Residual clinical specimens from a state public health laboratory
Residual nasopharyngeal aspirate/wash samples collected during routine clinical influenza confirmation testing were used to evaluate the performance of the BioSign Flu A+B test against an FDA-cleared RT-PCR assay.
Residual clinical specimens; Public health laboratory; Clinical performance evaluation
Clinical Evidence
Study Design
Population
Comparator
Key Endpoints
2017-2018 Clinical Study; Retrospective analysis of residual clinical specimens; Follow-up/Duration: October 2017 to March 2018; Study Period: 2017-2018
Patients with respiratory infection symptoms requiring influenza confirmation testing; Sample Size: 226; Number of Sites: 1
FDA-cleared influenza RT-PCR assay
Sensitivity and specificity of BioSign Flu A+B compared to RT-PCR
Indications for Use
BioSign® Flu A+B is an in vitro rapid qualitative test that detects influenza type A and type B nucleoprotein 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. Negative test results are presumptive and it is recommended these results be confirmed by viral culture or an FDA-cleared influenza A and B molecular assay. Negative results do not preclude influenza virus infection and should not be used as the sole basis for treatment or other management decisions. Performance characteristics for influenza were established during the 2007-2009 and the 2014-2016 influenza seasons when influenza A/H1N1, A/H1N1 pandemic, A/H3N2, influenza B/Victoria lineage, and B/Yamagata lineage were the predominant influenza viruses in circulation according to the Flu Activity & Surveillance report from the CDC. When other influenza viruses are emerging, performance characteristics may vary. If infection with a novel influenza virus is suspected based on current clinical and epidemiological screening criteria recommended by public health authorities, specimens should be collected with appropriate infection control precautions for novel virulent influenza viruses and sent to state or local health department for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens.
Device Story
In vitro rapid qualitative immunoassay; detects influenza A and B nucleoprotein antigens; utilizes solid phase chromatographic technology with colloidal gold test line; requires 1-minute extraction incubation; 10-minute read time. Used in professional/laboratory settings. Input: nasal/nasopharyngeal swabs or aspirate/wash specimens. Output: visual presence/absence of test lines. Results are presumptive; intended to aid clinical diagnosis; negative results require confirmation via viral culture or molecular assay. Modification involves updated clinical performance labeling based on additional 2017-2018 study data.
Clinical Evidence
Prospective clinical study (2017-2018) evaluated 226 nasopharyngeal aspirate/wash specimens against an FDA-cleared RT-PCR assay. Results: Flu A sensitivity 85.1% (95% CI: 78.5-90.0%), specificity 100% (95% CI: 95.3-100%); Flu B sensitivity 85.7% (95% CI: 72.2-93.3%), specificity 99.5% (95% CI: 97.0-99.9%). Additional data provided via re-analysis of 2007-2009 and 2014-2016 prospective studies.
Technological Characteristics
Solid phase chromatographic immunoassay; colloidal gold test line; reddish-purple internal control line. Manual test procedure; 1-minute extraction incubation; 10-minute result read time. No electronic components, software, or connectivity.
Indications for Use
Indicated for patients with signs and symptoms of respiratory infection to aid in 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.
Submission Summary (Full Text)
{0}
# SPECIAL 510(K): DEVICE MODIFICATION
## OIR DECISION SUMMARY
510(k) Number: K182157
This 510(k) submission contains information/data on modifications made to the applicant's own class II device requiring 510(k). The following items are present and acceptable:
1. The name and 510(k) number of the applicant's previously cleared device.
| 510(k) Number | Device Name | Clearance Date | Primary Reason for 510(k) Submission |
| --- | --- | --- | --- |
| K133474 | BioSign® Flu A+B | 12/10/2013 | K133474 was the most recent regulatory action for this device, originally cleared as K083746 on 11/10/2010. K133474 was a special 510(k) submission for device modification to expand the Analytical Inclusivity section of the package insert to include reactivity information for two strains of the H5N1 subtype of influenza A virus, A/Vietnam/1194/2004 and A/Anhui/01/2005. |
2. Applicant's statement that the INDICATION/INTENDED USE of the modified device as described in its labeling HAS NOT CHANGED along with the proposed instructions for use.
3. A description of the device MODIFICATION(S) in sufficient detail to demonstrate that the FUNDAMENTAL SCIENTIFIC TECHNOLOGY of the modified device has not changed.
A. PBM conducted an additional clinical study during the 2017 to 2018 influenza season, testing nasophyngeal aspirate specimens sequentially obtained from a state public health laboratory, against an FDA-cleared RT-PCR assay (see Section 6 below). The results of this additional study demonstrate that the BioSign Flu A+B performance for testing nasophyngeal aspirate/wash specimens meet the performance criteria specified in 21 CFR 866.3328.
B. The product package insert has been revised for the modified device, reflecting a re-organization of the Clinical Performance section as follows:
1) Prospective Clinical Study from 2007 to 2009
a) Nasophyngeal Aspirate Samples: Performance against Viral Culture
b) Nasophyngeal/Nasal Swab Samples: Performance against Viral Culture
c) Nasophyngeal/Nasal Swab Samples: Performance against an FDA-cleared RT-PCR Assay
2) Prospective Clinical Study from 2014 to 2016
a) Nasophyngeal/Nasal Swab Samples: Performance against an FDA-cleared RT-PCR Assay
3) All Prospective Clinical Studies Combined (2007 to 2009 and 2014 to 2016)
a) Nasophyngeal/Nasal Swab Samples: Performance against an FDA-cleared RT-PCR Assay
4) Clinical Study from 2017 to 2018
1
{1}
a) Nasophyngeal Aspirate/Wash Samples: Performance against an FDA-cleared RT-PCR Assay
Table 1 below is a new performance table based on the re-analysis of the performance data generated from the 2007 to 2009 prospective clinical study, testing nasophyngeal (NP) swab and nasal swab specimens, against virus culture. This table is added to section 1b) of the Clinical Performance section of the revised product package insert as described above.
Table 1: Nasophyngeal/Nasal Swab Samples - Performance against Viral Culture (Prospective Clinical Study from 2007 to 2009)
| | Viral Culture Results | | | |
| --- | --- | --- | --- | --- |
| BioSign Flu A+ B | Flu A Positive | Flu A Negative | Total | Performance |
| Flu A Positive | 59 | 131 | 190 | Sensitivity: 90.8% 95% CI: 81.3-95.7% |
| Flu A Negative | 6 | 413 | 419 | Specificity: 75.9% 95% CI: 72.2-79.3% |
| Total | 65 | 222 | 609 | |
| | Viral Culture Results | | | |
| --- | --- | --- | --- | --- |
| BioSign Flu A+ B | Flu B Positive | Flu B Negative | Total | Performance |
| Flu B Positive | 47 | 55 | 102 | Sensitivity: 85.5% 95% CI: 73.8-92.4% |
| Flu B Negative | 8 | 499 | 507 | Specificity: 90.1% 95% CI: 87.3-92.3% |
| Total | 55 | 554 | 609 | |
Table 2 below is a new performance table based on a re-analysis of the performance data generated from the 2007 to 2009 prospective clinical study, testing nasophyngeal swab and nasal swab specimens, against an FDA-cleared RT-PCR assay. This re-analysis of the prospective performance data was conducted employing a statistical method to project results for the specimens with missing data from the FDA-cleared RT-PCR comparator assay in the 2007 to 2009 prospective clinical study. The statistical method employed in this data re-analysis is consistent with the principles outlined in the FDA guidance document entitled Design Considerations for Pivotal Clinical Investigations for Medical Devices: Guidance for Industry, Clinical Investigators, Institutional Review Boards and Food and Drug Administration Staff. This table is added to section 1c) of the Clinical Performance section of the revised product package insert as described above.
