epoc Blood Urea Nitrogen Test, epoc Total Carbon Dioxide Test

K171247 · Epocal, Inc. · CDS · Jan 17, 2018 · Clinical Chemistry

Device Facts

• Record ID: K171247
• Device Name: epoc Blood Urea Nitrogen Test, epoc Total Carbon Dioxide Test
• Applicant: Epocal, Inc.
• Product Code: CDS · Clinical Chemistry
• Decision Date: Jan 17, 2018
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1770
• Device Class: Class 2

Intended Use

The Blood Urea Nitrogen and Total Carbon Dioxide tests, as part of the epoc Blood Analysis System, is intended for use by trained medical professionals as an in vitro diagnostic device for the quantitative testing of samples of heparinized or unanticoagulated arterial, venous or capillary whole blood in the laboratory or at the point of care. Blood Urea Nitrogen measurements from the epoc Blood Analysis System are used in the diagnosis and treatment of certain renal and metabolic diseases. Total Carbon Dioxide measurements from the epoc Blood Analysis System are used in the diagnosis and treatment of disorders associated with changes in body acid-base balance.

Device Story

The epoc Blood Analysis System is a point-of-care diagnostic platform consisting of a handheld reader, host device, and single-use BGEM test cards. This submission adds BUN and TCO2 sensors to the existing card. The BUN sensor uses an enzymatic potentiometric method where urease hydrolyzes urea into ammonium ions, which are detected by an ion-selective electrode. The TCO2 test is calculated using the Henderson-Hasselbalch equation based on measured pH and pCO2, with calibration traceable to the IFCC reference method. The operator inserts a blood sample into the test card, which is then inserted into the reader for automated analysis. Results are displayed on the host device, allowing clinicians to make immediate decisions regarding renal function and acid-base status. The system provides rapid, bedside diagnostic information, reducing turnaround time compared to central laboratory testing.

Clinical Evidence

No clinical trials were performed. Evidence consists of analytical bench testing, including precision (CLSI EP05-A3), linearity (CLSI EP06-A), detection limits (CLSI EP17-A2), and interference studies (CLSI EP07-A2). Method comparison studies were conducted at 3 point-of-care sites comparing the epoc system against the Roche Cobas 8000 (BUN) and i-STAT CHEM8+ (TCO2). Results showed high correlation (R² > 0.94) across venous, arterial, and capillary samples. Matrix comparison confirmed suitability of lithium heparin, sodium heparin, and un-anticoagulated blood.

Technological Characteristics

The system uses an electrochemical multi-sensor array on a single-use test card. BUN sensing is enzymatic potentiometric (urease-based). TCO2 is calculated via the Henderson-Hasselbalch equation using measured pH and pCO2. The system is a handheld, point-of-care device. Calibration is performed using NIST-traceable standards. The device is designed for use with the epoc Reader and Host. Sterilization and specific material standards are not detailed beyond general laboratory equipment safety (IEC 61010-1).

Indications for Use

Indicated for trained medical professionals to perform quantitative testing of heparinized or un-anticoagulated arterial, venous, or capillary whole blood for BUN and TCO2 levels in laboratory or point-of-care settings. Used for diagnosis and treatment of renal, metabolic, and acid-base balance disorders.

Regulatory Classification

Identification

A urea nitrogen test system is a device intended to measure urea nitrogen (an end-product of nitrogen metabolism) in whole blood, serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of certain renal and metabolic diseases.

Predicate Devices

• i-STAT Chem8+ Cartridge (with i-STAT Portable Clinical Analyzer) (k053110)

Submission Summary (Full Text)

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Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo in blue, with the words "U.S. FOOD & DRUG" stacked on top of the word "ADMINISTRATION".

January 17, 2018

Epocal Inc. Jennifer Armstrong Regulatory Affairs Manager 2060 Walkley Road Ottawa, ON K1G 3P5 Canada

Re: K171247

Trade/Device Name: epoc Blood Urea Nitrogen Test, epoc Total Carbon Dioxide Test Regulation Number: 21 CFR 862.1770 Regulation Name: Urea nitrogen test system Regulatory Class: II Product Code: CDS. JFL Dated: December 11, 2017 Received: December 13, 2017

Dear Jennifer Armstrong:

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 Part 801 and Part 809); medical device 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

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Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email ([e-mail]) or phone [phone] or 301-796-7100).

