(88 days)
The RAMP RSV Assay is a qualitative immunochromatographic test for the detection of Respiratory Syncytial Virus (RSV) F-protein antigens in nasal wash/aspirate, nasopharyngeal aspirate and nasopharyngeal swab samples. It is an in vitro diagnostic assay that aids in the rapid diagnosis of RSV infections in symptomatic patients 21 years of age and younger. A negative test is presumptive and it is recommended that all negative results be confirmed by cell culture or direct specimen fluorescence assay (DSFA). Negative results do not preclude RSV infection and should not be used as the sole basis for treatment or other management decisions. The test is intended for professional use.
The RAMP RSV Assay is a qualitative immunochromatographic test for the detection of Respiratory Syncytial Virus (RSV) in nasal wash/aspirate, nasopharyngeal aspirate, and nasopharyngeal swab samples from symptomatic patients 21 years of age and younger. A wash/aspirate or swab sample is mixed with Sample buffer and applied into the sample well of the Test Cartridge. The sample migrates along the strip. Fluorescent-dyed latex (test) particles. coated with anti-RSV antibodies bind to RSV antigens, if present in the sample. As the sample migrates along the strip, RSV-bound particles are captured at the RSV detection zone, and additional particles are captured at the internal standard zone.
This document describes the RAMP® RSV Assay, a qualitative immunochromatographic test for detecting Respiratory Syncytial Virus (RSV). The study presented focuses on its analytical and clinical performance.
Here's the breakdown of the acceptance criteria and the study that proves the device meets them:
1. Table of Acceptance Criteria and Reported Device Performance:
| Performance Metric | Acceptance Criteria (Implied/Standard for Assay) | Reported Device Performance |
|---|---|---|
| Analytical Performance | ||
| Analytical Sensitivity (LoD) | Device should detect RSV at low concentrations | Ranged from 3.5x10^2 to >1.7x10^5 TCID50/mL depending on strain and sample matrix. Achieved 90-100% positivity for LoD samples. |
| Precision & Reproducibility | High agreement across sites and operators | 99.2% overall agreement with expected results. RAMP Ratio %CV 13-16%. |
| Interference | No interference from common substances | None of the tested interfering substances (whole blood, mucin, various medications/OTC products) interfered with negative or positive RSV results. |
| Analytical Specificity | No cross-reactivity with common viruses/bacteria | None of the 16 viruses and 17 bacteria tested gave a positive result. |
| Transport Media Compatibility | No interference with common transport media | None of the 7 transport media tested interfered with performance. |
| Swab Material Compatibility | No interference with common swab types | None of the 4 swab materials tested interfered with performance. |
| Clinical Performance | ||
| Overall Sensitivity | Reasonable sensitivity for RSV detection | 87.3% |
| Overall Specificity | High specificity for RSV detection | 95.6% |
| Sensitivity (NP Swab, All Ages) | 88.2% (95% CI: 81.4 - 92.7) | |
| Specificity (NP Swab, All Ages) | 97.4% (95% CI: 94.6 - 98.7) | |
| Sensitivity (NP Swab, Age <6) | 88.5% (95% CI: 81.7 - 93.0) | |
| Specificity (NP Swab, Age <6) | 98.9% (95% CI: 96.2 - 99.7) | |
| Sensitivity (NP Aspirate, All Ages) | 85.3% (95% CI: 79.7 - 89.6) | |
| Specificity (NP Aspirate, All Ages) | 95.1% (95% CI: 92.1 - 97.0) | |
| Sensitivity (NP Aspirate, Age <6) | 85.9% (95% CI: 80.3 - 90.1) | |
| Specificity (NP Aspirate, Age <6) | 96.5% (95% CI: 93.4 - 98.1) | |
| Sensitivity (Nasal Wash/Aspirate, All Ages) | 89.9% (95% CI: 82.8 - 94.3) | |
| Specificity (Nasal Wash/Aspirate, All Ages) | 93.4% (95% CI: 88.0 - 96.5) | |
| Sensitivity (Nasal Wash/Aspirate, Age <6) | 89.7% (95% CI: 82.5 - 94.2) | |
| Specificity (Nasal Wash/Aspirate, Age <6) | 93.6% (95% CI: 87.8 - 96.7) |
2. Sample Size Used for the Test Set and Data Provenance:
- Clinical Test Set Sample Size: 1,279 fresh specimens were collected; valid results were obtained from 1,140 specimens.
