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K Number
K152343
Device Name
Direct Bilirubin
Manufacturer
RANDOX LABORATORIES LIMITED
Date Cleared
2016-02-16

(181 days)

Product Code
JFM
Regulation Number
862.1110
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP Authorized
Intended Use
The Direct Bilirubin test system is a device intended for the quantitative in vitro determination of Direct Bilirubin in serum and plasma. Bilirubin measurements can be used in the diagnosis and treatment of liver, hematological and metabolic disorders including hepatitis and gall bladder block. This device is for prescription use only.
Device Description
The Randox Direct Bilirubin kit consists of ready to use reagent solutions. CATALOGUE NUMBER: BR8308 COMPONENTS: R1. 4 x 20ml, R2. 4 x 8ml REAGENT COMPOSITION R1. Direct Bilirubin RI Tartrate buffer, pH2.9 Detergent Antimicrobials and Preservatives Inhibitors Initial Concentration of Solutions 0.1 mol/L R2. Direct Bilirubin R2 Phosphate buffer, pH 7.0 Sodium Metavanadate Initial Concentration of Solutions 10 mmol/L 4 mmol/L
More Information

K053132

K942458, K053153

No
The device description and performance studies focus on the chemical reagents and analytical performance of a quantitative in vitro diagnostic test, with no mention of AI or ML.

No
The device is an in vitro diagnostic (IVD) test system for quantitative determination of Direct Bilirubin, used in diagnosis and treatment monitoring, not for direct therapy.

Yes
The "Intended Use / Indications for Use" section explicitly states that "Bilirubin measurements can be used in the diagnosis and treatment of liver, hematological and metabolic disorders including hepatitis and gall bladder block," indicating its utility for diagnostic purposes.

No

The device description clearly states it consists of "ready to use reagent solutions" and lists chemical components. This indicates a physical, chemical-based in vitro diagnostic device, not a software-only device.

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

  • Intended Use: The "Intended Use / Indications for Use" section explicitly states that the device is "intended for the quantitative in vitro determination of Direct Bilirubin in serum and plasma." The term "in vitro" is a key indicator of an IVD.
  • Purpose: The intended use also describes the purpose of the test: "Bilirubin measurements can be used in the diagnosis and treatment of liver, hematological and metabolic disorders including hepatitis and gall bladder block." This aligns with the diagnostic purpose of IVDs.
  • Device Description: The device is described as a "test system" consisting of "ready to use reagent solutions." This is consistent with the components of many IVD kits used for chemical analysis of biological samples.
  • Performance Studies: The document details various performance studies (Precision, Linearity, Detection limit, Analytical Specificity, Method comparison, Matrix comparison) which are standard evaluations for IVD devices to demonstrate their analytical performance.
  • Predicate Device: The mention of a "Predicate Device(s)" with a K number (K053132 Wako Direct Bilirubin V) is a strong indication that this device is being submitted for regulatory clearance as an IVD, as comparisons to legally marketed predicate IVDs are a common part of the regulatory process.

N/A

Intended Use / Indications for Use

The Direct Bilirubin test system is a device intended for the quantitative in vitro determination of Direct Bilirubin in serum and plasma. Bilirubin measurements can be used in the diagnosis and treatment of liver, hematological and metabolic disorders including hepatitis and gall bladder block.
This device is for prescription use only.

Product codes (comma separated list FDA assigned to the subject device)

JFM

Device Description

The Randox Direct Bilirubin kit consists of ready to use reagent solutions.
CATALOGUE NUMBER: BR8308 COMPONENTS: R1. 4 x 20ml, R2. 4 x 8ml

REAGENT COMPOSITION
Contents: RI. Direct Bilirubin RI Tartrate buffer, pH2.9 Detergent Antimicrobials and Preservatives Inhibitors; Initial Concentration of Solutions: 0.1 mol/L
Contents: R2. Direct Bilirubin R2 Phosphate buffer, pH 7.0 Sodium Metavanadate; Initial Concentration of Solutions: 10 mmol/L, 4 mmol/L

