(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
-
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++.
-
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.
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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002 December 14, 2016
INSTRUMENTATION LABORATORY CO. CAROL MARBLE REGULATORY AFFAIRS DIRECTOR 180 HARTWELL ROAD BEDFORD MA 01730
Re: K160225
Trade/Device Name: GEM Premier 5000 (Measured Parameters: Sodium, Potassium, Chloride, Ionized Calcium), GEM System Evaluator, GEM Hematocrit Evaluator, GEM CVP 5 tBili Regulation Number: 21 CFR 862.1665 Regulation Name: Sodium Test System Regulatory Class: II Product Code: JGS, CEM, CGZ, JFP, JJY, JJE, GLK Dated: December 6, 2016 Received: December 7, 2016
Dear Ms. Marble:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food. Drug. and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA), You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the
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electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Courtney H. Lias -S
Courtney H. Lias, PhD Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K160225
Device Name
GEM Premier 5000 (Measured Parameters: Sodium, Potassium, Chloride, Ionized Calcium) GEM System Evaluator, GEM Hematocrit Evaluator, GEM CVP 5 tBili
Indications for Use (Describe)
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.
| Type of Use (Select one or both, as applicable) | |
|---|---|
| ☒ Prescription Use (Part 21 CFR 801 Subpart D) | ☐ Over-The-Counter Use (21 CFR 801 Subpart C) |
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510(k) Summary
This 510(k) Summary of Safety and Effectiveness is being submitted in accordance with the requirements of the Safe Medical Device Act of 1990 and 21 CFR 807.92.
| Submitter's Information | Instrumentation Laboratory (IL) Co.180 Hartwell RoadBedford, MA 01730, USA |
|---|---|
| ------------------------- | ------------------------------------------------------------------------------------ |
| Contact Person | Carol Marble, Regulatory Affairs Director |
|---|---|
| Phone: 781-861-4467 | |
| Fax: 781-861-4207 | |
| Email: cmarble@ilww.com |
| Preparation Date | December 6, 2016 |
|---|---|
| ------------------ | ------------------ |
| Device Trade Names | GEM Premier 5000(Measured Parameters: Sodium, Potassium, Chloride, Ionized Calcium) GEM CVP 5 tBili GEM System Evaluator GEM Hematocrit Evaluator |
|---|---|
| -------------------- | ------------------------------------------------------------------------------------------------------------------------------------------------------- |
| Predicate Devices | GEM Premier 4000 | K133407 |
|---|---|---|
| GEM CVP 5 tBili | ||
| GEM System Evaluator | ||
| GEM Hematocrit Evaluator |
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| Regulatory Information | |||||
|---|---|---|---|---|---|
| System | RegulationSection | Regulatory Description | Class | ProductCode | Panel |
| Instrument | 862.2160 | Discrete photometric chemistryanalyzer for clinical use | I | JJE | 75 |
| Sodium | 862.1665 | Sodium test system | II | JGS | |
| Potassium | 862.1600 | Potassium test system | II | CEM | 75 |
| Chloride | 862.1170 | Chloride test system | II | CGZ | |
| Ionized Calcium | 862.1145 | Calcium test system | II | JFP | |
| Controls(InternalPCS D and E) | 862.1660 | Quality control material(assayed and unassayed) | I(Reserved) | JJY | 75 |
| 864.8625 | Hematocrit Control | II | GLK | 81 | |
| GEM CVP 5 tBili | |||||
| RegulationSection | Regulatory Description | Class | ProductCode | Panel | |
| 862.1660 | Quality control material (assayed and unassayed) | I(Reserved) | JJY | 75 | |
| GEM System Evaluator | |||||
| RegulationSection | Regulatory Description | Class | ProductCode | Panel | |
| 862.1660 | Quality control material (assayed and unassayed) | I(Reserved) | JJY | 75 | |
| GEM Hematocrit Evaluator | |||||
| RegulationSection | Regulatory Description | Class | ProductCode | Panel | |
| 864.8625 | Hematocrit Control | II | GLK | 81 |
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Device Description
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 | Description |
|---|---|
| Analyzer | Employs a unique color touch screen and a simple set of menus andbuttons for user interaction. The analyzer guides operators through thesampling process with simple, clear messages and prompts. |
| GEM Premier 5000 PAK(disposable, multi-use GEM PAK) | Houses all required components necessary to operate the instrumentonce the cartridge is validated. These components include the sensors,CO-Ox/tBili optical cell, Process Control (PC) Solutions, sampler, pumptubing, distribution valve and waste bag. The GEM PAK has flexiblemenus and test volume options to assist facilities in maximizingefficiency.NOTE: The EEPROM on the GEM PAK includes all solution values andcontrols the analyte menu and number of tests.Step 1: After inserting the GEM PAK, the instrument will perform anautomated PAK warm-up during which the sensors arehydrated and a variety of checks occur, all of which takeabout 40 minutes. During warm-up, the instrument requiresno user intervention.Step 2: After GEM PAK warmup, Auto PAK Validation (APV) process isautomatically completed: two completely independentsolutions (PC Solution D and E) that are traceable to NISTstandards, CLSI procedures or internal standards, containingtwo levels of concentration for each analyte, are run by theanalyzer to validate the integrity of the PC Solutions and theoverall performance of the analytical system.NOTE: For total bilirubin, CVP 5 tBili (Calibration Valuation Product)must be run prior to performing tBili samples.Step 3: After successful performance of APV, iQM2 manages thequality control process, replacing external quality controls. |
| Intelligent Quality Management 2(iQM2) | iQM2 is an active quality process control program designed to providecontinuous monitoring of the analytical process before, during andafter sample measurement with real-time, automatic error detection,automatic correction of the system and automatic documentation of allcorrective actions.iQM2 is a statistical process control system that performs 5 types ofcontinuous, quality checks to monitor the performance of the GEMPAK, sensors, CO-Ox, and reagents. These checks include System,Sensor, IntraSpect, Pattern Recognition and Stability Checks. |
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| Indications for Use / Intended Use | |
|---|---|
