Predicate Devices

GEM Premier 4000 K133407

Reference Devices

AI/ML (Artificial Intelligence / Machine Learning)

No
The summary describes a critical care blood gas analyzer with automated quality control features (iQM2), but there is no mention of AI or ML being used for analysis, interpretation, or any other function. The quality control system appears to be based on statistical process control, not AI/ML.

Therapeutic

No.
Explanation: The device is an in-vitro diagnostic device that provides quantitative measurements of blood parameters to aid in diagnosis, not to treat a condition.

Diagnostic

Yes

Explanation: The "Intended Use / Indications for Use" section explicitly states that the parameters measured by the device, along with derived parameters, "aid in the diagnosis of a patient's oxygen delivery capacity" and specifically mentions "aid in the diagnosis of carbon monoxide poisoning" and "determine different conditions of methemoglobinemia." This directly indicates its role in diagnosis.

SaMD (Software as a Medical Device)

No

The device description clearly outlines hardware components such as an "Analyzer" with a touch screen, a "GEM Premier 5000 PAK" which is a disposable cartridge containing sensors, an optical cell, solutions, a sampler, pump tubing, a valve, and a waste bag. These are physical components, not solely software.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

Intended Use: The intended use explicitly states that the device is used to "rapidly analyze heparinized whole blood samples" and provides "quantitative measurements" of various blood parameters. These measurements "aid in the diagnosis of a patient's oxygen delivery capacity" and are used for purposes like "detection of anemia," "diagnosis of carbon monoxide poisoning," and determining "different conditions of methemoglobinemia." These are all diagnostic purposes performed on biological samples in vitro (outside the body).
Device Description: The device description details the components used to perform these analyses on blood samples, including sensors, an optical cell, and solutions. This further supports its function as an in vitro diagnostic device.
Performance Studies: The performance studies describe various tests conducted on blood samples (aqueous controls, whole blood, capillary samples) to evaluate the device's accuracy, precision, linearity, and interference. These are typical studies performed for IVD devices to demonstrate their analytical performance.
Predicate Device: The mention of a predicate device (GEM Premier 4000, K133407) which is also a critical care blood gas analyzer, strongly suggests that the GEM Premier 5000 falls under the same regulatory classification as an IVD.

The device analyzes biological samples (whole blood) in vitro to provide information used for diagnostic purposes. This aligns perfectly with the definition of an In Vitro Diagnostic device.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

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 Hematocrit and Total Hemoglobin from venous and arterial heparinized whole blood, as well as quantitative measurements of O₂Hb, COHb, MetHb, HHb, sO₂ from venous, arterial and capillary heparinized whole blood. These parameters, along with derived parameters, aid in the diagnosis of a patient's oxygen delivery capacity.

Hematocrit (Hct) measurements in whole blood of the packed red cell volume of a blood sample are used to distinguish normal from abnormal states, such as anemia and erythrocytosis (an increase in the number of red cells).
Total Hemoglobin (tHb): Total hemoglobin measurements are used to measure the hemoglobin content of whole blood for the detection of anemia.
COHb: Carboxyhemoglobin measurements are used to determine the carboxyhemoglobin content of human blood as an aid in the diagnosis of carbon monoxide poisoning.
MetHb: Methemoglobin measurements are used to determine different conditions of methemoglobinemia.
HHb: Deoxyhemoglobin, as a fraction of total hemoglobin, is used in combination with oxyhemoglobin to measure oxygenation status.
O₂Hb: Oxyhemoglobin, as a fraction of total hemoglobin, is used in combination with deoxyhemoglobin to measure oxygenation status.
sO₂: Oxygen saturation, more specifically the ratio between the concentration of oxyhemoglobin and oxyhemoglobin plus deoxyhemoglobin, is used to measure oxygenation status.

Product codes

GKF, GHS, GKR, GLY

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 Hematocrit and Total Hemoglobin from venous and arterial heparinized whole blood, as well as quantitative measurements of O₂Hb, COHb, MetHb, HHb, sO2 from venous, arterial and capillary heparinized whole blood.

Key Components:

Analyzer: Employs a unique color touch screen and a simple set of menus and buttons for user interaction. The analyzer guides operators through the sampling process with simple, clear messages and prompts.
GEM Premier 5000 PAK (disposable, multi-use GEM PAK): Houses all required components necessary to operate the instrument once the cartridge is validated. These components include the sensors, CO-Ox 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.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Not Found

Indicated Patient Age Range

Not Found

Intended User / Care Setting

Health care professionals, clinical setting, central laboratory, point of health care delivery.

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

An internal 20-day precision study was performed on the GEM Premier 5000 with GEM System Evaluator and GEM Hematocrit. 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).

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).

An internal precision study was performed using four (4) or 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).

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 PAK (cartridges). Each site used the same lots of GEM System Evaluator (GSE) and GEM Hematocrit Evaluator (GHE), running each control level in triplicate, twice a day, for a total of 30 replicates per level (N=90 pooled).

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 analytes, micro mode (65 µL) for Hct, and tBili/CO-Ox mode (100 µL) mode for the CO-Ox fractions. 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.

LoB, LoQ were established using three (3) lots of GEM Premier 5000 PAKs (cartridges).

Eight (8) or nine (9) 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 or standard reference procedures (i.e. CNMetHb procedure - CLSI H15-A3 for tHb).

An interference study was conducted on the GEM Premier 5000.

An internal method comparison study was conducted using clinical samples to compare the GEM Premier 5000 to the GEM Premier 4000. Samples were altered as needed to cover the medical decision levels.

