(54 days)
Not Found
No
The summary describes a standard turbidimetric assay for measuring albumin concentration, which relies on chemical reactions and light scattering principles, not AI/ML algorithms. There is no mention of AI, ML, or related concepts in the device description or performance studies.
No
This device is an in vitro diagnostic (IVD) reagent used for the quantitation of albumin, which aids in the diagnosis of kidney diseases, not for therapeutic purposes.
Yes
The device aids in the diagnosis of kidney diseases by measuring albumin concentration in urine and CSF.
No
The device description clearly states it is a reagent kit and calibrator in liquid format, intended for use on Beckman Coulter AU clinical chemistry systems. 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 Statement: The "Intended Use / Indications for Use" section explicitly states: "For in vitro diagnostic use only." This is a clear indicator that the device is intended for use outside of the body to diagnose conditions.
- Purpose: The device is intended for the "quantitation of albumin concentration in human urine and cerebrospinal fluid (CSF) on the Beckman Coulter AU clinical chemistry systems as an aid in the diagnosis of kidney diseases." This describes a diagnostic purpose using biological samples.
- Device Description: The description details reagents and calibrators used to perform a chemical test (turbidimetric method) on biological samples (urine and CSF) to measure a specific analyte (albumin). This aligns with the nature of IVD devices.
N/A
Intended Use / Indications for Use
Urine/CSF Albumin:
The Urine/CSF Albumin reagent is intended to be used for the quantitation of albumin concentration in human urine and cerebrospinal fluid (CSF) on the Beckman Coulter AU clinical chemistry systems as an aid in the diagnosis of kidney diseases. For in vitro diagnostic use only.
Urine/CSF Albumin Calibrator:
The Urine/CSF Albumin calibrator is intended to be used to calibrate the Urine/CSF Albumin reagent on the Beckman Coulter AU clinical chemistry systems. For in vitro diagnostic use only.
Product codes (comma separated list FDA assigned to the subject device)
DCF, JIT
Device Description
The Urine/CSF Albumin reagent kit is in a liquid, ready to use format. There are two kit concepts available. Each kit concept contains an R1 and an R2 reagent vial with different fill volumes. The Urine/CSF Albumin calibrator kit is in a liquid, ready to use format and contains 5 x 2 mL calibrator levels. It is packaged and sold separately to the reagent kit. Urine/CSF Albumin reagent is used to measure albumin concentration by a turbidimetric method. In the reaction, anti-human serum albumin antibodies combine with albumin from the sample to form immune complexes that scatter light in proportion to their size, shape and concentration. The absorbance of these aggregates is proportional to the albumin concentration in the sample. Change in absorbance is measured at 380nm with subtraction of a reference wavelength at 800nm. The Urine/CSF Albumin reagent and calibrator is designed for optimal performance on Beckman Coulter AU clinical chemistry analyzers.
The calibrator is manufactured from human material; therefore it should be handled as though capable of transmitting infectious disease. Each serum or plasma donor unit used in the preparation of this material was tested by United States Food and Drug Administration (FDA) approved methods and found to be negative for the antibodies to HIV and HCV and nonreactive for HB Ag. Because no test method can offer complete assurance that HIV. hepatitis B virus, and hepatitis C virus or other infectious agents are absent, this material and all patient samples should be handled as though capable of transmitting infectious disease. This product may also contain other human source material for which there is no approved test. The FDA recommends such samples be handled as specified in the Centers for Disease Control's Biosafety Level 2 guidelines.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Human urine, cerebrospinal fluid (CSF)
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)
Performance Characteristics - Analytical Performance:
a. Precision:
Type: Within run (repeatability) and total imprecision (within laboratory) studies.
Protocol: CLSI guideline EP05-A2 "Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline - Second Edition".
Instrument: AU5800 analyzer.
Training: Pooled human urine samples spiked with purified human serum albumin for urine pools. Pooled human CSF samples diluted with 0.9% saline or spiked with purified human serum albumin for CSF pools.
Experimental Design: Duplicate sample analysis, twice daily, over 20 working days (n=80) for 3 sample levels, with a minimum interval of 2 hours between runs.
