Predicate Devices

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The device description details a standard immunochromatographic assay read by an instrument that measures fluorescence and compares ratios to pre-defined thresholds. There is no mention of AI or ML in the description, performance studies, or key metrics.

Therapeutic

No
This device is an in vitro diagnostic assay used for the rapid differential diagnosis of influenza viral infections. It does not provide any therapeutic function.

Diagnostic

Yes

The RAMP® Influenza A/B Assay is described as an "in vitro diagnostic assay that aids in the rapid differential diagnosis of influenza viral infections in symptomatic patients." Its purpose is to identify the presence of Influenza A and B nucleoprotein antigens, which directly relates to diagnosing a condition.

SaMD (Software as a Medical Device)

No

The device description explicitly states it utilizes the "RAMP 200" instrument to measure fluorescence and calculate results, indicating a hardware component is essential to the device's function.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

The "Intended Use / Indications for Use" section explicitly states: "It is an in vitro diagnostic assay that aids in the rapid differential diagnosis of influenza viral infections in symptomatic patients."

This statement directly identifies the device as an in vitro diagnostic assay.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / 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.

Product codes (comma separated list FDA assigned to the subject device)

GNX

Device Description

The RAMP Influenza A/B Assay is a qualitative immunochromatographic test that utilizes the RAMP 200 for the differential determination of Influenza B in nasal wash, nasal aspirate, nasopharyngeal aspirate, and nasopharyngeal swab samples. A wash/aspirate or swab sample is added to the Sample Buffer. The Sample Buffer is optimized to improve binding of the anti-influenza antibodies to the nucleoprotein antigens and reduce non-specific binding and fluorescent signal background. This sample is then mixed using the Assay Tip containing fluorescent-dyed particles conjugated to specific antibodies and applied into the sample well of the Test Cartridge. The sample migrates along the strip. Fluorescent-dyed 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 excess fluorescent- dyed 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.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

nasal cavity or nasopharynx

Indicated Patient Age Range

Not Found

Intended User / Care Setting

central laboratory, stat-lab and point-of-care facilities

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Not Found

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

ANALYTICAL PERFORMANCE CHARACTERISTICS

Assay Precision: Evaluation using a panel of high negative, LoD positive, and 2x LoD positive samples for Influenza A and B (strains: Influenza A/Hong Kong/8/68 and Influenza B/Lee/40). Multiple operators across multiple sites tested replicates of each sample on 5 different days.
- Sample Size: 540 samples (180 per site)
- Results: 100% agreement (540/540) with expected test results for all specimens tested. No significant differences within run, between run, operators, or sites. The overall RAMP Ratio %CV across all sites ranged from 9.6% to 15.1%.
Analytical Sensitivity: Evaluated by testing 2 strains of Influenza A (Hong Kong/8/68 and PR/8/34) and 2 strains of Influenza B (Lee/40 and Allen/45) at LoD, cut-off, and high negative concentrations in VTM or PBS.
- Sample Size: Not explicitly stated for total test runs but involves multiple strains and conditions.
- Results: LoD ranged from 3.0x10^2 to 6.4x10^2 EID50/mL for Influenza A strains and 2.8x10^2 to 7.1x10^4 EID50/mL for Influenza B strains.
Analytical Reactivity: Tested 5 strains of Influenza A (FM/1/47, NWS/33, New Jersey/8/76, Aichi/2/68, and Victoria/3/75) and 3 strains of Influenza B (GL/1739/54, Taiwan/2/62, and Hong Kong/5/72) prepared in VTM at concentrations to consistently give positive results. 5 replicates were tested for each viral strain.
- Results: Analytical reactivity was established for all strains, with concentrations ranging from 3.0x10^2 EID50/mL for Influenza A strains and 1.6x10^1 to 9.5x10^3 EID50/mL for Influenza B strains. 100% Flu A Positive or 100% Flu B Positive results were observed for all tested concentrations of infectious agents.
Analytical Specificity (Potential Cross-Reactive Organisms): Tested a panel of 15 viruses and 17 bacteria. n=3 replicates each.
- Results: None of the organisms tested gave a positive result.
Interference: Evaluated whole blood and potentially interfering substances (medications, OTC products) added to negative and positive (LoD, 2x LoD) samples for Influenza A/B (strains: Influenza A/Hong Kong/8/68 and Influenza B/Lee/40). n=3 replicates tested.
- Results: 100% agreement with expected results. None of the substances tested interfered with test results.
Transport Media Compatibility: Evaluated six commercially available and two clinical-site-prepared transport media using negative, LoD positive, and 2x LoD positive samples for Influenza A/B (strains: Influenza A/Hong Kong/8/68 and Influenza B/Lee/40).
- Results: None of the tested transport media interfered with the performance. All influenza positive samples tested 100% positive and negative samples 100% negative.
Sample Collection Swabs Compatibility: Evaluated four swab materials (Foam, Polyester, Rayon, Nylon) using negative, LoD positive, and 2x LoD positive samples for Influenza A/B (strains: Influenza A/Hong Kong/8/68 and Influenza B/Lee/40). Each swab was dosed and extracted into Copan Universal Transport media.
- Results: Negative samples tested negative. At least 67% of each swab type inoculated with Influenza B at the LoD tested positive.

