New FDA Approvals, Guidelines and Letters Address Zika Testing

After garnering Food and Drug Administration (FDA) approval, a diagnostic test for the Zika virus is being distributed to certified labs by the Centers for Disease Control and Prevention (CDC) in March.

The test, called the CDC Zika IgM Antibody Capture Enzyme-Linked Immunosorbent Assay (Zika MAC-ELISA)—is regarded as the first FDA-approved commercial diagnostic test for Zika.

The CDC, which made an emergency use request for the test, is sharing it with labs in the Laboratory Response Network, a group of domestic and international labs that respond to public health emergencies. Hospitals and other providers seeking the tests for patients need to work through CDC and CDC-certified labs. But while this test got the green light by the FDA, the agency wrote other test-makers to challenge their Zika tests, seeking agency review of their design, validation and performance.

Finally, on March 1, the FDA issued recommendations to reduce risk of Zika virus transmission by human cell and tissue products. And in mid-February the agency advised how to reduce risk of Zika virus transmission through blood transfusions. Here is an overview of the FDA activities regarding new tests and the agency's recent guidance.

New Zika Test by CDC Detects Antibodies
How the test works: The Zika MAC-ELISA, developed by the CDC, works by detecting antibodies the body, when infected, makes to fight the Zika virus. The test can detect antibodies in blood—immunoglobulin M (IgM)—beginning four to five days after onset of symptoms through about 12 weeks, the CDC said.

Zika and its symptoms: Zika, a disease caused by the Zika virus, spreads to people primarily through the bite of an infected Aedes species mosquito, according to the CDC, which said sexual transmission is also possible. Diagnosis is challenging because about 80% of people show no signs of the disease, points out the FDA, adding that mild symptoms that may appear two to 12 days after a mosquito bite are low-grade fever, joint and muscle pain, headache and maculopapular rash. The virus has been linked by health care officials with microcephaly (causing an infant's head to be smaller than expected) in babies born to mothers with the infection.

Who needs Zika MAC-ELISA? The blood test is intended for people with a history of Zika symptoms or who have traveled to an area active with Zika, according to a CDC statement. It is being performed by labs experienced in high-complexity testing. Results, too, need to be carefully interpreted because false positives can occur in patients who had similar viruses such as dengue, CDC notes. Also, a false negative result may be reported when blood samples are collected before enough antibodies are available for measurement.

Other Zika Tests
Also, MD Biosciences Clinical and Diagnostic Services Laboratory announced in March a rapid assay to detect the Zika virus in human blood and urine samples. The nucleic acid test, with no relation to MAC–ELISA, is a diagnostic service by MD Biosciences of St. Paul, Minn. The company, after receiving a letter from the FDA, said it "will proceed with the Zika test services following clarification with the FDA regarding any pre-market approval requirements pertaining to this assay. Testing services will not be offered pending this clarification."

"Our assay is laboratory-developed test, performed by qPCR, to determine the presence of the virus. We are able to do this specifically without cross-reacting with other potential viruses such as dengue or West Nile," Eddie Moradian, PhD, chief executive officer of MD Biosciences, told National Intelligence Report. The FDA issued a letter to MD Biosciences, Inc. indicating the test "appears to meet the definition of a device" under section 201(h) of the Federal Food, Drug, and Cosmetic Act and should be subject to premarket clearance, approval or Emergency Use Authorization. The letter added that "it is particularly important for the FDA to review information related to your Zika Virus RNA by RT-PCR Assay's design, validation and performance characteristics."

The FDA has issued similar letters regarding other tests: to First Diagnostic Corporation for its ATFirst's One Step Zika Antibody Test and to Texas Children's Hospital and Houston Methodist Hospital for their Zika Direct Test intended as a rapid diagnostic test. The FDA states in those letters as well the need for the agency to review the "design, validation, and performance characteristics of those tests."

FDA Urges Caution in Donations of Human Cells and Tissues
FDA is intent on reducing risk of transmitting the Zika virus from human cells, tissues and cellular and tissue-based products (HCT/Ps) The agency released March 1 recommendations for handling these donations from living and deceased donors.

"[G]iven what we know about the virus at this point, ... we must address the potential risk of Zika virus transmission by human cells and tissues," said Peter Marks, MD, PhD, director of the FDA's Center for Biologics Evaluation and Research in a statement.

The FDA said people should be considered ineligible for donating HCT/Ps if they were: 1) diagnosed with the Zika virus infection; 2) were in an area with active Zika virus transmission; or 3) had sex with a male with either of those risk factors within the past six months.

As to donations of HCT/Ps from deceased, the FDA advises they not be accepted when the donor had the Zika virus within six months of death.

The FDA points out in its guidance document that HCT/Ps with the highest potential for transmission of the Zika virus are those recovered from living donors. For example, the virus was detected in two men's semen 62 days and 10 weeks, respectively, after onset of symptoms.

FDA Addresses Blood Transfusions
Blood transfusions and risk of Zika virus have also garnered FDA attention. In mid-February, the agency issued recommendations on how to reduce risk in the U.S. The agency said then there are no reports to date of Zika virus in the U.S. blood supply, but the risk exists given how the Zika virus and others like it spread.

Blood establishments, in areas with active Zika virus transmission, need to obtain whole blood and blood components for transfusion from areas of the U.S. without active transmission. Collection and preparation of platelets and plasmas can continue as long as FDA-approved pathogen-reduction device is used.

For those blood facilities in areas without Zika virus transmission, FDA noted importance of deferral of donors at risk of Zika virus for four weeks.

Takeaway: After an emergency request by the CDC, the FDA has approved use of a new tool to diagnose Zika virus. FDA has also promulgated guidelines for reducing risk of Zika virus transmission by human cell and tissues donations and blood transfusions.