ELITech Clinical Systems BILIRUBIN TOTAL 4+1, ELITech Clinical Systems BILIRUBIN DIRECT 4+1
Device Facts
| Record ID | K171401 |
|---|---|
| Device Name | ELITech Clinical Systems BILIRUBIN TOTAL 4+1, ELITech Clinical Systems BILIRUBIN DIRECT 4+1 |
| Applicant | Elitechgroup |
| Product Code | CIG · Clinical Chemistry |
| Decision Date | Jul 11, 2017 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 862.1110 |
| Device Class | Class 2 |
Intended Use
ELITech Clinical Systems BILIRUBIN TOTAL 4+1 is intended for the quantitative in vitro diagnostic determination of total bilirubin in human serum and plasma on ELITech Clinical Systems Selectra Pro Series Analyzers. Measurements of the levels of bilirubin (direct or total), an organic compound formed during the normal and abnormal distruction of red blood cells, are used in the diagnosis and treatment of liver, hematological, and metabolic disorders, including hepatitis and gall bladder block. It is not intended for use in Point of Care settings. ELITech Clinical Systems BILIRUBIN DIRECT 4+1 is intended for the quantitative in vitro diagnostic determination of direct bilirubin in human serum and plasma on ELITech Clinical Systems Selectra Pro Series Analyzers. Measurements of the levels of bilirubin (direct or total), an organic compound formed during the normal and abnormal distruction of red blood cells, are used in the diagnosis and treatment of liver, hematological, and metabolic disorders, including hepatitis and gall bladder block. It is not intended for use in Point of Care settings.
Device Story
Quantitative colorimetric assays for total and direct bilirubin in human serum and plasma; performed on Selectra Pro Series Analyzers. Reagents utilize Malloy-Evelyn modified chemistry; sulfanilic acid reacts with sodium nitrite to form diazotized sulfanilic acid; total bilirubin assay uses cetrimide accelerator to react both conjugated and unconjugated bilirubin; direct bilirubin assay excludes accelerator to react only conjugated bilirubin. Increase in absorbance at 546 nm proportional to bilirubin concentration. Used in clinical laboratories; operated by trained personnel. Output provides quantitative bilirubin levels to assist clinicians in diagnosing liver, hemolytic, and metabolic disorders. Supports auto-dilution for samples exceeding measuring range.
Clinical Evidence
No clinical data. Bench testing only. Analytical performance included precision (n=80 per level), linearity (11-level studies), LoB/LoD/LoQ determination, and interference testing (triglycerides, hemoglobin, acetaminophen, ascorbic acid, acetylsalicylic acid). Method comparison (n=100 samples) against predicate yielded r²=0.999 for total bilirubin and r²=0.995 for direct bilirubin. Matrix comparison (n=40) confirmed suitability of serum and lithium heparin plasma.
Technological Characteristics
Quantitative colorimetric assay; Malloy-Evelyn modified principle. Reagents: sulfanilic acid, sodium nitrite, and cetrimide (total only). Form factor: liquid, ready-to-use kit. Instrumentation: Selectra Pro Series Analyzers. Measuring range: 0.25-25.0 mg/dL (total), 0.08-10.55 mg/dL (direct). Connectivity: standalone analyzer. Sterilization: not applicable.
Indications for Use
Indicated for quantitative in vitro diagnostic determination of total or direct bilirubin in human serum and plasma to aid in the diagnosis and treatment of liver, hematological, and metabolic disorders (e.g., hepatitis, gall bladder block). Not for Point of Care use.
Regulatory Classification
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.
