Stat Profile Prime Plus Analyzer System

K180186 · Nova Biomedical Corporation · GGZ · Aug 23, 2018 · Hematology

Device Facts

• Record ID: K180186
• Device Name: Stat Profile Prime Plus Analyzer System
• Applicant: Nova Biomedical Corporation
• Product Code: GGZ · Hematology
• Decision Date: Aug 23, 2018
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 864.7500
• Device Class: Class 2

Indications for Use

The Stat Profile® Prime Plus Analyzer System is indicated for use by healthcare professionals in clinical laboratory settings for quantitative determination of Hematocrit, Oxygen Saturation, Total Hemoglobin, Oxyhemoglobin, Carboxyhemoglobin, Methemoglobin, and Deoxyhemoglobin, in heparinized arterial and venous whole blood.

Device Story

Stat Profile Prime Plus Analyzer System; clinical laboratory use; quantitative analysis of whole blood samples (heparinized arterial/venous). Input: whole blood sample via peristaltic pump. Principle: Hematocrit via impedance sensor; CO-Oximeter parameters (tHb, SO2, O2Hb, COHb, MetHb, HHb) via spectrophotometric absorbance (422-695 nm). Processing: chemometrics and computational mapping function. Output: concentration values for analytes displayed on 10.1" touchscreen. Workflow: barcode/manual sample ID; sensor cartridge detection; onboard thermal printer. Clinical utility: assessment of anemia, erythrocytosis, pulmonary function, tissue oxygenation, cyanosis, and carbon monoxide/nitrate/chemical exposure. Benefits: rapid diagnostic information for clinical decision-making regarding oxygen transport and patient metabolic status.

Clinical Evidence

Bench testing only. Precision/reproducibility assessed via QC materials and whole blood (n=20 replicates). Linearity evaluated across 8-11 concentrations per analyte. Method comparison performed against predicate (n=199-209 samples) showing high correlation (r > 0.99). Interference testing conducted for various substances (e.g., bilirubin, lipids, dyes). No clinical studies performed.

Technological Characteristics

Impedance sensor for Hct; spectrophotometric CO-Oximeter (422-695 nm) for hemoglobin derivatives. 10.1" WXGA color touchscreen. Modular sensor cartridges. Lithium heparin whole blood sample requirement. Connectivity: barcode scanner, onboard thermal printer. Electrical safety: IEC 61010-1:2010, IEC 61010-2-101:2015.

Indications for Use

Indicated for healthcare professionals in clinical laboratory settings to quantitatively measure Hematocrit, Oxygen Saturation, Total Hemoglobin, Oxyhemoglobin, Carboxyhemoglobin, Methemoglobin, and Deoxyhemoglobin in heparinized arterial and venous whole blood. Not for point of care use.

Regulatory Classification

Identification

A whole blood hemoglobin assay is a device consisting or reagents, calibrators, controls, or photometric or spectrophotometric instrumentation used to measure the hemoglobin content of whole blood for the detection of anemia. This generic device category does not include automated hemoglobin systems.

Special Controls

*Classification.* Class II (special controls). An acid hematin intended for use with whole blood hemoglobin assays is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 864.9.

Predicate Devices

• Stat Profile pHOx Ultra Analyzer System (K110648)

Submission Summary (Full Text)

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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE

A. 510(k) Number:
k180186

B. Purpose for Submission:
New device

C. Measurand:
Hct, SO₂, tHb, O₂Hb, COHb, MetHb, and HHb

D. Type of Test:
Hct: quantitative, impedance sensor
SO₂, tHb, O₂Hb, COHb, MetHb, HHb: quantitative, spectrophotometric

E. Applicant:
Nova Biomedical Corporation

F. Proprietary and Established Names:
Stat Profile® Prime Plus Analyzer System

G. Regulatory Information:

| Regulation section | Classification | Product code | Panel |
| --- | --- | --- | --- |
| 21 CFR § 864.7500 Whole blood hemoglobin assays (Oxyhemoglobin) | Class II | GGZ | Hematology (81) |
| 21 CFR § 864.7500 Whole blood hemoglobin assays (Cyanomethemoglobin) | Class II | GKK | |
| 21 CFR § 864.6400 Hematocrit measuring device | Class II | JPI | |
| 21 CFR § 864.7425 Carboxyhemoglobin assay | Class II | GHS | |
| 21 CFR § 864.5620 Automated hemoglobin system | Class II | GKR | |

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H. Intended Use:

1. Intended use(s):

See Indication(s) for Use below.

