(345 days)
No
The device is a standard ELISA assay for measuring a biomarker. There is no mention of AI/ML in the device description, intended use, or performance studies. The analysis of results is based on a calibration curve, not an AI/ML algorithm.
No
This device is an in vitro diagnostic device used to measure galectin-3 levels in patient samples, which aids in assessing the prognosis of patients with chronic heart failure. It does not provide any treatment or therapeutic intervention.
Yes
Explanation: The "Intended Use / Indications for Use" section explicitly states, "BGM Galectin-3 is an in vitro diagnostic device." It also describes its purpose as "an aid in assessing prognosis of patients diagnosed with chronic heart failure (HF)," which is a diagnostic function.
No
The device is an in vitro diagnostic device that uses a microtiter plate-based ELISA method to measure galectin-3 levels. This involves physical reagents, a microtiter plate, and a colorimetric reader, which are all hardware components. The description clearly outlines a wet lab assay procedure, not a software-only function.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use/Indications for Use: The very first sentence explicitly states, "BGM Galectin-3 is an in vitro diagnostic device..." It also describes its function as quantitatively measuring a substance (galectin-3) in biological samples (serum or EDTA-plasma) to aid in assessing prognosis of patients with chronic heart failure. This aligns perfectly with the definition of an IVD.
- Device Description: The description details a laboratory-based assay (ELISA) performed on biological samples using reagents and a microtiter plate. This is characteristic of an in vitro diagnostic test.
- Input Imaging Modality/Anatomical Site: The "Not Applicable" entries for these categories further support that it's not an imaging device, but rather a test performed on biological specimens.
- Summary of Performance Studies: The studies described (Precision, Linearity, Dilution Parallelism, etc.) are standard performance evaluations for in vitro diagnostic assays.
- Key Metrics: The metrics listed (Hazard Ratio, Cumulative Probability of Event, Precision, etc.) are relevant to the clinical performance and analytical characteristics of an IVD.
The information provided clearly indicates that the BGM Galectin-3 device is designed to be used outside of the body to examine specimens from the human body for the purpose of providing information for the diagnosis, monitoring, or treatment of a medical condition, which is the definition of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
BGM Galectin-3 is an in vitro diagnostic device that quantitatively measures galectin-3 in serum or EDTA-plasma by enzyme-linked immunosorbant assay (ELISA) on a microtiter plate platform to be used in conjunction with clinical evaluation as an aid in assessing prognosis of patients diagnosed with chronic heart failure (HF). BGM Galectin-3 is indicated for prescription use only.
Product codes (comma separated list FDA assigned to the subject device)
OSX
Device Description
BGM Galectin-3 is a microtiter plate-based sandwich enzyme-linked immunosorbant assay (ELISA) for the quantitative determination of galectin-3 levels in human serum and plasma. BGM Galectin-3 consists of a rat monoclonal anti-mouse galectin-3 antibody coated microtiter plate serving as the solid phase capture antibody and a horseradish peroxidase (HRP)-labeled mouse monoclonal anti-human galectin-3 antibody functioning as the liquid phase tracer antibody for detecting bound galectin-3.
In the testing procedure, galectin-3 in the standard, control, or patient specimen binds to the immobilized capture antibody; after a wash step, bound galectin-3 is detected by the addition of HRP-labeled anti-galectin-3 antibody. Following a second wash step, the presence of bound galectin-3 is demonstrated by an enzymatic blue color development resulting from the addition of tetramethylbenzidene (TMB) solution as the substrate. Color development is stopped by adding sulfuric acid, changing the color to yellow. Color intensity is read at an absorbance of 450 nm using a colorimetric reader. The absorbance is proportional to the galectin-3 levels in the samples, and test results of the samples are determined using a calibration curve derived from the standards.
BGM Galectin-3 contains the microtiter plate, reagents, assayed quality control materials and standards required to perform analyses on serum or EDTA-plasma samples.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Not Found
Description of the training set, sample size, data source, and annotation protocol
Galectin-3 levels were measured in 582 individuals with HF to derive cutoff values: Galectin-3 25.9 ng/mL.
Description of the test set, sample size, data source, and annotation protocol
A separate study of 895 individuals with HF was conducted in order to validate the proposed cutoff values. This independent set of 895 banked EDTA-plasma samples from patients in the United States and Canada were from a controlled multi-center clinical study, the Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) study. The HF-ACTION study involved 2,331 chronic HF patients with left ventricular dysfunction and with NYHA class II, III or IV symptoms. The average age of the 895 participants whose galectin-3 levels were assessed in the clinical validation study was 58 years, 29% were female, and 36% were non-white. Sensitivity analysis was performed comparing the set of 895 HF-ACTION subjects having evaluable galectin-3 values with all other HF-ACTION participants, and it was found that the clinical validation results based on the evaluable set of subjects were robust and representative of the larger study population. The median follow-up time was approximately 30 months.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Precision Study:
Precision of BGM Galectin-3 was assessed in an evaluation according to the CLSI EPS-A2 guideline. Six (6) EDTA-plasma pools spanning a range of galectin-3 concentrations were analyzed in duplicate with two (2) runs per day over twenty (20) days using one (1) reagent lot, two (2) operators and one (1) microtiter plate reader. Estimates of withinrun, run-to-run, day-to-day and total precision were calculated and met acceptance criteria.