CLINICAL PERFORMANCE

Method Comparison (Prospective Testing): Comparison to cell culture in a multi-center trial (2006-2007 influenza season).
- Sample Size: 844 fresh specimens (nasal wash/aspirate, nasopharyngeal aspirate, or nasopharyngeal swab).
- Data Source: Four independent laboratories in North America.
- Annotation Protocol: Specimens were collected from symptomatic patients, across approximately equal mix of pediatric (0 – 21 years) and adult (21+ years) patients, and equal numbers of male and female patients. Mean age 28.6 (30.7) years.
- Key Results (Sensitivity/Specificity vs. Culture for Fresh Nasopharyngeal Swab):
  - Age 0-5 (n=211):
    - Influenza A: Sensitivity 91.7% (11/12), Specificity 94.0% (187/199)
    - Influenza B: Sensitivity 100% (1/1), Specificity 97.1% (204/210)
  - Age 6-21 (n=85):
    - Influenza A: Sensitivity 80.0% (12/15), Specificity 94.3% (66/70)
    - Influenza B: Sensitivity 50.0% (2/4), Specificity 95.1% (77/81)
  - Age 22-59 (n=160):
    - Influenza A: Sensitivity 69.6% (16/23), Specificity 99.3% (136/137)
    - Influenza B: Sensitivity 50.0% (2/4), Specificity 99.4% (155/156)
  - Age ≥60 (n=170):
    - Influenza A: Sensitivity 87.5% (14/16), Specificity 98.7% (152/154)
    - Influenza B: Sensitivity 66.7% (2/3), Specificity 99.4% (166/167)
- Key Results (Sensitivity/Specificity vs. Culture for Fresh Wash/Aspirate):
  - Age 0-5 (n=151):
    - Influenza A: Sensitivity 85.7% (24/28), Specificity 95.1% (117/123)
    - Influenza B: Sensitivity 100% (6/6), Specificity 99.3% (144/145)
  - Age 6-21 (n=63):
    - Influenza A: Sensitivity 70.6% (12/17), Specificity 89.1% (41/46)
    - Influenza B: Sensitivity 100% (3/3), Specificity 98.3% (59/60)
  - Age 22-59 (n=3):
    - Influenza A: Sensitivity NA (0/0), Specificity 100% (3/3)
    - Influenza B: Sensitivity NA (0/0), Specificity 100% (3/3)
  - Age ≥60 (n=1):
    - Influenza A: Sensitivity NA (0/0), Specificity 100% (1/1)
    - Influenza B: Sensitivity NA (0/0), Specificity 100% (1/1)
- Overall Sensitivity/Specificity by Collection Type (Fresh Nasopharyngeal Swab, n=626):
  - Influenza A: Sensitivity 80.3% (53/66), Specificity 96.6% (541/560)
  - Influenza B: Sensitivity 58.3% (7/12), Specificity 98.0% (602/614)
- Overall Sensitivity/Specificity by Collection Type (Fresh Nasal Wash/Aspirate, n=218):
  - Influenza A: Sensitivity 80.0% (36/45), Specificity 93.6% (162/173)
  - Influenza B: Sensitivity 100% (9/9), Specificity 99.0% (207/209)
Method Comparison (Retrospective Testing): Evaluation comparing to original cell culture performed using fresh specimens.
- Sample Size: 75 retrospective frozen clinical nasopharyngeal swab samples and 130 retrospective frozen clinical wash/aspirate samples.
- Data Source: Two independent laboratories.
- Key Results (Positive/Negative Percent Agreements for Frozen Nasopharyngeal Swab, n=75):
  - Influenza A: Positive Percent Agreement 84.6% (11/13), Negative Percent Agreement 100% (62/62)
  - Influenza B: Positive Percent Agreement 76.7% (23/30), Negative Percent Agreement 100% (45/45)
- Key Results (Positive/Negative Percent Agreements for Frozen Nasal Wash/Aspirate, n=130):
  - Influenza A: Positive Percent Agreement 77.8% (35/45), Negative Percent Agreement 97.6% (83/85)
  - Influenza B: Positive Percent Agreement 84.6% (33/39), Negative Percent Agreement 97.8% (89/91)

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Analytical Performance:

Precision: 100% agreement with expected results. Overall RAMP Ratio %CV across all sites ranged from 9.6% to 15.1%.
Analytical Sensitivity (LoD):
- Influenza A: 3.0x10^2 to 6.4x10^2 EID50/mL
- Influenza B: 2.8x10^2 to 7.1x10^4 EID50/mL
Analytical Reactivity: 100% positive results for tested viral strains.
Analytical Specificity: 100% negative results for all tested cross-reactive organisms.
Interference: 100% agreement with expected results for samples with interfering substances.

Clinical Performance (Sensitivity and Specificity relative to Cell Culture):

Fresh Nasopharyngeal Swab (Overall, n=626):
- Influenza A: Sensitivity 80.3%, Specificity 96.6%
- Influenza B: Sensitivity 58.3%, Specificity 98.0%
Fresh Nasal Wash/Aspirate (Overall, n=218):
- Influenza A: Sensitivity 80.0%, Specificity 93.6%
- Influenza B: Sensitivity 100%, Specificity 99.0%
Retrospective Frozen Nasopharyngeal Swab (n=75):
- Influenza A: Positive Percent Agreement 84.6%, Negative Percent Agreement 100%
- Influenza B: Positive Percent Agreement 76.7%, Negative Percent Agreement 100%
Retrospective Frozen Nasal Wash/Aspirate (n=130):
- Influenza A: Positive Percent Agreement 77.8%, Negative Percent Agreement 97.6%
- Influenza B: Positive Percent Agreement 84.6%, Negative Percent Agreement 97.8%

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.