- Data Provenance: Prospective study conducted during the 2008-2009 RSV season. Data collected from eight independent centers located in distinct geographical regions across the United States (NY, MO(2), MD, OH(2), MA, AR).
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of those Experts:
- The document does not specify the number or qualifications of experts used to establish the ground truth. It states that the RAMP RSV Assay's performance was compared to "cell culture and DSFA" (Direct Specimen Fluorescence Assay), which are established methods for viral detection and are considered gold standards or highly reliable reference methods. Staff included "laboratory and non-laboratory personnel" for the RAMP RSV Assay testing, but not for the ground truth establishment itself.
4. Adjudication Method for the Test Set:
- The primary ground truth was established by cell culture and DSFA (Direct Specimen Fluorescence Assay).
- For "samples for which the results of DSFA, culture and RAMP RSV did not all agree," PCR was used as an investigational method for additional analysis. This acts as a form of secondary adjudication or further investigation for discrepant cases, though the PCR results were not formally incorporated into the main sensitivity and specificity tables.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
- This is not an MRMC comparative effectiveness study in the context of human readers and AI assistance. The RAMP RSV Assay is a diagnostic device, an immunochromatographic test, not an AI-powered image analysis or diagnostic support system. Therefore, this question is not applicable.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, the performance presented for the RAMP RSV Assay is its standalone performance. It is a laboratory diagnostic assay where the result (positive/negative) is determined by the reaction in the test cartridge, not by human interpretation of complex data that could be influenced by a human-in-the-loop. The "testing staff included both laboratory and non-laboratory personnel," but their role is in performing the test and reading the direct output, not interpreting intricate images or data.
7. The Type of Ground Truth Used:
- The primary ground truth used for the clinical performance evaluation was expert reference methods: Viral Cell Culture (culture) and Direct Specimen Fluorescence Assay (DSFA).
- For discrepant cases, PCR was used for supplementary analysis.
8. The Sample Size for the Training Set:
- This document describes the validation of a diagnostic immunoassay, not a machine learning or AI model. Therefore, there is no "training set" in the context of AI. The analytical performance evaluations (sensitivity, precision, interference, specificity, transport media, swab compatibility) use laboratory-prepared samples and controls to characterize the device's technical capabilities.
9. How the Ground Truth for the Training Set Was Established:
- As stated above, there is no "training set" in the AI sense for this device. The ground truth for the analytical evaluations was established by preparing samples with known concentrations of RSV or known interfering substances, or by testing against known panels of organisms.
{0}------------------------------------------------
JUL 2 4 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: K091235
Establishment:
Response Biomedical Corporation 1781 – 75th Avenue W. Vancouver, B.C. Canada, V6P 6P2
Tel: (604) 456-6010 Fax: (604) 456-6066
Contact: Ken Pilgrim Director - Quality / Regulatory
22 July, 2009 Prepared:
Regulatory Information:
| Trade Name: | RAMP® RSV Assay |
|---|---|
| Common Name: | RSV immunological test system |
| Classification Name: | RSV immunological test system |
| Regulation Number: | 866.3480, Respiratory syncytial virus serological reagents. |
| Classification: | Class I |
| Product Code: | GQG |
| Panel: | Microbiology |
Predicate Device:
Quidel QuickVue RSV Assay
Intended Use
The RAMP RSV Assay is a qualitative immunochromatographic test for the detection of Respiratory Syncytial Virus (RSV) F-protein antigens in nasal wash/aspirate, nasopharyngeal aspirate and nasopharyngeal swab samples. It is an in vitro diagnostic assay that aids in the rapid diagnosis of RSV infections in symptomatic patients 21 vears of age and younger. A negative test is presumptive and it is recommended that all negative results be confirmed by cell culture or direct specimen fluorescence assay (DSFA). Negative results do not preclude RSV infection and should not be used as the sole basis for treatment or other management decisions. The test is intended for professional use.