Results:
Within-run imprecision: 2.1-5.7% CV from 6.1-72.2 ng/mL
Total imprecision: 4.2-12.0 % CV from 6.1-72.2 ng/mL
Clinical Laboratory Precision Study:
Precision was also evaluated at three (3) CLIA-certified clinical laboratories according the CLSI EP5-A2 guideline. The study included testing of EDTA-plasma pools spanning three (3) galectin-3 concentrations, across two (2) reagent lots, using three (3) different models of microtiter plate readers, and a total of four (4) different operators. Total testing days were 17, 18 and 20 days across the three sites, yielding 110 unique analytical runs.
Results: Within run and total imprecision estimates were within acceptable limits.
Linearity Study:
The linearity of BGM Galectin-3 was established according to the recommendations of the Clinical and Laboratory Standards Institute Evaluation Protocol 6 (CLSI EP6-A guideline). Linearity of BGM Galectin-3 was demonstrated between 1.4 and 94.8 ng/mL.
Clinical Validation Study (Cox Regression Models):
Objective: To evaluate the association of baseline galectin-3 levels in HF patients with various endpoints.
Sample Size: 895 banked EDTA-plasma samples from patients in the HF-ACTION study.
Endpoints:
(i) composite of all-cause mortality and all-cause hospitalization
(ii) cardiovascular mortality
(iii) composite of cardiovascular mortality and heart failure-related hospitalization
(iv) all-cause mortality
Key Results:
Galectin-3 levels were found to be significantly associated with increased risk of each of these endpoints in Cox regression models.
Galectin-3 remained significantly associated with increased risk upon adjustment for baseline risk factors of age, gender, NYHA functional classification, left ventricular ejection fraction, diabetes status, and smoking status.
Heart failure patients with galectin-3 levels >17.8 ng/mL had a statistically significantly increased hazard of death or hospitalization relative to heart failure patients with levels 25.9 ng/mL: 1.46 (95% CI: 1.11-1.92, p=0.006)
Cardiovascular Mortality:
Galectin-3 Category 25.9 ng/mL: 2.33 (95% CI: 1.43-3.80, p 25.9 ng/mL: 1.70 (95% CI: 1.19-2.42, p=0.004)
All-Cause Mortality:
Galectin-3 Category 25.9 ng/mL: 2.06 (95% CI: 1.31-3.23, p=0.002)
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.
Biosite, Inc. Triage® B-Type Natriuretic Peptide (BNP) Test (K080269)
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.
K052789, K051787, K033383, K032235, K030286, K021317, K010266, and K003475
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 862.1117 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.”
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Image /page/0/Picture/0 description: The image shows the text "BGMEDICINE" in a bold, sans-serif font. To the right of the text is a cluster of circular shapes, possibly representing cells or molecules. The overall impression is that of a logo or branding element for a medical or healthcare-related entity.
510(k) Summary
NOV 1 7 2010
は
| Company Name: | BG Medicine, Inc. |
|---|---|
| Address: | 610N Lincoln Street |
| Waltham, MA 02451 | |
| Telephone: | (781) 405-8772 |
| Fax: | (781) 895-1119 |
| Contact person: | Carol A. Adiletto, M.S. |
| Date summary prepared: | November 16, 2010 |
Device Name
| Trade Name: | BGM Galectin-3™ |
|---|---|
| Common / Usual name: | Galectin-3 assay |
| Classification name: | Galectin-3 IVD assay |
| Product Code: | OSX |
Predicate Device
Biosite, Inc. Triage® B-Type Natriuretic Peptide (BNP) Test (K080269, K052789, K051787, K033383, K032235, K030286, K021317, K010266, and K003475).
Device Description
BGM Galectin-3 is a microtiter plate-based sandwich enzyme-linked immunosorbant assay (ELISA) for the quantitative determination of galectin-3 levels in human serum and plasma. BGM Galectin-3 consists of a rat monoclonal anti-mouse galectin-3 antibody coated microtiter plate serving as the solid phase capture antibody and a horseradish peroxidase (HRP)-labeled mouse monoclonal anti-human galectin-3 antibody functioning as the liquid phase tracer antibody for detecting bound galectin-3.
In the testing procedure, galectin-3 in the standard, control, or patient specimen binds to the immobilized capture antibody; after a wash step, bound galectin-3 is detected by the addition of HRP-labeled anti-galectin-3 antibody. Following a second wash step, the presence of bound galectin-3 is demonstrated by an enzymatic blue color development resulting from the addition of tetramethylbenzidene (TMB) solution as the substrate. Color development is stopped by adding sulfuric acid, changing the color to yellow. Color intensity is read at an absorbance of 450 nm using a colorimetric reader. The absorbance is proportional to the galectin-3 levels in the samples, and test results of the samples are determined using a calibration curve derived from the standards.
BGM Galectin-3 contains the microtiter plate, reagents, assayed quality control materials and standards required to perform analyses on serum or EDTA-plasma samples.
