The U.S. diagnostic market celebrated three regulatory firsts last week.
1. FDA Authorizes Marketing of First Zika Test
Until now, tests for detecting Zika virus immunoglobulin (IgM) antibodies in blood were only authorized for emergency use under FDA's Emergency Use Authorization (EUA) authority. On Thursday, the agency said it has authorized marketing of the ZIKV Detect 2.0 IgM Capture ELISA under the agency's traditional premarket authority. The test is manufactured by InBios International.
“At the onset of the Zika virus outbreak, when little was known about the disease or how to diagnose it, the FDA worked quickly with manufacturers to encourage the development of diagnostic tests and ensure they were available using our emergency use authorities,” said FDA Acting Commissioner Ned Sharpless, MD.
Authorizing tests under EUA allowed manufacturers and the agency to respond quickly to the Zika emergency while continuing to review the safety and effectiveness of the test under the traditional regulatory pathway.
The Zika virus is spread to people primarily through the bite of an infected Aedes species mosquito. While many people with Zika virus infection experience no symptoms, the virus can pose potentially serious risks to public health. Links between Zika virus infection and neurological complications (i.e., Guillain-Barré Syndrome), as well as microcephaly (abnormal smallness of the head) and other poor outcomes associated with Zika virus infection during pregnancy, have increased the importance of having diagnostic tests available for Zika virus. In 2016, the Centers for Disease Control and Prevention announced that limited local mosquito-borne Zika virus transmission had been reported in the continental U.S. In 2018 and 2019, no local mosquito-borne Zika virus transmission was reported in the continental United States.
The ZIKV Detect 2.0 IgM Capture ELISA is designed to identify proteins (antibodies) produced by the body's immune system when it tests for Zika virus infection in the blood. IgM antibodies indicate an early immune response. The FDA reviewed data from a clinical study of 807 test samples and a variety of analytical studies, which demonstrated that the ZIKV Detect 2.0 IgM Capture ELISA was safe and effective at identifying IgM antibodies against Zika virus in blood.
The ZIKV Detect 2.0 IgM Capture ELISA is for use only in patients with clinical signs and symptoms consistent with Zika virus infection, and/or who meet the CDC’s Zika virus epidemiological criteria, such as a history of residence in or travel to a geographic region with active Zika transmission at the time of travel. Results of this test are intended to be used in conjunction with clinical observations, patient history, epidemiological information, and other laboratory evidence to make patient management decisions. Negative results may be seen in specimens collected before day four after the onset of symptoms or after the window of detectable IgM closes, and therefore do not preclude the possibility of Zika virus infection, past or present. This test is not authorized by FDA for testing blood or plasma donors.
2. FDA Clears First Extragenital Tests for Chlamydia and Gonnorrhea
Previously, if you needed to be tested for chlamydia and gonorrhea, you either had to give a urine sample or have a vaginal and endocervical swab test. Now, U.S. testing can be performed using samples from the patient's throat or rectum.
FDA cleared two tests designed to detect the presence of the bacteria Chlamydia trachomatis and Neisseria gonorrhoeae, which cause the sexually-transmitted infections, respectively, chlamydia and gonorrhea, through diagnostic testing of extragenital specimens. The agency cleared Hologic's Aptima Combo 2 Assay and Cepheid's Xpert CT/NG for extragenital diagnostic testing of these infections via the throat and rectum.
According to the agency, the two tests will fill an unmet public health need by allowing more screening. Both tests were reviewed through the premarket notification 510(k) pathway.
In its evaluation of the devices, the FDA reviewed clinical data collected through a cross-sectional study coordinated by the Antibacterial Resistance Leadership Group, which is funded and supported by the National Institute of Allergy and Infectious Diseases. The study was a collaborative, multi-site clinical study of more than 2,500 patients that evaluated the diagnostic accuracy of multiple commercially available nucleic acid amplification tests for detection of Neisseria gonorrhoeae and Chlamydia trachomatis from the throat and rectal sites. The results of this study, along with other information reviewed by the FDA, demonstrated that the Aptima Combo 2 Assay and the Xpert CT/NG for extragenital specimens are safe and effective for extragenital testing for chlamydia and gonorrhea.
3. FDA Greenlights First Test to Help Detect Prosthetic Joint Infections
FDA permitted marketing of the Synovasure Lateral Flow Test Kit as an aid for the detection of periprosthetic joint infection (infection around a joint replacement) in the synovial (lubricant) fluid of patients being evaluated for revision surgery, which is surgery performed to replace or compensate for a failed implant.
“Prior to today’s authorization, there were no FDA-authorized diagnostic tests specifically designed to help health care professionals determine whether the inflammation around a prosthetic joint was due to an infection or another cause,” said Tim Stenzel, MD, PhD, director of the Office of In Vitro Diagnostics and Radiological Health in FDA’s Center for Devices and Radiological Health. “With this test, health care professionals now have an additional option available to aid their clinical assessment as to whether the patient has an infection and requires revision surgery. Whereas before surgeons may have opted for surgery when the presence of infection was unclear, with this test, they have more information and could potentially reduce patient risk by avoiding unnecessary revision operations for replacement joints.”
Manufactured by CD Diagnostics, the Synovasure Lateral Flow Test Kit detects proteins called human alpha defensins in the synovial fluid of patients with a total joint replacement in roughly 10 minutes. The test kit is intended as an aid in determining whether there is an infection present in synovial fluid. It is not intended to identify a specific type of infection. The test results are also intended to be used in conjunction with other clinical and diagnostic findings to aid in a patient’s diagnosis of prosthetic joint infection.
FDA reviewed data from a clinical study that analyzed 305 prospective synovial fluid samples collected from individuals with a total knee or hip joint replacement who were being evaluated for revision surgery. The study showed that 89.5% of subjects with an infection diagnosis based on the standard of care criteria were also identified as positive for alpha defensin by the Synovasure Lateral Flow Test Kit.
The product was reviewed through the de novo premarket pathway. FDA said it is also establishing criteria called special controls, which determine the requirements for demonstrating the safety and effectiveness of tests to detect and measure non-microbial analytes (substances) that aid in the detection and identification of localized human infections. These special controls, when met along with general controls, provide a reasonable assurance of safety and effectiveness for these tests.