Table 2: Nasophyngeal/Nasal Swab Samples - Performance against an FDA-cleared RT-PCR Assay (Prospective Clinical Study from 2007 to 2009)
| | RT-PCR Results | | | |
| --- | --- | --- | --- | --- |
| BioSign Flu A+ B | Flu A Positive | Flu A Negative | Total | Performance |
| Flu A Positive | 165 | 25 | 190 | Sensitivity: 92.2% 95% CI: 87.3-95.3% |
| Flu A Negative | 14 | 405 | 419 | Specificity: 94.2% 95% CI: 91.6-96.0% |
| Total | 179 | 430 | 609 | |
| | RT-PCR Results | | | |
| --- | --- | --- | --- | --- |
| BioSign Flu A+ B | Flu B Positive | Flu B Negative | Total | Performance |
| Flu B Positive | 72 | 30 | 102 | Sensitivity: 90.0% 95% CI: 81.5-94.8% |
| Flu B Negative | 8 | 499 | 507 | Specificity: 94.3% 95% CI: 92.0-96.0% |
| Total | 80 | 529 | 609 | |
2
{2}
Table 3 below is a new performance table based on the analysis of a subset of the performance data generated from the 2014 to 2016 CLIA Waiver clinical study that represents all prospective performance data generated from the 2014 to 2016 CLIA Waiver clinical study testing nasophyngeal swab and nasal swab specimens. This table is added to section 2a) of the Clinical Performance section of the revised product package insert as described above.
Table 3: Nasophyngeal/Nasal Swab Samples - Performance against an FDA-cleared RT-PCR Assay (Prospective Clinical Study from 2014 to 2016)
| | RT-PCR Results | | | |
| --- | --- | --- | --- | --- |
| BioSign Flu A+ B | Flu A Positive | Flu A Negative | Total | Performance |
| Flu A Positive | 101 | 2 | 103 | Sensitivity: 90.2% 95% CI: 83.3-94.4% |
| Flu A Negative | 11 | 193 | 204 | Specificity: 99.0% 95% CI: 96.3-99.7% |
| Total | 112 | 195 | 307 | |
| | RT-PCR Results | | | |
| --- | --- | --- | --- | --- |
| BioSign Flu A+ B | Flu B Positive | Flu B Negative | Total | Performance |
| Flu B Positive | 27 | 3 | 30 | Sensitivity: 81.8% 95% CI: 65.9-91.4% |
| Flu B Negative | 6 | 271 | 277 | Specificity: 98.9% 95% CI: 96.8-99.6% |
| Total | 33 | 274 | 307 | |
Table 4 below is a new performance table based on the analysis of all the performance data generated from the 2007 to 2009 and the 2014 to 2016 prospective clinical studies testing nasophyngeal swab and nasal swab specimens. This table is added to section 3a) of the Clinical Performance section of the revised product package insert as described above.
Table 4: Nasophyngeal/Nasal Swab Samples - Performance against an FDA-cleared RT-PCR Assay (Prospective Clinical Study from 2007 to 2009 and Prospective Clinical Study from 2014 to 2016)
| | RT-PCR Results | | | |
| --- | --- | --- | --- | --- |
| BioSign Flu A+ B | Flu A Positive | Flu A Negative | Total | Performance |
| Flu A Positive | 266 | 27 | 293 | Sensitivity: 91.4% 95% CI: 87.6-94.1% |
| Flu A Negative | 25 | 598 | 623 | Specificity: 95.7% 95% CI: 93.8-97.0% |
| Total | 291 | 625 | 916 | |
| | RT-PCR Results | | | |
| --- | --- | --- | --- | --- |
| BioSign Flu A+ B | Flu B Positive | Flu B Negative | Total | Performance |
| Flu B Positive | 99 | 33 | 132 | Sensitivity: 87.6% 95% CI: 80.3-92.5% |
| Flu B Negative | 14 | 770 | 784 | Specificity: 95.9% 95% CI: 94.3-97.1% |
| Total | 113 | 803 | 916 | |
Table 5 below is a new performance table based on the analysis of performance data generated from a new 2017 to 2018 clinical study (see Section 6 below) testing nasophyngeal (NP) aspirate/wash specimens. This table is added to section 4a) of the Clinical Performance section of the revised product package insert as described above.