Key Results:
CSF: Low (Mean 6.30 mg/dL): Repeatability SD 0.07 mg/dL (CV 1.0%), Within Laboratory SD 0.11 mg/dL (CV 1.8%).
CSF: Mid (Mean 26.5 mg/dL): Repeatability SD 0.4 mg/dL (CV 1.6%), Within Laboratory SD 0.6 mg/dL (CV 2.4%).
CSF: High (Mean 35.0 mg/dL): Repeatability SD 0.7 mg/dL (CV 1.9%), Within Laboratory SD 0.9 mg/dL (CV 2.5%).
Urine: Low (Mean 1.68 mg/dL): Repeatability SD 0.02 mg/dL (CV 0.9%), Within Laboratory SD 0.07 mg/dL (CV 4.3%).
Urine: Mid (Mean 3.28 mg/dL): Repeatability SD 0.02 mg/dL (CV 0.6%), Within Laboratory SD 0.08 mg/dL (CV 2.5%).
Urine: High (Mean 20.0 mg/dL): Repeatability SD 0.3 mg/dL (CV 1.4%), Within Laboratory SD 0.4 mg/dL (CV 2.1%).
b. Analytical Range (Linearity):
Type: Linearity studies.
Protocol: CLSI guidelines EP06-A "Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach: Approved Guideline".
Instrument: AU5800 analyzer.
Training: High and low albumin pools prepared by spiking with HSA. High urine and CSF pools diluted with urine and CSF respectively to generate lower concentrations.
Experimental Design: 11 linearity concentration levels, each dilution assayed in quadruplicate. Polynomial regression analysis performed.
Key Results: Acceptable linearity for claimed measuring ranges: Urine (0.7 - 45 mg/dL), CSF (1 - 45 mg/dL).
d. Reagent and Calibrator Stability:
Type: Shelf-Life (Accelerated stability testing).
Protocol: CLSI guideline EP25-A "Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline".
Instrument: AU5800 analyzer.
Experimental Design: Testing at multiple elevated temperatures using three reagent lots and three calibrator lots.
Key Results: Reagent and calibrator are stable for 18 months at 2 - 8°C.
Type: Reagent On-Board, Calibration Frequency and Calibrator Open Vial Stability.
Protocol: CLSI guideline EP25-A "Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline".
Instrument: AU5800 analyzer.
Experimental Design: Testing using three reagent lots, three calibration runs on the first day. Urine & CSF control material run in duplicate at each time point.
Key Results: 60-day reagent on-board claim, 60-day calibration frequency claim, and 30-day calibrator open vial stability claim established.
e. Sensitivity (Detection Limits):
Type: LoB (Limit of Blank), LoD (Limit of Detection) and LoQ (Limit of Quantitation) studies.
Protocol: CLSI guideline EP17-A2 "Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures Approved Guideline - Second Edition".
Instrument: AU5800 analyzer.
LoB and LoD Experimental Design: Replicate measurements on blank and low level samples using three lots of reagent across multiple days (60 blank replicates per reagent lot, 60 low level sample replicates per reagent lot). Comprised of 4 blank samples and 4 low levels samples for urine and CSF, run 5-fold for 3 days. Four separate saline pools used as blanks.
LoQ Experimental Design: Functional sensitivity used (6 pools with concentrations of approximately 0.1, 0.2, 0.35, 0.5, 0.7 and 1 mg/dL albumin in urine and CSF). Samples measured in duplicate, twice daily, over 20 working days (n=80).
Key Results: Sensitivity ≤ 0.7 mg/dL for Urine and ≤ 1.0 mg/dL for CSF.
LoB (mg/dL): Urine 0.00, CSF 0.00.
LoD (mg/dL): Urine 0.07, CSF 0.13.
LoQ (mg/dL): Urine 0.70, CSF 0.70.
f. Interferences (Analytical Specificity):
Type: Interference studies.
Protocol: CLSI Guideline EP07-A2: "Interference Testing in Clinical Chemistry: Approved Guideline - Second Edition".
Instrument: AU5800 analyzer.
Experimental Design: Tested at two Urine/CSF Albumin concentrations (1.5-3 mg/dL and 10-20 mg/dL for Urine; 10-20 mg/dL and 25-35 mg/dL for CSF). Urine pools prepared by spiking with HSA. CSF pools prepared by diluting with 0.9% saline. Sample pools tested at ≥ 5 different levels of interferent, each tested in quadruplicate.
