The potential for drug-drug interactions (DDIs) involving membrane transporters has become an area of intense regulatory review over the past seven years.
As our understanding of the central role transporters play in drug absorption, distribution, and elimination expands, regulatory agencies have increased expectations for drug developers to provide information regarding the contribution of transporters to the clinical efficacy and safety of therapeutic agents.
In an ongoing effort to provide expert review of the latest transporter developments, the International Transporter Consortium (ITC) recently published a series of white papers on a variety of topics related to transporters and their importance in drug development.
The publication of these papers was initiated during the 2nd ITC workshop, held in Washington DC last year. The topics range from emerging clinically relevant transporters to the potential of transporter mediated DDIs at the blood-brain barrier (BBB).
These white papers give clear directions on the transporters to study, the methods to use, and the development strategy to apply. Also included are industry case studies covering experience conducting clinical development programs under the regulatory guidelines on transporters, future perspectives, and recommendations on where additional research is required.
The regulatory landscape for transporter-drug interactions has undergone a dramatic shift over recent years, with multiple revisions to relevant guidance documents released by US Food and Drug Administration (FDA), European Medicines Agency (EMA), and Japanese Pharmaceuticals and Medical Devices Agency (PMDA). With over 20 years’ focused experience on drug transporters, and the broadest array of transporter products and services available on the market, SOLVO Biotechnology has partnered with hundreds of companies world-wide to design, conduct, and interpret experiments that conform to the latest regulatory standards and requirements.
The choice of transporter experiments to be performed for a new chemical entity or new molecular entity (NCE/NME) depends on several factors, including pharmacokinetic properties, indication and patient population, and chemical structural information. However, it is by no means required to study all transporters in all cases. We work closely to avoid unnecessary and costly experiments with our clients, designing and performing transporter studies based on all available data and in light of specific compound information. While guidance documents on transporter-drug interaction studies differ in many aspects, a general guide to the required assays for EMA (Europe), FDA (United States), and PMDA (Japan) is shown in the table below.
FDA Guidance for Industry: In Vitro Drug Interactions Studies – Cytochrome P450 Enzyme- and Transporter-Mediated Drug Interactions, 2020
EMA Guideline on Investigation of Drug Interactions, 2012
PMDA Guideline on drug interaction for drug development and appropriate provision of information, 2018