ABL90 FLEX

K132691 · Radiometer Medical Aps · MQM · Nov 13, 2014 · Clinical Chemistry

Device Facts

• Record ID: K132691
• Device Name: ABL90 FLEX
• Applicant: Radiometer Medical Aps
• Product Code: MQM · Clinical Chemistry
• Decision Date: Nov 13, 2014
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1113
• Device Class: Class 1
• Attributes: Pediatric

Intended Use

The ABL90 FLEX analyzer is an in vitro diagnostic, portable, automated analyzer that quantitatively measures neonatal bilirubin in heparinised capillary whole blood. The ABL90 FLEX analyzer 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. Bilirubin measurements on the ABL90 FLEX analyzer are intended to aid in assessing the risk of kernicterus in neonates.

Device Story

The ABL90 FLEX is a portable, automated in vitro diagnostic analyzer for whole blood analysis. It utilizes a sensor cassette containing electrochemical sensors and an optical oxygen sensor, alongside a 256-pixel array spectrophotometer for co-oximetry and bilirubin measurements. Operated by trained clinicians in laboratory or point-of-care settings, the device processes heparinized capillary whole blood samples. The spectrophotometric module performs multi-component analysis on hemolyzed sample portions to quantify neonatal bilirubin. Results are provided to healthcare providers to aid in assessing kernicterus risk in neonates, facilitating timely clinical decision-making. The system uses a two-point liquid calibration method.

Clinical Evidence

Bench testing only. Precision evaluated per CLSI EP05-A2 across three POC sites and laboratory settings using aqueous samples and spiked whole blood (N=240 per aqueous sample; N=75 per spiked blood sample). Method comparison per CLSI EP09-A2 (N=224 capillary, N=210 syringe) showed good correlation with the predicate (R²=0.99). Linearity confirmed per CLSI EP6-A. Interference testing per CLSI EP07-A2 identified specific substances (e.g., Fluorescein, Methylene Blue) causing significant interference. LoB/LoD/LoQ determined per CLSI EP17-A2 as 1.1 mg/dL, 1.60 mg/dL, and 1.60 mg/dL, respectively.

Technological Characteristics

Portable, automated analyzer. Features miniaturized electrochemical sensors (film technology) and an optical oxygen sensor integrated into a replaceable sensor cassette. Uses a 256-pixel array spectrophotometer for optical measurements. Connectivity includes laboratory/POC integration. Calibration via two-point liquid method. Software-based analysis of spectrophotometric data.

Indications for Use

Indicated for neonates requiring quantitative measurement of bilirubin in heparinised capillary whole blood to aid in assessing the risk of kernicterus. Intended for use by trained healthcare professionals in laboratory or point-of-care settings under physician order.

Regulatory Classification

Identification

A bilirubin (total and unbound) in the neonate test system is a device intended to measure the levels of bilirubin (total and unbound) in the blood (serum) of newborn infants to aid in indicating the risk of bilirubin encephalopathy (kernicterus).

Predicate Devices

• ABL800 FLEX (K050869)

Submission Summary (Full Text)

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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

November 13, 2014

RADIOMETER MEDICAL APS SOREN BOGESTRAND REGULATORY AFFAIRS SPECIALIST AKANDEVEJ 21 BRONSHOJ DK-2700

Re: K132691

Trade/Device Name: ABL90 Flex Regulation Number: 21 CFR 862.1113 Regulation Name: Bilirubin (total and unbound) in the neonate test system Regulatory Class: I. reserved Product Code: MQM Dated: October 24, 2014 Received: October 31, 2014

Dear Mr. Bogestrand:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number [phone] or [phone] or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number [phone] or [phone] or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

# Courtney H. Lias -S

Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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# Indications for Use

510(k) Number (if known) K132691

Device Name ABL90 FLEX

Indications for Use (Describe)

Intended Use:

The ABL90 FLEX analyzer is an in vitro diagnostic, portable, automated analyzer that quantitatively measures neonatal bilirubin in heparinised capillary whole blood. The ABL90 FLEX analyzer 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. Bilirubin measurements on the ABL90 FLEX analyzer are intended to aid in assessing the risk of kernicterus in neonates.