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. Three (3) external point-of-care (POC) sites and 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.

To support capillary claims, finger-stick samples were collected at an external POC site (N=52 native samples) and the IL internal Customer Simulation Laboratory (CSL) (N=100 native samples) with POC operators. The data from the native capillary samples (finger-stick samples) were pooled with contrived capillary samples prepared internally.

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

Internal Precision Study – Aqueous Controls:

Study Type: Internal 20-day precision study.
Sample Size: N=120 for each level/analyte combination.
Key Results: All results were within specification.

Internal Precision Study – GEM PAK (Cartridge) Process Control Solutions D and E:

Study Type: Internal 20-day precision study.
Sample Size: N=120 per analyte/per level.
Key Results: All results were within specification.

Internal Precision Study – Whole Blood:

Study Type: Internal precision study.
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.
Sample Size: N=90 pooled per level.
Key Results: All results at all sites were within specification.

External Precision – Whole Blood:

Study Type: External precision study to evaluate whole blood precision in central laboratory and point-of-care (POC) settings.
Sample Size: POC-All N=126 for Hct & tHb (Normal Mode), N=90 for O2Hb & sO2 (Normal Mode), N=114 for O2Hb & sO2 (tBili/CO-Ox Mode), N=126 for COHb (Normal Mode), N=114 for COHb (tBili/CO-Ox Mode), N=45 for MetHb (Normal Mode), N=54 for MetHb (tBili/CO-Ox Mode), N=54 for HHb (Normal Mode), N=36 for HHb (tBili/CO-Ox Mode). Lab-All N=96 for Hct, N=93 for tHb, N=90 for O2Hb, N=96 for COHb, N=72 for HHb.
Key Results: Precision results summarized in tables.

LoB, LoD and LoQ:

Study Type: Limit of Blank (LoB), Limit of Detection (LoD), and Limit of Quantitation (LoQ) determination.
Sample Size: Not explicitly stated beyond "three (3) lots of GEM Premier 5000 PAKs (cartridges)".
Key Results: LoB, LoD, and LoQ values established for each analyte.

Linearity:

Study Type: Linearity study.
Sample Size: 9 samples/each of 9 levels for Hct, tHb, COHb, MetHb, HHb. 9 samples/each of 8 levels for O2Hb. 120 samples/each of 5 levels for COHb and MetHb (additional low-end against predicate).
Key Results: Slopes, intercepts, and R² values provided, demonstrating linearity across tested ranges. Linearity supports the claimed reportable ranges.

Analytical Specificity:

Study Type: Interference study.
Key Results: Listed substances with no observed interference. Listed substances that demonstrated interference with hematocrit and CO-Oximetry results, along with concentrations, bias, and impact.

Internal Method Comparison:

Study Type: Method comparison study using clinical samples comparing GEM Premier 5000 to GEM Premier 4000.
Sample Size: N=376 for Hct & tHb, N=373 for O2Hb & SO2, N=374 for COHb, N=270 for MetHb, N=195 for HHb.
Key Results: Slopes, intercepts, and R² values provided. All parameter levels passed specification for all sample modes.

Whole Blood Performance at Medical Decision Levels:

Study Type: Assessment of performance at medical decision levels using combined data from internal method comparison and precision studies.
Key Results: Total Error Observed values calculated for each analyte at medical decision levels, demonstrating performance against specifications.

Clinical Testing:

Study Type: Method comparison study comparing GEM Premier 5000 to GEM Premier 4000 in POC setting using heparinized whole blood patient samples. Also includes capillary claims support.
Sample Size:
- Pooled Point-of-Care Site and CSL Data - Normal Mode (with Syringe Samples): N=490 for Hct, N=496 for tHb & O2Hb & sO2, N=485 for COHb, N=297 for MetHb, N=258 for HHb.
- Pooled Point-of-Care Site and CSL Data with Native Capillary Samples Only: N=152 for O2Hb & sO2, N=151 for COHb & HHb, N=180 for COHb, N=98 for MetHb. (Insufficient native samples for certain MDLs).
- Pooled Point-of-Care Site and CSL Data with Additional Contrived Capillary Results: N=182 for O2Hb, N=180 for COHb & sO2, N=98 for MetHb, N=181 for HHb.
Key Results:
- Normal Mode (Syringe Samples): Regression analysis results (slope, intercept, r, sample range) for all analytes showed strong correlation.
- Native Capillary Samples: Observed total error at medical decision levels provided. Some MDLs had insufficient native samples.
- Pooled Contrived Capillary Results: Regression analysis results (slope, intercept, r, sample range) for O2Hb, COHb, MetHb, HHb, sO2 showed strong correlation.

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Key metrics presented are in terms of precision (SD, %CV), linearity (Slope, Intercept, R²), bias, and total error. Specificity is assessed through interference studies. No sensitivity, specificity, PPV, or NPV metrics are provided as the device is not a diagnostic test in the typical sense for these metrics.

Predicate Device(s)

GEM Premier 4000 K133407

Reference Device(s)

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information

Not Found

Regulation Number and Section

§ 864.5600 Automated hematocrit instrument.

(a)
Identification. An automated hematocrit instrument is a fully automated or semi-automated device which may or may not be part of a larger system. This device measures the packed red cell volume of a blood sample to distinguish normal from abnormal states, such as anemia and erythrocytosis (an increase in the number of red cells).(b)
Classification. Class II (performance standards).