Table 5: Nasophyngeal Aspirate/Wash Samples - Performance against an FDA-cleared RT-PCR Assay (Clinical Study from 2017 to 2018)
| | RT-PCR Results | | | |
| --- | --- | --- | --- | --- |
| BioSign Flu A+ B | Flu A Positive | Flu A Negative | Total | Performance |
| | RT-PCR Results | | | |
| --- | --- | --- | --- | --- |
| BioSign Flu A+ B | Flu B Positive | Flu B Negative | Total | Performance |
3
{3}
| Flu A Positive | 126 | 0 | 126 | Sensitivity: 85.1% 95% CI: 78.5-90.0% |
| --- | --- | --- | --- | --- |
| Flu A Negative | 22 | 78 | 100 | Specificity: 100% 95% CI: 95.3-100% |
| Total | 148 | 78 | 226 | |
| Flu B Positive | 36 | 1 | 37 | Sensitivity: 85.7% 95% CI: 72.2-93.3% |
| --- | --- | --- | --- | --- |
| Flu B Negative | 6 | 183 | 189 | Specificity: 99.5% 95% CI: 97.0-99.9% |
| Total | 42 | 184 | 226 | |
#### 4. Comparison Information (similarities and differences) to applicant's legally marketed predicate device.
| Item | Predicate Device | Modified Device |
| --- | --- | --- |
| Features | BioSign® Flu A+B (K133474) | BioSign® Flu A+B (K182157) |
| Intended Use | BioSign® Flu A+B is an in vitro rapid qualitative test that detects influenza type A and type B nucleoprotein 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. Negative test results are 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. Performance characteristics for influenza were established during the 2007-2009 influenza seasons when influenza A viruses A/New Caledonia/20/99 (H1N1), A/Solomon Islands/3/2006 (H1N1), A/Brisbane/59/2007 (H1N1), A/California/07/2009 (H1N1), A/Wisconsin/67/2005 (H3N2), A/Brisbane/ 10/2007 (H3N2) and influenza B viruses B/Ohio/01/2005, B/Florida/4/2006, B/Brisbane/60/2008 were the predominant influenza viruses in circulation according to the Flu Activity & Surveillance report by CDC. Performance characteristics may vary against other emerging influenza viruses. If infection with a novel influenza virus is suspected based on current clinical and epidemiological screening criteria recommended by public health authorities, specimens should be collected with appropriate infection control precautions for novel virulent influenza viruses and sent to state or local health department for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens. | BioSign® Flu A+B is an in vitro rapid qualitative test that detects influenza type A and type B nucleoprotein 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. Negative test results are presumptive and it is recommended these results be confirmed by viral culture or an FDA-cleared influenza A and B molecular assay. Negative results do not preclude influenza virus infection and should not be used as the sole basis for treatment or other management decisions. Performance characteristics for influenza were established during the 2007-2009 and the 2014-2016 influenza seasons when influenza A/H1N1, A/H1N1 pandemic, A/H3N2, influenza B/Victoria lineage, and B/Yamagata lineage were the predominant influenza viruses in circulation according to the Flu Activity & Surveillance report from the CDC. When other influenza viruses are emerging, performance characteristics may vary. If infection with a novel influenza virus is suspected based on current clinical and epidemiological screening criteria recommended by public health authorities, specimens should be collected with appropriate infection control precautions for novel virulent influenza viruses and sent to state or local health department for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens. |
| Specimen Types | Nasopharyngeal swabs, nasal swabs, and nasopharyngeal aspirate/wash specimens, from patients with signs and symptoms of respiratory infection. | Same |
| Analitical Principle | Solid phase chromatographic immunoassay | Same |
4
{4}
| Item | Predicate Device | Modified Device |
| --- | --- | --- |
| Features | BioSign® Flu A+B (K133474) | BioSign® Flu A+B (K182157) |
| Extraction | Incubated for 1 minute in the extraction reagent | Same |
| Result Read Time | 10 minutes | Same |
| Test Line | Colloidal gold | Same |
| Internal Control Line | Reddish-purple line | Same |
| Control Samples (supplied as prepared swabs) | Positive Control Swab: Influenza A and B antigens (non-infective recombinant nucleoprotein) Negative Control Swab: Inactivated Group B Streptococcus antigen (non-infective) | Same |
| Product Package Insert | See K133474 | Clinical Performance section of the product package insert is revised and re-organized. |
### 5. A Design Control Activities Summary which includes:
a) Identification of Risk Analysis method(s) used to assess the impact of the modification on the device and its components, and the results of the analysis.