Key Results: No significant interference (NSI) (≤ ± 10% or ± 0.2 mg/dL) for tested substances (Calcium, Creatinine, Glucose, Urea, Ascorbic Acid, Citrate, Magnesium, Oxalate, Conjugated Bilirubin, Hemoglobin, Acetone, Uric Acid, Urobilinogen, Acetaminophen, Ibuprofen, Metronidazole, 5-aminosalicylic acid in urine; Hemoglobin, Conjugated Bilirubin in CSF) up to specified levels.
g. Prozone:
Type: Prozone study.
Instrument: AU5800 analyzer.
Experimental Design: Human urine and CSF spiked with human serum to create high prozone pool (≥ 2000 mg/dL). Albumin concentration determined using 3 replicates of at least 3 dilutions. Series of dilutions prepared. Run n = 3.
Key Results: All samples from the upper end of the linear range up to the claimed prozone tolerance generated a flagged result indicating a result above the linear range.
Performance Characteristics - Comparison Studies:
a. Method Comparison:
Type: Method comparison and bias estimation experiments.
Protocol: CLSI Guideline EP09-A3 "Measurement Procedure Comparison and Bias Estimation Using Patient Samples; Approved Guideline".
Urine Application:
Compared against another commercially available assay.
Results: Slope = 1.09, Intercept = 0.03 mg/dL, r = 1.0, n = 131, Sample range = (0.81 - 40.7 mg/dL).
CSF Application:
Compared against another commercially available assay.
Results: Slope = 1.05, Intercept = -0.77 mg/dL, r = 0.99, n = 131, Sample range = (1.72 - 41.2 mg/dL).
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
LoB (Limit of Blank) for Urine: 0.00 mg/dL
LoB (Limit of Blank) for CSF: 0.00 mg/dL
LoD (Limit of Detection) for Urine: 0.07 mg/dL
LoD (Limit of Detection) for CSF: 0.13 mg/dL
LoQ (Limit of Quantitation) for Urine: 0.70 mg/dL
LoQ (Limit of Quantitation) for CSF: 0.70 mg/dL
Precision (CV%):
CSF: Low (1.0% repeatability, 1.8% within laboratory)
CSF: Mid (1.6% repeatability, 2.4% within laboratory)
CSF: High (1.9% repeatability, 2.5% within laboratory)
Urine: Low (0.9% repeatability, 4.3% within laboratory)
Urine: Mid (0.6% repeatability, 2.5% within laboratory)
Urine: High (1.4% repeatability, 2.1% within laboratory)
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.
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.
Not Found
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
§ 866.5040 Albumin immunological test system.
(a)
Identification. An albumin immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the albumin (a plasma protein) in serum and other body fluids. Measurement of albumin aids in the diagnosis of kidney and intestinal diseases.(b)
Classification. Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 866.9.
0
Image /page/0/Picture/1 description: The image shows the logo for the Department of Health & Human Services - USA. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is a stylized image of three human profiles facing to the right. The profiles are stacked on top of each other, with the first profile being the most prominent.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
October 15, 2014
BECKMAN COULTER IRELAND, INC. ANNE-MARIE SHINE REGULATORY AFFAIRS SPECIALIST LISMEEHAN, O'CALLAGHANS MILLS CO. CLARE, IRELAND
Re: K142346
Trade/Device Name: Urine/CSF Albumin and Urine/CSF Albumin Calibrator Regulation Number: 21 CFR 866.5040 Regulation Name: Albumin immunological test system Regulatory Class: II Product Code: DCF, JIT Dated: August 20, 2014 Received: August 22, 2014
Dear Ms. Anne-Marie Shine:
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.
Courtney
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
510(k) Number (if known) K142346
Device Name
Urine/CSF Albumin and Urine/CSF Albumin Calibrator
Indications for Use (Describe)
Urine/CSF Albumin:
The Urine/CSF Albumin reagent is intended to be used for the quantitation of albumin concentration in human urine and cerebrospinal fluid (CSF) on the Beckman Coulter AU clinical chemistry systems as an aid in the diagnosis of kidney diseases. For in vitro diagnostic use only.