2. Indication(s) for use:

The Stat Profile® Prime Plus Analyzer System is indicated for use by healthcare professionals in clinical laboratory settings for quantitative determination of Hematocrit, Oxygen Saturation, Total Hemoglobin, Oxyhemoglobin, Carboxyhemoglobin, Methemoglobin, and Deoxyhemoglobin, in heparinized arterial and venous whole blood.

| Hct | Hematocrit (Hct) measurements of the packed red blood cell volume are used to distinguish normal from abnormal states, such as anemia and erythrocytosis. |
| --- | --- |
| SO2 | Oxygen Saturation (SO2) measurements are used to assess the oxygenation of the hemoglobin and the adequacy of tissue oxygenation in the evaluation of pulmonary function. Measurements are also used to diagnose and treat cyanosis. |
| tHb | Total Hemoglobin (tHb) measurements are used in the evaluation of chronic and acute anemia as well as the oxygen transport capability of the hemoglobin. |
| O2Hb | Oxyhemoglobin (O2Hb) measurements are used to assess pulmonary function in combination with Deoxyhemoglobin and are also used in the diagnosis and treatment of cyanosis. |
| COHb | Carboxyhemoglobin (COHb) measurements are used to determine if and to what level carbon monoxide has been inhaled by the patient. High levels of carbon monoxide can lead to tissue anoxia and death. |
| MetHb | Methemoglobin (MetHb) measurements are used to determine congenital methemoglobinemia or determine the ingestion of nitrates, chlorates, or any other drug or chemical that can cause methemoglobin formation. High levels of methemoglobin can lead to cyanosis and death. |
| HHb | Deoxyhemoglobin (HHb) measurements are used to assess pulmonary function in combination with Oxyhemoglobin. |

3. Special conditions for use statement(s):

Not for point of care use.

4. Special instrument requirements:

Stat Profile® Prime Plus Analyzer System

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I. Device Description:

The Stat Profile® Prime Plus Analyzer System is designed to be used in a clinical laboratory setting. It consists of the analyzer, sensor cartridges, calibrator packs, auto-cartridge quality control packs (internal controls), ampiled quality control materials (external controls) and thermal paper for an onboard printer. Specimens are identified by scanning a barcode or by manually entering the information via the touchscreen.

The Stat Profile® Prime Plus Analyzer has slots to accommodate two sensor cartridges (primary and auxiliary). The analyzer will determine the configuration of the system by detecting which sensor cards are installed. The reporting of CO-Oximeter parameters (or not reporting them) will also be determined by the selection of the Sensor Cards, for which there are two options:

- Primary Sensor Card 1 reports the following analytes: pO₂, pCO₂, pH, Hct, tHb, Na, Cl, K, iCa, iMg, Glu, SO₂, O₂Hb, COHb, MetHb, HHb, and tBil
- Primary Sensor Card 2 reports the following analytes: pO₂, pCO₂, pH, Hct, tHb, Na, Cl, K, iCa, iMg, Glu, and SO₂

J. Substantial Equivalence Information:

1. Predicate device name(s):

Nova Biomedical Stat Profile pHOx Ultra Analyzer System

2. Predicate 510(k) number(s):

k110648

3. Comparison with predicate:

| Similarities | | |
| --- | --- | --- |
| Item | Candidate Device - Stat Profile® Prime Plus Analyzer (k180186) | Predicate Device - Stat Profile pHOx Ultra Analyzer (k110648) |
| Intended Use | For the quantitative determination of Hematocrit, Oxygen Saturation, Total Hemoglobin, Oxyhemoglobin, Carboxyhemoglobin, Met-hemoglobin, and Deoxyhemoglobin, in heparinized arterial and venous whole blood. | Same |

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| Similarities | | |
| --- | --- | --- |
| Item | Candidate Device - Stat Profile® Prime Plus Analyzer (k180186) | Predicate Device - Stat Profile pHOx Ultra Analyzer (k110648) |
| Measuring range SO2 | 30-100% | Same |
| Measuring range Hct | 12-70% | Same |
| Measuring range tHb | 5.0 - 25.0 g/dL | Same |
| Measurement Principle- Hct | Impedance sensor | Same |
| Measurement Principle- SO2, tHb, O2Hb, COHb, MetHb, HHb | Spectrophotometric | Same |
| Differences | | |
| --- | --- | --- |
| Item | Candidate Device - Stat Profile® Prime Plus Analyzer (k180186) | Predicate Device - Stat Profile pHOx Ultra Analyzer (k110648) |
| Measuring range O2Hb | 1.8-100% | 0-100% |
| Measuring range COHb | 0.3-60% | 0-100% |
| Measuring range MetHb | 0.3-60% | 0-100% |
| Measuring range HHb | 0.4-40% | 0-100% |
| Acceptable sample types | Lithium heparin whole blood | Sodium or lithium heparinized whole blood, serum, or plasma |
| Sample Volume | 135 μL | 60 – 200 μL (dependent on panel selected) |
| Touch Screen | 10.1” WXGA 1280 x 800 color touch screen | 12.1" LCD, 1024x768 pixel, Resistive Touch |