| GEM Premier 5000with Intelligent QualityManagement 2 (iQM2) | The GEM Premier 5000 is a portable critical care system for use byhealth care professionals to rapidly analyze heparinized wholeblood samples at the point of health care delivery in a clinicalsetting and in a central laboratory. The instrument providesquantitative measurements of sodium and ionized calcium fromvenous, arterial and capillary heparinized whole blood, as well asquantitative measurements of potassium and chloride from venousand arterial heparinized whole blood. These parameters, alongwith derived parameters, aid in the diagnosis of electrolytebalance.Sodium ( $Na^+$ ) measurements are used in the diagnosis andtreatment of aldosteronism, diabetes insipidus, adrenalhypertension, Addison's disease, dehydration, inappropriateantidiuretic secretion, or other diseases involving electrolyteimbalance.Potassium ( $K^+$ ) measurements are used to monitor electrolytebalance in the diagnosis and treatment of disease conditionscharacterized by low or high blood potassium levels.Chloride ( $Cl^-$ ) measurements are used in the diagnosis andtreatment of electrolyte and metabolic disorders, such as cysticfibrosis and diabetic acidosis.Ionized calcium ( $Ca^{++}$ ) measurements are used in the diagnosisand treatment of parathyroid disease, a variety of bone diseases,chronic renal disease and tetany. |
| GEM CVP 5 tBili | GEM CVP 5 tBili is an external Calibration Valuation Product used tocomplete the calibration process of the GEM Premier 4000 andGEM Premier 5000 analyzers prior to use with patient samples fortotal bilirubin (tBili) testing. |
| GEM System Evaluator | GEM System Evaluator is a three-level assayed quality controlmaterial for evaluating performance characteristics of pH, pCO2,pO2, Electrolytes, Metabolites, Total Bilirubin (tBili) andCO-Oximetry on the GEM Premier 4000 and GEM Premier 5000analyzers. |
| GEM Hematocrit Evaluator | GEM Hematocrit Evaluator is a three-level assayed quality controlmaterial intended for evaluating performance characteristics ofhematocrit on the GEM Premier 4000 and GEM Premier 5000analyzers. |
Special Conditions for Use Statement
- . For prescription use only.
- For clinical laboratory and point-of-care use. .
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| Substantial Equivalency | |||
|---|---|---|---|
| The GEM Premier 5000 system is substantially equivalent in function and intended use to the following predicate device for Na+, K+, Cl- and Ca++: | |||
| Item | Predicate Device | New Device | |
| Trade Name | GEM Premier 4000 | GEM Premier 5000 | |
| 510(k) No. | K133407 | K160225 | |
| Manufacturer | Instrumentation Laboratory Co. | Instrumentation Laboratory Co. | |
| Indicationsfor Use | The GEM Premier 4000 is a portable critical care system for use byhealth care professionals to rapidly analyze whole blood samples atthe point of health care delivery in a clinical setting and in a centrallaboratory. The instrument provides quantitative measurements ofpH, 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 bequantitated from heparinized plasma samples when analyzed in thetBili/CO-Ox mode. These parameters, along with derivedparameters, 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 andmanagement of biliary tract obstructions, liver disease and varioushemolytic diseases and disorders involving the metabolism ofbilirubin. In neonates, the level of total bilirubin is used to aid inassessing the risk of kernicterus. | The GEM Premier 5000 is a portable critical care system for useby health care professionals to rapidly analyze heparinized wholeblood samples at the point of health care delivery in a clinicalsetting and in a central laboratory. The instrument providesquantitative measurements of sodium and ionized calcium fromvenous, arterial and capillary heparinized whole blood, as well asquantitative measurements of potassium and chloride fromvenous and arterial heparinized whole blood. These parameters,along with derived parameters, aid in the diagnosis of electrolytebalance.Sodium (Na+) measurements are used in the diagnosis andtreatment of aldosteronism, diabetes insipidus, adrenalhypertension, Addison's disease, dehydration, inappropriateantidiuretic secretion, or other diseases involving electrolyteimbalance.Potassium (K+) measurements are used to monitor electrolytebalance in the diagnosis and treatment of disease conditionscharacterized by low or high blood potassium levels.Chloride (Cl-) measurements are used in the diagnosis andtreatment of electrolyte and metabolic disorders, such as cysticfibrosis and diabetic acidosis.Ionized calcium (Ca++) measurements are used in the diagnosisand treatment of parathyroid disease, a variety of bone diseases,chronic renal disease and tetany. | |
| Substantial Equivalency (Cont.) | |||
| Item | Predicate Device | New Device | |
| Trade Names | GEM Premier 4000K133407 | GEM Premier 5000K160225 | |
| Intended User | Central Laboratory and Point-of-Care | Same | |
| Sample Type | Heparinized whole blood | Na+, Ca++Arterial, venous or capillary heparinized whole bloodK+, Cl-Arterial or venous heparinized whole blood | |
| Electrolyte Measurement | Potentiometry | Same | |
| Sample Introduction | Aspiration | Same | |
| PAK Shelf-Life Stability | Up to 180 days | Same | |
| PAK Storage Temperature | 15-25°C | Same | |
| System Operating Temperature | 12-32°C | Same | |
| Operating System Software | Linux-based | Same | |
| Calibration | 2-point calibration | Same | |
| QC Material | CVP 1 and 2 | PC Solution D and E (PAK Internal) | |
| CVP 3 and 4 | PC Solution D and E (PAK Internal) | ||
| CVP 5 tBili | Same; No Formulation Change | ||
| GEM System Evaluator | GEM Premier 5000 claims added | ||
| GEM Hematocrit Evaluator | |||
| Substantial Equivalency (Cont.) | |||
| Item | Predicate Device | New Device | |
| Trade Name | GEM Premier 4000K133407 | GEM Premier 5000K160225 | |
| Instrument Dimensions | GEM Premier 4000 Instrument:• Height: 18 inches• Width: 12 inches• Depth: 15 inches• Weight: 44 pounds | GEM Premier 5000 Instrument:• Height: 18.6 inches• Width: 13.0 inches• Depth: 16.4 inches• Weight: 45.4 pounds | |
| Cartridge (PAK) Dimensions | GEM Premier 4000 Cartridge (PAK):• Height: 6.75 inches• Width: 10 inches• Depth: 8 inches• Weight: 8 pounds | GEM Premier 5000 Cartridge (PAK):• Height: 6.75 inches• Width: 10 inches• Depth: 8 inches• Weight: 8.1 pounds | |
| Reportable Range | AnalyteNa+K+Cl-Ca++ | GEM Premier 4000100 to 180 mmol/L0.2 to 19.0 mmol/L40 to 158 mmol/L0.10 to 4.25 mmol/L | GEM Premier 5000100 to 180 mmol/L1.0 to 19.0 mmol/L40 to 158 mmol/L0.11 to 4.25 mmol/L |
| Substantial Equivalency (Cont.) | |||
| NOTE: The following table compares iQM on the GEM Premier 4000 to iQM2 on the GEM Premier 5000. | |||
| Item | Predicate Device | New Device | |
| Trade Names | iQM (Intelligent Quality Management) | iQM2 (Intelligent Quality Management 2) | |
| Instrument | GEM Premier 4000 | GEM Premier 5000 | |
| 510(k) No. | K133407 | K160225 | |
| Quality ControlPrinciple | Active quality process control programusing five levels of external CalibrationValuation Product (CVP), four internalProcess Control Solutions (PCSs) andPattern Recognition (PR) software, all ofwhich are designed to provide immediateerror detection and automatic remedialaction, replacing the use of traditionalexternal quality controls. | Active quality process control programusing a combination of internal AutoPAK Validation (APV) and one level ofexternal Calibration Valuation Product(CVP 5), five internal Process ControlSolutions (PCSs) Pattern Recognition(PR) software and IntraSpect sampleintegrity quality checks, all of which aredesigned to provide immediate errordetection and automatic remedialaction, replacing the use of traditionalexternal quality controls. | |
