Blood Products Advisory Committee Meeting

 March 14-15, 2002

FDA’s Current Thinking on Parvovirus B19 NAT for Blood and Plasma

Issue:

FDA seeks to clarify the circumstances under which the Agency would regard NAT testing for Human parvovirus B19 to be “in-process” testing, medical diagnostic testing and/or donor screening.

Background

Consistent with the advice of BPAC (held in September 1999), FDA has allowed the testing of plasma pools for parvovirus B19 by NAT as “in-process” tests to ensure the quality of Source Plasma and Solvent/Detergent Treated Pooled Plasma.  Test results were used to reject reactive units, but donors were not notified or deferred.   BPAC did not recommend resolving the reactive manufacturing pool to the individual donor.  FDA has reviewed these NAT methods as analytical procedures with respect to sensitivity, specificity and reproducibility under license supplements for the manufactured products, and in the absence of “free-standing” approvals for the NAT tests per se.

FDA has become aware that Source Plasma fractionators have been performing high-titer minipool testing and resolving reactive to individual donorsFDA understands that such high-titer, i.e., insensitive, screening may not capture all infectious donors and hence products (especially unpooled components).  The viremic period for B19 infected donors can be very lengthy.  The infectivity is largely depending upon the balance between virus and the presence of anti-B19 antibodies (which can potentially complex with or neutralize the virus).   A sensitive test may remove low-level B19 DNA and anti-B19 IgG positive donations, which may adversely affect anti-B19 levels in plasma pools and resulting products.

FDA is also aware that Whole Blood industry would like to implement similar high-titer B19 NAT screening as those by Source Plasma fractionators.  It has been proposed that such testing should be regarded by FDA as “in-process” testing on recovered plasma, and not as donor screening.   At least initially, reactive minipools would not be resolved to identify individual reactive donors.   Additionally, it has been stated that pre-release testing and labeling are not feasible for blood components, for lack of an appropriate technology infrastructure.  As proposed, test kit manufacturers may provide their systems and reagents for such testing.   The validation of these test methods would be reviewed under the license supplement mechanism submitted by fractionators. 

FDA’s Current Thinking

The following points summarize FDA’s current thinking on parvovirus B19 NAT for Blood and Plasma.  FDA is considering recommending that: