FDA Clarifies Syphilis Screening Procedures for Blood, Plasma Donations

Regulatory NewsRegulatory News | 28 August 2014

A new guidance document issued by the US Food and Drug Administration (FDA) finalizes an earlier draft set of recommendations on how blood and plasma collection centers can screen donors and samples for syphilis.


Blood and plasma donations, like the donation of all cell and tissue products, are already subject to a battery of tests to ensure they are not contaminated with any serious diseases. At present, those tests include ones to detect hepatitis B and C, HIV-1/2, the West Nile virus, Chagas disease, human T-lymphotropic virus (HTLV), and syphilis.

Syphilis is a sexually transmitted bacterium that undergoes three distinct stages. During the first stage, a patient will experience visible sores lasting between three and six weeks. In the second stage of the disease, the initial sores heal, but the disease causes skin rashes and sores to emerge in other areas. In the final and latent stages of the disease, syphilis can cause dementia, blindness, paralysis and organ damage, sometimes not for decades after the initial infection.

While syphilis infections are rare—the American Red Cross reported just 324 cases in potential donors between 2007-2008—they’re still considerably more common than other transmissible diseases reported during that same time period.

Final Guidance

FDA's new final guidance, Recommendations for Screening, Testing, and Management of Blood Donors and Blood and Blood Components Based on Screening Tests for Syphilis, is intended to supersede a June 2003 one entitled, Guidance for Industry: Revised Recommendations for Donor and Product Management Based on Screening Tests for Syphilis.

At its most basic level, the guidance explains that donation facilities are required to perform a serological screening test on each donation of blood for the presence of syphilis. Donors must be tested upon their first plasmapheresis, and then every four months thereafter so long as they do not fail the first test. Donors may later be re-qualified if the test is found to be a false-positive, and must be tested every 12 months.

FDA recommends using both non-treponemal assays and treponemal assays to test for the bacteria, though the latter are noted as being somewhat less useful than the former since they do not monitor the progression of the disease or its response to antibiotics, whereas the former does. When used together, the tests offer a measure of redundancy.

However, neither is particularly useful in catching the disease in its most critical stage: early infection, when antibodies are not yet present.

To catch donors within this "window period,"—and all periods—FDA advises sponsors utilize a multi-pronged approach including questionnaires to assess risk factors, frequent donor screening (every four months) using FDA-approved test methods and redundant retesting of all positive results.

Comments and Changes

Comments submitted to FDA by the American Association of Blood Banks (AABB) and others indicated some desire for changes to FDA's draft guidance. AABB, for example, requested more than a half-dozen minor word changes to the document to, in its words, allow for greater flexibility. Some of those word changes have been included in the final guidance.

Another group, the Plasma Protein Therapeutics Association (PPTA), however, called on FDA to eliminate syphilis testing as a donor eligibility screening test for plasma products altogether, saying that testing requirements were "outdated" and had "limited public health benefit" since the required tests "cannot discern between active, untreated infections and old, treated infections in 'serofast' individuals for up to 1-2 years after treatment." EU regulators, PPTA noted, don't have syphilis screening requirements for source plasma. FDA did not accommodate this request in its final guidance.

Another comment noted that "of the four tests listed on the CBER [website] cleared for donor screening for Treponema Pallidum, only two of the approved tests are even available for [purchase] in the US." One test has since been discontinued, while the other is not cleared for use in the US. The same commenter noted that of the remaining two tests, one was not suitable for small-scale laboratories such as the one employing the commenter. Another comment advanced similar arguments. FDA has now expanded its list of acceptable syphilis screening tests to include several others.


Recommendations for Screening, Testing, and Management of Blood Donors and Blood and Blood Components Based on Screening Tests for Syphilis (FR)


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