Workshop Archive

13th International Marbach Castle DDI Workshop

June 4 – June 6, 2023

2023 International Drug-Drug Interaction (DDI) Workshop at Marbach Castle

The 13th workshop extended previous year’s “back-to-normal success” with physical attendance reaching more than 60 participants and online attendance of 20 from a total of 13 different countries. With another exceptional program mixing top-notch presentations and panel discussions, the Marbach Castle DDI Workshop series is truly a go-to event for global researchers, drug developers, regulators, and practitioners.

On Day 1, Prof. Amin Rostami from University of Manchester kicked off the workshop by announcing the winner of Hartmut Derendorf Young Scientist Award to Dr. Kenta Yoshida, Genentech, US. He then kicked off the first session dedicated to Pharmacodynamic (PD) Interactions by introducing Prof. Don Mager (University of Buffalo, US) as this year’s plenary lecture speaker. Professor Mager reviewed the state-of-the-art models that can be used to predict PD-DDIs. His lecture was followed by Prof. Luca Marchetti (University of Trento, Italy) who presented “A Systems Approach to PD interactions: Implications for combination Therapy”.

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Session II ICH M12 mirrored last year’s Roadmap to ICH M12 because a draft guideline of M12 has been published in late 2022. Three speakers, Drs. Brian Ogilvie from BioIVT/Xenotech, Raj Madabushi from FDA, and Vikram Sinha from Novartis reviewed in vitro aspects, in vivo aspects, and industry perspectives of the M12 guideline, respectively. Chaired by Dr. Ping Zhao (Bill & Melinda Gates Foundation), this session was immediately followed by a panel discussion with presenters joined by Drs. Baerbel Wittke (Swiss Medic), Esther Brandon (MEB of the Netherlands), and Xinning Yang (FDA). Panel members commented on the important roles of PBPK in guiding dosing decisions at initial approval stage for many complex DDI scenarios (some of which are difficult to study clinically), and called for a concerted effort by industry and regulators to compile and share experience of DDI assessments.

Session III Biomakers for Detecting Clinical DDIs was chaired by Prof. Rostami. The session featured lectures by Dr. Kenta Yoshida (Genentech) on “Industry Application and Kinetic Considerations of Transporter Endogenous Biomarkers” (Young scientist award lecture) and by Dr. Andrew Parkinson (XPD Consulting) on “Where are we in DDI biomarkers? What has been settled and what has not? Specificity and feasibility of developing tools to identify DDIs”. Discussions during Q&A session raised attention to the maturity of using certain biomarkers such as coproporphyrins along with PBPK modeling to assess OATP DDI risk for investigational drugs.

Day 2 continued the biomarker session with Prof. Andrew Rowland (Flinders University, Australia), who provided an update of the use of liquid biopsy in assessing the induction/suppression of enzymes and transporters.

Then, Dr. Robert Hermann (cr.appliance, Germany) chaired Session IV Smoking Interactions with Prof. Isabelle Ragueneau-Majlessi (Univ Washington, US) reporting the recent publication reviewing 30 years’ experience of clinical smoking DDI studies. A panel discussion of the session contrasted methodological standards between food effect studies and smoking studies, and critiqued the lack of updated recommendations by global regulators on this matter.

Session V Excipient DDIs is the first time for Marbach workshop to systematically offer a collection of novel research in this area. Along with the previous session on smoking DDI, this session represents Marbach’s recognition of interactions beyond those between drug substances, and its signature of mixing emerging research with real-world application of the findings through mechanistic modeling and simulations in its scientific programs. Chaired by Prof. Rostami, the session included lectures by Drs. Lei Zhang (US FDA), Yuan Chen (Genentech), and Mark Warren (BioIVT) on FDA’s effort to evaluate excipient-drug interactions, the use of PBPK to entangle excipient effect from CYP inhibition effect on the PK of an investigational oncology drug, and a systematic effort to generate in vitro inhibition data for major pharmaceutical excipients.

Session VI Regulatory Session, chaired by Dr. Zhao and Dr. Hermann, was in fact on knowledge integration. Dr. Jingjing Yu (Univ. Washington, US) updated the audience with a systematic review of DDI assessment in 2022 US FDA drug approvals. This was followed by Dr. Zhao who presented the vision on building PBPK model repository that can efficiently be employed to manage clinical DDIs in diverse populations around the world. The presentations echoed Day 1’s ICH M12 session with regards to knowledge sharing.