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Not Found

Indicated Patient Age Range

Not Found

Intended User / Care Setting

Not Found

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Not Found

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

Analytical Performance:
a) Precision/Reproducibility:

  • Study Type: Precision evaluation consistent with C.L.S.I standard EP5-A2.
  • Sample Size: Not explicitly stated, but involved control material and unaltered human serum samples (Pool 1, 2, 4) tested in replicates of two per run over 20 non-consecutive days.
  • Key Results:
    • Serum Pool 1 (Mean 0.65): Within Run CV 3.0, Among Run CV 1.6, Among Day CV 2.4, Total CV 4.2.
    • Serum Pool 2 (Mean 2.31): Within Run CV 3.1, Among Run CV 0.0, Among Day CV Not Stated, Total CV 3.1.
    • Serum Pool 4 (Mean 8.41): Within Run CV 1.5, Among Run CV 0.8, Among Day CV 0.9, Total CV 1.9.

b) Linearity/Assay Reportable Range:

  • Study Type: Linearity studies in accordance with C.L.S.I. standard EP6-A.
  • Sample Size: 11 levels of linearity samples.
  • Key Results:
    • Slope: 1.01
    • Intercept: -0.07
    • r (correlation coefficient): 0.9995
    • Syx: 0.10
    • Linearity: 12.6mg/dl
    • Reportable Range: 0.1-12.6mg/dl
    • The Rx Daytona Plus analyser has an auto-dilution feature that is automatically activated when measuring samples >12.6mg/dl.

d) Detection limit:

  • Study Type: Sensitivity studies in accordance with C.L.S.I. guideline EP17-A2.
  • Sample Size: 240 determinations, with 4 low level samples.
  • Key Results:
    • LoD (Limit of Detection): 0.064mg/dl
    • LoB (Limit of Blank): 0.006mg/dl
    • LoQ (Limit of Quantification): 0.133mg/dl (at ≤20% CV imprecision).

e) Analytical Specificity:

  • Study Type: Interference studies in accordance with C.L.S.I guideline EP7-A2.
  • Key Results: No significant interference up to the following levels at Bilirubin concentrations of 0.14mg/dl and 5.03mg/dl:
    • Haemoglobin: 1000mg/dl
    • Triglycerides: 750mg/dl
    • Intralipid®: 1000mg/dl
    • Ascorbic Acid: 25mg/dl

f) Method comparison with predicate device:

  • Study Type: Correlation studies in accordance with C.L.S.I. guideline EP9-A2.
  • Sample Size: 103 serum patient samples.
  • Key Results:
    • Range tested: 0.123-12.46mg/dl.
    • Linear regression equation: Y = 1.01x + 0.01
    • Correlation coefficient: r = 0.997

g) Matrix comparison:

  • Study Type: Matrix method comparisons.
  • Sample Size: A minimum of 40 matched patient sample pairs (serum and lithium heparin plasma).
  • Key Results:
    • Range tested: 0.091-12.48mg/dl.
    • Linear regression equation: Y = 0.99x + 0.01
    • Correlation coefficient: r = 1.00

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

  • LoD (Limit of Detection): 0.064mg/dl
  • LoB (Limit of Blank): 0.006mg/dl
  • LoQ (Limit of Quantification): 0.133mg/dl

Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.

K053132

Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.

K942458, K053153

Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).

Not Found

§ 862.1110 Bilirubin (total or direct) test system.

(a)
Identification. A bilirubin (total or direct) test system is a device intended to measure the levels of bilirubin (total or direct) in plasma or serum. Measurements of the levels of bilirubin, an organic compound formed during the normal and abnormal distruction of red blood cells, if used in the diagnosis and treatment of liver, hemolytic hematological, and metabolic disorders, including hepatitis and gall bladder block.(b)
Classification. Class II.

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Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized image of three human profiles facing to the right, stacked on top of each other.

