RAMP MYOGLOBIN ASSAY

K012040 · Response Biomedical Corp. · DDR · Dec 18, 2001 · Immunology

Device Facts

• Record ID: K012040
• Device Name: RAMP MYOGLOBIN ASSAY
• Applicant: Response Biomedical Corp.
• Product Code: DDR · Immunology
• Decision Date: Dec 18, 2001
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.5680
• Device Class: Class 2

Intended Use

The RAMP Reader is a general use fluorometer that analyzes results produced by immunoassays that use a fluorophore having an excitation wavelength at 560 nm and an emission wavelength of 610 nm. The RAMP™ Myoglobin Assay is an immunochromatographic test for the quantitative determination of myoglobin in human EDTA whole blood, using the RAMP Reader.

Device Story

RAMP Myoglobin Assay is an immunochromatographic test for quantitative myoglobin measurement in human EDTA whole blood. Input: EDTA whole blood applied to test cartridge. Process: Plasma migrates via capillary action; myoglobin binds to fluorescent latex particles coated with mouse monoclonal anti-myoglobin antibodies; complexes are immobilized at detection and internal control zones. RAMP Reader measures fluorescence at 560 nm excitation/610 nm emission. Output: Quantitative myoglobin concentration calculated via ratio of detection zone to internal control zone fluorescence. Used in clinical settings by laboratory personnel. Output assists clinicians in diagnosing acute myocardial infarction (AMI). Benefits include rapid, quantitative assessment of myoglobin levels.

Clinical Evidence

Clinical performance evaluated via method comparison study (N=415) against Beckman ACCESS Myoglobin Assay. Population included 196 healthy individuals and 219 patients suspected of AMI. Combined population correlation r=0.932. Precision study (N=179) showed total precision ranging from 10.6% to 14.3% CV. Linearity study (N=5 replicates per standard) showed R=0.998. Analytical sensitivity (LLD) is 2.36 ng/mL. No high-dose hook effect up to 8000 ng/mL. No interference observed for common substances (Hb, triglyceride, bilirubin, cholesterol, coumadin) up to specified physiological limits.

Technological Characteristics

Immunochromatographic test cartridge using fluorescent latex particles. Detection system: RAMP Reader (fluorometer) with 560 nm excitation and 610 nm emission wavelengths. Quantitative measurement based on fluorescence ratio between detection and internal control zones. Sample type: EDTA whole blood. Connectivity: Standalone reader. Software: Embedded firmware for signal processing and ratio calculation.

Indications for Use

Indicated for the quantitative determination of myoglobin in human EDTA whole blood to aid in the diagnosis of acute myocardial infarction (AMI). Intended for use in clinical laboratory settings.

Regulatory Classification

Identification

A myoglobin immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the myoglobin (an oxygen storage protein found in muscle) in serum and other body fluids. Measurement of myoglobin aids in the rapid diagnosis of heart or renal disease.

Predicate Devices

• Triage Cardiac Panel®; Myoglobin Assay (K973126)
• ACCESS® Myoglobin Assay (K000196)

Submission Summary (Full Text)

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### 510(K) SUMMARY OF SAFETY AND EFFECTIVENESS 1.0

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

(012040 The assigned 510(k) number is: _______________________________________________________________________________________________________________________________________________

#### 1. Establishment:

Response Biomedical Corp. 8855 Northbrook Court Burnaby, British Columbia V5J5J1 Canada

Tel: [phone] Fax: [phone]

Contact: William J. Radvak President and CEO

June 27, 2001 Prepared:

- 2. Trade Name: Response Biomedical Corp. RAMP™ Myoglobin Assay Common Name: Myoglobin immunological test system Classification Name: Myoglobin immunological test system
### 3. Predicate Device:

| Immunoassay: | Triage Cardiac Panel®; Myoglobin Assay (K973126) which is<br>currently being marketed by Biosite Diagnostics, Inc. |
|--------------|--------------------------------------------------------------------------------------------------------------------|
| Immunoassay: | ACCESS® Myoglobin Assay (K000196) which is currently being<br>marketed by Beckman Coulter, Inc. |

#### 4. Description of the Device:

The RAMP Myoglobin Assay is an immunochromatographic test for the quantitative determination of myoglobin in human EDTA whole blood, using the RAMP Reader.

