(306 days)
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No
The description of iQM2 focuses on statistical process control and automated checks, not AI/ML techniques. There is no mention of training data, models, or learning algorithms.
No
The device aids in diagnosis by measuring pH, pCO2, and pO2 in blood samples, but it does not directly treat or prevent a disease.
Yes
The "Intended Use / Indications for Use" section explicitly states that the device aids in the "diagnosis of a patient's acid/base status" and that its measurements are "used in the diagnosis and treatment of life-threatening acid-base disturbances." This clearly indicates its role as a diagnostic device.
No
The device description clearly outlines hardware components like the "Analyzer" and the "GEM Premier 5000 PAK (disposable, multi-use GEM PAK)" which houses sensors, optical cells, and other physical elements necessary for operation. While software is involved (e.g., iQM2, menus), it is integral to a physical system that performs analytical measurements on blood samples.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states that the system is used to "rapidly analyze heparinized whole blood samples" and that the measurements "aid in the diagnosis of a patient's acid/base status" and are "used in the diagnosis and treatment of life-threatening acid-base disturbances." This clearly indicates that the device is intended for use in the examination of specimens derived from the human body (whole blood) to provide information for diagnostic purposes.
- Device Description: The device description details how the system measures specific analytes (pH, pCO2, pO2) in whole blood using sensors and reagents housed within a disposable cartridge (GEM PAK). This aligns with the typical components and function of an in vitro diagnostic device.
- Performance Studies: The document includes extensive performance studies such as precision, linearity, analytical specificity (interference), and method comparison studies using whole blood samples. These types of studies are standard for demonstrating the analytical performance of an IVD.
- Comparison to Predicate Device: The document mentions a predicate device (GEM Premier 4000), which is common practice for demonstrating substantial equivalence for IVD devices seeking regulatory clearance.
The core function of the GEM Premier 5000 is to analyze a biological specimen (whole blood) in vitro (outside the body) to provide quantitative measurements that are used to aid in diagnosis and treatment. This directly fits the definition of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
The GEM Premier 5000 is a portable critical care system for use by health care professionals to rapidly analyze heparinized whole blood samples at the point of health care delivery in a clinical setting and in a central laboratory. The instrument provides quantitative measurements of pH and pO2 from venous, arterial and capillary heparinized whole blood, as well as quantitative measurements of pCO2 from venous and arterial heparinized whole blood. These parameters, along with derived parameters, aid in the diagnosis of a patient's acid/base status.
pH, pCO2 and pO2 measurements in whole blood are used in the diagnosis and treatment of life-threatening acid-base disturbances.
Product codes (comma separated list FDA assigned to the subject device)
CHL
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 pH and pQ2 from venous, arterial and capillary heparinized whole blood, as well as quantitative measurements of pCO₂ 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 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. NOTE: The EEPROM on the GEM PAK includes all solution values and controls the analyte menu and number of tests.
Step 1: After inserting the GEM PAK, the instrument will perform an automated PAK warm-up during which the sensors are hydrated and a variety of checks occur, all of which take about 40 minutes. During warm-up, the instrument requires no user intervention.
Step 2: After GEM PAK warmup, Auto PAK Validation (APV) process is automatically completed: two completely independent solutions (PC Solution D and E) that are traceable to NIST standards, CLSI procedures or internal standards, containing two levels of concentration for each analyte, are run by the analyzer to validate the integrity of the PC Solutions and the overall performance of the analytical system.
Step 3: After successful performance of APV, iQM2 manages the quality control process, replacing external quality controls.
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.
Mentions image processing
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Mentions AI, DNN, or ML
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Input Imaging Modality
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Anatomical Site
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Indicated Patient Age Range
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Intended User / Care Setting
health care professionals in a clinical setting and in a central laboratory, Point-of-Care (PCC) sites.
Description of the training set, sample size, data source, and annotation protocol
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Description of the test set, sample size, data source, and annotation protocol
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Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Internal Precision Study - Aqueous Controls
Study Type: Precision study (CLSI EP05-A3)
Sample Size: n=120 per level
Key Results: All results were within specification.
Internal Precision Study – GEM PAK (Cartridge) Process Control Solutions D and E
Study Type: Precision study (CLSI EP05-A3)
Sample Size: N=120 per analyte/per level
Key Results: All results were within specification.
