ABL90 FLEX PLUS System

K241037 · Radiometer Medicals Aps · CEM · Jan 14, 2025 · Clinical Chemistry

Device Facts

• Record ID: K241037
• Device Name: ABL90 FLEX PLUS System
• Applicant: Radiometer Medicals Aps
• Product Code: CEM · Clinical Chemistry
• Decision Date: Jan 14, 2025
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1600
• Device Class: Class 2

Intended Use

The ABL90 FLEX PLUS System is an in vitro diagnostic, portable, automated analyzer that quantitatively measures electrolytes (cK+, cNa+, cCa2+), glucose, and lactate in heparinized arterial and venous whole blood. The ABL90 FLEX PLUS System is intended for use by trained technologists, nurses, physicians and therapists. It is intended for use in a laboratory environment, near patient, or point-of-care setting. These tests are only performed under a physician's order. Potassium (cK+): Potassium measurements are used to monitor electrolyte balance in the diagnosis and treatment of disease conditions characterized by low or high blood potassium levels. Sodium (cNa+): Sodium measurements are used in the diagnosis and treatment of aldosteronism, diabetes insipidus, adrenal hypertension, Addison's disease, dehydration, inappropriate antidiuretic secretion, or other diseases involving electrolyte imbalance. Calcium (cCa2+): Calcium measurements are used in the diagnosis and treatment of parathyroid disease, a variety of bone diseases, chronic renal disease and tetany. Glucose (cGlu): Glucose measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus and idiopathic hypoglycemia, and of pancreatic islet cell carcinoma. Lactate (cLac): The lactate measurements measure the concentration of lactate. Lactate measurements are used to evaluate the acid-base status and are used in the diagnosis and treatment of lactic acidosis (abnormally high acidity of the blood).

Device Story

Portable, automated in vitro diagnostic analyzer; measures electrolytes (cK+, cNa+, cCa2+), glucose, and lactate in heparinized arterial/venous whole blood. Operates via potentiometry (electrolytes) and amperometry (glucose, lactate). Features automated sample inlet mechanism supporting syringe (S65) and short probe (SP65) modes. Used in laboratory, near-patient, or point-of-care settings by trained clinicians. Input: 65 µL blood sample. Output: Quantitative concentration values displayed on touch screen. Assists clinicians in monitoring electrolyte balance, diagnosing metabolic/endocrine disorders, and evaluating acid-base status. Benefits patient through rapid, point-of-care diagnostic information for timely clinical decision-making.

Clinical Evidence

No clinical data. Performance supported by analytical bench testing: precision/reproducibility (multi-day, multi-site), linearity (CLSI EP06-A2), analytical specificity/interference (paired-difference and dose-response), and method comparison (CLSI EP09c-ED3) against predicate using 353 heparinized whole blood samples. Deming regression showed high correlation (R2 ≥ 0.994) across all parameters.

Technological Characteristics

Portable analyzer; potentiometric sensors (cK+, cNa+, cCa2+); amperometric sensors (cGlu, cLac). Consumables: sensor cassette, solution pack. Sample volume: 65 µL. Modes: S65 syringe, SP65 short probe. Connectivity: barcode reader, communication ports. User interface: touch screen. Power: optional battery pack. Software-controlled fluid transport and analysis.

Indications for Use

Indicated for trained technologists, nurses, physicians, and therapists to quantitatively measure electrolytes (cK+, cNa+, cCa2+), glucose, and lactate in heparinized arterial and venous whole blood in laboratory, near-patient, or point-of-care settings under physician order. Used for monitoring electrolyte balance, diagnosing/treating electrolyte imbalances (aldosteronism, diabetes insipidus, adrenal hypertension, Addison's disease, dehydration, SIADH), parathyroid/bone/renal diseases, tetany, carbohydrate metabolism disorders (diabetes mellitus, idiopathic hypoglycemia, pancreatic islet cell carcinoma), and evaluating acid-base status/lactic acidosis.

Regulatory Classification

Identification

A potassium test system is a device intended to measure potassium in serum, plasma, and urine. Measurements obtained by this device are used to monitor electrolyte balance in the diagnosis and treatment of diseases conditions characterized by low or high blood potassium levels.

Predicate Devices

• ABL90 Flex (K092686)

Submission Summary (Full Text)

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January 14, 2025

Radiometer Medicals ApS Andrea Swingle Senior Specialist, Regulatory Affairs Åkandevej 21 2700 Brønshøj Denmark

Re: K241037

Trade/Device Name: ABL90 FLEX PLUS System Regulation Number: 21 CFR 862.1600 Regulation Name: Potassium Test System Regulatory Class: Class II Product Code: CEM, JGS, JFP, CGA, KHP Dated: December 10, 2024 Received: December 10, 2024

Dear Andrea Swingle:

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 (the 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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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.

Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

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Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

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 Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

All medical devices, including Class I and unclassified devices and combination product device constituent parts are required to be in compliance with the final Unique Device Identification System rule ("UDI Rue"). The UDI Rule requires, among other things, that a device bear a unique device identifier (UDI) on its label and package (21 CFR 801.20(a)) unless an exception or alternative applies (21 CFR 801.20(b)) and that the dates on the device label be formatted in accordance with 21 CFR 801.18. The UDI Rule (21 CFR 830.300(a) and 830.320(b)) also requires that certain information be submitted to the Global Unique Device Identification Database (GUDID) (21 CFR Part 830 Subpart E). For additional information on these requirements, please see the UDI System webpage at https://www.fda.gov/medical-device-advicecomprehensive-regulatory-assistance/unique-device-identification-system-udi-system.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

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For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). 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 (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email ([e-mail]) or phone [phone] or 301-796-7100).

Sincerely,

# Paula V. Caposino -S

Paula Caposino, Ph.D. Deputy Division Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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# Indications for Use

510(k) Number (if known) K241037

Device Name ABL90 FLEX PLUS System

#### Indications for Use (Describe)

The ABL90 FLEX PLUS System is an in vitro diagnostic, portable, automated analyzer that quantitatively measures electrolytes (cK+, cNa+, cCa2+), glucose, and lactate in heparinized arterial and venous whole blood.

The ABL90 FLEX PLUS System is intended for use by trained technologists, nurses, physicians and therapists. It is intended for use in a laboratory environment, near patient, or point-of-care setting. These tests are only performed under a physician's order.

Potassium (cK+): Potassium measurements are used to monitor electrolyte balance in the diagnosis and treatment of disease conditions characterized by low or high blood potassium levels.

Sodium (cNa+): Sodium measurements are used in the diagnosis and treatment of aldosteronism, diabetes insipidus, adrenal hypertension, Addison's disease, delydration, inappropriate antidiuretic secretion, or other diseases involving electrolyte imbalance.

Calcium (cCa2+): Calcium measurements are used in the diagnosis and treatment of parathyroid disease, a variety of bone diseases, chronic renal disease and tetany.

Glucose (cGlu): Glucose measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus and idiopathic hypoglycemia, and of pancreatic islet cell carcinoma.

Lactate (cLac): The lactate measure the concentration of lactate. Lactate measurements are used to evaluate the acid-base status and are used in the diagnosis and treatment of lactic acidity of the blood).

| Type of Use (Select one or both, as applicable) | | | |
|--------------------------------------------------------------------------------------------------|-----------------------------------------------------------------|-----------------------------------------------------------------------------------|---------------------------------------------|
| <table><tr><td><span> Prescription Use (Part 21 CFR 801 Subpart D) </span></td></tr></table> | <span> Prescription Use (Part 21 CFR 801 Subpart D) </span> | <table><tr><td> Over-The-Counter Use (21 CFR 801 Subpart C) </td></tr></table> | Over-The-Counter Use (21 CFR 801 Subpart C) |
| <span> Prescription Use (Part 21 CFR 801 Subpart D) </span> | | | |
| Over-The-Counter Use (21 CFR 801 Subpart C) | | | |

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# 510(k) Summary - K240137

The information provided in this 510(k) summary are in accordance with 21 CFR 807.92

Submitter Information:

| Company Name: | Radiometer Medical ApS |
|-----------------|---------------------------------------------|
| ER Number: | 3002807968 |
| Address: | Aakandevej 21<br>2700 Broenshoej<br>Denmark |
| Contact Person: | Hsiao-Qing Chow |
| Phone: | [phone] |

Application Correspondent:

| Name: | Andrea Swingle |
|-----------|---------------------------------------|
| Function: | Senior Specialist, Regulatory Affairs |
| Email: | [e-mail] |
| Phone: | [phone] |

Date prepared: January 14, 2024

# Device Information

| Device Trade Name: | ABL90 FLEX PLUS System |
|-----------------------|--------------------------------------------|
| Common Name: | Blood Gas Analyzer |
| Regulations: | - 21 CFR 862.1600, Potassium test system |
| | - 21 CFR 862.1665, Sodium test system |
| | - 21 CFR 862.1145, Calcium test system |
| | - 21 CFR 862.1345, Glucose test system |
| | - 21 CFR 862.1450, Lactic acid test system |
| Product Codes: | CEM, JGS, JFP, CGA, KHP |
| Device Class: | Class I for KHP; All others: Class II |
| Classification Panel: | Clinical Chemistry |

Predicate Device

| Device Trade Name: | ABL90 FLEX |
|--------------------|--------------------------------------------|
| Common Name: | Blood Gas Analyzer |
| 510(k) | K092686 |
| Regulations: | - 21 CFR 862.1600, Potassium test system |
| | - 21 CFR 862.1665, Sodium test system |
| | - 21 CFR 862.1145, Calcium test system |
| | - 21 CFR 862.1345, Glucose test system |
| | - 21 CFR 862.1450, Lactic acid test system |

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Product Codes: Device Class: Classification Panels: CEM, JGS, JFP, CGA, KHP Class I for KHP; All others: Class II Clinical Chemistry

## Device Description

The ABL90 FLEX PLUS System consists of the ABL90 FLEX PLUS analyzer, sensor cassette and solution pack consumables, and related accessories for the analyzers. The ABL90 FLEX PLUS is a portable, automated system intended for in vitro testing of samples of balanced heparinized whole blood for electrolytes (cK+, cNa*, cCa²), glucose, and lactate. The ABL90 FLEX PLUS System has an automated sample inlet mechanism, which can collect blood through two different measuring modes: the S65 syringe mode and the SP65 short probe mode.

