(320 days)
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 sodium from venous, arterial and capillary heparinized whole blood, as well as quantitative measurements of potassium and chloride from venous and arterial heparinized whole blood. These parameters, along with derived parameters, aid in the diagnosis of electrolyte balance.
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.
Chloride (Cl-) measurements are used in the diagnosis and metabolic disorders, such as cystic fibrosis and diabetic acidosis.
Ionized calcium (Ca++) measurements are used in the diagnosis and treatment of parathyroid disease, a variety of bone diseases, chronic renal disease and tetany.
GEM System Evaluator is a three-level assayed quality control material for evaluating performance characteristics of pH, pCO2, pO2, Electrolytes, Metabolites, Total Bilirubin (tBili) and CO-Oximetry on the GEM Premier 4000 and GEM Premier 5000 analyzers.
GEM Hematocrit Evaluator is a three-level assayed quality control material intended for evaluating performance characteristics of hematocrit on the GEM Premier 4000 and GEM Premier 5000 analyzers.
GEM CVP 5 tBili is an external Calibration Valuation Product used to complete the callbration process of the GEM Premier 4000 and GEM Premier 5000 analyzers prior to use with patient samples for total bilirubin (tBili) testing.
The GEM Premier 5000 system provides health care professionals in central laboratory or point-of-care clinical settings with fast, accurate, quantitative measurements of sodium and ionized calcium from venous, arterial and capillary heparinized whole blood, as well as quantitative measurements of potassium and chloride from venous and arterial 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.
Here's a summary of the acceptance criteria and the studies that prove the device meets them, based on the provided text:
Device: GEM Premier 5000 (Measured Parameters: Sodium, Potassium, Chloride, Ionized Calcium) and associated evaluators.
Clinical Context: Rapid analysis of heparinized whole blood samples in clinical and central laboratory settings for diagnosis and treatment of electrolyte imbalances.
1. Table of Acceptance Criteria (Implicit) and Reported Device Performance
The document doesn't explicitly list "acceptance criteria" with numerical targets for each performance metric, but rather presents the results of various studies and states that "all results were within specification" or "all parameter levels passed specification," implying that the observed performance met predefined internal acceptance criteria.
Below is a table summarizing the reported device performance from the various studies. The "Acceptance Criteria" column reflects the implied successful performance indicated by the text.
| Performance Metric Category | Specific Measurement / Analyte | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|---|
| Precision (Internal Aqueous Controls) | Na+ (Level 1, 2, 3) | Within specification | Levels 1, 2, 3: Total %CV 0.6%, 0.4%, 0.5% respectively |
| K+ (Level 1, 2, 3) | Within specification | Levels 1, 2, 3: Total %CV 0.7%, 1.1%, 0.6% respectively | |
| Cl- (Level 1, 2, 3) | Within specification | Levels 1, 2, 3: Total %CV 0.7%, 0.6%, 1.0% respectively | |
| Ca++ (Level 1, 2, 3) | Within specification | Levels 1, 2, 3: Total %CV 1.0%, 0.6%, 1.1% respectively | |
| Precision (Internal Process Control Solutions D & E) | Na+ (PCS D, E) | Within specification | PCS D: Within Analyzer %CV 0.3%; PCS E: Within Analyzer %CV 0.2% |
| K+ (PCS D, E) | Within specification | PCS D: Within Analyzer %CV 0.2%; PCS E: Within Analyzer %CV 0.3% | |
| Cl- (PCS D, E) | Within specification | PCS D: Within Analyzer %CV 0.5%; PCS E: Within Analyzer %CV 0.3% | |
| Ca++ (PCS D, E) | Within specification | PCS D: Within Analyzer %CV 0.3%; PCS E: Within Analyzer %CV 1.3% | |
| Precision (Internal Whole Blood - Normal Mode) | Na+ (Levels 1-5) | Within specification | Total %CV 0.6%, 0.4%, 0.4%, 0.4%, 0.8% |
| K+ (Levels 1-5) | Within specification | Total %CV 2.8%, 2.0%, 1.7%, 2.5%, 3.0% | |
| Cl- (Levels 1-5) | Within specification | Total %CV 1.1%, 0.6%, 0.4%, 0.9%, 1.4% | |
| Ca++ (Levels 1-5) | Within specification | Total %CV 5.2%, 2.3%, 0.7%, 1.4%, 2.0% | |
