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 Description

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.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the ABL90 FLEX device, based on the provided FDA 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance:

Performance Characteristic	Acceptance Criteria (Implicit)	Reported Device Performance
Precision (Repeatability & Device/Method Precision)	Acceptable precision in POC and laboratory settings, and in both capillary and syringe mode.	Aqueous Solutions (20-day pooled):- Capillary mode: Total %CV from 1.4% to 3.8%- Syringe mode: Total %CV from 1.3% to 4.6%Spiked Adult Whole Blood (1-day pooled):- Capillary mode: Total %CV from 1.6% to 14.0%- Syringe mode: Total %CV from 1.0% to 8.7%Spiked Adult Whole Blood & Cord Blood (1-day lab):- Capillary mode: Total %CV from 1.1% to 7.7% for adult, 0.9% to 7.4% for cord.
Method Comparison (vs. Predicate ABL800 FLEX)	Good correlation with the predicate device and very good agreement between the two modes.	Syringe mode (pooled): Slope = 0.9903 (95% CI: 0.975-1.005), Intercept = 0.6574, R² = 0.9878Capillary mode (pooled): Slope = 0.9760 (95% CI: 0.961-0.991), Intercept = 0.7741, R² = 0.9861
Linearity	Linear over the entire measuring range and fulfills requirements for allowable error due to non-linearity.	Linear (first order) over the entire measuring range. R² = 0.9996 for Bilirubin: ABL90 vs. Sample Conc.
Interference (Non-Significant)	< ± 10% interference	Evans Blue: 5 mg/LIntralipid: 1000 mg/dLHbF: 82%Hemolysis: 20% (approx. 3 g/dL hemoglobin)Triglyceride: 500 mg/dL
Interference (Significant)	Significant interference is ≥ ± 10%. Dose-response studies determine highest levels free from significant interference.	Fluorescein: 1.5 mg/L (at 5 mg/dL Bilirubin), 4 mg/L (at 15 mg/dL Bilirubin)Patent Blue V: 1.5 mg/L (at 5 mg/dL Bilirubin), 2.5 mg/L (at 15 mg/dL Bilirubin)Methylene Blue: 0.75 mg/L (at 5 mg/dL Bilirubin), 2 mg/L (at 15 mg/dL Bilirubin)Cardio Green: 3 mg/L (at 5 mg/dL Bilirubin), 10 mg/L (at 15 mg/dL Bilirubin)SHb: 1.1% (at 5 mg/dL Bilirubin), 1.6% (at 15 mg/dL Bilirubin)Hydroxocobalamin Hydrochloride: 0.19 g/L (at 5 mg/dL Bilirubin), 0.5 g/L (at 15 mg/dL Bilirubin)Cyanocobalamin: 0.2 g/L (at 5 mg/dL Bilirubin), 0.7 g/L (at 15 mg/dL Bilirubin)pH: No significant interference in range 6.8 – 7.9.
Limits of Blank (LoB)	Not explicitly stated, but determined.	1.1 mg/dL (18 µmol/L)
Limits of Detection (LoD)	Not explicitly stated, but determined.	1.60 mg/dL (27.4 µmol/L)
Limits of Quantitation (LoQ)	Not explicitly stated, but determined.	1.60 mg/dL (27.4 µmol/L)

2. Sample Size Used for the Test Set and Data Provenance:

Precision Studies:
- Aqueous Solutions (20-day): 240 samples (pooled data for capillary and syringe modes) across three point-of-care (POC) sites.
- Spiked Adult Whole Blood (1-day): 75 samples (pooled data for capillary and syringe modes) across three POC sites.
- Spiked Adult Whole Blood and Cord Blood (1-day laboratory): 25 samples per category (Adult Blood Samples 1, 2, 3 and Cord Blood Samples 1, 2, 3) for both capillary and syringe modes an additional sample for adult blood for syringe and capillary, making it 150 samples just for adult blood samples and 150 for cord blood samples.
Method Comparison:
- Syringe Mode: 210 samples (pooled from 74, 51, and 85 samples from three sites).
- Capillary Mode: 224 samples (pooled from 77, 56, and 91 samples from three sites).
Linearity: The specific number of samples is not explicitly stated, but data points appear to cover a range shown in the figure.
Interference: The specific number of samples per interferent tested is not explicitly stated.
LoB, LoD, LoQ: The specific number of samples used for these determinations is not explicitly stated.
Data Provenance: Studies were conducted at three point-of-care (POC) sites and Radiometer's laboratory facility. The country of origin for the data is not specifically mentioned, but the manufacturer is based in Denmark. The studies appear to be prospective as they were specifically conducted to evaluate the device's performance.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:

The ground truth for this device (Bilirubin measurement) is established by quantitative measurement against a reference method (the predicate device) or known concentrations (aqueous solutions, spiked blood).
Therefore, the concept of "experts" to establish a ground truth for a diagnostic measurement device like this (unlike image-based diagnostic AI) is not directly applicable in the same way. The accuracy is determined by comparing its measurements to established, validated methods or known standards.