## Intended Use

The ABL90 FLEX PLUS System is an in vitro diagnostic, portable, automated analyzer that quantitatively measures electrolytes (cK+, cNa*, cCa²+), glucose, and lactate in heparinized arterial and venous whole blood.

The ABL90 FLEX PLUS System is intended for use by trained technologists, nurses, physicians and therapists. It is intended for use in a laboratory environment, near patient, or point-of-care setting.

These tests are only performed under a physician's order.

Potassium (cK+): Potassium measurements are used to monitor electrolyte balance in the diaqnosis and treatment of disease conditions characterized by low or high blood potassium levels.

Sodium (cNa+); Sodium measurements are used in the diagnosis and treatment of aldosteronism, diabetes insipidus, adrenal hypertension, Addison's disease, dehydration, inappropriate antidiuretic secretion, or other diseases involving electrolyte imbalance.

Calcium (cCa2+): Calcium measurements are used in the diagnosis and treatment of parathyroid disease, a variety of bone diseases, chronic renal disease and tetany.

Glucose (cGlu): Glucose measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus and idiopathic hypoglycemia, and of pancreatic islet cell carcinoma.

Lactate (cLac): The lactate measurements measure the concentration of lactate. Lactate measurements are used to evaluate the acid-base status and are used in the diagnosis and treatment of lactic acidosis (abnormally high acidity of the blood).

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# Substantial Equivalence Comparison

# Substantial equivalence comparison table

| | ABL90 FLEX PLUS System<br>(This 510(k)) | ABL90 FLEX<br>(510(k) K092686) | |
|--------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------|
| Manufacturer | Radiometer Medical ApS | Radiometer Medical ApS | |
| Indications for<br>Use | The ABL90 FLEX PLUS System is an <i>in vitro</i> diagnostic, portable, automated<br>analyzer that quantitatively measures<br>electrolytes (cK+, cNa+, cCa2+),<br>glucose, and lactate in heparinized<br>arterial and venous whole blood. | The ABL90 FLEX is a portable,<br>automated analyzer that measures<br>pH, blood gases, electrolytes,<br>glucose, lactate and oximetry in<br>heparinized whole blood. The ABL90<br>FLEX is intended for use by trained<br>technologists, nurses, physicians and<br>therapists. It is intended for use in a<br>laboratory environment, near patient<br>or point-of-care setting. | |
| Intended Use | Measurement of cK+, cNa+, cCa2+,<br>cGlu and cLac | Measurement of cK+, cNa+, cCa2+,<br>cGlu and cLac | |
| Intended use<br>environment | Laboratory environment, near patient<br>or point-of-care setting | Laboratory environment, near patient<br>or point-of-care setting | |
| Prescription/OTC<br>Use | Prescription | Prescription | |
| Sample requirements | | | |
| Sample type | Heparinized whole blood (arterial,<br>venous) | Heparinized whole blood (arterial,<br>venous) | |
| Compatible<br>sampling devices | Radiometer samplers (in S65 mode)<br>and non-Radiometer samplers (in<br>SP65 mode) | Radiometer samplers and non-<br>Radiometer samplers | |
| Sample volume | 65 µL | 65 µL | |
| Sample<br>preparation | With balanced heparin anticoagulant | With balanced heparin anticoagulant | |
| Device design | | | |
| Operating | Potentiometry: cK+, cNa+, cCa2+ | Potentiometry: cK+, cNa+, cCa2+ | |
| principles | Amperometry: cGlu and cLac | Amperometry: cGlu and cLac | |
| Major<br>components | ● Touch screen<br>● Barcode reader<br>● Sample mixer<br>● Inlet module<br>● Fluid transport system<br>● Oximetry module<br>● Electronics<br>● Software<br>● Printer<br>● Optional battery pack<br>● Communication ports | ● Touch screen<br>● Barcode reader<br>● Sample mixer<br>● Inlet module<br>● Fluid transport system<br>● Oximetry module<br>● Electronics<br>● Software<br>● Printer<br>● Communication ports | |
| Consumables | ● Sensor cassette<br>● Solution pack | ● Sensor cassette<br>● Solution pack | |
| Performance characteristics | | | |
| | | ABL90 FLEX PLUS System<br>(This 510(k)) | ABL90 FLEX<br>(510(k) K092686) |
| Reportable<br>ranges | cK+: | 2.1 - 10.5 mEq/L | cK+: 2.1 - 10.5 mEq/L |
| | cCa2+: | 2.00 - 9.94 mg/dL | cCa2+: 2.00 - 9.92 mg/dL |
| | cNa+: | 116 - 180 mEq/L | cNa+: 116 - 180 mEq/L |
| | cGlu: | 18 - 738 mg/dL | cGlu: 9 - 738 mg/dL |
| | cLac: | 4 - 216 mg/dL | cLac: 4 - 216 mg/dL |

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## Analytical Performance Testing Summary

The ABL90 FLEX PLUS System has been tested for analytical performance, including tests for linearity, limit of blank, detection and quantification, precision, bias, interference, stability. The tests were conducted in general accordance with Clinical Laboratory Standards Institute (CLSI) guidelines, all of which are FDA-recognized consensus standards.