Summary

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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: K160415

Trade/Device Name: GEM Premier 5000 (Measured Parameters: Hematocrit, Total Hemoglobin, Carboxyhemoglobin, Methemoglobin, Deoxyhemoglobin, Oxyhemoglobin, Oxygen Saturation) Regulation Number: 21 CFR 864.5600 Regulation Name: Automated hematocrit instrument Regulatory Class: Class II Product Code: GKF, GHS, GKR, GLY Dated: 12/7/2016 Received: 12/8/2016

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

1

as set forth in the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the 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 regulation (21 CFR Part 801), 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/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 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,

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) K160415

Device Name

GEM Premier 5000 (Measured Parameters: Hemoglobin, Carboxyhemoglobin, Methemoglobin, Deoxyhemoglobin, Oxyhemoglobin, Oxygen Saturation)

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 Hematocrit and Total Hemoglobin from venous and arterial heparinized whole blood, as well as quantitative measurements of O2Hb. COHb. MetHb. HHb. sO2 from venous, arterial and capillary heparinized whole blood. These parameters, along with derived parameters, aid in the diagnosis of a patient's oxygen delivery capacity.

Hematocrit (Hct) measurements in whole blood of the packed red cell volume of a blood sample are used to distinguish normal from abnormal states, such as anemia and erythrocytosis (an increase in the number of red cells).
Total Hemoglobin (tHb): Total hemoglobin measure the hemoglobin content of whole blood for the detection of anemia.
· COHb: Carboxyhemoglobin measurements are used to determine the carboxyhemoglobin content of human blood as an aid in the diagnosis of carbon monoxide poisoning.
· MetHb: Methemoglobin measurements are used to determine different conditions of methemoglobinemia.

· HHb: Deoxyhemoglobin, as a fraction of total hemoglobin, is used in combination with oxyhemoglobin to measure oxygenation status.

· O2Hb: Oxyhemoglobin, as a fraction of total hemoglobin, is used in combination with deoxyhemoglobin to measure oxygenation status.

· sO2: Oxygen saturation, more specifically the ratio between the concentration of oxyhemoglobin and oxyhemoglobin plus deoxyhemoglobin, is used to measure oxygenation status.

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)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

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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 8, 2016
------------------	------------------

| Device Trade Name | GEM Premier 5000
(Measured Parameters: Hematocrit, Total Hemoglobin,
Carboxyhemoglobin, Methemoglobin, Deoxyhemoglobin,
Oxyhemoglobin, Oxygen Saturation) |

-------------------	--------------------------------------------------------------------------------------------------------------------------------------------------------------------

Predicate Device	GEM Premier 4000	K133407
------------------	------------------	---------

Regulatory Information
GEM Premier 5000
Analyte	Regulation
Section	Regulatory Description	Class	Product
Code	Panel
Hematocrit	864.5600	Automated hematocrit instrument	II	GKF	81
CO-Oximetry	864.7425	Carboxyhemoglobin assay	II	GHS
	864.5620	Automated hemoglobin system	II	GKR
	864.7500	Whole blood hemoglobin assays	II	GLY

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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 Hematocrit and Total Hemoglobin from venous and arterial heparinized whole blood, as well as quantitative measurements of O₂Hb, COHb, MetHb, HHb, sO2 from venous, arterial and capillary 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, |

*sO2 = Ratio between the concentration of oxyhemoglobin plus deoxyhemoglobin plus deoxyhemoglobin.

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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 Hematocrit and Total Hemoglobin
from venous and arterial heparinized whole blood, as well as
quantitative measurements of O₂Hb, COHb, MetHb, HHb, sO₂ from
venous, arterial and capillary heparinized whole blood. These
parameters, along with derived parameters, aid in the diagnosis of
a patient's oxygen delivery capacity.
	• Hematocrit (Hct) measurements in whole blood of the packed
red cell volume of a blood sample are used to distinguish
normal from abnormal states, such as anemia and
erythrocytosis (an increase in the number of red cells).
	• Total Hemoglobin (tHb): Total hemoglobin measurements are
used to measure the hemoglobin content of whole blood for
the detection of anemia.
	• COHb: Carboxyhemoglobin measurements are used to
determine the carboxyhemoglobin content of human blood as
an aid in the diagnosis of carbon monoxide poisoning.
	• MetHb: Methemoglobin measurements are used to determine
different conditions of methemoglobinemia.
	• HHb: Deoxyhemoglobin, as a fraction of total hemoglobin, is
used in combination with oxyhemoglobin to measure
oxygenation status.
	• O₂Hb: Oxyhemoglobin, as a fraction of total hemoglobin, is
used in combination with deoxyhemoglobin to measure
oxygenation status.
	• sO₂: Oxygen saturation, more specifically the ratio between the
concentration of oxyhemoglobin and oxyhemoglobin plus
deoxyhemoglobin, is used to measure oxygenation status.

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 Hematocrit and CO-Oximetry:
Item	Predicate Device	New Device
Trade Name	GEM Premier 4000	GEM Premier 5000
510(k) No.	K133407	K160415
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.
NOTE: The GEM Premier 4000 also reports SO₂ results as a ratio result.	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 Hematocrit and Total Hemoglobin from venous and arterial heparinized whole blood, as well as quantitative measurements of O₂Hb, COHb, MetHb, HHb, sO₂ from venous, arterial and capillary heparinized whole blood. These parameters, along with derived parameters, aid in the diagnosis of a patient's oxygen delivery capacity. Hematocrit (Hct) measurements in whole blood of the packed red cell volume of a blood sample are used to distinguish normal from abnormal states, such as anemia and erythrocytosis (an increase in the number of red cells). Total Hemoglobin (tHb): Total hemoglobin measurements are used to measure the hemoglobin content of whole blood for the detection of anemia. COHb: Carboxyhemoglobin measurements are used to determine the carboxyhemoglobin content of human blood as an aid in the diagnosis of carbon monoxide poisoning. MetHb: Methemoglobin measurements are used to determine different conditions of methemoglobinemia. HHb: Deoxyhemoglobin, as a fraction of total hemoglobin, is used in combination with oxyhemoglobin to measure oxygenation status. O₂Hb: Oxyhemoglobin, as a fraction of total hemoglobin, is used in combination with deoxyhemoglobin to measure oxygenation status. sO₂: Oxygen saturation, more specifically the ratio between the concentration of oxyhemoglobin and oxyhemoglobin plus deoxyhemoglobin, is used to measure oxygenation status.