Sincerely,

# Kellie B. K

for 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) K171247

Device Name epoc® Blood Urea Nitrogen Test epoc® Total Carbon Dioxide Test

#### Indications for Use (Describe)

The Blood Urea Nitrogen and Total Carbon Dioxide tests, as part of the epoc Blood Analysis System, is intended for use by trained medical professionals as an in vitro diagnostic device for the quantitative testing of samples of heparinized or un-anticoagulated arterial, venous or capillary whole blood in the laboratory or at the point of care.

Blood Urea Nitrogen measurements from the epoc Blood Analysis System are used in the diagnosis and treatment of certain renal and metabolic diseases.

Total Carbon Dioxide measurements from the epoc Blood Analysis System are used in the diagnosis and treatment of disorders associated with changes in body acid-base balance.

| Type of Use (Select one or both, as applicable) |
|-------------------------------------------------|
|-------------------------------------------------|

> Prescription Use (Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR 801 Subpart C)

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### 510(k) SUMMARY K171247

#### GENERAL INFORMATION

| Applicant Name: | Epocal Inc.<br>2060 Walkley Road<br>Ottawa, ON K1G 3P5 Canada |
|------------------|-------------------------------------------------------------------------------------------------------------------------|
| Company Contact: | Jennifer Armstrong<br>Manager, Regulatory Affairs<br>Phone: [phone] x2227<br>Email: [e-mail] |
| Date Prepared: | January 15, 2018 |

#### DEVICE IDENTIFICATION

Trade or Proprietary Names: epoc® Blood Urea Nitrogen Test epoc® Total Carbon Dioxide Test

#### REGULATORY INFORMATION

| Classification Regulation: | 21 CFR 862.1770 | Urea nitrogen test system |
|----------------------------|------------------------------------------------------------------|----------------------------------------|
| | 21 CFR 862.1160 | Bicarbonate/carbon dioxide test system |
| Regulatory Class: | Class II | |
| Product Codes: | CDS | Electrode, Ion Specific, Urea Nitrogen |
| | JFL | pH Rate Measurement, Carbon-Dioxide |
| Predicate Device: | i-STAT CHEM8+ Cartridge (K053110; cleared by i-STAT Corporation) | |

#### DEVICE DESCRIPTION

The epoc Blood Analysis System is an in vitro diagnostic device system for the quantitative testing of blood gases, electrolytes, and metabolites in venous, arterial, and capillary whole blood samples. The epoc System is comprised of 3 major subsystems: epoc Host, epoc Reader and epoc BGEM Test Card. The main accessory used with the epoc System includes the epoc Care-Fill Capillary Tubes used to collect and introduce capillary blood samples into the epoc Test Card.

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The epoc Blood Analysis System was previously cleared for prescription use to quantitate pH, pCO2, pO2, Na, K, iCa, Cl, Glu, Lact, Crea, and Hct in arterial, venous, and capillary blood samples per k061597, k090109, k092849, k093297, and k113726. This premarket notification submission adds blood urea nitrogen (BUN) and total carbon dioxide (TCO2) quantitation to the epoc BGEM Test Card and Blood Analysis System.

#### INTENDED USE

The Blood Urea Nitrogen and Total Carbon Dioxide tests, as part of the epoc Blood Analysis System, is intended for use by trained medical professionals as an in vitro diagnostic device for the quantitative testing of samples of heparinized or unanticoagulated arterial, venous or capillary whole blood in the laboratory or at the point of care.

Blood Urea Nitrogen measurements from the epoc Blood Analysis System are used in the diagnosis and treatment of certain renal and metabolic diseases.