In summary, the 2023 Marbach workshop continues to offer highly relevant programs for DDI researchers, highlight the indispensable roles of PBPK in predicting a wide range of often complex, untested clinical scenarios, and transitions to a paradigm of evaluating substance-substance interaction.

The Faculty

Robert Hermann MD, FCP
Amin Rostami-Hodjegan, PhD, FCP
Ping Zhao, PhD

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Speakers 2023

Mager, Donald E. (PharmD, PhD)
Department of Pharmaceutical Sciences, University of Buffalo; Buffalo, USA

Marchetti, Luca (PhD)
Fondazione The Microsoft Research – University of Trento, Centre for Computational and Systems Biology (COSBI), University of Trento, Italy

Ogilvie, Brian (PhD)
BioIVT/Xenotech, Kansas City, KS, USA

Madabushi, Rajanikanth (PhD)
Office of Clinical Pharmacology, Center for Drug Evaluation and Research, FDA, Silver Spring, MD, USA

Sinha, Vikram (PhD)
Global Head, Therapeutic Areas PK Sciences / Translational Medicine,Novartis Institute of Biomedical Research (NIBR), Novartis Pharmaceuticals, Berwyn, PA, USA

Yoshida, Kenta (PhD)
Genentech, USA

Parkinson, Andrew (PhD)
XPD Consulting, Shawnee, Kansas, USA

Rowland, Andrew (PhD, BSc)
Flinders University, Adelaide, Australia

Ragueneau-Majlessi, Isabelle (MD)
Dept. of Pharmaceutics, Drug Interaction Solutions, University of Washington, Seattle, WA, USA

Zhang, Lei (PhD)
Office of Generic Drugs, FDA, Silver Spring, MD 20993, USA

Chen, Yuan (PhD)
Genentech, South San Francisco, CA, USA

Warren, Mark S. (PhD)
BioIVT, Santa Clara, CA, USA

Yu, Jingjing (MD, PhD)
Drug Interaction Solutions, School of Pharmacy, University of Washington, Seattle, WA, USA

Zhao, Ping (PhD)
Bill and Melinda Gates Foundation, Seattle WA, USA

Attendee and Speaker Quotations 2023

  • Dear Robert and Karen, Amin and Ping! A 1000 thanks again for the great meeting! Excellent scientific presentations and discussions, fantastic organization and you made me feel “at home”.
  • Dear All, thank you all for organizing such a wonderful workshop! I enjoyed it.
  • Dear All, it was great meeting you in person, and thank you so much for all your effort to make this meeting so successful.
  • Dear Karen, I would like to thank you for all your efforts and support of the DDI Workshop. This was my first time attending this meeting, and I thoroughly enjoyed the experience. The scientific and social programming were outstanding, and it is very nice catching up with old friends and making new acquaintances. The planning and organization was exceptional, and thank you again for all your contributions to this event.
  • Dear Robert, Thank you very much. Thanks again to you, Amin, and Ping for organizing this wonderful workshop. Very interesting topics. Excellent presentations. Active participation from audience and great discussions.
  • I would like to echo the sentiment expressed by other participants and thank Robert, Amin, and Ping for creating the opportunity for the scientific exchange.
  • I am much impressed by the work of all your organizers!
  • Dear Robert, The Marbach DDI workshop is such a unique and wonderful experience. I truly appreciate the time and effort you and Karen have contributed to this successful meeting. Looking forward to the next one! I also had a great experience biking with some folks on Monday afternoon.
  • Dear Robert, Thank you very much for the most memorable time at Marbach DDI Workshop. Many thanks again for the excellent organization.
  • Dear Robert, Karen, Ping, Amin, Thank you so very much for having me as one of the speakers at the Marbach DDI meeting.  This was such a wonderful honour, experience, and opportunity to interact with leading scientists in the field across the world, and I clearly see the value of having a smaller group that greatly enhances the interactivity and the depth of discussions. I am also touched by the hospitality for making our experience as smooth as it can be.
  • Dear Karen and Robert, I feel honoured to have been a part of this impactful workshop. Once again, thank you for your endless efforts to make the event unforgettable.
  • Beautiful setting for Marbach Castle; Great presentation & discussions; Relaxed small informal environment to stimulate good conversations and opportunity to meet a lot of attendees.
  • Good mix of science subjects and time for informal discussion; most valuable content: biomarker section, smoking, excipients; Thanks for an inspiring, well organized, pleasant conference.
  • Thank you very much for the most memorable time at Marbach DDI Workshop. Many thanks again for the excellent organization.
  • Thank you for organising such a lovely event. We very much enjoyed our introduction to PBPK modelling in such a lovely setting. We hope to meet again at the upcoming meetings.
  • Thank you for all the excellent help and organization as always for Marbach. It was a pleasure to be here again this year.