K062109

Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).

Not Found

Regulation Number and Section

§ 866.3328 Influenza virus antigen detection test system.

(a)
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.(b)
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.

Summary

0

APR 1 6 2008

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: _______________________________________________________________________________________________________________________________________________

Establishment:

Response Biomedical Corporation 100-8900 Glenlyon Parkway Burnaby, British Columbia Canada, V5J 5J8

Tel: (604) 456-6010 Fax: (604) 456-6066

Ken Pilgrim Contact: Director - Quality / Regulatory

Prepared: April 15, 2008

Regulatory 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:

lmmunoassay:

BinaxNOW® Influenza A & B Test, (K062109), which is currently marketed by Binax, Inc.

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.

1

Description of the Device:

The RAMP Influenza A/B Assay is a qualitative immunochromatographic test that utilizes the RAMP 200 for the differential determination of Influenza B in nasal wash, nasal aspirate, nasopharyngeal aspirate, and nasopharyngeal swab samples. A wash/aspirate or swab sample is added to the Sample Buffer. The Sample Buffer is optimized to improve binding of the anti-influenza antibodies to the nucleoprotein antigens and reduce non-specific binding and fluorescent signal background. This sample is then mixed using the Assay Tip containing fluorescent-dyed particles conjugated to specific antibodies and applied into the sample well of the Test Cartridge. The sample migrates along the strip. Fluorescent-dyed 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 excess fluorescent- dyed 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.

Comparison of Technological Characteristics:

The RAMP Influenza A/B Assay and BinaxNOW Influenza A & B Test are rapid immunochromatographic tests used for the detection of influenza virus antigen utilizing antibodies targeted toward the nucleoprotein (NP) of the virus and thus do not require viable virus particles for detection. The RAMP and BinaxNOW tests provide results in approximately 15 minutes. Viral cell culture relies on the growth of cell lines and their infection with virus contained in the clinical sample. The time required to get a definitive result using these culture methods can be up to 30 days depending on the samples and methods used.

The RAMP Influenza A/B Assay and BinaxNOW Influenza A & B Test are for use in the central laboratory, stat-lab and point-of-care facilities, while viral cell culture is for use in the central laboratories due to its requirement for specialized equipment and highly trained operators.

These methods are indicated for use in the differential determination of Influenza B in nasal wash/aspirate, nasopharyngeal aspirate, and nasopharyngeal swab samples.

Summary of Studies:

ANALYTICAL PERFORMANCE CHARACTERISTICS

Assay Precision

The total intra-assay and inter-assay precision of the RAMP Influenza A/B Assay was evaluated using a panel consisting of high negative Influenza A, Influenza A LoD (Limit of Detection) positive, Influenza A 2x LoD positive, high negative Influenza B, Influenza B LoD positive, and Influenza B 2x LoD positive samples. The influenza strains used to prepare the samples were Influenza A/Hong Kong/8/68 and Influenza B/Lee/40 following viral titer determinations. Multiple operators across multiple sites tested replicates of each sample on 5 different days. There was 100% (540/540) agreement with the expected test results for all specimens tested, with no significant differences within run (same operator on same day), between run, operators, or sites. The RAMP Flu A/B assay is a qualitative assay based on numerical RAMP Ratio values. The overall RAMP Ratio %CV across all sites ranged from 9.6% to 15.1% depending upon analyte type and concentration tested.

2

| Panel
Member ID | Influenza A
High
Negative | Influenza A
Low
Positive | Influenza A
Medium
Positive | Influenza B
High
Negative | Influenza B
Low
Positive | Influenza B
Medium
Positive | Total
Agreement
All (%) | |
|---------------------------|--------------------------------------------------|--------------------------------|-----------------------------------|---------------------------------|--------------------------------|-----------------------------------|-------------------------------|-------------------|
| Viral Titer
(EID50/mL) | 50 | 300 | 600 | 60 | 316 | 632 | | |
| Site 1 | Agreement
with
Expected
result | 30/30 | 30/30 | 30/30 | 30/30 | 30/30 | 30/30 | 180/180
(100%) |
| | % CV | 11.6% | 6.3% | 7.9% | 16.4% | 8.9% | 7.9% | |
| Site 2 | Agreement
with
Expected
result | 30/30 | 30/30 | 30/30 | 30/30 | 30/30 | 30/30 | 180/180
(100%) |
| | % CV | 7.7% | 8.1% | 9.3% | 15.6% | 9.5% | 7.0% | |
| Site 3 | Agreement
with
Expected
result | 30/30 | 30/30 | 30/30 | 30/30 | 30/30 | 30/30 | 180/180
(100%) |
| | % CV | 14.5% | 9.9% | 13.5% | 11.3% | 9.5% | 10.5% | |
| | Total
Agreement
with
Expected
result | 90/90
(100%) | 90/90
(100%) | 90/90
(100%) | 90/90
(100%) | 90/90
(100%) | 90/90
(100%) | 540/540
(100%) |
| | 95% Cl | 96%-100% | 96%-100% | 96%-100% | 96%-100% | 96%-100% | 96%-100% | 99%-100% |
| | Overall
% CV | 11.9% | 10.4% | 12.6% | 15.1% | 10.6% | 9.6% | |

Analytical Sensitivity

The RAMP Influenza A/B Assay was evaluated for analytical sensitivity after was determined by testing 2 strains of Influenza A (Hong Kong/8/68 and PR/8/34) and 2 strains of Influenza B (Lee/40 and Allen/45) at the Limit of Detection (LoD) concentration, the cut-off concentration, and at a high negative concentration in either VTM (Viral Transport Medium, to simulate a swab sample type) or PBS (Phosphate Buffered Saline, to simulate a wash sample type). Although the specific influenza strains causing infection in humans can vary year to year, all contain the conserved nucleoproteins targeted by the RAMP Influenza A/B Assay. Analytical sensitivity (LoD) ranged from 3.0x102 to 6.4x102 ElDgomL for the Influenza A strains and 2.8x102 to 7.1x104 EID50/mL for the Influenza B strains in VTM and PBS.