#### Linearity

Linearity testing was conducted in general accordance with CLSI EP06, Evaluation of the Linearity of Quantitative Measurement Procedures, 2nd Edition and EP39, A Hierarchical Approach to Selecting Surrogate Samples for the Evaluation of In Vitro Medical Laboratory Tests, 1st Edition. The resulting linearity intervals are listed in Table 1.

| Parameter<br>(unit) | Reportable<br>Range | Tested<br>Range | Slope | Intercept | R2 |
|---------------------|---------------------|-----------------|-------|-----------|-------|
| cCa2+ (mg/dL) | 2.00-9.94 | 1.896-11.146 | 0.883 | 0.445 | 1.000 |
| cK+ (mEq/L) | 2.1-10.5 | 0.99-11.99 | 1.001 | 0.027 | 1.000 |
| cNa+ (mEq/L) | 116-180 | 90.0-194.9 | 1.001 | -0.642 | 1.000 |
| cGlu (mg/dL) | 18-738 | 17.5-926.1 | 1.032 | -1.073 | 1.000 |
| cLac (mg/dL) | 4-216 | 1.9-252.9 | 0.971 | -0.433 | 1.000 |

#### Table 1: Linearity results

## Detection

Detection capability testing in terms of limit of blank (LoB), limit of detection (LoD) and limit of quantitation (LoQ) was conducted. in general accordance with CLSI EP17-A2, Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures, and EP39, A Hierarchical Approach to Selecting Surrogate Samples for the Evaluation of In Vitro Medical Laboratory Tests, 1st Edition. Table 2 shows the results of the detection testing.

| Parameter | Unit | LoB | LoD | LoQ |
|-----------|-------|--------|-----|------|
| cCa2+ | mg/dL | N/A | N/A | 1.26 |
| cK+ | mEq/L | N/A | N/A | 1.6 |
| cNa+ | mEq/L | N/A | N/A | 99 |
| cGlu | mg/dL | -0.023 | 5 | 5 |

#### Table 2: Detection results

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| Parameter | Unit | LoB | LoD | LoQ |
|-----------|-------|------|------|-----|
| cLac | mg/dL | -0.7 | -0.3 | 2 |

N/A: Not applicable

#### Precision

Two precision studies were performed; both were in general accordance with CLSI EP05-A3, Evaluation of Precision of Quantitative Measurement Procedures.

#### Precision using stable, aqueous ampoule-based QC material

The primary endpoints of the study were repeatability and within laboratory precision for pooled across several sites. The secondary endpoint was reproducibility between sites. The sample material was Radiometer QUALICHECK5+ QC ampoules, a QC material that comes in four "levels". Testing occurred at three external sites. Table 3 presents the data on the primary and secondary endpoints.

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| Parameter | QC<br>ampoule | N | Mean | Repeatability | | Within Lab Precision | | Reproducibility | |
|------------------|---------------|-----|------|---------------|-----|----------------------|-----|-----------------|-----|
| | | | | SD | CV% | SD | CV% | SD | CV% |
| cCa2+<br>(mg/dL) | QC5+ L 1 | 243 | 3.99 | 0.010 | 0.3 | 0.018 | 0.5 | 0.019 | 0.5 |
| | QC5+ L 2 | 244 | 2.11 | 0.003 | 0.1 | 0.012 | 0.6 | 0.013 | 0.6 |
| | QC5+ L 3 | 244 | 1.52 | 0.003 | 0.2 | 0.015 | 1.0 | 0.015 | 1.0 |
| | QC5+ L 4 | 244 | 6.34 | 0.014 | 0.2 | 0.030 | 0.5 | 0.036 | 0.6 |
| cGlu<br>(mg/dL) | QC5+ L 1 | 243 | 28 | 0.3 | 1.1 | 0.5 | 2.0 | 0.6 | 2.1 |
| | QC5+ L 2 | 244 | 101 | 0.6 | 0.6 | 1.2 | 1.2 | 1.2 | 1.2 |
| | QC5+ L 3 | 244 | 247 | 1.3 | 0.5 | 5.4 | 2.2 | 6.3 | 2.5 |
| cK+<br>(meq/L) | QC5+ L 1 | 243 | 1.7 | 0.00 | 0.2 | 0.02 | 1.0 | 0.02 | 1.1 |
| | QC5+ L 2 | 244 | 3.7 | 0.00 | 0.1 | 0.01 | 0.2 | 0.01 | 0.2 |
| | QC5+ L 3 | 244 | 5.4 | 0.01 | 0.1 | 0.01 | 0.2 | 0.01 | 0.2 |
| | QC5+ L 4 | 244 | 6.1 | 0.01 | 0.1 | 0.02 | 0.3 | 0.02 | 0.3 |
| cLac<br>(mg/dL) | QC5+ L 1 | 243 | 39 | 0.3 | 0.8 | 0.5 | 1.3 | 0.5 | 1.3 |
| | QC5+ L 2 | 244 | 15 | 0.2 | 1.1 | 0.2 | 1.5 | 0.2 | 1.6 |
| | QC5+ L 3 | 244 | 97 | 0.3 | 0.3 | 1.2 | 1.3 | 1.2 | 1.3 |
| cNa+<br>(meq/L) | QC5+ L 1 | 243 | 162 | 0.2 | 0.1 | 0.2 | 0.1 | 0.3 | 0.2 |
| | QC5+ L 2 | 244 | 141 | 0.1 | 0.1 | 0.1 | 0.1 | 0.1 | 0.1 |
| | QC5+ L 3 | 244 | 126 | 0.1 | 0.1 | 0.2 | 0.1 | 0.2 | 0.1 |
| | OC5+ L 4 | 244 | 119 | 0.1 | 0.1 | 0.3 | 0.3 | 0.3 | 0.3 |