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Substantial Equivalency (Cont.)
Item	Predicate Device		New Device
Trade Names	GEM Premier 4000	K133407	GEM Premier 5000	K160415
Intended User	Central Laboratory and Point-of-Care		Same
Sample Type	Heparinized Whole Blood		Hct, tHb	Arterial or venous heparinized whole blood
			O₂Hb, COHb, MetHb, HHb, SO₂	Arterial, venous or capillary heparinized whole blood
Hemoglobin Measurement	Spectrophotometry: tHb, O₂Hb, COHb, MetHb, HHb, SO₂		Same
Hematocrit Measurement	Conductivity		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
Substantial Equivalency (Cont.)
Item	Predicate Device	New Device
Trade Name	GEM Premier 4000 K133407	GEM Premier 5000 K160415
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
	Hematocrit	15 to 72%	15 to 72%
	tHb	3.0 to 23.0 g/dL	3.0 to 23.0 g/dL
	O₂Hb	0.0 to 98.0%	0.7 to 100.0%
	COHb	0.0 to 99.0%	0.3 to 75.0%
	MetHb	0.0 to 28.0%	0.7 to 30.0%
	HHb	0.0 to 96.0%	1.0 to 100.0%
	SO₂	0.0 to 100.0%	0.7 to 100.0%

9

10

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 and GEM Hematocrit. 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 | tHb
(g/dL) | Level 1 | 20.8 | 120 | 0.14 | 0.7% | 0.16 | 0.8% |
| | | Level 2 | 14.6 | 120 | 0.13 | 0.9% | 0.18 | 1.2% |
| | | Level 3 | 7.8 | 120 | 0.13 | 1.7% | 0.16 | 2.1% |
| | O2Hb
(%) | Level 1 | 37.3 | 120 | 0.00 | 0.0% | 0.00 | 0.0% |
| | | Level 2 | 73.7 | 120 | 0.04 | 0.1% | 0.05 | 0.1% |
| | | Level 3 | 93.0 | 120 | 0.04 | 0.0% | 0.05 | 0.1% |
| | COHb
(%) | Level 1 | 31.7 | 120 | 0.03 | 0.1% | 0.04 | 0.1% |
| | | Level 2 | 16.8 | 120 | 0.05 | 0.3% | 0.06 | 0.3% |
| | | Level 3 | 3.1 | 120 | 0.07 | 2.3% | 0.09 | 2.8% |
| | MetHb
(%) | Level 1 | 8.3 | 120 | 0.05 | 0.6% | 0.06 | 0.7% |
| | | Level 2 | 2.6 | 120 | 0.06 | 2.5% | 0.08 | 3.1% |
| | | Level 3 | Not Applicable | | | | | |
| | HHb
(%) | Level 1 | 22.6 | 120 | 0.05 | 0.2% | 0.05 | 0.2% |
| | | Level 2 | 6.9 | 120 | 0.05 | 0.7% | 0.06 | 0.9% |
| | | Level 3 | 3.3 | 120 | 0.09 | 2.6% | 0.11 | 3.2% |
| | sO2
(%) | Level 1 | 62.2 | 120 | 0.05 | 0.1% | 0.05 | 0.1% |
| | | Level 2 | 91.4 | 120 | 0.06 | 0.1% | 0.07 | 0.1% |
| | | Level 3 | 96.6 | 120 | 0.09 | 0.1% | 0.11 | 0.1% |
| GEM
Hematocrit
Evaluator | Hct
(%) | Level 1 | 21 | 120 | 0.2 | 1.2% | 0.3 | 1.3% |
| | | Level 2 | 41 | 120 | 0.2 | 0.6% | 0.2 | 0.6% |
| | | Level 3 | 65 | 120 | 0.4 | 0.6% | 0.4 | 0.6% |

11

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
PCS D	Hct
(%)	27	120	0.2	0.6%
PCS E	Hct
(%)	37	120	0.0	0.1%
PCS D	tHb
(g/dL)	7.4	120	0.05	0.6%
PCS E	tHb
(g/dL)	16.5	120	0.04	0.2%
PCS D	O2Hb
(%)	79.9	120	0.13	0.2%
PCS E	O2Hb
(%)	49.8	120	0.06	0.1%
PCS D	COHb
(%)	4.0	120	0.11	2.7%
PCS E	COHb
(%)	10.1	120	0.04	0.4%
PCS D	MetHb
(%)	3.9	120	0.12	3.0%
PCS E	MetHb
(%)	8.0	120	0.05	0.6%
PCS D	HHb
(%)	12.2	120	0.35	2.9%
PCS E	HHb
(%)	32.1	120	0.14	0.4%
PCS D	sO2
(%)	86.8	120	0.35	0.4%
PCS E	sO2
(%)	60.8	120	0.13	0.2%

12

Internal Precision Study – Whole Blood

In accordance with CLSI EP05-A3, an internal precision study was performed using four (4) or 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
tBili/CO-Ox Mode 100 µL .