Total Carbon Dioxide measurements from the epoc Blood Analysis System are used in the diagnosis and treatment of disorders associated with changes in body acid-base balance.

| Attribute | Predicate Device<br>i-STAT CHEM8+ Cartridge<br>(with i-STAT Portable Clinical<br>Analyzer) [k053110] | Candidate Device<br>epoc BGEM Test Card with epoc Blood<br>Analysis System |
|-------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------|
| Intended use | Portable, prescription use test system | Prescription, point-of-care test system |
| Measured<br>Parameter | Urea Nitrogen (BUN);<br>Total CO2 (TCO2) | Blood Urea Nitrogen (BUN);<br>Total CO2 (TCO2) |
| Calculated<br>Parameter | Anion Gap (AnGap); | Anion Gap (AGap, AGapK);<br>BUN/Creatinine ratio (BUN/Crea) |
| Where used | hospital, point of care | Same |
| Sample type | Venous, arterial and capillary whole<br>blood | Same |
| Technology | An electrochemical multi-sensor array<br>integrated into a single-use test that is<br>interpreted by a handheld reader and<br>associated software | Same |
| Reportable ranges<br>(BUN and TCO2) | BUN 3-140 mg/dL<br>TCO2 5-50 mmol/L | BUN 3-120 mg/dL<br>TCO2 same |
| Sample volume | 95 µL | At least 92 µL |

#### COMPARISON WITH PREDICATE

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#### PERFORMANCE CHARACTERISTICS

### 1. Analytical Sensitivity

This study evaluated and verified the performance of the epoc Blood Analysis System for BUN and TCO2 quantitation at the low end of their respective concentration ranges by determining the Limit of Blank (LoB), Limit of Detection (LoD) and Limit of Quantitation (LoQ) according to CLSI EP17-A2. Test samples were prepared from dialyzed whole blood. Results from this study are shown below:

| Analyte | LoB | LoD | LoQ |
|---------|---------|---------|---------|
| BUN | 2 mg/dL | 3 mg/dL | 3 mg/dL |
| TCO2 | 4.0 mM | 4.3 mM | 4.3 mM |

### 2. Linearity

Linearity was performed in-house on multiple whole blood samples with BUN or TCO2 values spanning the reportable range. Linearity is reported versus theoretical BUN values based on gravimetric mixtures of high and low BUN samples (as measured using an in-house standard whole blood BUN method). Three card lots were used in this study. The study was conducted per CLSI EP06-A.

| BUN | | | |
|-------------|-------|-----------|--------|
| Test Range | Slope | Intercept | R |
| 4-119 mg/dL | 1.020 | 0.4 | 0.9989 |
| TCO2 | | | |
| Test Range | Slope | Intercept | R |
| 4-49 mmol/L | 0.903 | 3.32 | 0.9997 |

#### 3. Precision (Aqueous Controls)

Analytical precision for BUN and TCO2 measurements was conducted with four card lots using at least 25 epoc Readers where replicate measurements were run in-house twice a day for twenty days for each fluid per CLSI EP05-A3. In the precision data tables below, Swx denotes within-run standard deviation, %CVwr denotes within-run coefficient of variation, Sr denotes total standard deviation, and %CVr denotes total coefficient of variation.

| Aqueous Control | Units | N | Mean | SWR | %CVWR | ST | %CVT |
|-------------------|--------|-----|------|------|-------|------|------|
| High Level (BUN) | mg/dL | 320 | 51.7 | 1.01 | 2.0% | 1.16 | 2.3% |
| Low Level (BUN) | mg/dL | 320 | 7.1 | 0.30 | 4.2% | 0.32 | 4.5% |
| High Level (TCO2) | mmol/L | 320 | 30.7 | 0.82 | 2.7% | 0.92 | 3.0% |
| Low Level (TCO2) | mmol/L | 320 | 16.2 | 0.88 | 5.4% | 1.02 | 6.3% |

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#### 4. Interference

Interferent testing of the BUN and TCO2 measurements on the epoc System was performed as recommended in the CLSI guideline EP07-A2. In each of these tests, human serum specimens were aliquoted into two (2) samples. The test sample was spiked by addition of interferent, while the control sample was spiked by the addition of the solvent of the interferent. The bias between the mean of six (6) replicates on both the control sample and the test sample with added interferent was calculated. Unacceptable interference bias was defined as producing a significant error more than 5% of the time.