Urine/CSF Albumin Calibrator:
The Urine/CSF Albumin calibrator is intended to be used to calibrate the Urine/CSF Albumin reagent on the Beckman Coulter AU clinical chemistry systems. For in vitro diagnostic 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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3
510(k) Summary
Urine/CSF Albumin and Urine/CSF Albumin Calibrator
1.0 Submitted By:
Anne-Marie Shine Regulatory Affairs Specialist Beckman Coulter Ireland Inc., Lismeehan, O'Callaghan's Mills, Co. Clare, Ireland. Phone: +353-65-683-1138 FAX: +353-65-683-1122 email: amshine@beckman.com
2.0 Date Prepared:
20th August 2014
3.0 Device Identifications
| Proprietary Name: | Urine/CSF Albumin and Urine/CSF Albumin Calibrator |
|---|---|
| Common Name: | Urine/CSF Albumin and Urine/CSF Albumin Calibrator |
| Classification: | Class II (Limitations tripped)/Class II |
| Product Codes: | DCF and JIS |
| Regulation Number: | 21CFR 866.5040/862.1150 |
4.0 Predicate Devices
Urine Predicate
| Proposed Device | Predicate Device | Manufacturer | Docket Number |
|---|---|---|---|
| Urine/CSF Albumin, | |||
| Model Nos. | |||
| B38858 | |||
| B46435 | SYNCHRON® Systems | ||
| Microalbumin (MA) Reagent, | |||
| Model No. 475100 | Beckman Coulter, Inc. | K082251 |
CSF Predicate
| Proposed Device | Predicate Device | Manufacturer | Docket Number |
|---|---|---|---|
| Urine/CSF Albumin, | |||
| Model Nos. | |||
| B38858 | |||
| B46435 | IMMAGE® Immunochemistry | ||
| System Albumin (ALB) Reagent, | |||
| Model No. 447600 | Beckman Coulter, Inc. | ||
| (Previously Beckman | |||
| Instruments, Inc.) | K964695 |
Calibrator Predicate
| Proposed Device | Predicate Device | Manufacturer | Docket Number |
|---|---|---|---|
| Urine/CSF Albumin | |||
| Calibrator, | |||
| Model No. | |||
| B38859 | SYNCHRON® Systems | ||
| Microalbumin (MA) Calibrator, | |||
| Model No. 475089 | Beckman Coulter, Inc. | K000331 |
Urine/CSF Albumin and Urine/CSF Albumin Calibrator are substantially equivalent to the Beckman Coulter, Inc. predicate products listed above currently in commercial distribution.
4
5.0 Description
The Urine/CSF Albumin reagent kit is in a liquid, ready to use format. There are two kit concepts available. Each kit concept contains an R1 and an R2 reagent vial with different fill volumes. The Urine/CSF Albumin calibrator kit is in a liquid, ready to use format and contains 5 x 2 mL calibrator levels. It is packaged and sold separately to the reagent kit. Urine/CSF Albumin reagent is used to measure albumin concentration by a turbidimetric method. In the reaction, anti-human serum albumin antibodies combine with albumin from the sample to form immune complexes that scatter light in proportion to their size, shape and concentration. The absorbance of these aggregates is proportional to the albumin concentration in the sample. Change in absorbance is measured at 380nm with subtraction of a reference wavelength at 800nm. The Urine/CSF Albumin reagent and calibrator is designed for optimal performance on Beckman Coulter AU clinical chemistry analyzers.
The calibrator is manufactured from human material; therefore it should be handled as though capable of transmitting infectious disease. Each serum or plasma donor unit used in the preparation of this material was tested by United States Food and Drug Administration (FDA) approved methods and found to be negative for the antibodies to HIV and HCV and nonreactive for HB Ag. Because no test method can offer complete assurance that HIV. hepatitis B virus, and hepatitis C virus or other infectious agents are absent, this material and all patient samples should be handled as though capable of transmitting infectious disease. This product may also contain other human source material for which there is no approved test. The FDA recommends such samples be handled as specified in the Centers for Disease Control's Biosafety Level 2 guidelines.
