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

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 three switches are needed to optimize the detection of potential PK differences, 2) the initial incidence of anti-drug antibodies (ADA) 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 two biological products. This article is protected by copyright. All rights reserved.