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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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The Total Bilirubin2 assay is used for the quantitation of total bilirubin in human serum or plasma, of adults and neonates, on the ARCHITECT c System.

Measurement of total bilirubin, an organic compound formed during the normal destruction of red blood cells, is used in the diagnosis and treatment of liver, hematological, and metabolic disorders, including hepatitis and disorders of the biliary tract. In newborn infants, the Total Bilirubin2 assay is intended to measure the levels of total bilirubin (conjugated and unconjugated) in serum or plasma to aid in the diagnosis and management of neonatal jaundice and hemolytic disease of the newborn.

The Total Bilirubin2 assay (subject device) is an automated clinical chemistry assay for the quantitation of total bilirubin in human serum or plasma, of adults and neonates, on the ARCHITECT c System. Total (conjugated and unconjugated) bilirubin couples with a diazo reagent in the presence of a surfactant to form azobilirubin. The diazo reaction is accelerated by the addition of surfactant as a solubilizing agent. The increase in absorbance at 548 nm due to azobilirubin is directly proportional to the total bilirubin concentration. The methodology is Diazonium salt.

The provided text describes a 510(k) premarket notification for a medical device called "Total Bilirubin2", an in vitro diagnostic assay. This type of submission focuses on demonstrating substantial equivalence to a legally marketed predicate device, rather than proving clinical effectiveness through the extensive studies typically associated with AI/ML diagnostic tools. Therefore, the questions related to AI/ML specific criteria (like MRMC studies, number of experts for ground truth, sample size for training sets, etc.) are not applicable in this context.

The document primarily details the analytical performance of the Total Bilirubin2 assay.

Here's an analysis based on the information provided, adhering to the request:

Acceptance Criteria and Reported Device Performance

The acceptance criteria for this in vitro diagnostic device are typically defined by ranges of acceptable analytical performance, following established CLSI (Clinical and Laboratory Standards Institute) guidelines. The reported device performance is compared against these internal acceptance criteria.

Study Details:

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

   • Precision (Within-Laboratory): 80 replicates for each control/panel (on a representative combination out of 3 multi-lot/instrument combinations).
   • Reproducibility (System): 84 replicates for each control/panel.
   • Lower Limits of Measurement: ≥ 60 replicates for LoB and LoD for each of 3 lots on 2 instruments.
   • Interfering Substances: Not explicitly stated, but "Each substance was tested at 2 levels of the analyte."
   • Method Comparison:
     • Serum: 167 samples
     • Neonatal serum: 163 samples
   • Tube Type: Samples collected from a minimum of 40 donors.
   • Dilution Verification: 5 samples prepared with varying concentrations.
   • Data Provenance: Not explicitly stated regarding country of origin or whether retrospective/prospective. However, given the nature of in vitro diagnostic analytical studies, samples are typically acquired prospectively or from biobanks for specific analytical testing purposes.

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

   • For in vitro diagnostic devices like this bilirubin assay, "ground truth" is established by reference methods or highly characterized calibrators/control materials, not by expert human readers. The accuracy study, for example, compares results to material standardized to the Doumas Total Bilirubin reference method, which represents the "ground truth" for bilirubin measurement. Therefore, expert readers/adjudicators as typically seen in imaging AI studies are not applicable here.

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

   • Not applicable. This is an in vitro diagnostic assay, and its performance is evaluated against analytical measurements, not human interpretations requiring adjudication.

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 device is an in vitro diagnostic test, not an AI/ML-driven imaging or diagnostic algorithm designed to assist human readers.

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

   • Not applicable. This is an assay performed on an automated system, providing a quantitative result. Its "performance" is inherently "standalone" in generating the numerical value, but it's not an AI algorithm in the sense of image interpretation or complex diagnostic inference.

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

   • For analytical performance studies, the "ground truth" for bilirubin concentration is established by reference methods (e.g., the Doumas method for accuracy) or by using certified reference materials and calibrators with known concentrations. This is the gold standard for quantitative in vitro diagnostic measurements.

7. The sample size for the training set:

   • Not applicable. This is not an AI/ML device that requires a "training set" in the computational sense. The device's performance is a function of its reagents, instrument, and established methodology, not a learned algorithm.

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

   • Not applicable. See above.

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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.

3

· 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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The RAPIDPoint® 500e Blood Gas System is in vitro diagnostic use and is designed to provide the determination in whole blood for the following parameters:

• Partial pressure of carbon dioxide ●
• Partial pressure of oxygen
• pH
• Sodium ●
• Potassium
• lonized Calcium ●
• Chloride .
• Glucose ●
• . Lactate
• . Total Hemoglobin and fractions: FO2Hb, FCOHb, FMetHb, FHHb
• . Neonatal Bilirubin

The RAPIDPoint 500e Blood Gas System is also intended for in vitro testing of pleural fluid samples for the pH measurement of pleural fluid can be a clinically useful tool in the management of patients with parapneumonic effusions.

The following critical value applies to pleural fluid pH > 7.3 is measured in uncomplicated parapneumonic effusions. All pleural fluids with a pH measurement

The RAPIDPoint 500e Blood Gas System is a compact, bench-top analyzer designed for in vitro diagnostic testing and is suitable for professional use in a point-of-care or central laboratory environment. This system measures the following: blood gases, electrolytes, total hemoglobin, and hemoglobin derivatives in arterial, venous, and capillary whole blood samples. Additionally, the RAPIDPoint 500e Blood Gas System measures pH in pleural fluid.

The RAPIDPoint 500e Blood Gas System incorporates a cartridge-based design with no external reagent bottles or gas tanks. The system uses self-contained measurement and wash/waste cartridges that are replaced when depleted. The system automatically calibrates the measurement sensors and reports results within 60 seconds for display on a color touch screen for easy viewing.