Workshop Programme 2023

12th International Marbach Castle DDI Workshop

May 29 – June 1, 2022

2022 International Drug-Drug Interaction (DDI) Workshop at Marbach Castle a Back-to-Normal Success!

The 12th workshop was attended by academic, industry, and regulatory scientists around the world. With physical attendance reached 45 participants, the event had a true back-to-normal feel. This year, the workshop continued to use hybrid format with additional 35 virtual attendees. The workshop offered another exceptional program with top-notch presentations and unique opportunity for active dialogues. The Marbach Castle DDI Workshop series continues to be a go-to event concerning DDIs for many colleagues around the world.

Professor Amin Rostami from University of Manchester kicked off the workshop by announcing the winner of Hartmut Derendorf Young Scientist Award to Professor Henrike Bruckmüller, University Schleswig-Holstein, Kiel, Germany, and The Arctic University of Norway, and introducing Dr. Douglas McNair (Bill & Melinda Gates Foundation) to present on “Concepts and Utility of Real-World Data Analyses to Evaluate DDIs”. Real-world data analyses (RWDA) was specifically featured in the 2022 workshop. Hence, the first session, chaired by Dr. Ping Zhao, included three RWDA-related presentations: “Understanding Contraceptive DDIs through Combining Pharmacology Models and RWDA” by Professor Stephan Schmidt, University of Florida, “DDI Labelling: Can RWE Complement Regulatory Decisions on DDI Management in Product Labels?” by Dr. Joseph Grillo, US FDA; and “Utility of Clinical Practice Research Datalink (CPRD) to Evaluate Drug-Drug Interactions and DDI in Special Populations”, by Dr. Justin Hay, Certara, UK. These presentations conveyed attendees a flavor of how RWDA can be effectively applied to address different R&D and regulatory questions.

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Session II titled “Roadmap to ICH M12” included two presentations and was chaired by Dr. Robert Hermann, Gelnhausen, Germany. “Highlight of DDI guideline of Chinese NMPA” by Dr. Li Li, NMPA, China, was the first time in Marbach history to include a regulatory update by a national authority that is outside the familiar group of stringent regulators such as US FDA, EMA, and Japan’s PMDA. The second presentation “EMA DDI Guideline and ICH M12” was given by Dr. Carolien Versantvoort, Medicines Evaluation Board, The Netherlands. Dr. Versantvoort is currently member of the ICH-M12 team as EU expert on the harmonisation of the DDI guidelines, and both presenters were joined by current and former regulatory colleagues in a lively panel discussion.

Session III was chaired by professor Rodrigo Cristofoletti (University of Florida). Titled “Usefulness of PBPK Modelling to Address Complex/Network PK Interactions”, the session was in panel discussion format and included two topics: excipient-drug interactions, and endogenous biomarkers for transporter DDIs. Panel members were faculty members, Professor Schmidt (Florida), and Dr. Hannah Jones (Certara). The session highlighted strong engagement of attendees and panelists in a lively discussion, a hallmark of Marbach DDI Workshop.

Day 1 was completed by a presentation by Dr. Beatrice Saint-Salvi, ANSM, France, introducing a proposal for an advanced training of scientific employees of European Health Authorities in DDI assessment. Her talk was entitled “Planning of a European Professional Development Curriculum for the Comprehensive Assessment of Drug-Drug Interactions.”

Day 2 started with Session IV titled “Covid-19 and Conduct of DDI” and was chaired by Professor Rostami. The session included “Informing Dosing Decisions Early in Pandemics” by Professor Dongyang Liu, Peking University Third Hospital, China, “Remdesivir Approval Supported by Mechanistic Modelling” by Ramesh Palaparthy, PhD, Gilead Sciences, USA, and “PBPK Modelling to Support DDI Assessment for Regulatory Submissions – General Observations during the COVID Era” by Dr. Hannah Jones, Certara, UK. These presentations offered a unique package on experiences and lessons learned in applying PBPK modeling in R&D of repurposed and investigational new medicines to combat the viral infection, highlighting the efficient and practical use of PBPK at different stages of the pandemic around the world.

