Immunogenicity

Immunogenicity Testing
Biotherapeutics (“Biologics”) unfortunately often induce unwanted immune responses. Formation of anti-drug antibodies (ADA) may cause adverse reactions leading to reduction in efficacy and drug safety, or induction of autoimmunity. The risk of ADA-formation is related to a number of factors including the production process, formulation and dosing. Careful assessment of immunogenic risks is required by the regulatory bodies. The development and validation of immunogenicity assays currently is currently under constant discussion within the industry. Chimera Biotec is involved in international workshops in Europe and North America to keep ahead of the latest developments in this area.
Following current guidelines, we use a variety of technologies (ELISA, ECL, Imperacer®) in a stepwise approach (screening assay > confirmatory assay > neutralization assay > characterization assay) to systematically assess the extent and the nature of an immunogenic response. Recently we worked with:

  • Therapeutic Antibodies
  • Therapeutic Proteins (unpegylated¸ pegylated)
  • Peptide Drugs

Assessing the Immunogenic Risk
Chimera Biotec has the expertise and capability to provide the most powerful immunoassays for immunogenicity testing from ADA-screening to immune response characterization. These are key requirements for immunogenicity assays:

  1. Minimal Drug Interference: Residual drug strongly interferes with ADA detection. Therefore Chimera uses extremely drug tolerant assays (Imperacer®) showing drug tolerances better than 1:1000, without dissociation procedure or sample purification steps [1].
  2. Sensitivity in the Detection of Low Affinity Antibodies: Due to ultra-sensitivity Imperacer® is a powerful tool for the detection of low affinity antibodies in early stages of development. On average, Imperacer® assays show sensitivities of approximately 1000-fold greater than ELISA and 10 to 100-fold greater than ECL, while using the same set of antibodies.
  3. Large Dynamic Range: Imperacer® assays typically have a dynamic range for reliable analyte quantification of 4-6 logs (linear range: 3-4 logs) with usually one sample dilution to cover the entire assay range. 
  4. Minimal Matrix Interferences, high precision, excellent Drug Tolerance: In combination with Chimera´s AnySource® sample preparation technology, Imperacer® assays have the capability for high sample dilution ratios. This leads to the minimization of matrix effects and typical standard deviation of less than 5%.  

You need assistance with your ADA-testing? Request information from our support Team.


Industry Guidance Documents:

  • Recommendations for the design and optimization of immunoassays used in the detection of host antibodies against biotechnology products. JIM (2004) 289 (1-2):1-16
  • Recommendations for the design, optimization, and qualification of cell-based assays used for the detection of neutralizing antibody responses elicited to biological therapeutics. JIM (2007) 321 (1-2):1-18
  • Recommendations on risk-based strategies for detection and characterization of antibodies against biotechnology products. JIM (2008) 333 (1-2):1-9
  • Key Elements of Bioanalytical Method Validation for Macromolecules. The AAPS Journal (2007) 9 (2) E156-E163

 

Literature:

[1] M. Spengler, M. Adler, A. Jonas, C.M. Niemeyer, Immuno-PCR assays for immunogenicity testing, Biochem. Biophys. Res. Commun. 387 (2) (2009) 278-282.