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Intended Use
BGM Galectin-3 is an in vitro diagnostic device that quantitatively measures galectin-3 in serum or EDTA-plasma by enzyme-linked immunosorbant assay (ELISA) on a microtiter plate platform to be used in conjunction with clinical evaluation as an aid in assessing prognosis of patients diagnosed with chronic heart failure (HF). BGM Galectin-3 is indicated for prescription use only.
| Comparison
| Item | Predicate Device | Subject Device |
|---|---|---|
| Biosite, Inc. Triage® BNP Test1,2 | BGM Galectin-3TM | |
| Intended | ||
| Use | Quantitative Measurement of B-Type | |
| Natriuretic Peptide (BNP) | Quantitative measurement of galectin-3 | |
| Indications | ||
| for Use | An aid in the: | |
| • Risk stratification of patients with heart | ||
| failure | ||
| • Diagnosis of heart failure | ||
| • Assessment of heart failure severity | ||
| • Risk stratification of patients with acute | ||
| coronary syndromes | ||
| • Diagnostic utility of BNP in patients with | ||
| heart failure | An aid in: | |
| • Assessing the prognosis of patients with | ||
| chronic heart failure | ||
| Test | ||
| Principle | Sandwich ELISA | Sandwich ELISA |
| Specimen | Whole blood and EDTA-plasma | EDTA-plasma and serum |
| Analyte | Human B-type natriuretic peptide | Human galectin-3 |
| Antibody | Mouse monoclonal and polyclonal antibodies | |
| against BNP, labeled with a fluorescent dye | ||
| and immobilized on the solid phase, and | ||
| stabilizers | Two monoclonal antibodies against galectin- | |
| 3; one immobilized on the solid phase and the | ||
| other labeled with horseradish peroxidase | ||
| Instrument | Fluorometer: either the Triage® Meter or the | |
| Beckman Coulter (Access, Access 2, Synchron | ||
| LXi 725, and UniCel Dxl 800) | Spectrophotometer (plate reader). (Not | |
| supplied.) | ||
| Detection Method: Optical Density at 450 nm | ||
| Controls | Triage® BNP Controls | BGM Galectin-3 Quality Control materials |
| Comparison | ||
| Item | Predicate Device | Subject Device |
| Precision | Biosite, Inc. Triage® BNP Test | |
| Average within-day 8.8-11.6 % CV from 71.3-4087.9 pg/mL Average total 9.9-12.2 % CV from 71.3-4087.9 pg/mL | BGM, Galectin-3TM | |
| Within-run imprecision: 2.1-5.7% CV from 6.1-72.2 ng/mL Total imprecision: 4.2-12.0 % CV from 6.1-72.2 ng/mL | ||
| Expected | ||
| Values | ||
| (Reference | ||
| Range) | BNP levels were measured in 1,286 individuals (676 women, 610 men) without CHF using the Triage® BNP Test. A statistically significant difference between males and females and among age groups is shown. Descriptive statistics and the 95th percentile are reported for males and females by age category. A "decision threshold" of 100 pg/mL is recommended for use as an aid in the diagnosis of heart failure indication. | Galectin-3 levels were measured in 1,099 individuals (575 women, 524 men) without heart failure using the BGM Galectin-3 test. Gender-specific or age category-specific reference intervals were found not to be warranted, per NCCLS (CLSI) guidelines. Descriptive statistics and percentiles are reported. Clinical cutoffs were derived in a separate study (see below). |
| Clinical | ||
| Study | ||
| Results | K051787 – FDA Decision Summary states: "In support of the new intended use, the sponsor provided five peer-reviewed articles from the scientific literature assessing the clinical utility of BNP measurements as an aid in the risk stratification of patients with heart failure. All five studies utilized the Biosite Triage BNP device in their test method." Biosite Triage labeling states: "A systematic review of studies investigating BNP for prognostic utility in patients with heart failure concluded that every 100 pg/mL increase in BNP concentration was associated with a 35% increase in the relative risk of death. | Galectin-3 levels were measured in 582 individuals with HF to derive cutoff values: Galectin-3 ≤ 17.8 ng/mL Galectin-3 17.8 - 25.9 ng/mL Galectin-3 > 25.9 ng/mL A separate study of 895 individuals with HF was conducted in order to validate the proposed cutoff values. Heart failure patients with galectin-3 levels >17.8 ng/mL had a statistically significantly increased hazard of death or hospitalization relative to heart failure patients with levels ≤ 17.8 ng/mL. Elevated galectin-3 levels remained statistically significantly associated with increased hazard after adjustment for other baseline risk factors of age, gender, NYHA class, left ventricular ejection fraction, diabetes status, and smoking status. Levels above 25.9 ng/mL confer a further increase in risk. |
Table 1. Comparison of Similarities and Differences to Predicate
1 Triage® BNP Test package insert 2234en Rev. E ©2006 Biosite Incorporated
2 510(k) summaries from FDA website
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·
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Summary of Performance Data
Precision
Precision of BGM Galectin-3 was assessed in an evaluation according to the CLSI EPS-A2 guideline. Six (6) EDTA-plasma pools spanning a range of galectin-3 concentrations were analyzed in duplicate with two (2) runs per day over twenty (20) days using one (1) reagent lot, two (2) operators and one (1) microtiter plate reader. Estimates of withinrun, run-to-run, day-to-day and total precision were calculated and met acceptance criteria. Results are summarized in Table 2.