Sessions V “Pharmacogenetics” was chaired by Professor Ingolf Cascorbi, University Schleswig-Holstein, Kiel, Germany, who introduced Dr. Henrike Bruckmüller to present a lecture on “Drug-Drug-Gene Interactions”; Session VI “Biologics DDIs” was chaired by Professor Rostami, who introduced Dr. Carolina Säll, Novo Nordisk, Denmark to present an industry case example on “Assessing Therapeutic Peptide DDIs During Drug Development”.

Session VII “Gut DDI” was chaired by Dr. Zhao. The first presentation “Physiology Based Biopharmaceutics Modeling (PBBM) based food effect predictions: Current state and future perspectives.” by Dr. Christian Wagner, Merck KGaA, Germany walked the audience through the evolution of PBBM from an earlier assessment of predictability of PBPK for food effect to progresses being made by the IQ consortium. The second presentation “Absorption DDIs by Drugs Affecting GI-Tract Motility – A Case Example of a Fixed Drug Combination Development” by Dr. Hermann, cr.appliance, Gelnhausen, Germany, provided a thought-process on understanding and interpretating complex DDIs associated with fixed dose combination (FDC) products.

The workshop ended with a new format “Marbach Debate”, which revisited two topics discussed extensively in 2021 workshop as well as this year’s workshop. These topics were the planning on DDI studies related to the use of herbal products, and the conduct of clinical studies evaluating the effect of CYP3A induction.

The event was blessed by beautiful late spring weather. As usual, the attendees enjoyed the tranquil surroundings and fresh products in season including different berries, lake fish, and white asparagus. We look forward to seeing many of you at 2023 workshop!

The Faculty

Robert Hermann MD, FCP
Amin Rostami-Hodjegan, PhD, FCP
Ping Zhao, PhD

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Speakers 2022

McNair, Douglas (MD/PhD)
BMGF, USA

Schmidt, Stephan (PhD)
University of Florida, Gainesville, USA

Grillo, Joseph A. (PharmD)
Winchester, VA, USA

Hay, Justin (PhD)
Certara, UK

Li, Li (PhD)
National Medical Products Administration, China

Versantvoort, Carolien (PhD)
Medicines Evaluation Board, The Netherlands

Saint-Salvi, Béatrice (PhD)
DDI Unit, ANSM, France

Liu, Dongyang (PhD)
Peking University, Third Hospital, Beijing, China

Palaparthy, Ramesh (PhD)
Gilead Sciences, South San Francisco, CA, USA

Jones, Hannah (PhD)
Certara, UK

Bruckmüller, Henrike (PhD)
Institute of Experimental and Clinical Pharmacology, University Hospital Schleswig-Holstein, Kiel, Germany; University of Tromsø, The Arctic University of Norway, Norway

Säll, Carolina (PhD)
Novo Nordisk, Denmark

Wagner, Christian (PharmD/PhD)
Merck KGaA

Hermann, Robert (MD, FCP)
cr.appliance, Gelnhausen, Germany

Attendee Quotations 2022

  • I’ve enjoyed attenting and listening to discussion of such different stake holders (Industry, regulatory, academia).
  • Highlights of the Workshop were meeting again the community after such a long Covid 19 time; In general, high quality presentations and speakers; big thank to the faculty and the organizers. Great work!
  • For me from academia the combination of the content was quite good as it gives a good overview over the field.
  • Most valuable were insights into Chinese regulatory authorities; update on ICH-M12 roadmap – very beneficial that this harmonization will be finalized soon.
  • I’ve enjoyed the personal interaction with attendance and discussions, experience with colleagues! Super! Also, discussions with authorities and other attendees was very helpful; I know it (the Workshop) is happening every year for many years, but never made it, so happy to join this year …
  • My favourite contents included the ICH guideline presentation and all discussions of the presentations. It was great to have Chinese representatives in. I hope this can be done also in the future. There is a need to connect.
  • Important aspects of the meeting were socializing and networking with colleagues from the field of clinical pharmacology, DMPB, modelling and others, and receiving insight from regulatory agents/professionals with regulatory experience and the regulatory panel!
  • Contents such as EMA DDI guideline and ICH M12; informing of dosing discussion using mechanistic modelling were extremely useful; also glimpse into specific DDI such as contraceptives; use of PBPK modelling to support DDI assessment, food interactions; specific case report examples etc;
  • The scenery and atmosphere were wonderful and set the background to an efficient learning experience.