Internal Precision Study – Whole Blood
Study Type: Precision study (CLSI EP05-A3)
Sample Size: N=120 per analyte/per sample mode
Key Results: All results were within specification.
Reproducibility Study with Aqueous Controls – Point-of-Care (POC) Setting
Study Type: Reproducibility study (CLSI EP05-A3)
Sample Size: 90 per analyte/level (pooled)
Key Results: All results at all sites were within specification.
External Precision – Whole Blood
Study Type: Precision study
Setting: 2 external central laboratories, 1 internal Customer Simulation Laboratory (CSL), 3 external POC locations.
Key Results: Precision results summarized in tables.
LoB, LoD and LoQ
Study Type: Limit of Blank, Limit of Detection, Limit of Quantitation study (CLSI EP17-A2)
Sample Size: Three (3) lots of GEM Premier 5000 PAKs (cartridges).
Key Results: LoB, LoD, and LoQ values established for pH, pCO2, and pO2.
Linearity
Study Type: Linearity study (CLSI EP06-A)
Method: Eight (8) or nine (9) levels per analyte were prepared by tonometering whole blood. Each blood level was analyzed in triplicate on three (3) GEM Premier 5000 test analyzers and results compared to standard reference procedures.
Key Results: Slope, Intercept, R² values reported for pH, pCO2, and pO2 within tested and reportable ranges.
Analytical Specificity
Study Type: Interference study (EP07-A2)
Method: Screening test to identify substances producing clinically significant interference.
Key Results: Listed substances showed no observed interference on pH, pCO₂ and pO₂ results.
Internal Method Comparison
Study Type: Method comparison study (EP09-A3)
Method: Clinical samples compared GEM Premier 5000 to Tonometry (for pO2, pCO2) and GEM Premier 4000 (for pH).
Sample Size: pH (N=373), pCO2 (N=150), pO2 (N=148)
Key Results: Slope, Intercept, R² values reported. All parameter levels passed specification.
Whole Blood Performance at Medical Decision Levels
Method: Total Error was computed based on combined data from internal method comparison and precision studies.
Key Results: Total Error Observed values for pH, pCO2, and pO2 at various medical decision levels reported.
Clinical Testing
Study Type: Method comparison study (EPO9-A3)
Setting: Three (3) external point-of-care (POC) sites and one (1) internal Customer Simulation Laboratory (CSL) at IL.
Sample Type: Heparinized whole blood patient samples (syringes) from intended use population. Finger-stick capillary samples also collected.
Sample Size: Normal Mode (Syringe Samples): pH (N=479), pCO2 (N=492), pO2 (N=506). Native Capillary Samples: pH (N=171), pO2 (N=167). Pooled Point-of-Care Site and CSL Data with Additional Contrived Capillary Results: pH (N=189), pO2 (N=218).
Key Results: Regression analysis (slope, intercept, r, sample range) for normal mode and capillary samples. Total error and bias for native capillary samples.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Performance metrics reported are precision (SD, %CV), total error, bias, linearity (slope, intercept, R²), and correlation coefficient (r). Specificity is reported in terms of analytical specificity (interference testing). Sensitivity, PPV, NPV, AUC, and MRMC are not explicitly reported.
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
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Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
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§ 862.1120 Blood gases (P
CO2 , PO2 ) and blood pH test system.(a)
Identification. A blood gases (PCO2 , PO2 ) and blood pH test system is a device intended to measure certain gases in blood, serum, plasma or pH of blood, serum, and plasma. Measurements of blood gases (PCO2 , PO2 ) and blood pH are used in the diagnosis and treatment of life-threatening acid-base disturbances.(b)
Classification. Class II.