NOTE: Capillary not claimed for Hct and tHb on the GEM Premier 5000.

| Analyte | Mode | Level | Mean | N | Within
Run
SD | Within
Run
%CV | Total SD | Total
%CV |
|---------------|---------------------|-------|------|-----|---------------------|----------------------|----------|--------------|
| Hct
(%) | Normal
Mode | 1 | 18 | 120 | 0.3 | 1.9% | 0.4 | 2.5% |
| | | 2 | 33 | 120 | 0.3 | 1.0% | 0.6 | 1.9% |
| | | 3 | 45 | 120 | 0.5 | 1.0% | 0.8 | 1.8% |
| | | 4 | 57 | 120 | 0.6 | 1.1% | 1.0 | 1.8% |
| | | 5 | 65 | 120 | 0.7 | 1.1% | 0.9 | 1.4% |
| tHb
(g/dL) | Normal
Mode | 1 | 6.2 | 120 | 0.04 | 0.6% | 0.07 | 1.1% |
| | | 2 | 11.2 | 120 | 0.04 | 0.4% | 0.14 | 1.3% |
| | | 3 | 15.1 | 120 | 0.05 | 0.3% | 0.20 | 1.3% |
| | | 4 | 18.8 | 120 | 0.06 | 0.3% | 0.23 | 1.2% |
| | | 5 | 21.7 | 120 | 0.08 | 0.4% | 0.23 | 1.1% |
| Analyte | Mode | Level | Mean | N | Within
Run
SD | Within
Run
%CV | Total SD | Total
%CV |
| O₂Hb
(%) | Normal
Mode | 1 | 9.1 | 120 | 0.21 | 2.4% | 0.22 | 2.4% |
| | | 2 | 38.4 | 120 | 0.26 | 0.7% | 0.26 | 0.7% |
| | | 3 | 77.0 | 120 | 0.20 | 0.3% | 0.21 | 0.3% |
| | | 4 | 90.6 | 120 | 0.21 | 0.2% | 0.23 | 0.3% |
| | | 5 | 96.4 | 120 | 0.18 | 0.2% | 0.20 | 0.2% |
| O₂Hb
(%) | tBili/CO-Ox
Mode | 1 | 8.7 | 120 | 0.20 | 2.3% | 0.25 | 2.9% |
| | | 2 | 38.0 | 120 | 0.27 | 0.7% | 0.29 | 0.8% |
| | | 3 | 76.5 | 120 | 0.23 | 0.3% | 0.34 | 0.4% |
| | | 4 | 90.2 | 120 | 0.22 | 0.2% | 0.33 | 0.4% |
| | | 5 | 96.0 | 120 | 0.21 | 0.2% | 0.31 | 0.3% |
| COHb
(%) | Normal
Mode | 1 | 1.6 | 120 | 0.14 | 8.6% | 0.22 | 13.4% |
| | | 2 | 5.6 | 120 | 0.16 | 2.9% | 0.21 | 3.7% |
| | | 3 | 15.3 | 120 | 0.17 | 1.1% | 0.23 | 1.5% |
| | | 4 | 30.3 | 120 | 0.21 | 0.7% | 0.26 | 0.9% |
| | | 5 | 64.3 | 120 | 0.26 | 0.4% | 0.31 | 0.5% |
| COHb
(%) | tBili/CO-Ox
Mode | 1 | 1.8 | 120 | 0.18 | 9.9% | 0.29 | 15.6% |
| | | 2 | 5.8 | 120 | 0.16 | 2.7% | 0.24 | 4.2% |
| | | 3 | 15.4 | 120 | 0.20 | 1.3% | 0.26 | 1.7% |
| | | 4 | 30.4 | 120 | 0.23 | 0.8% | 0.31 | 1.0% |
| | | 5 | 64.3 | 120 | 0.31 | 0.5% | 0.46 | 0.7% |
| MetHb
(%) | Normal
Mode | 1 | 5.0 | 120 | 0.17 | 3.4% | 0.22 | 4.4% |
| | | 2 | 9.9 | 120 | 0.19 | 1.9% | 0.21 | 2.1% |
| | | 3 | 14.5 | 120 | 0.27 | 1.9% | 0.29 | 2.0% |
| | | 4 | 25.5 | 120 | 0.28 | 1.1% | 0.32 | 1.2% |
| MetHb
(%) | tBili/CO-Ox
Mode | 1 | 5.1 | 120 | 0.16 | 3.2% | 0.19 | 3.7% |
| | | 2 | 10.0 | 120 | 0.21 | 2.1% | 0.23 | 2.2% |
| | | 3 | 14.8 | 120 | 0.34 | 2.3% | 0.36 | 2.4% |
| | | 4 | 25.6 | 120 | 0.21 | 0.8% | 0.21 | 0.8% |
| Analyte | Mode | Level | Mean | N | Within
Run SD | Within
Run %CV | Total SD | Total
%CV |
| HHb
(%) | Normal
Mode | 1 | 6.6 | 120 | 0.23 | 3.5% | 0.30 | 4.6% |
| | Normal
Mode | 2 | 20.5 | 120 | 0.24 | 1.2% | 0.42 | 2.1% |
| | Normal
Mode | 3 | 59.9 | 120 | 0.29 | 0.5% | 0.46 | 0.8% |
| | Normal
Mode | 4 | 90.0 | 120 | 0.22 | 0.2% | 0.32 | 0.4% |
| HHb
(%) | tBili/CO-Ox
Mode | 1 | 6.8 | 120 | 0.26 | 3.8% | 0.51 | 7.4% |
| | tBili/CO-Ox
Mode | 2 | 20.9 | 120 | 0.25 | 1.2% | 0.48 | 2.3% |
| | tBili/CO-Ox
Mode | 3 | 60.2 | 120 | 0.29 | 0.5% | 0.60 | 1.0% |
| | tBili/CO-Ox
Mode | 4 | 90.1 | 120 | 0.23 | 0.3% | 0.53 | 0.6% |
| sO2
(%) | Normal
Mode | 1 | 9.2 | 120 | 0.21 | 2.3% | 0.21 | 2.3% |
| | Normal
Mode | 2 | 39.0 | 120 | 0.27 | 0.7% | 0.30 | 0.8% |
| | Normal
Mode | 3 | 79.0 | 120 | 0.23 | 0.3% | 0.37 | 0.5% |
| | Normal
Mode | 4 | 93.2 | 120 | 0.24 | 0.3% | 0.29 | 0.3% |
| | Normal
Mode | 5 | 98.7 | 120 | 0.25 | 0.2% | 0.39 | 0.4% |
| sO2
(%) | tBili/CO-Ox
Mode | 1 | 8.8 | 120 | 0.19 | 2.2% | 0.25 | 2.8% |
| | tBili/CO-Ox
Mode | 2 | 38.7 | 120 | 0.27 | 0.7% | 0.36 | 0.9% |
| | tBili/CO-Ox
Mode | 3 | 78.6 | 120 | 0.24 | 0.3% | 0.43 | 0.6% |
| | tBili/CO-Ox
Mode | 4 | 92.9 | 120 | 0.26 | 0.3% | 0.50 | 0.5% |
| | tBili/CO-Ox
Mode | 5 | 98.5 | 120 | 0.27 | 0.3% | 0.35 | 0.4% |

