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HemosIL Chromogenic Factor IX is an automated assay for the photometric, quantitative determination of factor IX activity in 3.2% citrated plasma on the ACL TOP® Family and ACL TOP Family 50 Series in the laboratory setting by a healthcare professional. HemosIL Chromogenic Factor IX is indicated for use on patients when identifying factor IX deficiency or measuring factor IX activity from patients on replacement therapy. For adult population only. For prescription use only.

Factor IX activity in a patient's plasma is determined using a chromogenic method, in which human factor IX is activated by human factor XIa, and, when formed, factor IXa activates human factor X in the presence of human factor VIII, calcium and phospholipid. The amount of factor Xa generated is proportionate to the factor IX activity and is determined from the hydrolysis of a chromogenic factor Xa substrate. Results are determined by comparing a chromogenic signal to a calibration curve.

Here's a breakdown of the acceptance criteria and the studies that demonstrate the device's performance, based on the provided FDA 510(k) summary for the HemosIL Chromogenic Factor IX:

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly list "acceptance criteria" in a separate table. However, it presents performance characteristics that implicitly serve as success metrics for the device's substantial equivalence. I've extrapolated these based on the study findings.

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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

• Low Multi-Ab Control: 1.6%
• High Multi-Ab Control: 1.2%
• Plasma Samples A-E: 1.6% - 9.6% |
  | Reproducibility (Low CV across sites/runs)| Reproducibility (% CV):
• Low Multi-Ab Control: 7.0%
• High Multi-Ab Control: 7.4%
• Clinical Samples 1-4: 4.5% - 9.5% |
  | Analytical Sensitivity (LoD/LoQ) | LoD: 1.0 U/mL
  LoQ: 1.0 U/mL |
  | Linearity Range | 2.7 - 500.0 U/mL |
  | Analytical Specificity (No interference) | No interference for: Hemoglobin, Bilirubin, Triglycerides, Heparin (LMW/UF), Rheumatoid Factor, Acetylsalicylic acid, Atorvastatin, Warfarin, Prednisone, Acid Citric Dextrose, Hydroxychloroquine, Rituximab at specified concentrations. |
  | Method Comparison (Strong correlation to predicate) | Slope (95% CI): 1.00 (0.98 - 1.01)
  r: 1.00 |
  | Diagnostic Performance (Sensitivity/Specificity vs. APS Classification - provided for context, not a direct "acceptance criterion" in the same way as analytical measures) | Sensitivity: 40.5% (33.8% - 47.6%)
  Specificity: 91.9% (88.4% - 94.5%) |

HemosIL CL Anti-β2 Glycoprotein-I IgM

• Low Multi-Ab Control: 12.8%
• High Multi-Ab Control: 11.5%
• Plasma Samples A-E: 3.6% - 7.2% |
  | Reproducibility (Low CV across sites/runs)| Reproducibility (% CV):
• Low Multi-Ab Control: 8.3%
• High Multi-Ab Control: 7.7%
• Clinical Samples 1-4: 4.8% - 8.3% |
  | Analytical Sensitivity (LoD/LoQ) | LoD: 2.0 U/mL
  LoQ: 2.0 U/mL |
  | Linearity Range | 1.9 - 400.0 U/mL |
  | Analytical Specificity (No interference) | No interference for: Hemoglobin, Bilirubin, Triglycerides, Heparin (LMW/UF), Rheumatoid Factor, Acetylsalicylic acid, Atorvastatin, Warfarin, Prednisone, Acid Citric Dextrose, Hydroxychloroquine, Rituximab at specified concentrations. |
  | Method Comparison (Strong correlation to predicate) | Slope (95% CI): 0.94 (0.92 – 0.96)
  r: 0.99 |
  | Diagnostic Performance (Sensitivity/Specificity vs. APS Classification - provided for context, not a direct "acceptance criterion" in the same way as analytical measures) | Sensitivity: 33.0% (26.7% - 39.9%)
  Specificity: 94.6% (91.4% - 96.6%) |

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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The GEM Premier 7000 with iQM3 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 pH, pCO2, sodium, potassium, chloride, ionized calcium, glucose, lactate, hematocrit, total bilirubin, and CO-Oximetry (tHb, O2Hb, MetHb, HHb, sO2*) parameters from arterial, venous, or capillary lithium 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.

*s02 = ratio between the concentration of oxyhemoglobin and oxyhemoglobin 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 insividus, 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 and dysfunctional hemoglobin species.