Viral Strain	LoD Concentration
Influenza A/Hong Kong/8/68 (H3N2),
ATCC VR-544 in VTM	3.0 X $10^2$ EID50/mL
Influenza A/Hong Kong/8/68 (H3N2),
ATCC VR-544 in PBS	5.0 X $10^2$ EID50/mL
Influenza A/PR/8/34 (H1N1),
ATCC VR-95 in VTM	2.0 X $10^2$ EID50/mL
Influenza A/PR/8/34 (H1N1),
ATCC VR-95 in PBS	6.4 X $10^2$ EID50/mL
Influenza B/Lee/40,
ATCC VR-101 in VTM	3.2 X $10^2$ EID50/mL
Influenza B/Lee/40,
ATCC VR-101 in PBS	2.8 X $10^2$ EID50/mL
Influenza B/Allen/45,
ATCC VR-102 in VTM	5.3 X $10^4$ EID50/mL
Influenza B/Allen/45,
ATCC VR-102 in PBS	7.1 X $10^4$ EID50/mL

3

Analytical Reactivity

The RAMP Influenza A/B Assay was evaluated for analytical reactivity by testing of Influenza A (FM/1/47, NWS/33, New Jersey/8/76, Aichi/2/68, and Victoria/3/75) and 3 strains of Influenza B (GL/1739/54, Taiwan/2/62, and Hong Kong/5/72) prepared in VTM at concentrations that would consistently give positive results. Five (5) replicates were tested for each viral strain. The viral titers of these influenza strains were determined prior to analytical sensitivity testing. Analytical reactivity was established for the 5 Influenza A and 3 Influenza B strains tested. The concentrations for reactivity ranged from 3.0x102 EIDsy/mL for the Influenza A strains and 1.6x10 to 9.5x10 EID50/mL for the Influenza B strains.

| Strain | Reactivity
Concentration | RAMP Result |
|----------------------------------------------------|-----------------------------|---------------------|
| Influenza A/FM/1/47 (H1N1)
ATCC VR-97 | 3.0 X 103 EID50/mL | 100% Flu A Positive |
| Influenza A/NWS/33 (H1N1)
ATCC VR-219 | 3.0 X 102 EID50/mL | 100% Flu A Positive |
| Influenza A/New Jersey/8/76
(H1N1), ATCC VR-897 | 3.0 X 102 EID50/mL | 100% Flu A Positive |
| Influenza A/Aichi/2/68 (H3N2)
ATCC VR-547 | 9.0 X 102 EID50/mL | 100% Flu A Positive |
| Influenza A/Victoria/3/75
(H3N2), ATCC VR-822 | 9.0 X 102 EID50/mL | 100% Flu A Positive |
| Influenza B/GL/1739/54
ATCC VR-103 | 9.5 X 103 EID50/mL | 100% Flu B Positive |
| Influenza B/Taiwan/2/62
ATCC VR-295 | 1.6 X 101 EID50/mL | 100% Flu B Positive |
| Influenza B/Hong Kong/5/72
ATCC VR-823 | 6.3 X 103 EID50/mL | 100% Flu B Positive |

Analytical Specificity (Potential Cross-Reactive Organisms)

The analytical specificity of the RAMP Influenza A/B Assay was determined by testing a panel consisting of 15 viruses and 17 bacteria that may be present in the nasal cavity or nasopharynx. Viral and bacterial isolates were tested at the concentrations listed after titer determination at n=3 replicates each. None of the organisms tested cave a positive result in the RAMP Influenza A/B RAMP Influenza A/B Assay potential cross-reactivity with Chlamydophilia Note: Assay. pneumoniae has not been determined.

| Strain/Isolate | Concentration | RAMP Flu A
result | RAMP Flu B
result |
|-----------------------------------|------------------|----------------------|----------------------|
| Adenovirus, Type 1 | 105 TCID50/mL | Negative | Negative |
| Adenovirus, Type 7a | 105.15 TCID50/mL | Negative | Negative |
| Respiratory Syncytial Virus (RSV) | 105 TCID50/mL | Negative | Negative |
| Human coronavirus, strain OC43 | 105 TCID50/mL | Negative | Negative |
| Human coronavirus Strain 229E | 105.23 TCID50/mL | Negative | Negative |
| Cytomegalovirus | 105.15 TCID50/mL | Negative | Negative |
| Enterovirus, Type 71 | 105.15 TCID50/mL | Negative | Negative |
| Epstein Barr Virus | 105 TCID50/ML | Negative | Negative |
| Measles | 105 TCID50/mL | Negative | Negative |