# K. Standard/Guidance Document Referenced (if applicable):

- IEC 61010-1:2010 Safety requirements for electrical equipment for measurement, control, and laboratory use - Part 1: Gen. reqmnts.
- IEC 61010-2-101:2015 - Particular requirements for in vitro diagnostic (IVD) medical equipment

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L. Test Principle:

Hematocrit is obtained by measuring electrical resistance of the blood sample. Two standard solutions are used to calibrate the hematocrit sensor and to obtain the slope. The analyzer then measures the electrical resistance of the blood sample to obtain the hematocrit value.

The Prime Plus CO-Oximeter subsystem is used to measure the hemoglobin parameters of whole blood such as total hemoglobin (tHb), carboxyhemoglobin (COHb), deoxyhemoglobin (HHb), oxyhemoglobin (O₂Hb), methemoglobin and (MetHb) using chemometrics applied to optical absorbance. Whole blood is drawn into a cuvette via a peristaltic pump. The analyzer then measures the light transmittance through the sample over a plurality of wavelengths in the 422 to 695 nm spectral region. This output signal is processed using a computational mapping function technique to determine the concentration of tHb, COHb, O₂Hb, MetHb, and HHb. Oxygen saturation (SO₂) represents the percent of hemoglobin bound to oxygen, expressed as a fraction of the amount of hemoglobin capable of binding to oxygen.

M. Performance Characteristics (if/when applicable):

1. Analytical performance:

a. Precision/Reproducibility:

Within run and between analyzer precision was assessed by analyzing QC materials and whole blood samples in replicates of 20 on each of three analyzers. Results are summarized below.

Internal Quality Control within – run results:

All three analyzers yielded similar results. The results of one representative analyzer are summarized in the table below.

| Within-Run Precision | | | | |
| --- | --- | --- | --- | --- |
| Parameter | n = 20 | Control Level 1 | Control Level 2 | Control Level 3 |
| SO₂ (%) | Mean | 48.8 | 83.1 | 92.2 |
| | SD | 0.1 | 0.1 | 0.1 |
| Hct (%) | Mean | 56 | 43 | 25.0 |
| | SD | 0.0 | 0.4 | 0.0 |
| tHb (g/dL) | Mean | 19 | 16 | 7 |
| | SD | 0.1 | 0.1 | 0.0 |
| | CV% | 0.4 | 0.4 | 0.3 |
| O₂Hb (%) | Mean | 20.1 | 52.5 | 81.7 |
| | SD | 0.1 | 0.1 | 0.2 |
| | CV% | 0.4 | 0.2 | 0.2 |

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| Within-Run Precision | | | | |
| --- | --- | --- | --- | --- |
| Parameter | n = 20 | Control Level 1 | Control Level 2 | Control Level 3 |
| COHb (%) | Mean | 29.8 | 18.0 | 5.4 |
| | SD | 0.2 | 0.1 | 0.2 |
| | CV% | 0.6 | 0.5 | 3.9 |
| MetHb (%) | Mean | 29.1 | 18.0 | 5.9 |
| | SD | 0.1 | 0.3 | 0.3 |
| | CV% | 0.3 | 1.5 | 5.5 |
| HHb (%) | Mean | 21.1 | 10.7 | 6.9 |
| | SD | 0.1 | 0.1 | 0.1 |
| | CV% | 0.6 | 0.9 | 0.1 |

Within – run precision using whole blood:

All three analyzers yielded similar results. The results from one representative analyzer are summarized in the tables below. Note: the samples below were selected to evaluate a specific parameter over a specific range, so all parameters were not evaluated on all samples.