Predicate Devices
- ABX Pentra Bilirubin, Total CP (k060325)
- ABX Pentra Bilirubin, Direct CP (k060325)
Related Devices
- K981883 — ROCHE DIAGNOSTICS, BOEHRINGER MANNHEIM CORPORATION LIQUID DIRECT BILIRUBIN REAGENT, CATALOG NUMBER 1877844 · Boehringer Mannheim Corp. · Jul 7, 1998
- K110780 — ELITECH CLINICAL SYSTEMS BILIRUBIN TOTAL 4+1, ELITECH CLINICAL SYSTEMS ELICAL 2, ELITECH CLINICAL SYSTMES ELITROL I & II · Elitechgroup · Oct 7, 2011
- K981632 — ROCHE DIAGNOSTICS, BOEHRINGER MANNHEIM LIQUID TOTAL BILIRUBIN REAGENT · Roche Diagnostics/Boehringer Mannheim GmbH · Jun 15, 1998
Submission Summary (Full Text)
{0}------------------------------------------------
Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is circular, with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. In the center of the circle is a stylized image of a caduceus, which is a symbol of medicine.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
July 11, 2017
ELITECHGROUP TERRY TRIMINGHAM, REGULATORY AFFAIRS MANAGER 21720 23RD DRIVE SE, SUITE 150 BOTHELL, WA 98021
Re: K171401 Trade/Device Name: ELITech Clinical Systems BILIRUBIN TOTAL 4+1, ELITech Clinical Systems BILIRUBIN DIRECT 4+1 Regulation Number: 21 CFR 862.1110 Regulation Name: Bilirubin (total or direct) test system Regulatory Class: II Product Code: CIG Dated: May 3, 2017 Received: May 12, 2017
Dear Terry Trimingham:
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,
Kellie B. Kelm -S
for Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
{2}------------------------------------------------
# Indications for Use
Expiration Date: January 31, 2017 See PRA Statement below.
510(k) Number (if known) k171401
#### Device Name
ELITech Clinical Systems BILIRUBIN TOTAL 4+1 ELITech Clinical Systems BILIRUBIN DIRECT 4+1
Indications for Use (Describe)
ELITech Clinical Systems BILIRUBIN TOTAL 4+1 is intended for the quantitative in vitro diagnostic determination of total bilirubin in human serum and plasma on ELITech Clinical Systems Selectra Pro Series Analyzers.
ELITech Clinical Systems BILIRUBIN DIRECT 4+1 is intended for the quantitative in vitro diagnostic determination of direct bilirubin in human serum and plasma on ELITech Clinical Systems Selectra Pro Series Analyzers.
It is not intended for use in Point of Care settings.
Measurements of the levels of bilirubin (direct or total), an organic compound formed during the normal and abnormal distruction of red blood cells, are used in the diagnosis and treatment of liver, hematological, and metabolic disorders, including hepatitis and gall bladder block.
| 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)
### CONTINUE ON A SEPARATE PAGE IF NEEDED.
This section applies only to requirements of the Paperwork Reduction Act of 1995.
### *DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.*
The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:
> Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."
{3}------------------------------------------------
## 510(k) Summary
## ELITech Clinical Systems BILIRUBIN TOTAL 4+1 ELITech Clinical Systems BILIRUBIN DIRECT 4+1
| 1. | Date: | July 11, 2017 |
|----|---------------------|-------------------------------------------------------------------|
| 2. | Submitter: | ELITech Clinical Systems SAS |
| | | Zone Industrielle |
| | | 61500 SEES |
| | | FRANCE |
| 3. | Contact Person: | Terry Trimingham |
| | | 21720 23rd Dr SE, Suite 150 |
| | | Bothell, WA 98021 |
| | | Phone: 425-482-5190 |
| | | Fax: 425-482-5550 |
| | | Email: t.trimingham@elitechgroup.com |
| 4. | Device Description: | ELITech Clinical Systems BILIRUBIN TOTAL 4+1 |
| | Classification | Class II |
| | | CIG - Diazo Colorimetry, Bilirubin |
| | | Clinical Chemistry |
| | | 21 CFR 862.1110 |
| | Device Description: | ELITech Clinical Systems BILIRUBIN DIRECT 4+1 |
| | Classification | Class II |
| | | CIG - Diazo Colorimetry, Bilirubin |
