Prospective clinical study (physician offices and clinics); Archived remnant clinical samples from hospital patients
The sponsor used prospective clinical data from patients presenting with respiratory symptoms in routine clinical settings and archived clinical samples to evaluate the performance (sensitivity/specificity) of the BioSign Flu A+B test compared to viral culture.
Prospective clinical study; Prospective clinical study; Follow-up/Duration: January 2007 to March 2008 and March to April 2009; Study Period: 2007-2009
Patients visiting physicians' offices and clinics with signs and symptoms of respiratory infection; Sample Size: 862; Number of Sites: 5
Viral culture
Sensitivity and specificity of BioSign Flu A+B for influenza A and B detection
Archived Sample Test; Retrospective analysis of archived samples
Influenza positive patients visiting Columbia NY Presbyterian Hospital; Sample Size: 80; Number of Sites: 1
Viral culture
Agreement between BioSign Flu A+B and viral culture
Indications for Use
The BioSign® Flu A+B test is an in vitro rapid qualitative test that detects influenza type A and type B nucleoproteins antigens directly from nasal swab, nasopharyngeal swab, and nasopharyngeal aspirate/wash specimens obtained from patients with signs and symptoms of respiratory infection. It is intended to aid in the rapid differential diagnosis of influenza A and B viral infections. A negative test result is presumptive and it is recommended these results be confirmed by viral 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 is intended for professional and laboratory use.
Device Story
In vitro immunochromatographic lateral flow immunoassay; detects influenza A and B nucleoprotein antigens. Input: nasal/nasopharyngeal swab or aspirate/wash specimens. Process: specimen extraction in well; migration through pads with gold-conjugated anti-influenza antibodies; antigen-antibody-dye complex formation; binding to immobilized antibodies on membrane. Output: visual colored lines (A, B, and Control) in test window. Used in clinical/laboratory settings by professionals. Interpretation: presence of test line indicates positive result; control line validates migration. Aids rapid differential diagnosis; negative results require confirmation by viral culture.
Clinical Evidence
Prospective clinical study (n=862) across 5 US sites compared BioSign Flu A+B to viral culture. Sensitivity ranged 82.4%–95.3% and specificity 75.2%–97.5% depending on specimen type. Discrepant results were further evaluated via PCR. Archived samples (n=80) showed 100% agreement with culture. Analytical testing included LoD determination (96.7% detection rate), inclusivity (21 strains), cross-reactivity (multiple respiratory pathogens), and interference studies.
Technological Characteristics
Lateral flow immunochromatographic assay; nitrocellulose test strip; gold-dye conjugated antibodies; internal procedural control; external positive/negative controls. Qualitative visual readout. No electronic components or software.
Indications for Use
Indicated for patients of all ages with signs and symptoms of respiratory infection to aid in the rapid differential diagnosis of influenza A and B viral infections using nasal swab, nasopharyngeal swab, or nasopharyngeal aspirate/wash 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.
{0}
# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY
A. 510(k) Number:
K083746
B. Purpose for Submission:
New Device Clearance
C. Measurand:
Influenza A and B nucleoprotein antigens
D. Type of Test:
Qualitative, *in vitro* immunochromatographic assay
E. Applicant:
Princeton BioMeditech Corporation
F. Proprietary and Established Names:
BioSign® Flu A+B
G. Regulatory Information:
1) Regulation section:
21CFR 866.3330; Influenza Virus Serological Reagents
2) Classification:
Class I
3) Product Code
GNX, Antigens, CF, including CF controls, Influenza A, B, and C.
4) Panel:
Microbiology (83)
H. Intended Use:
1) Intended use(s):
The BioSign® Flu A+B test is an *in vitro* rapid qualitative test that detects influenza type A and type B nucleoproteins antigens directly from nasal swab, nasopharyngeal swab, and nasopharyngeal aspirate/wash specimens obtained from patients with signs and symptoms of respiratory infection. It is intended to aid in the rapid differential diagnosis of influenza A and B viral infections.