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

| <div> <span></span> <span></span>Prescription Use (Part 21 CFR 801 Subpart D) </div> |
|-----------------------------------------------------------------------------------------|
| <div> <span></span> <span></span>Over-The-Counter Use (21 CFR 801 Subpart C) </div> |

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## 510(k) Summary

## 1. Submitter and contact information

| Submitter | |
|---------------|---------------------------------------------|
| Company Name: | Radiometer Medical ApS |
| ER Number: | 3002807968 |
| Address: | Aakandevej 21<br>2700 Broenshoej<br>Denmark |
| Phone: | [phone] |
| Fax: | [phone] |

#### Contact Person

| Name: | Søren Bøgestrand |
|-----------|--------------------------------|
| Function: | Senior RA Specialist |
| E-mail: | [e-mail] |
| Phone: | [phone] |
| Fax: | [phone] |

#### Date prepared

| Date: | November 11, 2014 | |
|-------|-------------------|--|
| | | |

# 2. a. Device Information

| Device Name: | ABL90 FLEX analyzer |
|--------------|--------------------------------------------------|
| Common Name: | Blood gases, Cooximetry, and Metabolite analyzer |

Classification:

| Classification name | CFR Section | | Device Class Product Code |
|--------------------------------------|-------------|------------|------------------------------|
| Bilirubin in the neonate test system | 862.1113 | 1,reserved | MOM |

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## 2. b. Device Description

## Instrument name, manufacturer, models and accessories

The name of the device is the ABL90 FLEX. The device is manufactured by Radiometer Medical ApS, Brønshøj, Denmark.

The ABL90 FLEX is a portable, automated system intended for in vitro testing of samples of whole blood for the parameters pH, pO2, pCO2, potassium, sodium, chloride, glucose, lactate, neonatal bilirubin and co-oximetry parameters (total hemoglobin, oxygen saturation, and the hemoglobin fractions FO2Hb, FCOHb, FMetHb, FHHb and FHbF).

The ABL90 FLEX consists of an instrument with a sensor cassette and a solution pack as the main accessories. Multiple models of sensor cassettes are available.

The various sensor cassette models for different parameter combinations. For each parameter combination, models allowing for different test load are available.

The solution pack is available in one model.

The ABL 90 FLEX electrochemical sensors are miniaturized, manufactured by film technology and integrated in a common sensor cassette. Likewise, the ABL90 FLEX optical oxygen sensor is integrated in the sensor cassette. A 256-pixel array spectrophotometer is used for the co-oximetry parameters and bilirubin.

## 2. c. Purpose of submission

Addition of neonatal bilirubin measurement to previously cleared ABL90 FLEX analyzer (K092686)

#### Clinical Utility neonatal Bilirubin

Neonatal Bilirubin test is intended for use to aid in assessing the risk of kernicterus in neonates.

## 3. Intended Use/Indications for use

The ABL90 FLEX analyzer is an in vitro diagnostic, portable, automated analyzer that quantitatively measures neonatal bilirubin in heparinised capillary whole blood. The ABL90 FLEX analyzer 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. Bilirubin measurements on the ABL90 FLEX analyzer are intended to aid in assessing the risk of kernicterus in neonates.

## 4. Predicate device: ABL800 FLEX analyzer (K050869)

#### Substantial Equivalence

The ABL90 FLEX analyzer with neonatal bilirubin is substantially equivalent in Intended Use, fundamental scientific technology, features, and characteristics to the predicate:

## 510(k) Number/Device Manufacturer:

K050869 ABL800 FLEX, Radiometer Medical ApS

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| Similarities | | |
|-----------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------|
| Issue | SE Device | Predicate Device (K050869) |
| Intended use | The ABL90 FLEX analyzer is an in vitro<br>diagnostic, portable, automated analyzer<br>that quantitatively measures neonatal<br>bilirubin in heparinised capillary whole<br>blood. The ABL90 FLEX analyzer is intended<br>for use by trained technologists, nurses,<br>physicians and therapists. It is intended for<br>use in a laboratory environment, near<br>patient or point-of-care setting. These tests<br>are only performed under a physician's<br>order. Bilirubin measurements on the<br>ABL90 FLEX analyzer are intended to aid in<br>assessing the risk of kernicterus in<br>neonates. | Same |
| Measuring method<br>for neonate bilirubin<br>test | Using spectrophotometric multi-component<br>analysis through the instrument's existing<br>CO-Oximetry module on a hemolyzed part<br>of the sample. | Same |
| Calibration Method<br>for neonate bilirubin<br>test | Two-point liquid calibration. | Same |