1
{1}------------------------------------------------
Description of the Device:
The RAMP RSV Assay is a qualitative immunochromatographic test for the detection of Respiratory Syncytial Virus (RSV) in nasal wash/aspirate, nasopharyngeal aspirate, and nasopharyngeal swab samples from symptomatic patients 21 years of age and younger. A wash/aspirate or swab sample is mixed with Sample buffer and applied into the sample well of the Test Cartridge. The sample migrates along the strip. Fluorescent-dyed latex (test) particles. coated with anti-RSV antibodies bind to RSV antigens, if present in the sample. As the sample migrates along the strip, RSV-bound particles are captured at the RSV detection zone, and additional particles are captured at the internal standard zone.
Comparison of Technological Characteristics:
The RAMP RSV Assay and QuickVue RSV Assay are rapid immunochromatographic tests used for the detection of RSV virus antigen utilizing antibodies targeted toward the highly conserved, membrane-bound F-protein of the virus and thus do not require viable virus particles for detection. The RAMP and QuickVue RSV Assay tests provide results in approximately 15 minutes. Two methods used in the clinical laboratory are viral cell culture (culture) and Direct Specimen Fluorescence Assay (DSFA). 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. DSFA relies on antigen detection and thus does not require viable virus particles in the sample to be evaluated. DSFA can be completed in several hours.
The RAMP RSV. Assay and QuickVue RSV Assay are for use in the central laboratory, stat-lab and point-of-care facilities, while viral cell culture or DSFA are for use in the central laboratories due to their requirement for specialized equipment and highly trained operators.
These methods are indicated for use in the detection of RSV in nasal wash/aspirate, nasopharyngeal aspirate, and nasopharyngeal swab samples.
Summary of Studies:
ANALYTICAL PERFORMANCE
Analytical Sensitivity and Reactivity
The RAMP RSV Assay was evaluated for analytical sensitivity and reactivity after was determined by testing 6 strains of RSV (RSV A-Long, RSV A (A-2), RSV B CH93 (18)-18, RSV B Wash/18537/62. RSV B WV/14617/85. RSV B9320) at the LoD concentration in either viral transport media (VTM) to simulate a swab sample type or saline solution to simulate a wash sample type. Although the specific RSV strains causing infection in humans can vary year to year, all contain the conserved membrane-bound F-protein antigens targeted by the RAMP RSV Assay. Analytical sensitivity (LOD) ranged from 3.5x102 to >1.7x10° TCID26/mL.
| RSV Sample | LoD Concentration(TCID50/mL) | RAMP Result |
|---|---|---|
| A-Long in Saline | 6.5x103 | 100% RSV Positive |
| A-Long in VTM | 2.5x103 | 100% RSV Positive |
| A (A-2) in Saline | 1.0x103 | 100% RSV Positive |
2
{2}------------------------------------------------
| RSV Sample | LoD Concentration(TCID50/mL) | RAMP Result |
|---|---|---|
| A (A-2) in VTM | $1.2x10^3$ | 100% RSV Positive |
| B CH93(18)-18 in Saline | $3.5x10^2$ | 100% RSV Positive |
| B CH93(18)-18 in VTM | $3.5x10^2$ | 100% RSV Positive |
| B Wash/18537/62 in Saline | $7.0x10^3$ | 95% RSV Positive |
| B Wash/18537/62 in VTM | $6.0x10^3$ | 100% RSV Positive |
| B WV/14617/85 in Saline | $5.0x10^3$ | 100% RSV Positive |
| B WV/14617/85 in VTM | $2.5x10^3$ | 100% RSV Positive |
| B9320 in ZMC matrix | $> 1.7x10^5$ | 90% RSV Positive |
Precision and Reproducibiity
The precision and reproducibility of the RAMP RSV Assay was evaluated using a panel consisting of a high negative RSV sample, a limit of detection (LoD) RSV sample (low positive), and a 2x LoD RSV sample (moderate positive). The RSV strain used to prepare the samples was RSV A (A-2) (ATCC VR-1540) following viral titer determinations. To evaluate reproducibility, multiple operators at multiple sites tested each of the three precision samples on 5 different days. Testing at Site 2 was performed in a point-of-care (POC) setting (near patient). At one site (Site 3), to evaluate precision, operators tested each of the three precision samples an additional 7 days for a total of 12 days.