| Test
Specimen # | Galectin-3
mean
(ng/mL) | Within run | | Run to run | | Day to day | | Total | |
|--------------------|-------------------------------|------------|-----|------------|------|------------|-----|-------|------|
| | | SD | CV% | SD | CV% | SD | CV% | SD | CV% |
| 1 | 6.1 | 0.3 | 5.7 | 0.6 | 10.5 | 0.0 | 0.0 | 0.7 | 12.0 |
| 2 | 17.6 | 0.4 | 2.1 | 0.7 | 3.8 | 0.5 | 2.8 | 0.9 | 5.1 |
| 3 | 20.7 | 0.7 | 3.4 | 1.4 | 6.7 | 0.3 | 1.7 | 1.6 | 7.7 |
| 4 | 26.3 | 0.6 | 2.2 | 0.8 | 3.0 | 0.5 | 2.1 | 1.1 | 4.2 |
| 5 | 46.2 | 1.1 | 2.4 | 1.6 | 3.6 | 0.5 | 1.1 | 2.0 | 4.4 |
| 6 | 72.2 | 2.4 | 3.3 | 4.3 | 6.0 | 2.9 | 4.0 | 5.7 | 8.0 |
Table 2. Precision of BGM Galectin-3
The table above shows the results of the precision evaluation with EDTA-plasma pools. An additional experiment was performed using serum pools which yielded similar results. Additional test pools at multiple galectin-3 concentrations were also tested and yielded similar results.
Clinical Laboratory Precision
Precision was also evaluated at three (3) CLIA-certified clinical laboratories according the CLSI EP5-A2 guideline. The study included testing of EDTA-plasma pools spanning three (3) galectin-3 concentrations, across two (2) reagent lots, using three (3) different models of microtiter plate readers, and a total of four (4) different operators. Total testing days were 17, 18 and 20 days across the three sites, yielding 110 unique analytical runs. Results from each of the CLIA laboratories were within acceptable limits. Within run and total imprecision estimates are summarized in Table 3.
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| CLIA
Lab | # days,
runs | Galectin-3
mean
(ng/mL) | Within Run | | Total | |
|-------------|---------------------|-------------------------------|------------|-----|-------|------|
| | | | SD | CV% | SD | CV% |
| A | 20 days,
40 runs | 6.0 | 0.30 | 5.0 | 0.46 | 7.7 |
| A | | 20.1 | 0.59 | 2.9 | 1.20 | 6.0 |
| A | | 68.3 | 2.71 | 4.0 | 9.97 | 14.6 |
| B | 17 days,
34 runs | 6.7 | 0.36 | 5.4 | 0.63 | 9.4 |
| B | | 21.6 | 0.56 | 2.6 | 1.55 | 7.2 |
| B | | 75.5 | 1.71 | 2.3 | 12.75 | 16.9 |
| C | 18 days,
36 runs | 6.3 | 0.46 | 7.3 | 0.59 | 9.4 |
| C | | 21.2 | 0.71 | 3.3 | 1.19 | 5.6 |
| C | | 71.5 | 2.16 | 3.0 | 6.25 | 8.7 |
Table 3. Clinical Laboratory Precision - Within Run and Total Imprecision
Linearity
The linearity of BGM Galectin-3 was established according to the recommendations of the Clinical and Laboratory Standards Institute Evaluation Protocol 6 (CLSI EP6-A guideline). Samples were prepared to span a clinically-meaningful measurement range of galectin-3 concentrations. Linearity of BGM Galectin-3 was demonstrated between 1.4 and 94.8 ng/mL. These linearity data are shown in Figure 1.
Image /page/4/Figure/5 description: The image shows a graph titled "BGM Galectin-3TM Linearity Testing". The graph plots "Measured Galectin-3 (ng/mL)" on the y-axis against "Expected Galectin-3 (ng/mL)" on the x-axis. A linear trendline is shown on the graph, with the equation y = 0.9905x - 0.41 and an R-squared value of 0.9985.
Figure 1: Linearity of BGM Galectin-3
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Dilution Parallelism
Dilution parallelism was evaluated by analyzing ten (10) clinical specimens with endogenous native galectin-3 concentrations from 21.6 ng/mL to 88.5 ng/mL at 1:20, 1:40. 1:80 and 1:160 dilutions. Results support ten-fold sample dilution only (1:10). Samples that vield galectin-3 results greater than the upper end of the measurement range (94.8 ng/mL) should NOT be diluted beyond 1:10 and should be reported as "galectin-3 value exceeds the upper limit of the measurement range" or utilize language consistent with laboratory or institutional policies.
High Dose Hook Effect
There is no high dose hook effect at galectin-3 levels up to 500 ng/mL.
Sample Matrices
The BGM Galectin-3 assay has been validated for use with EDTA-plasma or serum samples. The equivalence of these sample matrices were demonstrated in a study of forty-nine (49) matched serum and EDTA-plasma samples with values spanning the measurement range. The regression equation is shown in the x/y scatter plot in Figure 2.
Image /page/5/Figure/7 description: This image is a scatter plot comparing Galectin-3 levels in EDTA-plasma and serum, both measured in ng/mL. The x-axis represents Galectin-3 levels in serum, while the y-axis represents Galectin-3 levels in EDTA-plasma. A linear regression line is fitted to the data, with the equation y = 0.96x + 0.72 and an R-squared value of 0.96, indicating a strong positive correlation between the two measurements. The data points are clustered closely around the regression line, showing a consistent relationship between Galectin-3 levels in EDTA-plasma and serum.
