(305 days)
Not Found
No
The device description and performance studies focus on a standard immunoassay technology and statistical analysis (Cox proportional hazards regression model) for risk assessment, with no mention of AI or ML.
No.
This device is an in vitro diagnostic (IVD) test used to measure galectin-3 levels in patient samples, which aids in assessing the prognosis of patients with chronic heart failure. It does not directly provide therapy or treatment.
Yes
The device is a quantitative immunoassay used as an aid in assessing the prognosis of patients diagnosed with chronic heart failure, which directly relates to diagnosis and patient management.
No
The device is a reagent kit, calibrators, and controls used with a specific hardware system (ARCHITECT i System) to perform a chemiluminescent immunoassay. It is not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states that the ARCHITECT Galectin-3 assay is for the "quantitative determination of galectin-3 in human serum and EDTA plasma." It also states it "may be used in conjunction with clinical evaluation as an aid in assessing the prognosis of patients diagnosed with chronic heart failure (HF)." This clearly indicates the device is intended to be used in vitro (outside the body) to analyze human biological samples for diagnostic or prognostic purposes.
- Device Description: The description details a "chemiluminescent microparticle immunoassay (CMIA)" which is a laboratory technique used to measure substances in biological fluids. It describes the process of combining the sample with reagents and measuring the resulting reaction, all of which are characteristic of in vitro diagnostic procedures.
- Sample Type: The assay is designed to be used with "human serum and EDTA plasma," which are biological samples collected from patients.
- Clinical Validation: The summary of performance studies describes a clinical validation study using "specimens from a multicenter cohort of outpatients with chronic heart failure (HF)." This further supports the use of the device for analyzing patient samples.
- Predicate Device: The mention of a "Predicate Device" (K093758; BG Medicine, Inc. Galectin-3 Assay) which is also a Galectin-3 assay, strongly suggests that this device is intended for the same regulatory pathway as other IVDs.
Based on these points, the ARCHITECT Galectin-3 assay, along with its calibrators and controls, fits the definition of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
Reagent Kit:
The ARCHITECT Galectin-3 assay is a chemiluminescent microparticle immunoassay (CMIA) for the quantitative determination of galectin-3 in human serum and EDTA plasma.
The ARCHITECT Galectin-3 assay may be used in conjunction with clinical evaluation as an aid in assessing the prognosis of patients diagnosed with chronic heart failure (HF). The ARCHITECT Galectin-3 assay is used with the ARCHITECT i System with STAT protocol capability.
Calibrators:
The ARCHITECT Galectin-3 Calibrators are for the calibration of the ARCHITECT i System when used for the quantitative determination of galectin-3 in human serum and EDTA plasma.
Controls:
The ARCHITECT Galectin-3 Controls are for the verification of the ARCHITECT i System when used for the quantitative determination of galectin-3 in human serum and EDTA plasma.
Product codes (comma separated list FDA assigned to the subject device)
OSX, JIT, JJX
Device Description
The ARCHITECT Galectin-3 assay is a two-step immunoassay for the guantitative determination of galectin-3 in human serum or EDTA plasma using CMIA technology with flexible assay protocols, referred to as Chemiflex.
In the first step, sample and M3/38 anti-galectin-3 coated paramagnetic microparticles are combined. Galectin-3 present in the sample binds to the anti-galecin-3 coated microparticles. After washing, 87B5 anti-galectin-3 acridinium-labeled conjugate is added to create a reaction mixture in the second step. Following another wash cycle, pre-trigger solutions are added to the reaction mixture. The resulting chemiluminescent reaction is measured as relative light units (RLUs).
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
The mean subject age was 58 years.
Intended User / Care Setting
Clinical and Hospital laboratories
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
A study was performed based on guidance from the National Committee for Clinical Laboratory Standards (NCCLS) document EP5-A2. Testing was conducted using one (1) lot of ARCHITECT Galectin-3 Reagents, Calibrators, and Controls, and one (1) ARCHITECT i 2000sg instrument. Three (3) levels of controls and five (5) levels of human serum and plasma panels were assayed with a minimum of two (2) replicates at two (2) separate times per day for twenty (20) different days. A single calibration curve was used throughout the study.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
- Precision Study:
- Sample Size: 3 levels of controls and 5 levels of human serum and plasma panels.
- Key Results: The total precision for one (1) lot individually is ≤ 5.8% for all samples in this study.
- System Reproducibility Study:
- Sample Size: 3 levels of controls and 5 levels of human serum and plasma panels.
- Key Results: The total reproducibility for two (2) lots is ≤ 4.7% for all samples in this study.
- Linearity/Assay Reportable Range Study:
- Sample Size: Two (2) serum samples (one low and one high for galectin-3 levels) and two (2) plasma samples (one low and one high for galectin-3 levels).
- Key Results: Supports a linear range of 5.5 to 103.1 ng/mL for the ARCHITECT Galectin-3 assay based on a +/-10% deviation from linearity (%DL).
- Detection Limit Study:
- Sample Size: 7 normal human serum samples, 2 lots of ARCHITECT Galectin-3 Calibrator A, and Low Level Panel Set. (N= 5x2x3x2x2 = 120 total replicates)
- Key Results: Limit of Blank (LoB) of 1.0 ng/mL, Limit of Detection (LoD) of 1.1 ng/mL, and Limit of Quantitation (LoQ) of 2.8 ng/mL. The LoQ met the predetermined acceptance criteria of LoD ≤ 4.0 ng/mL.
