Pharmacokinetic, pharmacodynamic and immunogenicity comparability assessment strategies for monoclonal antibodies

Chronotherapeutics: A Novel Approach in the Pharmacotherapy of Various Diseases

“…Many regulatory systems take a different approach between biosimilars and generics, because the bioequivalence for a biosimilar product cannot be easily established [17]. This is due to their structural complexity, the use of living organisms for manufacturing processes, difficulties in achieving consistency of manufactured batches and sometimes complex long term effects of their patient administration.…”

“…These changes may lead to structural differences, resulting in efficacy modifications and with potential insurgence of adverse effects, i.e., immunogenicity. In these cases, further non-clinical and clinical evaluations might be needed to evaluate the product, depending on the extent of modifications brought [16,17].…”

Biosimilars 2.0

“…Experience shows that some effects of relevant differences in structure or formulation can be detected at early stages like PK and hence, these results should be considered the first gate in a demonstration of similarity or cause for remediation before evaluations of clinical performance are initiated. 29 A unique characteristic of Biosimilar 2.0 products in comparison to their Biosimilar 1.0 predecessors is that many of these products will be mAbs, which are structurally more complex and may have more than one mechanism of action involved in their pharmacological effect through target-antigen binding, Fc-effector function(s) or Fc-receptor binding. Due to this structural and functional complexity, it is critical that any differences that exist between the various structural attributes of a biosimilar fusion molecule or mAb and its reference product are evaluated in nonclinical in vitro or in vivo pharmacology studies.…”

The Utility of Modeling and Simulation Approaches to Evaluate Immunogenicity Effect on the Therapeutic Protein Pharmacokinetics

“…While immune responses to a TP can occur in nonclinical animal species, it is often not possible to predict immunogenicity in healthy subjects and patients from animal observations (9). Hence, clinical assessment of immunogenicity in the target population and evaluation of the resulting changes in pharmacokinetics (PK) as a surrogate for pharmacodynamic variables, safety, and efficacy in the individual subject is absolutely necessary (10,11). Moreover, there is an urgent need for further research in this area given the substantial increase in the number of biological products, including biosimilars, under clinical development.…”