A negative test result is presumptive and it is recommended these results be confirmed by viral 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 is intended for professional and laboratory use.
{1}
Page 2 of 10
2) Indication(s) for use:
Same as intended use
3) Special condition for use statement(s):
The device is for prescription use only
4) Special instrument Requirements:
NA
I. Device Description:
In vitro immunochromatographic membrane immunoassay
J. Substantial Equivalence Information:
1) Predicate device name(s):
QuickVue Influenza A+B Test by Quidel Corp.
2) Predicate 510(k) number(s): K053146
3) Comparison with predicate:
Table 1: Summary of Device Similarities
| Characteristics | BioSign® Flu A+B Test | QuickVue Influenza A+B Test |
| --- | --- | --- |
| Device Type | | |
| Technology | Single use, rapid, lateral flow immunoassay | same |
| In vitro diagnostic device | Yes | Yes |
| Controls | Yes | Yes |
| Calibrator | No | No |
| Intended Use | | |
| Detection of influenza A antigen | Yes | Yes |
| Detection of influenza B antigen | Yes | Yes |
| Screening test | No | No |
| Diagnostic test | Yes | Yes |
| Strain identification test | No | No |
| Monitoring therapy | No | No |
| Acceptable Samples | | |
| Nasal Swab | Yes | Yes |
| Nasopharyngeal Swab | Yes | Yes |
| Nasal Aspirates/Washes | Yes | Yes |
{2}
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| Reagents/Components Provided | | |
| --- | --- | --- |
| Nitrocellulose test strip | Yes | Yes |
| Conjugate reagent | Yes | Yes |
| Sample Diluent/Negative Control (external) | Yes | Yes |
| Internal procedural control | Yes | Yes |
| External positive control | Yes | Yes |
K. Standard/Guidance Document Referenced (if applicable):
N/A
L. Test Principle:
The BioSign® Flu A+B test utilizes the chemical extraction of viral antigens followed by solid-phase immunoassay technology for the detection of extracted antigen, influenza A and/or B. In the test procedure, a specimen is collected and placed for one minute into the extraction well of the test device containing extraction solution, during which time antigen is extracted from disrupted virus particles. The test device is then raised, tapped and laid back down onto a level surface to allow the solution in the extraction well to migrate through the pads containing lyophilized detector antibodies conjugated to gold dye and then through the test membrane. If influenza antigens are present in the specimen, they will react with anti-influenza antibody coupled to gold dye particles, migrate through the membrane as antigen-antibody-dye complexes, bind to the immobilized anti-influenza antibody on the membrane, and generate a colored line in the test line position (A and/or B). The rest of the sample and unbound/bound dye complexes continue to migrate to the control line position (C), where antibody to the anti-influenza antibody is immobilized, and forms the control line.
Interpretation of Results
Formation of the Control line serves as an internal control to demonstrate that lyophilized antibodies in the dye pad have been hydrated and that sufficient sample has been applied to allow for migration to the Test line and beyond. If the Control line does not appear within the designated incubation time, the result is invalid and the test should be repeated. The BioSign® Flu A+B test has two test line indicators, one for influenza A and one for influenza B. The two test line indicators allow for the separate and differential identification of influenza A and/or B from the same specimen. If either test line appears in the test result window, together with the control line, the test result is positive for influenza.
M. Performance Characteristics (if/when applicable):
1) Analytical performance:
{3}
# a) Precision/Reproducibility:
The reproducibility study for the BioSign® Flu A+B test was conducted at two physicians' offices and one laboratory using a panel of 90 coded specimens for each site. Testing was performed by two personnel for five days at each site. The panel consists of coded samples of high negative, low positive and moderate positive specimens for each of influenza A and B. For influenza A and B positive samples, A/PR/8/34 (H1N1) and B/Maryland/1/59 were used. The low positive was the LoD level of each strain. Each specimen level was tested in triplicate every day per operator. Each operator conducted test using the coded samples following the test protocol given in the package insert as if they are testing patient sample including the sample extraction step.