There was 99.2% agreement (393/396) 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 RSV Assay is a qualitative assay based on numerical RAMP Ratio values. The overall RAMP Ratio %CV across all sites ranged from 13% to 16% depending on concentration tested.
| Sample | RSV High Negative | RSV Low Positive | RSV Moderate Positive | Total AgreementAll (%) | |
|---|---|---|---|---|---|
| Viral Titer(TCID50/mL) | 200 | 1200 | 2400 | ||
| Site 1 | Agreement | 30/30 | 30/30 | 30/30 | 90/90(100%) |
| % CV | 11% | 11% | 9% | ||
| Site 2 | Agreement | 30/30 | 29/30 | 30/30 | 89/90(98.9%) |
| % CV | 13% | 14% | 18% | ||
| Site 3 | Agreement | 71/72 | 71/72 | 72/72 | 214/216(99.1%) |
| % CV | 17% | 12% | 11% | ||
| TotalAgreement | 131/132(99.2%) | 130/132(98.5%) | 132/132(100%) | 393/396(99.2%) | |
| 95% CI | 95.8 - 99.9% | 94.6 - 99.6% | 97.1 - 100% | 97.8 - 99.7% | |
| Overall% CV | 16% | 13% | 14% |
{3}------------------------------------------------
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 RSV Assay. The substances were added to a negative sample (saline), an RSV LoD positive sample, and an RSV 2x LoD positive sample and tested in the RSV test at n=3 replicates. The RSV strain used to prepare the samples was RSV A (A-2) following titer determination. Interference was not evaluated with an RSV B strain. None of the substances tested at the concentrations indicated interfered with the test results of negative and positive RSV samples in the RAMP RSV Assay based on the RAMP Result acceptance · criteria of 3/3 (Negative and 2x LOD) and ≥2/3 (LoD). The RAMP RSV Assay is a qualitative assay based on numerical RAMP Ratio values. The Percent of Mean Control Ratio values were calculated using these RAMP Ratios.
| Negative | RSV LoD | RSV 2x LoD | |||||
|---|---|---|---|---|---|---|---|
| SubstanceTested | Conc.Tested | RAMPResults | Percent ofMeanControlRatio | RAMPResults | Percent ofMeanControlRatio | RAMPResults | Percent ofMeanControlRatio |
| Control Saline(0.85%) only(No interferingsubstance) | N/A | Neg 3/3 | 100% | Pos 3/3 | 100% | Pos 3/3 | 100% |
| Whole Blood | 2% v/v | Neg 3/3 | 118% | Pos 2/3 | 89% | Pos 3/3 | 86% |
| Mucin | 1% w/v | Neg 3/3 | 123% | Pos 3/3 | 96% | Pos 3/3 | 94% |
| Scope® Mouthwash | 40% v/v | Neg 3/3 | 117% | Pos 2/3 | 91% | Pos 3/3 | 85% |
| Good and Kind™Mouthwash | 40% v/v | Neg 3/3 | 122% | Pos 3/3 | 93% | Pos 3/3 | 83% |
| Cepacol® MouthWash | 40% v/v | Neg 3/3 | 128% | Pos 2/3 | 90% | Pos 3/3 | 78% |
| Cepacol® Lozenge(Benzocaine) | 30% w/v | Neg 3/3 | 115% | Pos 3/3 | 93% | Pos 3/3 | 69% |
