Both the FDA and the EMA have advised that Sponsors determine the risk their biotherapeutic has of inducing an immune response. The risk is a combination of the likelihood of inducing an immune response combined with the impact an immune response would have. There are host-specific and product specific factors to take into account. Because immunogenicity is a safety consideration the sponsor should prepare a risk assessment and management plan prior to human trials that details the likelihood and impact of immunogenicity and the extent of ADA characterization.
Immunogenicity References
- Mire-Sluis, A.R., Barrett, Y.C., Devanarayan, V., Koren, E., Liu, H., Maia, M., Parish, T., Scott, G., Shankar, G., Shores, E., Swanson, S.J., Taniguchi, G., Wierda, D., Zuckerman, L.A. (2004) Recommendations for the design and optimization of immunoassays used in the detection of host antibodies against biotechnology products. J. Immunol. Methods, 289, 1-16.
- Gupta, S., Indelicato, S.R., Jethwa, V., Kawabata, T., Kelley, M., Mire-Sluis, A.R., Richards, S.M., Rup, B., Shores, E., Swanson, S.J., Wakshull, E. (2007) Recommendations for the design, optimization, and qualification of cell-based assays used for the detection of neutralizing antibody response elicited to biological therapeutics. J. Immunol. Methods, 321 (1-2), 1-18.
- Koren, E., Smith, H.W., Shores, E., Shankar, G., Finco-Kent, D., Rup, B., Barrett, Y.C., Devanarayan, V., Gorovits, B., Gupta, S., Parish, R., Quarmby, V., Moxness, M., Swanson, S.J., Taniguchi, G., Zuckerman, L.A., Stebbins, C.C., Mire-Sluis, A.R. Recommendations on risk-based strategies for detection and
characterization of antibodies against biotechnology products, (in press). - Shankar, G., Shores, E., Wagner, C., and Mire-Sluis, A., Trends in Biotechnology, vol 24, no. 6, June 2006 “Scientific and regulatory considerations on the immunogenicity of biologics”
- Shankar, G., Pendley C., and Stein, K. Nature Biotechnology, vol 25, no. 5, May 2007 (www.nature.com/naturebiotechnology) “A risk-based bioanalytical strategy for the assessment of antibody immune responses against biological drugs”
- Rosenberg, Amy S., and Worobec, Alexandra, Biopharm International, Nov 2004, 17, 11 pg 22, A Risk- Based Approach to Immunogenicity Concerns of Therapeutic Protein Products, Considering Consequences of the Immune Response to a Protein
- Rosenberg, Amy S., and Worobec, Alexandra, Biopharm International, Dec 2004, 17, 12 pg 34, A Risk- Based Approach to Immunogenicity Concerns of Therapeutic Protein Products, Considering Host-Specific and Product-Specific Factors Impacting Immunogenicity
- Rosenberg, Amy S., and Worobec, Alexandra, Biopharm International, Jan 2005, 18, 1 pg 32, A Risk- Based Approach to Immunogenicity Concerns of Therapeutic Protein Products, Effect of Manufacturing Change on Immunogenicity and the Utility of Animal Immunogenicity Studies
- Wadwa, M, Thorpe,R., Unwanted Immunogenicity: Implications for Follow-On Biologics, Drug Information Journal, Vol 41 pp1-10, 2007