Paradigm of combination biologics: analytical challenges related to pharmacokinetic assays and interpretation of pharmacokinetic and immunogenicity results.

摘要

BACKGROUND: Combination biologic therapy is an emerging area of clinical development and the physiological and analytical impact of one treatment on the other requires careful assessment. Significant analytical challenges are associated with developing the corresponding pharmacokinetic assays and further challenges arise in interpreting the subsequent in vivo data, which may be confounded by immunogenicity to one or both of the biologics. RESULTS: A case study of two monoclonal antibody therapeutics, given in combination, is presented where the immunogenicity rates differed significantly when the drug(s) were administered as monotherapy or in combination. CONCLUSION: The interpretation of the in vivo data is inextricably linked to an in-depth understanding of the formats and performance attributes of the associated pharmacokinetic and immunogenicity assays.