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

RANDOX LABORATORIES LIMITED PAULINE ARMSTRONG, SENIOR MANAGER QA/RA 55 DIAMOND ROAD, CRUMLIN COUNTY ANTRIM BT29 4QY GREAT BRITAIN

February 16, 2016

Re: K152343

Trade/Device Name: Direct Bilirubin Regulation Number: 21 CFR 862.1110 Regulation Name: Bilirubin (total or direct) test system Regulatory Class: II Product Code: JFM Dated: January 04, 2016 Received: January 06, 2016

Dear Pauline Armstrong:

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

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

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR 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 (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

1

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/Resourcesfor You/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.

Katherine Serrano -S

Courtney H. Lias, Ph.D. For:

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) K152343

Device Name Direct Bilirubin

Indications for Use (Describe)

The Direct Bilirubin test system is a device intended for the quantitative in vitro determination of Direct Bilirubin in serum and plasma. Bilirubin measurements can be used in the diagnosis and treatment of liver, hematological and metabolic disorders including hepatitis and gall bladder block.

This device is for prescription use only.

Type of Use (Select one or both, as applicable)
X Prescription Use (Part 21 CFR 801 Subpart D)Over-The-Counter Use (21 CFR 801 Subpart C)

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510(K) SUMMARY, DIRECT BILIRUBIN REAGENT

    1. SAFETY AND EFFECTIVENESS AS REQUIRED BY 21 CFR 807.92 STATEMENT
      This summary of the 510(k) safety and effectiveness information is being submitted in accordance with the requirement 21 CFR 807.92.

2. SUBMITTER NAME AND ADDRESS

  • Name: Dr Pauline Armstrong Address: Randox Laboratories Limited 55 Diamond Road, Crumlin, County Antrim, BT29 4QY, United Kingdom
    Telephone: +44 (0) 28 9442 2413 Fax: +44 (0) 28 9445 2912 E-mail: Pauline.Armstrong@randox.com

Date of Summary Preparation: Feb 10, 2016

    1. 510k NUMBER, DEVICE PROPRIETARY NAME, COMMON NAME, PURPOSE FOR SUBMISSION, REGULATORY CLASSIFCATION, PANEL, PRODUCT CODE AND 21 CFR NUMBER
      510k No.: K152343 Device Proprietary Name: Direct Bilirubin Common Name: Direct Bilirubin Purpose for Submission: New Device

| Product

CodeRegulation NameClassificationRegulation SectionPanel
JFMBilirubin (total or
direct) test systemII21 CFR 862.1110Clinical
Chemistry (75)

4. PREDICATE DEVICE PROPRIETARY NAMES AND 510(k) NUMBERS

Predicate Device Proprietary Name: Wako Direct Bilirubin V 510(k) No .: K053132 Cataloque numbers: 02188390 & 02189494

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5. INTENDED USE

The Direct Bilirubin test system is a device intended for the quantitative in vitro determination of Direct Bilirubin in serum and plasma. Bilirubin measurements can be used in the diagnosis and treatment of liver, hemolytic, hematological and metabolic disorders including hepatitis and gall bladder block. This device is for prescription use only.

6. DEVICE DESCRIPTION

The Randox Direct Bilirubin kit consists of ready to use reagent solutions.

CATALOGUE NUMBER: BR8308 COMPONENTS: R1. 4 x 20ml, R2. 4 x 8ml

REAGENT COMPOSITION

| Contents | | Initial Concentration
of Solutions |
|----------|--------------------------------------------------------------------------------------------------------------|---------------------------------------|
| RI. | Direct Bilirubin RI
Tartrate buffer, pH2.9
Detergent
Antimicrobials and Preservatives
Inhibitors | 0.1 mol/L |
| R2. | Direct Bilirubin R2
Phosphate buffer, pH 7.0
Sodium Metavanadate | 10 mmol/L
4 mmol/L |

MATERIALS REQUIRED BUT NOT PROVIDED

Randox Assayed Multisera Level 2 (Cat. No. HN1530) and Level 3 (Cat. No. HE1532); 510(k) # K942458 Randox Calibration Serum Level 3 (Cat. No. CAL2351): 510(k) # K053153 RX series Saline (Cat.No. SA8396)

7. PREDICATE DEVICE COMPARISON TABLE Table 1 Comparison of Direct Bilirubin test system for the RX Daytona plus to predicate device

| CHARACTERISTICS | Randox Direct Bilirubin Assay for RX
Daytona Plus (New Device) | Direct Bilirubin (K053132)
(Predicate Device) |
|-----------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------|
| SIMILARITIES | | |
| INTENDED USE | The Direct Bilirubin test system is a device
intended for the quantitative in vitro
determination of Direct Bilirubin in serum and
plasma. Bilirubin measurements can be used
in the diagnosis and treatment of liver,
haemolytic, haematological and metabolic
disorders including hepatitis and gall bladder
block. This device is for prescription use only. | Same |
| SAMPLE TYPE | Serum
Plasma (Li Heparin) | Same |
| ASSAY PROTOCOL | Vanadate Oxidation Method | Same |

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CHARACTERISTICSRandox Direct Bilirubin Assay for RX Daytona Plus (New Device)Randox Direct Bilirubin (K053132) (Predicate Device)
DIFFERENCES
STORAGE
(UNOPENED)Reagents are stable up to the expiry date
when stored unopened at +2 to +8°C.2-10°C
CALIBRATION
FREQUENCYA two point calibration is recommended every
28 days.Recommended every 30 days.
CONTROL
FREQUENCYTwo levels of control should be assayed at
least once a dayAt least two levels of control should be
assayed once a day, or change of lot
On-board StabilityOn board stability has been determined as 28
days.On board stability has been determined
as 30 days.
REAGENT
COMPOSITIONR1. Direct Bilirubin
Tartrate Buffer, pH2.9, 0.1mol/l
Detergent
Antimicrobials and Preservatives
Inhibitors
R2. Direct Bilirubin
Phosphate Buffer, pH7.0, 10mmol/l
Sodium Metavanadate, 4mmol/lR1.
Tartrate Buffer, pH2.9, 0.1mol/l
Detergent

R2.
Phosphate Buffer, pH7.0, 10mmol/l
Sodium Metavanadate, 4mmol/l |

8. Test Principle

The bilirubin is oxidised by vanadate at approximately pH3.0 to produce biliverdin. In the presence of detergent and vanadate, conjugate (direct) bilirubin is oxidised. This oxidation reaction causes a decrease in the optical density of the yellow colour, which is specific to bilirubin. The decrease in optical density at 450/546nm is proportional to the direct bilirubin concentration in the sample. The concentration is measured as an endpoint reaction.

Conjugated Bilirubin + VO3-

Tokuda K, Tanimoto K. New method of measuring serum bilirubin using vanadic acid. Jpn J Clin Chem. 1993:22:116-122.

9. PERFORMANCE CHARACTERISTICS

Analytical performance

a) Precision/Reproducibility

Precision was evaluated consistent with C.L.S.I standard EP5-A2. Precision studies were performed by two operators, on two RX Daytona plus systems using control material and unaltered human serum samples that were spiked with direct bilirubin concentrations or diluted to achieve concentrations based on established ranges up to 0.2mg/dl. Testing was conducted for two reagent lots of direct bilirubin, one lot on each RX Daytona plus system, twice per day for 20 non-consecutive days. Two replicates per run were performed for each sample. - No assay recalibrations were required throughout the duration of the study. The results are summarized in the following tables.

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System: Rx Daytona PlusWithin Run Amonq RunAmong DayTotal
MethodProductMEANSDCVSDCVSDCVSDCV
DBILSerum Pool 10.650.023.0 0.011.60.022.40.034.2
DBILSerum Pool 22.310.073.1 0.000.00.010.4 0.073.1
DBILSerum Pool 48.410.131.5 0.070.80.070.90.161.9

Table 1 Precision Summary - Lot 2

b) Linearity/assay reportable range

Linearity studies have been carried out in accordance with C.L.S.I. standard EP6-A. - Linearity studies were performed at 11 levels to determine the analytical range of an assay - that is the range where the reported result is a linear function to the analyte concentration (or where deviation from linearity is less than 5%).