The results obtained at each site agreed $100\%$ with the expected results. No differences were observed within run (15 replicates), between runs (five different days), or between sites (two POL sites and one lab).
# b) Linearity/assay reportable range: NA
# c) Traceability, Stability, Expected values (controls, calibrators, or method): NA
# d) Detection limit:
The Limit of Detection (LoD) were determined for each of the two strains selected from the influenza type A and type B strains listed in the analytical sensitivity section below. The sensitivity level of each selected viral strain established in the analytical sensitivity study was tested 60 times to confirm the sensitivity level as LoD level, which gives $95\%$ detection rate. All four viral strains tested were detected $96.7\%$ of the time in 60 replicates.
| Influenza Type | Viral Strain | TCID50/mL | #Positive/#Total | % Positive |
| --- | --- | --- | --- | --- |
| A | A/PR/8/34(H1N1) | 1.05 × 102 | 58/60 | 96.7 |
| A | A/Victoria/3/75(H3N2) | 9.95 × 101 | 58/60 | 96.7 |
| B | B/Taiwan/2/62 | 1.58 × 103 | 58/60 | 96.7 |
| B | B/Maryland/1/59 | 1.99 × 101 | 58/60 | 96.7 |
# e) Analytical reactivity
The analytical sensitivity (inclusivity) was established for a total of 21 influenza strains: 11 strains of influenza A type and 10 strains of influenza B type. The results are shown in the table below.
| Influenza Type | Viral Strain | TCID50/mL | Influenza Type | Viral Strain | TCID50/mL |
| --- | --- | --- | --- | --- | --- |
| A | A/PR/8/34(H1N1) | 1.05 × 102 | B | B/Lee/40 | 5.00 × 100 |
| B | B/Taiwan/2/62 | 1.58 × 103 | B | B/Lee/40 | 5.00 × 100 |
| B | B/Maryland/1/59 | 1.99 × 101 | B | B/Lee/40 | 5.00 × 100 |
{4}
| A | A/FM/1/47(H1N1) | 1.73 × 101 | B | B/Allen/45 | 1.58 × 100 |
| --- | --- | --- | --- | --- | --- |
| A | A/NWS/33(H1N1) | 4.10 × 103 | B | B/GL/1739/54 | 9.95 × 102 |
| A | A/Hong Kong/8/68(H3N2) | 8.5 × 102 | B | B/Taiwan/2/62 | 1.58 × 103 |
| A | A/Denver/1/57(H1N1) | 7.20 × 100 | B | B/Maryland/1/59 | 1.99 × 101 |
| A | A/Aichi/2/68(H3N2) | 9.95 × 100 | B | B/Mass/3/66 | 5.00 × 101 |
| A | A/Port Chalmers/1/73 | 1.99 × 102 | B | B/R22 Barbara | 1.6 × 10-1 |
| A | A/Victoria/3/75(H3N2) | 9.95 × 101 | B | B/R75 | 2.94 × 103 |
| A | A/New Jersey/8/76(H1N1) | 9.95 × 101 | B | B/Russia/69 | 3.16 × 103 |
| A | A/WS/33(H1N1) | 5.00 × 101 | B | B/Hong Kong/5/72 | 2.88 × 101 |
| A | A/Swine/1976/31 | 1.58 × 102 | | | |
NOTE: The performance characteristics of the test with cultured avian influenza A subtype H5N1 virus, or with specimens from human infected with H5N1 or other avian influenza viruses are unknown.
The performance of the BioSign® Flu A+B test was evaluated with human specimens obtained from patients infected with the 2009 H1N1 influenza virus consisting of sixty six (66) frozen clinical nasal and nasopharyngeal swab samples that had previously tested positive for 2009 H1N1 by the cleared CDC RT-PCR test. The BioSign® Flu A+B test detected $71\%$ (47/66) of the CDC RT-PCR test positive specimens. The detection rate was $91\%$ with the higher tittered specimens and $38\%$ with the lower tittered specimens.
