Objective 4: Diagnostics 

For influenza infection care, either pandemic or seasonal, antiviral treatments are most effective when initiated soon after symptom onset. Therefore, the primary objective of the BARDA pandemic influenza diagnostics program is to speed up the availability of diagnostic information to inform rapid antiviral prescription and treatment. 
 

Current Preparedness 
 

For almost two decades, the BARDA pandemic influenza diagnostics program has funded the development of influenza diagnostics that can detect both seasonal and pandemic influenza strains. This ability to detect seasonal along with pandemic strains ensures the tests are produced in high volumes annually and ensures commercial inventory and production capability are available whenever these tests are needed to respond to an influenza pandemic. Initially, tests were developed for laboratory use since the vast majority of tests were performed in that use-setting. As antiviral treatments became available, BARDA's investments pivoted to moving testing closer to where the patients live and work to make test results available more quickly. In 2018, BARDA began funding the development of molecular tests that could be used in people's homes while still producing lab quality results. Progress in the home testing space was greatly accelerated during the COVID-19 pandemic, and, in many cases, leveraged BARDA's prior investments in home-use influenza tests.

Currently BARDA is funding development of influenza tests for use wherever testing is needed, including in homes, doctor's offices, pharmacies, and clinical laboratories. These investments have resulted in 9 FDA cleared tests and 6 EUA tests that include influenza in a respiratory test panel that also detects one or more influenza strains with pandemic potential, such as H5. 

BARDA has also funded development of influenza subtyping tests. These tests are not typically needed for care of patients infected with seasonal strains but will be critical in the early days of a novel influenza outbreak. One subtyping test has achieved FDA 510(k) clearance and a second test that runs on a platform widely placed in domestic clinical labs is currently in development. 

As was evident during the COVID-19 pandemic, viruses such as influenza and coronavirus undergo antigenic drift over time, resulting in multiple variants within a population. To ensure tests authorized for use in the US continue to be effective for currently circulating variants, FDA monitors test performance, including test reactivity to currently circulating H5 variants. When a reduction in sensitivity is detected, FDA works with the test manufacturer to restore performance. There are currently a substantial number of influenza tests that are FDA cleared or under EUA that can detect H5 flu strains. 
 

Ongoing & Future Research Priorities 
 

Going forward, BARDA will continue investing in moving testing closer to the patient, both speeding up test results and increasing testing access. Home-use/remote use molecular flu test investments will focus on tests that are lower cost to manufacture, and hopefully more affordable to the patient, and tests with increased ability to multiplex, providing more test results in a single testing action (e.g., Flu A, Flu B, COVID-19, RSV in a single test). Of course, these tests will continue to be reactive to both seasonal and high pandemic potential strains, including avian influenza. BARDA will also continue investing in influenza tests for use in pharmacies and doctor's offices since home testing is not the best solution for some patients. We will also continue with our ongoing investments for laboratory influenza tests, particularly influenza subtyping tests.

A key lesson from the COVID-19 pandemic response is the importance of rapid testing availability for a novel emerging disease. This lesson is important for any type of emerging disease, including novel influenza strains. BARDA is investing in use of Next Generation Sequencing (NGS) platforms as diagnostics to inform clinical patient care. These platforms are routinely used in life sciences research, but currently see limited use to inform clinical patient care, mostly in cancer patient treatment. An advantage of NGS based tests is that no specialty chemicals are required to perform these tests, regardless of the disease for which a sample is being tested. The development, production, and validation of disease-specific specialty reagents for traditional technology tests for a new novel disease causes much of the delay in their availability. Unfortunately, NGS tests are more expensive to perform than traditional tests and currently are limited to use in laboratories, but they will fill an important role in the early days of a novel disease outbreak until lower cost, easier to use, traditional technology threat-specific tests can be developed.