| SO₂ (%), (n=20) | | |
| --- | --- | --- |
| Sample | Mean | SD |
| Sample 1 | 100 | 0.1 |
| Sample 2 | 92 | 0.2 |
| Sample 3 | 80 | 0.4 |
| Sample 4 | 100 | 0.1 |
| Neonatal Whole Blood | 99.0 | 0.0 |
| Hct (%), (n=20) | | |
| --- | --- | --- |
| Sample | Mean | SD |
| Sample 1 | 49 | 0.4 |
| Sample 2 | 42 | 0.7 |
| Sample 3 | 46 | 0.5 |
| Sample 4 | 28 | 0.5 |
| tHb (g/dL) (n=20) | | | |
| --- | --- | --- | --- |
| Sample | Mean | SD | %CV |
| Sample 1 | 13.6 | 0.1 | 1.1 |
| Sample 2 | 15.1 | 0.2 | 1.4 |
| Sample 3 | 16.3 | 0.1 | 0.9 |
| Sample 4 | 20.3 | 0.1 | 0.3 |
| Neonatal Whole Blood | 16.1 | 0.1 | 0.5 |

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| O2Hb (%) (n=20) | | | |
| --- | --- | --- | --- |
| Sample | Mean | SD | %CV |
| Sample 1 | 91.4 | 0.3 | 0.3 |
| Sample 2 | 78.5 | 0.6 | 0.7 |
| Sample 3 | 90.8 | 0.5 | 0.6 |
| Sample 4 | 97.6 | 0.2 | 0.2 |
| Neonatal Whole Blood | 96.3 | 0.3 | 0.3 |
| COHb (%) (n=20) | | | |
| --- | --- | --- | --- |
| Sample | Mean | SD | %CV |
| Sample 1 | 1.5 | 0.1 | 10.1 |
| Sample 2 | 1.0 | 0.3 | 29.8 |
| Sample 3 | 0.8 | 0.3 | 38.4 |
| Sample 4 | 6.5 | 0.2 | 2.5 |
| Neonatal Whole Blood | 4.1 | 0.2 | 5.7 |
| MetHb (%) (n=20) | | | |
| --- | --- | --- | --- |
| Sample | Mean | SD | %CV |
| Sample 1 | 0.4 | 0.1 | 24.3 |
| Sample 2 | 0.4 | 0.1 | 18.7 |
| Sample 3 | 0.7 | 0.1 | 20.2 |
| Sample 4 | 0.7 | 0.1 | 11.6 |
| Neonatal Whole Blood | 0.9 | 0.1 | 11.1 |
| HHb (%) (n=20) | | | |
| --- | --- | --- | --- |
| Sample | Mean | SD | %CV |
| Sample 1 | 0.5 | 0.1 | 13.9 |
| Sample 2 | 20.0 | 0.4 | 1.9 |
| Sample 3 | 8.0 | 0.3 | 3.7 |
| Sample 4 | 0.5 | 0.1 | 22.1 |
| Neonatal Whole Blood | 0.5 | 0.0 | 0.0 |

# Run-to-run precision using internal QC material

Estimates of the run-to-run precision were determined for each of three Stat Profile Prime Plus Analyzers by testing Stat Profile Prime Plus Internal Controls, Levels 1-3 for each parameter in QC mode in duplicate, with two runs per day for a total of forty runs.

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| Hct (%) | | | | |
| --- | --- | --- | --- | --- |
| Sample | Pooled Mean | N | Within run SD (Sr) | Total Imprecision SD (St) |
| QC Level 1 | 58 | 240 | 0.1 | 0.1 |
| QC Level 2 | 44 | 240 | 0.1 | 0.5 |
| QC Level 3 | 25 | 240 | 0.2 | 0.2 |
| SO2(%) | | | | |
| --- | --- | --- | --- | --- |
| Sample | Pooled Mean | N | Within run SD (Sr) | Total Imprecision SD (St) |
| QC Level 1 | 49 | 240 | 0.6 | 0.8 |
| QC Level 2 | 83 | 240 | 0.1 | 0.9 |
| QC Level 3 | 93 | 240 | 0.1 | 0.6 |
| tHb (g/dL) | | | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| Sample | Pooled Mean | N | Within run SD (Sr) | Within run %CV | Total Imprecision SD (St) | Total Imprecision %CV |
| QC Level 1 | 19.0 | 240 | 0.4 | 2.1 | 0.5 | 0.9 |
| QC Level 2 | 15.9 | 240 | 0.0 | 0.3 | 0.2 | 2.0 |
| QC Level 3 | 6.9 | 240 | 0.0 | 0.3 | 0.1 | 1.4 |
| O2Hb (%) | | | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| Sample | Pooled Mean | N | Within run SD (Sr) | Within run %CV | Total Imprecision SD (St) | Total Imprecision %CV |
| QC Level 1 | 20.2 | 240 | 0.2 | 0.8 | 0.5 | 2.5 |
| QC Level 2 | 52.5 | 240 | 0.1 | 0.1 | 0.4 | 0.8 |
| QC Level 3 | 82.3 | 240 | 0.1 | 0.1 | 0.5 | 0.5 |
| COHb (%) | | | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| Sample | Pooled Mean | N | Within run SD (Sr) | Within run %CV | Total Imprecision SD (St) | Total Imprecision %CV |
| QC Level 1 | 29.9 | 240 | 0.5 | 1.5 | 0.7 | 2.0 |
| QC Level 2 | 18.2 | 240 | 0.1 | 0.7 | 0.5 | 3.8 |
| QC Level 3 | 5.4 | 240 | 0.1 | 2.4 | 0.3 | 3.9 |