	Specificity; Potential Cross-Reactive Substances

4

| Strain/Isolate result | RAMP Flu B
result |
|----------------------- | Mumps virus | Human Parainfluenza, Type 1 | Human Parainfluenza, Type 2 | Human Parainfluenza, Type 3 | Human metapneumovirus | Human Rhinovirus, Strain 1A | Bordetella pertussis | Corynebacterium Sp. | Escherichia coli | Haemophilus influenzae | Lactobacillus casei | Legionella pneumophila | Moraxella catarrhalis | Mycobacterium | Mycoplasma pneumoniae | Neisseria menigitidis | Neisseria sicca | Pseudomonas aeruginosa | Streptococcus pneumoniae | Streptococcus pyogenes (Group A) | Streptococcus salivarius | Staphylococcus epidermidis | Staphylococcus aureus (Protein A
producer) | 106 cfu/mL | Concentration | RAMP Flu A
------------------------|------------------|----------------------|----------------------|
| 105 TCID50/mL | Negative | Negative |
| 104.75 TCID50/mL | Negative | Negative |
| 105 TCID50/mL | Negative | Negative |
| 105 TCID50/mL | Negative | Negative |
| 105 TCID50/mL | Negative | Negative |
| 105 TCID50/mL | Negative | Negative |
| 106 cfu/mL | Negative | Negative |
| 106 cfu/mL | Negative | Negative |
| 106 cfu/mL | Negative | Negative |
| 106 cfu/mL | Negative | Negative |
| 106 cfu/mL | Negative | Negative |
| 106 cfu/mL | Negative | Negative |
| 106 cfu/mL | Negative | Negative |
tuberculosis avirulent | 106 cfu/mL | Negative | Negative |
| 106 cfu/mL | Negative | Negative |
| 106 cfu/mL | Negative | Negative |
| 106 cfu/mL | Negative | Negative |
| 106 cfu/mL | Negative | Negative |
| 106 cfu/mL | Negative | Negative |
| 106 cfu/mL | Negative | Negative |
| 106 cfu/mL | Negative | Negative |
| 106 cfu/mL | Negative | Negative |
| Negative | Negative |

Interference

Whole blood and a number of other potentially interfering substances (medications and over the counter (OTC) products) that may be present naturally or artificially introduced in the nasal cavity or nasopharynx were evaluated in the RAMP Influenza A/B Assay. The substances were added to a negative sample (viral transport media), an Influenza A LoD positive sample, an Influenza A to a nogative sample, an Influenza B LoD positive sample and an Influenza B 2x LoD positive sample and tested in the RAMP Influenza A/B Assay. The influenza strains used to prepare the samples were Influenza A/Hong Kong/8/68 and Influenza B/Lee/40 following titer determination. There was 100% agreement with expected results for all replicates (for n=3 replicates tested). None of the substances tested at the concentrations indicated interfered with the test results of None of the oubsitive influenza samples in the RAMP Influenza A/B Assay. The RAMP Flu A/B negative and positive assay based on numerical RAMP Ratio values. The Percent of Mean Control Ratio values were calculated using these RAMP Ratios.

Interfering Substances Study Results

| Substance Tested | Conc.
Tested | RAMP Results: Percent of Mean Control Ratio | | | | |
|------------------------------------------|-------------------|---------------------------------------------|--------------------|-----------------------|--------------------|-----------------------|
| | | Negative
FluA / Flu B | Influenza A
LoD | Influenza A
2x LoD | Influenza B
LoD | Influenza B
2x LoD |
| Control
(No interfering
substance) | Not
Applicable | 100% / 100% | 100% | 100% | 100% | 100% |
| Substance Tested | Conc.
Tested | RAMP Results: Percent of Mean Control Ratio | | | | |
| | | Negative
FluA / Flu B | Influenza A
LoD | Influenza A
2x LoD | Influenza B
LoD | Influenza B
2x LoD |
| Fisherman's Friend
Throat Drop | 15% w/v | 120% / 105% | 101% | 103% | 99% | 120% |
| Halls Throat Drop | 15% w/v | 96% / 104% | 101% | 111% | 91% | 111% |
| Cepacol Throat Drop | 15% w/v | 91% / 101% | 98% | 101% | 105% | 118% |
| 4-Acetamidophenol | 10 mg/mL | 110% / 117% | 99% | 100% | 104% | 117% |
| Acetylsalicylic Acid | 15 mg/mL | 89% / 106% | 98% | 97% | 110% | 118% |
| Chloropheniramine | 5 mg/mL | 107% / 110% | 101% | 95% | 112% | 118% |
| Diphenylhydramine | 5 mg/mL | 109% / 126% | 99% | 100% | 115% | 116% |
| Phenylpropanolamine
HCl | 20 mg/mL | 126% / 100% | 91% | 96% | 113% | 113% |
| Oseltamivir Phosphate
(Tamiflu) | 50 mg/mL | 106% / 101% | 105% | 105% | 106% | 111% |
| Rimantadine HCl | 500 ng/mL | 103% / 103% | 105% | 94% | 111% | 113% |
| Ribavirin (Rebetol) | 100 mg/mL | 137% / 136% | 111% | 106% | 118% | 120% |
| Good and Kind
Mouthwash | 20% v/v | 97% / 118% | 97% | 106% | 99% | 125% |
| Cepacol Mouth Wash | 20% v/v | 88% / 85% | 103% | 104% | 98% | 118% |
| Scope Mouthwash | 20% v/v | 88% / 99% | 96% | 94% | 98% | 112% |
| Rhinocort Nasal Spray | 15% v/v | 85% / 88% | 109% | 101% | 90% | 122% |
| Nasonex Nasal Spray | 15% v/v | 104% / 90% | 103% | 106% | 92% | 113% |
| Flonase Nasal Spray | 15% v/v | 103% / 104% | 109% | 100% | 95% | 113% |
| Oxymetazoline HCl | 0.05% v/v | 116% / 95% | 101% | 103% | 97% | 108% |
| Phenylephrine HCl | 10 mg/mL | 126% / 119% | 101% | 99% | 106% | 117% |
| Guaiacol Glycerol Ether
(Benylin) | 20 mg/mL | 166% / 153% | 118% | 113% | 118% | 124% |
| Dextromethorphan | 2 mg/mL | 95% / 101% | 115% | 115% | 126% | 134% |
| Salbutamol Sulfate | 400 ng/mL | 102% / 92% | 98% | 99% | 111% | 116% |
| Substance Tested | Conc.
Tested | RAMP Results: Percent of Mean Control Ratio | | | | |
| | | Negative
FluA / Flu B | Influenza A
LoD | Influenza A
2x LoD | Influenza B
LoD | Influenza B
2x LoD |
| Whole Blood* | 2% v/v | 126%/91% | 75% | 90% | 106% | 98% |