6.0 Intended Use
Urine/CSF Albumin
The Urine/CSF Albumin reagent is intended to be used for the quantitation of albumin concentration in human urine and cerebrospinal fluid (CSF) on the Beckman Coulter AU clinical chemistry systems as an aid in the diagnosis of kidney diseases. For in vitro diagnostic use only.
Urine/CSF Albumin Calibrator
The Urine/CSF Albumin calibrator is intended to be used to calibrate the Urine/CSF Albumin reagent on the Beckman Coulter AU clinical chemistry systems. For in vitro diagnostic use only.
5
7.0 Comparison to the Predicate(s)
Urine/CSF Albumin claims to be substantially equivalent to the predicate identified in section 4. The following tables show similarities and differences between the reagent predicates and proposed device.
| Test System | Urine Predicate | Proposed New System |
|---|---|---|
| Proprietary and | ||
| Established | ||
| Names | SYNCHRON® Systems Microalbumin (MA) | |
| Reagent | Urine/CSF Albumin | |
| SIMILARITIES | ||
| Intended use | MA reagent, when used in conjunction with | |
| UniCel® DxC 600/800 System(s) and | ||
| SYNCHRON® Systems MA Calibrator is | ||
| intended for quantitative determination of | ||
| Albumin concentration in human urine. | Same | |
| The Urine/CSF Albumin reagent is | ||
| intended to be used for the | ||
| quantitation of albumin | ||
| concentration in human urine. | ||
| Technology | Photometric | Same |
| Operating | ||
| Principle | Turbidimetric Method | Same |
| Sample Types | Urine | Same |
| Reagent | ||
| Material: | ||
| Antibodies | Antibody specific for human albumin (goat | |
| polyclonal) | Same | |
| Reagent | ||
| Material: Buffer | Phosphate buffer with PEG | Same |
| Reagent On- | ||
| Board Stability | 60 days | Same |
| Reagent | ||
| Storage/ Closed | ||
| Shelf Life | 2-8°C until expiration date | Same |
| Precision | ||
| Within Run | ≤ 5.4% CV or 0.125 mg/dL | Similar |
| ≤ 5% CV or 0.1 mg/dL | ||
| Reference | ||
| Interval | Reference Interval Based on Literature | |
| Reference: | ||
| American Diabetes Association, "Diabetic | ||
| Nephropathy", Diabetes Care, 20 [Suppl 1]: | ||
| 524 7 (1997) | Same |
Urine Application
6
| Test System | Urine Predicate | Proposed New System |
|---|---|---|
| Proprietary | ||
| and | ||
| Established | ||
| Names | SYNCHRON® Systems Microalbumin (MA) | |
| Reagent | Urine/CSF Albumin | |
| DIFFERENCES | ||
| Technology | ||
| Type | Instrumentation: SYNCHRON LX® Systems, | |
| UniCel® DxC 600/800 Systems | Instrumentation: Beckman Coulter | |
| AU clinical chemistry systems | ||
| Analyzers | SYNCHRON LX® Systems, | |
| UniCel® DxC 600/800 Systems | AU Clinical Chemistry Analyzers |
CSF Application
| Test System | CSF Predicate | Proposed New System |
|---|---|---|
| Proprietary and | ||
| Established | ||
| Names | IMMAGE® Immunochemistry System Albumin | |
| (ALB) Reagent | Urine/CSF Albumin | |
| SIMILARITIES | ||
| Intended use | ALB reagent, when used in conjunction with | |
| IMMAGE® Immunochemistry Systems and | ||
| Calibrator 3, is intended for quantitative | ||
| determination of Albumin (ALB) in human | ||
| serum or cerebrospinal fluid (CSF) by rate | ||
| nephelometry. | Same | |
| The Urine/CSF Albumin reagent is | ||
| intended to be used for the | ||
| quantitation of albumin | ||
| concentration in cerebrospinal | ||
| fluid (CSF). | ||
| Technology | Photometric | Same |
| Reagent | ||
| Material: | ||
| Antibodies | Antibody specific for human albumin (goat | |
| polyclonal) | Same | |
| Reagent | ||
| Material: Buffer | Phosphate buffer with PEG | Same |
| Sample Types | Serum and CSF | Similar |
| CSF | ||
| Reagent | ||
| Storage/ Closed | ||
| Shelf Life | 2-8°C until expiration date | Same |
7
| Test System | CSF Predicate | Proposed New System |
|---|---|---|
| Proprietary | ||
| and | ||
| Established | ||
| Names | IMMAGE® Immunochemistry System | |
| Albumin (ALB) Reagent | Urine/CSF Albumin | |
| DIFFERENCES | ||
| Technology | ||
| Type | Instrumentation: Beckman IMMAGE | |
| Immunochemistry Systems | Instrumentation: Beckman Coulter AU | |
| clinical chemistry systems | ||
| Operating | ||
| Principle | Rate nephelometry | Turbidimetric |
| Analyzers | IMMAGE Immunochemistry System | AU Clinical Chemistry Analyzers |
| Sample Types | Serum and CSF | CSF |
Urine/CSF Albumin Calibrator claims to be substantially equivalent to the predicate identified in section 4. The following table shows similarities and differences between the calibrator predicate and proposed device.
