quality Management (iQM): Intelligent Quality Management (iQM) is used as the quality control and assessment system for the GEM Premier ChemSTAT system. iQM is an active quality process control program designed to provide continuous monitoring of the analytical process before and after sample measurement with real-time, automatic error detection, automatic correction and automatic documentation of all corrective actions. iQM performs 4 types of continuous, quality checks to monitor the performance of the GEM PAK, sensors, and reagents throughout the cartridge use-life. These checks include System, Sensor, Pattern Recognition (PR) and Stability Checks.

The provided FDA 510(k) summary for the GEM Premier ChemSTAT describes the device's analytical performance, which is a type of acceptance criteria study. This document is not for an AI/ML device, but rather for an in-vitro diagnostic device that measures specific analytes. Therefore, many of the requested elements pertaining to AI/MRMC studies, expert ground truth, and training sets are not applicable or not provided in this type of submission. However, I can extract information related to the device's analytical performance and the studies conducted to demonstrate its performance against predefined criteria.

Here's a breakdown of the acceptance criteria and performance study details, focusing on what is available in the provided document:

Acceptance Criteria and Reported Device Performance

The acceptance criteria are implicitly defined by the analytical performance specifications and the comparison to the predicate device. The performance studies aim to demonstrate that the device meets these standards.

Table 1: Acceptance Criteria (Implicit from Study Outcomes) and Reported Device Performance for GEM Premier ChemSTAT

Details of the Study

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

   • Internal Precision Study – Whole Blood: 120 replicates per level for each of 5 levels (N=600 total samples analyzed for each analyte). Data provenance is internal (Instrumentation Laboratory Co.). The study simulates an internal lab environment.
   • Reproducibility Study with Aqueous Controls – POC Setting: 90 pooled replicates per level for each of 7 levels (N=630 samples analyzed for each analyte). The study was performed at three (3) external clinical point-of-care (POC) sites.
   • External Precision – Whole Blood: Variable N per site. For the Na+, K+, Ca++, Cl- main ranges, N=~63-69 samples per site for 3 sites, pooled N=195. For specific lower/higher ranges, N=3 samples per site for 3 sites, pooled N=9. The study was performed at three (3) external clinical point-of-care (POC) sites. Less than 10% of samples were "contrived" (meaning artificially prepared or modified) and the rest were patient samples from the intended use population. Data provenance is implied to be mixed: patient samples are real-world, while contrived samples are laboratory-sourced. The locations are referred to as "external clinical point-of-care (POC) sites", implying real-world clinical settings, likely within the US given FDA submission. It is a prospective study as samples were "run" during the study.
   • LoB, LoD, LoQ: No specific N mentioned, but involved testing with three (3) lots of GEM Premier ChemSTAT PAKs.
   • Linearity: 18 replicates per level (9 levels, total of 162 samples) for each analyte. Whole blood samples, prepared by spiking or diluting, were used.
   • Analytical Specificity (Interference): Not explicitly stated, but various substances were screened at different concentrations. Implied to be laboratory-based evaluation.
   • Clinical Testing (Method Comparison):
     • Na+: N=436 patient samples.
     • K+: N=442 patient samples.
     • Ca++: N=444 patient samples.
     • Cl-: N=435 patient samples.
     • Data provenance: Patient samples from the intended use population, collected at three (3) point-of-care (POC) sites. Less than 10% of samples were contrived. Implied to be prospective as a method comparison study involving running samples.

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

   • For this type of in-vitro diagnostic device, "ground truth" for clinical samples is typically established by comparative measurement against a predicate device or a reference method, rather than by expert consensus (as would be the case for image interpretation, for example).
   • The "ground truth" in the Clinical Testing (Method Comparison) was established by comparing the GEM Premier ChemSTAT's measurements to those of the GEM Premier 4000 (K133407), which is the legally marketed predicate device. Operator qualifications involved "health care professionals" for point-of-care use, and "internal precision studies" would be performed by qualified lab personnel. Specific expert qualifications are not detailed beyond "health care professionals."

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

   • Not applicable/Not mentioned. This is a quantitative measurement device, not an interpretation task requiring adjudication. The performance is assessed statistically (SD, CV, R, slope, intercept).

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:

   • Not applicable. This is not an AI/ML device or an imaging device requiring human reader interpretation. It is an IVD device providing quantitative measurements.

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

   • This is an in-vitro diagnostic instrument. Its primary function is "standalone" measurement of analytes. The performance studies (precision, linearity, interference, method comparison) assess the instrument's inherent analytical capabilities. There is no "human-in-the-loop performance" in the sense of an AI assisting human interpretation; direct measurement is the output.

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

   • For LoB, LoD, LoQ, Linearity, Analytical Specificity, and Internal Precision: Ground truth is against known concentrations in prepared samples (standards, calibrators, controls, spiked/diluted samples). This is a metrological approach.
   • For Clinical Testing (Method Comparison) and External Precision (Whole Blood): Ground truth is established by the measurements from the predicate device (GEM Premier 4000) for patient samples. The assumption is that the predicate device provides clinically acceptable and accurate measurements for comparison.

7. The sample size for the training set:

   • Not applicable. This is not an AI/ML device, so there is no "training set" in the machine learning sense. The device is based on established electrochemical principles (potentiometry).

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

   • Not applicable, as there is no "training set" for an AI/ML model. The device's calibration and internal quality control use known standards and calibrated reference materials.

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