| | | Clinical Chemistry |
| | | 21 CFR 862.1110 |
| 5. | Predicate Device: | K060325 |
| | | ABX Pentra Bilirubin, Total CP<br>ABX Pentra Bilirubin, Direct CP |
{4}------------------------------------------------
| Intended Use | |
|------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| ELITech Clinical<br>Systems BILIRUBIN<br>TOTAL 4+1: | ELITech Clinical Systems BILIRUBIN TOTAL 4+1 is<br>intended for the quantitative <i>in vitro</i> diagnostic<br>determination of total bilirubin in human serum and<br>plasma on ELITech Clinical Systems Selectra Pro Series<br>Analyzers.<br><br>Measurements of the levels of bilirubin (direct or total), an<br>organic compound formed during the normal and<br>abnormal distruction of red blood cells, are used in the<br>diagnosis and treatment of liver, hemolytic hematological,<br>and metabolic disorders, including hepatitis and gall<br>bladder block.<br><br>It is not intended for use in Point of Care settings. |
| ELITech Clinical<br>Systems BILIRUBIN<br>DIRECT 4+1: | ELITech Clinical Systems BILIRUBIN TOTAL 4+1 is<br>intended for the quantitative <i>in vitro</i> diagnostic<br>determination of total bilirubin in human serum and<br>plasma on ELITech Clinical Systems Selectra Pro Series<br>Analyzers.<br><br>Measurements of the levels of bilirubin (direct or total), an<br>organic compound formed during the normal and<br>abnormal distruction of red blood cells, are used in the<br>diagnosis and treatment of liver, hemolytic hematological,<br>and metabolic disorders, including hepatitis and gall<br>bladder block.<br><br>It is not intended for use in Point of Care settings. |
Special conditions for use statement(s):
Rx only.
6.
This device is intended for prescription use and in vitro diagnostic only.
CAUTION: Federal Law restricts this device to sale by or on the order of a licensed healthcare practitioner. It is not intended for use in Point of Care settings.
### Reagent Special instrument requirements:
For use with ELITech Clinical Systems Selectra Pro Series Analyzers. Performance data was obtained on the Selectra ProM Analyzer.
{5}------------------------------------------------
#### 7. Device Descriptions
Both ELITech Clinical Systems BILIRUBIN TOTAL 4+1 and ELITech Clinical Systems BILIRUBIN DIRECT 4+1 are available as a kit only.
Each kit consists of a bi-reagent R1 & R2 whose composition is:
### ELITech Clinical Systems BILIRUBIN TOTAL 4+1 :
Reagent 1: R1
Sulphanilic acid 29 mmol/L,
Cetrimide 29 mmol/L.
Reagent 2: R2
Sodium nitrite 11 mmol/L.
### ELITech Clinical Systems BILIRUBIN DIRECT 4+1 :
Reagent 1: R1
Sulphanilic acid 29 mmol/L,
Reagent 2: R2
Sodium nitrite 11 mmol/L.
### Substantial Equivalence Information
#### Assay (reagent)
- 1. Predicate Device Name
ABX Pentra Bilirubin, Total CP & ABX Pentra Bilirubin, Direct CP
- 2. K060325
3. Comparison with predicate ABX Pentra Bilirubin, Total CP & ABX Pentra Bilirubin, Direct CP
### Similarities
8.
| Similarities | | |
|--------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | | |
| Parameter | New Device<br>ELITech Clinical Systems BILIRUBIN<br>TOTAL 4+1 & ELITech Clinical<br>Systems BILIRUBIN DIRECT 4+1 | Predicate Device<br>ABX Pentra Bilirubin, Total CP & ABX<br>Pentra Bilirubin, Direct CP, K060325 |
| Intended Use | ELITech Clinical Systems<br>BILIRUBIN TOTAL 4+1: | ABX Pentra Bilirubin, Total CP: |
| | ELITech Clinical Systems BILIRUBIN<br>TOTAL 4+1 is intended for the<br>quantitative <i>in vitro</i> diagnostic<br>determination of total bilirubin in<br>human serum and plasma on ELITech<br>Clinical Systems Selectra Pro Series<br>Analyzers. | ABX Pentra Bilirubin, Total CP reagent<br>is intended for the quantitative <i>in vitro</i><br>diagnostic determination of total<br>bilirubin in human serum and plasma<br>based on a photometric test using 2,4-<br>dichloroaniline (DCA) and detergents. |
| | It is not intended for use in Point of<br>Care settings. | |