| Precision (Internal Whole Blood - Micro Mode) | Na+ (Levels 1-5) | Within specification | Total %CV 0.5%, 0.4%, 0.3%, 0.3%, 0.6% |
| Ca++ (Levels 1-5) | Within specification | Total %CV 2.8%, 1.4%, 0.6%, 1.0%, 1.6% | |
| Reproducibility (Aqueous Controls - POC) | Na+ (GSE 1, 2, 3) | All results within specification | Reproducibility %CV 0.4%, 0.4%, 0.2% |
| K+ (GSE 1, 2, 3) | All results within specification | Reproducibility %CV 0.0%, 0.8%, 0.4% | |
| Cl- (GSE 1, 2, 3) | All results within specification | Reproducibility %CV 0.4%, 0.3%, 0.4% | |
| Ca++ (GSE 1, 2, 3) | All results within specification | Reproducibility %CV 0.6%, 0.6%, 0.8% | |
| Accuracy (Linearity) | Na+ (85 to 214 mmol/L) | R² ≥ 0.995 (implied good linearity) | R² = 0.999 |
| K+ (0.7 to 21.9 mmol/L) | R² ≥ 0.995 (implied good linearity) | R² = 0.999 | |
| Cl- (35 to 189 mmol/L) | R² ≥ 0.995 (implied good linearity) | R² = 1.000 | |
| Ca++ (0.10 to 5.05 mmol/L) | R² ≥ 0.995 (implied good linearity) | R² = 0.999 | |
| Method Comparison (vs. Predicate) | Na+ (3 medical decision levels) | Passed specification (implied acceptable bias) | Bias: -0.2, 0.2, 0.5 |
| K+ (3 medical decision levels) | Passed specification (implied acceptable bias) | Bias: 0.04, 0.13, 2.5% | |
| Cl- (2 medical decision levels) | Passed specification (implied acceptable bias) | Bias: 0.6%, 0.4% | |
| Ca++ (3 medical decision levels) | Passed specification (implied acceptable bias) | Bias: -0.021, -0.007, 1.0% | |
| Total Error (at Medical Decision Levels) | Na+, K+, Cl-, Ca++ | All results within GEM Premier 5000 Total Error Specifications (explicitly stated) | Reported Total Error Observed values for all analytes at all medical decision levels |
| Clinical Testing (Normal Mode POC vs. Predicate) | Na+ | High correlation (implied by high r) | r = 0.991 |
| K+ | High correlation (implied by high r) | r = 0.998 | |
| Cl- | High correlation (implied by high r) | r = 0.990 | |
| Ca++ | High correlation (implied by high r) | r = 0.998 | |
| Clinical Testing (Native Capillary Samples) | Na+ (3 medical decision levels) | Meets TEa (Explicit) | Bias within 95% CI of Bias at MDL for all levels & within TEa |
| Ca++ (3 medical decision levels) | Meets TEa (Explicit) | Bias within 95% CI of Bias at MDL for all levels & within TEa | |
| Clinical Testing (Pooled Capillary Samples w/ Contrived) | Na+ | High correlation (implied by high r) | r = 0.981 |
| Ca++ | High correlation (implied by high r) | r = 0.998 |
2. Sample Sizes and Data Provenance
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Test Set Sample Sizes:
- Internal Precision (Aqueous Controls): 120 replicates per control level per analyte (3 analyzers x 20 days x 2 runs/day x 1 replicate = 120).
- Internal Precision (Process Control Solutions D & E): 120 replicates per PCS per analyte (3 analyzers x 20 days x 2 runs/day x 1 replicate = 120).
- Internal Precision (Whole Blood): 120 replicates per concentration level per analyte (3 analyzers x 5 days x 1 run/day x 8 replicates = 120).
- Reproducibility (Aqueous Controls - POC): 90 replicates per control level per analyte (3 sites x 3 replicates/run x 2 runs/day x 5 days = 90).
- External Precision (Whole Blood):
- POC Sites: 30-54 samples for Na+, 30-54 for K+, 30-54 for Cl-, 27-54 for Ca++ (per site)
- Central Labs (Lab1, Lab2) / CSL: 30-33 samples for Na+, 30-33 for K+, 30-36 for Cl-, 27-33 for Ca++ (per site/lab)
- Linearity: 9 or 10 levels per analyte, each analyzed in triplicate (9-10 levels x 3 replicates per level = 27-30 measurements per analyte).
- Method Comparison (GEM Premier 5000 vs. GEM Premier 4000): 373 samples for each analyte (Na+, K+, Cl-, Ca++).
- Clinical Testing (Normal Mode Syringe Samples): 485-491 samples per analyte.
- Clinical Testing (Native Capillary Samples): 171 samples for Na+ and Ca++.
- Clinical Testing (Pooled Native & Contrived Capillary Samples): 201 samples for Na+, 205 samples for Ca++.
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Data Provenance: The data is a mix of internal studies (Instrumentation Laboratory Co.) and external studies at clinical point-of-care (POC) sites and central laboratories.
- Internal Studies: Conducted by Instrumentation Laboratory Co. (Bedford, MA, USA). Some CSL (Customer Simulation Laboratory) data included contrived samples.