Diluted EDTA whole blood is applied into the sample well of the Test Cartridge. The red blood cells are retained in the sample pad, and the separated plasma migrates along a strip, through a contact zone where it interacts with fluorescent latex particles. Latex (test) particles, coated with mouse monoclonal anti-myoglobin antibodies bind to myoglobin in the sample.

The sample moves by capillary action towards the end of the strip. As the sample migrates to the detection zone, myoglobin anti-myoglobin particles are immobilized at the detection zone. and additional particles are immobilized at the internal control zone.

The RAMP Reader then measures the amount of fluorescence emitted by the complexes bound at the detection zone and at the internal control zone. Using a ratio between the two fluorescence values, a quantitative reading is calculated.

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### Comparison of Technological Characteristics ട്.

The RAMP Myoglobin Assay, Triage Cardiac Panel - Myoglobin; and ACCESS Myoglobin Assay are for the quantitative measurement of myoglobin in human whole blood (RAMP and Triage) or plasma (Triage and ACCESS). All three immunoassays utilize the binding of myoglobin to specific antibodies and utilize light in their respective detection systems. Both the RAMP and Triage assays measure light production from a fluorescence reaction using a fluorometer while the ACCESS Test measures light production from a chemiluminescent reaction using a luminometer. Both the RAMP Myoglobin and the Triage Cardiac Panel -Myoglobin are quantitative immunochromatographic tests, whereas the ACCESS Myoglobin test is an enzyme immunoassay.

### Summary of Studies 6.

## PERFORMANCE CHARACTERISTICS

PRECISION : The intra-assay and the inter-assay precision of the RAMP Myoglobin Assay were determined by one operator assaying duplicates of each standard (50, 100 and 200 ng/mL myoglobin standards) twice each day over 10 days. The mean, standard deviation and % CV were calculated for the predicted myoglobin at each concentration. Within run precision ranged between 13.0 to 6.5%. Between run precision ranged from 9.1 to 13.8%. Total precision ranged from 10.6 to 14.3%.

LINEARITY: Discrete myoglobin antigen concentrations of 10, 50, 75, 100, 150, 200 and 350 ng/mL were prepared in bovine calf serum. The linearity is determined by assaying five replicates of each standard. The mean, standard deviation and % CV were calculated for the predicted myoglobin at each concentration. Linear regression analysis of expected myoglobin concentration versus actual myoglobin concentration results with an R = 0.998 and a slope of 1.07 with an offset of 1.143.

HOOK EFFECT: There is no high dose hook effect in the RAMP Myoglobin Assay up to the highest level tested (8000 ng/mL myoglobin).

ANALYTICAL SENSITIVITY: The lower limit of detection (LLD) is defined as the analyte concentration corresponding to the mean (n=20) plus 2 standard deviations of the zero. The LLD is 2.36 na/mL myoalobin levels in excess of 400 ng/mL are reported as greater than (>) 400 ng/mL.

ANALYTICAL SPECIFICITY: Samples containing rheumatoid factor at levels greater than 1300 Rf IU/mL may interfere with the test and cause erroneous results. If this occurs, another specimen should be obtained and tested by an alternate method.

INTERFERENCE: Potentially interfering substances were evaluated by spiking different concentrations of interferents in blood with 100 ng/mL of myoglobin added. Different blood samples were used for each interferent. Interference was evaluated by calculating the myoglobin concentration of interferent-spiked blood, expressed as a percentage of the myoglobin concentration of the unspiked (no interferent) blood sample. No evidence of crossreactivity or interference was observed for hemoglobin (Hb), triglyceride, bilirubin, cholesterol, or coumidin at levels exceeding the highest expected physiological concentration of up to 2000 mg/dL, 3000mg/dL, 60 mg/dL, 2000 mg/dL, and 200 ug/mL, respectively. No trend was observed in the myoglobin predictions as the concentration of interferent was increased.