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

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

• 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 7000 with iQMs system provides health care professionals with quantitative measurements of lithium heparinized whole blood pH, pCO2, pO2, Na*, K*, Ch, Ca**, glucose, lactate, Hct, total bilirubin and CO-Oximetry (tHb, O2Hb, COHb, MetHb, HHb, sO₂*) from arterial, venous or capillary samples at the point of health care delivery in a clinical setting and in a central laboratory.

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

Key Components:
Instrument: 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): All required components for sample analysis are contained in the GEM PAK, including sensors, optical cell for CO-Oximetry and total bilirubin, sampler, pump tubing, distribution valve, waste container and Process Control Solutions. The GEM PAK is an entirely closed analytical system. The operator cannot introduce changes to the analytical process before or during the GEM PAK's use-life on board the instrument. The GEM PAK has flexible menus and test volume options to assist facilities in maximizing efficiency. The EEPROM on the GEM PAK includes all solution values and controls the analyte menu and number of tests. The setup of the instrument consists of inserting the GEM PAK into the instrument. The instrument will perform an automated GEM PAK start-up during which the following is performed: warm-up (15 minutes), sensor conditioning (10 minutes), Process Control Solution (PCS) performance (15 minutes), all of which take about 40 minutes. After GEM PAK start-up, Auto PAK Validation (APV) process is automatically completed: two completely independent solutions traceable to NIST standards, CLSI procedures or internal standards, containing two levels of concentration for each analyte (PC Solution D and E), are run by the analyzer to validate the integrity of the PC Solutions and the overall performance of the analytical system. Note: GEM PAKs that include tBili analyte will require the successful performance of CVP 5 tBili. Includes all necessary components for hemolysis detection, such as an acoustofluidic flow cell, an LED light source and an optical detector, for appropriate flagging of potassium measurements in whole blood samples without additional sample volume or sample processing steps.
Intelligent Quality Management (iQM3): iQM3 is used as the quality control and assessment system for the GEM Premier 7000 system. iQM3 is an active quality process control program designed to provide continuous monitoring of the analytical process before, during and after sample measurement with real-time, automatic error detection, automatic correction of the system and automatic documentation of all corrective actions, replacing the use of traditional external QC. iQM3 introduces hemolysis detection in whole blood samples, enhancing quality assessment in the pre-analytical phase of testing.

Based on the provided text, the device in question is the GEM Premier 7000 with iQM3, which is a portable critical care system for analyzing blood samples. The document describes its comparison to a predicate device, the GEM Premier 5000, and discusses its performance studies.

Here's an analysis of the acceptance criteria and the study proving the device meets them:

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

The document does not provide a direct table of specific numerical acceptance criteria for each analyte's performance (e.g., pH, pCO2, Na+, etc.) nor does it list the reported device performance in those exact terms. Instead, it states that "All verification activities were performed in accordance to established plans and protocols and design control procedures. Testing verified that all acceptance criteria were met."

The "Performance Summary" section lists the types of studies conducted to demonstrate that the modifications (specifically the new iQM quality check/Hemolysis detection module) do not impact the performance data represented in the Operators Manual, aligning with recognized guidelines. This implies the acceptance criteria are tied to maintaining performance comparable to the predicate device and being within acceptable ranges as defined by the mentioned CLSI guidelines.

Therefore, a table of explicit numerical acceptance criteria and reported performance values for each analyte is NOT AVAILABLE in the provided text. The document broadly states that the device met its acceptance criteria.

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

The document mentions several types of performance studies:

• Verification (Internal Method Comparison, Internal Whole Blood Precision, Hemolysis Interference on Potassium, Hemolysis Verification)
• Shelf-life and Use-life studies

However, the specific sample sizes used for these test sets are NOT provided in the text. There is also no information about the data provenance (e.g., country of origin of the data, retrospective or prospective).

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

This information is NOT available in the provided text. The device is an in-vitro diagnostic (IVD) instrument that provides quantitative measurements of various blood parameters. The "ground truth" for such devices typically comes from reference methods, calibrated standards, or comparative analyses with established, highly accurate laboratory instruments, rather than human expert consensus on interpretations like with imaging.

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

Given that this is an IVD device for quantitative measurements of blood parameters, the concept of "adjudication" by multiple human readers (like in imaging studies) does not directly apply. Performance is assessed through analytical accuracy, precision, and interference studies against known standards or reference methods. Therefore, no adjudication method in the sense of expert consensus on interpretations is described or implied.