# f) Analytical specificity
The potential cross-reactivity of the non-influenza respiratory pathogens and other microorganisms with which the majority of the population may be infected was tested using the BioSign® Flu A+B test at medically relevant levels, $10^{6}$ cfu/mL for bacteria and $10^{5}$ pfu/mL for non-flu viruses. None of the organisms or viruses listed in the table below gave a positive result with BioSign® Flu A+B at the tested concentration.
| Viruses Tested | |
| --- | --- |
| Adenovirus* | Measles** |
| Human coronavirus** | Human metapneumovirus** |
| Cytomegalovirus** | Mumps virus** |
| Enterovirus** | Respiratory syncytial virus; Type B* |
| Epstein Barr Virus** | Rhinovirus; Type 1A** |
| Human parainfluenza; Type 1, 2 and 3* | |
**In the study the virus was confirmed using commercially available PCR (not approved by FDA).
* In the study the virus was confirmed using FDA approved immunofluorescence assay
{5}
| Bacteria Tested | |
| --- | --- |
| Bordetella pertussis | Neisseria sp. |
| Chlamydia pneumoniae | Pseudomonas aeruginosa |
| Corynebacterium sp. | Staphylococcus aureus: Protein A Producer |
| Escherichia coli | Staphylococcus epidermidis |
| Hemophilus influenzae | Streptococcus pneumoniae |
| Lactobacillus sp. | Streptococcus pyogenes |
| Legionella spp | Streptococcus salivarius |
| Moraxella catarrhalis | |
| Mycobacterium tuberculosis avirulent | |
| Mycoplasma pneumoniae | |
| Neisseria meningitides | |
# g) Interfering substances
The interference study was conducted using medically relevant concentrations of the potentially interfering substances listed below with two strains each of influenza type A and type B to assess the potential interference of the substances on the performance of the BioSign® Flu A+B test. The test was conducted by spiking each substance into samples containing the lowest detectable virus level of influenza Type A or Type B for the positive interference testing and into samples without influenza virus for the negative interference testing. Each substance had no inhibitory effect on the BioSign® Flu A+B test performance at the concentration listed in the table below.
| Substances Tested | Concentration Tested |
| --- | --- |
| Mucin | 1 mg/ml |
| Whole Blood | 1% |
| Phenylephrine | 10 mg/mL |
| Oxymetazoline | 10 mg/mL |
| Sodium Chloride with preservative | 20% |
| Beclomethasone | 1 mg/mL |
| Dexamethasone | 1 mg/mL |
| Flunisolide | 1 mg/mL |
| Triamcinolone | 1 mg/mL |
| Budesonide | 1 mg/mL |
| Mometasone | 1 mg/mL |
| Fluticasone | 0.5 mg/mL |
| Luffa opperculata, sulfur | 1% |
| Galphimia glauca | 1% |
| Histaminum hydrochloricum | 1% |
| Live intranasal influenza virus vaccine | 1% |
| Benzocaine | 1 mg/mL |
| Menthol | 1 mg/mL |
| Zanamivir | 1 mg/mL |
| Mupirocin | 1 mg/mL |
| Tobramycin | 1 mg/mL |
{6}
Page 7 of 10
2) Comparison studies
a. Method comparison with predicate device:
N/A
b. Matrix comparison:
NA
3) Clinical studies
a) Clinical sensitivity:
A prospective clinical study was conducted from January 2007 to March 2008 and during March and April 2009 to determine the performance of the BioSign® Flu A+B test for nasopharyngeal aspirate/wash, nasopharyngeal swab, and nasal swab specimens. The samples were collected at 5 sites in the USA from patients who visited physicians' offices and clinics with signs and symptoms of respiratory infection during the study period. All collected samples were tested with BioSign® Flu A+B, and were cultured to confirm the results of BioSign® Flu A+B. The total number of patients tested was 862, of which 30% were 5 and younger, 38% were 6-21 years old, and the rest were older than 21. Forty eight (48) percent were male and 52% were female.