Table 3: Precision results using QC materials

N: Number of data points for analysis SD: Standard Deviation CV%: %Coefficient of Variation QC5+ L X: QUALICHECK5+ Level X

#### Precision using blood

The primary endpoint of the study was repeatability, designated SD, pooled across sites. Two levels of concentration were covered for all parameters. Testing was conducted in both samples collection modes: syringe/S65 mode and short probe/SP65 mode. Table 4 summarizes the results of the study.

| | | | | Repeatability | |
|--------------|-----|----------------|-------|---------------|--------|
| Parameter | N | Test interval | Mean | SD | CV (%) |
| S65 Mode | | | | | |
| Ca2+ (mg/dL) | 18 | 2.605 - <3.407 | 3.165 | 0.007 | 0.23 |
| | 70 | 3.407 - <4.609 | 4.403 | 0.016 | 0.37 |
| | 154 | 4.609 - <5.17 | 4.826 | 0.022 | 0.45 |
| | 4 | 5.17 - <5.812 | 5.313 | 0.003 | 0.06 |
| K+ (mEq/L) | 18 | 2.5 - <3 | 2.682 | 0.009 | 0.35 |
| | 4 | 3 - <3.4 | 3.185 | 0.007 | 0.22 |
| | 202 | 3.4 - <4.5 | 3.908 | 0.010 | 0.25 |
| | 22 | 4.5 - <6 | 5.090 | 0.007 | 0.14 |

Table 4: Precision results using whole blood

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| Parameter | N | Test interval | Mean | Repeatability | |
|--------------|-----|----------------|--------|---------------|--------|
| | | | | SD | CV (%) |
| Na+ (mEq/L) | 18 | 116 - <120 | 117.54 | 0.118 | 0.10 |
| | 24 | 120 - <136 | 133.56 | 0.194 | 0.14 |
| | 164 | 136 - <146 | 140.95 | 0.194 | 0.14 |
| | 40 | 146 - <155 | 150.02 | 0.161 | 0.11 |
| Glu (mg/dL) | 16 | 23 - <47 | 40.275 | 0.316 | 0.79 |
| | 2 | 47 - <65 | 49.150 | 0.354 | 0.72 |
| | 200 | 65 - <200 | 140.29 | 1.018 | 0.73 |
| | 28 | 200 - <595 | 262.32 | 2.221 | 0.85 |
| Lac (mg/dL) | 178 | 4 - <20 | 10.264 | 0.231 | 2.25 |
| | 14 | 20 - <27 | 22.686 | 0.177 | 0.78 |
| | 14 | 27 - <36 | 30.236 | 0.379 | 1.25 |
| SP65 Mode | | | | | |
| Ca2+ (mg/dL) | 18 | 2.605 - <3.407 | 3.171 | 0.005 | 0.16 |
| | 66 | 3.407 - <4.609 | 4.389 | 0.013 | 0.31 |
| | 156 | 4.609 - <5.17 | 4.823 | 0.012 | 0.24 |
| | 4 | 5.17 - <5.812 | 5.258 | 0.008 | 0.14 |
| K+ (mEq/L) | 18 | 2.5 - <3 | 2.673 | 0.026 | 0.96 |
| | 8 | 3 - <3.4 | 3.280 | 0.005 | 0.15 |
| | 198 | 3.4 - <4.5 | 3.899 | 0.009 | 0.22 |
| | 20 | 4.5 - <6 | 5.031 | 0.007 | 0.14 |
| Na+ (mEq/L) | 16 | 116 - <120 | 118.04 | 0.061 | 0.05 |
| | 24 | 120 - <136 | 133.48 | 0.094 | 0.07 |
| | 160 | 136 - <146 | 140.93 | 0.083 | 0.06 |
| | 42 | 146 - <155 | 149.79 | 0.091 | 0.06 |
| Glu (mg/dL) | 18 | 23 - <65 | 39.583 | 0.207 | 0.52 |
| | 194 | 65 - <200 | 138.79 | 1.098 | 0.79 |
| | 32 | 200 - <595 | 263.24 | 0.912 | 0.35 |
| Lac (mg/dL) | 178 | 4 - <20 | 10.222 | 0.200 | 1.96 |
| | 14 | 20 - <27 | 22.818 | 0.235 | 1.03 |
| | 14 | 27 - <36 | 30.813 | 0.231 | 0.75 |

N: Number of data points for analysis Test interval: Range of values studied SD: Standard Deviation CV%: %Coefficient of Variation

## Method comparison

Bias was determined by conducting a method comparison study in general accordance with CLSI EP09c, 3rd Edition, Measurement Procedure Comparison and Bias Estimation Using Patient Samples. The comparator device was the ABL90 FLEX PLUS analyzer as it was designed at the time of the clearance of K160153, in terms of its characteristics related to analytical performance. Testing was conducted using both arterial and venous blood, and in both samples collection modes: syringe/S65 mode and short probe/SP65 mode. Analysis was performed by linear regression over the reportable range. Results are presented in Table 5 and Table 6.