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

There is no indication that a multi-reader multi-case (MRMC) comparative effectiveness study was performed. This type of study is relevant for AI-assisted diagnostic tools where human interpretation is part of the workflow. The GEM Premier 7000 with iQM3 is described as an analytical instrument providing direct quantitative measurements, not an AI system assisting human readers with interpretation. The "iQM3" refers to Intelligent Quality Management, which is an automated quality control system for the instrument itself, not an AI for human diagnostic assistance.

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

The device itself is a standalone analytical instrument. The performance studies described (Internal Method Comparison, Internal Whole Blood Precision, Hemolysis Verification, etc.) essentially represent "standalone" performance, as they evaluate the accuracy and precision of the instrument's measurements directly. The iQM3 system is an internal quality control mechanism for the device's measurements. Therefore, yes, a standalone performance evaluation of the device's analytical capabilities was implicitly done.

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

For a device that provides quantitative measurements of blood parameters, the "ground truth" for the test set would typically be established using:

• Reference methods: Highly accurate and precise laboratory methods for measuring each analyte.
• Calibrated standards: Solutions with precisely known concentrations of the target analytes.
• Comparison to predicate device: As this is a 510(k) submission, a primary method of establishing "ground truth" performance for the new device is by comparing its measurements against those of a legally marketed predicate device (GEM Premier 5000), which itself would have been validated against reference methods and standards.

The text mentions "two completely independent solutions traceable to NIST standards, CLSI procedures or internal standards" for "Auto PAK Validation (APV)". This strongly suggests that traceable standards and potentially CLSI-defined reference methods were used to establish the ground truth for performance evaluation.

8. The sample size for the training set

The document describes the GEM Premier 7000 with iQM3 as a medical device for quantitative measurements, not explicitly as a machine learning/AI model that requires a "training set" in the conventional sense (i.e., for supervised learning). The iQM3 is an "active quality process control program" with "Pattern Recognition (PR) software." While pattern recognition might involve some form of "training" or calibration, the document does not specify a separate "training set" in terms of data volume for such a process. It focuses on the validation of the device's analytical performance. Therefore, the concept of a "training set" sample size as applicable to AI/ML devices is not explicitly discussed or provided.

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

As noted above, the primary function of GEM Premier 7000 with iQM3 is quantitative measurement. If the "iQM3" component involved training for its "Pattern Recognition (PR) software," the document does not detail how a specific ground truth for such training was established. It primarily discusses the use of "Process Control Solutions (PCS)" and "Calibration Valuation Product (CVP 5)" for system checks and validation ("Auto PAK Validation (APV) process"). These solutions, traceable to NIST or CLSI standards, function as internal reference points for the device's operational checks and quality control, which could be considered an ongoing form of "ground truth" to maintain analytical performance, rather than a one-time "training set" for model development.

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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.

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The ACL TOP Family 70 Series (ACL TOP 370, ACL TOP 570 and ACL TOP 770 / 770s / 770 LAS) are bench top, fully automated, random access analyzers designed specifically for in vitro diagnostic clinical use by health care professionals in the hemostasis laboratory for coagulation and/or fibrinolysis testing in the assessment of thrombosis and/or hemostasis. The systems provide results for both direct hemostasis measurements and calculated parameters.

The ACL TOP Family 70 Series are fully automated coagulation analyzers that utilize the same intuitive software, the same consumables, reagents, calibrators and controls, and provide the same analytical methodology for routine and specialty assay result reporting as the predicate ACL TOP Family 50 Series.

The ACL TOP Family 70 Series instrument performs the following types of tests, using the same optical measuring wavelengths and test parameters as the predicate ACL TOP Family 50 Series:

• . Coagulometric (Turbidimetric) Measurements
• Chromogenic (Absorbance) Measurements .
• . Immunological Measurements

The ACL TOP Family 70 Series also offers the same pre-analytical features available on the ACL TOP Family 50 Series. These features alert the instrument operator to a potential HIL (Hemoglobin, Icteric and Lipemia) interference situation specific to the assays requested for a sample, underfilled sample tubes or a detected clog.

Here's a breakdown of the acceptance criteria and study details for the ACL TOP Family 70 Series device, based on the provided document:

Acceptance Criteria and Reported Device Performance

The core acceptance criterion for the ACL TOP Family 70 Series appears to be demonstrating equivalent analytical performance to its predicate device, the ACL TOP Family 50 Series, across various representative assays. This equivalency is assessed through precision and method comparison studies.