{6}------------------------------------------------
| | ELITech Clinical Systems<br>BILIRUBIN DIRECT 4+1 : | ABX Pentra Bilirubin, Direct CP : |
|---------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | ELITech Clinical Systems BILIRUBIN<br>DIRECT 4+1 is intended for the<br>quantitative <i>in vitro</i> diagnostic<br>determination of direct bilirubin in<br>human serum and plasma on ELITech<br>Clinical Systems Selectra Pro Series<br>Analyzers. | ABX Pentra Bilirubin, Direct CP reagent<br>is intended for the quantitative <i>in vitro</i><br>diagnostic determination of direct<br>bilirubin in human serum and plasma<br>based on a photometric test using 2,4-<br>dichloroaniline (DCA). |
| | It is not intended for use in Point of<br>Care settings. | |
| Indication for<br>Use | Measurements of the levels of bilirubin<br>(direct or total), an organic compound<br>formed during the normal and<br>abnormal destruction of red blood cells,<br>are used in the diagnosis and<br>treatment of liver, hemolytic<br>hematological, and metabolic<br>disorders, including hepatitis and gall<br>bladder block. It is not intended for use<br>in Point of Care settings. | Same |
| Sample Type | Serum, plasma | Same |
| Appearance<br>of reagents | Liquid form, ready to use | Same |
## Differences
| Parameter | New Device<br>ELITech Clinical Systems BILIRUBIN<br>TOTAL 4+1 & ELITech Clinical<br>Systems BILIRUBIN DIRECT 4+1 | Predicate Device<br>ABX Pentra Bilirubin, Total CP & ABX<br>Pentra Bilirubin, Direct CP K060325 |
|---------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------|
| Assay Format | ELITech Clinical Systems<br>BILIRUBIN TOTAL 4+1 :<br>R1: 8 x 20 mL<br>R2: 8 x 5 mL<br>ELITech Clinical Systems<br>BILIRUBIN DIRECT 4+1 :<br>R1: 8 x 20 mL<br>R2: 8 x 5 mL | ABX Pentra Bilirubin, Total CP :<br>R1 : 29.5 mL<br>R2 : 9.8 mL<br>ABX Pentra Bilirubin, Direct CP :<br>R1 : 24 mL<br>R2 : 7 mL |
| Assay<br>Technology | Malloy-Evelyn modified. End point. | Photometric test using 2,4-<br>dichloroaniline (DCA), and a specific<br>mixture of detergents. |
{7}------------------------------------------------
{8}------------------------------------------------
| Reference<br>Values | ELITech Clinical Systems<br>BILIRUBIN TOTAL 4+1 : | ABX Pentra Bilirubin, Total CP : |
|-----------------------|------------------------------------------------------------------------------|----------------------------------------------------------------------------|
| | 0.2-1.2 mg/dL (3.4-21 µmol/L)<br>ELITech Clinical Systems | Adults: 0.1 - 1.2 mg/dL (1.7 - 21<br>µmol/L) |
| | BILIRUBIN DIRECT 4+1 : | ABX Pentra Bilirubin, Direct CP : |
| | < 0.2 mg/dL (3.4 µmol/L) | Adults and children: ≤ 0.2 mg/dL (≤<br>3.4 µmol/L). |
| | | |
| Controls | Recommended quality control<br>material (not included): | Recommended quality control<br>material (not included): |
| | | ABX Pentra N Control & ABX Pentra |
| | ELITech Clinical Systems ELITROL I | P Control |
| | (Normal control) (cleared in k110780)<br>ELITech Clinical Systems ELITROL II | |
| | (Pathologic control) (cleared in<br>k110780) | |
| Calibrator | Recommended calibration material<br>(not included): | Recommended calibration material<br>(not included):<br>ABX Pentra Multical |
| | ELITech Clinical Systems ELICAL 2<br>(cleared in k110780) | |
| Limit of<br>Detection | ELITech Clinical Systems<br>BILIRUBIN TOTAL 4+1 : | ABX Pentra Bilirubin, Total CP :<br>1.49 µmol/L (0.09 mg/dL). |
| | 0.04 mg/dL (0.7 µmol/L) | |
| | ELITech Clinical Systems<br>BILIRUBIN DIRECT 4+1 : | ABX Pentra Bilirubin, Direct CP : |
| | 0.01 mg/dL (0.2 µmol/L) | 0.69 µmol/L (0.04 mg/dL). |
{9}------------------------------------------------