4. Adjudication Method for the Test Set:

Adjudication methods (like 2+1, 3+1) are typically used in clinical studies where subjective interpretation by multiple readers is involved (e.g., radiologists reviewing images).
For a quantitative in vitro diagnostic device measuring a biomarker, the "adjudication" is inherent in the reference method used for comparison (e.g., the ABL800 FLEX predicate device in the method comparison study, or the gravimetric methods for preparing known concentrations in precision and linearity studies). There is no explicit expert adjudication process described for the quantitative measurements themselves.

5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:

No, an MRMC comparative effectiveness study was not done.
This device is an in vitro diagnostic analyzer that quantitatively measures neonatal bilirubin, not an AI-assisted diagnostic tool that aids human readers in interpreting clinical data or images. Therefore, the concept of "human readers improve with AI vs. without AI assistance" does not apply to this device.

6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done:

Yes, this entire study is a standalone performance evaluation.
The ABL90 FLEX analyzer is an automated device designed to provide a direct readout of neonatal bilirubin. The performance data presented (precision, method comparison, linearity, interference, LoB/LoD/LoQ) all represent the performance of the device itself, without human intervention in the measurement process after the sample is introduced. Human users are involved in operating the device and interpreting its results within a clinical context, but the measurements themselves are fully automated.

7. The Type of Ground Truth Used:

Reference Method / Known Concentrations:
- For Precision, the ground truth was established by aqueous samples and spiked adult whole blood samples with known concentrations of bilirubin.
- For Method Comparison, the ground truth was the measurements obtained from the predicate device (ABL800 FLEX analyzer).
- For Linearity, the ground truth was samples with known target values of bilirubin concentration.
- For Interference, the ground truth was the expected bilirubin value in the presence of varying concentrations of potential interferents.
- For LoB, LoD, LoQ, the ground truth would be based on statistical analysis of samples with very low or no analyte present, often using a highly sensitive reference method to confirm absence or very low levels.

8. The Sample Size for the Training Set:

This is a traditional in-vitro diagnostic device, not an AI/Machine Learning algorithm that requires a "training set" in the conventional sense. The device's spectrophotometric multi-component analysis method is based on established scientific principles and calibrated using known standards. Therefore, the concept of a "training set" as it applies to AI models is not relevant here. The device is developed and validated, not "trained."

9. How the Ground Truth for the Training Set Was Established:

As mentioned above, there is no "training set" for this type of device in the AI sense. The principle behind the device's measurement (spectrophotometric multi-component analysis) relies on fundamental physics and chemistry, with calibration done using solutions of known concentrations. This calibration process ensures accuracy, but it's not "training" an algorithm to learn from data.

Summary

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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 (800) 638 2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (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 (800) 638-2041 or (301) 796-7100 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:

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

1. Submitter and contact information

Submitter
Company Name:	Radiometer Medical ApS
ER Number:	3002807968
Address:	Aakandevej 212700 BroenshoejDenmark
Phone:	+45 3827 3827
Fax:	+45 3827 2727

Contact Person

Name:	Søren Bøgestrand
Function:	Senior RA Specialist
E-mail:	soren.bogestrand@radiometer.dk
Phone:	+45 3827 3852
Fax:	+45 3827 2727

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 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

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 vitrodiagnostic, portable, automated analyzerthat quantitatively measures neonatalbilirubin in heparinised capillary wholeblood. The ABL90 FLEX analyzer is intendedfor use by trained technologists, nurses,physicians and therapists. It is intended foruse in a laboratory environment, nearpatient or point-of-care setting. These testsare only performed under a physician'sorder. Bilirubin measurements on theABL90 FLEX analyzer are intended to aid inassessing the risk of kernicterus inneonates.	Same
Measuring methodfor neonate bilirubintest	Using spectrophotometric multi-componentanalysis through the instrument's existingCO-Oximetry module on a hemolyzed partof the sample.	Same
Calibration Methodfor neonate bilirubintest	Two-point liquid calibration.	Same

Differences
l ssue		SE Device	Predicate Device(K050869)
Intended use site		Clinical laboratory and point-of-care.	Clinical laboratory.
Neonatal bilirubinreportable range	μmol/L:mg/dL:mg/L:	28 - 6481.6 - 37.916 - 379	umol/L:mg/dL:mg/L:	1 - 10000.0 - 58.50 - 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(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(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(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(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(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(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(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(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(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(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(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(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(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(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(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(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

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Laboratory studies

Precision study on aqueous solutions, 20 days:

Capillary mode:

Sample	N	Mean(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(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(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(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

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

Syringe mode:

Capillary mode:

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

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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.

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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 concentrationtested (mg/dL)	Highest level ofinterferent free fromsignificant 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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HydroxocobalaminHydrochloride	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.

Regulation Number and Section

§ 862.1113 Bilirubin (total and unbound) in the neonate test system.

(a)
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).(b)
Classification. Class I.