Workshop Programme 2022

11th International Marbach Castle DDI Workshop

May 30th – June 1st, 2021

Despite the heartbreaking rescheduling due to 2020 COVID-19 pandemic, the International Drug-Drug Interaction (DDI) Workshop at Marbach Castle returned strong in 2021 with a stellar program and a high attendance.

Using a hybrid format, the 11th workshop was attended by an international audience of academic, industry, and regulatory scientists across multiple time zones. The combined virtual and physical attendance ranged from 60 to more than 100 throughout the two-day event, a powerful testimony of an exceptional program that offered top-notch presentations and unique opportunity for active dialogues. The Marbach Castle DDI Workshop series has now proven to be a true go-to event concerning DDIs for all of those with active interest in the field around the world.

Professor Amin Rostami from University of Manchester kicked off the workshop by paying a tribute to Late Professor Hartmut Derendorf and announcing the winner of Hartmut Derendorf Young Scientists Award to Professor Daniel Gonzalez from University of North Carolina. The annual award was created to commemorate the contributions of this beloved founding faculty member of the Marbach Castle DDI Workshop. Professor Phil Hansten from University of Washington then presented workshop’s keynote speech on “The Philosophy of Drug Interactions”. He characterized philosophy as a way of “clearer thinking about any subject”, an important source of scientific inspiration. He presented many nice examples illustrating why scientists and health care professionals should worry about philosophy, and how philosophy can help to avoid DDI by applying smart treatment decisions in the presence of uncertainty.

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On Day 1, Session I “Food-Drug Interactions & Beyond” included four presentations: “Gut Feeling – Proteomics of Gut Wall and Relevance to Drug Absorption and Interactions” by Dr. Stefan Oswald (University of Rostock), “Can we Predict Formulation-Dependent Food-Drug Interactions?” by Professor Rodrigo Cristofoletti (University of Florida), “Food-Drug Interactions – Considerations from the IQ Working Group and Food Effect Case Studies” by Dr. Tycho Heimbach (Merck), and “Regulatory Science on Assessing Food Drug Interaction – Highlights from New FDA Guidance” by Dr. Rajanikanth Madabushi (US FDA). This is the first time in Marbach history to collectively highlight the current understanding of food-drug interactions even though the subject has been the focus of individual lectures in 2011 , 2015, and 2016. The ability of PBPK models to predict food effects on and absorption of drugs, and formulation-dependent nature of it, and evolving regulatory thinking on the risk assessment of food-drug interactions via such modelling was subject of intense discussions.

Session II “Pharmacodynamic Interactions” was requested by many participants and on the Workshop agenda for years, and was featured this year for the first time. The session had two speakers. Dr. David Juurlink (Sunnybrook Health Sciences Centre) presented “Common Pharmacodynamic Interactions of Clinical Importance”; Dr. Jin Yan Jin (Genentech) presented “Revisiting Pharmacodynamic Interactions: Benefits and Watch-outs in Oncology”. The attendees appreciated the need to understand DDIs at the PD level, especially in times with increasing poly-pharmacotherapy in ageing populations.

The last session on day 1 (Session III) was “The Final FDA Guidance Documents on Drug Interactions”. Dr. Andrew Parkinson (XPD Consulting) and Dr. Robert Hermann (Clinical Research Appliance) presented introductory lectures “What did the FDA Change when it Finalized its In Vitro Drug Interaction Guidance in January, 2020?” and “The Final FDA Guidance on Clinical Drug Interaction Studies — Cytochrome P450 Enzyme- and Transporter-Mediated Drug Interactions”, respectively. Each presentation was followed by active panel discussions contributed by Drs. Esther Brendon (Dutch, MEB), Eva Gil Berglund (Certara, former Swedish MPA), Raj Madabushi (US FDA), Xinning Yang (US FDA), Margareta Bego (Croatian Drug Regulatory Agency) and Stéphanie Hueber (French ANSM).