| Interferences | ELITech Clinical Systems<br>BILIRUBIN TOTAL 4+1 :<br>Triglycerides: No significant<br>interference up to 2100 mg/dL (23.73<br>mmol/L).<br>Hemoglobin: No significant<br>interference up to 500 mg/dL.<br>Acetaminophen: No significant<br>interference up to 30 mg/dL.<br>Ascorbic acid: No significant<br>interference up to 4 mg/dL.<br>Acetylsalicylic acid: No significant<br>interference up to 200 mg/dL. | ABX Pentra Bilirubin, Total CP :<br>Haemoglobin: No significant influence<br>is observed up to 290 µmol/L (500<br>mg/dL).<br>Triglycerides: No significant influence<br>is observed up to 7 mmol/L (612.5<br>mg/dL). |
|--------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | ELITech Clinical Systems<br>BILIRUBIN DIRECT 4+1 :<br>Triglycerides: No significant<br>interference up to 2000 mg/dL (22.60<br>mmol/L)<br>Hemoglobin: No significant<br>interference up to 125 mg/dL.<br>Acetaminophen: No significant<br>interference up to 30 mg/dL.<br>Ascorbic acid: No significant<br>interference up to 0.5 mg/dL.<br>Acetylsalicylic acid: No significant<br>interference up to 200 mg/dL. | ABX Pentra Bilirubin, Direct CP :<br>Haemoglobin: Do not use hemolysed<br>samples.<br>Triglycerides: No significant influence<br>is observed up to an Intralipid®<br>concentration (representative of<br>lipemia) of 7 mmol/L (612.5 mg/dL). |
| On-board<br>stability | 28 days | ABX Pentra Bilirubin, Total CP :<br>25 days<br>ABX Pentra Bilirubin, Direct CP :<br>30 days |
| Calibration<br>frequency | Calibration frequency: 28 days<br>Recalibrate when reagent lots<br>change, when quality control results<br>fall outside the established range, and<br>after a maintenance operation. | The reagent is calibrated on Day 0.<br>The calibration stability is checked by<br>testing 2 control specimens. The<br>calibration stability is 10 days.<br>Note: A recalibration is recommended<br>when reagent lots change, and when<br>quality control results fall outside the<br>range established. |
{10}------------------------------------------------
#### 9. Test Principle:
#### ELITech Clinical Systems BILIRUBIN TOTAL 4+1 :
Sulphanilic acid reacts with sodium nitrite to form diazotized sulphanilic acid. In the presence of accelerator (cetrimide), conjugated and unconjugated bilirubin react with diazotized sulphanilic acid to form azobilirubin.
The increase of absorbance at 546 nm is proportional to bilirubin concentration.
#### ELITech Clinical Systems BILIRUBIN DIRECT 4+1 :
Sulphanilic acid reacts with sodium nitrite to form diazotized sulphanilic acid. In the absence of accelerator, only conjugated bilirubin reacts with diazoted sulphanilic acid to form azobilirubin.
The increase of absorbance at 546 nm is proportional to bilirubin concentration.
#### Performance Characteristics - Analytical Performance 10.
#### a. Precision/Reproducibility
#### Precision
Within-run and total precision results were obtained by performing two runs per day, two measures per run, for 3 concentrations of samples on 2 instruments during twenty operating days. The results are presented in the tables below:
#### For ELITech Clinical Systems BILIRUBIN TOTAL 4+1:
| Level | n | Mean (mg/dL) | Precision % | |
|---------|----|--------------|----------------|-----------|
| | | | Within-run CV% | Total CV% |
| Level 1 | 80 | 1.15 | 1.8 | 5.0 |
| Level 2 | 80 | 4.08 | 0.4 | 3.1 |
| Level 3 | 80 | 14.61 | 0.5 | 2.9 |
#### For ELITech Clinical Systems BILIRUBIN DIRECT 4+1:
| Level | n | Mean (mg/dL) | Precision % | |
|---------|----|--------------|----------------|-----------|
| | | | Within-run CV% | Total CV% |
| Level 1 | 80 | 0.36 | 3.8 | 5.2 |
| Level 2 | 80 | 1.51 | 1.9 | 5.3 |
| Level 3 | 80 | 3.99 | 0.9 | 4.7 |
{11}------------------------------------------------
#### b. Linearity/assay reportable range
The linearity of ELITech Clinical Systems BILIRUBIN TOTAL 4+1 was studied by mixing a sample with high value (25.13 mg/dL) and a sample with low value (0.25 mg/dL) to obtain 11 levels with equidistant concentrations and then measuring the Total Bilirubin concentration of each of the 11 levels using ELITech Clinical Systems BILIRUBIN TOTAL 4+1.