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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: K160412
Trade/Device Name: GEM Premier 5000 (Measured Parameters: pH. pCO2, pO2) Regulation Number: 21 CFR 862. 1120 Regulation Name: Blood gases (pCO2 and pO2) and blood pH test system Regulatory Class: II Product Code: CHL Dated: December 7, 2016 Received: December 8, 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 electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
1
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, Ph.D. 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) K160412
Device Name
GEM Premier 5000 (Measured Parameters: pH, pCO2, pO2)
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 pH and pO2 from venous, arterial and capillary heparinized whole blood, as well as quantitative measurements of pCO2 from venous and arterial heparinized whole blood. These parameters, along with derived parameters, aid in the diagnosis of a patient's acid/base status.
pH, pCO2 and pO2 measurements in whole blood are used in the diagnosis and treatment of life-threatening acid-base disturbances.
| Type of Use (Select one or both, as applicable) | |
|---|---|
| ------------------------------------------------- | -- |
X 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 Road
Bedford, 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 7, 2016 |
|---|---|
| ------------------ | ------------------ |
| Device Trade Name | GEM Premier 5000
(Measured Parameters: pH, pCO2 and pO2) |
| ------------------- | ------------------------------------------------------------- |
|---|
| Predicate Device | GEM Premier 4000 | K133407 |
|---|---|---|
| ------------------ | ------------------ | --------- |
| Regulatory Information | |||||
|---|---|---|---|---|---|
| Analyte | Regulation Section | Regulatory Description | Class | Product Code | Panel |
| pH, pCO₂, pO₂, | 862.1120 | Blood Gases (pCO₂, pO₂) and Blood pH system | II | CHL | 75 |
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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 pH and pQ2 from venous, arterial and capillary heparinized whole blood, as well as quantitative measurements of pCO₂ from venous and arterial heparinized whole blood.
| Key Components | Description |
|---|---|
| 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 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. | |
| NOTE: The EEPROM on the GEM PAK includes all solution values and | |
| controls the analyte menu and number of tests. | |
| Step 1: | After inserting the GEM PAK, the instrument will perform an |
| automated PAK warm-up during which the sensors are | |
| hydrated and a variety of checks occur, all of which take | |
| about 40 minutes. During warm-up, the instrument requires | |
| no user intervention. | |
| Step 2: | After GEM PAK warmup, Auto PAK Validation (APV) process is |
| automatically completed: two completely independent | |
| solutions (PC Solution D and E) that are traceable to NIST | |
| standards, CLSI procedures or internal standards, containing | |
| two levels of concentration for each analyte, are run by the | |
| analyzer to validate the integrity of the PC Solutions and the | |
| overall performance of the analytical system. | |
| Step 3: | After successful performance of APV, iQM2 manages the |
| quality control process, replacing external quality controls. | |
| 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. |
5
| Indications for Use / Intended Use | ||
|---|---|---|
| GEM Premier 5000 | The GEM Premier 5000 is a portable critical care system for use by | |
| health care professionals to rapidly analyze heparinized whole | ||
| blood samples at the point of health care delivery in a clinical | ||
| setting and in a central laboratory. The instrument provides | ||
| quantitative measurements of pH and pO2 from venous, arterial | ||
| and capillary heparinized whole blood, as well as quantitative | ||
| measurements of pCO2 from venous and arterial heparinized whole | ||
| blood. These parameters, along with derived parameters, aid in the | ||
| diagnosis of a patient's acid/base status. |
pH, pCO2, pO2 measurements in whole blood are used in the
diagnosis and treatment of life-threatening acid-base disturbances. | |
| Substantial Equivalency | | |
| The GEM Premier 5000 system is substantially equivalent in function and intended use to the following predicate device for pH, pCO2, pO2: | | |
| Item | Predicate Device | New Device |
| Trade Name | GEM Premier 4000 | GEM Premier 5000 |
| 510(k) No. | K133407 | K160412 |
| Manufacturer | Instrumentation Laboratory Co. | Instrumentation Laboratory Co. |
| Indications
for Use | 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. | The GEM Premier 5000 is a portable critical care system for use
by health care professionals to rapidly analyze heparinized
whole blood samples at the point of health care delivery in a
clinical setting and in a central laboratory. The instrument
provides quantitative measurements of pH and pO2 from
venous, arterial and capillary heparinized whole blood, as well
as quantitative measurements of pCO2 from venous and arterial
heparinized whole blood. These parameters, along with derived
parameters, aid in the diagnosis of a patient's acid/base status.
pH, pCO2, pO2 measurements in whole blood are used in the
diagnosis and treatment of life-threatening acid-base
disturbances. |
| Substantial Equivalency (Cont.) | | |
| Item | Predicate Device | New Device |
| Trade Names | GEM Premier 4000
K133407 | GEM Premier 5000
K160412 |
| Intended User | Central Laboratory and Point-of-Care | Same |
| Sample Type | Heparinized whole blood | $pH, pO2$ Arterial, venous or capillary heparinized whole blood
$pCO2$ Arterial or venous heparinized whole blood |
| Blood Gas Measurement | Potentiometry: $pH$ and $pCO2$
Amperometry: $pO2$ | 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 |
Special Conditions for Use Statement
- . For prescription use only.