13

Internal Precision Study – Whole Blood (Cont.)

14

Internal Precision Study – Whole Blood (Cont.)

15

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) stess 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 PAK (cartidges). Each site used the same lots of GEM System Evaluator (GSE) and GEM Hematorit Evaluator (GHE), running each control level in triplicate, twice a datal of 30 replicates per level (N=90 pooled). All results at all sites were within specification.

	Pooled Multi-Site POC Data
Analyte	Material/
Level		Insert
Range		SD/CV
Spec		Repeatability		Between-Run		Between-Day		Between-Site		Reproducibility
		N		Target		Mean	SD	%CV	SD	%CV	SD	%CV	SD	%CV	SD	%CV
Hct
(%)	GHE 1	90	19-23	21	2	21	0.0	0.0%	0.0	0.0%	0.0	0.0%	0.0	0.0%	0.0	0.0%
Hct
(%)	GHE 2	90	38-44	41	2	41	0.0	0.0%	0.0	0.0%	0.0	0.0%	0.0	0.0%	0.0	0.0%
Hct
(%)	GHE 3	90	62-70	66	2	66	0.3	0.4%	0.1	0.1%	0.2	0.4%	0.4	0.6%	0.6	0.9%
tHb
(g/dL)	GSE 1	90	19.5-21.9	20.7	0.5	20.7	0.14	0.7%	0.00	0.0%	0.05	0.2%	0.07	0.3%	0.16	0.8%
tHb
(g/dL)	GSE 2	90	13.8-15.4	14.6	0.35	14.5	0.10	0.7%	0.00	0.0%	0.05	0.3%	0.07	0.5%	0.13	0.9%
tHb
(g/dL)	GSE 3	90	7.0-8.4	7.7	0.35	7.7	0.10	1.3%	0.02	0.3%	0.03	0.4%	0.01	0.1%	0.10	1.4%
O₂Hb
(%)	GSE 1	90	36.3-40.3	38.3	1.5	37.3	0.01	0.0%	0.00	0.0%	0.00	0.0%	0.00	0.0%	0.01	0.0%
O₂Hb
(%)	GSE 2	90	72.6-76.6	74.6	1.5	73.7	0.04	0.0%	0.00	0.0%	0.00	0.0%	0.03	0.0%	0.05	0.1%
O₂Hb
(%)	GSE 3	90	92.0-96.0	94.0	1.5	93.0	0.03	0.0%	0.00	0.0%	0.02	0.0%	0.01	0.0%	0.04	0.0%

