Zika Virus Testing and the Continuing Saga of FDA Oversight of Lab-Developed Tests

The ongoing epidemic of Zika virus in the Northern and Southern hemispheres has certainly generated a lot of angst by patients and clinicians alike. While Pennsylvania is not a hotbed for Zika infections, a total of 17 cases for 2016 have been reported among Pennsylvania residents to date. According to a recent PA DOH alert, in each of the cases, exposure to the virus occurred during travel outside the continental United States and additional travel-associated Zika virus infections among Pennsylvania residents are expected. Most Zika virus infections are transmitted through infected Aedes mosquito bites. One species, Aedes albopictus, is common in Pennsylvania, particularly in southern Pennsylvania. Additional information on recognizing and diagnosing Zika infections and preventing local mosquito populations from becoming a reservoir of infection can be found on the PA DOH website (PDF).

One of the frustrating aspects from a laboratory point of view is the lack of commercially available test kits to detect the virus or antibodies against the virus for use in our own laboratories. That is why we were pleased to see the Texas Children’s Hospital and Houston Methodist develop an in-house LDT to detect Zika virus and is offering the test only for patients seen within their health system.

Developing an in-house test using appropriate methods to validate the test according to rules outlined by CLIA and/or CAP, and offering testing to patients is something we have been doing in Pathology and Laboratory Medicine for decades and lab validation has been part of our process since the first lab tests were described (if you know what this is, send me an email).

However, in a letter to TCH on March 2, 2016 (PDF), the FDA wasted no time by suggesting that TCH/HM were marketing the test and potentially violating rules meant to apply to commercial in vitro diagnostic manufacturers.

Several societies, The Infectious Diseases Society of America (IDSA), American Society for Microbiology (ASM) and Pan-American Society for Clinical Virology (PASCV) recently published a joint opinion paper on recommendations on the regulation of laboratory developed tests (Caliendo AM et al. Clin Infect Dis. [2016] doi:10.1093/cid/ciw260).

In this joint commentary, the authors recommend to ensure that the standards used to assess the clinical validity of LDTs are clear and streamlined. The FDA proposal, if implemented, would cost 2-5 million per test to an institution if clinical labs had to comply with rules designed for IVD manufacturers. As mentioned in my previous blog post on Lab Developed Tests, CLIA as well as CAP already have strict requirements for test validation and FDA should not require labs to repeat validation studies via an FDA-mandated process.

The authors also recommend that the FDA must use appropriate classification of tests to assess the risk of the test recognizing different patterns of use in different disease areas and to balance the risk associated with the current use of the test against the risk of curtailing patient access to the test under the proposed regulations. Further, the lab response to public health emergencies must not be hindered by these regulations.

Irving Nachamkin, DrPH, MPH, D(ABMM), FAAM, FIDSA, is the Director of the William Pepper Laboratory and the Division of Laboratory Medicine at Penn Medicine.

Disclaimer: The views and opinions expressed in this blog column are those of the authors or other attributed individuals and do not necessarily represent the official position of the Department, Penn Medicine, or the University of Pennsylvania. Health information is provided for educational purposes and should not be used as a source of medical advice or diagnosis.

Image: Neural Cells Infected with Zika Virus, courtesy of Sarah C. Ogden, Florida State University, Tallahassee (CC BY 4.0 License)