A Longitudinal Study of Measles Antibody Titers in IVIG

1. A Longitudinal Study of Measles Antibody Titers in IVIG BPAC Don Baker August 16, 2007

2. Longitudinal Study – Measles Antibody • Longitudinal study - A study that involves the repeated observation of a variable over time. • Hypothesis: Given the efficacy of the measles vaccination program in the United States, the prevalence of plasma donors with a history of natural infection with measles is declining. As natural infection provides a longer lasting immunity, this decline will lead to a decrease in titer of measles antibody in IVIG. • Study: Examine the change in measles antibody titer in Gammagard S/D IGIV for the period January 1997 through June 2007.

3. Prevalence of Source Plasma Donors Naturally Infected With Measles Measles immunization began being widely practiced in the United States in the mid 1960s. Given the efficacy of the vaccine program, within a few years donors who had been infected with wild type measles will represent <5% of the donor population. Cohort currently naturally immunized to measles

4. Prevalence of Recovered Plasma Donors Naturally Infected With Measles

5. Assay Standard Process Donors Hemagglutination Inhibition – No change CBER Reference – No change No product impact change No change – Baxter source and ARC recovered Longitudinal Study – Measles Antibody Decline • The key assumption is that there are no other factors which changed over time that could also impact the measles antibody titer. • For this analysis significant potential confounding variables include, assay methodology, assay standard, production process and donor base.

6. Selected Characteristics of Gammagard S/D • Current production process approved in 1994. • Manufactured from source and recovered plasma. • Lyophilized preparation stabilized with albumin, glycine and glucose • Low IgA content • No enzyme treatment • No low pH treatment

7. = Average = Trend Gammagard S/D 5% IGIV(Source Plasma 1997-July 2007) = Specification

8. = Trend = Average Gammagard S/D 5% IGIV(Recovered Plasma 1997-July 2007) = Specification

9. Conclusion • The data from the longitudinal study of measles antibody titers in IGIV derived from source and recovered plasma reasonably supports the hypothesis that the decline of donors with a history of natural measles infection leads to a decrease in titer of antibody to measles virus. • Absent a change in the specification for measles antibody or other mitigating step IGIV lots will begin to fail the measles titer requirement.