The combined data from all sites of the prospective study are presented in the tables below. The samples that produced discrepant results between BioSign® Flu A+B and viral culture were further evaluated with an FDA cleared PCR based assay (real time RT-PCR, PCR hereafter). These results are presented in the footnote below each table.
Nasopharyngeal Aspirate Samples
| | Reference (Virus Culture) Results | | | |
| --- | --- | --- | --- | --- |
| BioSign Flu A+ B | Flu A Positive | Flu A Negative | Total | Performance |
| Flu A Positive | 41 | 30* | 71 | Sensitivity: 95.3%
95% CI: 92.1–98.5% |
| Flu A Negative | 2** | 180 | 182 | Specificity: 85.7%
95% CI: 83.3–88.1% |
| Total | 43 | 210 | 253 | |
*Of 30 discrepant results, 22 were positive by both BioSign and PCR
** Of 2 discrepant results, 1 was negative by both BioSign and PCR
{7}
Page 8 of 10
| | Reference (Virus Culture) Results | | | |
| --- | --- | --- | --- | --- |
| BioSign Flu A+ B | Flu B Positive | Flu B Negative | Total | Performance |
| Flu B Positive | 11 | 6* | 17 | Sensitivity: 91.6%
95% CI: 83.6–99.6% |
| Flu B Negative | 1** | 235 | 236 | Specificity: 97.5%
95% CI: 96.5–98.5% |
| Total | 12 | 241 | 253 | |
Of 6 discrepant results, all 6 were positive by BioSign and by PCR
** The discrepant sample was positive by PCR
## Nasopharyngeal Swab Samples
| | Reference (Virus Culture) Results | | | |
| --- | --- | --- | --- | --- |
| BioSign Flu A+ B | Flu A Positive | Flu A Negative | Total | Performance |
| Flu A Positive | 26 | 51* | 77 | Sensitivity: 89.6%
95% CI: 84.0–95.2% |
| Flu A Negative | 3** | 171 | 174 | Specificity: 77.0%
95% CI: 74.2–79.8% |
| Total | 29 | 222 | 251 | |
Of 51 discrepant results, 41 were positive by both BioSign and PCR
** Of 3 discrepant results, 1 was negative by both BioSign and PCR
| | Reference (Virus Culture) Results | | | |
| --- | --- | --- | --- | --- |
| BioSign Flu A+ B | Flu B Positive | Flu B Negative | Total | Performance |
| Flu B Positive | 33 | 15* | 48 | Sensitivity: 86.8%
95% CI: 81.4–92.2% |
| Flu B Negative | 5** | 198 | 203 | Specificity: 92.9%
95% CI: 91.2–94.6% |
| Total | 38 | 213 | 251 | |
**Of the 15 discrepant results, 8 were positive by both BioSign and PCR
** Of the 5 discrepant results, 2 were negative by both BioSign and PCR
{8}
Page 9 of 10
# Nasal Swab Samples
| | Reference (Virus Culture) Results | | | |
| --- | --- | --- | --- | --- |
| BioSign Flu A+B | Flu A Positive | Flu A Negative | Total | Performance |
| Flu A Positive | 33 | 80* | 113 | Sensitivity: 91.7%
95% CI: 78.2–97.1% |
| Flu A Negative | 3** | 242 | 245 | Specificity: 75.2%
95% CI: 70.2–79.6% |
| Total | 36 | 322 | 358 | |
*Of 80 discrepant results, 65 were positive by both BioSign and PCR
** Of 3 discrepant results, all 3 were positive by PCR
| | Reference (Virus Culture) Results | | | |
| --- | --- | --- | --- | --- |
| BioSign Flu A+ B | Flu B Positive | Flu B Negative | Total | Performance |
| Flu B Positive | 14 | 40* | 54 | Sensitivity: 82.4%
95% CI: 59.0–93.8% |
| Flu B Negative | 3** | 301 | 304 | Specificity: 88.3%
95% CI: 84.4–91.3% |
| Total | 17 | 341 | 358 | |
*Of 40 discrepant results, 18 were positive by both BioSign and PCR
** Of 3 discrepant results, 1 was negative by both BioSign and PCR
As further verification of the PCR test results shown from the samples with discrepant results between BioSign and viral culture, available archived remnant samples from the clinical studies with concordant results were also tested by PCR. The specificity for both Flu A and Flu B was 100%, while the sensitivity for Flu A was 90% and the sensitivity for Flu B was 91.7%.