| Fisherman's Friend®Throat Drop(Menthol) | 30% w/v | Neg 3/3 | 107% | Pos 3/3 | 94% | Pos 3/3 | 80% |
| Rhinocort® NasalSpray (Budesonide) | 15% v/v | Neg 3/3 | 125% | Pos 3/3 | 102% | Pos 3/3 | 76% |
| Nasacort® NasalSpray(Triamcinolone) | 15% v/v | Neg 3/3 | 141% | Pos 3/3 | 98% | Pos 3/3 | 85% |
| Flonase® NasalSpray (FluticasoneFuroate) | 30% v/v | Neg 3/3 | 145% | Pos 3/3 | 105% | Pos 3/3 | 85% |
| Nasonex® NasalSpray (MometasoneFuroate) | 15% v/v | Neg 3/3 | 134% | Pos 3/3 | 94% | Pos 3/3 | 79% |
| Conc.Tested | Negative | RSV LoD | RSV 2x LoD | ||||
| SubstanceTested | RAMPResults | Percent ofMeanControlRatio | RAMPResults | Percent ofMeanControlRatio | RAMPResults | Percent ofMeanControlRatio | |
| Tylenol® Tablets(4-Acetamidophenol) | 20mg/mL | Neg 3/3 | 96% | Pos 3/3 | 90% | Pos 3/3 | 81% |
| Aspirin® Tablets(Acetylsalicylic Acid) | 30mg/mL | Neg 3/3 | 127% | Pos 3/3 | 98% | Pos 3/3 | 80% |
| Chlor-Tripolon™Tablets(Chloropheniramine) | 10mg/mL | Neg 3/3 | 106% | Pos 3/3 | 110% | Pos 3/3 | 98% |
| Benadryl™ AllergyTablet(Diphenhydramine) | 5 mg/mL | Neg 3/3 | 136% | Pos 3/3 | 107% | Pos 3/3 | 91% |
| Delsym® DM CoughSyrup(Dextromethorphan) | 2 mg/mL | Neg 3/3 | 135% | Pos 3/3 | 121% | Pos 3/3 | 105% |
| Robitussin® Syrup(Guaiacol GlycerolEther) | 40mg/mL | Neg 3/3 | 140% | Pos 3/3 | 89% | Pos 3/3 | 82% |
| Phenylpropanol-amine HCI (pure) | 40mg/mL | Neg 3/3 | 142% | Pos 3/3 | 105% | Pos 3/3 | 96% |
| Afrin® Nasal Spray(Oxymetazoline HCI) | 0.05% v/v | Neg 3/3 | 103% | Pos 3/3 | 86% | Pos 3/3 | 76% |
| Neo-Synephrine®Nasal Spray(Phenylephrine HCI) | 20mg/mL | Neg 3/3 | 121% | Pos 3/3 | 87% | Pos 3/3 | 84% |
| Otrivin® Saline(NaClw/preservatives) | 1.4% w/v | Neg 3/3 | 122% | Pos 3/3 | 91% | Pos 3/3 | 94% |
| Rebetol® (Ribavirin) | 100ng/mL | Neg 3/3 | 116% | Pos 2/3 | 92% | Pos 3/3 | 82% |
| Relenza®(Zanamivir) | 20mg/mL | Neg 3/3 | 105% | Pos 3/3 | 89% | Pos 3/3 | 76% |
| Rimantadine HCI | 500ng/mL | Neg 3/3 | 118% | Pos 3/3 | 87% | Pos 3/3 | 85% |
| Tamiflu®(OseltamivirPhosphate) | 50mg/mL | Neg 3/3 | 146% | Pos 3/3 | 127% | Pos 3/3 | 108% |
র্ব
{4}------------------------------------------------
Analytical Specificity (Potential Cross-Reactive Organisms)
The analytical specificity of the RAMP RSV Assay was determined by testing a panel consisting of 16 viruses and 17 bacteria that may be present in the nasal cavity or nasopharynx. Bacterial and viral isolates were tested at the concentrations listed after titer determination. None of the organisms tested gave a positive result in the RAMP RSV Assay. Note: RAMP RSV Assay potential cross-reactivity with Chlamydophila pneumoniae has not been determined.