Figure 2: BGM Galectin-3 Serum and EDTA-Plasma Regression
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Detection Limit
The limit of detection and limit of quantitation of BGM Galectin-3 were established according to the recommendation of the CLSI EP17-A guideline. The limit of blank (LoB) was determined as the 95th percentile value of forty-eight (48) replicate measurements of the BGM Galectin-3 Assay Buffer. The limit of detection (LoD) was LoD = LoB + cg SDs, where SDs is the pooled standard deviations from four (4) serum samples with different levels of galectin-3, each of which was measured in sixteen (16) replicates (for a total of sixty-four (64) measurements) and co is the 95th percentile of the standard Gaussian distribution corrected for the degree of freedom. The Limit of quantitation (LoQ) was specified as the lowest galectin-3 concentration of the serum samples closest to while above the LoD, which is 1.32 ng/mL. For this sample, the coefficient of variation (CV) for the galectin-3 measurement was 10.4%.
| Limit of Blank (LoB): | LoB = 0.86 ng/mL |
|---|---|
| Limit of Detection (LoD): | LoD = 1.13 ng/mL |
| Limit of Quantitation (LoQ): | LoQ = 1.32 ng/mL |
Note: The LoQ does not represent the lower end of the measuring range and should not be used for that purpose. The measuring range is 1.4 to 94.8 ng/mL as reported in the Measuring Range and Linearity sections of this document.
Cross Reactivity
BGM Galectin-3 displayed no significant cross-reactivity when tested in the presence of the following compounds: galectin-1, galectin-4, galectin-4, galectin-7, galectin-8, galectin-9, galectin-12, collagen I and collagen III, all at a concentration of 500 ng/mL. The mean % cross-reactivity of the above potential cross-reactants is at or below 0.3%.
Interfering Substances
BGM Galectin-3 was evaluated for the effects of potential interfering substances, both endogenous and exogenous, according to the recommendations of the CLSI EP7-A guideline, using an interference acceptance limit of +/-10%. Conjugated bilirubin (up to 16.8 mg/dL), unconjugated bilirubin (up to 40.3 mg/dL), albumin (BSA, up to 12 g/dL), triglycerides (up to 3000 mg/dL), cholesterol (up to 747 mg/dL), and creatinine (up to 5 mg/dL) do not show any significant interference in the assay based on the interference acceptance limit (+/- 10%). Purified hemoglobin (up to 500 mg/dL) does not show significant interference in BGM Galectin-3; however, packed blood cell Iysate does show interference. Human anti-mouse antibodies (HAMA) and rheumatoid factor (RF) cause significant positive interference and rheumatoid factor (RF) greater than 50 IU/mL causes significant positive interference with BGM Galectin-3. High levels of gamma globulins (> 2.5 g/dL) may cause false elevation in galectin-3 levels. This information is summarized in Table 4.
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Table 4. Endogenous Interference Summary
| Potential interfering substance | Result of interference study based on an
interference acceptance limit of +/- 10% |
|---------------------------------------|--------------------------------------------------------------------------------------|
| Conjugated bilirubin | No significant interference up to 16.8 mg/dL |
| Unconjugated bilirubin | No significant interference up to 40.3 mg/dL |
| Albumin | No significant interference up to 12 g/dL |
| Triglycerides | No significant interference up to 3000 mg/dL |
| Cholesterol | No significant interference up to 747 mg/dL |
| Creatinine | No significant interference up to 5 mg/dL |
| Purified hemoglobin | No significant interference up to 500 mg/dL |
| Whole blood lysate | Hemolyzed specimens should not be used with BGM
Galectin-3™ |
| Human anti-mouse antibodies
(HAMA) | Specimens from patients with HAMA should not be
used with BGM Galectin-3™ |
| Rheumatoid Factor (RF) | Interference seen at levels > 50 IU/mL |
| Gamma globulins | Interference seen at levels ≥ 2.5 g/dL |
BGM Galectin-3 measurements were not significantly affected when tested in the presence of thirty-four (34) common pharmaceutical substances; including HF drugs (refer to Table 5). All analytes fall within the interference acceptance limit of +/- 10%.
| Acetaminophen | Carvedilol | Dopamine | Lisinopril | Quinidine |
|---|---|---|---|---|
| Acetylsalicylic acid | Captopril | Enalaprilat | Losartan | Ramipril |
| Amlodipine | Chloramphenicol | Furosemide | Lovastatin | Spironolactone |
| Ampicillin | Diclofenac | Hydrochlorothiazide | Methyldopa | Theophylline |
| Ascorbic Acid | Digoxin | Ibuprofen | Metoprolol | Verapamil |
| Atenolol | Diltiazem | Indomethacin | Naproxen | Warfarin |
| Caffeine | Disopyramide | Lidocaine | Nifedipine |
Table 5: Common Drugs That Did Not Show Interference with BGM Galectin-3
Expected Values (Reference Range)
A reference distribution for galectin-3 was determined through an observational study. Galectin-3 levels were measured in 1,099 banked plasma samples from a population of apparently healthy subjects without known heart disease but that otherwise resemble, by age and gender distribution, the HF patient population. Specimens were from women between the ages of 60 and 80 years (n=575) and men between the ages of 55 and 80 (n=524). This reference population comprised individuals of different ethnic background, as follows: Black or African-American (n=307, 27.9%), Caucasian (n=691, 62.9%), Hispanic (n=42, 3.8%), Asian or Pacific Islander (n=30, 2.7%), and not specified (n=29, 2.6%). All subjects had detectable galectin-3 levels (min-max. 3.2 - 94.6 ng/mL) within the measuring range of BGM Galectin-3. Blood plasma samples were collected from study participant into tubes containing
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EDTA. The blood was processed and blood plasma was subsequently frozen at -80°C or colder.
