(207 days)
The GEM Premier 4000 is a portable critical care system for use by health care professionals to rapidly analyze 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, potassium, chloride, ionized calcium, glucose, lactate, hematocrit, total bilirubin and CO-Oximetry (tHb, O2Hb, COHb, MetHb, HHb) parameters. Total bilirubin can also be quantitated from heparinized plasma samples when analyzed in the tBili/CO-Ox mode. 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. Total bilirubin measurements are used in the diagnosis and management of biliary tract obstructions, liver disease and various hemolytic diseases and disorders involving the metabolism of bilirubin. In neonates, the level of total bilirubin is used to aid in assessing the risk of kernicterus.
Intelligent Quality Management (iQM) is used as the quality control and assessment system for the GEM Premier 4000 system. iQM is an active quality process control program designed to provide continuous monitoring of the analytical process with real-time, automatic error detection, automatic correction of the system and automatic documentation of all corrective actions, replacing the use of traditional external quality controls. Facilities should follow local, state and federal regulatory guidelines to ensure that a total quality management system is followed.
As part of this program, GEM CVP (Calibration Valuation Product) with CO-Ox, GEM CVP tBili and GEM CVP Hematocrit are external solutions intended to complete the calibration process and final accuracy assessment of the iQM cartridge calibration following warm-up. The reported values for GEM CVP (two levels for pH, blood gases, electrolytes, total bilirubin, CO-Oximetry and hematocrit) must meet IL's specifications before the iQM cartridge can be used for patient sample measurements. Once the cartridge calibration is verified, the internal iQM program monitors the status of the system during the cartridge use life.
GEM System Evaluator is a three-level assayed quality control material intended for evaluating performance characteristics of pH, pCO2, pO2, Electrolytes, Metabolites, Total Bilirubin (tBili) and CO-Oximetry on the GEM Premier 4000 analyzer.
GEM Hematocrit Evaluator is a three-level assayed quality control material intended for evaluating performance characteristics of hematocrit on the GEM Premier 4000 analyzer.
GEM Premier 4000 - Introductions / Modifications:
- Addition of total bilirubin (tBili) measurement with whole blood and heparinized plasma on the GEM Premier 4000 performed using spectrophotometric multi-component analysis through the instrument's existing CO-Oximetry module. Following the electrochemical measurements for blood gases, electrolytes and metabolites, a portion of the sample is chemically hemolyzed and brought into an optical cell for the CO-Oximetry measurements and the additional total bilirubin measurement. There were no hardware or mechanical changes required, and no changes to the reagent cartridge (PAK) formulation or sensors. The measurement of total bilirubin was implemented through software.
- Expansion of the low-end reportable range for total hemoglobin (tHb) parameter from 5 g/dL to 3 g/dL through additional testing.
- Addition of a new 100 uL sample size for total bilirubin and CO-Oximetry mode only.
- Automation of fetal hemoglobin correction for CO-Oximetry. Previously the user would input the age of the patient to apply the correction. The new software applies the correction automatically based on the presence of fetal hemoglobin in the sample without user input.
- GEM CVP 2 with CO-Ox: This currently marketed external solution for the GEM Premier 4000 will also be value assigned for total bilirubin. No change in formulation.
- GEM CVP 5 tBili: An additional external solution for the GEM Premier 4000, containing purified human hemoglobin, stabilizers and biocide in a physiologically buffered matrix, is being introduced at another level of total bilirubin.
- GEM System Evaluator: Three-level aqueous buffered bicarbonate solution intended for use with the GEM Premier 4000 analyzer, containing inorganic salts and organic metabolites, dye and biocides; equilibrated with carbon dioxide and oxygen.
- GEM Hematocrit Evaluator: Three-level aqueous buffered bicarbonate solution intended for use with the GEM Premier 4000 analyzer, containing inorganic salts and biocides; equilibrated with carbon dioxide and oxygen.
Here's a breakdown of the acceptance criteria and study information for the GEM Premier 4000 with iQM, focusing on the total bilirubin (tBili) measurement, based on the provided 510(k) summary:
The document is a 510(k) summary for a medical device. These summaries typically do not contain the full details of clinical studies with extensive data on sample sizes, expert qualifications, or detailed statistical analyses that would be found in a full submission or peer-reviewed publication. Instead, they focus on demonstrating "substantial equivalence" to predicate devices through various tests.
1. Table of Acceptance Criteria and Reported Device Performance
The document doesn't explicitly state "acceptance criteria" in a quantitative table format. Instead, it describes differences and similarities to predicate devices and states that "data in the Premarket Notification on safety and effectiveness supports a finding of substantial equivalence... Equivalence is demonstrated through imprecision, method comparison, interference, sample matrix and stability studies, along with software development information."
However, it does provide information about the Tested Range for total bilirubin measurement, which can be seen as an informal performance characteristic:
| Characteristic | Acceptance Criteria (Implied / Predicate Performance) | Reported Device Performance (GEM Premier 4000 with tBili) |
|---|---|---|
| Total Bilirubin Tested Range | 0.0 to 23.5 mg/dL (ABL 735 Analyzer, Predicate) | 0.3 to 40.0 mg/dL (GEM Premier 4000 with tBili) |
| Imprecision | Not explicitly stated, inferred to be comparable to predicate | Demonstrated (details not provided in summary) |
| Method Comparison | Not explicitly stated, inferred to be comparable to predicate | Demonstrated (details not provided in summary) |
| Interference | Not explicitly stated, inferred to be comparable to predicate | Demonstrated (details not provided in summary) |
| Sample Matrix | Not explicitly stated, inferred to be comparable to predicate | Demonstrated (details not provided in summary) |
| Stability | Not explicitly stated, inferred to be comparable to predicate | Demonstrated (details not provided in summary) |
The "acceptance criteria" for the new device appear to be that its performance characteristics (imprecision, method comparison, interference, sample matrix, stability) are substantially equivalent to the predicate devices, and its claimed detection range (0.3 to 40.0 mg/dL) is within acceptable clinical limits and potentially an improvement over the predicate's range.
2. Sample Size Used for the Test Set and Data Provenance
The 510(k) summary does not provide details on specific sample sizes used for the various tests (imprecision, method comparison, interference, sample matrix, stability studies). It only states that these studies were performed as part of the Premarket Notification.
The data provenance is not explicitly stated in terms of country of origin or whether it was retrospective or prospective. However, safety and effectiveness studies for 510(k) submissions are typically conducted by the manufacturer, often at their own facilities or contracted labs, using in-house developed protocols. Given the nature of a 510(k) for a laboratory instrument, the data would likely be prospective testing performed specifically for the submission.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
This type of information is not provided in the 510(k) summary. For a device like a blood gas analyzer measuring total bilirubin, the "ground truth" for method comparison and accuracy studies would typically be established by comparing against a reference method (e.g., a highly accurate laboratory method) rather than human experts interpreting images or clinical cases.
4. Adjudication Method for the Test Set
Adjudication methods (like 2+1, 3+1) are usually relevant for studies where human expert disagreement on a qualitative assessment (e.g., image interpretation) needs to be resolved. This is not applicable to the type of analytical performance studies described for this device, which focuses on quantitative measurements.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No MRMC comparative effectiveness study was done or is applicable to this device. An MRMC study is relevant for evaluating diagnostic aids that assist human readers in making interpretations (e.g., radiologists interpreting images). This device is an automated in vitro diagnostic instrument that provides quantitative measurements, not an AI assistant for human interpretation.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study
This device, the GEM Premier 4000 with iQM for total bilirubin measurement, is a standalone algorithm/instrument. Its performance is its standalone performance. The measurements it provides are direct outputs from the instrument's spectrophotometric analysis. The iQM system is an internal quality control system that functions automatically without human intervention for real-time error detection and correction.
7. Type of Ground Truth Used
For analytical performance studies of quantitative in vitro diagnostic devices like this one, the "ground truth" (or reference method) is typically:
- Reference method comparison: A recognized, highly accurate, and precise analytical method (e.g., a laboratory gold standard method like a direct spectrophotometric method or HPLC for bilirubin) with known accuracy and traceability.
- Known concentration samples: Using materials with certified or precisely known concentrations (e.g., calibrators, certified reference materials, spiked samples) for accuracy and linearity.
The summary indicates "method comparison" studies were performed. This implies comparison against another established analytical method.
8. Sample Size for the Training Set
No "training set" information is provided, nor is it directly applicable in the conventional sense of machine learning for image analysis. This device is a spectrophotometric analyzer, not a machine learning model that learns from large datasets of labeled cases in the same way typical AI/ML medical devices do. The software implements the measurement algorithm, and its "training" would be more akin to algorithm development and calibration, using controlled samples with known values.
9. How the Ground Truth for the Training Set Was Established
As noted above, a "training set" in the machine learning sense is not applicable here. The analytical algorithms and instrument calibration would be developed and verified using:
- Known chemical standards: Solutions with precisely measured concentrations of the analytes.
- Calibrators: Materials specifically designed to calibrate the instrument to known values.
- Reference methods: Comparisons against established, highly accurate analytical techniques to ensure the instrument's measurements are correct.
This information would be part of the instrument's design validation and verification, not typically detailed as a "training set ground truth" in a 510(k) summary.
§ 862.1110 Bilirubin (total or direct) test system.
(a)
Identification. A bilirubin (total or direct) test system is a device intended to measure the levels of bilirubin (total or direct) in plasma or serum. Measurements of the levels of bilirubin, an organic compound formed during the normal and abnormal distruction of red blood cells, if used in the diagnosis and treatment of liver, hemolytic hematological, and metabolic disorders, including hepatitis and gall bladder block.(b)
Classification. Class II.