The provided text concerns the FDA 510(k) summary for the RAPIDPoint® 500e Blood Gas System. This document describes a modification to an existing device (RAPIDPoint 500 System) and asserts its substantial equivalence for FDA clearance. Therefore, a study to prove the device meets specific acceptance criteria for a new clinical claim (such as disease diagnosis accuracy based on images) is not applicable here.

The submission is a Special 510(k), meaning the changes are minor and do not alter the intended use, fundamental scientific technology, labeling, or principle of operation. The primary changes are an operating system update and minor hardware/software enhancements.

Key points from the document regarding "acceptance criteria" and "study:

• No new performance claims: The document explicitly states: "There is no change to labeled performance claims." This implies that the performance criteria previously established for the predicate device (RAPIDPoint 500 System) are still considered valid and met by the modified device.
• Verification and validation activities: The document states: "All verification and validation activities were performed in accordance to relevant standards, established plans and protocols and Siemens Design Control procedures. Testing verified all acceptance criteria were met." This refers to internal engineering and design control testing to ensure the modifications haven't negatively impacted the known performance characteristics of the device.

Given this context, I cannot generate a table of acceptance criteria and reported device performance in the typical sense of a clinical diagnostic study with new performance endpoints. The "acceptance criteria" here refers to demonstrating that the modified device performs comparably to the predicate for all existing measurements and that the new software/hardware features function as intended without compromising safety or effectiveness.

Therefore, the requested information elements cannot be fully addressed in the way they would for a device making new diagnostic claims based on a primary clinical study.

Here's an attempt to answer the questions based on the available information, noting where specific details are not provided:

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

   As this is a Special 510(k) for a modified device with "no change to labeled performance claims" and "no change to principle of operation," there isn't a new set of clinical performance acceptance criteria and reported performance figures presented in this summary document. The acceptance criteria implicitly refer to demonstrating that the modified device's performance is substantially equivalent to the predicate device across all analytes and clinical uses, meaning it continues to meet the predicate's established performance specifications. The document states: "Performance testing results were also comparable."

   Inferred Acceptance Criteria (based on substantial equivalence to predicate):
   The modified device (RAPIDPoint 500e Blood Gas System) must demonstrate performance comparable to the legally marketed predicate device (RAPIDPoint 500 System) for all measured analytes (pCO2, pO2, pH, Sodium, Potassium, Ionized Calcium, Chloride, Glucose, Lactate, Total Hemoglobin and fractions, Neonatal Bilirubin) in whole blood and pH in pleural fluid. This comparability would typically be assessed by demonstrating agreement (e.g., bias, precision, linearity) within acceptable limits as defined for the predicate device.

   Reported Device Performance:
   The document states: "Performance testing results were also comparable." Specific numerical performance data (e.g., accuracy, precision) for each analyte for the modified device are not provided in this 510(k) summary, as the submission focuses on substantial equivalence of the modified device to the predicate, rather than establishing new performance specifications.

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

   Not explicitly stated in the provided document. The document refers to "verification and validation activities" and "performance testing results," but does not detail the sample sizes or the provenance (e.g., country of origin, retrospective/prospective) of the data used for establishing "comparable" performance. Given it's a diagnostic device for blood analysis, samples would typically be human blood and pleural fluid.

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

   Not applicable or not specified. For laboratory diagnostic devices like blood gas analyzers, "ground truth" is typically established by reference methods or highly accurate laboratory instruments, not by a panel of human experts interpreting data.

4. Adjudication method for the test set

   Not applicable or not specified. Adjudication methods (e.g., 2+1, 3+1) are typically used in clinical studies for endpoint determination (e.g., presence of disease from images) based on multiple expert opinions. For a blood gas system, the performance is evaluated by comparing measurements against reference methods, not subjective adjudication.

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

   Not applicable. This device is an in vitro diagnostic (IVD) blood gas system, not an AI-assisted diagnostic imaging or interpretation device that involves human "readers."

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

   This device is an automated in vitro diagnostic system. Its "standalone" performance means the accuracy and reliability of its measurements of various blood parameters. While the document mentions software changes and cybersecurity enhancements, it is not an algorithm that interprets human-generated data or makes a diagnosis. Its performance is inherent to its measurement capabilities. The 510(k) summary asserts that its performance is "substantially equivalent" to the predicate, implying successful internal testing to confirm this.

7. The type of ground truth used

   For IVD devices measuring physiological parameters, "ground truth" is typically established by:

   • Reference methods: Highly accurate and validated analytical methods (e.g., gas chromatography for blood gases, gravimetric methods for electrolytes) or
   • Comparison to predicate/established devices: Comparing measurements from the device under evaluation to a legally marketed and well-characterized predicate device or other established clinical laboratory instruments.

   This document explicitly states the modified device is "substantially equivalent to the comparative method" (referring to the predicate device).

8. The sample size for the training set

   Not applicable or not specified. This is a measurement device for chemical and physiological parameters, not a machine learning model that requires a distinct "training set" of clinical data in the typical sense. Any internal developmental data would be for engineering optimization rather than model training.

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

   Not applicable (as it's not an AI/ML device requiring a training set in that context).

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The ABL90 FLEX analyzer is an in vitro diagnostic, portable, automated analyzer that quantitatively measures neonatal bilirubin in heparinized capillary, venous and arterial whole blood.
The ABL90 FLEX analyzer is intended for use by trained technologists, nurses, physicians and therapists.
It is intended for use in a laboratory environment, near patient or point-of-care setting.
These tests are only performed under a physician's order.
Bilirubin measurements on the ABL90 FLEX analyzer are intended to aid in assessing the risk of kernicterus in neonates.