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Г

| Parameter | Blood<br>type | Mode | n | Min-max | Intercept | Slope | R2 | Medical<br>decision<br>point | Bias at<br>MD |
|------------------|---------------|------|-----|-------------|-----------|-------|-------|------------------------------|---------------|
| cNa+<br>(meq/L) | A | S65 | 225 | 117.2-179.5 | 0.039 | 1.002 | 0.999 | 136.00 | 0.287 |
| | A | SP65 | 218 | 116.8-179.7 | -0.227 | 1.003 | 0.999 | | 0.223 |
| | V | S65 | 234 | 117.2-179.5 | -0.012 | 1.002 | 0.999 | | 0.242 |
| | V | SP65 | 224 | 116.8-179.7 | -0.276 | 1.004 | 0.999 | | 0.220 |
| cK+<br>(meq/L) | A | S65 | 222 | 2.12-10.4 | 0.018 | 0.996 | 0.999 | 3.400 | 0.004 |
| | A | SP65 | 218 | 2.11-10.45 | 0.033 | 0.993 | 0.997 | | 0.008 |
| | V | S65 | 233 | 2.12-10.4 | 0.014 | 0.996 | 0.999 | | 0.000 |
| | V | SP65 | 225 | 2.11-10.45 | 0.033 | 0.992 | 0.997 | | 0.007 |
| cCa2+<br>(mg/dL) | A | S65 | 222 | 2.114-9.791 | -0.014 | 1.003 | 0.999 | 4.600 | 0.001 |
| | A | SP65 | 214 | 2.127-9.651 | -0.046 | 1.011 | 0.999 | | 0.003 |
| | V | S65 | 231 | 2.114-9.791 | -0.019 | 1.004 | 0.999 | | 0.000 |
| | V | SP65 | 220 | 2.127-9.651 | -0.049 | 1.011 | 0.999 | | 0.003 |
| cGlu<br>(mg/dL) | A | S65 | 224 | 20.5-728.1 | 0.425 | 0.988 | 0.999 | 65.000 | -0.337 |
| | A | SP65 | 215 | 20.1-712.7 | -0.024 | 0.990 | 0.999 | | -0.664 |
| | V | S65 | 232 | 20.5-728.1 | 0.184 | 0.989 | 0.999 | | -0.558 |
| | V | SP65 | 219 | 20.1-712.7 | -0.045 | 0.990 | 0.999 | | -0.696 |
| cLac<br>(mg/dL) | A | S65 | 221 | 4.1-209.7 | -0.182 | 1.007 | 0.995 | 18.000 | -0.053 |
| | A | SP65 | 216 | 4-209.9 | -0.093 | 0.999 | 0.995 | | -0.119 |
| | V | S65 | 233 | 4.3-209.7 | -0.333 | 1.008 | 0.994 | | -0.181 |
| | V | SP65 | 223 | 4.3-209.9 | -0.202 | 1.000 | 0.995 | | -0.208 |

Table 5: Method comparison results using reportable ranges specified in the protocol

A: Arterial

V: Venous

Min-max: Range of values measured

Table 6: Method comparison results, arterial and venous combined, additional medical decision levels

| Parameter | n | Intercept | Slope | R2 | Medical<br>decision<br>point | Bias at MD |
|-------------|-----|-----------|-------|-------|------------------------------|------------|
| <b>S65</b> | | | | | | |
| Ca (mg/dL) | 437 | -0.018 | 1.004 | 0.998 | 4.600 | 0.001 |
| | | | | | 5.170 | 0.003 |
| Glu (mg/dL) | 439 | 0.295 | 0.988 | 0.999 | 65.000 | -0.460 |
| | | | | | 200.00 | -2.028 |
| K (mEq/L) | 438 | 0.015 | 0.996 | 0.998 | 3.400 | 0.002 |
| | | | | | 4.500 | -0.002 |
| Lac (mg/dL) | 436 | -0.245 | 1.007 | 0.995 | 18.000 | -0.116 |
| | | | | | 36.000 | 0.013 |
| Na (mEq/L) | 441 | -0.077 | 1.003 | 0.999 | 136.00 | 0.265 |
| | | | | | 146.00 | 0.290 |
| <b>SP65</b> | | | | | | |
| Ca (mg/dL) | 420 | -0.047 | 1.011 | 0.998 | 4.600 | 0.003 |
| | | | | | 5.170 | 0.009 |

