MODIFICATION TO: RAMP INFLUENZA A/B ASSAY

K093116 · Response Biomedical Corp. · PSZ · Oct 21, 2009 · Microbiology

Device Facts

• Record ID: K093116
• Device Name: MODIFICATION TO: RAMP INFLUENZA A/B ASSAY
• Applicant: Response Biomedical Corp.
• Product Code: PSZ · Microbiology
• Decision Date: Oct 21, 2009
• Decision: SESE
• Submission Type: Special
• Regulation: 21 CFR 866.3328
• Device Class: Class 2

Intended Use

The RAMP® Influenza A/B Assay is a qualitative immunochromatographic assay used to identify the presence of Influenza A and Influenza B nucleoprotein antigens in nasal wash, nasal aspirate, nasopharyngeal aspirate, and nasopharyngeal swab specimens from symptomatic patients. It is an in vitro diagnostic assay that aids in the rapid differential diagnosis of influenza viral infections in symptomatic patients. A negative test is presumptive and it is recommended these results be confirmed by cell culture. Negative results do not preclude influenza virus infection and should not be used as the sole basis for treatment or other management decisions. The test performance characteristics for Influenza B were established primarily with retrospective, frozen specimens. Users may wish to further evaluate the sensitivity performance of this test for Influenza B using fresh samples.

Device Story

RAMP Influenza A/B Assay is a qualitative immunochromatographic test for detecting Influenza A and B nucleoprotein antigens. Input: nasal wash, nasal aspirate, nasopharyngeal aspirate, or nasopharyngeal swab samples mixed with buffer. Process: sample migrates along a test cartridge strip; fluorescent-dyed latex particles coated with anti-Influenza A/B antibodies bind to viral antigens; complexes captured at specific detection zones and an internal standard zone. The RAMP 200 instrument measures fluorescence at these zones. Output: RAMP Ratio calculated by instrument; compared against pre-defined thresholds to determine positive/negative results. Used in clinical settings to aid rapid differential diagnosis. Benefits: provides rapid identification of influenza infection, though negative results are presumptive and require culture confirmation.

Clinical Evidence

Bench testing only. Analytical reactivity evaluated using an isolate strain of Influenza A (Swine NY/02/2009) in Copan UTM. Reactivity determined to be 1.0x10^2 TCID50/mL. No clinical performance data provided for 2009 H1N1 influenza virus.

Technological Characteristics

Qualitative immunochromatographic assay. Utilizes fluorescent-dyed latex particles coated with anti-Influenza A and anti-Influenza B antibodies. Requires RAMP 200 instrument for fluorescence measurement and ratio calculation. Sample types: nasal wash, nasal aspirate, nasopharyngeal aspirate, nasopharyngeal swab.

Indications for Use

Indicated for symptomatic patients requiring differential diagnosis of Influenza A and B viral infections via nasal wash, nasal aspirate, nasopharyngeal aspirate, or nasopharyngeal swab specimens.

Regulatory Classification

Identification

An influenza virus antigen detection test system is a device intended for the qualitative detection of influenza viral antigens directly from clinical specimens in patients with signs and symptoms of respiratory infection. The test aids in the diagnosis of influenza infection and provides epidemiological information on influenza. Due to the propensity of the virus to mutate, new strains emerge over time which may potentially affect the performance of these devices. Because influenza is highly contagious and may lead to an acute respiratory tract infection causing severe illness and even death, the accuracy of these devices has serious public health implications.