- For clinical laboratory and point-of-care use. .
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7
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| Substantial Equivalency (Cont.) | ||||
|---|---|---|---|---|
| Item | Predicate Device | New Device | ||
| Trade Name | GEM Premier 4000 | K133407 | GEM Premier 5000 | K160412 |
| 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 | Analyte | GEM Premier 4000 | GEM Premier 5000 | |
| pH | 7.00 to 8.00 | 7.00 to 7.92 | ||
| pCO2 | 6 to 125 mmHg | 6 to 125 mmHg | ||
| pO2 | 5 to 690 mmHg | 6 to 690 mmHg |
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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 | Within
Analyzer
SD | Within
Analyzer
%CV | Total SD | Total
%CV |
|-------------------------|----------------|---------|------|-----|--------------------------|---------------------------|----------|--------------|
| GEM System
Evaluator | pH | Level 1 | 7.14 | 120 | 0.008 | 0.1% | 0.008 | 0.1% |
| | | Level 2 | 7.38 | 120 | 0.004 | 0.1% | 0.006 | 0.1% |
| | | Level 3 | 7.57 | 120 | 0.003 | 0.0% | 0.003 | 0.0% |
| | pCO2
(mmHg) | Level 1 | 87 | 120 | 2.3 | 2.7% | 2.3 | 2.7% |
| | | Level 2 | 35 | 120 | 0.7 | 1.9% | 0.8 | 2.3% |
| | | Level 3 | 14 | 120 | 0.3 | 2.2% | 0.3 | 2.3% |
| | pO2
(mmHg) | Level 1 | 31 | 120 | 1.9 | 6.1% | 2.4 | 7.9% |
| | | Level 2 | 88 | 120 | 1.2 | 1.4% | 2.2 | 2.4% |
| | | Level 3 | 370 | 120 | 4.8 | 1.3% | 5.9 | 1.6% |
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 Analyzer
SD | Within Analyzer
%CV |
|----------|----------------|------|-----|-----------------------|------------------------|
| PCS D | pH | 7.35 | 120 | 0.001 | 0.0% |
| PCS E | pH | 7.21 | 120 | 0.001 | 0.0% |
| PCS D | $pCO_2$ (mmHg) | 25 | 120 | 0.1 | 0.4% |
| PCS E | $pCO_2$ (mmHg) | 68 | 120 | 0.3 | 0.5% |
| PCS D | $pO_2$ (mmHg) | 55 | 120 | 1.1 | 1.9% |
| PCS E | $pO_2$ (mmHg) | 98 | 120 | 1.1 | 1.1% |
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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
| Analyte | Mode | Level | Mean | N | Within Run
SD | Within Run
%CV | Total SD | Total %CV |
|----------------|----------------|-------|------|-----|------------------|-------------------|----------|-----------|
| pH | Normal
Mode | 1 | 7.11 | 120 | 0.004 | 0.1% | 0.005 | 0.1% |
| | | 2 | 7.33 | 120 | 0.007 | 0.1% | 0.007 | 0.1% |
| | | 3 | 7.35 | 120 | 0.004 | 0.1% | 0.005 | 0.1% |
| | | 4 | 7.42 | 120 | 0.005 | 0.1% | 0.006 | 0.1% |
| | | 5 | 7.68 | 120 | 0.012 | 0.1% | 0.014 | 0.2% |
| | Micro
Mode | 1 | 7.10 | 120 | 0.006 | 0.1% | 0.007 | 0.1% |
| | | 2 | 7.32 | 120 | 0.004 | 0.1% | 0.006 | 0.1% |