{5}------------------------------------------------
| Strain/Isolate | Concentration | RAMP result |
|---|---|---|
| Adenovirus, Type 1 | 105 TCID50/mL | Negative |
| Adenovirus, Type 7a | 105 TCID50/mL | Negative |
| Human coronavirus, Strain OC43 | 105 TCID50/mL | Negative |
| Human coronavirus, Strain 229E | 105 TCID50/mL | Negative |
| Cytomegalovirus | 105 TCID50/mL | Negative |
| Enterovirus, Type 71 | 105 TCID50/mL | Negative |
| Epstein Barr Virus | 105 TCID50/mL | Negative |
| Human Parainfluenza, Type 1 | 105 TCID50/mL | Negative |
| Human Parainfluenza, Type 2 | 105 TCID50/mL | Negative |
| Human Parainfluenza, Type 3 | 105 TCID50/mL | Negative |
| Influenza A, Brisbane/10/07 | 105 EID50/mL | Negative |
| Influenza B, Ohio/01/06 | 105 TCID50/mL | Negative |
| Measles | 105 TCID50/mL | Negative |
| Human metapneumovirus | 105 TCID50/mL | Negative |
| Mumps virus | 105 TCID50/mL | Negative |
| Human Rhinovirus, Strain 1A | 105 TCID50/mL | Negative |
| Bordetella pertussis | 106 cfu/mL | Negative |
| Corynebacterium Sp. | 106 cfu/mL | Negative |
| Escherichia coli | 106 cfu/mL | Negative |
| Haemophilus influenzae | 106 cfu/mL | Negative |
| Lactobacillus casei | 106 cfu/mL | Negative |
| Legionella pneumophila | 106 cfu/mL | Negative |
| Moraxella catarrhalis | 106 cfu/mL | Negative |
| Mycobacterium tuberculosis, Avirulent | 106 cfu/mL | Negative |
| Mycoplasma pneumoniae | 106 cfu/mL | Negative |
| Neisseria meningitides | 106 cfu/mL | Negative |
| Neisseria sicca | 106 cfu/mL | Negative |
| Pseudomonas aeruginosa | 106 cfu/mL | Negative |
| Staphylococcus aureus, Strain 176 | 106 cfu/mL | Negative |
| Staphylococcus epidermidis, Strain 78 | 106 cfu/mL | Negative |
| Streptococcus pneumoniae | 106 cfu/mL | Negative |
| Streptococcus pyogenes | 106 cfu/mL | Negative |
| Streptococcus salivarius | 106 cfu/mL | Negative |
Transport Media
Multiple lots of each of seven (7) commercially available transport media were evaluated for compatibility in the RAMP RSV Assay by testing a negative sample (transport media only), an RSV LoD positive sample and an RSV 2x LoD positive sample. The RSV strain used to prepare the samples was RSV A (A-2) following titer determination. The RAMP RSV 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 RSV Assay.
{6}------------------------------------------------
| TransportMedia Tested | RAMP Results | ||
|---|---|---|---|
| Negative | RSV LoD | RSV 2x LoD | |
| CopanUniversalTransport Media(UTM) | 100% Neg | 100% Pos | 100% Pos |
| RemelM4 Media | 100% Neg | 100% Pos | 100% Pos |
| RemelM4-RT Media | 100% Neg | 100% Pos | 100% Pos |
| RemelM5 Media | 100% Neg | 100% Pos | 100% Pos |
| StarplexTransport Media | 100% Neg | 100% Pos | 100% Pos |
| 0.85% SalineSolution | 100% Neg | 93% Pos | 100% Pos |
| PhosphateBuffered Saline(PBS) Solution | 100% Neg | 93% Pos | 100% Pos |
| Average RAMPRatio% CV | 12% | 16% | 14% |
Sample Collection Swabs
