Impact of Switching on Pharmacokinetics of Therapeutic Biologics and Interchangeability Assessment—A Simulation Study

Abstract

The risk in terms of safety or diminished efficacy of switching between an originator biological product and a proposed interchangeable product is an important consideration for interchangeability evaluation in the regulatory framework. This simulation study evaluated the impact of several switching study design scenarios on the pharmacokinetic (PK) assessment between a virtual originator biological product and a virtual proposed interchangeable product. Our results show that (1) at least 3 switches are needed to optimize the detection of potential PK differences, (2) the initial incidence of antidrug antibodies after treatment with the reference product in the lead-in period is a significant covariate affecting the PK results, and (3) the area under the concentration-time curve is more sensitive than peak concentration in assessing the impact of switching on PK similarity. Our simulation work illustrates that a range of factors should be carefully considered when designing a switching study for the assessment of interchangeability between 2 biological products.

Switching between reference adalimumab and biosimilars in chronic immune‐mediated inflammatory diseases: A systematic literature review

“…No information about pharmacokinetics aspects has been described in our review, because we considered efficacy, safety and immunogenicity as the main areas of concern in clinical practice after switching. However, pharmacokinetic assessment could be an important aspect when designing a switching study to evaluate interchangeability 54 …”

“…However, pharmacokinetic assessment could be an important aspect when designing a switching study to evaluate interchangeability. 54 Nevertheless, the overall analysis of switching of adalimumab in different pathologies is a strength in our study, reflecting a high homogeneity of the results in terms of safety and immunogenicity among the different diseases.…”

No two classes of biosimilars: Urgent advice to the US Congress and the FDA

“…The confidence of stakeholders is essential to the success of the adoption of biosimilars. In a recent systematic review, 26 one survey showed that 6%–38% of physicians believe biosimilars and reference products are interchangeable. At the same time, another study indicated that 28% of rheumatologists feel biosimilars and reference products cannot be interchanged 27 .…”