Table of Acceptance Criteria and Reported Device Performance:

• HemosIL D-Dimer HS 500: Low Control Total %CV 4.8, High Control Total %CV 2.1
• HemosIL Factor VIII: Normal Control Total %CV 3.4, Abnormal Control Total %CV 4.8
• HemosIL RecombiPlasTin 2G (PT): Normal Control Total %CV 1.8, High Abn Control %CV 4.0
• HemosIL RecombiPlasTin 2G (Fibrinogen): Normal Control Total %CV 3.9, Low Fibrinogen Control %CV 8.1
• HemosIL Liquid Anti-Xa: UF Low Control Total %CV 1.8, LMW High Control Total %CV 2.2 |
  | Method Comparison | Linear regression analysis (slope, intercept, correlation coefficient 'r') between the subject device and predicate device should demonstrate equivalent performance across the analytical measuring range (AMR), according to established guidelines (CLSI EP09c. 3rd Ed). | Successfully met criteria. All studies showed strong correlation (r ≥ 0.998) and slopes close to 1 with intercepts close to 0, indicating equivalence. Examples:
• HemosIL D-Dimer HS 500: Slope 1.022, Intercept 0.5575, r 0.998
• HemosIL Factor VIII: Slope 1.006, Intercept -0.0587, r 0.998
• HemosIL RecombiPlasTin 2G (PT): Slope 1.012, Intercept -0.0940, r 1.000
• HemosIL RecombiPlasTin 2G (Fibrinogen): Slope 0.9756, Intercept -1.1220, r 0.999
• HemosIL Liquid Anti-Xa: Slope 0.9804, Intercept -0.0145, r 0.999 |
  | Overall Conclusion | Updates introduced do not impact the labeled performance data of the current menu of FDA-cleared assays. Device is safe and effective for its intended purpose and equivalent in performance to the predicate device. | Analytical study results demonstrate that the ACL TOP Family 70 Series, with updated non-analytical features, is safe and effective for its intended purpose and equivalent in performance to the predicate device (K150877). |

Study Details:

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

   • Precision Studies:
     • For each material/control for the selected representative assays, samples were run for 20 days at two runs per day, 2 replicates per run, resulting in a total of n=80 data points per material.
     • Provenance: Not explicitly stated, but based on the context of an FDA submission for an in vitro diagnostic device, these would typically be laboratory-generated samples or commercial control materials. The studies were performed internally by the manufacturer ("Instrumentation Laboratory Company").
   • Method Comparison Studies:
     • Sample sizes varied per assay:
       • HemosIL D-Dimer HS 500: N = 116 clinical samples
       • HemosIL Factor VIII: N = 104 clinical samples
       • HemosIL RecombiPlasTin 2G (PT): N = 116 clinical samples
       • HemosIL RecombiPlasTin 2G (Fibrinogen): N = 114 clinical samples
       • HemosIL Liquid Anti-Xa: N = 207 clinical samples
     • Provenance: The studies included "clinical samples spanning each assay's analytical measuring range (AMR)." The country of origin of these clinical samples is not specified, but they are prospectively collected or selected for the study based on their span across the AMR.

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

   • This being an in vitro diagnostic (IVD) device for laboratory analysis, the "ground truth" for the test set is established by the measurement itself on a recognized, cleared, and well-characterized comparator device (the predicate ACL TOP Family 50 Series), or by the known concentrations/activity of control materials. It's not a subjective interpretation task that requires human adjudication or expert consensus in the same way as, for example, image-based diagnostic AI. Therefore, no human experts are explicitly mentioned as establishing a subjective ground truth for these analytical performance studies. The "ground truth" for method comparison is the performance of the predicate device.

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

   • None. Adjudication methods like 2+1 or 3+1 are typically used in studies involving subjective human interpretation (e.g., radiology reads) where discrepancies need to be resolved. For analytical performance studies of a medical device measuring quantitative analytes, the ground truth is objective (the measured value from the predicate device or a known concentration in a control).

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:

   • No. An MRMC study is not applicable here as this is an in vitro diagnostic instrument, not an AI-assisted diagnostic tool that involves human readers interpreting cases. The device automatically performs coagulation and/or fibrinolysis testing.