- Analytical Specificity (Cross-Reactivity with Proteins) Study:
- Sample Size: Four (4) serum and four (4) patient plasma samples.
- Key Results: All individual patient samples supplemented with the various human recombinant galectin and collagen proteins resulted in a percent cross reactivity with the ARCHITECT Galectin-3 assay of ≤ 0.3% (below 0.5%).
- Analytical Specificity (Interfering Drugs) Study:
- Study Type: Evaluation of potentially interfering drugs as per CLSI document EP07-A2.
- Sample Size: Serum and plasma samples with galectin-3 values within or near target ranges (10-13 ng/mL and ≈26 ng/mL).
- Key Results: Percent difference from -2.9% to 4.0% for various therapeutic agents.
- Analytical Specificity (Interfering Substances) Study:
- Study Type: Evaluation of potentially interfering substances as per CLSI document EP07-A2.
- Sample Size: Serum and plasma samples with galectin-3 values within or near target ranges (10-13 ng/mL and ≈26 ng/mL).
- Key Results: Mean % Difference from -4.7% to 4.7% for various endogenous substances.
- Clinical Validation Study:
- Study Type: Clinical validation study of the ARCHITECT Galectin-3 assay.
- sample size: 405 serum specimens.
- Key Results:
- multivariable Cox proportional hazards regression model demonstrated a statistically significant higher risk for the occurrence of the primary endpoint (hospitalization due to worsening HF, ventricular assist device placement, cardiac transplantation, or all-cause mortality) in subjects with galectin-3 levels in the high risk category (> 17.8 nq/mL), compared with galectin-3 levels in the low risk category ( 17.8 ng/mL), adjusted for baseline risk factors.
- Elevated baseline levels of galectin-3 (>17.8 ng/mL) in chronic HF patients were shown to be significantly and independently associated with a higher risk of the primary endpoint.
- Cumulative probability of event for primary endpoint at 36 months: ≤ 17.8 ng/mL: 43.4% (33.3 - 53.6); > 17.8 ng/mL: 64.4% (56.4 - 72.4).
- Event rates by joint Galectin-3 and NT-proBNP Category:
- Galectin-3 ≤ 17.8 ng/mL and NT-proBNP ≤ median (N=99): 24.2% event rate, Hazard Ratio: 1 (referent category).
- Galectin-3 ≤ 17.8 ng/mL and NT-proBNP > median (N=64): 48.4% event rate, Hazard Ratio: 2.077 (1.216-3.549), p-value: 0.0075.
- Galectin-3 > 17.8 ng/mL and NT-proBNP ≤ median (N=83): 48.2% event rate, Hazard Ratio: 1.835 (1.104-3.050), p-value: 0.0191.
- Galectin-3 > 17.8 ng/mL and NT-proBNP > median (N=115): 66.1% event rate, Hazard Ratio: 4.014 (2.533-6.362), p-value:
§ 862.1117 B-type natriuretic peptide test system.
(a)
Identification. The B-type natriuretic peptide (BNP) test system is an in vitro diagnostic device intended to measure BNP in whole blood and plasma. Measurements of BNP are used as an aid in the diagnosis of patients with congestive heart failure.(b)
Classification. Class II (special controls). The special control is “Class II Special Control Guidance Document for B-Type Natriuretic Peptide Premarket Notifications; Final Guidance for Industry and FDA Reviewers.”
0
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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
FUJIREBIO DIAGNOSTICS, INC. STACEY DOLAN MANAGER, REGULATORY AFFAIRS 201 GREAT VALLEY PKWY. MALVERN PA 19355-1307
December 23,2014
Re: K140436
Trade/Device Name: ARCHITECT Galectin-3 Reagent Kit ARCHITECT Galectin-3 Calibrators ARCHITECT Galectin-3 Controls Regulation Number: 21 CFR 862.1117 Regulation Name: B-type natriuretic peptide test system Regulatory Class: II Product Code: OSX, JIT, JJX Dated: November 12, 2014 Received: November 13, 2014
Dear Ms. Stacey Dolan:
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
1
electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Katherine Serrano -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
510(k) Number (if known) K140436
Device Name ARCHITECT Galectin-3
Indications for Use (Describe) Reagent Kit:
The ARCHITECT Galectin-3 assay is a chemiluminescent microparticle immunoassay (CMIA) for the quantitative determination of galectin-3 in human serum and EDTA plasma.
The ARCHITECT Galectin-3 assay may be used in conjunction with clinical evaluation as an aid in assessing the prognosis of patients diagnosed with chronic heart failure (HF). The ARCHITECT Galectin-3 assay is used with the ARCHITECT i System with STAT protocol capability.
Calibrators:
The ARCHITECT Galectin-3 Calibrators are for the calibration of the ARCHITECT i System when used for the quantitative determination of galectin-3 in human serum and EDTA plasma.
Controls:
The ARCHITECT Galectin-3 Controls are for the verification of the ARCHITECT i System when used for the quantitative determination of galectin-3 in human serum and EDTA plasma.
| Type of Use (Select one or both, as applicable) |
|---|
| Prescription Use (Part 21 CFR 801 Subpart D) Over-The-Counter Use (21 CFR 801 Subpart C) |
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Section 5 510(k) SUMMARY
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR 807.92.