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| MetHb (%) | | | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| Sample | Pooled Mean | N | Within run SD (Sr) | Within run %CV | Total Imprecision SD (St) | Total Imprecision %CV |
| QC Level 1 | 28.9 | 240 | 0.2 | 0.7 | 0.4 | 0.9 |
| QC Level 2 | 18.4 | 240 | 0.2 | 0.9 | 0.3 | 1.3 |
| QC Level 3 | 5.8 | 240 | 0.2 | 3.8 | 0.3 | 2.1 |
| HHb (%) | | | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| Sample | Pooled Mean | N | Within run SD (Sr) | Within run %CV | Total Imprecision SD (St) | Total Imprecision %CV |
| QC Level 1 | 21 | 240 | 0.5 | 2.4 | 0.7 | 3.0 |
| QC Level 2 | 10.9 | 240 | 0.1 | 0.7 | 0.6 | 2.6 |
| QC Level 3 | 6.4 | 240 | 0.1 | 2.0 | 0.5 | 4.8 |

# Day-to-day imprecision using whole blood

To simulate total day-to-day precision for whole blood, triplicate analyses were performed on a single tonometered whole blood (WB) sample in ten separate runs during a single day. Samples were delivered to the instrument from a syringe. The systems were recalibrated before each triplicate run. The results from one representative analyzer are summarized in the table below.

| Sample | Mean | SD | %CV |
| --- | --- | --- | --- |
| Hct % | 48 | 0.6 | - |
| SO2% | 99.0 | 0.2 | - |
| tHb (g/dL) | 14.8 | 0.1 | 0.7 |
| O2Hb(%) | 97.6 | 0.4 | 0.4 |
| COHb (%) | 1.0 | 0.2 | 19.1 |
| MetHb (%) | 0.4 | 0.1 | 22.1 |
| HHb (%) | 1.1 | 0.2 | 21.1 |

# b. Linearity/assay reportable range:

A linearity study was performed using lithium heparin whole blood samples. Some samples were altered to provide between eight and eleven total analyte concentrations throughout the analytical measurement range. Each blood level was analyzed in triplicate on each of the three Stat Profile® Prime Plus Analyzers and on the Stat Profile pHOx Ultra analyzer. The pHOx Ultra analyzer was used to establish the target value of each blood level for each parameter. Results of the linear regression analysis for one representative analyzer are shown below.

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| Parameter | Specimen Range Tested | Claimed Measuring Range | Slope | Intercept | r |
| --- | --- | --- | --- | --- | --- |
| Hct (%) | 8 – 73 | 12 - 70 | 0.9990 | -0.4464 | 0.9983 |
| SO_{2} (%) | 15 - 99 | 30 - 100 | 0.9681 | 2.2089 | 0.9994 |
| tHb (g/dL) | 4.1 – 25.6 | 5.0 - 25.0 | 0.9860 | 0.3173 | 0.9995 |
| O_{2} Hb (%) | 0.4 - 97.8 | 1.8 - 100 | 0.9968 | 1.6902 | 0.9989 |
| COHb (%) | 0.1 - 64.2 | 0.3 - 60 | 0.9939 | 0.1736 | 0.9994 |
| MetHb (%) | 0.4 - 62.3 | 0.3 - 60 | 1.0011 | -0.1386 | 0.9996 |
| HHb (%) | 0.8 - 52.3 | 0.4 - 40 | 0.9885 | 0.9920 | 0.9992 |

c. Traceability, Stability, Expected values (controls, calibrators, or methods):

The traceability for Hct, SO₂, tHb, O₂Hb, COHb, MetHb, and HHb is as follows:

Hct: Measurements were performed by the microhematocrit method which calls for whole blood to be centrifuged and the percentage of packed red cells calculated. Results from the reference method were compared to measurements from a Nova analyzer. A least squares regression analysis of the data was performed.