Table 6 summarizes the galectin-3 distribution results. The 97.5th percentile of the galectin-3 distribution from this reference population is 26.2 ng/mL.
Each laboratory should establish a reference range that is representative of the patient population to be evaluated. Additionally, each laboratory should consider their current practice in the evaluation of heart failure patients at each institution.
| Percentile | Galectin-3 (ng/mL) |
|---|---|
| 2.5th | 5.4 |
| 5th | 6.3 |
| 25th | 9.7 |
| 50th | 12.4 |
| 75th | 15.6 |
| 90th | 19.0 |
| 95th | 22.1 |
| 97.5th | 26.2 |
Table 6. Distribution of Galectin-3 Levels in Subjects without Known Heart Disease
Clinical Studies and Interpretation of Results
To validate the clinical effectiveness of the BGM Galectin-3 assay, galectin-3 levels were measured in an independent set of 895 banked EDTA-plasma samples from patients in the United States and Canada in a controlled multi-center clinical study, the Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) study. The HF-ACTION study involved 2,331 chronic HF patients with left ventricular dysfunction and with NYHA class II, III or IV symptoms. The average age of the 895 participants whose galectin-3 levels were assessed in the clinical validation study was 58 years, 29% were female, and 36% were non-white. Sensitivity analysis was performed comparing the set of 895 HF-ACTION subjects having evaluable galectin-3 values with all other HF-ACTION participants, and it was found that the clinical validation results based on the evaluable set of subjects were robust and representative of the larger study population. The median follow-up time was approximately 30 months. Participants were categorized based on galectin-3 risk categories defined below:
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The derived galectin-3-dependent risk categories are as follows:
- 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
For the clinical validation study, Cox regression models were used to evaluate the association of baseline galectin-3 levels in HF patients with the endpoints of: (i) composite of all-cause mortality and all-cause hospitalization, (ii) cardiovascular mortality, and (iii) composite of cardiovascular mortality and heart failure-related hospitalization, and (iv) all-cause mortality. Galectin-3 levels were found to be significantly associated with increased risk of each of these endpoints in Cox regression models (Table 7, Table 9, Table 11, and Table 14). Galectin-3 remained significantly associated with increased risk upon adjustment for baseline risk factors of age, gender, NYHA functional classification, left ventricular ejection fraction, diabetes status, and smoking status. Figure 3 displays Kaplan Meier curves for the composite endpoint of allcause mortality or all-cause hospitalization, by baseline galectin-3 category.
Figure 4, Figure 5 and Figure 6 display cumulative probabilities for events for the endpoints of the composite of all-cause mortality and all-cause hospitalization, cardiovascular mortality, and the composite of cardiovascular mortality and heart failurerelated hospitalization in the clinical validation study, by baseline galectin-3 category at timepoints of 6, 12, 24 and 36 months after baseline.
All-Cause Mortality and All-Cause Hospitalization
| Hazard Ratio (95% CI, p value) | |||
|---|---|---|---|
| Galectin-3 Category | ≤ 17.8 ng/mL | 17.8-25.9 ng/mL | > 25.9 ng/mL |
| Number of Subjects | 647 | 170 | 78 |
| Galectin-3* | 1.0 | 1.35 (1.10-1.65, p=0.004) | 1.46 (1.11-1.92, p=0.006) |
Table 7. Hazard Ratios for All-Cause Mortality and All-Cause Hospitalization Events for HF Subjects in the Clinical Validation Study
*adjusted for baseline risk factors: age, gender, NYHA functional classification, left ventricular ejection fraction, diabetes status, and smoking status.
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Image /page/10/Figure/0 description: The image is a survival plot showing event probability versus months from baseline to death/hospitalization. There are three lines on the plot, representing different levels of a variable in ng/mL. The top line represents >25.9 ng/mL, the middle line represents 17.8-25.9 ng/mL, and the bottom line represents ≤ 17.8 ng/mL.
Figure 3: Kaplan-Meier Curves for the Composite Endpoint of All-Cause Mortality or All-Cause Hospitalization, for HF Subjects in the Clinical Validation Study, by Baseline Galectin-3 Level
Image /page/10/Figure/2 description: This image is a bar graph that shows the percentage of people with different levels of a certain substance in their blood over time. The x-axis represents time in months (6, 12, 24, and 36), and the y-axis represents the percentage of people. There are three categories of substance levels: less than or equal to 17.8 ng/mL, between 17.8 and 25.9 ng/mL, and greater than 25.9 ng/mL. At 36 months, the percentages for the three categories are approximately 69.8%, 81.7%, and 82.1% respectively.