| Differences | | | | | | | |
|----------------------------------------|----------------------------|----------------------------------------|-------------------------------|-----------------------------------|--|--|--|
| l ssue | | SE Device | Predicate Device<br>(K050869) | | | | |
| Intended use site | | Clinical laboratory and point-of-care. | Clinical laboratory. | | | | |
| Neonatal bilirubin<br>reportable range | μmol/L:<br>mg/dL:<br>mg/L: | 28 - 648<br>1.6 - 37.9<br>16 - 379 | umol/L:<br>mg/dL:<br>mg/L: | 1 - 1000<br>0.0 - 58.5<br>0 - 585 | | | |

# 5. Performance Characteristics

## Precision

Repeatability and Device/Method Precision was evaluated according to CLSI guideline "Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline – Second Edition", EP05-A2. The study was conducted at three point-of-care (POC) sites and on two instruments in Radiometer's laboratory facility on aqueous samples. In addition, a one-day study was conducted using spiked adult whole blood samples adjusted to mimic neonatal whole blood.

The test verified that neonatal bilirubin can be measured with acceptable precision in both POC and laboratory settings and in both capillary and syringe mode.

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## Point-of-care studies

# 20 day precision performance on aqueous solutions, all sites pooled:

| Capillary mode: | | | | | | |
|-----------------|-----|-----------------|----------------|-----|-----------|-----|
| Sample | N | Mean<br>(mg/dL) | Within run, Sr | | Total, ST | |
| | | | SD (Sr) | %CV | SD (ST) | %CV |
| Sample 1 | 240 | 2.1 | 0.04 | 2.1 | 0.08 | 3.8 |
| Sample 2 | 240 | 7.4 | 0.09 | 1.2 | 0.11 | 1.5 |
| Sample 3 | 240 | 30.6 | 0.32 | 1.1 | 0.42 | 1.4 |

#### Syringe mode:

| Sample | N | Mean<br>(mg/dL) | Within run, Sr | | Total, ST | |
|----------|-----|-----------------|----------------|-----|-----------|-----|
| | | | SD (Sr) | %CV | SD (ST) | %CV |
| Sample 1 | 240 | 2.1 | 0.06 | 2.7 | 0.10 | 4.6 |
| Sample 2 | 240 | 7.4 | 0.06 | 0.8 | 0.11 | 1.5 |
| Sample 3 | 240 | 30.7 | 0.20 | 0.7 | 0.40 | 1.3 |

## 20 day precision performance on aqueous solutions, site 1:

## Capillary mode:

| Sample | N | Mean<br>(mg/dL) | Within run, Sr | | Total, ST | |
|----------|----|-----------------|----------------|-----|-----------|-----|
| | | | SD (Sr) | %CV | SD (ST) | %CV |
| Sample 1 | 80 | 2.1 | 0.04 | 1.8 | 0.08 | 3.7 |
| Sample 2 | 80 | 7.3 | 0.06 | 0.8 | 0.10 | 1.3 |
| Sample 3 | 80 | 30.2 | 0.19 | 0.6 | 0.49 | 1.6 |

| Sample | N | Mean<br>(mg/dL) | Within run, Sr | | Total, ST | |
|----------|----|-----------------|----------------|-----|-----------|-----|
| | | | SD (Sr) | %CV | SD (ST) | %CV |
| Sample 1 | 80 | 2.1 | 0.05 | 2.4 | 0.08 | 4.1 |
| Sample 2 | 80 | 7.3 | 0.05 | 0.7 | 0.09 | 1.3 |
| Sample 3 | 80 | 30.3 | 0.09 | 0.3 | 0.50 | 1.6 |

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## 20 day precision performance on aqueous solutions, site 2:

#### Capillary mode:

| Sample | N | Mean<br>(mg/dL) | Within run, Sr | | Total, ST | |
|----------|----|-----------------|----------------|-----|-----------|-----|
| | | | SD (Sr) | %CV | SD (ST) | %CV |
| Sample 1 | 80 | 2.2 | 0.05 | 2.3 | 0.08 | 3.6 |
| Sample 2 | 80 | 7.5 | 0.10 | 1.4 | 0.13 | 1.7 |
| Sample 3 | 80 | 31.3 | 0.38 | 1.2 | 0.40 | 1.3 |

#### Syringe mode:

| Sample | N | Mean<br>(mg/dL) | Within run, Sr | | Total, ST | |
|----------|----|-----------------|----------------|-----|-----------|-----|
| | | | SD (Sr) | %CV | SD (ST) | %CV |
| Sample 1 | 80 | 2.2 | 0.06 | 2.9 | 0.11 | 4.9 |
| Sample 2 | 80 | 7.6 | 0.07 | 0.9 | 0.13 | 1.6 |
| Sample 3 | 80 | 31.6 | 0.28 | 0.9 | 0.41 | 1.3 |

## 20 day precision performance on aqueous solutions, site 3:

# Capillary mode:

| Sample | N | Mean<br>(mg/dL) | Within run, Sr | | Total, ST | |
|----------|----|-----------------|----------------|-----|-----------|-----|
| | | | SD (Sr) | %CV | SD (ST) | %CV |
| Sample 1 | 80 | 2.1 | 0.05 | 2.3 | 0.09 | 4.2 |
| Sample 2 | 80 | 7.3 | 0.09 | 1.2 | 0.11 | 1.5 |
| Sample 3 | 80 | 30.3 | 0.37 | 1.2 | 0.34 | 1.1 |

| Sample | N | Mean<br>(mg/dL) | Within run, Sr | | Total, ST | |
|----------|----|-----------------|----------------|-----|-----------|-----|
| | | | SD (Sr) | %CV | SD (ST) | %CV |
| Sample 1 | 80 | 2.1 | 0.06 | 2.8 | 0.10 | 4.8 |
| Sample 2 | 80 | 7.3 | 0.06 | 0.9 | 0.11 | 1.5 |
| Sample 3 | 80 | 30.4 | 0.20 | 0.7 | 0.27 | 0.9 |

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# 1 day precision performance on spiked adult whole blood, all sites pooled:

#### Capillary mode:

| Sample | N | Mean<br>(mg/dL) | Within run, Sr | | Total, ST | |
|----------|----|-----------------|----------------|-----|-----------|------|
| | | | SD (Sr) | %CV | SD (ST) | %CV |
| Sample 1 | 75 | 2.1 | 0.12 | 5.7 | 0.30 | 14.0 |
| Sample 2 | 75 | 7.1 | 0.16 | 2.3 | 0.44 | 6.3 |
| Sample 3 | 75 | 30.0 | 0.28 | 0.9 | 0.49 | 1.6 |

#### Syringe mode:

| Sample | N | Mean<br>(mg/dL) | Within run, Sr | | Total, ST | |
|----------|-----|-----------------|----------------|-----|-----------|-----|
| SD (Sr) | %CV | SD (ST) | %CV | | | |
| Sample 1 | 75 | 2.5 | 0.13 | 5.0 | 0.22 | 8.7 |
| Sample 2 | 75 | 7.2 | 0.14 | 2.0 | 0.21 | 2.9 |
| Sample 3 | 75 | 30.8 | 0.27 | 0.9 | 0.31 | 1.0 |

## 1 day precision performance on spiked adult whole blood, site 1:

## Capillary mode:

| Sample | N | Mean<br>(mg/dL) | Within run, Sr | | Total, ST | |
|----------|----|-----------------|----------------|-----|-----------|------|
| | | | SD (Sr) | %CV | SD (ST) | %CV |
| Sample 1 | 25 | 2.3 | 0.14 | 6.1 | 0.31 | 13.4 |
| Sample 2 | 25 | 7.1 | 0.15 | 2.1 | 0.61 | 8.5 |
| Sample 3 | 25 | 30.4 | 0.16 | 0.5 | 0.37 | 1.2 |

| Sample | N | Mean<br>(mg/dL) | Within run, Sr | | Total, ST | |
|----------|----|-----------------|----------------|-----|-----------|-----|
| | | | SD (Sr) | %CV | SD (ST) | %CV |
| Sample 1 | 25 | 2.5 | 0.12 | 4.8 | 0.12 | 4.9 |
| Sample 2 | 25 | 7.2 | 0.14 | 1.9 | 0.14 | 1.9 |
| Sample 3 | 25 | 31.1 | 0.21 | 0.7 | 0.19 | 0.6 |