The risk assessment process was based on Princeton BioMeditech (PBM) internal Risk Management process (QA#11800), which meets the requirements of ISO14971:2012. According to the procedure, a failure mode and effect analysis (FMEA) has been used for analysis of the risk and the following items are analyzed:
- The hazard
- Failure Mode
- Potential Effect of Failure
- Potential Cause/Mechanism of Failure
- Mitigating Factors (any existing control measure)
- The probability of hazard severity, occurrence, and detectability
b) Based on the Risk Analysis, an identification of the verification and/or validation activities required, including methods or tests used and acceptance criteria to be applied.
Based on a resulting calculated risk index, risk control measures are identified, required verification and validation activities are determined, and verification of the effectiveness of risk control measures is determined.
1) The inclusion of the additional performance tables for nasopharyngeal swab and nasal swab specimens against an FDA-cleared RT-PCR assay in the Clinical Performance section of the product package insert (PI) does not create any new product risks. There has been no change in the product formulation. The change is exclusively a labeling change. The current performance being observed by customers will not change as there is no change to the design or production process for this product. Therefore, because the addition of performance tables does not impact the risk associated with the device, the current risk assessment table will not change.
5
{5}
2) PBM conducted an additional clinical study during the 2017 to 2018 influenza season, testing nasophyngeal aspirate specimens sequentially obtained from a state public health laboratory, against an FDA-cleared RT-PCR assay (see Section 6 below). The results of this additional study demonstrate that the BioSign Flu A+B performance for testing nasophyngeal aspirate/wash specimens meet the performance criteria specified in 21 CFR 866.3328. The inclusion of an additional performance table for nasopharyngeal aspirate specimens against an FDA-cleared RT-PCR assay in the Clinical Performance section of the product package insert (PI) does not create any new product risks. There has been no change in the product formulation. The change is exclusively a labeling change. The current performance being observed by customers will not change as there is no change to the design or production process for this product. Therefore, because the addition of performance tables does not impact the risk associated with the device, the current risk assessment table will not change.
# 6. Clinical Performance
A supplementary clinical study was conducted to collect additional data for assessing BioSign Flu A+B performance compared against an FDA-cleared RT-PCR assay for nasopharyngeal aspirate/wash specimens, and to demonstrate that the BioSign Flu A+B performance for testing nasopharyngeal aspirate/wash specimens meets the performance criteria specified in 21 CFR 866.3328.
From October 2017 to March 2018, residual nasopharyngeal aspirate/wash samples were sequentially collected from the specimens that were received at a state public health laboratory for influenza confirmation testing. The state public health laboratory recorded the specimen collection date, gender, and age for each patient from whom the specimen was collected on a log sheet as each specimen was received at the laboratory for influenza confirmation testing. The samples were blinded and numbered before they were frozen at -70° C and shipped to PBM on dry ice.
Samples received at PBM were thawed and tested using the BioSign Flu A+B test¹ according to the standard procedure in the package insert. The remaining sample was frozen at -70° C and shipped frozen on dry ice to a reference laboratory for RT-PCR testing using an FDA-cleared influenza RT-PCR assay².
The total number of samples tested was 226, of which 147 samples were Flu A positive, 41 were flu B positive, one sample was both Flu A and Flu B positive, and 37 samples were both Flu A and Flu B negative by FDA-cleared influenza RT-PCR assay. Fifteen (15) percent of the total number of samples were from patients aged 5 and younger, 9% were from patients 6-21 years
¹ An internal analytical validation study conducted at PBM demonstrated that freeze/thaw of NP aspirate/wash specimens neither favorably nor adversely impact the performance of the BioSign Flu A+B.