16

| 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 | | |
| COHb
(%) | GSE 1 | 90 | 28.7-32.7 | 30.7 | 1.0 | 31.7 | 0.04 | 0.1% | 0.02 | 0.1% | 0.00 | 0.0% | 0.02 | 0.1% | 0.05 | 0.2% | | |
| COHb
(%) | GSE 2 | 90 | 13.5-17.5 | 15.5 | 1.0 | 16.8 | 0.04 | 0.2% | 0.00 | 0.0% | 0.01 | 0.1% | 0.01 | 0.1% | 0.04 | 0.3% | | |
| COHb
(%) | GSE 3 | 90 | 0.0-4.0 | 2.0 | 1.0 | 3.2 | 0.06 | 1.9% | 0.00 | 0.0% | 0.03 | 0.8% | 0.01 | 0.4% | 0.07 | 2.1% | | |
| MetHb
(%) | GSE 1 | 90 | 7.8-11.8 | 9.8 | 1.0 | 8.3 | 0.05 | 0.6% | 0.00 | 0.0% | 0.00 | 0.0% | 0.02 | 0.3% | 0.06 | 0.7% | | |
| MetHb
(%) | GSE 2 | 90 | 2.2-6.2 | 4.2 | 1.0 | 2.5 | 0.04 | 1.7% | 0.02 | 0.6% | 0.02 | 0.7% | 0.04 | 1.5% | 0.06 | 2.4% | | |
| MetHb
(%) | GSE 3 | Not Applicable | | | | | | | | | | | | | | | | |
| HHb
(%) | GSE 1 | 90 | 19.2-23.2 | 21.2 | 1.5 | 22.6 | 0.04 | 0.2% | 0.00 | 0.0% | 0.01 | 0.0% | 0.04 | 0.2% | 0.06 | 0.2% | | |
| HHb
(%) | GSE 2 | 90 | 3.7-7.7 | 5.7 | 1.5 | 6.9 | 0.05 | 0.7% | 0.01 | 0.2% | 0.00 | 0.0% | 0.03 | 0.5% | 0.06 | 0.8% | | |
| HHb
(%) | GSE 3 | 90 | 0.0-4.0 | 2.0 | 1.5 | 3.4 | 0.06 | 1.9% | 0.02 | 0.5% | 0.03 | 0.8% | 0.03 | 0.8% | 0.08 | 2.3% | | |
| SO2
(%) | GSE 1 | 90 | | | 1.5 | 62.2 | 0.04 | 0.1% | 0.00 | 0.0% | 0.01 | 0.0% | 0.04 | 0.1% | 0.06 | 0.1% | | |
| SO2
(%) | GSE 2 | 90 | NA | NA | 1.5 | 91.4 | 0.05 | 0.1% | 0.01 | 0.0% | 0.00 | 0.0% | 0.04 | 0.0% | 0.07 | 0.1% | | |
| SO2
(%) | GSE 3 | 90 | | | 1.5 | 96.5 | 0.06 | 0.1% | 0.02 | 0.0% | 0.03 | 0.0% | 0.03 | 0.0% | 0.08 | 0.1% | | |

Reproducibility Study with Aqueous Controls – Point-of-Care (POC) Setting (Cont.)

17

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 analytes, micro mode (65 µL) for Hct, and tBili/CO-Ox mode (100 µL) mode for the CO-Ox fractions. 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.

Analyte	Mode	Site	N	Mean	Within Sample SD
Hct
(%)	Normal
Mode	POC1	54	27	0.3
		POC2	42	26	0.6
		POC3	30	28	0.7
		POC-All	126	27	0.5
		CSL	36	44	0.5
		Lab1	30	28	0.4
		Lab2	30	રે રેણવાડી તેમ જ દિવસ તાલુકામાં આવેલું એક ગામનાં મુખ્યત્વે ખેત-ઉપયોગના મધ્યમાં આવેલું એક ગામનાં મુખ્યત્વે ખેત-ઉપયોગના મધ્યમાં આવેલું એક ગામનાં મુખ્યત્વે ખેત-ઉપયોગના મધ્યમાં	0.5
		Lab-All	ರಿಲ	36	0.5

The precision results are summarized below:

18

Analyte	Mode	Site	N	Mean	Within Sample SD
tHb
(g/dL)	Normal
Mode	POC1	54	8.9	0.10
		POC2	42	9.4	0.15
		POC3	30	9.6	0.15
		POC-All	126	9.2	0.13
		CSL	33	13.5	0.05
		Lab1	30	9.5	0.07
		Lab2	30	11.5	0.05
		Lab-All	93	11.6	0.06
O₂Hb
(%)	Normal
Mode	POC1	54	86.5	0.57
		POC2	42	93.2	0.31
		POC3	30	94.2	0.48
		POC-All	126	90.6	0.48
		CSL	30	76.7	0.27
		Lab1	30	81.4	0.73
		Lab2	30	81.7	0.65
		Lab-All	90	79.9	0.59
O₂Hb
(%)	tBili/
CO-Ox
Mode	POC1	45	91.2	1.00
		POC2	39	88.5	0.49
		POC3	30	97.0	0.31
		POC-All	114	91.8	0.71
		CSL	30	77.2	0.30
		Lab1	30	74.6	0.49
		Lab2	30	87.6	0.96
		Lab-All	90	79.8	0.65
Analyte	Mode	Site	N	Mean	Within Sample SD
COHb (%)	Normal Mode	POC1	54	2.6	0.31
		POC2	42	1.8	0.19
		POC3	30	1.7	0.19
		POC-All	126	2.1	0.25
		CSL	36	3.3	0.15
		Lab1	30	1.6	0.16
		Lab2	30	1.3	0.16
		Lab-All	96	2.2	0.16
COHb (%)	tBili/
CO-Ox Mode	POC1	45	2.6	0.32
		POC2	39	1.9	0.21
		POC3	30	1.6	0.20
		POC-All	114	2.1	0.26
		CSL	36	3.3	0.10
		Lab1	30	1.4	0.19
		Lab2	30	1.6	0.18
		Lab-All	96	2.2	0.16
MetHb (%)	Normal Mode	POC1	9	1.6	0.22
		POC2	36	1.2	0.16
		POC-All	45	1.3	0.17
	tBili/
CO-Ox Mode	POC1	21	1.3	0.25
		POC2	33	1.5	0.27
		POC-All	54	1.4	0.27
Analyte	Mode	Site	N	Mean	Within Sample SD
HHb
(%)	Normal
Mode	POC1	24	23.1	0.84
		POC2	15	10.0	0.41
		POC3	15	6.7	0.53
		POC-All	54	13.3	0.66
		CSL	30	21.1	0.34
		Lab1	27	18.4	0.69
		Lab2	15	32.6	0.81
		Lab-All	72	24.0	0.60
	tBili/
CO-Ox
Mode	POC1	15	15.4	1.63
		POC2	21	14.7	0.58
		POC-All	36	15.0	1.14
		CSL	30	20.5	0.30
		Lab1	24	29.2	1.32
		Lab2	21	14.9	0.60
		Lab-All	75	21.5	0.80
	sO2
(%)	Normal
Mode	POC1	54	89.4
			POC2	42	96.0
			POC3	30	96.3
			POC-All	126	93.2
		CSL	30	78.5	0.34
		Lab1	30	83.0	0.70
		Lab2	30	83.3	0.61
		Lab-All	90	81.6	0.57
	tBili/
CO-Ox
Mode	POC1	45	94.5	1.04
			POC2	39	91.5
			POC3	30	99.1
			POC-All	114	94.7
		CSL	30	79.1	0.30
		Lab1	30	76.2	0.55
		Lab2	30	89.4	1.06
		Lab-All	90	81.6	0.71