5

6

*A warning is added to the package insert to reflect that samples contaminated with whole blood in greater concentrations (visibly bloody samples) may interfere in the interpretation of the assay.

Transport Media

Six commercially available and two clinical-site-prepared transport media were evaluated for compatibility in the RAMP Influenza A/B Assay by testing a negative sample (transport media only), an Influenza A LoD positive sample, an Influenza A 2x LoD positive sample, an Influenza B LoD positive sample, and an Influenza B 2x LoD positive sample in the RAMP Influenza A/B Assay. The influenza strains used to prepare the samples were Influenza A/Hong Kong/8/68 and Influenza B/Lee/40 following titer determination. The RAMP Flu A/B assay is a qualitative assay based on numerical RAMP Ratio values. The %CVs were calculated for the RAMP Ratios. None of the tested transport media interfered with the performance of the RAMP Influenza A/B Assay.

| Transport Media

Tested	RAMP Results
	Negative	Influenza A
LoD	Influenza A
2x LoD	Influenza B
LoD	Influenza B
2x LoD
Copan Universal
Transport Media
(UTM)	100% Neg	100%
Flu A Pos	100%
Flu A Pos	100%
Flu B Pos	100%
Flu B Pos
Remel M4 Media	100% Neg	100%
Flu A Pos	100%
Flu A Pos	100%
Flu B Pos	100%
Flu B Pos
Remel M4-RT
Media	100% Neg	100%
Flu A Pos	100%
Flu A Pos	100%
Flu B Pos	100%
Flu B Pos
Remel M5 Media	100% Neg	100%
Flu A Pos	100%
Flu A Pos	100%
Flu B Pos	100%
Flu B Pos
Starplex Transport
Media	100% Neg	100%
Flu A Pos	100%
Flu A Pos	100%
Flu B Pos	100%
Flu B Pos
Phosphate
Buffered Saline
(PBS) Solution	100% Neg	100%
Flu A Pos	100%
Flu A Pos	100%
Flu B Pos	100%
Flu B Pos
Site B In-house
Media	100% Neg	100%
Flu A Pos	100%
Flu A Pos	100%
Flu B Pos	100%
Flu B Pos
Site A In-house
Media	100% Neg	100%
Flu A Pos	100%
Flu A Pos	100%
Flu B Pos	100%
Flu B Pos
RAMP Ratio % CV	Flu A 19%
Flu B 13%	4%	9%	7%	11%

Sample Collection Swabs

Four swab materials were evaluated for compatibility in the RAMP Influenza A/B Assay by testing a negative sample (swab alone with no virus present), an Influenza A low positive sample (LoD), an Influenza A positive sample (2x LoD), an Influenza B low positive sample (LoD), and an Influenza B positive sample (2x LoD) in the RAMP Influenza A/B Assay. The Flu strains used to prepare the samples were Influenza A/Hong Kong/8/68 and Influenza B/Lee/40 following titer

7

Each swab was dosed with the appropriate sample and extracted into Copan determination. Universal Transport media prior to testing in the RAMP Influenza A/B Assay. The RAMP Flu A/B assay is a qualitative assay based on numerical RAMP Ratio values. The %CVs were calculated based on the RAMP Ratios for the testing. The negative sample (swab alone) tested negative. At least 67% of each swab type inoculated with Influenza B at the LoD tested positive for the virus.

Note: In general, calcium alginate swabs are not recommended because they may be cytotoxic to cells and cause viral culture assay inhibition.2.

	RAMP Results
Swab Material Tested	Negative	Influenza A
LoD	Influenza A
2x LoD	Influenza B
LoD	Influenza B
2x LoD
Foam	100% Neg	100%
Flu A Pos	100%
Flu A Pos	100%
Flu B Pos	100%
Flu B Pos
Polyester	100% Neg	67%
Flu A Pos	100%
Flu A Pos	67 %
Flu B Pos	100%
Flu B Pos
Rayon	100% Neg	100%
Flu A Pos	100%
Flu A Pos	67 %
Flu B Pos	100%
Flu B Pos
Nylon	100% Neg	100%
Flu A Pos	100%
Flu A Pos	100%
Flu B Pos	100%
Flu B Pos
RAMP Ratio % CV	Flu A 17%
Flu B 22%	15%	8%	29%	24%