| Test System | Calibrator Predicate | Proposed New System |
|---|---|---|
| Proprietary and | ||
| Established | ||
| Names | SYNCHRON® Systems | |
| MA Calibrator | Urine/CSF Albumin Calibrator | |
| SIMILARITIES | ||
| Intended use | MA Calibrator, when used in conjunction | |
| with SYNCHRON Systems MA Reagent (P/N | ||
| 475100), is intended for use on the | ||
| SYNCHRON LX® and UniCel® DxC Systems for | ||
| the calibration of Microalbumin. | Similar | |
| The Urine/CSF Albumin calibrator | ||
| is intended to be used to calibrate | ||
| the Urine/CSF Albumin reagent | ||
| on the Beckman Coulter AU | ||
| clinical chemistry systems. | ||
| For in vitro diagnostic use only. | ||
| Single | ||
| Constituent | ||
| Calibrator | ||
| Composition | pH buffered human serum albumin | Same |
| Calibrator | ||
| Matrix Base | Aqueous pH buffer | Same |
| Calibrator | ||
| Traceability | ERM® - DA470 | Same |
| Calibrator | ||
| Storage/ Closed | ||
| Shelf Life | 2-8°C until expiration date | Same |
8
| Test System | Calibrator Predicate | Proposed New System |
|---|---|---|
| Proprietary | ||
| and | ||
| Established | ||
| Names | SYNCHRON® Systems | |
| MA Calibrator | Urine/CSF Albumin Calibrator | |
| DIFFERENCES | ||
| Calibrator | SYNCHRON® Systems | |
| MA Calibrator | ||
| 475089 | ||
| (1 Level) | Urine/CSF Albumin Calibrator | |
| B38859 | ||
| (5 levels) | ||
| Calibration | ||
| Frequency | Every 30 days | Every 60 days |
9
8.0 Performance Characteristics - Analytical Performance
Precision a.
Within run (repeatability) and total imprecision (within laboratory) studies were designed from CLSI quideline EP05-A2 "Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline - Second Edition". All testing was carried out using an AU5800 analyzer.
Pooled human urine samples were spiked using purified human serum albumin and used for the urine pools. Pooled human CSF samples were either diluted using 0.9% saline or spiked using purified human serum albumin and used for the CSF pools.
The experimental design utilized duplicate sample analysis, twice daily, over the course of 20 working days (n=80) for 3 sample levels. There was a minimum interval of 2 hours between the two runs on each day. The results are presented in the table below:
| Sample
Type | Pool | Mean
mg/dL | Repeatability/
Within-Run | | Within
Laboratory/
Total | |
|----------------|------|---------------|------------------------------|------|--------------------------------|------|
| | | | SD
mg/dL | CV % | SD
mg/dL | CV % |
| CSF | Low | 6.30 | 0.07 | 1.0 | 0.11 | 1.8 |
| CSF | Mid | 26.5 | 0.4 | 1.6 | 0.6 | 2.4 |
| CSF | High | 35.0 | 0.7 | 1.9 | 0.9 | 2.5 |
| Urine | Low | 1.68 | 0.02 | 0.9 | 0.07 | 4.3 |
| Urine | Mid | 3.28 | 0.02 | 0.6 | 0.08 | 2.5 |
| Urine | High | 20.0 | 0.3 | 1.4 | 0.4 | 2.1 |
b. Analytical Range (Linearity)
Analytical range (linearity) studies were designed to meet the requirements of CLSI guidelines EP06-A "Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach: Approved Guideline". All testing was carried out using an AU5800 analyzer.