From this study, a measuring range from 0.25 - 25 mg/dL has been determined. Auto-dilution 1 to 5 allows the use of the ELITech Clinical Systems BILIRUBIN TOTAL 4+1 with analyte concentration up to 60.00 mg/dL.
The linearity of ELITech Clinical Systems BILIRUBIN DIRECT 4+1 was studied by mixing a sample with high value (10.59 mg/dL) and a sample with low value (0.06 mg/dL) to obtain 11 levels with equidistant concentrations and then measuring the Direct Bilirubin concentration of each of the 11 levels using ELITech Clinical Systems BILIRUBIN DIRECT 4+1.
From this study, a measuring range from 0.08 - 10.55 mg/dL has been determined. Auto-dilution 1 to 5 allows the use of the ELITech Clinical Systems BILIRUBIN DIRECT 4+1 with analyte concentration up to 50.00 mg/dL.
#### c. Detection limit
#### Limit of Detection:
#### ELITech Clinical Systems BILIRUBIN TOTAL 4+1 :
The limit of Detection was obtained from 15 measurements of 4 samples prepared from 4 patient samples measured using ELITech Clinical Systems BILIRUBIN TOTAL 4+1 and diluted with Albumin 6 q/dL - NaCl 0.9 % down to a concentration of circa 0.15 mg/dL. The data are not Gaussian. so LoD= LoB + DS.ß (where DS.ß is determined by calculating the median minus the 5th percentile of the low activity sample distribution). Limit of Detection : 0.04 mg/dL (0.7 umol/L)
#### ELITech Clinical Systems BILIRUBIN DIRECT 4+1 :
The limit of Detection was obtained from 15 measurements of 4 samples prepared from 4 patient samples measured using ELITech Clinical Systems BILIRUBIN DIRECT 4+1 and diluted with Albumin 6 g/dL - NaCl 0.9 % to obtain a concentration of approximately 4 times the LoB.
The data are not Gaussian, so LoD= LoB + DS,ß (where DS,ß is determined by calculating the median minus the 5th percentile of the low activity sample distribution). Limit of Detection : 0.01 mg/dL (0.2 umol/L)
Limit of Quantification:
#### ELITech Clinical Systems BILIRUBIN TOTAL 4+1 :
The limit of Quantification was obtained from 15 measurements of 4 samples prepared from 4 patient samples measured using ELITech Clinical Systems BILIRUBIN TOTAL 4+1 reagent and diluted with Albumin 6 g/dL - NaCl 0.9 % down to a concentration circa 0.15 ma/dL.
Acceptance criteria: The acceptable Total Error for the determination Limit of Quantification is ≤ 0.07 mg/dL. The value must be equal or higher than the Limit of Detection. Limit of Quantification = 0.15 mq/dL (2.6 umol/L)
{12}------------------------------------------------
#### ELITech Clinical Systems BILIRUBIN DIRECT 4+1 :
The limit of Quantification was obtained from 15 measurements of 4 samples prepared from 4 patient samples measured using ELITech Clinical Systems BILIRUBIN DIRECT 4+1 reagent and diluted with Albumin 6 g/dL - NaCl 0.9 % down to a concentration circa of 0.08 ma/dL.
