By Nitisha Pyndiah, PhD

Source: CDC/ Cynthia Goldsmith (2016).

This is a transmission electron microscopic (TEM) image of the Zika virus, which is a member of the family, Flaviviridae. Virus particles are 40nm in diameter, with an outer envelope, and an inner dense core. The arrow identifies a single virus particle.’

What is Zika Virus (ZIKV)?

ZIKV is an RNA virus from the Flaviviridae family, first isolated in 1947 from a rhesus monkey, and transmitted to human through infected Aedes species mosquitos. Most infected individuals are asymptomatic and even when symptoms are experienced, they are usually mild. Importantly, Zika infections have been associated with neurologic manifestations. The virus can be transmitted to a fetus during pregnancy including from asymptomatic mothers. Reports of congenital infections include microcephaly, ophthalmologic abnormalities and other neurologic abnormalities.

It has been reported that ZIKV can be transmitted through blood and blood products. There is also a theoretical risk for transmission of the virus by cellular and tissue-based products (HCT/Ps).

What is new in this guidance document?

The updated guidance document supersedes the version from March 2016 and provides ample details about results of more recent studies. Those studies include recent epidemiological studies and impact on public health, new data about the transmission of ZIKV, the current status of availability of ZIKV tests, sexual contact risk factors and deciding when an area is considered to have an increased risk for ZIKV transmission.

Furthermore, ZIKV is a virus that is still not well characterized and there are no appropriate testing measures to prevent the transmission of ZIKV through HCT/Ps.

Those updated results still highlight the importance of applying appropriate precautions and following recommendations when considering the eligibility of living donors and cadaveric donors of HCT/Ps.

Due, in part, to the reported presence of ZIKV in semen and umbilical cord blood and other gestational tissues long after viral RNA in plasma, and that ZIKV has been identified in hematopoietic stem/ progenitor cells (HPCs) from peripheral blood; FDA urges to follow recommendations to reduce the risk of transmission of ZIKV by HCT/Ps. HPCs recipients often being severely immunocompromised may affect the outcome of the viral infection as well and increase the risk for life threatening outcomes. ZIKV disease outcome in this population still needs to be studied further to allow for better understanding.

When is an area considered to have an increased risk for ZIKV transmission?

For an area to be considered at risk for ZIKV transmission, local transmission through mosquito-borne ZIKV should have been reported or the potential risk is based on epidemiological evidence.

FDA refers to the Centers for Disease Control and Prevention (CDC) website for areas of increased risk for ZIKV infection:

What are FDA recommendations for HCT/Ps donor screening?

FDA considers ZIKV to be a relevant communicable disease agent or disease (RCDAD) under 21 CFR 1271.3(r)(2).

-For living donors of HCT/Ps to be considered ineligible:

  • Medical diagnosis of ZIVK in the past 6 months
  • Residence in, or travel to, an area with an increased risk for ZIKV transmission within the past 6 months
  • Sex within the past six months with a person who has either of the risk factors listed in items 1 or 2, above.

Additionally, donors of umbilical cord blood, placenta, or other gestational tissues should be considered ineligible if the donor has any of the following risk factors:

  • Medical diagnosis of ZIKV infection at any point during that pregnancy
  • Residence in, or travel to, an area with an increased risk for ZIKV transmission at any point during that pregnancy
  • Sex at any point during that pregnancy with a person who has either of the risk factors listed in items 1 or 2, above.

– For cadaveric donors of HCT/Ps to be considered ineligible:

  • Persons with a medical diagnosis of ZIKV infection in the past 6 months.

Finally, keep in mind that FDA is implementing this guidance document as soon as possible and within 4 weeks of the guidance issue date!

FDA Guidance for Industry. Updated May 2018. Donor Screening Recommendations to Reduce the Risk of Transmission of Zika Virus by Human Cells, Tissues, and Cellular and Tissue-Based Products.

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Suzanne Sensabaugh

Nitisha Pyndiah, PhD, is a Consultant where she provides advice for the development of biological, biotechnological, and biosimilar products.

Nitisha provides expertise in the areas of virology, molecular biology, microbiology, immunology, immunogenicity, quality control, GLP and GMP. She prepares and evaluates CMC sections, including FDA meeting documents; and conducts scientific and regulatory gap analyses. She supports technical, strategic, and operational regulatory affairs for recombinant proteins, monoclonal antibodies, and vaccines.