Preclinical / Clinical Immunogenicity Risk Assessment & Mitigation Planning

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

  1. 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.
  2. 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.
  3. 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).
  4. 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”
  5. 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”
  6. 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
  7. 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
  8. 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
  9. Wadwa, M, Thorpe,R., Unwanted Immunogenicity: Implications for Follow-On Biologics, Drug Information Journal, Vol 41 pp1-10, 2007
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