Four swab materials were evaluated for compatibility in the RAMP RSV Assay by testing a neqative sample (swab alone with no virus present), an RSV LoD positive sample and an RSV 2x LoD positive sample in the RSV test. The RSV strain used to prepare the samples was RSV A (A-2) following titer determination. Each swab was dosed with the appropriate sample and extracted into Copan Universal Transport Media prior to testing in the RAMP RSV Assay. The RAMP RSV Assay is a qualitative assay based on numerical RAMP Ratio values. The %CVs were calculated for the RAMP Ratios. The neqative sample (swab alone) tested negative and all 2x LoD samples tested positive. None of the swabs tested interfered with the performance of the RAMP RSV Assay. Note: In general, calcium alginate swabs are not recommended because they may be cytotoxic to cells and cause viral culture assay inhibition.1
| SwabMaterialTested | RAMP Results | ||
|---|---|---|---|
| Negative | RSV LoD | RSV 2x LoD | |
| Foam | 100% Neg | 100% Pos | 100% Pos |
| Polyester | 100% Neg | 67% Pos | 100% Pos |
{7}------------------------------------------------
| Rayon | 100% Neg | 67% Pos | 100% Pos |
|---|---|---|---|
| Nylon | 100% Neg | 100% Pos | 100% Pos |
| Average RAMPRatio% CV | 9% | 21% | 21% |
CLINICAL PERFORMANCE
Method Comparison
The performance of the RAMP RSV Assay was compared to cell culture and DSFA in a prospective study conducted as part of a multi-center trial during the 2008-2009 RSV season. Eight (8) independent centers located in distinct geographical regions across the United States (NY, MO(2), MD, OH(2), MA, AR) evaluated the RAMP RSV Assay in parallel with cell culture and DSFA. Testing staff included both laboratory and non-laboratory personnel, and two centers (MO, AR) also performed testing in point of care settings (near patient). The sites included an Emergency Department and Pediatric Testing Unit. One thousand, two hundred and seventy nine (1279) fresh specimens were collected from subjects 21 years of age and younger. Of these specimens, valid results were obtained from 1140, with an approximately equal mix of male and female patients.
Clinical Sensitivity and Specificity
Overall Sensitivity and Specificity Relative to Culture and DSFA
| N = 1140 | |
|---|---|
| Sensitivity | 87.3% |
| Specificity | 95.6% |
Sensitivity and Specificity by Age Relative to Culture and DSFA
| NP Swab (All Ages) | ||||
|---|---|---|---|---|
| Culture / DSFA | RAMP | |||
| Positive | Negative | Total | ||
| Positive | 112 | 15 | 127 | |
| Negative | 7* | 257 | 264 | |
| Total | 119 | 272 | 391 | |
| 95% CI | ||||
| Sensitivity | 88.2% | 81.4 - 92.7 | ||
| Specificity | 97.4% | 94.6 - 98.7 |
- 1 was positive by the RAMP RSV Assay and by the Prodesse ProFlu RT-PCR analysis.
8
{8}------------------------------------------------
| NP Swab (Age <6) | |||
|---|---|---|---|
| RAMP | |||
| Culture / DSFA | Positive | Negative | Total |
| Positive | 108 | 14 | 122 |
| Negative | 2 | 184 | 186 |
| Total | 110 | 198 | 308 |
| 95% CI | |||
| Sensitivity | 88.5% | 81.7 - 93.0 | |
| Specificity | 98.9% | 96.2 - 99.7 |
.
.
.
: .
:
.
:
·
| NP Aspirate (All Ages) | |||
|---|---|---|---|
| Culture / DSFA | RAMP | ||
| Positive | Negative | Total | |
| Positive | 168 | 29* | 197 |
| Negative | 15** | 291 | 306 |
| Total | 183 | 320 | 503 |
| 95% CI | |||
| Sensitivity | 85.3% | 79.7 - 89.6 | |
| Specificity | 95.1% | 92.1 - 97.0 |
| NP Aspirate (Age <6) | |||
|---|---|---|---|
| RAMP | |||
| Culture / DSFA | Positive | Negative | Total |
| Positive | 165 | 27 | 192 |
| Negative | 9 | 245 | 254 |
| Total | 174 | 272 | 446 |
| 95% CI | |||
| Sensitivity | 85.9% | 80.3 - 90.1 | |
| Specificity | 96.5% | 93.4 - 98.1 |
.`
.