Oxygen Saturation SO₂ = 100%: The oxygen saturation percentage (SO₂%) traceability is established through FO₂Hb and FHHb using the following equation: SO₂% = FO₂Hb/(FO₂Hb+FHHb)

Total Hemoglobin: Traceability of total hemoglobin was established using the benchmark cyanmethhemoglobin method (see NCCLS Document H15-A3: Reference and Selected Procedures for the Quantitative Determination of Hemoglobin in Whole Blood; Approved Standard). Absorbance readings from a spectrophotometer at 530 nm are used as reference samples and are compared to absorbance readings from Nova instruments.

O₂Hb: The primary working standard is a non-smoker whole blood sample, having ctHb in the normal range, which is tonometered with 5% CO₂, 95% O₂, traceable to NIST SRM gases. This blood sample is then used in calibration of the CO-Oximeter.

COHb – Normal Value: The primary working standard is a mixture of certified gas having 8.00% CO with the balance N2 (3000 ppm propane). A known aliquot of whole blood is mixed with a known volume of gas mixture to produce a secondary standard. Validation of the mixing is performed using a calibrated Siemens Radiometer ABL800 Flex analyzer. The secondary whole blood standard is then used to calibrate the CO-Oximeter.

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MetHb: Traceability of methemoglobin was established using the cyanmethemoglobin method. THb is converted to MetHb by potassium ferric cyanide and then further to cyanmethemoglobin by potassium cyanide. The calibration is established by measuring the decrease in absorbance at 630 nm on a spectrophotometer.

HHb: The primary working standard used is a non-smoker whole blood sample. The blood sample is treated with dithionite to remove oxygen. This sample is then used to calibrate the CO-Oximeter.

## d. Detection limit:

The sponsor performed a study to evaluate the limit of blank (LoB), limit of detection (LoD) and limit of quantitation (LoQ) for tHb, O₂Hb, COHb, MetHb and HHb using altered whole blood samples. Study samples were prepared from heparinized venous whole blood samples. CO-Oximetry blank and low level samples were prepared using a tonometer to control the gas content in the blood samples. A sodium hydrosulfite spiking solution was also used to scavenge the residual oxygen for the blank O₂Hb samples. All prepared samples were analyzed on the reference analyzer to obtain the target values. Calculated Total Error is less than the accuracy goal for Total Error, so the LoQ = LoD. Results were as follows:

| Analyte | units | LoB | LoD | TE | LoQ | Acceptance Criteria for TE (<=) | Claimed Measurement Range |
| --- | --- | --- | --- | --- | --- | --- | --- |
| tHB | g/dL | 2.9 | 3.2 | 0.9 | 3.2 | 1.3 | 5 - 25 |
| O₂Hb | % | 0.4 | 1.8 | 1.0 | 1.8 | 2.6 | 1.8 - 100 |
| COHb | % | 0.2 | 0.3 | 0.2 | 0.3 | 1.5 | 0.3 - 60 |
| MetHb | % | 0.1 | 0.3 | 0.3 | 0.3 | 1.5 | 0.3 - 60 |
| HHb | % | 0.2 | 0.4 | 0.2 | 0.4 | 1.5 | 0.4 - 40 |

The performance at the lower end of the measuring range for SO₂ and Hct is supported by the linearity studies in section M.1.b.

## e. Analytical specificity:

An interference testing study was performed using whole blood collected in lithium heparin vacutainers. The possible interfering substances were tested at two analyte concentrations. Samples were divided to create two separate pools of blood, one for control samples and the other for test samples that were spiked with potential interferent substance. The control and test samples were measured on the same analyzers in replicates of eight. If interference was identified, a dose response study was performed to determine the concentration where the interfering substance may alter results. For all analytes, the sponsor defined interference as a specified % bias from the test concentration as shown in the following table.

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| Analyte | Interference %Bias Specification |
| --- | --- |
| SO2 | >±3.0% |
| Hct | >±4.0% |
| tHb | >±0.7 g/dL |
| O2Hb | >±3.0% |
| COHb | >±2.0% |
| MetHb | >±2.0% |
| HHb | >±3.0% |

$\mathbf{SO}_2$

| Substance | Highest concentration tested that did not cause significant interference |
| --- | --- |
| Beta-Carotene | 2 mg/L |
| Cyanocobalamin | 0.1 g/L |
| Cyanomethemoglobin (Drabkin's reagent) | 10% |
| Evans Blue | 1 mg/dL |
| Fluorescein | 0.4 mg/mL |
| Hemolysis | 10% |
| Hydroxycobalamin | 0.6 g/L |
| Indocyanine Green/ Cardiogreen | 10 mg/L |
| Intralipid | 4.0% |
| Methylene Blue | 2 mg/dL |
| Patent Blue | 2.5 mg/L |
| Sulfhemoglobin | 1.5% |