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# 1 day precision performance on spiked adult whole blood, site 2:

## Capillary mode:

| Sample | N | Mean<br>(mg/dL) | Within run, Sr | | Total, ST | |
|----------|----|-----------------|----------------|-----|-----------|-----|
| | | | SD (Sr) | %CV | SD (ST) | %CV |
| Sample 1 | 25 | 1.8 | 0.11 | 5.7 | 0.14 | 7.3 |
| Sample 2 | 25 | 7.2 | 0.19 | 2.6 | 0.20 | 2.8 |
| Sample 3 | 25 | 29.5 | 0.22 | 0.7 | 0.41 | 1.4 |

## Syringe mode:

| Sample | N | Mean<br>(mg/dL) | Within run, Sr | | Total, ST | |
|----------|----|-----------------|----------------|-----|-----------|-----|
| | | | SD (Sr) | %CV | SD (ST) | %CV |
| Sample 1 | 25 | 2.6 | 0.11 | 4.2 | 0.12 | 4.5 |
| Sample 2 | 25 | 7.5 | 0.16 | 2.1 | 0.15 | 2.0 |
| Sample 3 | 25 | 30.9 | 0.21 | 0.7 | 0.20 | 0.6 |

## 1 day precision performance on spiked adult whole blood, site 3:

## Capillary mode:

| Sample | N | Mean<br>(mg/dL) | Within run, Sr | | Total, ST | |
|----------|----|-----------------|----------------|-----|-----------|------|
| | | | SD (Sr) | %CV | SD (ST) | %CV |
| Sample 1 | 25 | 2.2 | 0.11 | 5.2 | 0.39 | 17.7 |
| Sample 2 | 25 | 6.9 | 0.14 | 2.1 | 0.42 | 6.2 |
| Sample 3 | 25 | 30.0 | 0.40 | 1.3 | 0.65 | 2.2 |

| Sample | N | Mean<br>(mg/dL) | Within run, Sr | | Total, ST | |
|----------|----|-----------------|----------------|-----|-----------|------|
| | | | SD (Sr) | %CV | SD (ST) | %CV |
| Sample 1 | 25 | 2.4 | 0.15 | 6.1 | 0.34 | 13.9 |
| Sample 2 | 25 | 6.8 | 0.13 | 1.9 | 0.30 | 4.5 |
| Sample 3 | 25 | 30.5 | 0.36 | 1.2 | 0.46 | 1.5 |

{10}------------------------------------------------

## Laboratory studies

#### Precision study on aqueous solutions, 20 days:

#### Capillary mode:

| Sample | N | Mean<br>(mg/dL) | Within run, Sr | | Total, ST | |
|----------|----|-----------------|----------------|-----|-----------|-----|
| | | | SD (Sr) | %CV | SD (ST) | %CV |
| Sample 1 | 80 | 2.1 | 0.05 | 2.3 | 0.07 | 3.4 |
| Sample 2 | 80 | 7.4 | 0.12 | 1.6 | 0.13 | 1.7 |
| Sample 3 | 80 | 30.7 | 0.48 | 1.6 | 0.46 | 1.5 |

#### Syringe mode:

| Sample | N | Mean<br>(mg/dL) | Within run, Sr | | Total, ST | |
|----------|----|-----------------|----------------|-----|-----------|-----|
| | | | SD (Sr) | %CV | SD (ST) | %CV |
| Sample 1 | 80 | 2.1 | 0.05 | 2.4 | 0.07 | 3.2 |
| Sample 2 | 80 | 7.4 | 0.11 | 1.5 | 0.14 | 1.9 |
| Sample 3 | 80 | 30.9 | 0.45 | 1.4 | 0.57 | 1.8 |