CLINICAL PERFORMANCE

Method Comparison

The performance of the RAMP Influenza A/B Assay was compared to cell culture in a prospective study conducted as part of a multi-center trial in North America during the 2006-2007 influenza season when influenza A/H3 (36.5%) and A/H1 (63.5%) were the predominant Influenza A viruses in circulation. Four independent laboratories (located in distinct geographic regions) evaluated the RAMP Influenza A/B Assay in parallel with cell culture. Eight hundred forty-four (844) fresh specimens (nasal wash/aspirate, nasopharyngeal aspirate, or nasopharyngeal swab samples) prospectively collected during the 2006-2007 influenza season were tested. Across the sites these samples were drawn from an approximately equal mix of pediatric (0 – 21 years) and adult patients (21+ years) with approximately equal numbers of male and female patients. The mean (standard deviation) age of the patients was 28.6 (30.7) years. In order to supplement the prospective study, performance of the RAMP Influenza A/B Test was also evaluated by two independent laboratories comparing to the original cell culture testing results (cell culture testing was performed using fresh specimens) on 75 retrospective frozen clinical nasopharyngeal swab samples and 130 retrospective frozen clinical wash/aspirate samples.

8

Prospective Testing

Sensitivity and Specificity by Age Relative to Culture – Fresh Nasopharyngeal Swab; Age 0-5

| Prospective Fresh
Nasopharyngeal
Swab

(Age 0-5)		RAMP Influenza A		RAMP Influenza B
Tissue Culture	Positive	Negative	Total	Positive	Negative	Total
Positive	11	1	12	1	0	1
Negative	12	187	199	6	204	210
Total	23	188	211	7	204	211
			95% CI			95% CI
Sensitivity	11/12	91.7%	61.5-99.8%	1/1	100%	NA
Specificity	187/199	94.0%	89.7-96.8%	204/210	97.1%	93.9-98.9%

Sensitivity and Specificity by Age Relative to Culture - Fresh Nasopharyngeal Swab; Age 6-21

| Prospective Fresh
Nasopharyngeal
Swab

(Age 6-21)	RAMP Influenza A			RAMP Influenza B
Tissue Culture	Positive	Negative	Total	Positive	Negative	Total
Positive	12	3	15	2	2	4
Negative	4	66	70	4	77	81
Total	16	69	85	6	79	85
			95% CI			95% CI
Sensitivity	12/15	80.0%	51.9-95.7%	2/4	50.0%	6.8-93.2%
Specificity	66/70	94.3%	86.0-98.4%	77/81	95.1%	87.8-98.6%

Sensitivity and Specificity by Age Relative to Culture - Fresh Nasopharyngeal Swab; Age 22-59

| Prospective Fresh
Nasopharyngeal
Swab

(Age 22-59)	RAMP Influenza A			RAMP Influenza B
Tissue Culture	Positive	Negative	Total	Positive	Negative	Total
Positive	16	7	23	2	2	4
Negative	1	136	137	1	155	156
Total	17	143	160	3	157	160
	95% CI			95% CI
Sensitivity	16/23	69.6%	47.1-86.8%	2/4	50.0%	6.8-93.2%
Specificity	136/137	99.3%	96.0-100%	155/156	99.4%	96.5-100%

Sensitivity and Specificity by Age Relative to Culture – Fresh Nasopharyngeal Swab; Age ≥60

| Prospective Fresh
Nasopharyngeal
Swab

(Age ≥60)	RAMP Influenza A			RAMP Influenza B
Tissue Culture	Positive	Negative	Total	Positive	Negative	Total
Positive	14	2	16	2	1	3
Negative	2	152	154	1	166	167
Total	16	154	170	3	167	170
			95% CI			95% CI
Sensitivity	14/16	87.5%	61.7-98.4%	2/3	66.7%	9.4-99.2%
Specificity	152/154	98.7%	95.4-99.8%	166/167	99.4%	96.7-100%

9

| Prospective Fresh
Nasal
Wash/Aspirate

Tissue Culture	RAMP Influenza A			RAMP Influenza B
	Positive	Negative	Total	Positive	Negative	Total
Positive	24	4	28	6	0	6
Negative	6	117	123	1	144	145
Total	30	121	151	7	144	151
			95% CI			95% CI
Sensitivity	24/28	85.7%	67.3-96.0%	6/6	100%	54.1-100%
Specificity	117/123	95.1%	89.7-98.2%	144/145	99.3%	96.2-100%

Sensitivity and Specificity by Age Relative to Culture - Fresh Wash/Aspirate; Age 0-5

Sensitivity and Specificity by Age Relative to Culture - Fresh Wash/Aspirate; Age 6-21

| Prospective Fresh
Nasal
Wash/Aspirate

Tissue Culture	RAMP Influenza A			RAMP Influenza B
	Positive	Negative	Total	Positive	Negative	Total
Positive	12	5	17	3	0	3
Negative	5	41	46	1	59	60
Total	17	46	63	4	59	63
			95% CI			95% CI
Sensitivity	12/17	70.6%	44.0-89.7%	3/3	100%	29.2-100%
Specificity	41/46	89.1%	76.4-96.4%	59/60	98.3%	91.1-100%

Sensitivity and Specificity by Age Relative to Culture - Fresh Wash/Aspirate; Age 22-59

| Prospective Fresh
Nasal
Wash/Aspirate

Tissue Culture	RAMP Influenza A			RAMP Influenza B
	Positive	Negative	Total	Positive	Negative	Total
Positive	0	0	0	0	0	0
Negative	0	3	3	0	3	3
Total	0	3	3	0	3	3
			95% CI			95% CI
Sensitivity	0/0	NA	NA	0/0	NA	NA
Specificity	3/3	100%	29.2-100%	3/3	100%	29.2-100%