| ErrorDetectionScheme | Multi-level checks for detecting cartridgeerrors.• System checks• Sensor/CO-Ox checks• Pattern Recognition (PR checks)• Process Control Solution (PCS) Stability | Same except addition of IntraSpect.IntraSpect provides continuous sampleintegrity quality checks that detectabnormal sensor response slope orabsorbance residual error during themeasurement process. | |
| Error Mitigation | Automatic error handling:• Performing special rinse cycle afterdetecting micro-clots and verifying thecartridge function after clot removal.• Permanently disabling failed sensor ifits functionality could not berecovered.• Rejecting cartridge for process stabilityfailure.• Alerting the user if interferences aredetected in a sample.• Automatically documenting the failureand action taken. | Same except addition of IntraSpect,which flags results if an abnormal sensorresponse slope or absorbance residualerror is detected. | |
| Documentation | Automatic documentation:• Process Control Solutions delta charts.• Error reporting and corrective actionreport.• GEM CVP report | Same; no change | |
| Substantial Equivalency (Cont.) | |||
| NOTE: The following table compares internal Process Control (PC) Solutions in the GEM Premier 4000 PAK(cartridge) to internal Process Control (PC) Solutions in the GEM Premier 5000 PAK (cartridge). | |||
| Item | Predicate Device | New Device | |
| Trade Names | Process Control (PC) Solutions | Process Control (PC) Solutions | |
| Instrument | GEM Premier 4000 | GEM Premier 5000 | |
| 510(k) No. | K133407 | K160225 | |
| PC Solutions | PC Solution B is the primary Process Control Solution measured at a minimum of every half hour or after every sample. Furthermore, Solution B is monitored every 30 seconds while residing in the sensor card between measurements. Further, PC Solution B is used as a reference blank for CO-Oximetry. PC Solution A is measured at a minimum of every 4 hours. All sensor slope values are also measured and checked. Slope, which is an indicator of sensor sensitivity and drift, must be within allowable limits. PC Solution A also contains dyes that are used for checking functionality of the optical cell and the CO-Oximetry. PC Solution C is measured at a minimum of once every 24 hours. PC Solution C is primarily used for measuring low-level oxygen; however, PC Solution C is also used to provide an additional measurement of pH, pCO2 and K+ sensor functionality. PC Solution D is measured every 12 hours. PC Solution D provides additional measurement for all analytes including CO-Oximetry. Reference values for analytes in PC Solution D are established within the first 3 days after cartridge insertion by averaging multiple measurements of the D solution. The D sensor check starts once the reference values are established. No PC Solution E on the GEM Premier 4000 | PC Solution B - Same PC Solution A - Same PC Solution C - Same PC Solution D - is measured every 12 hours. PC Solution D provides additional measurement for all analytes including CO-Oximetry. Reference values for analytes in PC Solution D are assigned at time of manufacturing. The D sensor check starts after the successful completion of Auto PAK Validation (APV). New PC Solution E - is measured every 12 hours. PC Solution E provides additional measurement for all analytes including CO-Oximetry. Reference values for analytes in PC Solution E are assigned at time of manufacturing. The E sensor check starts after the successful completion of Auto PAK Validation (APV). NOTE: The GEM Premier 5000 PAKs include a new PC Solution E. The new system uses PC Solution D and PC Solution E to replace the necessity to run CVP 1, 2, 3 and 4 after cartridge (PAK) warm-up. Only CVP 5 tBili is required if running total bilirubin.See the comparison of PC Solution D and PC Solution E to CVP 1-4 on the next page. | |
| Substantial Equivalency (Cont.) | |||
| Item | Predicate | New Device | |
| Trade Names | CVP 5 tBili | Same | |
| Value Assigned | GEM Premier 4000 | GEM Premier 4000 and GEM Premier 5000 | |
| 510(k) No. | K112995 | K160225 | |
| Indications for UseDifferences inbold/italic | GEM CVP 5 tBili is an externalCalibration Valuation Product used tocomplete the calibration process of theGEM Premier 4000 analyzer prior to usewith patient samples for total bilirubin(tBili) testing. | GEM CVP 5 tBili is an external CalibrationValuation Product used to complete thecalibration process of the GEM Premier4000 and GEM Premier 5000 analyzersprior to use with patient samples for totalbilirubin (tBili) testing. | |
| Formulation | Purified human hemoglobin, stabilizersand biocide in a physiologically bufferedsolution. | Same | |
| Storage | Store at 2-8°C | Same | |
| Item | Predicate | New Device | |
| Trade Names | GEM System Evaluator | Same | |
| Value Assigned | GEM Premier 4000 | GEM Premier 4000 and GEM Premier 5000 | |
| 510(k) No. | K093623 | K160225 | |
| Manufacturer | Instrumentation Laboratory Co. | Same | |
| Indications for UseDifferences inbold/italic | GEM System Evaluator is a three-levelassayed quality control material forevaluating performance characteristicsof pH, pCO2, pO2, Electrolytes,Metabolites, Total Bilirubin (tBili) andCO-Oximetry on the GEM Premier 4000analyzer. | GEM System Evaluator is a three-levelassayed quality control material forevaluating performance characteristics ofpH, pCO2, pO2, Electrolytes, Metabolites,Total Bilirubin (tBili) and CO-Oximetry onthe GEM Premier 4000 and GEM Premier5000 analyzers. | |
| Formulation | Aqueous buffered bicarbonate solution. | Same | |
| Storage | 2-8°C until expiration15-25°C for 4 months | Same | |
| Item | Predicate | New Device | |
| Trade Names | GEM Hematocrit Evaluator | Same | |
| Value Assigned | GEM Premier 4000 | GEM Premier 4000 and GEM Premier 5000 | |
| 510(k) No. | K093623 | Pending | |
| Manufacturer | Instrumentation Laboratory Co. | Same | |
| Indications for UseDifferences inbold/italic | 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 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. | |
| Formulation | Aqueous buffered bicarbonate solution. | Same | |
| Storage | 15-25°C until expiration | Same |
{9}------------------------------------------------
{10}------------------------------------------------
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{12}------------------------------------------------
{13}------------------------------------------------
{14}------------------------------------------------
Performance Summary
Internal Precision Study – Aqueous Controls
In accordance with CLSI EP05-A3, an internal 20-day precision study was performed on the GEM Premier 5000, with GEM System Evaluator. Each of the control levels was run on three (3) GEM Premier 5000 analyzers for twenty (20) days, with two (2) runs per day and one (1) replicate measured per run per level (n=120). All results were within specification.