## 1 day precision performance on spiked adult whole blood and cord blood:

#### Capillary mode:

| Sample | N | Mean<br>(mg/dL) | Within run, Sr | | Total, ST | |
|-----------------------|----|-----------------|----------------|-----|-----------|-----|
| | | | SD (Sr) | %CV | SD (ST) | %CV |
| Sample 1, Adult blood | 25 | 2.3 | 0.15 | 6.7 | 0.18 | 7.7 |
| Sample 2, Adult blood | 25 | 7.8 | 0.22 | 2.8 | 0.34 | 4.4 |
| Sample 3, Adult blood | 25 | 30.2 | 0.73 | 2.4 | 0.80 | 2.6 |
| Sample 1, Cord blood | 25 | 2.0 | 0.10 | 4.9 | 0.13 | 6.7 |
| Sample 2, Cord blood | 25 | 7.0 | 0.19 | 2.7 | 0.24 | 3.4 |
| Sample 3, Cord blood | 25 | 30.6 | 0.32 | 1.1 | 0.34 | 1.1 |

| Sample | N | Mean<br>(mg/dL) | Within run, Sr | | Total, ST | |
|-----------------------|----|-----------------|----------------|-----|-----------|-----|
| | | | SD (Sr) | %CV | SD (ST) | %CV |
| Sample 1, Adult blood | 25 | 2.6 | 0.13 | 5.0 | 0.21 | 8.3 |
| Sample 2, Adult blood | 25 | 7.4 | 0.09 | 1.2 | 0.15 | 2.1 |
| Sample 3, Adult blood | 25 | 29.4 | 0.51 | 1.7 | 0.52 | 1.8 |
| Sample 1, Cord blood | 25 | 2.4 | 0.12 | 4.9 | 0.18 | 7.4 |
| Sample 2, Cord blood | 25 | 7.1 | 0.24 | 3.4 | 0.28 | 4.0 |
| Sample 3, Cord blood | 25 | 29.9 | 0.21 | 0.7 | 0.26 | 0.9 |

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

## Method Comparison

Method comparison study versus the predicate has been conducted according to NCCLS guideline "Method Comparison and Bias Estimation Using Patient Samples", EP09-A2. The study was conducted for both capillary and syringe mode at three point-of-care sites and included a total of 224 samples for capillary mode and 210 samples for syringe mode spanning the entire measuring range.

Linear regression of the pooled data qives a slope of 0.9903/0.9760 and an R2 of 0.99/0.99 for syringe and capillary mode respectively showing good correlation with the predicate device and very good agreement between the two modes.

| Site | N | ABL 90 FLEX<br>range tested,<br>mg/dL | Slope<br>(95% CI) | Intercept<br>(95% CI)<br>mg/dL | R2 |
|--------------------|-----|---------------------------------------|---------------------------|--------------------------------|--------|
| Site 1 | 74 | 1.8 - 35.9 | 0.9922<br>(0.964 - 1.020) | 1.0207<br>(0.64 - 1.40) | 0.9857 |
| Site 2 | 51 | 2.0 - 37.9 | 1.0054<br>(0.980 - 1.031) | 0.3744<br>(0.00 - 0.75) | 0.9924 |
| Site 3 | 85 | 2.7 - 37.1 | 0.9917<br>(0.969 - 1.014) | 0.3623<br>(0.01 - 0.71) | 0.9895 |
| All sites combined | 210 | 1.8 - 37.9 | 0.9903<br>(0.975 - 1.005) | 0.6574<br>(0.44 - 0.88) | 0.9878 |

Syringe mode:

Capillary mode:

| Site | N | ABL 90 FLEX<br>range tested,<br>mg/dL | Slope<br>(95% CI) | Intercept<br>(95% CI)<br>mg/dL | R2 |
|--------------------|-----|---------------------------------------|---------------------------|--------------------------------|--------|
| Site 1 | 77 | 1.8 - 35.5 | 0.9774<br>(0.950 - 1.005) | 1.1199<br>(0.76 - 1.48) | 0.9853 |
| Site 2 | 56 | 2.1 - 37.3 | 0.9977<br>(0.974 - 1.021) | 0.5385<br>(0.19 - 0.88) | 0.9927 |
| Site 3 | 91 | 3.0 - 36.7 | 0.9737<br>(0.948 - 0.999) | 0.4862<br>(0.09 - 0.88) | 0.9845 |
| All sites combined | 224 | 1.8 - 37.3 | 0.9760<br>(0.961 - 0.991) | 0.7741<br>(0.55 - 1.00) | 0.9861 |

{12}------------------------------------------------

## Linearity

Linearity study has been conducted according to CLSI guideline "Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approved Guideline", EP6-A.