Clinically significant interfering substances for BUN measurements are itemized below:

- . Samples contaminated with benzalkonium salts used as coatings for in-dwelling lines may cause elevated BUN results. For proper line-flushing procedures refer to CLSI H11-A4.
- Citrate will have no significant effect up to 6.0 mmol/L (176.5 mg/dL) after which it will decrease the BUN concentration by up to 0.26 mg/dL BUN per mmol/L citrate.
- EDTA will have no significant effect up to 4.5 mmol/L (167 mg/dL) after which it ● will decrease the BUN concentration by up to 0.43 mg/dL BUN per mmol/L EDTA.
- . Glutathione reduced will have no significant effect up to 1.7 mmol/L (52.2 mg/dL), after which it will increase the BUN concentration by up to 1.91 mg/dL BUN per mmol/L glutathione reduced. Blood glutathione (GSH) in human subjects is ~0.79-1.05 mmol/L. Long term oral glutathione reduced supplementation (250-1,000 mg/day administered for 6 months) increases glutathione plasma levels by ~0.2-8 µmol/L (~0.01-0.25 mg/dL). Short-term, oral intake of glutathione reduced does not affect plasma glutathione levels.
- ß-Hydroxybutyrate will have no significant effect up to 17.2 mmol/L (216.9 mg/dL), after which it will decrease the BUN concentration by up to 0.11 mg/dL BUN per mmol/L hydroxybutyrate. The reference range for ß-hydroxybutyrate in plasma is <0.4 to 0.5 mmol/L. ß-hydroxybutyrate concentration over 3 mmol/L are indicative of ketoacidosis; in very severe diabetic ketoacidosis the concentration may exceed 25 mmol/L.
- Hydroxyurea will have no significant effect up to 1.3 mmol/L (9.9 mg/dL), after which it will increase the BUN concentration by up to 1.61 mg/dL BUN per mmol/L hydroxyurea. The recommended dose of hydroxyurea for patients range from 15 mg/kg/day to 30 mg/kg/day. A treatment dose of 2,000 mg/day (~30mg/kg) results in maximum plasma concentration of ~800µmol/L with oral administration and ~1 mmol/L with intravenous method.

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# ероса I Inc.

- . N-acetylcysteine will have no significant effect up to 9.2 mmol/L (150.1 mg/dL), after which it will increase the BUN concentration by up to 0.11 mg/dL BUN per mmol/L N- acetylcysteine. It has been reported that 1 mmol/L N-acetyl cysteine is therapeutically unattainable in plasma. The therapeutic level for N-acetyl cysteine is 0.3 mmol/L.
- Nithiodote will have no significant effect up to 4.1 mmol/L (64.8 mg/dL) after which it will decrease the BUN concentration by up to 0.41 mg/dL BUN per mmol/L Nithiodote. The expected peak sodium thiosulfate plasma concentration following a 12.5 g of Nithiodote is 16.7 mmol/L.

The following levels of exogenous interferences were tested and found to be clinically insignificant for BUN measurements: 1.324 mmol/L (20 mg/dL) acetaminophen, 2 mmol/L (21.6 mg/dL) Li acetoacetic acid, 3.62 mmol/L (65.2 mg/dL) acetyl salicylic acid, 1 mmol/L (5.349 mg/dL) ammonium chloride, 342 µmol/L (6.8 mg/dL) Na ascorbate, 37.5 mmol/L (386 mg/dL) Na bromide, 2.643 mmol/L (125.9 mg/dL) Na cefazolin, 1.46 mmol/L (96.6 mg/dL) Na ceftriaxone, 5.87 µmol/L (0.1 mg/dL) dopamine HCL, 86.8 mmol/L (400 mg/dL) ethanol, 50 umol/L (4.46 mg/dL) (Flaxedil™) gallamine triethiodide, 28 mmol/L (0.5 g/dL) glucose, 2.55 mmol/L (156 mg/dL) oxidized glutathione, 5 mmol/L (38 mg/dL) glycolic acid, 20 U/mL heparin, 2.43 mmol/L (50 mg/dL) ibuprofen, (0.5%) 500 mg/dL intralipid, 1.3 mmol/L (19.4 mg/dL) Na iodide, 1 mmol/L (12 mg/dL) L-cysteine, 25 µmol/L (~0.5 mg/dL) L-Dopa, 3.2 mmol/L (13.5 mg/dL) lithium chloride, 6 mmol/L (210.8 mg/dL) Na metamizole, 2 mmol/L (90 mg/dL) methotrexate, 0.22 mmol/L (4 mg/dL) oxalate (K) monohydrate, 248 µmol/L (6.5 mg/dL) Na pentothal, 1 mmol/L (12.2 mg/dL) Na perchlorate, 4.34 mmol/L (69.5 mg/dL) Na salicylate, 1.72 mmol/L (16.7 mg/dL) K thiocyanate.