Hct

| Substance | Highest concentration tested that did not cause significant interference |
| --- | --- |
| Acetylcysteine | 10.2 mmol/L |
| Bilirubin (Conjugate) | 342 μmol/L |
| Hemoglobin | 2 g/L |
| Hydroxycobalamin | 0.6 g/L |
| Intralipid | 4.0% |
| Sodium Heparin | 100 iU/mL |
| White Blood Cells | 83116 WBC/μL |

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tHb

| Substance | Highest concentration tested that did not cause significant interference |
| --- | --- |
| Bilirubin (Conjugate) | 342 μmol/L |
| Beta-Carotene | 2 mg/L |
| Cyanocobalamin | 0.1 g/L |
| Cyanomethemoglobin (Drabkin's reagent) | 10% |
| Fluorescein | 0.4 mg/mL |
| Hemolysis | 10% |
| Hydroxycobalamin | 0.6 g/L |
| Indocyanine Green/ Cardiogreen | 10 mg/L |
| Methylene Blue | 2 mg/dL |
| Patent Blue | 2.5 mg/L |
| Sulfhemoglobin | 1.5% |
| White Blood Cells | 83116 WBC/μL |

O2Hb

| Substance | Highest concentration tested that did not cause significant interference |
| --- | --- |
| Bilirubin (Conjugate) | 342 μmol/L |
| Beta-Carotene | 2 mg/L |
| Cyanocobalamin | 0.1 g/L |
| Cyanomethemoglobin (Drabkin's reagent) | 10% |
| Fluorescein | 0.4 mg/mL |
| Hemolysis | 10% |
| Hydroxycobalamin | 0.6 g/L |
| Indocyanine Green/ Cardiogreen | 10 mg/L |
| Methylene Blue | 2 mg/dL |
| Patent Blue | 2.5 mg/L |
| White Blood Cells | 83116 WBC/μL |

COHb

| Substance | Highest concentration tested that did not cause significant interference |
| --- | --- |
| Bilirubin (Conjugate) | 342 μmol/L |
| Beta-Carotene | 2 mg/L |
| Cyanocobalamin | 0.1 g/L |
| Cyanomethemoglobin (Drabkin's reagent) | 10% |
| Fluorescein | 0.4 mg/mL |

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| Substance | Highest concentration tested that did not cause significant interference |
| --- | --- |
| Hemolysis | 10% |
| Hydroxycobalamin | 0.6 g/L |
| Indocyanine Green/ Cardiogreen | 10 mg/L |
| Intralipid | 4.0% |
| Methylene Blue | 2 mg/dL |
| Patent Blue | 2.5 mg/L |
| White Blood Cells | 83116 WBC/μL |

MetHb

| Substance | Highest concentration tested that did not cause significant interference |
| --- | --- |
| Bilirubin (Conjugate) | 342 μmol/L |
| Beta-Carotene | 2 mg/L |
| Cyanocobalamin | 0.1 g/L |
| Cyanomethemoglobin (Drabkin's reagent) | 10% |
| Fluorescein | 0.4 mg/mL |
| Hemolysis | 10% |
| Hydroxycobalamin | 0.6 g/L |
| Indocyanine Green/ Cardiogreen | 10 mg/L |
| White Blood Cells | 83116 WBC/μL |

HHb

| Substance | Highest concentration tested that did not cause significant interference |
| --- | --- |
| Bilirubin (Conjugate) | 342 μmol/L |
| Beta-Carotene | 2 mg/L |
| Cyanocobalamin | 0.1 g/L |
| Cyanomethemoglobin (Drabkin's reagent) | 10% |
| Evans Blue | 1 mg/dL |
| Fluorescein | 0.4 mg/mL |
| Hemolysis | 10% |
| Hydroxycobalamin | 0.6 g/L |
| Indocyanine Green/ Cardiogreen | 10 mg/L |
| Intralipid | 4.0% |
| Methylene Blue | 2 mg/dL |
| Patent Blue | 2.5 mg/L |
| Sulfhemoglobin | 1.5% |
| White Blood Cells | 83116 WBC/μL |