A. 510(k) Number:
B. Purpose for Submission:
New device
C. Measurand:
Galectin-3
D. Type of Test:
Quantitative, Automated chemiluminescence immunoassay on the ARCHITECT i Systems
E. Applicant:
Address:
| Fujirebio Diagnostics, Inc. |
|---|
| 201 Great Valley Parkway |
| Malvern, PA 19355 |
| Contact person: | Stacey Dolan
(610) 240-3843
dolans@fdi.com |
| ----------------- | -------------------------------------------------- |
|---|
Summary preparation date: November 12, 2014
F. Proprietary and Established Names:
ARCHITECT Galectin-3 Reagent Kit ARCHITECT Galectin-3 Calibrators ARCHITECT Galectin-3 Controls
G. Regulatory Information:
-
- Regulation section: 21 CFR § 862.1117, Test, Natriuretic Peptide 21 CFR § 862.1150, Calibrator 21 CFR § 862.1660, Quality Control Material (Assayed and Unassayed)
-
- Classification: Class II
-
- Product code: OSX, Galectin-3 In Vitro Diagnostic Assay
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Image /page/4/Picture/1 description: The image shows the logo for Fujirebio Diagnostics, Inc. The logo consists of a blue and white abstract shape on the left, followed by the company name in blue and black text. The word "FUJIREBIO" is in a larger, bolder font than "Diagnostics, Inc."
JIT, Calibrator, Secondary JJX, Single (Specified) Analyte Controls (Assayed and Unassayed)
-
- Panel: 75, Chemistry
H. Intended Use:
-
- Intended use(s): See indications for use below.
-
- Indication(s) for use:
Reagent Kit
The ARCHITECT Galectin-3 assay is a chemiluminescent microparticle immunoassay (CMIA) for the quantitative determination of galectin-3 in human serum and EDTA plasma. The ARCHITECT Galectin-3 assay may be used in conjunction with clinical evaluation as an aid in assessing the prognosis of patients diagnosed with chronic heart failure (HF). The ARCHITECT Galectin-3 assay is used with the ARCHITECT i System with STAT protocol capability.
Calibrators
The ARCHITECT Galectin-3 Calibrators are for the calibration of the ARCHITECT i System when used for the quantitative determination of galectin-3 antigen in human serum and EDTA plasma.
Controls
The ARCHITECT Galectin-3 Controls are for the verification of the accuracy and precision of the ARCHITECT i System when used for the quantitative determination of galectin-3 in human serum and EDTA plasma.
-
- Special conditions for use statement(s): Prescription use only
-
- Special instrument requirements: Abbott ARCHITECT i 2000 SR System analyzers in STAT mode
-Device Description:
The ARCHITECT Galectin-3 assay is a two-step immunoassay for the guantitative determination of galectin-3 in human serum or EDTA plasma using CMIA technology with flexible assay protocols, referred to as Chemiflex.
In the first step, sample and M3/38 anti-galectin-3 coated paramagnetic microparticles are combined. Galectin-3 present in the sample binds to the anti-galecin-3 coated microparticles. After washing, 87B5 anti-galectin-3 acridinium-labeled conjugate is added to create a reaction mixture in the second step. Following another wash cycle, pre-trigger solutions are added to the reaction mixture. The resulting chemiluminescent reaction is measured as relative light units (RLUs).
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Image /page/5/Picture/1 description: The image shows the logo for Fujirebio Diagnostics, Inc. The logo consists of a stylized graphic on the left and the company name on the right. The graphic is a blue and white abstract shape, and the company name is written in blue and black text. The word "FUJIREBIO" is in blue, and the words "Diagnostics, Inc." are in black.
A direct relationship exists between the amount of galectin-3 in the sample and the RLUs detected by the ARCHITECT i System optics. The kit is composed of the following:
ARCHITECT Galectin-3 Reagent Kit (5P03)
The ARCHITECT Galectin-3 Reagent Kit consists of 100 (1 x 100) tests. Each kit contains paramagnetic microparticles coated with the anti-galectin-3 Rat monoclonal antibody M3/38, and an acridinium-labeled anti-galectin-3 mouse monoclonal antibody 87B5 conjugate. Reagents can be stored on-board the ARCHITECT i System in accordance with assay-specific instructions.
MICROPARTICLES| 1 Bottle (6.6 mL) Anti-galectin-3 (rat, monoclonal) coated microparticles in PBS buffer with protein (bovine) stabilizers. Minimum concentration: 0.08% solids. Preservative: ProClin 300.
CONJUGATE 1 Bottle (5.9 mL) Anti-galectin-3 (mouse, monoclonal) acridinium-labeled conjugate in PBS buffer with protein (bovine) stabilizers. Minimum concentration: 800 ng/mL. Preservative: ProClin 300.
ARCHITECT Galectin-3 Calibrators (5P03-01)
The ARCHITECT Galectin-3 Calibrators are used for the calibration of the ARCHITECT i System. Each calibrator kit contains one bottle each of Calibrators A, B, C, D, E, and F. The calibrator kit is packaged separately.
CALIBRATORS 6 Bottles (4.0 mL each) of ARCHITECT Galectin-3 Calibrators. Calibrators A through F are prepared with artificial matrix. Calibrators B through F contain recombinant human galectin-3. Preservatives: EDTA and ProClin 950.
| Calibrator | Concentration
(ng/mL) |
|------------|--------------------------|
| CAL A | 0.0 |
| CAL B | 5.7 |
| CAL C | 11.4 |
| CAL D | 22.8 |
| CAL E | 68.4 |
| CAL F | 114.0 |
The calibrators are at the following concentrations:
ARCHITECT Galectin-3 Controls (5P03-10)
The ARCHITECT Galectin-3 Controls are used for the verification of the accuracy and precision of the ARCHITECT i System. Each control kit contains one bottle each of low, medium, and high control. The control kit is packaged separately.