ABL90 FLEX PLUS:
The ABL90 FLEX PLUS analyzer is an in vitro diagnostic, portable, automated analyzer that quantitatively measures neonatal bilirubin in heparinized capillary, venous and arterial whole blood.
The ABL90 FLEX PLUS analyzer is intended for use by trained technologists, nurses, physicians and therapists.
It is intended for use in a laboratory environment, near patient or point-of-care setting.
These tests are only performed under a physician's order.
Bilirubin measurements on the ABL90 FLEX PLUS analyzer are intended to aid in assessing the risk of kernicterus in neonates.

The ABL90 FLEX and ABL90 FLEX PLUS analyzers are two models of the same portable, automated system intended for in vitro testing of samples of whole blood for the parameters pH, pO-, pCO3, potassium, sodium, calcium, chloride, glucose, lactate, neonatal bilirubin, and co-oximetry parameters (total hemoglobin, oxygen saturation, and the hemoglobin fractions FO-Hb, FCOHb, FMetHb, FHHb and FHbF).
The manufacturer of the ABL90 FLEX and ABL90 FLEX PLUS is Radiometer Medical ApS.
The ABL90 FLEX and ABL90 FLEX PLUS consist of an instrument with a sensor cassette and a solution pack as the main accessories. Multiple models of sensor cassettes are available.
The various sensor cassette models for different parameter combinations. For each parameter combination, models allowing for different test load are available.
The solution pack is available in two models differing in the number of tests available.
Technology:
The ABL 90 FLEX and ABL90 FLEX PLUS electrochemical sensors are miniaturized, manufactured by film technology and integrated in a common sensor cassette. Likewise, the ABL90 FLEX and ABL90 FLEX PLUS optical oxygen sensor is integrated in the sensor cassette. A 256-pixel array spectrophotometer is used for the co-oximetry parameters and bilirubin.
Clinical Utility ctBil:
For newborns up to an age of one month the method's reportable range covers the entire reference range. Neonatal Bilirubin test is intended for use to aid in assessing the risk of kernicterus in newborns.

The provided document is a 510(k) Premarket Notification from the FDA regarding the ABL90 FLEX and ABL90 FLEX PLUS devices for measuring neonatal bilirubin. It primarily focuses on demonstrating substantial equivalence to a predicate device, rather than defining and proving acceptance criteria as typically done for novel AI/ML medical devices.

Therefore, many of the requested points related to acceptance criteria, ground truth establishment, expert consensus, MRMC studies, and training sets are not applicable to this type of submission. This 510(k) is for an in-vitro diagnostic device that measures a chemical parameter (bilirubin) using established spectrophotometric technology, not an AI/ML-driven diagnostic or image analysis tool. The "performance" being evaluated is the analytical performance (accuracy, precision, linearity) of the device against a known predicate and reference methods, not the diagnostic performance of an algorithm.

However, I can extract the relevant information from the document that pertains to its performance evaluation.

Overview of Device Performance Evaluation (Not AI/ML focused)

The ABL90 FLEX and ABL90 FLEX PLUS analyzers are in vitro diagnostic devices designed to quantitatively measure neonatal bilirubin in heparinized capillary, venous, and arterial whole blood. The submission aims to extend the indicated sample types for neonatal bilirubin measurement to include arterial and venous whole blood, leveraging performance data already established for capillary whole blood in a previous 510(k) (K132691).

The core of the performance study for this specific submission is demonstrating method comparison (correlation) against a predicate device (ABL800 FLEX or ABL835 FLEX, which is part of the ABL800 FLEX family) for the new sample types.

Relevant Performance Information and Analysis (from the provided document):

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

   • Acceptance Criteria: Not explicitly stated as pass/fail thresholds in this document for the method comparison study. The goal is to demonstrate "substantial equivalence" based on the correlation characteristics (slope, intercept, R-squared) to the predicate device. The implicit acceptance is that the correlation is strong (R-squared close to 1) and the linear relationship is close to y=x (slope close to 1, intercept close to 0), indicating comparable performance to the predicate. The FDA's determination of substantial equivalence implies these criteria were met.

   • Reported Device Performance (from Table 1: Neonatal bilirubin linear regression data for ABL90 FLEX measurements compared to ABL835 FLEX measurements):

     Parameter	Units	Slope	Intercept (mg/dL)	R²	Sy.x (mg/dL)
     ctBil All (combined samples)	mg/dL	0.97	-0.38	1.00	0.60
     ctBil Arterial All	mg/dL	0.98	-0.54	0.97	0.53
     ctBil Venous All	mg/dL	0.98	-0.32	0.98	0.62
     ctBil site 1	mg/dL	0.96	-0.18	1.00	0.57
     ctBil site 2	mg/dL	0.98	-0.71	1.00	0.58

   Interpretation: The R-squared values are very high (0.97 to 1.00), indicating a very strong linear correlation between the ABL90 FLEX and the predicate ABL835 FLEX. The slopes are close to 1 (0.96-0.98) and intercepts are close to 0 (-0.18 to -0.71 mg/dL), suggesting good agreement (i.e., minimal proportional or constant bias) between the new device and the predicate.

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

   • Test Set Sample Sizes:
     • 44 arterial blood samples
     • 42 venous blood samples
     • 17 spiked cord blood samples
     • Total N = 103 samples (44 arterial + 42 venous + 17 spiked)
   • Data Provenance: The study was conducted at "two point-of-care sites." The document does not specify the country of origin of the data. It is a prospective method comparison study where new measurements were taken for the purpose of this submission.

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

   • Not applicable in the context of an AI/ML algorithm. For this in vitro diagnostic device, the "ground truth" for the method comparison is the measurement obtained from the predicate device (ABL835 FLEX), which is itself a validated diagnostic instrument. This is an analytical performance study, not a diagnostic performance study relying on expert interpretation.

4. Adjudication method for the test set:

   • Not applicable. This study involves direct quantitative measurements of a chemical analyte, not qualitative assessments or interpretations that would require adjudication.

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

   • Not applicable. This is an in vitro diagnostic device measuring a chemical substance, not an AI-assisted diagnostic tool that would involve human readers interpreting images or data.