{9}------------------------------------------------
| Nasal Wash / Aspirate (All Ages) | |||
|---|---|---|---|
| Culture / DSFA | RAMP | ||
| Positive | Negative | Total | |
| Positive | 98 | 11* | 109 |
| Negative | 9** | 128 | 137 |
| Total | 107 | 139 | 246 |
| 95% CI | |||
| Sensitivity | 89.9% | 82.8 - 94.3 | |
| Specificity | 93.4% | 88.0 - 96.5 |
- 1 was negative by the RAMP RSV Assay and by an investigational RT-PCR.
** 1 was positive by the RAMP RSV Assay and by an investigational RT-PCR.
| Nasal Wash / Aspirate (Age <6) | |||
|---|---|---|---|
| Culture / DSFA | RAMP | ||
| Positive | Negative | Total | |
| Positive | 96 | 11 | 107 |
| Negative | 8 | 116 | 124 |
| Total | 104 | 127 | 231 |
| 95% CI | |||
| Sensitivity | 89.7% | 82.5 - 94.2 | |
| Specificity | 93.6% | 87.8 - 96.7 |
Additional Sample Analysis
Samples for which the results of DSFA, culture and RAMP RSV did not all agree were evaluated with PCR. Results of sample testing showed that nine (9) subjects with a positive reference and a negative RAMP result (false negatives) were PCR negative and five (5) subjects with a negative reference and a positive RAMP result (false positives) were PCR positive. These data have not been incorporated in the sensitivity and specificity tables shown above.
REFERENCES:
- Lauer and Masters, Journal of Clinical Microbiology, 1988, January; 26(1): 54-56
{10}------------------------------------------------
Image /page/10/Picture/0 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the seal is a stylized symbol that resembles three wavy lines or stripes, often interpreted as representing the flow of people and services.
DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service
Food and Drug Administration 10903 New Hampshire Avenue Building 66 Silver Spring, MD 20993
Ken L. Pilgrim Director - Quality / Regulatory Response Biomedical Corporation 1781 - 75th Avenue West Vancouver, B.C. Canada V6P 6P2
JUL 2 4 2009
Re: K091235
Trade/Device Name: RAMP RSV Assay Regulation Number: 21 CFR 866.3480 Regulation Name: Respiratory syncytial virus serological reagents Regulatory Class: Class I Product Code: GQG Dated: April 23, 2009 Received: April 27, 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 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.
{11}------------------------------------------------
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). 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 information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 594-3084. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 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 (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.
Sincerely yours,
Taly Atogn
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
{12}------------------------------------------------
Statement of Indications for Use
Indications for Use
510(k) Number (if known): K091235
Device Name: RAMP® RSV Assay
Indications for Use:
The RAMP RSV Assay is a qualitative immunochromatographic test for the detection of Respiratory Syncytial Virus (RSV) F-protein antigens in nasal wash/aspirate, nasopharyngeal aspirate and nasopharyngeal swab samples. It is an in vitro diagnostic assay that aids in the rapid diagnosis of RSV infections in symptomatic patients 21 years of age and younger. A negative test is presumptive and it is recommended that all negative results be confirmed by cell culture or direct specimen fluorescence assay (DSFA). Negative results do not preclude RSV infection and should not be used as the sole basis for treatment or other management decisions. The test is intended for professional use.
Prescription Use X (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 Schuf
Division Sign-Off
Division Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) k 091235
§ 866.3480 Respiratory syncytial virus serological reagents.
(a)
Identification. Respiratory syncytial virus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to respiratory syncytial virus in serum. Additionally, some of these reagents consist of respiratory syncytial virus antisera conjugated with a fluorescent dye (immunofluorescent reagents) and used to identify respiratory syncytial viruses from clinical specimens or from tissue culture isolates derived from clinical specimens. The identification aids in the diagnosis of respiratory syncytial virus infections and provides epidemiological information on diseases caused by these viruses. Respiratory syncytial viruses cause a number of respiratory tract infections, including the common cold, pharyngitis, and infantile bronchopneumonia.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 866.9.