CONTROLS 3 Bottles (8.0 mL each) of ARCHITECT Galectin-3 Controls. The Low, Medium, and High Controls are prepared with artificial matrix and contain recombinant human galectin-3. Preservatives: EDTA and ProClin 950.
6
The calibrators are at the following concentrations:
| Control | Concentration
Target
(ng/mL) | Concentration
Range
(ng/mL) |
|----------------|------------------------------------|-----------------------------------|
| Low Control | 9.1 | 6.4 - 11.8 |
| Medium Control | 20.5 | 14.4 - 26.7 |
| High Control | 74.1 | 51.9 - 96.3 |
Other Materials/Equipment Required (not Provided):
- MULTI-ASSAY MANUAL DILUENT 1 Bottle (100 mL) ARCHITECT i Multi-Assay Manual O Diluent containing phosphate buffered saline solution. Preservative: antimicrobial agent.
- PRE-TRIGGER SOLUTION Pre-Trigger Solution containing 1.32 % (w/v) hydrogen O peroxide.
- TRIGGER SOLUTION Trigger Solution containing 0.35N sodium hydroxide. O
- WASH BUFFER| Wash Buffer containing phosphate buffered saline solution. Preservative: O Antimicrobial Agents.
- ARCHITECT i2000SR System in STAT mode O
- ARCHITECT i System |ASSAY CD-ROM US Addition A (3K50) O
- ARCHITECT i System e-Assay CD-ROM at www.abbottdiagnostics.com O
- ARCHITECT i REACTION VESSELS O
- ARCHITECT i SAMPLE CUPS o
- ARCHITECT iSEPTUM O
- ARCHITECT / REPLACEMENT CAPS O
- Pipettes / Pipette Tips o
J. Substantial Equivalence Information:
-
- Predicate device name(s): BG Medicine, Inc. Galectin-3 Assay
-
- Predicate 510(k) number(s): K093758
-
- Comparison with predicate:
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Image /page/7/Picture/1 description: The image contains the logo for Fujirebio Diagnostics, Inc. The logo features a stylized blue and green graphic to the left of the company name. The company name is written in blue, with "Diagnostics, Inc." written in a smaller font size below the main name.
| Similarities | ||
|---|---|---|
| ARCHITECT Galectin-3 | ||
| (Proposed Device) | BG Medicine Galectin-3 Assay | |
| (Predicate Device) | ||
| K093758 | ||
| Device Type | In vitro diagnostic | In vitro diagnostic |
| Classification | Class II | Class II |
| CFR section | 862.117 | 862.117 |
| Product Code | OSX | OSX |
| Product Usage | Clinical and Hospital laboratories | Clinical and Hospital laboratories |
| Intended Use | Quantitative determination of | |
| galectin-3 in human serum and | ||
| EDTA plasma. | ||
| ARCHITECT Galectin-3 assay | ||
| may be used in conjunction with | ||
| clinical evaluation as an aid in | ||
| assessing the prognosis of | ||
| patients diagnosed with chronic | ||
| heart failure (HF). | Quantitatively measures galectin-3 | |
| in serum or EDTA plasma by | ||
| enzyme-linked immunosorbent | ||
| assay (ELISA) on a microtiter plate | ||
| platform, to be used in conjunction | ||
| with clinical evaluation as an aid in | ||
| assessing the prognosis of | ||
| patients diagnosed with chronic | ||
| heart failure (HF). | ||
| Assay Range | 5.5 — 103.1 ng/mL | 1.4 – 94.8 ng/mL |
| Type of Specimen | Human Serum or EDTA plasma | Human Serum or EDTA plasma |
| Specimen Collection | ||
| Method | Routine Phlebotomy Techniques | Routine Phlebotomy Techniques |
| Capture Antibody | Mouse monoclonal (M3/38) | Mouse monoclonal (M3/38) |
| Detection Antibody | Mouse monoclonal (87B5) | Mouse monoclonal (87B5) |
| Analyte | Human galectin-3 | Human galectin-3 |
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Image /page/8/Picture/1 description: The image shows the logo for Fujirebio Diagnostics, Inc. The logo consists of a stylized blue and white graphic on the left, followed by the company name in blue and black text. The word "FUJIREBIO" is in a larger, bolder font than "Diagnostics, Inc."
