The formulation and immunogenicity of therapeutic proteins: Product quality as a key factor.
The formation of anti-drug antibodies represents a risk that should be assessed carefully during biopharmaceutical drug product (DP) development, as such antibodies compromise safety and efficacy and may alter the pharmacokinetic properties of a compound. This feature review discusses immunogenicity issues in biopharmaceutical DP development, with a focus on product quality. Excipient-induced and aggregate-induced immunogenicity are reviewed based on the concepts of 'aggregation-competent' species and 'provocative' aggregates. In addition, the influence of formulation parameters, such as particulates and contaminants appearing in the DP during processing and storage, on aggregate-induced immunogenicity are presented, including the role of fill-and-finish equipments and the effect of interactions with container materials. Furthermore, methods to detect and quantify aggregation and precursor conformational changes in a protein formulation are reviewed, and immunological mechanisms that may lead to aggregate-induced immunogenicity are proposed and discussed.
Richard
Joel
J
Ipsen, Dreux, France. joel.richard@ipsen.com
Prang
Nadia
N
D000818:Animals; D000917:Antibody Formation; D015195:Drug Design; D064420:Drug-Related Side Effects and Adverse Reactions; D005079:Excipients; D006801:Humans; D004364:Pharmaceutical Preparations / Q000737:chemistry; D011786:Quality Control; D011994:Recombinant Proteins / Q000009:adverse effects* / Q000737:chemistry / Q000276:immunology*
D005079:Excipients; D004364:Pharmaceutical Preparations; D011994:Recombinant Proteins