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

   • Yes, effectively. The entire study evaluates the analytical performance of the device itself (the ACL TOP Family 70 Series) in a standalone manner. While trained lab personnel operate the instrument, the performance metrics (precision, method comparison) are about the instrument's ability to produce accurate and precise results, independent of human interpretive intervention for the results themselves. The device's "algorithm" (its internal measurement and calculation processes) is being evaluated.

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

   • For precision studies, the ground truth is the known concentration/activity of control and plasma pool materials.
   • For method comparison studies, the ground truth is the measured values obtained from the predicate device (ACL TOP Family 50 Series) for the same clinical samples. The principle is to see if the new device produces equivalent results when compared to an already accepted diagnostic method.

7. The sample size for the training set:

   • The document does not mention a training set in the context of machine learning or AI model development. This device is an IVD instrument that utilizes established analytical methodologies (coagulometric, chromogenic, immunological measurements) and software, rather than a machine learning model that requires a discrete training phase with labeled data. The studies performed are verification and validation studies to demonstrate performance and equivalency to a predicate.

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

   • As there is no mention of a "training set" in the context of an AI/ML model, this question is not applicable. The device's operation is based on pre-defined analytical principles, not on learning from a training dataset to establish a ground truth.

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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+), Potassium (K+), Ionized Calcium (Ca++), Chloride (Cl-), Glucose (Glu), Lactate (Lac), Hematocrit (Hct), Creatinine (Crea), Blood Urea Nitrogen (BUN), Total Carbon Dioxide (tCO2), 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, electrolyte and metabolite 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 treatment of electrolyte and metabolic disorders, such as cystic fibrosis and diabetic acidosis.

· 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 lactic acidosis, 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 red cells).

· Creatinine (Crea) measurements are used in the diagnosis and treatment of renal diseases and in monitoring renal dialysis.

· Blood Urea Nitrogen (BUN) or urea measurements are used for the diagnosis, monitoring, and treatment of certain renal and metabolic diseases.

· Total carbon dioxide/tCO2 (also referred to as bicarbonate/HCO3-) is used in the diagnosis, monitoring, and treatment of numerous potentially serious disorders associated with changes in body acid-base balance.

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

The GEM Premier ChemSTAT system provides fast, accurate, quantitative measurements of Sodium (Na"), Potassium (K*), Ionized Calcium (Ca*), Chloride (Cl·), Glucose (Glu), Lactate (Lac), Hematocrit (Hct), Creatinine (Crea), Blood Urea Nitrogen (BUN), Total Carbon Dioxide (tCO2), pH, and partial pressure of carbon dioxide (pCO2) from arterial and venous lithium heparinized whole blood.

The provided text describes a Special 510(k) submission for an upgrade to the operating system of the GEM Premier ChemSTAT device. The device itself is an in vitro diagnostic (IVD) system for quantitative measurements of various blood parameters. The submission focuses on the software upgrade rather than a change in the device's fundamental function or performance.

Therefore, the "acceptance criteria" and "reported device performance" in this context refer to the successful verification and validation of the software upgrade and the continued adherence to the established performance of the unmodified device, as the indications for use and performance claims remain unchanged. The study proving this essentially consists of the software verification and validation activities.

Here's the information extracted from the document, tailored to the context of a software upgrade:

1. Table of Acceptance Criteria and Reported Device Performance

Since this is a software upgrade with no changes to the performance claims of the device, the general acceptance criteria are that the upgraded software performs as intended without adversely affecting the device's established performance specifications. The reported device performance is that these criteria were met.

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

The document does not specify a "test set sample size" or "data provenance" in the traditional sense for evaluating diagnostic performance. The focus is on software verification and validation. Therefore, the "sample" for testing the software functionality would be the various test cases and scenarios designed to validate the operating system upgrade and its interaction with the GEM Premier ChemSTAT application software.

The document states: "Performance data is limited to Software Verification and Validation as the scope of this Special 510(k) is specific to an operating system upgrade from Fedora 17 Linux to WindRiver LTS 18 Linux."

Further details on the specific number of test cases, the nature of the data (e.g., simulated, actual runs on the device), or its origin are not provided in this summary.

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

This information is not applicable to a software operating system upgrade as described. "Ground truth" in the context of expert consensus is typically relevant for diagnostic performance studies where human interpretation or a gold standard reference is needed (e.g., pathology for an imaging device). Here, the "ground truth" is the proper functioning of the software and its integration with the hardware, which is evaluated through engineering and software testing.