Acceptance criteria: The acceptable Total Error for the determination Limit of Quantification is ≤ 0.05 mg/dL. The value must be equal or higher than the Limit of Detection. Limit of Quantification = 0.08 mg/dL (1.4 µmol/L)
#### d. Interference/analytical specificity
#### ELITech Clinical Systems BILIRUBIN TOTAL 4+1:
Interferences due to Triglycerides, Hemoglobin, Acetaminophen, Ascorbic acid, and Acetylsalicylic acid were investigated.
For each potential interferent tested, 2 serum sample pools at two Total Bilirubin levels were prepared:
-1st pool: low concentration at nominal 1.00 mg/dL
-2nd pool: high concentration at nominal 15.00 mg/dL
Aliquots of each of the serum sample pools were spiked with increasing interferent concentration. Test ranges covered at least the interferent level. Thus, there were two series of interferent spike for each potential interferent tested. A control sample was prepared from the sample pool diluted in the appropriate diluent.
| Interferent | Test range | Number of different<br>concentrations tested |
|----------------------|------------------|----------------------------------------------|
| Triglycerides | up to 3000 mg/dL | 9 |
| Hemoglobin | up to 500 mg/dL | 9 |
| Acetaminophen | up to 30 mg/dL | 7 |
| Ascorbic acid | up to 20 mg/dL | 7 |
| Acetylsalicylic acid | up to 200 mg/dL | 7 |
Two (2) levels of control (ELITech Clinical Systems ELITROL I & II ) were tested to check the calibration.
For both sample pools for each interferent, each point was measured in triplicate per run. Acceptance criteria: an accepted bias of ±10% in sample pools with low (1.00 mg/dL) or high (15.00 mg/dL) nominal activity.
The results of testing interferences are the following:
- Triglycerides concentration up to 2100 mg/dL (23.73 mmol/L), Hemoglobin up to 500 mg/dL, Acetaminophen up to 30 mg/dL, Ascorbic acid up to 4 mg/dL. Acetylsalicylic acid up to 200 mg/dL.
- In very rare cases, monoclonal gammopathies (multiple myeloma), in particular IgM type (Waldenstrom's macroglobulinemia) can cause unreliable results.
The following statement will also be included in the labeling:
Many other substances and drugs may interfere. Some of them are listed in Young. -Young, D. S., Effects of preanalytical variables on clinical laboratory tests, 2nd Ed., AACC Press. (1997).
-Young, D. S., Effects of drugs on clinical laboratory tests, 4th Ed., AACC Press, (1995). -Berth, M. & Delanghe, J. Protein precipitation as a possible important pitfall in the clinical chemistry analysis of blood samples containing monoclonal immunoglobulins: 2 case reports and a review of literature, Acta Clin Belg., (2004), 59, 263.
{13}------------------------------------------------
### ELITech Clinical Systems DIRECT DIRECT 4+1:
Interferences due to Trialycerides. Hemoglobin, Acetaminophen, Ascorbic acid, and Acetylsalicylic acid were investigated.
For each potential interferent tested, 2 serum sample pools at two Direct Bilirubin levels were prepared:
-1st pool: low activity at nominal 0.40 mg/dL
-2nd pool: high activity at nominal 4.00 mg/dL
Aliquots of each of the serum sample pools were spiked with increasing interferent concentration. Test ranges covered at least the interferent level. Thus, there were two series of interferent spike for each potential interferent tested. A control sample was prepared from the sample pool diluted in the appropriate diluent.
| Interferent | Test range | Number of different<br>concentrations tested |
|----------------------|------------------|----------------------------------------------|
| Triglycerides | up to 3000 mg/dL | 9 |
| Hemoglobin | up to 500 mg/dL | 9 |
| Acetaminophen | up to 30 mg/dL | 7 |
| Ascorbic acid | up to 5 mg/dL | 8 |
| Acetylsalicylic acid | up to 200 mg/dL | 7 |
Two (2) levels of control (ELITech Clinical Systems ELITROL I & II ) were tested to check the calibration.
For both sample pools for each interferent, each point was measured in triplicate per run. Acceptance criteria: an accepted bias of ±10% in sample pools with low (0.40 mg/dL) or high (4.00 mg/dL) nominal activity.
The results of testing interferences are the following:
- Triglycerides concentration up to 2000 mg/dL (22.60 mmol/L), Hemoglobin up to 125 mg/dL, Acetaminophen up to 30 mg/dL, Ascorbic acid up to 0.5 mg/dL, Acetylsalicy/ic acid up to 200 mg/dL.
