 |
 |
 |
FDA
Home Page | Search FDA Site |
FDA A-Z Index | Contact FDA
NEW TOOL/TECHNOLOGY: The FDA rapidly developed the standards and blood test calibration tools that enabled product sponsors to design and produce high quality products to screen donated blood for the presence of West Nile Virus. This work involved extensive collaboration with public health laboratories, product sponsors, and the blood bank industry, as well as innovative applied research. CRITICAL PATH DIMENSION: Proof of Efficacy and Industrialization of West Nile Virus blood screening tests. |
West Nile Virus (WNV) is a mosquito-borne virus that primarily infects birds but can occasionally infect humans. While most human infections are asymptomatic or produce a mild, flu-like illness, roughly 1 in 150 infections results in meningitis or encephalitis. The encephalitis is fatal in roughly 1 in 1000 infections.
In 2002, there were major outbreaks of WNV illness in several parts of the country. In August of 2002, the Centers for Disease Control (CDC) confirmed that West Nile Virus could be transmitted through donated blood. That year, West Nile Virus caused 283 deaths and 2942 cases of neuroinvasive disease (meningitis, encephalitis, or meningoencephalitis ) -- and there were no tests to screen the blood supply.
In November 2002, FDA called together members of the American Association of Blood Banks (AABB), potential product sponsors, the CDC, the Health Resources and Services Administration, the Department of Defense, and the National Institutes of Health (NIH) to initiate the joint development of WNV blood screening tests. Over the next few months, there was intense collaboration in the race to develop an initial test prior to the next summer’s peak mosquito season. The shared goal was to have one or more WNV blood tests ready for use during the 2003 season. Information gathered from use of the initial tests during the 2003 season could be used to refine the standards and the tests, for final FDA licensure. While this collaboration was on-going, FDA kept the public informed about the progress of the epidemic and development of tests through Blood Product Advisory committee meetings.
Based on the best data available and input from collaborators, the FDA set the sensitivity standard for the initial WNV blood screening products: the products must detect WNV at concentrations no less than 100 copies of WNV per milliliter of plasma (plus or minus a small allowable error range).
In order to design a blood-screening product and prove that it meets this standard, the product sponsors needed benchmark plasma samples that contain the WNV at a variety of known concentrations, including the standard concentration. This official set of samples -- a “panel” -- is the tool that enables product sponsors to determine the sensitivity of their prototype products. Sponsors test their prototypes against the official panel benchmarks to develop a product that consistently detects the virus at or above the required standard. After approval, sponsors must also test each product lot against the panels, to ensure that the manufactured product continues to meet the standard.
To develop the necessary panel, FDA acquired plasma samples from public health laboratories, the CDC, the New York Department of Health (NYDOH), and AABB members including the American Red Cross, America ’s Blood Centers and the Gulf Coast Blood Center . Using these samples, and drawing on its previous experience with the Human Immunodeficiency Virus (HIV) and the Hepatitis C Virus (HCV), the FDA embarked on an innovative program of applied research. The FDA developed a method to isolate WNV from plasma samples and also a way to determine the concentration of WNV in such samples. With these new methods, FDA prepared prototype panels.
The prototype panels were analyzed in collaborative studies involving Gen-Probe Inc., Roche Molecular Systems, Inc., Boston Biomedica, Inc., Chiron Corporation, the National Genetics Institute, and the NYDOH. Based on the results, FDA produced the initial panel.
With validated panels in hand, the product sponsors could complete their product development work and achieve licensure of their tests. In May 2003 -- less than 6 months after the effort had begun -- the FDA gave interim approval to Gen-Probe and Roche to market new WNV blood screening tests. By July 14, 2003 , every civilian and military blood bank in the United States was using one of these tests to screen blood donations.
The FDA played three key roles in the development of a new WNV blood screening test: regulator, scientific expert, and convener. As the relevant regulating agency, only the FDA could set the sensitivity standard for blood screening tests. By setting the standard quickly, the FDA eliminated uncertainty, allowing the companies to proceed with product development even before validated panels were available. The FDA was able to create the benchmark panel quickly because of its expertise and experience with HIV and HCV. In addition, only the FDA could convene and coordinate the wide array of entities (blood banks, product developers, public health laboratories) needed to collaborate to address this public health emergency.
The FDA was the only entity that could respond to the problem quickly, but it could not solve it alone. The FDA relied on plasma samples, data, and on-going collaboration from the CDC, the NYDOH, the American Red Cross, America ’s Blood Centers , and Gulf Coast Blood Center . Validating the prototype panels involved laboratories at Gen-Probe, Roche, National Genetics Institute, and NYDOH. Significantly, both product sponsors already had approved HIV and HCV screening tests; their scientific expertise was another necessary component in the effort. The collaborations are on-going today, as we work together to refine the standard, the panel, and the tests, based on our ongoing experience with the WNV.
During 2003, roughly 8.6 million blood donations were tested. Of these, more than 1000 confirmed positive donations were identified and removed from the blood supply. Since blood donations are separated into component parts that may then be given to different recipients, the identification and removal of these donations represents well over 1,500 potential recipient infections prevented. Cases of transfusion acquired WNV infection dropped from 23 confirmed in 2002 to 6 confirmed in 2003.
The sensitivity standard and panel are being refined in a new round of testing involving a wider array of laboratories, including additional potential product sponsors. In addition, the FDA is studying WNV diversity to determine whether it will need to add more WNV strains to the panel over time, as the virus evolves.