The method is linear (first order) over the entire measuring range and fulfils the requirements for allowable error due to non-linearity established by Radiometer.

Image /page/12/Figure/3 description: The image is a scatter plot titled "Bilirubin: ABL90 vs Sample Conc." The x-axis is labeled "Bilirubin, mg/dL, Target value" and ranges from 0.0 to 50.0. The y-axis is labeled "Bilirubin, mg/dL, ABL90" and ranges from 0.0 to 50.0. A line of best fit is plotted on the scatter plot, and the equation of the line is y = 0.968x + 0.2984, with an R-squared value of 0.9996.

## Interference

Interference study has been conducted according to CLSI guideline "Interference Testing in Clinical Chemistry; Approved Guideline - Second Edition", EP07-A2.

Significant interference was observed from Fluorescein, Beta-carotene, Methylene Blue, Patent Blue V, Cardio Green, HiCN, Hydroxycobalamin, Cyanocobalamin, and SHb.

No clinically significant interference was observed from Evans Blue, HbF, Hemolysis, Intralipid or Triglyceride. Interference specifications are tabulated below.

{13}------------------------------------------------

There was non-significant interference with Evans Blue, Intralipid, HbF, Hemolysis, and Triglyceride at the highest concentration indicated below: (Sponsor defines non-significant interference as < ± 10%)

| Substances tested | Highest concentration tested with non-significant interference |
|-------------------|----------------------------------------------------------------|
| Evans Blue | 5 mg/L |
| Intralipid | 1000 mg/dL |
| HbF | 82% |
| Hemolysis | 20% (equivalent to approximately 3 g/dL hemoglobin) |
| Triglyceride | 500 mg/dL |

There was significant interference for Fluorescein, Patent Blue V, Methylene Blue, Cardio Green, SHb, Hydroxocobalamin Hydrochloride, and Cyanocobalamin (Sponsor defines significant interference as ≥ ± 10%). Dose-response studies were conducted to determine the highest levels of interferents at which significant interference could not be seen, the results are tabulated below:

| Interferents tested | Bilirubin concentration<br>tested (mg/dL) | Highest level of<br>interferent free from<br>significant interference |
|---------------------|-------------------------------------------|-----------------------------------------------------------------------|
| Fluorescein | 5 | 1.5 mg/L |
| | 15 | 4 mg/L |
| Patent Blue V | 5 | 1.5 mg/L |
| | 15 | 2.5 mg/L |
| Methylene Blue | 5 | 0.75 mg/L |
| | 15 | 2 mg/L |
| Cardio Green | 5 | 3 mg/L |
| | 15 | 10 mg/L |
| SHb | 5 | 1.1% |
| | 15 | 1.6% |

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| Hydroxocobalamin<br>Hydrochloride | 5 | 0.19 g/L |
|-----------------------------------|----|----------|
| | 15 | 0.5 g/L |
| Cyanocobalamin | 5 | 0.2 g/L |
| | 15 | 0.7 g/L |

pH was tested in the range from 6.8 – 7.9 and significant interference relative to physiological pH was not observed.

Limitation in the labeling: Since the spectra for HiCN and Beta-carotene overlap with the spectrum of bilirubin, these are known interfering substances. Results from samples containing these substances should not be used.

#### LoB, LoD, LoQ

Study has been conducted according to CLSI guideline "Protocols for Determination of Limits of Detection and Limits of Quantitation; Approved Guideline", EP17-A2.

LoB was determined to be 1.1 mg/dL (18 µmol/L). LoD was determined to be 1.60 mg/dL (27.4 umol/L) LoQ was determined to be 1.60 mg/dL (27.4 µmol/L)

#### 6. Conclusion

Based on the substantial equivalence comparison and the results of the conducted performance evaluations it has been concluded that the ABL90 FLEX analyzer with neonatal bilirubin is as safe and effective as the predicate device.