- In very rare cases, monoclonal gammopathies (multiple myeloma), in particular IgM । type (Waldenstrom's macroglobulinemia) can cause unreliable results.
The following statement will also be included in the labeling:
Many other substances and drugs may interfere. Some of them are listed in Young. -Young, D. S., Effects of preanalytical variables on clinical laboratory tests, 200 Ed., AACC Press. (1997).
-Young, D. S., Effects of drugs on clinical laboratory tests, 4th Ed., AACC Press, (1995). -Berth, M. & Delanghe, J. Protein precipitation as a possible important pitfall in the clinical chemistry analysis of blood samples containing monoclonal immunoglobulins: 2 case reports and a review of literature, Acta Clin Belg., (2004), 59, 263.
{14}------------------------------------------------
#### 11. Performance Characteristics - Comparison Studies
#### a. Method comparison
Correlation studies were performed between ELITech Clinical Systems BILIRUBIN TOTAL 4+1 & ELITech Clinical Systems BILIRUBIN DIRECT 4+1 reagents on a Selectra ProM Analyzer.
#### ELITech Clinical Systems BILIRUBIN TOTAL 4+1 :
This study was performed using 100 serum patient samples from 0.32 to 23.02 mg/dL over a span of 5 days. Regression analysis of the results yielded the following: y = 0.948 x - 0.11 mg/dL. r = 0.999 r2 = 0.999 Standard error of the estimate Sy.x = 0.19 mg/dL.
#### ELITech Clinical Systems BILIRUBIN DIRECT 4+1 :
This study was performed using 100 serum patient samples from 0.09 to 10.52 mg/dL over a span of 5 days. Regression analysis of the results yielded the following: y = 0.926 x - 0.03 mg/dL. r = 0.998 r2 = 0.995 Standard error of the estimate Sy.x = 0.15 mg/dL.
#### b. Comparison study: Matrix comparison
#### ELITech Clinical Systems BILIRUBIN TOTAL 4+1 :
40 plasma patients (in lithium heparin samples, ranging from 0.33 to 24.08 mg/dL), were tested on ELITech Clinical Systems Selectra ProM Analyzer. Regression analysis of the results yielded the following: y = 0.985x + 0.03 mg/dL r = 0.998 r2 = 0.997 Standard error of the estimate Sy.x = 0.36 mg/dL
#### ELITech Clinical Systems BILIRUBIN DIRECT 4+1 :
40 plasma patients (in lithium heparin samples, ranging from 0.09 to 7.78 mg/dL), were tested on ELITech Clinical Systems Selectra ProM Analyzer. Regression analysis of the results yielded the following: y = 0.990x - 0.01 mg/dL r = 0.999 r2 = 0.997 Standard error of the estimate Sy.x = 0.14 mg/dL
#### c. Expected values/Reference Range
As indicated in the instructions for use for both ELITech Clinical Systems BILIRUBIN TOTAL 4+1 & ELITech Clinical Systems BILIRUBIN DIRECT 4+1, each laboratory should establish and maintain its own reference values. The values given are used as guidelines only.
{15}------------------------------------------------
#### ELITech Clinical Systems BILIRUBIN TOTAL 4+1 :
Adults : 0.2-1.2 mg/dL ( 3.4-21 umol/L)
#### ELITech Clinical Systems BILIRUBIN DIRECT 4+1 :
< 0.2 mg/dL (3.4 µmol/L)
These reference values are from:
Wu, H.B., General Clinical Tests. Tietz Clinical guide to laboratory tests, 4th Ed., (W.B. Saunders eds. Philadelphia USA), (2006), 172
#### d. Clinical Studies:
Not applicable
#### e. Clinical Cut-off:
Not applicable
#### 12. Conclusion
The information on the principle and performance of the devices contained in this premarket notification is complete and supports a decision that both ELITech Clinical Systems BILIRUBIN TOTAL 4+1 & ELITech Clinical Systems BILIRUBIN DIRECT 4+1 are substantially equivalent to their respective predicate device.