² An internal analytical validation study conducted at the reference laboratory demonstrated that the limit of detection of the FDA-cleared influenza RT-PCR assay testing NP aspirate/wash specimens is equivalent to that of testing NP swab collected in VTM specimens. In addition, an internal analytical validation study conducted at the reference laboratory also demonstrated that the performance of the FDA-cleared influenza RT-PCR assay testing NP aspirate/wash specimens was not adversely impacted after three freeze/thaw cycles of the specimens.
6
{6}
old, and the remainder were from patients older than 21. Forty-four (44) percent of the total number of patients were male and 54% were female. For five of the samples the gender was not reported. Out of the 226 samples tested, there were no invalid BioSign Flu A+B test results.
The testing results compared against the FDA-cleared influenza RT-PCR assay are presented in Table 6 below.
Table 6: Nasophyngeal Aspirate/Wash Samples - Performance against an FDA-cleared RT-PCR Assay (Clinical Study from 2017 to 2018)
| | RT-PCR Results | | | |
| --- | --- | --- | --- | --- |
| BioSign Flu A+ B | Flu A Positive | Flu A Negative | Total | Performance |
| Flu A Positive | 126 | 0 | 126 | Sensitivity: 85.1%95% CI: 78.5-90.0% |
| Flu A Negative | 22 | 78 | 100 | Specificity: 100%95% CI: 95.3-100% |
| Total | 148 | 78 | 226 | |
| | RT-PCR Results | | | |
| --- | --- | --- | --- | --- |
| BioSign Flu A+ B | Flu B Positive | Flu B Negative | Total | Performance |
| Flu B Positive | 36 | 1 | 37 | Sensitivity: 85.7%95% CI: 72.2-93.3% |
| Flu B Negative | 6 | 183 | 189 | Specificity: 99.5%95% CI: 97.0-99.9% |
| Total | 42 | 184 | 226 | |
## 7. Conclusion
The labeling for this modified subject device has been reviewed to verify that the indication/intended use for the device is unaffected by the modifications. In addition, the applicant's description of the particular modification(s) and the additional clinical study performance data generated from testing nasopharyngeal aspirate/wash specimens demonstrate that the fundamental scientific technology has not changed. The applicant has provided the design control information as specified in The New 510(k) Paradigm and on this basis, I recommend the device be determined substantially equivalent to the predicate device.
7
Two short videos show you everything — or skip straight to the written tutorial if you'd rather read. You can reopen this any time from the Tutorial button in the top bar.
Part 1 — Search, results, and everyday workflows 16 min
Part 2 — Embeddings: the galaxy map 3 min
1. Search: exact and fuzzy
Type a phrase like "coronary artery calcification" into the search box. You get two kinds of results. Exact results match the literal phrase — prefix searches work ("coronary artery calcificati") but suffix searches do not. Fuzzy results match on the meaning and intent of your phrase rather than the exact words, and are sorted by relevance score. Hover over the Exact or Fuzzy badge on any row to see exactly why it matched.
Use the checkboxes above the results to narrow: SaMD keeps only software-only devices, AI / ML keeps only devices with AI.
Exact vs. fuzzy search: what's the difference?
Exact matches on the literal phrase (prefix search works, suffix does not). Fuzzy matches on the meaning and intent of the phrase rather than the exact words. Hover over the badge on any row to see why it matched.
You search "coronary artery calcification" and want only software devices with AI. What two filters do you apply?
Narrow by SaMD (software-only devices), then narrow by AI/ML (devices with AI).
2. The results table
Scroll right in the results table. The intended use is extracted for you — no need to open the PDF. The device story gives a high-level snapshot of what the device does and how it's used. The AI Performance sub-table shows each output name, acceptance criteria, observed values, and development/test dataset descriptions — the same format Innolitics uses for regulatory strategy outputs, and the fastest high-level fingerprint of an AI device. It is AI-generated but has been very reliable in practice.
Where do you find a device's intended use without opening the PDF?
Scroll right in the search results table. The intended use column is extracted for you; no need to dig into the 510(k) summary PDF.
What does the AI Performance sub-table show, and why is it useful?
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.