| Material | Analyte | Level | Mean | N | WithinAnalyzerSD | WithinAnalyzer%CV | Total SD | Total%CV |
|---|---|---|---|---|---|---|---|---|
| GEMSystemEvaluator | Na+(mmol/L) | Level 1 | 124 | 120 | 0.7 | 0.6% | 0.8 | 0.6% |
| Level 2 | 141 | 120 | 0.5 | 0.4% | 0.5 | 0.4% | ||
| Level 3 | 156 | 120 | 0.7 | 0.5% | 0.7 | 0.5% | ||
| K+(mmol/L) | Level 1 | 2.4 | 120 | 0.02 | 0.7% | 0.02 | 0.7% | |
| Level 2 | 4.7 | 120 | 0.04 | 0.9% | 0.05 | 1.1% | ||
| Level 3 | 7.7 | 120 | 0.04 | 0.5% | 0.05 | 0.6% | ||
| Cl-(mmol/L) | Level 1 | 85 | 120 | 0.6 | 0.7% | 0.6 | 0.7% | |
| Level 2 | 108 | 120 | 0.5 | 0.4% | 0.6 | 0.6% | ||
| Level 3 | 141 | 120 | 1.0 | 0.7% | 1.3 | 1.0% | ||
| Ca++(mmol/L) | Level 1 | 1.56 | 120 | 0.013 | 0.8% | 0.015 | 1.0% | |
| Level 2 | 1.16 | 120 | 0.006 | 0.5% | 0.006 | 0.6% | ||
| Level 3 | 0.64 | 120 | 0.006 | 1.0% | 0.007 | 1.1% |
{15}------------------------------------------------
Internal Precision Study – GEM PAK (Cartridge) Process Control Solutions D and E
In accordance with CLSI EP05-A3, an internal 20-day precision study was performed with the GEM PAK (cartridge) Process Control Solutions (PCS) D and E run on three (3) GEM Premier 5000 analyzers for twenty (20) days, with two (2) runs per day and one (1) replicate measured per run per level (N=120 per analyte/per level). All results were within specification.
| Material | Analyte | Mean | N | Within AnalyzerSD | Within Analyzer%CV |
|---|---|---|---|---|---|
| PCS D | Na+(mmol/L) | 167 | 120 | 0.4 | 0.3% |
| PCS E | Na+(mmol/L) | 128 | 120 | 0.2 | 0.2% |
| PCS D | K+(mmol/L) | 7.3 | 120 | 0.02 | 0.2% |
| PCS E | K+(mmol/L) | 4.5 | 120 | 0.01 | 0.3% |
| PCS D | Cl-(mmol/L) | 144 | 120 | 0.7 | 0.5% |
| PCS E | Cl-(mmol/L) | 102 | 120 | 0.3 | 0.3% |
| PCS D | Ca++(mmol/L) | 1.21 | 120 | 0.004 | 0.3% |
| PCS E | Ca++(mmol/L) | 0.56 | 120 | 0.007 | 1.3% |
{16}------------------------------------------------
Internal Precision Study – Whole Blood
In accordance with CLSI EP05-A3, an internal precision study was performed using five (5) different concentrations of whole blood per analyte, each run on three (3) GEM Premier 5000 analyzers per sample mode for five (5) days, with one (1) run per day and eight (8) replicates measured per run per level (N=120 per analyte/per sample mode). All results were within specification.
Sample Modes and Volumes:
- . Normal Mode 150 µL
- Micro Mode 65 µL
NOTE: Capillary not claimed for K* or Cl¯ on the GEM Premier 5000.