The following levels of endogenous interferences were tested and found to be clinically insignificant for BUN measurements: 342 µmol/L (28.8 mg/dL) bilirubin conjugated, 428 umol/L (25 mg/dL) bilirubin unconjugated, 35 mmol/L bicarbonate, Hct 20% to 60% PCV, 6.6 mmol/L (74 mg/dL) lactate, pH 6.8 to 8, 3.5% to 10% total protein, 1.4 mmol/L (23.5 mg/dL) uric acid.

Clinically significant interfering substances for TCO2 measurements are itemized below:

- Samples contaminated with benzalkonium salts used as coatings for in-dwelling lines may cause significant decrease in TCO2 results. For proper line-flushing procedures refer to CLSI H11-A4.
- Citrate will have no significant effect up to 11.8 mmol/L (347.0 mg/dL) after ● which it will increase the TCO2 concentration by up to 0.24 mmol/L TCO2 per mmol/L citrate.

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- EDTA will have no significant effect up to 4.8 mmol/L (178.7 mg/dL) after which it will increase the TCO2 concentration by up to 0.57 mmol/L TCO2 per mmol/L EDTA.
- N-acetyl cysteine will have no significant effect up to 9.6 mmol/L (156.7 mg/dL) ● after which it will increase the TCO2 concentration by up to 0.54 mmol/L TCO2 per mmol/L N-acetyl cysteine. It has been reported that 1 mmol/L N-acetyl cysteine is therapeutically unattainable in plasma. The therapeutic level for Nacetyl cysteine is 0.3 mmol/L.

The following levels of exogenous interferences were tested and found to be clinically insignificant for TCO2measurements: 1.324 mmol/L (20 mg/dL) acetaminophen, 2 mmol/L (21.6 mg/dL) Li acetoacetic acid, 3.62 mmol/L (65.2 mg/dL) acetyl salicylic acid, 1 mmol/L (5.349 mg/dL) ammonium chloride, 342 umol/L (6.8 mg/dL) Na ascorbate, 37.5 mmol/L (386 mg/dL) Na bromide, 2.643 mmol/L (125.9 mg/dL) Na cefazolin, 1.46 mmol/L (96.6 mg/dL) Na ceftriaxone, 5.87 µmol/L (0.1 mg/dL) dopamine HCL, 86.8 mmol/L (400 mg/dL) ethanol, 50 umol/L (4.46 mg/dL) (Flaxedil™) gallamine triethiodide, 28 mmol/L (0.5 g/dL) glucose, 2.55 mmol/L (156 mg/dL) oxidized glutathione, 2.55 mM (78.4 mg/dL) reduced glutathione, 5 mmol/L (38 mg/dL) glycolic acid, 20 U/mL heparin, 2 mmol/L (15 mg/dL) hydroxyurea, 2.43 mmol/L (50 mg/dL) ibuprofen, (0.5%) 500 mg/dL intralipid, 1.3 mmol/L (19.5 mg/dL) Na iodide, 1 mmol/L (12 mg/dL) L-cysteine, 25 µmol/L (~0.5 mg/dL) L-Dopa, 3.2 mmol/L (13.5 mg/dL) lithium chloride, 6 mmol/L (210.8 mg/dL) Na metamizole, 2 mmol/L (90 mg/dL) methotrexate, 16.7 mmol/L (264 mg/dL) Nithiodote, 0.22 mmol/L (4 mg/dL) oxalate (K) monohydrate, 248 µmol/L (6.5 mg/dL) Na pentothal, 1 mmol/L (12.2 mg/dL) Na perchlorate, 4.34 mmol/L (69.5 mg/dL) Na salicylate, 1.72 mmol/L (16.7 mg/dL) K thiocyanate.