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

   • This is inherently a "standalone" device in its measurement function. The device itself performs the measurement and provides a numerical output. Human involvement is in operating the device and interpreting the numerical result in a clinical context, but not in assisting an algorithm to produce the measurement.

7. The type of ground truth used:

   • The "ground truth" (or reference method for comparison) was measurements obtained from another legally marketed device (predicate device, ABL835 FLEX), which is widely considered a reliable method for bilirubin measurement. For in vitro diagnostics, this is a standard approach to demonstrating substantial equivalence – showing comparable performance to an established method.

8. The sample size for the training set:

   • Not applicable. This device uses established spectrophotometric technology and is not an AI/ML device that requires a training set in the conventional sense. The "training" here would be the design and calibration of the instrument based on chemical and optical principles.

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

   • Not applicable. As above, no training set in the AI/ML sense.

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For in vitro diagnostic use in the quantitative determination of total bilirubin in serum and plasma of adults and neonates on the ADVIA® Chemistry systems. Measurement of total bilirubin, an organic compound formed and abnormal destruction of red blood cells, is used in the diagnosis and treatment of liver, hemolytic hematological, and metabolic disorders, including hepatitis and gall bladder block. A total bilirubin measurement in newborn infants is intended to aid in indicating the risk of bilirubin encephalopathy (kernicterus).

The ADVIA® Chemistry Total Bilirubin_2 (TBIL_2) reagents are liquid ready to use. They are packaged as a kit with two kit sizes available as follows.
Kit Size – 70 mL Wedge Reagent 1 and 70 mL Reagent 2 Wedge
Reagent 1: 4 wedges x 68 mL
Reagent 2: 4 wedges x 25 mL
Kit Size - 40 mL Reagent 1 and 20 mL Reagent 2 Wedge
Reagent 1: 4 wedges x 38 mL
Each reagent kit consists of reagents of components and concentrations summarized below.
Reagent 1: Citrate buffer, pH 2.9 (0.1 mol/L); Detergent
Reagent 2: Phosphate buffer, pH 7.0 (10mmol/L); Sodium metavanadate (4 mmol/L)

Here's a breakdown of the acceptance criteria and study information for the ADVIA® Chemistry Total Bilirubin 2 (TBIL 2) device, based on the provided document:

Acceptance Criteria and Device Performance

The document doesn't explicitly state "acceptance criteria" for each performance characteristic as a distinct set of pre-defined thresholds. Instead, it presents the results of validation studies for various parameters. However, we can infer the implicit "acceptance criteria" by looking at industry standards (like CLSI guidelines cited) and typical performance expectations for such devices. The "reported device performance" directly comes from the study results.

Note: For some parameters, the "acceptance criteria" are implied by the method and regulatory guidelines (e.g., CLSI EP09-A3 for method comparison, which focuses on demonstrating accuracy through strong correlation and acceptable bias at medical decision points).

• Indican: 10 mg/dL
• Cyanokit: 40 ug/mL
• HbF: 1000 mg/dL
• HbA: 1000 mg/dL |
  | Expected Values (Reference Interval) | Reference intervals established or verified in accordance with CLSI guidelines and supported by literature. (Based on CLSI EP28-A3c and Wu AHB. Tietz Clinical Guide) | Verified expected values:
• 0-1 day: 5 days – 60 years: 0.3-1.2 mg/dL
• 60 - 90 years: 0.2-1.1 mg/dL

• 90 years: 0.2-0.9 mg/dL (Reference: Wu AHB. Tietz Clinical Guide to Laboratory Tests, 4th edition, 2006:172) |

Detailed Study Information:

The provided document describes analytical performance studies for the ADVIA® Chemistry Total Bilirubin 2 (TBIL 2) device. It is a standalone (algorithm only without human-in-the-loop performance) study, as it evaluates the analytical performance of a clinical chemistry assay, not a diagnostic imaging device with human interpretation.

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

   • Method Comparison: N = 119 patient samples.
   • Analytical Measuring Range/Linearity: The document states "9 levels" for linearity but does not specify the number of individual samples tested at each level or overall (implied to be an internally prepared linearity panel).
   • Limits of Detection and Quantitation: Not explicitly stated for specific test sets, usually involves multiple replicates of blank and low-concentration samples.
   • Interferences: Not explicitly stated for specific test sets; involved samples with low and high concentrations of bilirubin plus various interferents.
   • Data Provenance: Not explicitly stated. These are typically laboratory-generated samples or de-identified patient samples obtained for research purposes within the testing laboratory's region. The adult population data were previously cleared under K063845, implying this testing focused on neonatal-specific aspects or reaffirming general performance on the new instrument.

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

   • For this type of in vitro diagnostic device, "ground truth" is established through well-characterized reference methods or highly accurate comparator devices/methods. There are no "experts" in the human interpretation sense (like radiologists) involved in establishing the ground truth for these analytical measurements.
   • The "comparator method" for the method comparison study served as the reference for ground truth in that context. Its specifics (e.g., gold standard, reference material) are not detailed beyond being a "legally marketed comparator method."

3. Adjudication Method for the Test Set:

   • Not applicable. This is an analytical performance study of a quantitative assay, not a study involving human readers' interpretations of images or clinical reports requiring adjudication.

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

   • No, an MRMC study was not done. This document describes the analytical performance of an in vitro diagnostic assay, which traditionally does not involve human readers interpreting "cases" in the way an imaging device might.

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

   • Yes, a standalone study was done. The entire document details the analytical performance of the ADVIA® Chemistry Total Bilirubin 2 (TBIL 2) assay on an automated instrument (ADVIA® Chemistry 1800 System) without human interpretive input for the final result beyond loading samples and running the assay.