| Analyte | Mode | Level | Mean | N | WithinRunSD | WithinRun%CV | Total SD | Total%CV |
|---|---|---|---|---|---|---|---|---|
| Na+(mmol/L) | NormalMode | 1 | 104 | 120 | 0.5 | 0.5% | 0.6 | 0.6% |
| 2 | 114 | 120 | 0.4 | 0.4% | 0.4 | 0.4% | ||
| 3 | 132 | 120 | 0.4 | 0.3% | 0.5 | 0.4% | ||
| 4 | 148 | 120 | 0.6 | 0.4% | 0.7 | 0.4% | ||
| 5 | 187 | 120 | 1.1 | 0.6% | 1.4 | 0.8% | ||
| Na+(mmol/L) | MicroMode | 1 | 104 | 120 | 0.4 | 0.3% | 0.5 | 0.5% |
| 2 | 114 | 120 | 0.3 | 0.3% | 0.5 | 0.4% | ||
| 3 | 131 | 120 | 0.3 | 0.2% | 0.4 | 0.3% | ||
| 4 | 147 | 120 | 0.4 | 0.3% | 0.5 | 0.3% | ||
| 5 | 186 | 120 | 0.6 | 0.3% | 1.2 | 0.6% | ||
| K+(mmol/L) | NormalMode | 1 | 1.6 | 120 | 0.04 | 2.5% | 0.04 | 2.8% |
| 2 | 2.9 | 120 | 0.05 | 1.7% | 0.06 | 2.0% | ||
| 3 | 5.5 | 120 | 0.05 | 0.9% | 0.09 | 1.7% | ||
| 4 | 7.5 | 120 | 0.14 | 1.9% | 0.18 | 2.5% | ||
| 5 | 17.0 | 120 | 0.32 | 1.9% | 0.51 | 3.0% |
{17}------------------------------------------------
| Analyte | Mode | Level | Mean | N | WithinRunSD | WithinRun%CV | Total SD | Total%CV |
|---|---|---|---|---|---|---|---|---|
| Cl-(mmol/L) | NormalMode | 1 | 52 | 120 | 0.4 | 0.8% | 0.6 | 1.1% |
| 2 | 71 | 120 | 0.3 | 0.5% | 0.4 | 0.6% | ||
| 3 | 90 | 120 | 0.4 | 0.4% | 0.4 | 0.4% | ||
| 4 | 115 | 120 | 0.7 | 0.6% | 1.0 | 0.9% | ||
| 5 | 167 | 120 | 1.4 | 0.9% | 2.3 | 1.4% | ||
| Ca++(mmol/L) | NormalMode | 1 | 0.23 | 120 | 0.009 | 3.9% | 0.012 | 5.2% |
| 2 | 0.37 | 120 | 0.006 | 1.7% | 0.009 | 2.3% | ||
| 3 | 0.86 | 120 | 0.005 | 0.6% | 0.006 | 0.7% | ||
| 4 | 1.54 | 120 | 0.020 | 1.3% | 0.022 | 1.4% | ||
| 5 | 4.26 | 120 | 0.074 | 1.7% | 0.084 | 2.0% | ||
| Ca++(mmol/L) | MicroMode | 1 | 0.22 | 120 | 0.005 | 2.4% | 0.006 | 2.8% |
| 2 | 0.35 | 120 | 0.004 | 1.1% | 0.005 | 1.4% | ||
| 3 | 0.83 | 120 | 0.004 | 0.5% | 0.005 | 0.6% | ||
| 4 | 1.51 | 120 | 0.015 | 1.0% | 0.015 | 1.0% | ||
| 5 | 4.20 | 120 | 0.057 | 1.3% | 0.069 | 1.6% |
Internal Precision Study – Whole Blood (Cont.)
{18}------------------------------------------------
Reproducibility Study with Aqueous Controls – Point-of-Care (POC) Setting
In accordance with CLS EP05-A3, a reproducibility study was performed at three (3) external clinical point-of-care (POC) sites. The studies were run by a total of nine (9) different operators on three (3) different GEM Premier 5000 instruments, using a single lot of GEM Premier 5000 PAKs (cartidges). Each site used the same lots of GEM System Evaluator (GSE), running each control level in triplicate, twice a day for 5 days, for a total of 30 pooled). All results at all sites were within specification.
| Pooled Multi-Site POC Data | ||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Analyte | Material/Level | N | InsertRange | Target | SD/CVSpec | Mean | Repeatability | Between-Run | Between-Day | Between-Site | Reproducibility | |||||
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | |||||||
| Na+(mmol/L) | GSE 1 | 90 | 119-129 | 124 | 2 | 125 | 0.4 | 0.3% | 0.0 | 0.0% | 0.2 | 0.2% | 0.2 | 0.1% | 0.5 | 0.4% |
| GSE 2 | 90 | 136-146 | 141 | 2 | 141 | 0.3 | 0.2% | 0.1 | 0.1% | 0.3 | 0.2% | 0.3 | 0.2% | 0.5 | 0.4% | |
| GSE 3 | 90 | 149-161 | 155 | 2 | 155 | 0.3 | 0.2% | 0.0 | 0.0% | 0.2 | 0.1% | 0.1 | 0.1% | 0.4 | 0.2% | |
| K+(mmol/L) | GSE 1 | 90 | 2.1-2.7 | 2.4 | 0.25 | 2.4 | 0.00 | 0.0% | 0.00 | 0.0% | 0.00 | 0.0% | 0.00 | 0.0% | 0.00 | 0.0% |
| GSE 2 | 90 | 4.2-5.0 | 4.6 | 0.25 | 4.7 | 0.03 | 0.6% | 0.02 | 0.5% | 0.00 | 0.0% | 0.02 | 0.4% | 0.04 | 0.8% | |
| GSE 3 | 90 | 7.0-8.0 | 7.5 | 3.5% | 7.7 | 0.02 | 0.3% | 0.01 | 0.2% | 0.01 | 0.1% | 0.01 | 0.1% | 0.03 | 0.4% | |
| Cl-(mmol/L) | GSE 1 | 90 | 80-90 | 85 | 2.5% | 85 | 0.3 | 0.4% | 0.1 | 0.1% | 0.2 | 0.2% | 0.1 | 0.1% | 0.4 | 0.4% |
| GSE 2 | 90 | 102-112 | 107 | 2.5% | 108 | 0.2 | 0.2% | 0.0 | 0.0% | 0.2 | 0.2% | 0.0 | 0.0% | 0.3 | 0.3% | |
| GSE 3 | 90 | 136-146 | 141 | 2.5% | 142 | 0.4 | 0.3% | 0.3 | 0.2% | 0.1 | 0.1% | 0.2 | 0.2% | 0.6 | 0.4% | |
| Ca++(mmol/L) | GSE 1 | 90 | 1.45-1.65 | 1.55 | 5% | 1.58 | 0.007 | 0.4% | 0.004 | 0.3% | 0.002 | 0.1% | 0.002 | 0.1% | 0.009 | 0.6% |
| GSE 2 | 90 | 1.06-1.24 | 1.15 | 5% | 1.16 | 0.005 | 0.4% | 0.001 | 0.1% | 0.003 | 0.3% | 0.003 | 0.3% | 0.007 | 0.6% | |
| GSE 3 | 90 | 0.56-0.72 | 0.64 | 0.05 | 0.64 | 0.003 | 0.5% | 0.000 | 0.0% | 0.003 | 0.5% | 0.003 | 0.5% | 0.005 | 0.8% |
{19}------------------------------------------------
External Precision - Whole Blood
To evaluate whole blood precision on the GEM Premier 5000 system in the central laboratory and point-ofcare (POC) settings, whole blood patient samples were tested at 2 external central laboratories and 1 internal Customer Simulation Laboratory (CSL), as well as at 3 external POC locations. For the central laboratory setting, the studies were performed by 3 operators on 3 GEM Premier 5000 instruments using a single lot of GEM Premier 5000 PAK (cartridge). For the POC setting, the studies were performed by 11 operators on 3 GEM Premier 5000 instruments, using a single lot of GEM Premier 5000 PAK (cartridge). At least two whole blood specimens were analyzed in triplicate daily for 5 days in both normal mode (150 µL) for all 4 electrolytes, and micro capillary (65 µL) mode for Nat and Ca**. At the internal Customer Simulation Laboratory (CSL), contrived whole blood specimens were analyzed in addition to native specimens in order to cover the low and high medical decision levels of each analyte.