Image /page/10/Figure/3 description: The image is a title for a figure. The title reads, "Figure 4: Cumulative Probability of Event for the Composite Endpoint of All-Cause Mortality and All-Cause Hospitalization, at Various Time Points and By Baseline Galectin-3 Level, for HF Subjects in the Clinical Validation Study." The title describes the contents of the figure, which is about the cumulative probability of an event for the composite endpoint of all-cause mortality and all-cause hospitalization.
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Table 8. Cumulative Probability (with 95% Confidence Intervals) of Event for the Composite Endpoint of All-Cause Mortality and All-Cause Hospitalization, at Various Time Points and By Baseline Galectin-3 Level, for HF Subjects in the Clinical Validation Study
| | Cumulative Probability of All-Cause Mortality and All-Cause Hospitalization
(95% CI)
by Galectin-3 Category and Time Point (in percent) | | | |
|---------------------|-----------------------------------------------------------------------------------------------------------------------------------------------|------------------|------------------|------------------|
| Galectin-3 Category | 6 months | 12 months | 24 months | 36 months |
| 25.9 ng/mL | 44.2 (33.9-55.9) | 55.8 (45.2-67.1) | 79.8 (69.9-88.2) | 82.1 (72.0-90.0) |
Cardiovascular Mortality
Table 9. Hazard Ratios for Cardiovascular Mortality Events for HF Subjects in the Clinical Validation Study
| Hazard Ratio (95% CI, p value) | |||
|---|---|---|---|
| Galectin-3 Category | ≤ 17.8 ng/mL | 17.8-25.9 ng/mL | > 25.9 ng/mL |
| Number of Subjects | 647 | 170 | 78 |
| Galectin-3* | 1.0 | 1.91 | |
| (1.28-2.86, p= 0.002) | 2.33 | ||
| (1.43-3.80, p 25.9 ng/mL | 2.6(0.6-9.9) | 9.1(4.4-18.1) | 23.6(15.0-36.0) |
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Cardiovascular Mortality and Heart Failure-Related Hospitalization
Table 11. Hazard Ratios for Cardiovascular Mortality and Heart Failure-Related Hospitalization Events for HF Subjects in the Clinical Validation Study
| Hazard Ratio (95% CI, p value) | |||
|---|---|---|---|
| Galectin-3 Category | ≤ 17.8 ng/mL | 17.8-25.9 ng/mL | > 25.9 ng/mL |
| Number of Subjects | 647 | 170 | 78 |
| Galectin-3* | 1.0 | 1.51 | |
| (1.14-2.00, p=0.004) | 1.70 | ||
| (1.19-2.42, p=0.004) |
*adjusted for baseline risk factors: age, gender, NYHA functional classification, left ventricular ejection fraction, diabetes status, and smoking status.
Image /page/13/Figure/5 description: This bar graph compares the percentage of three groups of people at 6, 12, 24, and 36 months. The three groups are those with less than or equal to 17.8 ng/mL, those with 17.8-25.9 ng/mL, and those with greater than 25.9 ng/mL. At 36 months, the percentages for each group are 31.4%, 48.5%, and 54.8% respectively.
Image /page/13/Figure/6 description: The image is a title for a figure. The title is "Figure 6: Cumulative Probability of Event for the Composite Endpoint of Cardiovascular Mortality and Heart Failure-Related Hospitalization, at Various Time Points and By Baseline Galectin-3 Level, for HF Subjects in the Clinical Validation Study". The title describes the contents of the figure.
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Table 12. Cumulative Probability (with 95% Confidence Intervals) of Event for Cardiovascular Mortality and Heart Failure-Related Hospitalization, at Various Time Points and By Baseline Galectin-3 Level, for HF Subjects in the Clinical Validation Study
| | Cumulative Probability of Cardiovascular Mortality and Heart Failure-
Related Hospitalization (95% CI)
by Galectin-3 Category and Time Point (in percent) | | | |
|---------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------|------------------|------------------|
| Galectin-3 Category | 6 months | 12 months | 24 months | 36 months |
| 25.9 ng/mL | 15.6 (9.2-25.8) | 22.2 (14.4-33.2) | 50.2 (38.9-62.8) | 54.8 (42.9-67.6) |
All-Cause Mortality
Image /page/14/Figure/4 description: The image is a survival probability graph that shows the survival probability over time for three different groups. The x-axis represents time, ranging from 0 to 36, and the y-axis represents survival probability, ranging from 0.0 to 1.0. The three groups are defined by their levels of a certain substance: > 25.9 ng/mL, 17.8 - 25.9 ng/mL, and ≤ 17.8 ng/mL, with the group > 25.9 ng/mL having the highest survival probability and the group ≤ 17.8 ng/mL having the lowest survival probability.
Months From Baseline to Death
Figure 7: Kaplan-Meier Curves for the Endpoint of All-Cause Mortality, for HF Subjects in the Clinical Validation Study, by Baseline Galectin-3 Level
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Image /page/15/Picture/0 description: The image shows the logo for BG Medicine. The logo consists of the text "BG MEDICINE" in a simple, sans-serif font. To the right of the text is a graphic of four circles arranged in a cluster, resembling a molecular structure or a stylized representation of cells. The overall design is clean and professional, suggesting a company in the medical or scientific field.