| | | 3 | 7.35 | 120 | 0.004 | 0.1% | 0.005 | 0.1% |
| | | 4 | 7.41 | 120 | 0.005 | 0.1% | 0.006 | 0.1% |
| | | 5 | 7.67 | 120 | 0.013 | 0.2% | 0.015 | 0.2% |
| pCO2
(mmHg) | Normal
Mode | 1 | 112 | 120 | 2.7 | 2.4% | 2.9 | 2.3% |
| | | 2 | 70 | 120 | 1.1 | 1.5% | 1.5 | 2.0% |
| | | 3 | 50 | 120 | 0.6 | 1.2% | 0.8 | 1.5% |
| | | 4 | 36 | 120 | 0.5 | 1.3% | 0.8 | 1.9% |
| | | 5 | 10 | 120 | 0.5 | 4.6% | 0.8 | 7.7% |
11
| Analyte | Mode | Level | Mean | N | Within Run SD | Within Run %CV | Total SD | Total %CV |
|---|---|---|---|---|---|---|---|---|
| pO2 | ||||||||
| (mmHg) | Normal | |||||||
| Mode | 1 | 32 | 120 | 0.4 | 1.2% | 0.9 | 2.7% | |
| 2 | 62 | 120 | 0.7 | 1.1% | 0.9 | 1.2% | ||
| 3 | 204 | 120 | 2.3 | 1.1% | 3.1 | 1.4% | ||
| 4 | 415 | 120 | 8.6 | 2.1% | 13.0 | 2.8% | ||
| 5 | 722 | 120 | 18.6 | 2.6% | 32.7 | 4.3% | ||
| Micro | ||||||||
| Mode | 1 | 31 | 120 | 0.9 | 3.0% | 1.6 | 5.3% | |
| 2 | 62 | 120 | 0.7 | 1.1% | 0.9 | 1.4% | ||
| 3 | 204 | 120 | 4.3 | 2.1% | 5.5 | 2.5% | ||
| 4 | 402 | 120 | 15.3 | 3.8% | 16.4 | 3.8% | ||
| 5 | 693 | 120 | 26.5 | 3.8% | 34.0 | 4.8% |
Internal Precision Study – Whole Blood (Cont.)
12
Reproducibility Study with Aqueous Controls – Point-of-Care (POC) Setting
In accordance with CLSI EP05-A3, a reproducibility study was performed at three (3) external clinical point-of-care (PCC) 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 (cartridges). 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 poled). All results at all sites were within specification.
| Pooled Multi-Site POC Data | ||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Analyte | Material/ | |||||||||||||||
| Level | N | Insert | ||||||||||||||
| Range | Target | SD/CV | ||||||||||||||
| Spec | Mean | Repeatability | Between-Run | Between-Day | Between-Site | Reproducibility | ||||||||||
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | |||||||
| pH | GSE 1 | 90 | 7.10-7.18 | 7.14 | 0.02 | 7.14 | 0.002 | 0.0% | 0.001 | 0.0% | 0.000 | 0.0% | 0.000 | 0.0% | 0.002 | 0.0% |
| GSE 2 | 90 | 7.35-7.43 | 7.39 | 0.02 | 7.39 | 0.007 | 0.1% | 0.003 | 0.0% | 0.003 | 0.0% | 0.002 | 0.0% | 0.008 | 0.1% | |
| GSE 3 | 90 | 7.53-7.61 | 7.57 | 0.02 | 7.57 | 0.002 | 0.0% | 0.000 | 0.0% | 0.003 | 0.0% | 0.000 | 0.0% | 0.003 | 0.0% | |
| pCO2 | ||||||||||||||||
| (mmHg) | GSE 1 | 90 | 78-96 | 87 | 4% | 87 | 0.4 | 0.5% | 0.7 | 0.9% | 0.6 | 0.7% | 0.0 | 0.0% | 1.1 | 1.2% |
| GSE 2 | 90 | 29-39 | 34 | 2.5 | 34 | 0.9 | 2.5% | 0.0 | 0.0% | 0.3 | 0.9% | 0.0 | 0.0% | 0.9 | 2.7% | |
| GSE 3 | 90 | 10-16 | 13 | 2.5 | 13 | 0.4 | 3.3% | 0.0 | 0.0% | 0.2 | 1.2% | 0.0 | 0.0% | 0.5 | 3.5% | |