| Differences | ||
|---|---|---|
| ARCHITECT Galectin-3 | ||
| (Proposed Device) | BG Medicine Galectin- 3 Assay | |
| (Predicate Device) | ||
| K093758 | ||
| Instrument System | ARCHITECT i System | None |
| Principle of Operation | Chemiluminscent Microparticle | |
| Immunoassay (CMIA) | Manual Enzyme Linked | |
| Immunosorbent Assay (ELISA) | ||
| Calibrators | 6 Levels (0.0 - 114.0 ng/mL) | |
| Ready to Use | ||
| -Liquid | ||
| -Supplied as separate kit | 1 Level (12 ng/vial) Serial diluted | |
| prior to use | ||
| -Lyophilized | ||
| -Supplied with Kit | ||
| Controls | -3 Levels (9.1, 20.5, and 74.1 | |
| ng/mL) | ||
| -Liquid | ||
| -Supplied as separate kit | -2 Levels (18.4 and 69 ng/mL) | |
| -Lyophilized | ||
| -Supplied with Kit | ||
| Interpretation of Results | Calibrator Curve | Standard Curve |
| Cut-off | galectin-3 risk categories: | |
| • galectin-3 greater than 17.8 | ||
| ng/mL | ||
| •galectin-3 less than or equal to | ||
| 17.8 ng/mL | galectin-3 risk categories: | |
| • galectin-3 greater than 25.9 | ||
| ng/mL | ||
| • galectin-3 between 17.8 and 25.9 | ||
| ng/mL | ||
| •galectin-3 less than or equal to | ||
| 17.8 ng/mL |
K. Standard/Guidance Document Referenced (if applicable):
- . CLSI C28-A3c: Defining, Establishing and Verifying Reference Intervals in the Clinical Laboratory; Approved Guideline
- . CLSI EP6-A: Evaluation of Linearity of Quantitative Measurement Procedures, A Statistical Approach: Approved Guideline
- . CLSI EP07-A2: Interference Testing in Clinical Chemistry; Approved Guideline
- CLSI EP14-A2: Evaluation of Matrix Effects: Approved Guideline ●
- CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline
- . CLSI EP05-A2: Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline
- CEN13640: Stability Testing of In Vitro Diagnostic Reagents ●
- . Guidance on Informed Consent for In Vitro Diagnostic Device Studies Using Leftover Human Specimens that are Not Individually Identifiable - Guidance for Sponsors, Institutional Review Boards, Clinical Investigators and FDA Staff
- . Class II Special Control Guidance Document for B-Type Natriuretic Peptide Premarket Notifications; Final Guidance for Industry and FDA Reviewers. Document issued on: November 30, 2000
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Image /page/9/Picture/1 description: The image is a logo for Fujirebio Diagnostics, Inc. The logo features a stylized blue and green graphic to the left of the company name. The company name is in blue, with the word "FUJIREBIO" in a larger font than "Diagnostics, Inc." There is a registered trademark symbol next to the word "FUJIREBIO".
L. Test Principle
The ARCHITECT Galectin-3 assay is a two-step immunoassay for the guantitative determination of galectin-3 in human serum or EDTA plasma using CMIA technology with flexible assay protocols, referred to as Chemiflex. In the first step, sample and M3/38 antigalectin-3 coated paramagnetic microparticles are combined. Galectin-3 present in the sample binds to the anti-galecin-3 coated microparticles. After washing, 87B5 anti-galectin-3 acridinium-labeled conjugate is added to create a reaction mixture in the second step. Following another wash cycle, pre-trigger and trigger solutions are added to the reaction mixture. The resulting chemiluminescent reaction is measured as relative light units (RLUs). A direct relationship exists between the amount of galectin-3 in the RLUs detected by the ARCHITECT i System optics.
The ARCHITECT Galectin-3 Calibrators are for the ARCHITECT i System when used for the quantitative determination of galectin-3 antigen in human serum and EDTA plasma.
The ARCHITECT Galectin-3 Controls are for the verification of the accuracy and precision of the ARCHITECT i System when used for the quantitative determination of galectin-3 in human serum and EDTA plasma.
M. Performance Characteristics (if/when applicable):
Data were generated using the ARCHITECT i 2000SR System with the STAT protocol.
-
- Analytical performance:
- a. Precision/Reproducibility:
Precision
The ARCHITECT Galectin-3 assay is designed to have an imprecision of ≤ 10% Total CV for samples with galectin-3 concentrations ranging from 4.0 to 114.0 ng/mL.
A study was performed based on guidance from the National Committee for Clinical Laboratory Standards (NCCLS) document EP5-A2. Testing was conducted using one (1) lot of ARCHITECT Galectin-3 Reagents, Calibrators, and Controls, and one (1) ARCHITECT i 2000sg instrument. Three (3) levels of controls and five (5) levels of human serum and plasma panels were assayed with a minimum of two (2) replicates at two (2) separate times per day for twenty (20) different days. A single calibration curve was used throughout the study.
The precision analyses determined that the total precision for one (1) lot individually is ≤ 5.8% for all samples in this study.
System Reproducibility
A study was performed based on guidance from the NCCLS document EP5-A2. Testing was conducted using two (2) lots of ARCHITECT Galectin-3 Reagents, Calibrators, and Controls on
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two (2) different ARCHITECT i 2000SR instruments. Each reagent lot was matched with a different lot of calibrators and controls. Three (3) levels of controls and five (5) levels of human serum and plasma panels were assaved with a minimum of two (2) replicates at two (2) separate times per day for ten (10) different days for a total of forty (40) replicates for each lot. Each reagent lot used a single calibration curve throughout the study.
The precision analyses determined that the total reproducibility for two (2) lots is ≤ 4.7% for all samples in this study.
- b. Linearity/assay reportable range:
A study was performed based on guidance from the CLSI document EP6-A. Two (2) serum samples (one low and one high for galectin-3 levels) and two (2) plasma samples (one low and one high for galectin-3 levels) were used for this study.
The high serum and high plasma samples were diluted with their respective low sample. The neat and diluted panels were tested in replicates of three (3) using the ARCHITECT Galectin-3 assay on the ARCHITECT i2000SR System in STAT mode.
Based on a +/-10% deviation from linearity (%DL), the data supports a linear range of 5.5 to 103.1 ng/mL for the ARCHITECT Galectin-3 assay.