6. The Type of Ground Truth Used:

   • For the Method Comparison study, the ground truth was established by a legally marketed comparator method.
   • For Linearity, LoD/LoQ, and Interference studies, the ground truth involves carefully prepared samples (e.g., spiked samples, diluted samples, reference materials) with known concentrations or expected responses, tested against established analytical validation protocols.
   • For Expected Values (Reference Interval), the ground truth was established by literature reference (Wu AHB. Tietz Clinical Guide to Laboratory Tests, 4th edition, 2006:172) and verified according to CLSI guidelines.

7. Sample Size for the Training Set:

   • Not applicable. This document describes the validation of a finished assay and instrument system. Clinical chemistry assays are developed and optimized through iterative research and development, but there isn't a "training set" in the machine learning sense. The "reagent formulation and method parameters" (mentioned as remaining the same for adult claims from K063845) represent the output of prior development.

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

   • Not applicable. As a traditional in vitro diagnostic assay, the concept of a "training set" and associated ground truth is not relevant in the machine learning context. The assay's performance is governed by its chemical reaction principle and instrument calibration/characteristics.

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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 glucose, lactate and total bilirubin from venous, arterial and capillary heparinized whole blood. These parameters aid in the diagnosis of a patient's metabolite balance.

Glucose (Clu) 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 measurement is used to aid in assessing the risk of kernicterus and hyperbilirubinemia in neonates.

The GEM Premier 5000 system provides health care professionals in central laboratory or point-of-care clinical settings with fast, accurate, quantitative measurements of glucose, lactate and total bilirubin from venous, arterial and capillary heparinized whole blood.

Key Components:

• Analyzer: Employs a unique color touch 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.
• GEM Premier 5000 PAK (disposable, multi-use GEM PAK): Houses all required components necessary to operate the instrument once the cartridge is validated. These components include the sensors, CO-Ox/tBili optical cell, Process Control (PC) Solutions, sampler, pump tubing, distribution valve and waste bag. The GEM PAK has flexible menus and test volume options to assist facilities in maximizing efficiency.
• Intelligent Quality Management 2 (iQM2): iQM2 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. iQM2 is a statistical process control system that performs 5 types of continuous, quality checks to monitor the performance of the GEM PAK, sensors, CO-Ox, and reagents. These checks include System, Sensor, IntraSpect, Pattern Recognition and Stability Checks.

The provided text describes the performance of the GEM Premier 5000 device for measuring Glucose, Lactate, and Total Bilirubin. The document primarily focuses on analytical and clinical studies to demonstrate substantial equivalence to predicate devices, rather than establishing acceptance criteria against a specific benchmark.

However, we can infer acceptance criteria based on the "Total Error Observed" compared to "Total Error Specifications" in the "Whole Blood Performance at Medical Decision Levels" section. The document states, "Total Error was computed based on the following equation and the results were compared to the GEM Premier 5000 Total Error Specifications." This implies that the 'Total Error Specifications' are the acceptance criteria.

1. Table of acceptance criteria and the reported device performance:

Note: The document explicitly states "All results were within specification" for precision studies and "All parameter levels passed specification for all sample modes" for internal method comparison, and "The analytical and clinical study results demonstrate that the GEM Premier 5000 is safe and effective for its intended purpose and equivalent in performance to the predicate devices." While specific numerical acceptance criteria (Total Error Specifications) are not detailed in the provided excerpts, the text indicates that the observed total error for Glucose, Lactate, and tBili met these internal specifications. For the clinical testing section concerning capillary samples, a "TEa" (Total Error Allowable) is given, which serves as an acceptance criterion for those specific tests.

Capillary Samples Acceptance Criteria (TEa) and Performance:

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

• Internal Precision Study - Aqueous Controls: N=120 per analyte/level for each of the 3 controls (GEM System Evaluator and CVP 5 tBili). The study was internal to the manufacturer (Instrumentation Laboratory Co.).
• Internal Precision Study – GEM PAK (Cartridge) Process Control Solutions D and E: N=120 per analyte/level for each of the 2 solutions. The study was internal to the manufacturer.
• Internal Precision Study – Whole Blood: N=120 per analyte/level/sample mode (Normal and Micro) for five different concentrations of whole blood. The study was internal to the manufacturer.
• Reproducibility Study with Aqueous Controls – Point-of-Care (POC) Setting: N=90 pooled data (30 replicates per level) per analyte/level. This involved 3 external clinical POC sites, suggesting prospective data collection in a point-of-care setting.
• External Precision - Whole Blood: Patient samples were tested at 2 external central laboratories and 1 internal Customer Simulation Laboratory (CSL), and 3 external POC locations. At least two whole blood specimens were analyzed in triplicate daily for 5 days. Specific "N" values for each site and analyte are provided in the tables within the document (e.g., for Glu Normal Mode, POC1 N=51, POC2 N=39, POC3 N=27, CSL N=33, Lab1 N=30, Lab2 N=30). Data provenance is a mix of internal CSL (contrived and native specimens) and external clinical labs and POC sites (patient samples), implying prospective collection of patient samples.
• LoB, LoD, LoQ: Three (3) lots of GEM Premier 5000 PAKs (cartridges) were used.
• Linearity: Nine (9) levels per analyte, each analyzed in triplicate on three (3) GEM Premier 5000 test analyzers. Data provenance appears to be internal.
• Analytical Specificity: Interference study conducted on the GEM Premier 5000. Data provenance appears to be internal.
• Internal Method Comparison: N=373 for Glucose and Lactate, N=163 for tBili. Clinical samples were used, and samples were altered as needed to cover medical decision levels. Data provenance appears to be internal to the manufacturer, comparing to predicate devices.
• Clinical Testing (Method Comparison in POC):
  • Glucose and Lactate (Normal Mode): N=489 for Glucose, N=488 for Lactate. Pooled results from 3 external POC sites and 1 internal CSL. This included patient samples and spiked samples (at CSL).
  • Glucose and Lactate (Native Capillary Samples): N=171. Pooled results from an external POC site and the internal CSL using finger-stick samples.
  • Glucose and Lactate (Contrived Capillary Samples): N=197 for Glucose, N=201 for Lactate. Pooled native capillary samples with additional contrived capillary samples prepared internally.
  • Total Bilirubin (Normal, Capillary, and tBili/CO-Ox Modes): Against Roche Cobas 6000: N=53 (Normal), N=58 (Capillary), N=53 (tBili/CO-Ox). Against Ortho Clinical Diagnostics Vitros 5600: N=76 (Normal), N=77 (Capillary), N=77 (tBili/CO-Ox). Pooled results from external POC sites with neonate samples, adult samples, and spiked samples.