The linearity samples were prepared at 11 levels. The sponsor set a range from 0.1mq/dl analyte concentration up to a high concentration approximately 12.6mg/dl. Each level was run in replicates of five on two lots of direct bilirubin reagent on one RX Daytona plus system. The results are summarized in the following table:

Table 3 Linearity Summary including regression equation and correlation coefficient

Slope1.01
Intercept-0.07
r0.9995
Syx0.10

Table 4 Linearity Summary

AnalyteLinearityReportable Range
Direct Bilirubin12.6mg/dl0.1-12.6mg/dl

The Rx Daytona Plus analyser has an auto-dilution feature that is automatically activated when measuring samples >12.6mg/dl. Samples >12.6mg/dl are diluted and re-measured to obtain values within the measuring range.

  • Traceability, Stability, Expected values (controls, calibrators, or C) methods)
    Refer to 510(k) K053153 for Calibrator and K942458 Control information for Direct Bilirubin.

Randox Calibration Serum Level 3 is traceable to an internal master calibrator for Direct Bilirubin.

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d) Detection limit

Sensitivity studies have been carried out in accordance with C.L.S.I. guideline EP17-A2 'Protocols for Determination of Limits of Detection and Limits of Quantification; Approved Guideline'. A Limit of Blank (LoB), a Limit of Detection (LoD) and a Limit of Quantification (LoQ) were performed on two lots of reagents tested by two operators on one RX Davtona Plus svstem.

The LoD for Direct Bilirubin on the RX Daytona Plus is 0.064mg/dl based on 240 determinations, with 4 low level samples.

The LoB is 0.006mg/dl.

The LoQ is 0.133mg/dl as determined by the lowest concentration that can be detected with ≤20% CV imprecision.

e) Analytical Specificity

Interference studies have been carried out in accordance with C.L.S.I guideline EP7-A2 'Interference Testing in Clinical Chemistry; Approved Guideline Second Edition'. The effects of potential interferents were determined by calculating the mean value of the spiked interferent with the corresponding control solution. The spiked sample results were compared to control samples prepared without the potential interferents.

Acceptance Criteria: % of Control ± 10%

The analytes detailed below were tested up to the levels indicated at Bilirubin concentrations of 0.14mg/dl and 5.03mg/dl, and found not to interfere:

HaemoglobinNo significant interference up to 1000mg/dl
TriglyceridesNo significant interference up to 750mg/dl
Intralipid®No significant interference up to 1000mg/dl
Ascorbic AcidNo significant interference up to 25mg/dl

Table 5 Interference Summary

Method comparison with predicate device f)

Correlation studies were carried out in accordance with C.L.S.I. guideline EP9-A2 'Method Comparison and Bias Estimation Using Patient Samples: Approved Guideline - Second Edition'.

103 serum patient samples spanning the range 0.123-12.46mg/dl were tested by two operators on two lots of direct bilirubin reagent on a RX Daytona plus analyzer and a Siemens Advia system across 3 working days with each sample tested in singlicate. The test method was compared to the predicate device and the following linear regression equation was obtained:

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Y = 1.01x + 0.01 Correlation coefficient of r = 0.997

g) Matrix comparison

Matrix method comparisons for the direct bilirubin assay was tested by one operator on one RX Daytona plus system and was assessed for two lots of direct bilirubin reagents. Both serum and lithium heparin plasma were tested to determine whether method accuracy with lithium heparin specimens are equivalent to serum results and that lithium heparin plasma does not interfere with either the method or the system.

Direct bilirubin matrix comparison on the RX Daytona plus (Lithium Heparin) Patient samples were drawn in matched pairs – one sample serum (x) and the second sample lithium heparin plasma (y). A minimum of 40 matched patient sample pairs were analyzed spanning the range 0.091-12.48mg/dl and the following linear regression equation was obtained:

Y = 0.99x + 0.01 Correlation coefficient of r = 1.00

10. CONCLUSION

Testing results indicate that the proposed device is substantially equivalent to the predicate device.