- c. Traceability, Stability, Expected values (controls, calibrators, or methods):
The ARCHITECT Galectin-3 Calibrators are for the ARCHITECT i System when used for the quantitative determination of galectin-3 antigen in human serum and EDTA plasma. 6 Bottles (4.0 mL each) are supplied for the ARCHITECT Galectin-3 Calibrators. Calibrators A through F are prepared with artificial matrix. Calibrators B through F contain recombinant human galectin-3. Preservatives: EDTA and ProClin 950. The calibrators are at the following concentrations:
| Calibrator | Concentration
(ng/mL) |
|------------|--------------------------|
| CAL A | 0.0 |
| CAL B | 5.7 |
| CAL C | 11.4 |
| CAL D | 22.8 |
| CAL E | 68.4 |
| CAL F | 114.0 |
There is currently no known internationally recognized consensus reference method or reference material for standardization. Galectin-3 assay values are expressed as ng/mL. This value is related to a Fujirebio Diagnostics maintained reference preparation. The primary calibrators for the ARCHITECT Galectin-3 assay were manufactured gravimetrically and produced based on protein content.
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The stability data supports the current shelf life assignment for the ARCHITECT Galectin-3 Calibrators of 12 months.
The ARCHITECT Galectin-3 Controls are for the verification of the accuracy and precision of the ARCHITECT i System when used for the quantitative determination of galectin-3 in human serum and EDTA plasma. 3 Bottles (8.0 mL each) are supplied for the ARCHITECT Galectin-3 Controls. The Low, Medium, and High Controls are prepared with artificial matrix and contain recombinant human galectin-3. Preservatives: EDTA and ProClin 950. The controls are at the following concentrations:
| Control | Concentration
Target
(ng/mL) | Concentration
Range
(ng/mL) |
|----------------|------------------------------------|-----------------------------------|
| Low Control | 9.1 | 6.4 - 11.8 |
| Medium Control | 20.5 | 14.4 - 26.7 |
| High Control | 74.1 | 51.9 - 96.3 |
The stability data supports the current shelf life assignment for the ARCHITECT Galectin-3 Controls of 12 months.
- d. Detection limit:
The ARCHITECT Galectin-3 assay is designed to have a Limit of Quantitation (LoQ) of ≤ 4.0 ng/mL. Based on guidance from the CLSI document EP17-A2, a study was performed by diluting 7 normal human serum samples in ARCHITECT Galectin-3 Calibrator A. Two (2) lots of ARCHITECT Galectin-3 Calibrator A (run as the zero-level panel) and Low Level Panel Set were run in replicates of five (5), twice per day over three (3) days on two (2) ARCHITECT I2000SR Systems in STAT mode with two (2) ARCHITECT Galectin-3 assay reagent lots (N= 5x2x3x2x2 = 120).
The Limit of Blank (LoB). Limit of Detection (LoD). and Limit of Quantitation (LoQ) determined for the ARCHITECT Galectin-3 assay was 1.0 ng/mL. 1.1 ng/mL. and 2.8 ng/mL respectively.
The LoQ met the predetermined acceptance criteria of LoD ≤ 4.0 ng/mL. These data support the performance claims of the assay.
- e. Analytical specificity:
A study was conducted to evaluate the potential interference from other recombinant human galectin and collagen proteins in the ARCHITECT Galectin-3 assay.
Four (4) serum and four (4) patient plasma samples were used for this study. Three (3) serum samples and two (2) plasma samples were augmented with human galectin-3 antigen targeting a 'normal' concentration of galectin-3 (10-13 ng/mL) and an elevated concentration of galectin-3 (=26 ng/mL). The other 3 samples (One (1) serum and two (2) plasma) were at the target concentrations and did not require augmentation. The eight (8) samples were supplemented with the various cross reactants each prepared at a concentration of 10 µg/mL in PBS.
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The prepared samples were tested in replicates of three (3) using the ARCHITECT Galectin-3 assay on the ARCHITECT i2000SR System in STAT mode.
All individual patient samplemented with the various human recombinant galectin and collagen proteins resulted in a percent cross reactivity with the ARCHITECT Galectin-3 assay of ≤ 0.3% and support the performance claims of the assay (below 0.5%).
A study was performed based on guidance from the CLSI document EP07-A2. Potentially interfering drugs were evaluated to determine whether galectin-3 concentrations were affected when using the ARCHITECT Galectin-3 assay.
Serum and plasma samples selected based on their endogenous galectin-3 values which fell within or near the galectin-3 target ranges were used in this study. The predetermined galectin-3 targets were a 'normal' concentration of galectin-3 (10-13 ng/mL) and an elevated concentration near the upper end of the reference range for galectin-3 (≈26 ng/mL).
Each qalectin-3 sample pool was split into 2 equal aliquots for each therapeutic tested. One aliquot was spiked with the therapeutic agent stock for use as the test sample. The samples were not diluted more than 5% by the agent. The other aliquot (control) was spiked with an equal volume of the same solvent used for therapeutic agent preparation for each respective therapeutic agent.
The data are summarized in the following table.