- External Studies: Performed at:
- Three (3) external clinical point-of-care (POC) sites.
- Two (2) external central laboratories.
- One (1) internal Customer Simulation Laboratory (CSL) at IL, with POC users.
- Retrospective/Prospective: The studies appear to be prospective, designed specifically to evaluate the GEM Premier 5000's performance as per CLSI guidelines. The whole blood samples used in precision and method comparison studies include both native patient samples and, in some cases, contrived samples. The native clinical samples would be analogous to retrospective data if collected prior, but the studies describe active collection and testing to compare performance.
3. Number of Experts and Qualifications for Ground Truth
The document does not explicitly mention the number or qualifications of "experts" used to establish ground truth in the traditional sense (e.g., radiologists, pathologists). Instead, laboratory reference methods and predicate devices are used as the "ground truth" or reference for comparison.
- Ground Truth for Analytical Studies:
- Traceability: For Process Control Solutions (PCS), it states "traceable to NIST standards, CLSI procedures or internal standards."
- Reference Analyzers: For Linearity, results were "compared to reference analyzers."
- Predicate Device: For Method Comparison and Clinical Testing, the GEM Premier 4000 (K133407) served as the predicate device for comparison.
Since this is a clinical chemistry device for measuring electrolytes, the "ground truth" is typically established by highly calibrated and validated laboratory reference methods or proven predicate devices, rather than expert interpretation of images or clinical assessments.
4. Adjudication Method
Not applicable for this type of device performance study. Adjudication methods (like 2+1 or 3+1 expert consensus) are typically used in studies involving subjective assessments, such as radiology image interpretation, to establish a definitive ground truth when there might be inter-reader variability. For quantitative measurements by clinical chemistry analyzers, the ground truth is established by objective reference methods or well-characterized predicate devices.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. MRMC studies are specific to evaluating the impact of an AI system on human reader performance, often in diagnostic imaging. This document describes the analytical and clinical performance of a clinical chemistry device, which does not involve human "readers" interpreting cases in the same way. The studies focus on the device's accuracy, precision, linearity, and comparability to a predicate device.
6. Standalone (Algorithm Only) Performance
Yes, a standalone performance assessment was conducted for the device. The entire suite of analytical and clinical studies (precision, linearity, analytical specificity, method comparison) evaluates the performance of the GEM Premier 5000 system (which includes its embedded processing/algorithm) as a standalone diagnostic tool without direct human-in-the-loop interpretation of results that would alter the quantitative measurement it produces. The output values are direct physical measurements.
7. Type of Ground Truth Used
The ground truth used for this device includes:
- Reference Methods/Standards: For internal precision and calibration, traceability to NIST standards, CLSI procedures, or internal standards is mentioned for Process Control Solutions. "Reference analyzers" were used for linearity comparisons.
- Predicate Device Performance: For method comparison and clinical testing, the GEM Premier 4000 served as the gold standard or reference for comparison, indicating substantial equivalence.
- Known Concentrations: Contrived samples (e.g., in the CSL) were used to cover medical decision levels, implying that their concentrations were known or precisely measured by a separate method.
8. Sample Size for the Training Set
The document does not explicitly mention a "training set" in the context of machine learning or AI models. Given that this is a 510(k) submission for an in vitro diagnostic device, the "training" for such devices typically refers to the extensive development and internal testing/calibration cycles that occur before formal validation studies (like those presented in the performance section) are conducted. These early development data sets are generally not disclosed in 510(k) summaries but are part of the design control process. The performance data presented are from validation studies, which serve as the test set.
9. How the Ground Truth for the Training Set Was Established
As noted above, a distinct "training set" with established ground truth in the AI/ML sense is not detailed. However, the process for establishing "ground truth" during device development (analogous to training) would involve:
- Calibration Standards: Using certified reference materials and multi-point calibration procedures to ensure the device's sensors and algorithms accurately translate raw signals into quantitative concentrations.
- Inter-Instrument Reproducibility: Extensive internal testing against known values to optimize sensor performance and ensure consistency across multiple manufacturing units.
- Method Development & Optimization: Iterative testing with various samples (potentially including contrived and real patient samples) to refine the measurement algorithms and internal quality control mechanisms (like iQM2) to detect and correct errors. These steps would ensure measurements align with established reference methods or predicate devices.
§ 862.1665 Sodium test system.
(a)
Identification. A sodium test system is a device intended to measure sodium in serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of aldosteronism (excessive secretion of the hormone aldosterone), diabetes insipidus (chronic excretion of large amounts of dilute urine, accompanied by extreme thirst), adrenal hypertension, Addison's disease (caused by destruction of the adrenal glands), dehydration, inappropriate antidiuretic hormone secretion, or other diseases involving electrolyte imbalance.(b)
Classification. Class II.