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# CLINICAL PERFORMANCE

### EXPECTED VALUES

Whole blood samples from 196 healthy individuals, (92 males and 104 females) were assayed. The lower (LLN) and upper (ULN) limits for normal range were defined as the 5" and 95" percentile values, respectively. The normal range of the RAMP Myoglobin Assay was found to be from 19.15 ng/mL to 99.3 ng/mL in the normal population studied. Each laboratory should establish its own expected values.

### PRECISION STUDY

Of 179 subjects tested in duplicate, 77 were normal individuals (40 males and 37 females) and 102 were suspected of acute myocardial infarct (AMI) based on the individual hospital criteria (63 males and 39 females). The samples were selected randomly from those obtained during the Method Comparison Study. The samples were stored refrigerated for up to five days between analyses. Data were winsorized (ACCESS values>400) to adjust for differing reportable ranges between the methods and two outliers excluded. Data are presented below.

### Table 1-1

| Population | n | Slope (y =) | Intercept | r |
|---------------------------|-----|-------------|-----------|------|
| Patients with suspect AMI | 102 | 0.9750x | 1.9026 | .986 |
| Normal Individuals | 77 | 0.9013x | 3.7143 | .967 |
| Combined Populations | 179 | 0.9702x | 0.9349 | .968 |

# METHOD COMPARISON

Of the 415 subjects compared. 196 were normal individuals (92 males and 104 females) and 219 were patients suspected of AMI based on the individual hospital criteria (131 males and 88 females). An EDTA whole blood sample was obtained for each of these subjects. These samples were tested in RAMP Myoglobin Assay and results compared to those obtained with the Beckman ACCESS Myoglobin Assay. Data were winsorized (ACCESS results >400) to adjust for differing reportable ranges between the methods and three outliers excluded. Data are presented in Table 4-2 below. These results are comparable to correlations of the Biosite Triage Myoglobin Assay verses other clinical analyzers, (N=112) 1.25x+38.8; = 943 and (N=108) 1.31x+17.0; r=.877.

### Table 1-2

| Population | n | Slope (y =) | Intercept | r |
|---------------------------|-----|-------------|-----------|------|
| Patients with suspect AMI | 219 | 1.0059x | 29.576 | .928 |
| Normal Individuals | 196 | 1.3831x | 15.609 | .889 |
| Combined Populations | 415 | 1.0309x | 25.905 | .932 |

#### 7. Conclusion

The RAMP Myoglobin Assay when utilized with the RAMP Reader are substantially equivalent to other assays currently in commercial distribution for the measurement of myoglobin.

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Image /page/3/Picture/1 description: The image shows the seal of the U.S. Department of Health and Human Services. The seal features a stylized eagle with three stripes forming its wing, enclosed within a circle. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged around the circumference of the circle.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

# DEC 1 8 2001

Mr. William Radvak President and CEO Response Biomedical Corp. 8855 Northbrook Court Burnaby, B.C. V5J 5J1

k012040 Re:

Trade/Device Name: RAMPTM Myoglobin Assay; RAMP Reader Regulation Number: 21 CFR 866. 5680; 21 CFR 862.2560 Regulation Name: Myoglobin immunological test system; Fluorometer for clinical use Regulatory Class: Class II; Class I Product Code: DDR; KHO Dated: October 30, 2001 Received: October 31, 2001

Dear Mr. Radvak:

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 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 Part 801); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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Page 2 -

This letter will allow you to begin marketing your device as described in your 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and ' additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at [phone]. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at [phone]. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers International and Consumer Assistance at its toll-free number [phone] or [phone] or at its internet address "http://www.fda.gov/cdrh/dsma/dsmamain.html".

Sincerely yours,

Steven Sutman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory-Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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### STATEMENT OF INDICATIONS FOR USE 2.0

K012040 510(k) Number (if known):

Indications for Use:

The RAMP Reader is a general use fluorometer that analyzes results produced by immunoassays that use a fluorophore having an excitation wavelength at 560 nm and an emission wavelength of 610 nm.

The RAMP™ Myoglobin Assay is an immunochromatographic test for the quantitative determination of myoglobin in human EDTA whole blood, using the RAMP Reader.

Nora O'Neill & Jean Cooper

(Division Sign-Off) Division of Clinical Labora. יווי וינטנג Koj 2040 510(k) Number.

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE OF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

(Optional Format 3-10-98)