| pO2 | ||||||||||||||||
| (mmHg) | GSE 1 | 90 | 21-41 | 31 | 5 | 28 | 0.7 | 2.3% | 0.4 | 1.4% | 0.6 | 2.2% | 1.6 | 5.8% | 1.9 | 6.7% |
| GSE 2 | 90 | 77-97 | 87 | 5 | 87 | 1.4 | 1.7% | 0.0 | 0.0% | 0.6 | 0.7% | 1.0 | 1.2% | 1.9 | 2.2% | |
| GSE 3 | 90 | 325-389 | 357 | 5% | 357 | 7.9 | 2.2% | 0.0 | 0.0% | 0.0 | 0.0% | 4.8 | 1.3% | 9.3 | 2.6% |
13
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 pH, pCO2 and pO2, and micro capillary (65 µL) mode for pH and pO2. 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 |
|----------------|----------------|---------|------|-------|---------------------|
| pH | Normal
Mode | POC1 | 54 | 7.36 | 0.008 |
| | | POC2 | 42 | 7.33 | 0.009 |
| | | POC3 | 30 | 7.35 | 0.008 |
| | | POC-All | 126 | 7.35 | 0.008 |
| | CSL | 30 | 7.32 | 0.009 | |
| | Lab1 | 30 | 7.36 | 0.009 | |
| | Lab2 | 30 | 7.32 | 0.007 | |
| | Lab-All | 90 | 7.33 | 0.008 | |
| | Micro
Mode | POC1 | 30 | 7.29 | 0.009 |
| | | POC2 | 36 | 7.32 | 0.012 |
| | | POC3 | 36 | 7.28 | 0.012 |
| | | POC-All | 102 | 7.30 | 0.011 |
| | CSL | 30 | 7.30 | 0.008 | |
| | Lab1 | 30 | 7.33 | 0.007 | |
| | Lab2 | 30 | 7.26 | 0.009 | |
| | Lab-All | 90 | 7.30 | 0.008 | |
| Analyte | Mode | Site | N | Mean | Within Sample
SD |
| pCO2
(mmHg) | Normal
Mode | POC1 | 48 | 43 | 1.1 |
| | | POC2 | 39 | 42 | 0.8 |
| | | POC3 | 30 | 49 | 1.7 |
| | | POC-All | 117 | 44 | 1.2 |
| | Normal
Mode | CSL | 24 | 53 | 1.3 |
| | | Lab1 | 30 | 46 | 1.3 |
| | | Lab2 | 24 | 46 | 0.8 |
| | | Lab-All | 78 | 48 | 1.2 |
| pO2
(mmHg) | Normal
Mode | POC1 | 27 | 52 | 1.5 |
| | | POC2 | 12 | 63 | 0.4 |
| | | POC3 | 12 | 71 | 2.0 |
| | | POC-All | 51 | 59 | 1.5 |
| | | CSL | 30 | 52 | 0.6 |
| | Micro
Mode | Lab1 | 21 | 55 | 0.8 |
| | | Lab2 | 15 | 50 | 3.9 |
| | | Lab-All | 66 | 53 | 0.8 |
| | | POC1 | 21 | 53 | 1.5 |
| | Micro
Mode | POC2 | 6 | 45 | 1.2 |
| | | POC3 | 18 | 58 | 1.1 |
| | | POC-All | 45 | 54 | 1.3 |
| | | CSL | 30 | 54 | 0.8 |
| | Micro
Mode | Lab1 | 24 | 60 | 1.0 |
| | | Lab2 | 18 | 52 | 1.1 |
| | | Lab-All | 72 | 56 | 1.0 |
14
External Precision – Whole Blood (Cont.)
15
LoB, LoD and LoQ
In accordance with CLSI EP17-A2, LoB, LoD and LoQ were established for pH, pCO2 and pO2 using three (3) lots of GEM Premier 5000 PAKs (cartridges).
| Analyte | LoB | LoD | LoQ |
|---|---|---|---|
| pH* | 8.90 | 8.87 | 8.04 |
| pCO2 (mmHg) | 0 | 1 | 4 |
| pO2 (mmHg) | NA | NA | 2 |
Following are the combined data results for LoB, LoD and LoQ:
- *Note: By definition, LoQ must be ≥ LoD except for pH. Since pH is measured on a negative log scale, larger pH values represent lower analyte levels. Thus, for pH, LoQ must be ≤ LoD.