Table 13. Cumulative Probability (with 95% Confidence Intervals) of Event for the Endpoint of AJI-Cause Mortality, at Various Time Points and By Baseline Galectin-3 Level, for HF Subjects in the Clinical Validation Study
| | Cumulative Probability of All-Cause Mortality Event (95% CI)
by Galectin-3 Category and Time Point (in percent) | | | |
|---------------------|--------------------------------------------------------------------------------------------------------------------|----------------|------------------|------------------|
| Galectin-3 Category | 6 months | 12 months | 24 months | 36 months |
| ≤ 17.8 ng/mL | 1.2% (0.6%-2.5%) | 3.3 (2.1-5.0) | 8.7 (6.7-11.3) | 15.3 (12.4-18.8) |
| 17.8-25.9 ng/mL | 5.3 (2.8-10.0) | 8.9 (5.5-14.4) | 22.0 (16.3-29.4) | 30.5 (23.4-39.1) |
| > 25.9 ng/mL | 2.6 (0.6-9.9) | 9.1 (4.4-18.1) | 26.6 (17.5-39.1) | 35.5 (24.5-49.5) |
Table 14. Hazard Ratios for All-Cause Mortality Events for HF Subjects in the Clinical Validation Study
| Hazard Ratio (95% CI, p value) | |||
|---|---|---|---|
| Galectin-3 Category | ≤ 17.8 ng/mL | 17.8-25.9 ng/mL | > 25.9 ng/mL |
| Number of Subjects | 647 | 170 | 78 |
| Galectin-3* | 1.0 | $1.84$ | |
| $(1.28-2.64, p=0.001)$ | $2.06$ | ||
| $(1.31-3.23, p=0.002)$ |
*udjusted for baseline risk factors: age, gender, NYHA functional classification, left ventricular ejection fraction, diabetes status, and smoking status.
Interpretation
The BGM Galectin-3 assay results should be interpreted in conjunction with clinical evaluation as an aid in the assessment of prognosis of patients diagnosed with chronic heart failure.
Patients with chronic heart failure with galectin-3 levels over 17.8 ng/mL were found to have a higher risk of adverse outcomes including mortality or hospitalization compared to patients with levels below 17.8 ng/mL. Galectin-3 levels between 17.8 ng/mL and 25.9 ng/mL should be interpreted with caution because these values lie within the reference range.
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Interpretation Relative to Natriuretic Peptides
Galectin-3 and natriuretic peptides are measures of separate and distinct biological processes. Each marker provides independent and complementary information on the prognosis of patients with chronic heart failure.
Table 15 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.
Table 15. Event Rates at 6, 12, 24 and 36 Months for the Composite Endpoint of All-Cause Mortality and All-Cause Hospitalization, by Galectin-3 Category and NT-proBNP level, for HF Subjects in the Clinical Validation Study. The median value for NT-proBNP in the Clinical Validation Study was 848 pg/mL.
| | Galectin-3 $ \u2264 $ 17.8
ng/mL and NT-
proBNP $ \u2264 $ median | Galectin-3 $ \u2264 $ 17.8 ng/mL
and NT-proBNP >
median
or
Galectin-3 > 17.8 ng/mL
and NT-proBNP $ \u2264 $ median | Galectin-3 > 17.8
ng/mL and NT-
proBNP > median |
|-------------------------|-------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------|
| Event rate at 6 months | 19.4% | 31.8% | 42.7% |
| Event rate at 12 months | 32.0% | 50.0% | 58.0% |
| Event rate at 24 months | 55.3% | 71.1% | 85.7% |
| Event rate at 36 months | 76.1% | 85.8% | 93.0% |
Conclusion
Measurement of galectin-3 with the BGM Galectin-3 assay using a colorimetric microtiter plate reader is a safe and effective in vitro diagnostic device for use as an aid by clinicians in the assessment of prognosis of patients with chronic heart failure. Based on the foregoing, the performance of BGM Galectin-3 does not raise different questions of safety and effectiveness when used, as labeled, than those presented by the predicate device.
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Food and Drug Administration 10903 New Hampshire Avenue Building 66 Silver Spring, MD 20993
HOV 1 7 2010
BG Medicine, Inc. c/o Ms. Carol Adiletto VP Clinical and Regulatory Affairs 610N Lincoln Street Waltham, MA 02451
Re: K093758 Trade Name: BGM Galectin-3 Regulation Number: 21 CFR §862.1117 Regulation Name: Test, Natriuretic Peptide
Regulatory Class: Class II Product Code: OSX Dated: November 3, 2010 Received: November 5, 2010
Dear Ms. Adiletto:
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.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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); and good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820).
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Page 2 -
If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. 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 Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely yours.
C.C.
Courmey Harper, Ph.D. Director Division of Chemistry-and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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Indications for Use Statement
NOV 1 7 2010
510(k) Number (if known): K093758
BGM Galectin-3TM Device Name:
Indications for Use:
BGM Galectin-3 is an in vitro diagnostic device that quantitatively measures galectin-3 in serum or EDTA-plasma by enzyme linked immunosorbant assay (ELISA) on a microtiter plate platform. BGM Galectin-3 is indicated for use in conjunction with clinical evaluation as an aid in assessing the prognosis of patients diagnosed with chronic heart failure (HF).
Prescription Use X AND/OR (Part 21 CFR 801 Subpart D) (21 CFR 801 Subpart C) Over-The-Counter Use
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)
Carol C. Benson
Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safe 510(k) =======================================================================================================================================================================