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

The document does not specify the number or qualifications of experts for establishing ground truth. The devices being compared are laboratory diagnostic instruments. Therefore, "ground truth" is likely established by reference methods or predicate devices, which are themselves high-accuracy laboratory instruments (e.g., GEM Premier 4000, ABL 837, Roche Cobas 6000, Ortho Clinical Diagnostics Vitros 5600). The "experts" in this context would be the technicians or clinical laboratory scientists operating these reference systems, though their specific qualifications are not stated.

4. Adjudication method for the test set:

Not applicable. This is a medical device performance study, not a clinical trial with human interpretation requiring adjudication. Performance is assessed by comparing results to established reference methods or predicate devices.

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

Not applicable. This document pertains to an in vitro diagnostic device for quantitative measurements of analytes, not an AI-assisted diagnostic imaging or interpretation system involving human readers.

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

Yes, the studies presented are essentially "standalone" evaluations of the device's analytical performance, without direct human interpretation being part of the measurement process itself. The device (GEM Premier 5000) provides quantitative measurements, and its accuracy and precision are assessed against reference methods. While human operators are involved in running the device and collecting samples, the device's output is a direct quantitative result, not an interpretation that is then refined or improved by a human.

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

The "ground truth" for the performance studies is established through comparative analysis with predicate devices (GEM Premier 4000 for glucose and lactate, ABL 837 for total bilirubin) and commercially available laboratory reference analyzers (e.g., Roche Cobas 6000, Ortho Clinical Diagnostics Vitros 5600) for total bilirubin. These predicate and reference devices represent highly accurate and established measurement methods in clinical chemistry.

8. The sample size for the training set:

Not applicable. This document describes the validation of a laboratory instrument, not a machine learning model that requires a "training set." The device's performance is based on its internal design, sensors, and chemical reactions, which are validated through empirical studies rather than algorithm training.

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

Not applicable, as there is no "training set" in the context of this device validation.

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The ABL90 FLEX PLUS analyzer is an in vitro diagnostic, portable, automated analyser that quantitatively measures, pH, blood gases, electrolytes, glucose, lactate and oximetry in heparinized whole blood, and neonatal bilirubin in heparinized capillary whole blood.

The ABL90 FLEX PLUS analyzer is intended for use by trained technologists, nurses, physicians and therapists.

It is intended for use in a laboratory environment, near patient or point-of-care setting.

These tests are only performed under a physician's order.

Bilirubin measurements on the ABL90 FLEX PLUS analyzer are intended to aid in assessing the risk of kernicterus in neonates.

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

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

Sodium (cNa+); sodium 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.

Calcium (cCa2+): calcium measurements are used in the diagnosis and treatment of parathyroid disease, a variety of bone diseases, chronic renal disease and tetany.

Chloride (cCl-): chloride measurements are used in the diagnosis and treatment of electrolyte and metabolic disorders such a cystic fibrosis and diabetic acidosis.

Glucose (cGlu): qlucose measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus and idiopathic hypoqlycemia, and of pancreatic islet cell carcinoma.

Lactate (cLac): The lactate measurements measure the concentration of lactate in plasma. Lactate measurements are used to evaluate the acid-base status and are used in the diagnosis and treatment of lactic acidosis (abnormally high acidity of the blood.)

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

sO2: oxygen saturation, more specifically the ratio between the concentration of oxyhemoqlobin and oxyhemoglobin plus reduced hemoqlobin.

FO2Hb: oxyhemoqlobin as a fraction of total hemoqlobin.

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

FMetHb: methemoglobin as a fraction of total hemoglobin.

FHHb: reduced hemoqlobin as a fraction of total hemoglobin.

Fraction of Fetal Hemoglobin (FHbF): FHbF indicates the amount of fetal hemoglobin. FHbF is seldom used clinically.

The ABL90 FLEX PLUS is a portable, automated system intended for in vitro testing of samples of whole blood for the parameters pH, pO2, pCO2, potassium, sodium, chloride, glucose, lactate, neonatal bilirubin, and co-oximetry parameters (total hemoglobin, oxygen saturation, and the hemoglobin fractions FO-Hb, FCOHb, FMetHb, FHHb and FHbF).

The manufacturer of the ABL90 FLEX PLUS is Radiometer Medical ApS.

The ABL90 FLEX PLUS consists of an instrument with a sensor cassette and a solution pack as the main accessories. Multiple models of sensor cassettes are available.

The various sensor cassette models for different parameter combinations. For each parameter combination, models allowing for different test load are available. The solution pack is available in two models differing in the number of tests available.

The provided text describes the ABL90 FLEX PLUS analyzer, an in vitro diagnostic device. The submission is for a design change to an existing device, the ABL90 FLEX, with the introduction of the ABL90 FLEX PLUS which includes a mechanized inlet module (AutoInlet) and a Short Probe Mode.

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

1. Table of Acceptance Criteria and Reported Device Performance

The core of the performance evaluation is a "Method comparison of ABL90 FLEX PLUS Short Probe mode versus ABL90 FLEX syringe mode with inlet clip" and "Imprecision" studies. The reported device performance is that all acceptance criteria were met.