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| Therapeutic | Therapeutic
Concentration | Percent
Difference (%) |
|-----------------------------------|------------------------------|---------------------------|
| Acetaminophen (4-Acetamidophenol) | 1324 µmol/L | -2.9% |
| Acetylsalicylic Acid | 3.62 mmol/L | -0.7% |
| Amlodipine besylate | 10.6 µmol/L | -0.1% |
| Ampicillin | 152 µmol/L | -0.1% |
| L-Ascorbic Acid | 342 µmol/L | 1.9% |
| Atenolol | 37.6 µmol/L | -0.4% |
| Caffeine | 308 µmol/L | 0.7% |
| Carvedilol | 74 µmol/L | 2.4% |
| Captopril | 23 µmol/L | -1.9% |
| Chloramphenicol | 155 µmol/L | 1.1% |
| Diclofenac sodium salt | 169 µmol/L | -0.7% |
| Digoxin | 7.8 nmol/L | 0.8% |
| (+)-cis-Diltiazem hydrochloride | 576.5 µmol/L | -0.5% |
| Disopyramide | 29.5 µmol/L | -2.5% |
| Dopamine hydrochloride | 5.87 µmol/L | 4.0% |
| Enalaprilat dihydrate | 0.86 µmol/L | 1.6% |
| Furosemide | 181 µmol/L | 1.0% |
| Hydrochlorothiazide | 20.2 µmol/L | 0.0% |
| Ibuprofen | 2425 µmol/L | -0.6% |
| Indomethacin | 100 µmol/L | -1.7% |
| Lidocaine | 51.2 µmol/L | 0.1% |
| Lisinopril • 2H2O | 0.74 µmol/L | -0.9% |
| Losartan potassium | 130 µmol/L | -1.1% |
| Lovastatin (Simvastatin) | 191 µmol/L | 1.7% |
| Methyldopa | 71 µmol/L | -2.3% |
| (±)-Metoprolol (+)-tartrate salt | 18.7 µmol/L | -2.8% |
| Naproxen | 2170 µmol/L | -1.0% |
| Nifedipine | 1156 nmol/L | 0.4% |
| Quinidine | 37 µmol/L | -0.7% |
| Ramipril | 14.4 µmol/L | 0.0% |
| Spironolactone | 1.44 µmol/L | -2.0% |
| Theophylline | 222 µmol/L | -2.9% |
| Verapamil hydrochloride | 244 µmol/L | 0.6% |
| Warfarin | 32.5 µmol/L | -2.1% |
| Trasylol/Aprotinin | 100 KIE/mL | 0.0% |
A study was performed based on guidance from the Clinical and Laboratory Standards Institute (CLSI) document EP07-A2. Potentially interfering substances were evaluated to determine whether galectin-3 concentrations were affected when using the ARCHITECT Galectin-3 assay.
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Serum and plasma samples selected based on their endogenous galectin-3 values which fell within or near the galectin-3 target ranges were used in this study. The predetermined galectin-3 targets were a 'normal' concentration of galectin-3 (10-13 ng/mL) and an elevated concentration near the upper end of the reference range for galectin-3 (≈26 ng/mL).
Each galectin-3 sample was split into two (2) aliquots for each endogenous substance tested. One (1) aliquot was spiked with an endogenous substance for use as the test sample. One (1) aliquot was spiked with an equal volume of ARCHITECT PBS (phosphate-buffered solution) for use as a control samples were not diluted more than 20% by the agent.
The data are summarized in the following table.
| Potentially Interfering
Substance | Interferent
Concentration | Mean %
Difference |
|--------------------------------------|------------------------------|----------------------|
| Bilirubin (Unconjugated) | ≥ 40 mg/dL | -3.8 |
| Bilirubin (Conjugated) | ≥ 40 mg/dL | 0.7 |
| Hemoglobin | ≥ 250 mg/dL | 4.6 |
| Triglycerides | ≥ 3000 mg/dL | 4.4 |
| Human Serum Albumin | ≥ 12 g/dL | -4.7 |
| Human Gamma Globulin | ≥ 5 g/dL | -3.2 |
| Cholesterol | ≥ 500 mg/dL | 3.7 |
| Whole Blood Lysate b | 5 mg/dL | 4.7 |
| Creatinine | ≥ 5 mg/dL | 0.5 |
| Rheumatoid Factor | 800 IU/mL | 3.5 |
| Human Anti-Mouse
Antibodies | ≥1000 ng/mL | 1.1 |
-
f. Assay cut-off:
See Clinical Cutoff in M (4) below -
- Comparison studies: N/A
-
- Clinical studies:
- a. Clinical sensitivity:
See 3(c) below
- b. Clinical specificity:
See 3(c) below
- Other clinical supportive data (when a. and b. are not applicable): C.
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The clinical performance of the ARCHITECT Galectin-3 assay was evaluated in a clinical validation study with specimens from a multicenter cohort of outpatients with chronic heart failure (HF). A total of 405 serum specimens were obtained at time of study entry from patients with varying degrees of chronic HF, encompassing all New York Heart Association (NYHA) classification categories. The median follow-up time for the study population was approximately 652 days.
Of the 405 baseline samples, 143 (35.3%) were obtained from females and 262 (64.7%) were obtained from males. The mean subject age was 58 years. The specimens were tested using the ARCHITECT Galectin-3 assay and categorized based on galectin-3 value as high risk (>17.8ng/mL) or low risk (≤17.8 ng/mL). A total of 226 subjects were in the high risk category and the remaining 179 subjects were in the low risk category. A multivariable Cox proportional hazards regression model was used to evaluate the association of qalectin-3 category with the primary endpoint of hospitalization due to worsening HF, ventricular assist device placement, cardiac transplantation, or all-cause mortality.