Special Controls

*Classification.* Class II (special controls). The special controls for this device are:(1) The device's sensitivity and specificity performance characteristics or positive percent agreement and negative percent agreement, for each specimen type claimed in the intended use of the device, must meet one of the following two minimum clinical performance criteria: (i) For devices evaluated as compared to an FDA-cleared nucleic acid based-test or other currently appropriate and FDA accepted comparator method other than correctly performed viral culture method: (A) The positive percent agreement estimate for the device when testing for influenza A and influenza B must be at the point estimate of at least 80 percent with a lower bound of the 95 percent confidence interval that is greater than or equal to 70 percent. (B) The negative percent agreement estimate for the device when testing for influenza A and influenza B must be at the point estimate of at least 95 percent with a lower bound of the 95 percent confidence interval that is greater than or equal to 90 percent. (ii) For devices evaluated as compared to correctly performed viral culture method as the comparator method: (A) The sensitivity estimate for the device when testing for influenza A must be at the point estimate of at least 90 percent with a lower bound of the 95 percent confidence interval that is greater than or equal to 80 percent. The sensitivity estimate for the device when testing for influenza B must be at the point estimate of at least 80 percent with a lower bound of the 95 percent confidence interval that is greater than or equal to 70 percent. (B) The specificity estimate for the device when testing for influenza A and influenza B must be at the point estimate of at least 95 percent with a lower bound of the 95 percent confidence interval that is greater than or equal to 90 percent. (2) When performing testing to demonstrate the device meets the requirements in paragraph (b)(1) of this section, a currently appropriate and FDA accepted comparator method must be used to establish assay performance in clinical studies. (3) Annual analytical reactivity testing of the device must be performed with contemporary influenza strains. This annual analytical reactivity testing must meet the following criteria: (i) The appropriate strains to be tested will be identified by FDA in consultation with the Centers for Disease Control and Prevention (CDC) and sourced from CDC or an FDA-designated source. If the annual strains are not available from CDC, FDA will identify an alternative source for obtaining the requisite strains. (ii) The testing must be conducted according to a standardized protocol considered and determined by FDA to be acceptable and appropriate. (iii) By July 31 of each calendar year, the results of the last 3 years of annual analytical reactivity testing must be included as part of the device's labeling. If a device has not been on the market long enough for 3 years of annual analytical reactivity testing to have been conducted since the device received marketing authorization from FDA, then the results of every annual analytical reactivity testing since the device received marketing authorization from FDA must be included. The results must be presented as part of the device's labeling in a tabular format, which includes the detailed information for each virus tested as described in the certificate of authentication, either by: (A) Placing the results directly in the device's § 809.10(b) of this chapter compliant labeling that physically accompanies the device in a separate section of the labeling where the analytical reactivity testing data can be found; or (B) In the device's label or in other labeling that physically accompanies the device, prominently providing a hyperlink to the manufacturer's public Web site where the analytical reactivity testing data can be found. The manufacturer's home page, as well as the primary part of the manufacturer's Web site that discusses the device, must provide a prominently placed hyperlink to the Web page containing this information and must allow unrestricted viewing access. (4) If one of the actions listed at section 564(b)(1)(A)-(D) of the Federal Food, Drug, and Cosmetic Act occurs with respect to an influenza viral strain, or if the Secretary of Health and Human Services (HHS) determines, under section 319(a) of the Public Health Service Act, that a disease or disorder presents a public health emergency, or that a public health emergency otherwise exists, with respect to an influenza viral strain: (i) Within 30 days from the date that FDA notifies manufacturers that characterized viral samples are available for test evaluation, the manufacturer must have testing performed on the device with those viral samples in accordance with a standardized protocol considered and determined by FDA to be acceptable and appropriate. The procedure and location of testing may depend on the nature of the emerging virus. (ii) Within 60 days from the date that FDA notifies manufacturers that characterized viral samples are available for test evaluation and continuing until 3 years from that date, the results of the influenza emergency analytical reactivity testing, including the detailed information for the virus tested as described in the certificate of authentication, must be included as part of the device's labeling in a tabular format, either by: (A) Placing the results directly in the device's § 809.10(b) of this chapter compliant labeling that physically accompanies the device in a separate section of the labeling where analytical reactivity testing data can be found, but separate from the annual analytical reactivity testing results; or (B) In a section of the device's label or in other labeling that physically accompanies the device, prominently providing a hyperlink to the manufacturer's public Web site where the analytical reactivity testing data can be found. The manufacturer's home page, as well as the primary part of the manufacturer's Web site that discusses the device, must provide a prominently placed hyperlink to the Web page containing this information and must allow unrestricted viewing access.