Method Comparison Acceptance Criteria & Performance:

Imprecision Acceptance Criteria & Performance:

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

• Method Comparison Test Set: "more than 40 samples (N) per parameter"
• Data Provenance: Samples were "heparinized, leftover whole blood samples (analyzed 2-3 hours post draw)." The specific country of origin is not explicitly stated, but the submission is from Radiometer Medical ApS in Denmark, suggesting the study likely occurred in a European context or by their internal methods. The study is retrospective as it uses "leftover whole blood samples".

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

Not applicable to this type of in vitro diagnostic device and study. The ground truth for this device is based on measurements from a predicate device (ABL90 FLEX) or a reference instrument, not expert consensus.

4. Adjudication method for the test set

Not applicable. The study compares quantitative measurements between two devices, not subjective interpretations requiring adjudication.

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

Not applicable. This is an in vitro diagnostic device for quantitative measurements, not an AI-assisted diagnostic imaging or interpretation device that would involve human readers.

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

Yes, the performance studies described (Method Comparison and Imprecision) evaluate the standalone analytical performance of the ABL90 FLEX PLUS device (ABL90 FLEX PLUS Short Probe mode and ABL90 FLEX PLUS for imprecision). The comparisons are against a predicate device or reference instrument, not involving human interpretation.

7. The type of ground truth used

• Method Comparison: The predicate device, ABL90 FLEX syringe mode with inlet clip, served as the comparative "truth". The study assessed if the new ABL90 FLEX PLUS Short Probe mode yields equivalent results to this established method.
• Imprecision: "The total imprecision for all parameters except neonatal bilirubin was calculated as the imprecision of the bias towards a reference value determined for each sample on an ABL90 FLEX reference instrument." For neonatal bilirubin, the ground truth source is not explicitly defined beyond "aqueous solutions," but implies a known concentration.

8. The sample size for the training set

Not explicitly stated. For in vitro diagnostic devices, "training set" is not a standard term as it is in machine learning. The studies described are performance verification studies for a medical device. If there was an internal development phase for calibration or algorithm adjustment, that data is not detailed here.

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

Not applicable directly as this is not an ML/AI model with a "training set" in the conventional sense. For the performance studies, ground truth (or reference values) for comparison were established by:

• Method Comparison: Measurements from the predicate device (ABL90 FLEX syringe mode with inlet clip).
• Imprecision: Measurements on an "ABL90 FLEX reference instrument" for most parameters, and "aqueous solutions" for neonatal bilirubin (implying known concentrations).

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The Total Bilirubin assay is used for the quantitation of total bilirubin in human serum or plasma of adults and neonates on the ARCHITECT c8000 System.

Measurement of total bilirubin, an organic compound formed during the normal destruction of red blood cells, is used in the diagnosis and treatment of liver, hematological and metabolic disorders, including hepatitis and gall bladder block. A bilirubin (total and unbound) in the neonate test system is a device intended to measure the levels of bilirubin (total and unbound) in the blood (serum) of newborn infants to aid in indicating the risk of bilirubin encephalopathy (kernicterus).

The Total Bilirubin reagent kit contains Reagent 1 and Reagent 2. Reagent 1 contains Surfactants and HCl. Reagent 2 contains 2, 4-dichloroaniline, HCl, Sodium nitrite, and Surfactant. The principles of the procedure involve total (conjugated and unconjugated) bilirubin coupling with a diazo reagent in the presence of a surfactant to form azobilirubin. The increase in absorbance at 548 nm due to azobilirubin is directly proportional to the total bilirubin concentration. The detection of the analyte is end-point colorimetric.

Here's an analysis of the provided text regarding the acceptance criteria and study for the Total Bilirubin device:

1. Table of Acceptance Criteria and Reported Device Performance:

The document doesn't explicitly state "acceptance criteria" for each test in a formal table, but rather describes the methodology and then reports the results. I will infer the acceptance criteria from the statements provided about what is considered acceptable or how performance supports the claims.

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

• Limit of Quantitation (LOQ), Limit of Detection (LOD), Limit of Blank (LOB):
  • Zero-analyte samples: 4 samples. Tested in a minimum of 5 replicates on 5 separate runs.
  • Low-analyte samples: Minimum of 2 samples gravimetrically prepared at 8 target concentrations. Tested in a minimum of 10 replicates on 5 separate runs.
  • Data Provenance: Not explicitly stated (e.g., country of origin) but "human serum albumin" and "unconjugated bilirubin" are used. The study is prospective in nature, as samples are prepared for the purpose of the test.
• Linearity: 12 levels per pool in each of three combined bilirubin pools. Tested in a minimum of 4 replicates.
  • Data Provenance: "combined bilirubin pools" from "conjugated bilirubin stock" and "unconjugated bilirubin stock", "serum". Prospective.
• Within-Laboratory Precision: 4 control materials (Bio-Rad serum based). Tested in a minimum of 2 replicates, 2 times per day for 20 days.
  • Data Provenance: Commercial control materials (Bio-Rad Lyphochek Unassayed Chemistry Control, Bio-Rad Liquichek Pediatric Control). Prospective.
• Interference: Not specified.
  • Data Provenance: Not specified, but uses "bilirubin concnetrations". Prospective.
• Method Comparison:
  • Adult patient specimens: 124. 4 spiked.
  • Neonatal patient specimens: 64. 4 spiked.
  • Data Provenance: Patient specimens. Not specified if retrospective or prospective or country of origin, but generally method comparison studies use collected patient samples.
• Reference Range: 40 adult patient serum samples.
  • Data Provenance: Fresh, adult patient serum samples from a clinically healthy population. Stored at 2-8°C, protected from light. Assumed to be prospective as samples were collected for the study.
• Automated Dilution Protocol versus Manual Dilution Procedure: Not specified (samples were pooled to create desired concentrations).
  • Data Provenance: "Fresh serum specimens" obtained and pooled. Prospective.
• Specimen Tube Type (Matrix Equivalence): Minimum of 40 samples from adult subjects for each tube type. (Serum glass N=41, SST N=40, EDTA N=39, Lithium Heparin N=40, PST N=40, Sodium Heparin N=39).
  • Data Provenance: "Fresh or frozen sample sets" from subjects. Assumed to be prospective as these are explicitly collected to test tube types.

