Case Studies Assessing Immunogenicity Risk of Recombinant Therapeutic Protein Attributes with Implications for Parenteral Drug Product Manufacturing

Protein biotherapeutic drug product manufacturing can promote biophysical and degradative changes such as aggregation generation. Additionally, multiproduct manufacturing of biotherapeutic proteins generate cleaning-induced protein degradants because of extreme pH and temperature conditions during the cleaning process. Both aggregate generation during manufacturing and generation of cleaning induced degradants may increase the risk of immunogenicity and decrease the function of the biotherapeutic. Here, we present two case studies assessing the immunogenicity risk assessment of recombinant biotherapeutic protein attributes in two case studies. Case study 1 investigates the threshold of biotherapeutic aggregate numbers required to induce immunogenic responses in vitro, in vivo, and in clinical settings. Case study 2 explores the immunogenicity risk associated with cleaning-induced degradants of recombinant therapeutic proteins. The presented findings have implications for parenteral drug product manufacturing.