Immunogenicity studies

Rosenberg A, Worobec A. Risk-based approach to immunogenicity concerns of therapeutic protein products. Part 3 Effects of manufacturing changes in immunogenicity and the utility of animal immunogenicity studies. BioPharm Int 2005 17 34—42. 

If immunogenicity studies demonstrate that a similar immune response is obtained at intervals shorter than the proposed clinical dosing interval (e.g., 4-6 weeks), then a truncated dosing interval (2-3 weeks) can be used in the repeat dose safety studies. The FDA recommends that one more dose than the clinical dosing regimen (N) be used in animal studies. This is termed the N + 1 rule [61].The number of animals used per group should be sufficient to detect... 

Other mitogenicity in CHO-K1 and human BIO osteosarcoma cells, human hepatoma cells and MCF-7 cells to include drug binding study to IGF-1 and insulin receptors local tolerance in pigs immunogenicity studies in rabbits... 

Rennels M, King J Jr, Ryall R, Manoff S, Papa T, Weddle A, Froeschle J. Dose escalation, safety and immunogenicity study of a tetravalent meninogococcal polysaccharide diphtheria conjugate vaccine in toddlers. Pediatr Infect Dis J 2002 21(10) 978-9. 

Coblyn JS, Weinblatt M, Holdsworth D, et al. Gold-induced thrombocytopenia A clinical and immunogenic study of twenty-three patients. Ann Intern Med 1981 95 178-181. 

In terms of efficacy, data such as the number of infusions needed and treatment outcome rAHF-PFM were effective in preventing and controlling bleedings in patients with severe hemophilia A. In safety and immunogenicity studies, no serious adverse events reported to date have been deemed related to rAHF-PFM. The incidence rates for the most common non-serious adverse events indicate that drag-related adverse events were similar or even lower in number and in nature to those observed in chnical trials with other rFVlll concentrates. To date, no inhibitors have been reported. The first rAHF, Recombinate, was developed by Baxter and became commercially available in 1992. Its long record of efficacy and safety has made Recombinate the standard for care in hemophiha A therapy [9-11]. rAHF-PFM, Advate , received market authorization in 2003 in the US and in 2004 in Europe. 

Inactivated hepatitis A vaccines have been available in the United States since 1995. These vaccines, administered as a two-dose series, are safe, highly immunogenic, and efficacious. Immunogenicity studies indicate that 99%-100% of persons respond to one dose of hepatitis A vaccine the second dose provides long-term protection. Efficacy studies indicate that inactivated hepatitis A vaccines are 94%-100% effective in preventing HAV infection. 

Acetamido-2-deoxy-D-glucopyranosyl)-D-ribitol derivatives have been prepared from D-ribitol as artificial antigens for an immunogenicity study mono-allylation of 2,3,5-tri-O-benzyl-D-... 

When conjugates of the peptide as described in footnote b were used in immunogenicity studies in mice, the order of immunogenicity was KLH and TTd > BSA conjugates and thioethers > disulphide conjugates. 

Singh, M., Singh, O., Singh, A., and Talwar, G. P., 1992, Immunogenicity studies on diphtheria toxoid loaded biodegradable microspheres, Int. J. Pharm. 85 R5-R8. 

Pivotal safety studies in a single relevant species are usually appropriate for MAbs, as are single-dose pharmacokinetic studies, a multiple-dose toxicity assessment with toxico-kinetic sampling, and immunogenicity studies. 

---