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

This information is not applicable for a software operating system upgrade. Adjudication methods like 2+1 or 3+1 are used in clinical studies to resolve discrepancies in expert interpretation of diagnostic results. Software verification and validation typically rely on predefined test outcomes and engineering assessments.

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

This information is not applicable. An MRMC comparative effectiveness study is used to evaluate the impact of an AI algorithm on human reader performance, usually for diagnostic tasks. This submission is for a software operating system upgrade for an existing IVD device, not for a new AI algorithm.

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

The concept of "standalone performance" in the context of an algorithm's diagnostic capability (like an AI algorithm) is not directly applicable here. The device itself (GEM Premier ChemSTAT) operates to provide quantitative measurements. The software upgrade ensures the continued, correct operation of the device. The verification and validation activities demonstrate that the upgraded software performs its functions correctly as part of the overall device system.

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

For this software upgrade, the "ground truth" is the expected behavior and functionality of the software and the device. This is established through:

• Functional specifications: The software is expected to perform according to its design specifications.
• Risk analysis: The software should not introduce new risks or fail to mitigate existing ones.
• Cybersecurity standards: The software should meet cybersecurity requirements.
• Established device performance: The software upgrade should not negatively impact the established analytical and clinical performance of the GEM Premier ChemSTAT device (which relies on the physical and chemical principles of its measurements).

The document explicitly states that the changes "do not introduce...changes to labeled performance claims." This implies that the performance of the device (e.g., accuracy, precision of Na+, K+, Glu measurements) remains the same as previously cleared, and the software upgrade was validated not to alter these.

8. The sample size for the training set

This information is not applicable. Training sets are used for machine learning models. This submission describes a conventional software operating system upgrade (Fedora 17 Linux to WindRiver LTS 18 Linux) for an existing IVD device, not the development or retraining of a machine learning algorithm.

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

This information is not applicable, as there is no training set for a machine learning model; it is a software operating system upgrade.

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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.

• PT: UFH (1.0 IU/mL), LMWH (1.4 IU/mL), Hemoglobin (500 mg/dL), Triglycerides (1000 mg/dL), Bilirubin (Conjugated & Unconjugated) (50 mg/dL), Daptomycin (100 µg/mL)
• Fibrinogen: UFH (1.5 IU/mL), LMWH (1.7 IU/mL), Hemoglobin (500 mg/dL), Triglycerides (600 mg/dL), Bilirubin (Conjugated & Unconjugated) (50 mg/dL), Daptomycin (200 µg/mL) | New claims for daptomycin and conjugated bilirubin interference were added. The study used 2 clinical sample levels for both PT and Fibrinogen. |
  | Method Comparison | Strong correlation and agreement between the subject device and the predicate device (HemosIL RecombiPlasTin 2G). Slope should be near 1, intercept near 0, and correlation coefficient (r) close to 1. | ACL TOP Family:
• PT (INR): Slope 1.031 (95% CI 1.009, 1.053), Intercept -0.043 (-0.068, -0.018), r 0.997
• Fibrinogen (mg/dL): Slope 0.975 (95% CI 0.963, 0.986), Intercept 7.171 (3.842, 10.50), r 0.995
  ACL TOP Family 50 Series:
• PT (INR): Slope 1.021 (95% CI 0.999, 1.043), Intercept -0.034 (-0.060, -0.009), r 0.996
• Fibrinogen (mg/dL): Slope 1.015 (95% CI 1.003, 1.027), Intercept -0.811 (-4.148, 2.527), r 0.994 | All method comparison results demonstrated excellent correlation and agreement, supporting substantial equivalence. |
  | Open Vial Stability | Maintain performance for 10 days at 2-8°C in closed original vial after preparation. | "The results support the following labeled open vial stability claim: Once prepared for use, 10 days at 2-8℃ in closed original vial" | Tested across 3 lots per CLSI EP25-A. |
  | On-board Instrument Stability | Maintain performance for 10 days at 15°C on the ACL TOP Family and ACL TOP Family 50 Series after preparation. | "The results support the following labeled on-board instrument stability claim: Once prepared for use, 10 days at 15°C on the ACL TOP Family and ACL TOP Family 50 Series" | Tested across 3 lots per CLSI EP25-A. |
  | Real-time Shelf-life Stability | Device maintains stated performance throughout its claimed shelf-life. | "The study will continue to a point past final claim." (Ongoing assessment to support shelf-life). | Tested across 3 lots per CLSI EP25-A. |

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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