# Archived Samples
Eighty (80) frozen archived samples originally obtained from influenza positive patients visiting Columbia NY Presbyterian Hospital and confirmed as positive for either influenza A or Influenza B by viral culture were tested with BioSign Flu A+B.
The tables below present test results with archived samples.
Aspirate Sample
{9}
Page 10 of 10
| | Reference (Virus Culture) Results | | | |
| --- | --- | --- | --- | --- |
| BioSign Flu A+ B | Flu A Positive | Flu A Negative | Total | Agreement |
| Flu A Positive | 50 | 0 | 50 | 100% |
| Flu A Negative | 0 | 30 | 30 | 100% |
| Total | 50 | 30 | 80 | |
| | Reference (Virus Culture) Results | | | |
| --- | --- | --- | --- | --- |
| BioSign Flu A+ B | Flu B Positive | Flu B Negative | Total | Agreement |
| Flu B Positive | 30 | 0 | 30 | 100% |
| Flu B Negative | 0 | 50 | 50 | 100% |
| Total | 30 | 50 | 80 | |
Swab Sample
| T | Reference (Virus Culture) Results | | | |
| --- | --- | --- | --- | --- |
| BioSign Flu A+ B | Flu A Positive | Flu A Negative | Total | Agreement |
| Flu A Positive | 50 | 0 | 50 | 100% |
| Flu A Negative | 0 | 30 | 30 | 100% |
| Total | 50 | 30 | 80 | |
| | Reference (Virus Culture) Results | | | |
| --- | --- | --- | --- | --- |
| BioSign Flu A+ B | Flu B Positive | Flu B Negative | Total | Agreement |
| Flu B Positive | 30 | 0 | 30 | 100% |
| Flu B Negative | 0 | 50 | 50 | 100% |
| Total | 30 | 50 | 80 | |
## Proposed labeling:
The labeling is sufficient and it satisfies the requirement of 21 CFR Part 809.10.
## N. Conclusions
The submitted material in this premarket notification is complete and supports a substantial equivalence decision.
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Output name, acceptance criteria, observed values, development dataset description, and test dataset description. It's the same format we use for regulatory strategy output and Fast 510(k) input, and the fastest high-level fingerprint of an AI device. AI-generated but reliable in practice.
3. Judging fuzzy relevance
Fuzzy results trail off in relevance as you scroll. Use three signals to decide how far down to go: the fuzzy badge explanations, the intended use column, and whether your target output (e.g., Cobb angle) still appears in the AI Performance sub-table. Once it stops appearing, you're past the relevant zone. A top hit with a low score (~0.4) and a stretched explanation is a hint the closest predicates are far away — the project may be headed for De Novo. Note the fuzzy search is a pattern match: it doesn't handle negation ("not") well, and hardware devices can appear — filter by SaMD/AI ML to cut them.
How do you judge how far down fuzzy search results to go?
Use the relevancy signals: the fuzzy badge explanations, the intended use column, and whether the target output (e.g., Cobb angle) still appears in the AI Performance sub-table. Once it stops appearing, results are trailing off in relevancy.
