9th International Marbach Castle DDI Workshop

In its 9th year, the Workshop will cover a number of highly important regulatory topics in depth. The entire first day of the meeting will be dedicated to current regulatory issues.

The US FDA released two new drug-drug interaction (DDI) Guidance documents in October 2017 to replace the 2012 draft DDI Guidance. The two documents are entitled “Guidance on Clinical Drug Interaction Studies – Study Design, Data Analysis, and Clinical Implications” and “Guidance on In Vitro Metabolism- and Transporter-Mediated Drug-Drug Interaction Studies”. Both provide pharmaceutical companies comprehensive guidance on how to evaluate investigational drugs for potential clinical DDIs and drug labeling.

In the “Clinical Drug Interaction Studies Guidance”, the timing of clinical DDI trials, the design and conduct of the DDI studies, the reporting and interpreting of such study results and labeling recommendations are provided.

In turn, the “In Vitro Metabolism- and Transporter-mediated DDI Studies Guidance” provides recommendations on the in vitro approaches to the evaluation of potential DDIs that involved metabolizing enzymes and/or transporters, and how in vitro outcomes can inform clinical DDI studies. The presentation of both Guidance documents will examine and discuss the changes of the new guidances and their impact on in vitro and clinical study requirements. A second presentation on the In Vitro Metabolism- and Transporter-Mediated Guidance will provide an expert perspective on practical implications.

A second part of the regulatory session will comprise a Consortium perspective on the important issue of PBPK model qualification and reporting procedures for regulatory submissions, and a presentation on dynamic drug labels for optimal management of DDIs in patient care. Finally, a representative of the French Agency ANSM will share concepts of the regulatory assessment of two DDIs involving the activation of prodrugs by a distinct enzyme and their consequences.

Two regulatory panel discussions will provide ample opportunity for a lively discussion of the audience with the presenters.

The second meeting day will start with a session on mechanistic models and PBPK sensitivity assessment. In the latter, sensitivity analyses towards model credibility, uncertainty, verification and validation will be presented, while the talk on mechanistic models will address the search of sensitive endogenous markers for transporter DDIs, with creatine and coproporphyrin I as examples for renal and hepatic uptake-transporter DDI markers.

Furthermore, the 2018 workshop programme comprises two sessions dealing with the mechanistic assessment of pharmacokinetic DDIs (Session “Phenotyping Revisited”) including presentation of a microdosing cocktail approach for direct acting oral anticoagulants (DOACs), and a session on non-CYP related metabolic DDIs with a particular emphasis on UDP-glucuronyltransferase (UGT)-based DDIs.

As in the previous years, the topics of the 9th International DDI Workshop will be presented by distinguished international scientists and experts from academia, pharmaceutical companies, contract research organizations, consultancies as well as government and regulatory agencies. All topics will be presented from different angles by presenting non-clinical information from in vitro studies, clinical studies as well as PBPK simulations linking non-clinical and clinical data.

We are hoping to welcome you in Marbach in May of 2018       
The Workshop Organizers

Hartmut Derendorf, PhD, FCP 
Robert Hermann, MD, FCP 
Amin Rostami-Hodjegan, PhD, FCP       
Oliver von Richter, PhD, FCP

Workshop Programme 2018