High and low albumin pools were prepared to achieve albumin concentrations spanning the required linear range. The high pool was prepared by spiking pools with HSA. The high urine and CSF pools were diluted with urine and CSF respectively to generate the lower concentrations required for the 11 point linearity panel.
The studies were performed on 11 linearity concentration levels. Each dilution was assaved in quadruplicate and the mean analytical results were plotted versus the relative analyte concentration.
A polynomial regression analysis was performed on the data and the bias of the polynomial from the 1st order curve was evaluated.
This study demonstrates acceptable linearity for the claimed measuring ranges.
| Sample Type | Measuring Range (mg/dL) |
|---|---|
| Urine | 0.7 - 45 |
| CSF | 1 - 45 |
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C. Traceability and Value Assignment
The Urine/CSF Albumin calibrator values are traceable to the International Federation of Clinical Chemistry Certified Reference Material ERM® - DA470k.
The calibrator was standardized to the reference standard ERM®- DA470k. The assignment was carried out by determining multiple calibration curves using multiple dilutions of DA470k.
The assignment of the master calibrator from the international standard was carried out using an AU2700 analyzer and the values were confirmed and performance tested on an AU640 and AU2700 analyzer.
The assignment of other calibrator lots from the master calibrator was carried out using an AU680 analyzer and the values were confirmed and performance tested on an AU400 and AU680 analyzer.
Reagent and Calibrator Stability d.
Shelf-Life
Accelerated stability testing was carried out following CLSI quideline EP25-A "Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline"; with the aim to establish initial claims of 18 months for both reagent and calibrator. The testing followed the guidelines for a packaging design change to an existing product with established stability claims. All testing was carried out using an AU5800 analyzer. Testing was performed at multiple elevated temperatures using three reagent lots and three calibrator lots and demonstrated that the reagent and calibrator are stable for 18 months at 2 - 8°C.
Reagent On-Board, Calibration Frequency and Calibrator Open Vial Stability
On-Board (OB) stability, calibration frequency, and calibrator open vial stability testing was carried out following CLSI guideline EP25-A "Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline". All testing was carried out using an AU5800 analyzer.
Testing was performed using three reagent lots and three calibration was performed on the first day. At each time point Urine & CSF control material was run in duplicate. The maximum time point exceeded the claim. For the reagent. linearity was assessed after the final time point.
A 60 day reagent on-board claim, a 60-day calibration frequency claim, and a 30-day calibrator open vial stability claim was established.
Sensitivity (Detection Limits) e.
LoB (Limit of Blank), LoD (Limit of Detection) and LoQ (Limit of Quantitation) studies were designed from CLSI guideline EP17-A2 "Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures Approved Guideline - Second Edition". All testing was carried out using an AU5800 analyzer.
Correctly operating AU Systems should exhibit sensitivity less than or equal to 0.7 mg/dL for Urine and less than or equal to 1.0 mg/dL for CSF. LoB was calculated as the upper 95th percent confidence interval of a result from an analyte free sample. Where the calculated LoB is 4 y | 10 - 30 mg/dL |
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- American Diabetes Association. Diabetic Nephropathy. Diabetes Care 25:(Suppl. 1):S85-S89.
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- Painter PC, Cope JY, Smith JL. Reference information for the clinical laboratory. In: Burtis CA, Ashwood ER, eds. Tietz textbook of clinical chemistry, Philadelphia: WB Saunders Company, 1999; 1800pp.
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Urine Application:
CLSI guideline EP28-A3c "Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory; Approved Guideline - Third Edition" was used as a guideline to validate this reference interval using 20 urine samples.
Clinical Studies ﻥ
Not applicable
Clinical Cut-off d.
Not applicable
9.0 Conclusion
The conclusions drawn from the non-clinical testing (discussed above) demonstrate that the Urine/CSF Albumin and Urine/CSF Albumin Calibrator is as safe, as effective, and performs as well as the predicate devices. The submitted information in this pre-market notification is complete and supports a substantial equivalence decision.