Linearity
In accordance with CLSI EP06-A, eight (8) or nine (9) levels per analyte were prepared by tonometering 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 standard reference procedures (i.e. tonometry for gases).
Combined data from limit of quantitation (LOQ) and linearity were used to support the lower limits of the claimed reportable ranges.
| Analyte | # of
Levels | N per
Level | Slope | Intercept | R2 | Tested
Range | Reportable
Range |
|----------------|----------------|----------------|-------|-----------|-------|-----------------|---------------------|
| pH | 8 | 9 | 0.972 | 0.191 | 0.998 | 6.67 to 7.97 | 7.00 to 7.92 |
| pCO2
(mmHg) | 8 | 9 | 1.045 | -2.027 | 0.998 | 1 to 149 | 6 to 125 |
| pO2
(mmHg) | 9 | 9 | 1.028 | -4.069 | 0.995 | 5 to 727 | 6 to 690 |
16
Analytical Specificity
In accordance with EP07-A2, an interference study was conducted on the GEM Premier 5000. A screening test was used to identify substances that produce a clinically significant interference based on measurement at two different analyte concentrations. The table below lists substances that were screen tested with no observed interference on pH, pCO₂ and pO₂ results:
| No Observed Interference with pH, pCO2 and pO2 | |
|---|---|
| Substance | Concentration |
| Acetaminophen | 1324 µmol/L |
| Albumin (Human) | 60 g/L |
| Amoxicillin | 206 µmol/L |
| Aprotinin | 50 mg/L |
| Atracurium | 50 mg/L |
| Benzalkonium (Chloride) | 5 mg/L |
| Bilirubin | 20 mg/dL |
| Ceftriaxone | 1460 µmol/L |
| Ciprofloxin | 30.2 µmol/L |
| Diazepam | 18 µmol/L |
| Epinephrine | 0.5 µmol/L |
| Ethanol | 86.8 mmol/L |
| Etomidate | 50 mg/L |
| Fentanyl | 0.02 µg/ml |
| Gentamycin | 21 µmol/L |
| Halothane | 759 µmol/L |
| Hematocrit | 25% |
| 75% | |
| Hemoglobin (Hemolysis) | 2 g/dL (20%) |
| Lithium (Chloride) | 3.2 mmol/L |
| Methadone | 6.46 µmol/L |
| Midazolam | 0.5 µg/mL |
| Morphine | 1.75 µmol/L |
| Omeprazole | 17.4 µmol/L |
| Phenobarbital | 431 µmol/L |
| Propofol | 0.05 mg/mL |
| Suxamethonium | 68 µmol/L |
| Thiopental | 248 µmol/L |
| Thyroxine | 1.29 µmol/L |
| Triglycerides (Intralipids) | 2% or 4012 mg/dL |
17
Internal Method Comparison
In accordance with EP09-A3, an internal method comparison study was conducted using clinical samples to compare the GEM Premier 5000 to the following predicate devices:
- Tonometry: pO2, pCO2 (tonometry used due to instability of blood gases)
- . GEM Premier 4000: pH
Samples were altered as needed to cover the medical decision levels. All parameter levels passed specification for all sample modes.