External Precision – Whole Blood (Cont.)

19

External Precision – Whole Blood (Cont.)

20

External Precision – Whole Blood (Cont.)

21

LoB, LoD and LoQ

In accordance with CLSI EP17-A2, LoB, LoQ were established using three (3) lots of GEM Premier 5000 PAKs (cartridges).

Analyte	LoB	LoD	LoQ
Hematocrit (%)	4	4	7
Total Hemoglobin (g/dL)	0.2	0.3	1.3
O2Hb (%)	0.5	0.7	0.7
COHb (%)	0.1	0.3	0.3
MetHb (%)	0.4	0.7	0.7
HHb (%)	0.5	1.0	1.0

Following are the combined data results for LoB, LoD and LoQ:

Linearity

In accordance with CLSI EP06-A, eight (8) or nine (9) 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 or standard reference procedures (i.e. CNMetHb procedure - CLSI H15-A3 for tHb).

NOTE: Combined data from limit of quantitation (LOQ) and linearity studies were used to support lower limit of the claimed reportable range.

| Analyte | # of
Levels | N per
Level | Slope | Intercept | R² | Tested
Range | Reportable
Range |
|---------------|----------------|----------------|-------|-----------|-------|-----------------|---------------------|
| Hct
(%) | 9 | 9 | 0.970 | 1.904 | 0.998 | 7 to 82 | 15 to 72 |
| tHb
(g/dL) | 9 | 9 | 1.015 | 0.130 | 0.999 | 2.1 to 27.0 | 3.0 to 23.0 |
| O₂Hb
(%) | 8 | 9 | 1.002 | 0.918 | 1.000 | 0.3 to 99.3 | 0.7 to 100.0 |
| COHb
(%)* | 8 | 9 | 1.016 | 1.532 | 1.000 | 7.4 to 98.5 | 0.3 to 75.0 |
| | 5 | 120 | 1.004 | -0.109 | 1.000 | -0.08 to 10.2 | |
| MetHb
(%)* | 9 | 9 | 1.035 | 0.029 | 1.000 | 3.3 to 38.9 | 0.7 to 30.0 |
| | 5 | 120 | 0.988 | -0.149 | 1.000 | 0.3 to 9.9 | |
| HHb
(%) | 8 | 9 | 1.004 | -0.384 | 1.000 | -0.01 to 99.6 | 1.0 to 100.0 |

*Additional results at the low-end against the predicate device.

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 hematocrit and CO-Oximetry results:

Substance	Concentration	Tested analytes with no observed interference
Bilirubin	20 mg/dL	tHb/Hb fractions and sO2
Biliverdin	4 mg/dL	tHb/Hb fractions and sO2
Evans Blue	10 mg/L	tHb/Hb fractions and sO2
Fetal Hemoglobin	78%	tHb/Hb fractions and sO2
Indocyanine Green	10 mg/L	tHb/Hb fractions and sO2
Leukocytes	44.43 x 10³/μL	Hematocrit
Methylene Blue	20 mg/L	tHb/Hb fractions and sO2
Platelets	785.0 x 10³/μL	Hematocrit
Sulfhemoglobin	10%	tHb/Hb fractions and sO2
Turbidity (Intralipid)	1% or 2006
mg/dL	Hematocrit, tHb/Hb fractions and sO2

The table below lists substances that demonstrated interference with hematocrit results causing a clinically significant error (TEa) and the concentration of the interfering substance, as well as the bias and its direction (positive / negative):

| Interfering
Substance | Affected
Analyte | Analyte
Concentration | Interfering
Concentration
Tested | Bias
Observed
(Mean) | Lowest
Interfering
Concentration
with Analyte
Impact | Bias Observed
at the Lowest
Concentration |
|--------------------------|---------------------|--------------------------|----------------------------------------|----------------------------|------------------------------------------------------------------|-------------------------------------------------|
| Albumin | Hematocrit | 30% | 45.00 g/L | +4% | 43.92 g/L | +4% |
| | | 62% | 60.00 g/L | +5% | 49.90 g/L | +4% |
| Interfering
Substance | Affected
Analyte | Analyte
Concentration | Interfering
Concentration
Tested | Bias
Observed
(Mean) | Lowest
Interfering
Concentration
with Analyte
Impact | Bias Observed
at the Lowest
Concentration |
| Cyanocobalamin | tHb | 10.2 g/dL | 0.53 g/L* | +0.7 g/dL | 0.45 g/L |