4. Device detail page: chat and citations
Click a device name to open its detail page: device facts on the left, a chat window on the right. Ask something like "Describe the training data". The answer carries little citation bubbles — click one to jump to the highlighted passage in the source PDF, so you can verify every AI answer against the document. There's also a Download PDF button for sharing.
How do you verify an AI chat answer on the device detail page?
Click the citation bubbles to jump to the relevant highlight in the source document.
Reading rule for every project: how many summaries do you read in full?
At least the three most relevant 510(k) or De Novo summaries, in full. After that, use targeted chat questions to confirm your memory quickly. The tool supports this professional habit — it doesn't replace it.
5. Side-by-side comparison
Select multiple rows in the results table (aim for under ~10), then open the PDF Viewer tab. Ask one question — it goes to all selected devices in parallel, each with citations. This is the fastest way to compare and contrast devices: training data, PCCP scope, how they handled adding new scanners, and so on.
What does the side-by-side PDF viewer mode do?
Select multiple devices, open the PDF viewer tab, and ask one question (e.g., "Describe the training data"). It queries all selected devices simultaneously with citations, so you can compare and contrast quickly.
6. Collections
With rows selected, go to the Collections tab and create a labeled collection (e.g., "Cobb Angle Project"). Reload that selection any time — before a client call, pull up the collection and ask questions across all of its devices at once.
How do you save a set of selected devices for later use?
Select the rows, go to the Collections tab, and create a labeled collection (e.g., "Cobb Angle Project"). You can reload the selection anytime and carry it into the PDF viewer and other tabs that support selections.
7. Product codes and the regulations tree
Click a product code in the results to jump to it in the regulations tree — identification text, sibling product codes, and devices you can open in a PDF viewer on the right. Click a regulation number to see its identification, special controls, and related product codes. You can also search by product code or regulation number at the top of the tree. Always read the special controls if any exist for your device — it broadens your search and sharpens pre-kickoff research.
What can you do from the regulations tree view?
Browse product codes and regulation numbers, read the identification text and special controls, browse sibling product codes, open device PDFs on the right, and search by product code or regulation number at the top of the tree.
8. Chart view
Click Show Chart and segment by regulation number (or product code) to see which regulations dominate your result set. Clicking a regulation takes you into the regulations tree. Great for spotting that most matches are, say, hardware laparoscopic devices — a cue to go back and filter.
How do you see which regulations dominate a search result set?
Click "Show Chart" and segment by Regulation Number. Clicking a regulation takes you to the regulations tree.
9. The predicate graph
Open the Predicates tab for a family-tree view of predicate relationships. Click a node to trace its parents and children; selections from search carry over pre-selected. Commonly predicated devices are worth reading — a lot of people predicated them for a reason. The visual lineage is also handy on client calls, e.g. to show how a predicate family evolved and justify why your predicate still holds.
In the predicate graph, why are commonly predicated devices worth reading?
A lot of people predicated them for a reason. Clicking a node traces parents and children, and selections from search carry over pre-selected.
10. Embeddings: the galaxy map
The Embeddings tab plots every matching document in a 2-D "galaxy map" where semantically similar devices cluster together. Hover or click clusters to explore, and let AI label the clusters for you. Embeddings beat product codes for grouping: two devices can carry different product codes (LLZ vs. QIH) yet do the same thing — the embedding captures the meaning of the intended use and device story. This is also exactly how retrieval-augmented generation (RAG) works under the hood, and it makes a great visual on client calls.
Try it yourself
Head to the search page and work through a few of these AI/ML fuzzy searches to build intuition: perivascular fat on CT · aortic valve calcification opportunistic screening on noncontrast CT · breast cancer prediction on digital pathology slides · autism detection · gestational age prediction · a hearing aid that can also detect a pulse · foundation model based analysis of ECG · large language models · penetration test. Watch how the relevance scores, intended use, and AI Performance tables tell you when results stop being meaningful.