Day 2 started with Session IV titled “Translational DMPK”. Three lectures were: “Liquid Biopsy, its Applications, Limitations, and Potential Role for Characterising Individual Hepatic Drug Elimination Capacity” by Professor Brahim Achour (University of Manchester; now part of University of Rhode Island), “Metabolic Reaction Phenotyping: Do’s and Don’ts, and the Oscar Nomination Process (is Metabolism the Best Actor or the Best Supporting Actor?)” by Dr. Andrew Parkinson (XPD Consulting), and “ ‘SLC-Phenotyping’: Quantifying Contribution of Transporters to the Hepatic Uptake Clearance of Drugs” by Dr. Manthena V Varma (Pfizer).

Session V “Pediatric DDIs” was another new session topic of the Marbach Series which previously had been discussed as an individual lecture 2014. The session featured two presentations to raise awareness of evaluating DDI in specific populations. Professor Johannes N. van den Anker (Children’s National Hospital and University Children’s Hospital Basel) started the session with a somewhat provocative titled talk “Are Neonates and Young Infants Protected against DDIs Despite their Exposure to a Multitude of Medicines?”, which was followed by the delivery of the HDYS award lecture by Professor Daniel Gonzales (University of North Carolina at Chapel Hill) entitled “Application of Pharmacometric Approaches and Real-World Data to Characterize Drug-Drug Interactions in Infants and Children”, The lecture highlighted strategies to explore potential DDI susceptibilities in younger children using combination of clinical data and PBPK modelling.

The last session (Session VI “Herb-Drug DDIs” revisited the issue first brought up in 2014 with three new lectures: “Herbal Drug-Drug Interactions. A Meta-Analysis and Novel Insights” by Professor Ingolf Cascorbi (University of Kiel), “Looking Back 2 Decades: Revisiting Clinically Relevant Drug Interactions with St. John’s Wort” by Dr. Veronika Butterweck (Max Zeller und Söhne), and “Translational Approaches to Untangle Herb-Drug Interactions” by Professor Mary Paine (Washington State University).

The meeting then concluded with question and answers covering broad topics that were not captured in depth in each specific session. For example, one topic was around the conduct of clinical studies evaluating the effect of CYP3A induction that concerns topics on both days. Given the known and emerging challenges of using rifampicin in healthy volunteer studies because of a possible cancer risk due to N-nitrosodimethylamine (NDMA) impurities, alternative approaches such as the use of moderate inducer or alternative perpetrator drug (e.g., active ingredient in herbal products) are of interest. Accumulating experience of PBPK may play increasing roles to predict the effect of CYP3A inducers of different potency, alleviating drug developers concern on the need to conduct many clinical DDI studies in their drug development program. Evaluation of DDI associated with herbal products can be challenging because lack of standardization of active components and inactive ingredients and of regional differences in how herbal products are regulated.

The successful execution of the 11th Marbach Castle DDI Workshop using hybrid format set the stage for future annual events. We believe when we meet in 2022 (28th – 30th May) we will cherish the good memories of 2021 meeting and previous in-person meetings. We look forward to exchanging scientific and philosophical thoughts on DDI and sharing our personal stories face-to-face in the elegantly renovated castle, in the beautifully manicured garden, and by the tranquil water!

The Faculty

Robert Hermann MD, FCP
Amin Rostami-Hodjegan, PhD, FCP
Ping Zhao, PhD

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Speakers 2021

Hansten, Philip D (PharmD)
Professor Emeritus, University of Washington, USA

Oswald, Stefan (PhD)
University of Greifswald, Germany

Cristofoletti, Rodrigo (PhD)
Assistant Professor at the Center of Pharmacometrics &
Systems Pharmacology, University of Florida, Gainesville, USA

Heimbach, Tycho (PhD)
Biopharmaceutics, Sterile & Specialty Products Group,
Pharmaceutical Sciences, Merck & Co., Inc., Rahway, New Jersey, USA

Madabushi, Rajanikanth (PhD)
Office of Clinical Pharmacology, Center for Drug Evaluation
and Research, FDA, Silver Spring, MD, USA

Juurlink, David (MD, PhD, FRCPC)
Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada

Jin Yan Jin (PhD)
Genentech, San Francisco, California, USA

Parkinson, Andrew (PhD)
XPD Consulting, Shawnee KS, USA

Hermann, Robert (MD)
Clinical Research Appliance, Gelnhausen, Germany

Achour, Brahim (PhD)
University of Manchester, UK. Appointed Assistant Professor at the
Faculty of the College of Pharmacy, University of Rhode Island (URI) (from September 2021)

Varma, Manthena V (PhD)
Pfizer, Groton, CT, USA

van den Anker, Johannes N (MD, PhD)
Children’s National Hospital, University Children’s Hospital Basel, University of Basel, Switzerland

Gonzalez, Daniel (PharmD, PhD)
University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

Cascorbi, Ingolf (MD, PhD)
University of Kiel, Germany

Butterweck, Veronika (PhD)
Max Zeller und Söhne, Romanshorn, Switzerland

Paine, Mary (RPh, PhD)
Washington State University, Spokane, Washington, USA

Attendee Quotations 2021

  • Congratulations on what I thought was a very well organised and informative meeting. I look forward to hopefully attending in person next year.
  • Thanks again for a very special Marbach meeting. For me, everything went smoothly, so congratulations to you and all the team who made this possible with all the technicalities!
    As always, there were very refreshing and new thoughts from the different sessions, and some topics covered very new from my perspective, and I learned a lot.
  • Thank you again for the invitation to present at the meeting. I really enjoyed it. I also very much enjoyed all of our interactions over the past 1.5 years. I am grateful to you and the rest of the leadership team for all of your hard work.
  • I also wanted to say that I really enjoyed the meeting! And it was a great idea to take recordings – work very good!
  • The venue looked very intimate and conducive to lively and thoughtful discussions, and I was extremely impressed you were able to pull off those discussions virtually. My hat is off to the faculty organizers and the technical and administrative teams for a successful meeting. Unfortunately, we missed out on the in-person socializing – when great ideas typically evolve – but I would hope we’ll go back to the “old ways” in the near future.
  • Thank you so much to you, your team and the faculty for an amazing first hybrid Marbach.
    Thank you as always for the high quality scientific talks and highlighting new and emerging “hot topics”.
  • The workshop was really informative and I have enjoyed it immensely. Of course, being there in person would have been best but considering the circumstance, I would definitely say it was a success! Thank you all for the opportunity to present at such a highly esteemed event.
    I looked at the feedback form and especially the detailed feedback about the talks and for the first time in my career I could not fault any of the talks in relation to their content, presentation and engagement in the QA. Most of all, and perhaps surprisingly, the sessions and talks were all relevant, so congratulations to the organizers on the choice of speakers and panelists.
  • I missed the personal interaction, but under the current circumstances it was a good solution. The presentations were as good as always and the meeting worked well from a technical point of view.
  • I’m very glad there was an option to join virtually. The organization and all the technical details went very smoothly. All the compliments to the organizers, moderators and all the presenters! Great to have all the presentations recorded, much appreciated.
  • Thank you for offering the choice of online vs. physical participation.
  • Very flexible, and enabled better inclusion. I’m very grateful for pre-prepared slides and presentations.
  • As many other meetings over this pandemic, it was the best compromise out of the circumstances. The files for all material (presentations, references, abstracts) were downloaded easily.
  • Exceptionally good. The organizers did a great job bringing the content and discussions together.
  • I thought it was a very well organised and well-run conference. Thank you for trying to make it as “real” as possible, even though most people attended virtually. All the talks were very good and relevant, and the majority will be applicable to my job.
  • I think the varied backgrounds of the attendees and hence insightful discussions were the most valuable components.
  • I really love the first presentation on the ‘philisophy of DI’ by Pr Hansten as well as the two introductary lectures on DI FDA guidances (in vitro & clinical).

Workshop Programme 2021

10th International Marbach Castle DDI Workshop

May 26th – 28th, 2019

The 10th Anniversary of the International Drug-Drug Interaction (DDI) Workshop at Marbach Castle Enjoyed Continued Attention, Appreciation and Endorsement by International Academic, Industry and Regulatory Scientists

More than 80 experts attended the 10th International DDI Workshop and discussed current topics of regulatory requirements and scientific aspects of drug-drug interactions. The meeting was once again fully booked several weeks in advance, indicating that the DDI Workshop series has become a focal point in the calendar for those concerned with the topic and its unmet needs. Thus, the workshop continues to enjoy from an unbroken popularity, appreciation and endorsement by the participating speakers and attendees.