The precision results are summarized below:
| Analyte | Mode | Site | N | Mean | Within Sample SD or CV% |
|---|---|---|---|---|---|
| Na+ (mmol/L) | Normal Mode | POC1 | 54 | 138 | 0.5 |
| POC2 | 42 | 139 | 0.6 | ||
| POC3 | 30 | 138 | 0.5 | ||
| POC All | 126 | 138 | 0.5 | ||
| Micro Mode | CSL | 33 | 140 | 0.6 | |
| Lab1 | 30 | 141 | 0.5 | ||
| Lab2 | 30 | 137 | 0.5 | ||
| Lab All | 93 | 139 | 0.5 | ||
| K+ (mmol/L) | Normal Mode | POC1 | 30 | 136 | 0.6 |
| POC2 | 36 | 137 | 0.4 | ||
| POC3 | 36 | 138 | 0.4 | ||
| POC All | 102 | 137 | 0.5 | ||
| CSL | 33 | 140 | 0.3 | ||
| Lab1 | 30 | 142 | 0.6 | ||
| Lab2 | 30 | 136 | 0.5 | ||
| Lab All | 93 | 139 | 0.5 | ||
| K+ (mmol/L) | Normal Mode | POC1 | 54 | 4.2 | 0.05 |
| POC2 | 42 | 4.3 | 0.03 | ||
| POC3 | 30 | 4.1 | 0.05 | ||
| POC All | 126 | 4.2 | 0.04 | ||
| CSL | 33 | 4.0 | 0.07 | ||
| Lab1 | 30 | 4.2 | 0.04 | ||
| Lab2 | 30 | 4.2 | 0.05 | ||
| Lab All | 93 | 4.1 | 0.06 | ||
| Analyte | Mode | Site | N | Mean | WithinSample SDor CV% |
| Cl-(mmol/L) | NormalMode | POC1 | 54 | 105 | 0.2% |
| POC2 | 42 | 107 | 0.2% | ||
| POC3 | 30 | 104 | 0.3% | ||
| POC All | 126 | 106 | 0.2% | ||
| CSL | 36 | 105 | 0.3% | ||
| Lab1 | 30 | 110 | 0.3% | ||
| Lab2 | 30 | 104 | 0.4% | ||
| Lab All | 96 | 106 | 0.3% | ||
| Ca++(mmol/L) | NormalMode | POC1 | 54 | 1.17 | 0.6% |
| POC2 | 36 | 1.15 | 0.4% | ||
| POC3 | 27 | 1.12 | 0.6% | ||
| POC All | 117 | 1.15 | 0.6% | ||
| CSL | 33 | 1.23 | 0.6% | ||
| Lab1 | 27 | 1.16 | 0.3% | ||
| Lab2 | 27 | 1.20 | 0.9% | ||
| Lab All | 87 | 1.20 | 0.6% | ||
| MicroMode | POC1 | 27 | 1.15 | 0.8% | |
| POC2 | 27 | 1.17 | 0.5% | ||
| POC3 | 30 | 1.13 | 0.6% | ||
| POC All | 84 | 1.15 | 0.6% | ||
| CSL | 33 | 1.20 | 0.6% | ||
| Lab1 | 30 | 1.15 | 0.6% | ||
| Lab2 | 30 | 1.12 | 0.6% | ||
| Lab All | 93 | 1.16 | 0.6% |
NOTE: Capillary not claimed for K or Cl on the GEM Premier 5000.
{20}------------------------------------------------
External Precision – Whole Blood (Cont.)
{21}------------------------------------------------
LoB, LoD and LoQ
In accordance with CLSI EP17-A2, LoB, LoQ were established for Na*, K*, Ca** and Cl¯, using three (3) lots of GEM Premier 5000 PAKs (cartridges).
| Analyte | LoB | LoD | LoQ |
|---|---|---|---|
| Na+ (mmol/L) | 11 | 13 | 97 |
| K+ (mmol/L) | 0.0 | 0.1 | 0.9 |
| Cl- (mmol/L) | 5 | 7 | 38 |
| Ca++ (mmol/L) | 0.00 | 0.02 | 0.08 |
Following are the combined data results for LoB, LoD and LoQ:
Linearity
In accordance with CLSI EP06-A, nine (9) or ten (10) levels per analyte were prepared by spiking or diluting whole blood to challenge the claimed reportable range for each parameter. Each blood level was analyzed in triplicate on three (3) GEM Premier 5000 test analyzers and results compared to reference analyzers.