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| Parameter | n | Intercept | Slope | R2 | Medical<br>decision<br>point | Bias at MD |
|-------------|-----|-----------|-------|-------|------------------------------|------------|
| Glu (mg/dL) | 420 | 0.002 | 0.990 | 0.999 | 65.000 | -0.663 |
| | | | | | 200.00 | -2.045 |
| K (mEq/L) | 425 | 0.029 | 0.993 | 0.997 | 3.400 | 0.004 |
| | | | | | 4.500 | -0.004 |
| Lac (mg/dL) | 422 | -0.143 | 0.999 | 0.995 | 18.000 | -0.156 |
| | | | | | 36.000 | -0.169 |
| Na (mEq/L) | 425 | -0.302 | 1.004 | 0.999 | 136.00 | 0.221 |
| | | | | | 146.00 | 0.259 |

#### Interference

Interfering substances were evaluated based on testing conducted in general accordance with CLSI, EP07, Interference Testing in Clinical Chemistry, 3rd Edition, and CLSI EP37, Supplemental Tables for Interference Testing in Clinical Chemistry, 1st Edition. The interference testing consists of two parts: paired-difference and dose-response studies. The paired-difference study was conducted on a large panel of likely interferents, using clinically significant amount of the interferents. Dose-response studies were only conducted in cases where a clinically significant interferent effect was noted during the paired different study. Table 7 summarizes the testing that was performed. Specific values for level of interference are described in Table 8.

| Interferent | cCa2+ | cK+ | cNa+ | cGlu | cLac | Interferent | cGlu | cLac |
|------------------------|-------|-----|------|------|------|--------------------|------|------|
| Intralipid | - | - | X | - | - | Lactate | - | - |
| Hemolysis | X | X | X | - | - | Thiocyanate | X | X |
| Bilirubin (unconj) | - | - | - | - | - | Acetaminophen | - | - |
| Bilirubin (conj) | - | - | - | - | - | Acetoacetate | - | - |
| Biotin | - | - | - | - | - | Chlorpromazine HCl | - | - |
| Propofol | - | - | - | - | - | Creatinine | - | - |
| Fluoride | - | - | - | X | X | 2-deoxy Glucose | X | - |
| Potassium @ low level | - | - | - | - | - | EDTA | - | X |
| Potassium @ high level | - | - | - | - | - | Formaldehyde | - | - |
| Sodium @ low level | - | - | - | - | - | Formic acid | - | X |
| Sodium @ high level | - | - | - | - | - | Galactose | X | - |
| Calcium @ low level | - | - | - | - | - | Glucosamine HCl | - | - |
| Calcium @ high level | - | - | - | - | - | Glycolic acid | - | X |
| Lithium | - | - | - | - | - | Heparin | - | - |
| Ammoniumchloride | - | - | - | - | - | Ibuprofen | - | - |
| Ascorbate | - | - | - | - | - | Maltose | - | - |
| Benzalkonium chloride | X | X | X | - | - | Mannose | - | - |
| Leflunomide | X | - | - | - | - | Methanol | - | - |
| Nortriptyline | - | - | - | - | - | N-acetylcystein | - | X |

#### Table 7: Interference testing

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| Interferent | cCa²⁺ | cK⁺ | cNa⁺ | cGlu | cLac |
|----------------------|-------|-----|------|------|------|
| Teriflunomide | × | × | × | | |
| Thiopental | | | - | | |
| Magnesium | × | | - | | |
| pH @ low level | × | | | | |
| pH @ high level | × | | | | |
| Perchlorate | - | | | | |
| Strontium | - | | | | |
| Oxalate | | | | - | - |
| Salicylic acid | | | | - | - |
| Acetylsalicylic acid | | | | - | - |
| Citrate | | | | - | × |
| Zinc | × | - | - | | |

| Interferent | cGlu | cLac |
|---------------------------|------|------|
| Pralidoxime chloride | - | - |
| Pyruvate | - | - |
| Urea | - | - |
| Uric acid | - | - |
| Xylose | - | - |
| Dopamine<br>Hydrochloride | - | - |
| Ethanol | - | - |
| Povidone-iodine | X | - |
| D-Glucose | - | - |

Key

No clinically significant interference Clinically significant interference

י ×

Interferent not relevant to be tested for this parameter

#### Table 8: Interference values

| Interferent | Maximum test<br>concentration | Highest<br>concentration level<br>where interference<br>was not significant | Impact on result<br>for maximum test<br>concentration |
|-----------------------------------------------|-------------------------------|-----------------------------------------------------------------------------|-------------------------------------------------------|
| cCa2+ (test level: 4.6 mg/dL) | | | |
| Benzalkonium chloride | 2.4 mg/dL | 0.6 mg/dL | 1.94 mg/dL |
| Hemolysis | 20% | 5% | -1.43 mg/dL |
| Leflunomide | 30 mg/dL | 15 mg/dL | -0.73 mg/dL |
| Magnesium (-nitrate)<br>(test matrix: Plasma) | 385 mg/dL | 96 mg/dL | 1.13 mg/dL |
| pH @ low level<br>(test matrix: Plasmaᵃ) | 6.8 | Interference for<br>pH < 7.2 | 1.58 mg/dL |
| pH @ high level<br>(test matrix: Plasmaᵃ) | 8.0 | Interference for<br>pH > 7.6 | -1.20 mg/dL |
| Zn+ (Zinc chloride) | 2.3 mg/dL | 1.7 mg/dL | 0.58 mg/dL |
| cCa2+ (test level: 6.0 mg/dL) | | | |
| Benzalkonium chloride | 2.4 mg/dL | 0.45 mg/dL | 2.54 mg/dL |
| Hemolysis | 20% | 5% | -1.69 mg/dL |
| Leflunomide | 30 mg/dL | 22.5 mg/dL | -0.85 mg/dL |
| Magnesium (-nitrate)<br>(test matrix: Plasma) | 385 mg/dL | 72 mg/dL | 1.53 mg/dL |
| pH @ low level<br>(test matrix: Plasmaᵃ) | 6.8 | Interference for<br>pH < 7.2 | 2.35 mg/dL |
| pH @ high level<br>(test matrix: Plasmaᵃ) | 8.0 | Interference for<br>pH > 7.7 | -0.84 mg/dL |
| Teriflunomide | 30 mg/dL | 22.5 mg/dL | -0.79 mg/dL |