{14}

The sponsor lists the following interferents in the labeling:

| Parameter | Interferent | Interference Observed at Concentrations Above: |
| --- | --- | --- |
| Hct | Albumin | 2.8 g/dL |
| | Hemolysis | 5.0% |
| | Triglycerides | 335.5 mg/dL |
| O2Hb | Evans Blue | 0.125 mg/dL |
| | Intralipid | 1.0% |
| | Sulfhemoglobin | 0.63 % |
| COHb | Evans Blue | 0.25 mg/dL |
| | Sulfhemoglobin | 0.803% |
| MetHb | Evans Blue | 0.125 mg/dL |
| | Patent Blue | 1.875 mg/dL |
| | Intralipid | 1.0% |
| | Sulfhemoglobin | 0.63% |
| | Methylene Blue | Interference at all concentrations |
| tHb | Evans Blue | 0.25 mg/dL |
| | Intralipid | 1.0% |

f. Assay cut-off:

Not applicable.

# 2. Comparison studies:

a. Method comparison with predicate device:

Method comparison studies were conducted by testing lithium heparinized arterial and venous whole blood specimens in singlet on the three Stat Profile® Prime Plus analyzers and two pHOx Ultra analyzers (predicate device). In order to evaluate the claimed measuring range, some venous whole blood specimens were tonometered, spiked or diluted to achieve the desired concentrations. The singlet result from each test analyzer was compared to the average of the results from each comparative method. Linear regression analysis of one representative analyzer is shown below.

| Analyte | n | Sample concentration range | Slope | Intercept | r |
| --- | --- | --- | --- | --- | --- |
| Hct (%) | 209 | 15 - 67 | 0.9777 | 1.4149 | 0.9909 |
| SO2(%) | 204 | 31 - 100 | 1.0008 | 0.2589 | 0.9976 |
| tHb (g/dL) | 208 | 5.0 - 22.0 | 1.0088 | -0.1675 | 0.9940 |
| O2Hb (%) | 209 | 4.9 - 97.4 | 1.0222 | -0.7820 | 0.9987 |
| COHb (%) | 205 | 0.1 - 51.5 | 1.0071 | -0.3460 | 0.9959 |
| MetHb (%) | 208 | 0.2 - 56.1 | 1.0117 | -0.5811 | 0.9974 |
| HHb (%) | 199 | 0.2 - 39.3 | 1.0166 | -0.0026 | 0.9968 |

{15}

b. Matrix comparison:

Not applicable. For use with lithium heparinized whole blood only.

# 3. Clinical studies:

a. Clinical Sensitivity:

Not applicable.

b. Clinical specificity:

Not applicable.

c. Other clinical supportive data (when a. and b. are not applicable):

Not applicable.

# 4. Clinical cut-off:

Not applicable.

# 5. Expected values/Reference range:

Reference ranges for Hct, $\mathrm{SO}_2$ , tHb, $\mathrm{O}_2\mathrm{Hb}$ , COHb, MetHb, and HHb are cited from the literature:

| Analyte | Stat Profile® Prime Plus Reference ranges |
| --- | --- |
| Hematocrit (Hct) | Male: 39 - 49% Female: 35 - 45% |
| SO2 (Arterial Whole Blood) | 95 - 98% |
| Total Hemoglobin (tHb) | Male: 14.0 - 17.8 g/dL Female: 12.0 - 15.6 g/dL |
| O2Hb (Arterial Whole Blood) | 94 - 97% |
| COHb (Nonsmoking) | 0.0 - 1.5% |
| MetHb | 0.0 - 1.5% |
| HHb | 0.0 - 5.0% |

{16}

References:

Statland, Bernard, Clinical Decision Levels for Lab Tests, Medical Economics Books, 1987.

Burtis, Carl A. and Ashwood, Edward R., ed. 1994. Tietz Textbook of Clinical Chemistry, W. B. Saunders Co. Philadelphia, PA.

Williams, W.J., Beutler, E., Ersley, A.J., and Rundles, R.W., Hematology, Second Edition. McGraw-Hill Co, 1977.

Zijlstra, W.G. and van Kampem, E.J., “Spectrophotometry of Hemoglobin and Hemoglobin Derivatives,” Advances in Clinical Chemistry, Vol. 23: pp 199-257. 1983.

Kost, G.T., “The Significance of Ionized Calcium in Cardiac and Critical Care,” Arch. Pathol. Lab Med. Vol. 117: pp 890-896. 1993.

Tietz, Norbert W., ed. 1983. Clinical Guide to Laboratory Tests, W. B. Saunders Co., Philadelphia, PA.

N. Proposed Labeling:

The labeling is sufficient and it satisfies the requirements of 21 CFR Parts 801 and 809, as applicable.

O. Conclusion:

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.