BioScience

A Longitudinal Study of Measles Antibody Titers in IVIG

BPAC Don Baker August 16, 2007

BioScience

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.

BioScience Prevalence of Source Plasma Donors Naturally Infected With Measles 40% 35% 30% 25% 20% 15% Cohort currently naturally immunized to measles 10% 5% 0% 18-21 22-30 31-40 41-50 51-60 >60 Age 24.98% 35.65% 19.03% 14.70% 5.41% 0.23% 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.

BioScience Prevalence of Recovered Plasma Donors Naturally Infected With Measles 50 48 46 44 42 40 38 36 1997 1998 1999 2000 2001 2002 2003 2004 Birth Year <1957

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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.

• Assay  Hemagglutination Inhibition – No change • Standard • Process • Donors  CBER Reference – No change   No product impact change No change – Baxter source and ARC recovered

BioScience

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

Gammagard S/D 5% IGIV

(Source Plasma 1997-July 2007) BioScience

19 97 19 98 19 99 20 00 20 01 20 02

= Average = Trend = Specification

20 03 20 04 20 05 20 06 20 07

Gammagard S/D 5% IGIV

(Recovered Plasma 1997-July 2007) BioScience = Average = Trend = Specification

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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.