A significant proportion of anti-parvovirus B19 is considered to be neutralizing antibody. The apparent viral safety of plasma derivatives with respect to B19 has been attributed to the presence of appreciable anti-B19 antibodies in the starting plasma pools and hence the resulting products. IGIV has been used to treat B19 infection albeit an off-label use. However, we found varying levels of anti-B19 IgG among different IGIV products. An IGIV product had significantly lower anti-B19 levels than other IGIV products. The unique manufacturing procedure for the IGIV may be the contributing factor. Further monitoring the anti-B19 levels in IGIV products is needed to ensure that the minipool screening of plasma by B19 NAT recently implemented by some manufacturers has not adversely compromise the product safety. In collaboration with scientists in OVRR, we continued to monitor levels of anti-measles antibodies in IGIV products. Varying neutralizing antibody levels were also found among IGIV products and the same IGIV product mentioned above also had significantly lower antibody levels. Further studies are needed to determine the factors affecting the levels and to evaluate the neutralizing capabilities by the IgG fragments and subclasses. The existing CBER anti-D immunoglobulin standard, Lot 3, is about to be depleted and we found it to be HCV RNA positive. It contains white precipitous material and a high percentage of polymers (the latter detected by HPLC). The current International Reference Preparation (IRP) of anti-D immunoglobulin was also formulated many years ago and found HCV RNA positive. In collaboration with Dr. Susan Thorpe of NIBSC, an anti-D immunoglobulin preparation was formulated by diluting one manufacturer's anti-D immunoglobulin bulk and mixing with another low-titer bulk from another manufacturer to achieve appropriate anti-D potency, ca 300 IU/mL, and IgG concentration, ca 2% IgG. It was then filled into ampoules and freeze-dried. WHO/NIBSC, CBER and EDQM subsequently carried out a joint international collaborative study to calibrate this lyophilized preparation against the IRP and the CBER lot 3 standard, and to calibrate two reserve candidate European Pharmacopoeia (Ph Eur) Biological Reference Preparations. We set up an anti-D potency assay utilizing a flow cytometric method and were one of many testing laboratories participated. The data have been collected but are still being analyzed. The consensus level of this anti-D standard, which may be used as a global (International/US/Ph. Eur) standard, is still in the process of being determined. We evaluated our HPLC methods so that they can sensitively monitor the molecular integrity for respective immunoglobulin and albumin products. The purity of several recombinant protective antigen (rPA) preparations for Anthrax has been evaluated. In addition, the molecular integrity for some lots of Vaccinia Immune Globulin (Human), Vaccinia Immune Globulin Intravenous (Human), and other licensed/pending immunoglobulins has also been determined.