Combined data from limit of quantitation (LOQ) and linearity were used to support the lower limits of the claimed reportable ranges.
| Analyte | # ofLevels | N perLevel | Slope | Intercept | R² | TestedRange | ReportableRange |
|---|---|---|---|---|---|---|---|
| Na+(mmol/L) | 9 | 9 | 0.972 | 5.377 | 0.999 | 85 to 214 | 100 to 180 |
| K+(mmol/L) | 9 | 9 | 0.993 | -0.072 | 0.999 | 0.7 to 21.9 | 1.0 to 19.0 |
| Cl-(mmol/L) | 9 | 9 | 0.964 | 2.805 | 1.000 | 35 to 189 | 40 to 158 |
| Ca++(mmol/L) | 10 | 9 | 0.999 | 0.011 | 0.999 | 0.10 to 5.05 | 0.11 to 4.25 |
{22}------------------------------------------------
Analytical Specificity
In accordance with EP07-A2, an interference study was conducted on the GEM Premier 5000.
The table below lists substances that were screen tested with no observed interference on electrolyte results:
| Substance | Concentration | Tested analytes with no observed interference |
|---|---|---|
| Ammonium (Chloride) | 107 µmol/L | Sodium, Potassium, Calcium |
| Benzalkonium (Chloride) | 5 mg/L | Sodium, Potassium, Calcium |
| (Sodium) Bromide | 37.5 mmol/L | Potassium, Calcium |
| Calcium (Chloride) | 2.5 mmol/L | Sodium, Potassium |
| (Sodium) Citrate | 12 mmol/L | Potassium, Calcium |
| Ethanol | 86.8 mmol/L | Sodium, Potassium, Calcium, Chloride |
| (Sodium) Fluoride | 105 µmol/L | Potassium, Calcium, Chloride |
| Heparin | 100,000 U/L | Sodium, Potassium, Calcium, Chloride |
| Ibuprofen | 2425 µmol/L | Sodium, Potassium, Calcium, Chloride |
| (Sodium) lodide | 3 mmol/L | Potassium, Calcium |
| Ipratropium Bromide | 0.08 mg/L | Sodium, Potassium, Calcium, Chloride |
| Lithium (Chloride) | 3.2 mmol/L | Sodium, Potassium, Calcium |
| Magnesium (Chloride) | 15 mmol/L | Sodium, Potassium |
| (Sodium) Oxalate | 500 mg/dL | Potassium, Calcium, Chloride |
| (Sodium) Perchlorate | 20 mg/dL | Potassium, Chloride, Calcium |
| pH (with HCl) | 6.8 | Sodium, Potassium, Calcium |
| (Sodium) Salicylate | 4.34 mmol/L | Potassium, Calcium, Chloride |
| Sodium (Chloride) | 180 mmol/L | Potassium, Calcium |
| (Sodium) Thiocyanate | 6880 µmol/L | Potassium, Calcium |
| Thiopental | 248 µmol/L | Sodium, Potassium, Calcium, Chloride |
| (Sodium) Thiosulfate | 20 mmol/L | Potassium, Calcium, Chloride |
| Triglycerides (Intralipids) | 2% or 4012 mg/dL | Sodium, Calcium, Chloride |
{23}------------------------------------------------
Analytical Specificity (Cont.)
The table below lists substances that demonstrated interference with electrolyte results and the concentration of the interfering substance, as well as the bias observed and its direction (positive / negative):
| InterferingSubstance | AffectedAnalyte | AnalyteConcentration | InterferingConcentrationTested | BiasObserved(Mean) | LowestInterferingConcentrationwith AnalyteImpact | Bias Observedat the LowestConcentration |
|---|---|---|---|---|---|---|
| Bromide | Chloride | 90 mmol/L | 9.375 mmol/L | +31% | 1.346 mmol/L | +5% |
| (Sodium) | 108 mmol/L | 9.375 mmol/L | +25% | 1.880 mmol/L | +5% | |
| Citrate(Sodium) | Chloride | 88 mmol/L | 6.000 mmol/L | - 7% | 4.083 mmol/L | -5% |
| 111 mmol/L | 6.000 mmol/L | -5% | 5.344 mmol/L | -5% | ||
| lodide(Sodium) | Chloride | 88 mmol/L | 0.750 mmol/L | +6% | 0.700 mmol/L | +5% |
| 106 mmol/L | 1.500 mmol/L | +9% | 0.810 mmol/L | +5% | ||
| lonizedMagnesium(Chloride) | Calcium | 1.02 mmol/L | 3.938 mmol/L | +13% | 3.128 mmol/L | +10% |
| 2.00 mmol/L | 7.875 mmo/L | +11% | 6.862 mmol/L | +10% | ||
| Thiocyanate(Sodium) | Chloride | 87 mmol/L | 1720 µmol/L | +31% | 388.3 umol/L | +5% |
| 109 mmol/L | 1720 umol/L | +27% | 407.5 umol/L | +5% | ||
| Triglycerides | Potassium | 3.2 mmol/L | 1003 mg/dL | +14% | 522 mg/dL | +7% |
| (Intralipids) | 5.1 mmol/L | 1003 mg/dL | +11% | 662 mg/dL | +7% |
{24}------------------------------------------------
Internal Method Comparison
In accordance with EP09-A3, an internal method comparison study was conducted using clinical samples to compare the performance of the GEM Premier 5000 versus the GEM Premier 4000:
Samples were altered as needed to cover the medical decision levels. All parameter levels passed specification.
| Analyte | N | Slope | Intercept | R2 | Medical DecisionLevel | Bias at MedicalDecision Level |
|---|---|---|---|---|---|---|
| Na+(mmol/L) | 373 | 1.021 | -2.577 | 0.995 | 115 | -0.2 |
| 135 | 0.2 | |||||
| 150 | 0.5 | |||||
| K+(mmol/L) | 373 | 1.034 | -0.066 | 0.999 | 3.0 | 0.04 |
| 5.8 | 0.13 | |||||
| 7.5 | 2.5% | |||||
| Cl-(mmol/L) | 373 | 1.000 | 0.500 | 0.998 | 90 | 0.6% |
| 112 | 0.4% | |||||
| Ca++(mmol/L) | 373 | 1.031 | -0.033 | 0.999 | 0.37 | -0.021 |
| 0.82 | -0.007 | |||||
| 1.58 | 1.0% |
| NOTE: Capillary not claimed for K+ or Cl- on the GEM Premier 5000. | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
{25}------------------------------------------------
Whole Blood Performance at Medical Decision Levels
The data from the internal method comparison and precision studies were combined to assess the performance at medical decision levels.