| Analyte | N | Slope | Intercept | R² | Medical Decision
Level | Bias at Medical
Decision Level |
|----------------|-----|-------|-----------|-------|---------------------------|-----------------------------------|
| pH | 373 | 0.953 | 0.344 | 0.993 | 7.30 | 0.001 |
| | | | | | 7.35 | -0.001 |
| | | | | | 7.45 | -0.006 |
| pCO2
(mmHg) | 150 | 1.026 | -0.991 | 0.997 | 35 | -0.1 |
| | | | | | 50 | 0.3 |
| | | | | | 70 | 1.2% |
| pO2
(mmHg) | 148 | 1.027 | -1.266 | 0.999 | 30 | -0.5 |
| | | | | | 45 | 0.0 |
| | | | | | 60 | 0.4 |
18
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 | Medical
Decision
Level | Absolute Value of
Bias at Medical
Decision Level | 2*(SD or %CV) | Total Error Observed
Bias + 2*(SD or %CV) |
|----------------|------------------------------|--------------------------------------------------------|---------------|----------------------------------------------|
| pH | 7.30 | 0.001 | 0.013 | 0.014 |
| | 7.35 | 0.001 | 0.008 | 0.009 |
| | 7.45 | 0.006 | 0.010 | 0.016 |
| pCO2
(mmHg) | 35 | 0.1 | 0.9 | 1.0 |
| | 50 | 0.3 | 1.2 | 1.5 |
| | 70 | 1.2% | 3.0% | 4.2% |
| pO2
(mmHg) | 30 | 0.5 | 0.7 | 1.2 |
| | 45 | 0.0 | 1.4 | 1.4 |
| | 60 | 0.4 | 1.4 | 1.8 |
19
Reference Ranges
| Analyte | Reference Range | Unit |
|---|---|---|
| pH | 7.35 to 7.45 | pH |
| cH | 35.5 to 44.7 | nmol/L |
| cH | 35.5 to 44.7 | nEq/L |
| pH | 7.32 to 7.43 (venous) | pH |
| pCO₂ | Arterial blood: 35 to 48 (male) and 32 to 35 (female) | |
| Arterial blood: 4.6 to 6.4 (male) and 4.3 to 6.0 (female) | ||
| Venous blood (right atrium) - 6-7 mmHg (0.80-0.93 kPa) higher than arterial pCO₂ | mmHg | |
| kPa | ||
| pO₂ | 83 to 108 | |
| 11.0 to 14.4 | mmHg | |
| kPa | ||
| TCO₂ | 19.0 to 24.0 | |
| 22.0 to 26.0 (venous) | mmol/L | |
| BE | -2.0 to 3.0 | mmol/L |
| HCO₃⁻ | 21 to 28 | mmol/L |
| 21 to 28 | mEq/L | |
| 22 to 29 (venous) | mmol/L | |
| 22 to 29 (venous) | mEq/L |
Sources: Burtis, Carl and David Bruns, Tietz Textbook of Clinical Chemistry and Molecular Diagnostics, Elsevier Saunders, 7th edition, 2015, pp 952-982
Wu, A., Tietz Clinical Guide to Laboratory Tests, W.B. Saunders Co., St. Louis MO, 4th Edition, 2006: 951-982
TCO₂, HCO₃ and BE (Base Excess) are derived parameters. Note:
20
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 |
| pH | 479 | 0.941 | 0.427 | 0.991 | 7.01 to 7.92 |
| pCO2 (mmHg) | 492 | 0.955 | 3.545 | 0.991 | 11 to 117 |
| pO2 (mmHg) | 506 | 0.992 | 5.093 | 0.996 | 6 to 685 |
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:
| Pooled Point-of-Care Site and CSL Data with Native Capillary Samples Only | |||||||
|---|---|---|---|---|---|---|---|
| Analyte | N | Range | |||||
| Min | Range | ||||||
| Max | MDL | Bias at MDL | 95% CI of Bias at MDL | TEa | |||
| pH | 171 | 7.36 | 7.59 | 7.30 | 0.002 | -0.015 to 0.020 | $\pm$ 0.04 |
| 7.35 | 0.005 | -0.006 to 0.016 | $\pm$ 0.04 | ||||
| 7.45 | 0.010 | 0.005 to 0.014 | $\pm$ 0.04 | ||||
| pO2 | |||||||
| (mmHg) | 167 | 52 | 105 | 30 | 6.1 | 1.3 to 11.6 | $\pm$ 9.0 |
| 45 | 5.1 | 2.0 to 8.6 | $\pm$ 9.0 | ||||
| 60 | 4.1 | 2.0 to 5.7 | $\pm$ 9.0 |
21
Clinical Testing
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 |
| pH | 189 | 0.935 | 0.494 | 0.975 | 7.07 to 7.89 |
| pO2 (mmHg) | 218 | 1.008 | 2.545 | 0.996 | 6 to 676 |
| Conclusion | |
|---|---|
| The technological and functional characteristics of the new GEM Premier | |
| 5000 as described above are substantially equivalent to that of the | |
| predicate device (GEM Premier 4000) for pH, pCO2, pO2. |
The analytical and clinical study results demonstrate that the GEM
Premier 5000 is safe and effective for its intended purpose and equivalent
in performance to the predicate device. |