Sensitivity and Specificity by Age Relative to Culture - Fresh Wash/Aspirate; Age ≥60

| Prospective Fresh
Nasal
Wash/Aspirate

(Age ≥60)		RAMP Influenza A			RAMP Influenza B
Tissue Culture	Positive	Negative	Total	Positive	Negative	Total
Positive	0	0	0	0	0	0
Negative	0	1	1	0	1	1
Total	0	1	1	0	1	1
			95% CI			95% CI
Sensitivity	0/0	NA	NA	0/0	NA	NA
Specificity	1/1	100%	NA	1/1	100%	NA

10

| Prospective Fresh
Nasopharyngeal

Swab	RAMP Influenza A			RAMP Influenza B
Tissue Culture	Positive	Negative	Total	Positive	Negative	Total
Positive	53	13	66	7	5	12
Negative	19	541	560	12	602	614
Total	72	554	626	19	607	626
			95% CI			95% CI
Sensitivity	53/66	80.3%	68.7-89.1%	7/12	58.3%	27.7-84.8%
Specificity	541/560	96.6%	94.8-97.9%	602/614	98.0%	96.6-99.0%

Sensitivity and Specificity by Collection Type Relative to Culture - Fresh Nasopharyngeal Swab

Sensitivity and Specificity by Collection Type Relative to Culture - Fresh Wash/Aspirate

| Prospective Fresh
Nasal

Wash/Aspirate	RAMP Influenza A			RAMP Influenza B
Tissue Culture	Positive	Negative	Total	Positive	Negative	Total
Positive	36	9	45	9	0	9
Negative	11	162	173	2	207	209
Total	47	171	218	11	207	218
	95% CI			95% CI
Sensitivity	36/45	80.0%	65.4-90.4%	9/9	100%	66.4-100%
Specificity	162/173	93.6%	88.9-96.8%	207/209	99.0%	96.6-99.9%

Retrospective Testing

In order to supplement the prospective study, performance of the RAMP Influenza A/B Test was also evaluated by two independent laboratories comparing to the original cell culture that alle sythally by by here performed originally using fresh specimens) on 75 retrospective frozen clinical nasopharyngeal swab samples and 130 retrospective frozen clinical wash/aspirate samples. The results of the retrospective clinical trials based on sample type are given in the following tables:

Retrospective Positive and Negative Percent Agreements by Collection Type Relative to Culture; Nasopharyngeal Swab

| Retrospective
Frozen
Nasopharyngeal

Swab		RAMP Influenza A			RAMP Influenza B
Tissue Culture	Positive	Negative	Total	Positive	Negative	Total
Positive	11	2	13	23	7	30
Negative	0	62	62	0	45	45
Total	11	64	75	23	52	75
			95% CI			95% CI
Positive Percent
Agreement	11/13	84.6%	54.5-98.1 %	23/30	76.7%	57.7-90.1%
Negative Percent
Agreement	62/62	100%	94.2-100%	45/45	100%	92.1-100%

11

| Retrospective
Frozen Nasal

Wash/Aspirate	RAMP Influenza A			RAMP Influenza B
Tissue Culture	Positive	Negative	Total	Positive	Negative	Total
Positive	35	10	45	33	6	39
Negative	2	83	85	2	89	91
Total	37	93	130	35	95	130
	95% CI			95% CI
Positive Percent
Agreement	35/45	77.8%	62.9-88.8%	33/39	84.6%	69.5-94.1%
Negative Percent
Agreement	83/85	97.6%	91.8-99.7%	89/91	97.8%	92.3-99.7%

Retrospective Positive and Negative Percent Agreements by Collection Type Relative to Culture; Wash / Aspirate

REFERENCES

·

1 Storch GA, Rapid diagnostic tests for influenza. Current Opinion in Pediatrics 2003, 15:77-84.

2 Lauer and Masters, Journal Clinical Microbiology, 1988 January; 26(1): 54–56

:

3 Centers for Disease Control, Weekly Report: Influenza Summary Update, Week ending May 19, 2007 - Week 20

12

DEPARTMENT OF HEALTH & HUMAN SERVICES

DEPARTMENT OF HEALTH & HUMAN SERVICES (USA)

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Mr. Ken Pilgrim Director - Quality/Regulatory Response Biomedical Corporation 100-8900 Glenlyon Parkway Burnaby, B.C. Canada V5J 5J8

APR 1 6 2008

Re: K071591

Trade/Device Name: RAMP® Influenza A/B Assay Regulation Number: 21 CFR § 866.3330 Regulation Name: Influenza virus serological reagents Regulatory Class: I Product Code: GNX Dated: April 3rd, 2008 Received: April 7th, 2008

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 indicons 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 Amendmonts, 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, l'isting 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); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

13

Page 2 -

This letter will allow you to begin marketing your device as described in your Section 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), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at 240-276-0450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at 240-276-3474. For questions regarding the reporting of device adverse events (Medical Device Reporting (MDR)), please contact the Division of Surveillance Systems at 240-276-3464. 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 (240) 276-3150 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Sally attayna

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

Enclosure

14

Statement of Indications for Use

Indications for Use

510(k) Number (if known): K071591 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)

Uve Schef

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K071591