Predicate Devices

• RAMP® Influenza A/B Assay (k071591)

Submission Summary (Full Text)

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# OCT 2 1 2009

## 510(K) SUMMARY OF SAFETY AND EFFECTIVENESS

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.

The assigned 510(k) number is: k093116.

The purpose of this 510(k) submission is to provide additional Analytical Reactivity information for the currently 510(k) cleared RAMP® Influenza A/B Assay (k071591).

### Establishment:

Response Biomedical Corporation 1781 - 75th Avenue West Vancouver, British Columbia Canada, V6P 6P2

Tel: [phone] Fax: [phone]

Ken Pilarim Contact: Director - Quality / Regulatory

16 October 2009 Prepared:

### Requlatory Information:

| Trade Name: | RAMP® Influenza A/B Assay |
|----------------------|------------------------------------------------|
| Common Name: | Influenza A/B immunological test system |
| Classification Name: | Influenza A/B immunological test system |
| Regulation Number: | 866.3330, Influenza virus serological reagents |
| Classification: | Class I |
| Product Code: | GNX |
| Panel: | Microbiology |

### Predicate Device:

Immunoassay:

RAMP® Influenza A/B Assay, k071591

### Intended Use

The RAMP® Influenza A/B Assay is a qualitative immunochromatographic assay used to identify the presence of Influenza A and Influenza B nucleoprotein antigens in nasal wash, nasal aspirate, nasopharyngeal aspirate, and nasopharyngeal swab specimens from symptomatic patients. It is an in vitro diagnostic assay that aids in the rapid differential diagnosis of influenza viral infections in symptomatic patients. A negative test is presumptive and it is recommended these results be confirmed by cell culture. Negative results do not preclude influenza virus infection and should not be used as the sole basis for treatment or other management decisions.

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The test performance characteristics for Influenza B were established primarily with retrospective, frozen specimens. Users may wish to further evaluate the sensitivity performance of this test for Influenza B using fresh samples.

# RAMP Description of the Device:

The RAMP Influenza A/B Assay is a qualitative immunochromatographic test that utilizes the RAMP 200 instrument for the differential determination of Influenza B in nasal wash/aspirate, nasopharyngeal aspirate, and nasopharyngeal swab samples. A wash/aspirate or swab sample is mixed with Sample buffer and applied into the sample well of the Test Cartidge. The sample migrates along the strip. Fluorescent-dyed latex (test) particles, coated with anti-Influenza A and anti-Influenza B antibodies bind to Influenza A or B antigens, respectively, if present in the sample. As the sample migrates along the strip, Influenza-bound particles are captured at either the Influenza A or the Influenza B detection zone, and additional particles are captured at the internal standard zone.

The instrument then measures the amount of fluorescence emitted by the complexes at the two detection zones (Influenza A and Influenza B) and at the internal standard zone. The instrument calculates a ratio (RAMP Ratio) using the fluorescence reading of each detection zone (A or B) and the internal standard zone. The instrument compares these ratios to pre-defined threshold limits to determine a positive or negative result for Influenza B in the tested sample.

| Characteristic | Predicate RAMP Influenza A/B Assay<br>(k071591) | RAMP Influenza A/B Assay<br>Additional Analytical Sensitivity<br>(k093116) |
|---------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------|
| Intended Use | The RAMP® Influenza A/B Assay is a<br>qualitative immunochromatographic assay<br>used to identify the presence of Influenza<br>A and Influenza B nucleoprotein antigens<br>in nasal wash, nasal aspirate,<br>nasopharyngeal aspirate, and<br>nasopharyngeal swab specimens from<br>symptomatic patients. It is an in vitro<br>diagnostic assay that aids in the rapid<br>differential diagnosis of influenza viral<br>infections in symptomatic patients. A<br>negative test is presumptive and it is<br>recommended these results be confirmed<br>by cell culture. Negative results do not<br>preclude influenza virus infection and<br>should not be used as the sole basis for<br>treatment or other management decisions. | Same |
| Assay Type | Qualitative for differential determination of<br>Influenza A and Influenza B | Same |
| Test<br>Methodology | Rapid immunochromatographic tests used<br>for the detection of influenza virus antigen<br>utilizing antibodies targeted toward the<br>nucleoprotein (NP) of the virus and thus do<br>not require viable virus particles for<br>detection. | Same |