The multivariable Cox proportional hazards regression model was adjusted for the parameters of age, gender, NYHA class, left ventricular ejection fraction (LVEF), diabetes status, and smoking status. The results of the regression model demonstrated a statistically significant higher risk for the occurrence of the primary endpoint in subjects with galectin-3 levels in the high risk category (> 17.8 nq/mL), compared with galectin-3 levels in the low risk category ( 17.8 ng/mL) | 1.753 (1.265 – 2.427) |
adjusted for baseline risk factors: age, gender, NYHA functional classification, left ventricular ejection fraction, diabetes status, and smoking status.
6 Hazard ratio is relative to the galectin-3 low risk category (≤ 17.8 ng/mL)
Elevated baseline levels of galectin-3 (>17.8 ng/mL) in chronic HF patients were shown to be significantly and independently associated with a higher risk of hospitalization due to worsening HF, ventricular assist device placement, cardiac transplantation, or all-cause mortality (first to occur).
The figure below presents the Kaplan-Meier Survival Function Estimates time-to-event (hospitalization due to worsening HF, ventricular assist device placement, cardiac transplantation, or all-cause mortality) based on the galectin-3 cutoff value of 17,8 ng/ml., where the probability of survival is plotted with the elapsed time in days from baseline (i.e., follow-up time).
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Additional Information (AI) Request Premarket Notification (510(k)) ARCHITECT Galectin-3
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Image /page/16/Figure/2 description: This image is a survival probability graph that compares two groups: Galectin less than or equal to 17.8 ng/mL and Galectin greater than 17.8 ng/mL. The x-axis represents follow-up time in days, ranging from 0 to 1500. The y-axis represents survival probability, ranging from 0.0 to 1.0. The graph shows that the group with Galectin less than or equal to 17.8 ng/mL has a higher survival probability than the group with Galectin greater than 17.8 ng/mL.
Follow-up time (days)
The bar graph and table below depict the cumulative probability of the primary endpoint (hospitalization due to worsening HF, ventricular assist device placement, cardiac transplantation, or all-cause mortality) by galectin-3 category, at selected time points.
Image /page/16/Figure/5 description: The image is a bar graph that shows the cumulative probability of an event over time, broken down by two groups: those with 17.8 ng/mL. The x-axis represents time in months (6, 12, 24, and 36 months), and the y-axis represents the cumulative probability of the event. At 36 months, the cumulative probability of the event is 43.4% for the 17.8 ng/mL group.
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| | Cumulative Probability (95% Confidence
Interval) of Event for Primary Endpoint, by
Galectin-3 Category, at Selected Time
Points (in percent) | | | |
|------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------|--------------------------|--------------------------|
| Galectin-3
Category | 6
Months | 12
Months | 24
Months | 36
Months |
| ≤ 17.8 ng/mL | 11.7
(7.0 -
16.4) | 15.7
(10.4 -
21.0) | 23.4
(16.9 -
29.9) | 43.4
(33.3 -
53.6) |
| > 17.8 ng/mL | 21.2
(15.9 -
26.6) | 33.9
(27.7 -
40.1) | 43.2
(36.5 -
49.9) | 64.4
(56.4 -
72.4) |
Interpretation
ARCHITECT Galectin-3 assay results should be interpreted in conjunction with clinical evaluation as an aid in assessing the prognosis of patients diagnosed with chronic heart failure. In the clinical validation study, chronic heart failure patients with qalectin-3 levels over 17.8 ng/mL were found to have a higher risk of adverse outcomes, defined as hospitalization for HF, placement of left ventricular assist device, cardiac transplantation and mortality, when compared to patients with levels below 17.8 ng/mL.
Interpretation Relative to Natriuretic Peptides
Galectin-3 and natriuretic peptides, such as NT-proBNP and BNP, are measures of separate and distinct biological processes. Galectin-3 and natriuretic peptides provide independent and complementary information on the prognosis of patients with chronic heart failure.
Elevated baseline levels of both galectin-3 and a natriuretic peptide have been associated with poorer prognosis in chronic heart failure patients, when compared to patients with low baseline levels of both markers. Elevated levels of one or the other marker, but not both, have been associated with a poorer prognosis in chronic heart failure when compared to patients with low levels of both markers, and with a better prognosis when compared to patients with elevated baseline levels of both markers.
The table below illustrates this for N-terminal pro B-type natriuretic peptide (NT-proBNP) in the clinical validation study by evaluating primary endpoint event rates by categories of galectin-3 and NT-proBNP levels.
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Event Rates by Joint Galectin-3 and NT-proBNP Category. Median NT-proBNP value in study is 1222 pg/mL.
| | Subjects In Each Category Experiencing a Hospitalization
for Heart Failure, Ventricular Assist Device Placement,
Cardiac Transplantation, or Death | | |
|-----------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------|---------|
| | Within Overall
Study | Hazard Ratio
(95% Confidence
Interval) | P-value |
| Galectin-3 ≤ 17.8 ng/mL and
NT-proBNP
≤ median
(N=99) | 24.2% | 1
(referent category) | NA |
| Galectin-3 ≤ 17.8 ng/mL and
NT-proBNP
median
(N=64) | 48.4% | 2.077
(1.216-3.549) | 0.0075 |
| Galectin-3 > 17.8 ng/mL and
NT-proBNP
≤ median
(N=83) | 48.2% | 1.835
(1.104-3.050) | 0.0191 |
| Galectin-3 > 17.8 ng/mL and
NT-proBNP
median
(N=115) | 66.1% | 4.014
(2.533-6.362) |