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| Interferent | Maximum test<br>concentration | Highest<br>concentration level<br>where interference<br>was not significant | Impact on result<br>for maximum test<br>concentration |
|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------|-----------------------------------------------------------------------------|-------------------------------------------------------|
| Notes for Calcium: | | | |
| a) A change in the pH of blood has the physiological effect of changing the concentrations of<br>ionized calcium. An increase of 1 pH unit results in a decrease of approximately 2 mg/dL<br>cCa2+. | | | |
| | cK+ (test level: 3.5 mEq/L) | | |
| Benzalkonium chloride | 2.4 mg/dL | 0.6 mg/dL | 1.11 mEq/L |
| Hemolysis | 20% | 0.25% | 13.1 mEq/L |
| Teriflunomide | 30 mg/dL | 15 mg/dL | -0.53 mEq/L |
| | cK+ (test level: 5.0 mEq/L) | | |
| Benzalkonium chloride | 2.4 mg/dL | 0.6 mg/dL | 1.27 mEq/L |
| Hemolysis | 20% | 0.40% | 14.3 mEq/L |
| Teriflunomide | 30 mg/dL | 15 mg/dL | -0.88 mEq/L |
| | cNa+ (test level: 135 mEq/L) | | |
| Benzalkonium chloride | 2.4 mg/dL | 0.12 mg/dL | 28.0 mEq/L |
| Hemolysis | 20% | 2.5% | -15.3 mEq/L |
| Intralipid | 2000 mg/dL | 1000 mg/dL | 5.0 mEq/L |
| Teriflunomide | 30 mg/dL | 22.5 mg/dL | -4.3 mEq/L |
| | cNa+ (test level: 145 mEq/L) | | |
| Benzalkonium chloride | 2.4 mg/dL | 0.11 mg/dL | 29.6 mEq/L |
| Hemolysis | 20% | 2.5% | -14.8 mEq/L |
| Intralipid | 2000 mg/dL | 1000 mg/dL | 4.8 mEq/L |
| Teriflunomide | 30 mg/dL | 22.5 mg/dL | -4.8 mEq/L |
| | cGlu (test level: 39.6 mg/dL) | | |
| 2-deoxy glucose | 164 mg/dL | 3.3 mg/dL | 158 mg/dL |
| Bromide (sodium-) a) | 391 mg/dL | 49 mg/dL | -5.81 mg/dL |
| Fluoride (sodium-) b) | 210 mg/dL | 105 mg/dL | -5.6 mg/dL |
| Galactose | 59 mg/dL | 44 mg/dL | 3.5 mg/dL |
| Povidone-iodine | 1000 mg/dL | 500 mg/dL | 6.9 mg/dL |
| Thiocyanate (sodium-) | 195 mg/dL | 1.2 mg/dL | 94 mg/dL |
| | cGlu (test level: 220 mg/dL) | | |
| 2-deoxy glucose | 164 mg/dL | 25 mg/dL | 165 mg/dL |
| Thiocyanate (sodium-) | 195 mg/dL | 10 mg/dL | 99 mg/dL |
| Notes for Glucose:<br>a) Paired-difference cGlu test level: 101 mg/dL. Dose-Response cGlu test level: 88 mg/dL.<br>b) Do not use samples collected in fluorinated sampling tubes as exposure to high<br>concentrations of fluoride causes falsely low cGlu results and may cause falsely low cGlu results<br>in subsequent sample measurements." | | | |
| | | | |
| cLac (test level:9.0 mg/dL) | | | |
| Bromide (sodium-) a), b) | 391 mg/dL | 49 mg/dL | -3.4 mg/dL |
| EDTA (edetate disodium<br>2H2O) | 112 mg/dL | 84 mg/dL | -1.67 mg/dL |
| Formic acid e) | 115 mg/dL | 29 mg/dL | -1.36 mg/dL |
| Glycolic acid d) | 7.6 mg/dL | 0.2 mg/dL | 10 mg/dL |
| Interferent | Maximum test<br>concentration | Highest<br>concentration level<br>where interference<br>was not significant | Impact on result<br>for maximum test<br>concentration |
| N-acetylcysteine | 166 mg/dL | 125 mg/dL | -1.07 mg/dL |
| Thiocyanate (sodium-)…