# Comparison of Technological Characteristics:

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| Characteristic | Predicate RAMP Influenza A/B Assay<br>(k071591) | RAMP Influenza A/B Assay<br>Additional Analytical Sensitivity<br>(k093116) |
|----------------|--------------------------------------------------------------------------|----------------------------------------------------------------------------|
| Sample Type | Nasal wash/aspirate, nasopharyngeal<br>aspirate, and nasopharyngeal swab | Same |

### Summary of Studies:

# ANALYTICAL PERFORMANCE CHARACTERISTICS

### Analytical Reactivity

The RAMP Influenza A/B Assay was evaluated for analytical reactivity by testing an isolate strain of Influenza A (Swine NY/02/2009) prepared in Copan UTM. The isolate was tested at different dilutions to find the lowest concentration that would consistently give positive results. Five (5) replicates were tested at each concentration. The reactivity for Influenza A/Swine NY/02/2009 was determined to be 1.0x102 TCID50/mL.

| Titer tested<br>(TCID50/mL) | Flu A Result | Flu B Result |
|-----------------------------|--------------|--------------|
| $1 \times 10^5$ | 5/5 Pos | 5/5 Neg |
| $1 \times 10^4$ | 5/5 Pos | 5/5 Neg |
| $1 \times 10^3$ | 5/5 Pos | 5/5 Neg |
| $1 \times 10^2$ | 5/5 Pos | 5/5 Neg |
| $1 \times 10^1$ | 5/5 Neg | 5/5 Neg |

Although the RAMP Influenza A/B Assay has been shown to detect the 2009 H1N1 influenza virus in one culture isolate, the performance characteristics of this device with clinical specimens that are positive for the 2009 H1N1 influenza virus have not been established. The RAMP Influenza A/B Assay can distinguish between influenza A and B viruses, but it cannot differentiate influenza subtypes.

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Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized caduceus symbol, which is often associated with medicine and healthcare. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES-USA" is arranged around the symbol in a circular fashion.

Food and Drug Administration 10903 New Hampshire Avenue Document Mail Center - WO66-G609 Silver Spring, MD 20993-0002

OCT 12 1 2009

Ken L. Pilgrim, P.Eng. Director. Quality / Regulatory Response Biomedical Corporation 1781 - 75th Avenue W. Vancouver, BC V6P 6P2

Re: k093116

Trade/Device Name: RAMP Influenza A/B Assay Regulation Number: 21 CFR 866.3330 Regulation Name: Influenza Virus Serological Reagents Regulatory Class: Class I Product Code: GNX Dated: September 30, 2009 Received: October 2, 2009

Dear Mr. Pilgrim:

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 class II (Special Controls), 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 of medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the auality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of

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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 Parts 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at [phone]. 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 [phone] or [phone] or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely vours,

Sall attopm

Sally A. Hojvat, Ph.D. Director, Division of Microbiology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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### STATEMENT OF INDICATIONS FOR USE

### Indications for Use

510(k) Number (if known): 093116

Device Name: RAMP® Influenza A/B Assay

Indications for Use:

The RAMP® Influenza A/B Assay is a qualitative immunochromatographic assay used to identify the presence of Influenza A and Influenza B nucleoprotein antigens in nasal wash, nasal aspirate, nasopharyngeal aspirate, and nasopharyngeal swab specimens from symptomatic patients. It is an in vitro diagnostic assay that aids in the rapid differential diagnosis of influenza viral infections in symptomatic patients. A negative test is presumptive and it is recommended these results be confirmed by cell culture. Negative results do not preclude influenza virus infection and should not be used as the sole basis for treatment or other management decisions.

The test performance characteristics for Influenza B were established primarily with retrospective, frozen specimens. Users may wish to further evaluate the sensitivity performance of this test for Influenza B using fresh samples.

Prescription Use × (21 CFR Part 801 Subpart D) And/Or

Over the Counter Use _ (21 CFR Part 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)

Uwe Scherf

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) le093il6