The following levels of endogenous interferences were tested and found to be clinically insignificant for TCO2measurements: 342 µmol/L (28.8 mg/dL) bilirubin conjugated, 428 µmol/L (25 mg/dL) bilirubin unconjugated, Hct 20% to 60% PCV, 20 mmol/L (252 mg/dL) ß-hydroxybutyrate, 6.6 mmol/L (74 mg/dL) lactate, pH 6.8 to 8, 3.5% to 10% total protein, 1.4 mmol/L (23.5 mg/dL) uric acid.

#### 5. Clinical Field Precision

The external precision study was conducted to evaluate the precision of the BUN and TCO2 quantitation on the epoc System in the hands of the intended users. The study was evaluated based on CLSI guideline EP05-A3 at three different clinical sites using a different lot of epoc test card at each site. All testing was performed by existing or potential POC operators. Testing was comprised of three parts: 1) aqueous control precision using syringes, 2) whole blood precision using syringes, 3) whole blood precision using capillary tubes.

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# еросаllnc.

### Clinical Field Precision with Aqueous Controls

| Parameter | Aqueous Control Fluid | | |
|-----------------------------------------|-----------------------|--------------|--------------|
| | Level 1 | Level 2 | Level 3 |
| BUN [mg/dL] | | | |
| N | 170 | 171 | 168 |
| Mean BUN [mg/dL] | 52.1 | 17.7 | 7.1 |
| Repeatability (SWR [SD],<br>%CV) | 1.06<br>2.0% | 0.45<br>2.5% | 0.24<br>3.4% |
| Between-day (SD, %CV) | 0.94<br>1.8% | 0.48<br>2.7% | 0.03<br>0.5% |
| Between-site (SD, %CV) | 0.60<br>1.2% | 0.90<br>5.1% | 0.10<br>1.4% |
| Total Reproducibility<br>(ST [SD], %CV) | 1.54<br>3.0% | 1.11<br>6.3% | 0.26<br>3.7% |
| TCO2 [mM] | | | |
| N | 172 | 170 | 169 |
| Mean TCO2 [mM] | 15.9 | 19.7 | 30.4 |
| Repeatability (SWR [SD],<br>%CV) | 0.44<br>2.8% | 0.66<br>3.4% | 0.58<br>1.9% |
| Between-day (SD, %CV) | 0.16<br>1.0% | 0.20<br>1.0% | 0.76<br>2.5% |
| Between-site (SD, %CV) | 0.18<br>1.1% | 0.34<br>1.7% | 0.42<br>1.4% |
| Total Reproducibility<br>(ST [SD], %CV) | 0.50<br>3.1% | 0.78<br>3.9% | 1.05<br>3.4% |