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

• This device is an in vitro diagnostic (IVD) for quantitative measurement. The "ground truth" for such devices is typically established through analytical methods, reference materials, gravimetric preparation, or comparison to a gold standard reference method/device, rather than expert human interpretation.
• Therefore, the concept of "experts used to establish the ground truth" as it applies to image-based AI or clinical diagnostic interpretation by physicians is not applicable here. The ground truth is the chemical concentration of bilirubin.

4. Adjudication Method for the Test Set:

• Again, as this is a quantitative chemical measurement, adjudication methods for expert interpretation (like 2+1, 3+1) are not applicable. The "adjudication" is inherent in the analytical process (e.g., repeating measurements, using certified reference materials, performing statistical analysis of replicates).

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

• This is an in vitro diagnostic (IVD) device. MRMC studies, which assess human reader performance with and without AI assistance, are typically conducted for AI-powered medical image analysis or clinical decision support systems.
• Therefore, an MRMC comparative effectiveness study is not applicable to this type of device. There are no "human readers" interpreting an output in the same way a radiologist reads an image.

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

• Yes, this entire submission is a standalone performance evaluation of the assay (the "algorithm only" in a broader sense of the measurement procedure). The device is designed to quantitatively measure bilirubin, and the tests (LOQ, linearity, precision, interference, method comparison) evaluate its analytical performance without direct human interpretive intervention beyond running the instrument and analyzing the data.

7. The Type of Ground Truth Used:

• For LOQ, LOD, LOB: Gravimetrically prepared samples (human serum albumin and unconjugated bilirubin) provide the known "ground truth" concentrations.
• For Linearity: Combined bilirubin pools with known proportional compositions.
• For Precision: Commercial control materials with established (though perhaps unassayed) target ranges, tested repeatedly.
• For Method Comparison: The predicate device's measurements are used as the comparative "ground truth" or reference, as the goal is to show substantial equivalence.
• For Reference Range: Clinical health status of the adult population samples.
• For Automated Dilution: Known target concentrations and manual dilution results.
• For Specimen Tube Type: The control tube type (serum plastic tube) serves as the reference for comparison.

8. The Sample Size for the Training Set:

• This document describes the analytical validation of a re-agent kit for an existing instrument (ARCHITECT c8000 System). It's not an AI model that undergoes "training" in the conventional sense.
• Therefore, the concept of a "training set" for an AI algorithm is not applicable. The development of the reagent and its underlying chemical principles involved R&D and optimization, but not machine learning training on a dataset.

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

• As explained above, there is no "training set" in the context of an AI algorithm described here. The "ground truth" used during the development of the assay would have been based on established clinical chemistry principles, reference methods, and gravimetric preparations to ensure accurate concentration measurements during formulation and optimization.

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The ABL90 FLEX analyzer is an in vitro diagnostic, portable, automated analyzer that quantitatively measures neonatal bilirubin in heparinised capillary whole blood. The ABL90 FLEX analyzer is intended for use by trained technologists, nurses, physicians and therapists. It is intended for use in a laboratory environment, near patient or point-of-care setting. These tests are only performed under a physician's order. Bilirubin measurements on the ABL90 FLEX analyzer are intended to aid in assessing the risk of kernicterus in neonates.

The ABL90 FLEX is a portable, automated system intended for in vitro testing of samples of whole blood for the parameters pH, pO2, pCO2, potassium, sodium, chloride, glucose, lactate, neonatal bilirubin and co-oximetry parameters (total hemoglobin, oxygen saturation, and the hemoglobin fractions FO2Hb, FCOHb, FMetHb, FHHb and FHbF). The ABL90 FLEX consists of an instrument with a sensor cassette and a solution pack as the main accessories. Multiple models of sensor cassettes are available. The various sensor cassette models for different parameter combinations. For each parameter combination, models allowing for different test load are available. The solution pack is available in one model. The ABL 90 FLEX electrochemical sensors are miniaturized, manufactured by film technology and integrated in a common sensor cassette. Likewise, the ABL90 FLEX optical oxygen sensor is integrated in the sensor cassette. A 256-pixel array spectrophotometer is used for the co-oximetry parameters and bilirubin.

Here's a breakdown of the acceptance criteria and study information for the ABL90 FLEX device, based on the provided FDA 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance:

• Capillary mode: Total %CV from 1.4% to 3.8%
• Syringe mode: Total %CV from 1.3% to 4.6%
  Spiked Adult Whole Blood (1-day pooled):
• Capillary mode: Total %CV from 1.6% to 14.0%
• Syringe mode: Total %CV from 1.0% to 8.7%
  Spiked Adult Whole Blood & Cord Blood (1-day lab):
• Capillary mode: Total %CV from 1.1% to 7.7% for adult, 0.9% to 7.4% for cord. |
  | Method Comparison (vs. Predicate ABL800 FLEX) | Good correlation with the predicate device and very good agreement between the two modes. | Syringe mode (pooled): Slope = 0.9903 (95% CI: 0.975-1.005), Intercept = 0.6574, R² = 0.9878
  Capillary mode (pooled): Slope = 0.9760 (95% CI: 0.961-0.991), Intercept = 0.7741, R² = 0.9861 |
  | Linearity | Linear over the entire measuring range and fulfills requirements for allowable error due to non-linearity. | Linear (first order) over the entire measuring range. R² = 0.9996 for Bilirubin: ABL90 vs. Sample Conc. |
  | Interference (Non-Significant) |

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