Total Error was computed based on the following equation and the results were compared to the GEM Premier 5000 Total Error Specifications:
Total Error Observed = Bias + 2 * SD (or %CV)
Note: Previously shown bias and precision data were used in Total Error computations below.
| Analyte | MedicalDecisionLevel | Absolute Value ofBias at MedicalDecision Level | 2*(SD or %CV) | Total Error ObservedBias + 2*(SD or %CV) |
|---|---|---|---|---|
| Na+(mmol/L) | 115 | 0.2 | 0.8 | 1.0 |
| Na+(mmol/L) | 135 | 0.2 | 0.7 | 0.9 |
| Na+(mmol/L) | 150 | 0.5 | 1.1 | 1.6 |
| K+(mmol/L) | 3.0 | 0.04 | 0.10 | 0.14 |
| K+(mmol/L) | 5.8 | 0.13 | 0.10 | 0.23 |
| K+(mmol/L) | 7.5 | 2.5% | 3.7% | 6.2% |
| Cl-(mmol/L) | 90 | 0.6% | 0.8% | 1.4% |
| Cl-(mmol/L) | 112 | 0.4% | 1.2% | 1.6% |
| Ca++(mmol/L) | 0.37 | 0.021 | 0.012 | 0.033 |
| Ca++(mmol/L) | 0.82 | 0.007 | 0.010 | 0.017 |
| Ca++(mmol/L) | 1.58 | 1.0% | 2.6% | 3.6% |
{26}------------------------------------------------
| Analyte | Reference Range | Unit |
|---|---|---|
| Na+ | 136 to 145 | mmol/L |
| Na+ | 136 to 145 | mEq/L |
| K+ | 3.5 to 5.1 | mmol/L |
| K+ | 3.5 to 5.1 | mEq/L |
| Ca++ | 1.15 to 1.33 | mmol/L |
| Ca++ | 2.30 to 2.66 | mEq/L |
| Ca++ | 4.60 to 5.32 | mg/dL |
| Ca++ | 1.16 to 1.32 (venous) | mmol/L |
| Ca++ | 4.64 to 5.28 (venous) | mEq/L |
| Cl- | 98 to 107 | mmol/L |
| Cl- | 98 to 107 | mEq/L |
| Anion Gap | 10 to 20 (Na+ + K+) - (Cl- + HCO3-) | mEq/L |
| Anion Gap | 10 to 20 (Na+ + K+) - (Cl- + HCO3-) | mmol/L |
Reference Ranges
Source: Burtis, Carl and David Bruns, Tietz Textbook of Clinical Chemistry and Molecular Diagnostics, Elsevier Saunders, 7th edition, 2015, pp 952-982
{27}------------------------------------------------
Clinical Testing
In accordance with EPO9-A3, a method comparison study was conducted on the GEM Premier 5000 compared to the predicate device, the GEM Premier 4000, in the point-of-care (POC) setting using heparinized whole blood patient samples from the intended use population.
- Study Design:
- . Three (3) external point-of-care (POC) sites.
- One (1) internal Customer Simulation Laboratory (CSL) at IL, where three (3) intended POC users were brought on site to run the samples, allowing spiking to cover the reportable ranges.
The pooled results from the POC sites and the IL internal Customer Simulation Laboratory (CSL) for the Normal Mode (with samples collected in syringes) are presented below.
| Pooled Point-of-Care Site and CSL Data - Normal Mode (with Syringe Samples) | |||||
|---|---|---|---|---|---|
| Analyte | N | Slope | Intercept | r | Sample Range |
| Na+ (mmol/L) | 486 | 0.991 | 1.184 | 0.991 | 103 to 180 |
| K+ (mmol/L) | 491 | 1.000 | 0.100 | 0.998 | 1.0 to 15.7 |
| Cl- (mmol/L) | 485 | 1.000 | 1.000 | 0.990 | 40 to 157 |
| Ca++ (mmol/L) | 491 | 1.010 | 0.008 | 0.998 | 0.14 to 4.21 |
To support capillary claims, finger-stick samples were collected at an external POC site (N=65 native samples) and the IL internal Customer Simulation Laboratory (CSL) (N=106 native samples) with POC operators. The observed total error at the medical decision levels is shown below:
NOTE: Capillary not claimed for K* or Cl¯ on the GEM Premier 5000.
| Pooled Point-of-Care Site and CSL Data with Native Capillary Samples Only | |||||||
|---|---|---|---|---|---|---|---|
| Analyte | N | RangeMin | RangeMax | MDL | Bias atMDL | 95% CI of Bias at MDL | TEa |
| Na+(mmol/L) | 171 | 124 | 143 | 115.0 | -3.6 | -7.2 to -0.0 | ± 4.0 |
| 135 | 0.4 | 0.0 to 0.8 | ± 5.0 | ||||
| 150 | 3.4 | 0.8 to 5.9 | ± 5.0 | ||||
| Ca++(mmol/L) | 171 | 1.03 | 1.38 | 0.37 | -0.127 | -0.234 to 0.040 | ± 0.10 |
| 0.82 | -0.027 | -0.071 to 0.040 | ± 0.10 | ||||
| 1.58 | 9.0% | 3.2% to 12.7% | ± 10% |
{28}------------------------------------------------
Clinical Testing (Cont.)
In addition, the data from the native capillary samples (finger-stick samples) previously presented were pooled with contrived capillary samples prepared internally. The regression analysis is shown below:
| Pooled Point-of-Care Site and CSL Data with Additional Contrived Capillary Results | |||||
|---|---|---|---|---|---|
| Analyte | N | Slope | Intercept | r | Sample Range |
| Na+ (mmol/L) | 201 | 1.015 | -1.750 | 0.981 | 103 to 180 |
| Ca++ (mmol/L) | 205 | 1.050 | -0.016 | 0.998 | 0.14 to 4.25 |
NOTE: Capillary not claimed for K* or Cl¯ on the GEM Premier 5000.
| Conclusion | The technological and functional characteristics of the new GEM Premier5000 as described above are substantially equivalent to that of thepredicate device (GEM Premier 4000) for sodium, potassium, chloride andionized calcium. |
|---|---|
| Conclusion | The analytical and clinical study results demonstrate that the GEMPremier 5000 is safe and effective for its intended purpose and equivalentin performance to the predicate device. |
§ 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.