### Clinical Field Precision with Whole Blood

| Sample ID | Num.<br>Runs | Num. of<br>Operators | n | Avg | Min | Max | SWR | %CV |
|-------------|--------------|----------------------|-----|------|------|------|-----|------|
| BUN [mg/dL] | | | | | | | | |
| Hi-Syringe | 12 | 12 | 134 | 57.4 | 51.8 | 72.4 | 1.3 | 2.3% |
| Hi-Cap Tube | 12 | 12 | 136 | 55.5 | 51.3 | 60.3 | 1.6 | 2.9% |
| NB-Syringe | 12 | 12 | 136 | 17.3 | 12.5 | 35.3 | 0.7 | 4.1% |
| NB-Cap Tube | 12 | 12 | 135 | 15.6 | 11.9 | 20.8 | 0.6 | 3.9% |
| Lo-Syringe | 12 | 12 | 136 | 7.0 | 3.7 | 10.6 | 0.6 | 7.2% |
| Lo-Cap Tube | 12 | 12 | 135 | 7.6 | 5.9 | 9.7 | 0.5 | 7.0% |
| TCO2 [mM] | | | | | | | | |
| Hi-Syringe | 12 | 12 | 134 | 36.5 | 33.8 | 40.0 | 0.6 | 1.5% |
| Hi-Cap Tube | 12 | 12 | 139 | 34.1 | 31.7 | 36.2 | 0.7 | 2.1% |
| NB-Syringe | 12 | 12 | 136 | 27.5 | 22.3 | 30.9 | 0.4 | 1.4% |
| NB-Cap Tube | 12 | 12 | 137 | 25.6 | 22.4 | 28.3 | 0.7 | 2.9% |
| Lo-Syringe | 12 | 12 | 136 | 10.5 | 5.0 | 15.9 | 0.4 | 3.7% |
| Lo-Cap Tube | 12 | 12 | 134 | 13.5 | 11.2 | 15.0 | 0.5 | 3.5% |

Hi = High Level; NB = Normal Blood Range; Lo = Low Level

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Precision was additionally assessed on duplicate epoc test results during the Method Comparison Studies. Over 430 patient tests were run in duplicate with approximately equal numbers of venous, arterial and capillary samples. Pooled pair-wise precision was estimated over three concentration ranges for BUN and two concentration ranges for TCO2.

| Parameter | BUN [mg/dL] | | | TCO2 [mM] | |
|---------------------|-------------|--------|-------|-----------|------|
| Range | <22 | 22-100 | >100 | <40 | >40 |
| N | 253 | 143 | 12 | 524 | 23 |
| Average Reading | 13.1 | 44.2 | 111.1 | 24.5 | 44.8 |
| Pair Precision (SD) | 0.6 | 1.2 | 1.6 | 0.6 | 1.0 |
| %CV | 4.6% | 2.7% | 1.4% | 2.6% | 2.2% |

#### 6. Method Comparison

Urea method comparison studies were performed at three clinical sites per CLSI EP09-A3. Venous, arterial and capillary blood samples for a total of over 140 results for each blood type were compared an IDMS-traceable plasma/serum-based laboratory system. Pooled results are shown below.

| BUN [mg/dL] | Roche Cobas 8000 | | |
|-----------------------|------------------|--|--|
| N | 433 | | |
| Sxx | 0.5 | | |
| Syy | 0.9 | | |
| Intercept | 0.3 | | |
| Slope | 0.985 | | |
| Syx | 1.8 | | |
| Xmin | 3 | | |
| Xmax | 118 | | |
| R | 0.998 | | |
| Mean Bias at 26 mg/dL | -0.1+0.2 | | |

{11}------------------------------------------------

### ероса I In с.

TCO2 method comparison studies were performed at three clinical sites. Venous, arterial and capillary patient samples for a total of over 150 results for each blood type were compared with a whole blood point-of-care system. Pooled results are shown below.

| TCO2 [mM] | i-STAT-CHEM8+ |
|--------------------|---------------|
| N | 574 |
| Sxx | 0.68 |
| Syy | 0.64 |
| Intercept | -0.8 |
| Slope | 1.039 |
| Syx | 1.52 |
| Xmin | 7 |
| Xmax | 49 |
| R | 0.974 |
| Mean Bias at 20 mM | 0.0 + 0.2 |

#### 7. Matrix Comparison: Anticoagulant

A method comparison approach was used to compare the epoc BUN and TCO2 results in venous blood samples, collected from over 60 volunteer donors into evacuated tubes containing no additive, and further aliquoted into three (3) vacutainers containing noadditive, Li-heparin and Na-heparin to create 3-way matched samples. It was concluded from the analysis that there was no significant difference between BUN and TCO2 results in Li-heparinized, Na-heparinized and non-anticoagulated blood samples on the epoc System.

#### CONCLUSION

The information provided in this pre-market notification demonstrates that the epoc BGEM Test Card and Blood Analysis System is substantially equivalent to the legally marketed predicate device for its intended use.