The meeting began with a session on ‘Past, Present and Future of the Investigations of DDIs’ and was started with a historical perspective by Prof. Malcolm Rowland from the University of Manchester who led the audience through 50 years of DDI investigations. Prof. Rowland gave numerous examples. Often regarded clinically as all or none phenomena, drug-drug interactions (DDI) are graded with the extent varying with the concentrations of the interacting species and hence with their pharmacokinetics (PK) and dosage regimens. Initially, DDIs were identified from clinical observations, often adverse outcomes, and sometimes even drug withdrawals.

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Their origins were often unbeknown pharmacokinetic. To minimize such problems, studies in healthy subjects became part of drug development, with choice of study often governed by the high likelihood that the drugs would be co-administered in the patient population, rather than based on scientific principles. Changes were driven with improvements in analytical methods and mechanistic understanding of ADME processes, coupled with increasing adoption of physiologically based organ models, linking in vitro investigations with in vivo observations, heralding in the era of in vitro-in vivo extrapolation (IVIVE). Originally confined primarily to studies of competitive metabolic inhibition in preclinical species they rapidly extended to non-competitive inhibition and enzyme induction, and while animal studies were used to test methodologies underlining IVIVE, the availability of human tissue and cell-based systems allowed prediction of events in human. Early PK models assumed perfusion rate limited tissue distribution, which needed to be extended to allow for a membrane permeability rate limitation, increasingly apparent with larger and less lipophilic compounds, and a realization of the role of transporters, sometimes coupled with metabolic events. And while the use of in vitro findings was helping to identify likely risks of a DDI in vivo, incorporated into regulatory guidances, there was still much concern for false negatives, and false positives. As such, emphasis remained on undertaking clinical DDI investigations, but now on a more mechanistic basis. Also, many drugs produced multiple interactions at multiple sites within the body, which could no longer be considered discretely, a problem addressed with the use of whole body physiologically based PK (PBPK) models, dynamic models that integrated biochemical, physiological, pathophysiological, genetic and ontological information with drug specific information. However, with concerns for ensuring quality of associated studies and the PBPK software platforms, regulators have issued PBPK guidances, in which issues of validation and qualification play a significant part. Still, confidence is sufficiently high in many cases to both avoid the need for undertaking some DDI studies and allow statements to be made in the label based on PBPK predictions. The next presentations in the regulatory session was on ‘An industry view on the evolution of modelling and simulation in drug development with emphasis on DDI studies over the past decade’ given by Dr. Richard Lalonde, University of Florida. He showed numerous examples how modeling and simulation has made the drug development process more evidence-based and unbiased.

In the second session on “Changes in the International Regulatory DDI Landscapes” there were presentations on ‘Update on EMA Guidances Impacting the Assessment of DDIs’ given by Kevin Blake, PhD, from the EMA and on ‘The Japanese (PMDA) DDI Guideline and application of PBPK’ by Kiyomi Ito, PhD, Musashino University, Tokyo, Japan, followed by a lively discussion.

The subsequent program on Day 1 consisted of two more scientific sessions, as well as a concluding Questions & Answer session.

The third session of Day 1 was called ‘PBPK Modeling of Metabolism-Based DDIs’ with a presentation on ‘Predicting DDI with Integrated MiDD Capability’ given by Ping Zhao, PhD, Bill and Melinda Gates Foundation, Seattle.

The fourth session was about ‘Clinical Management of DDIs’ and featured presentations on ‘Getting Over Fatigue of DDI Warnings: What the Future Decision Support Tools Hold for Clinicians in the Era of Precision Dosing’ by Jean-Luc Reny, MD, Geneva University Hospital, Geneva, as well as ‘Late Breaking Topic! Ketoconazole and Liver Injury – A Five-Year Update’ by Gerd Mikus, MD, Heidelberg University Hospital where he made a strong point against banning ketoconazole in favor of itraconazole in DDI studies.

Day 2 started with a session titled ’Transporter-Based DDIs Revisited’. The first presentation was on ‘The Role of Intestinal Influx Transporters in Drug-Nutrient, Drug-Excipient and Drug-Drug Interactions’ presented by Kathleen Giacomini, PhD, University of California at San Francisco. Intestinal transporters play critical roles in the absorption of drugs and nutrients. Drug-drug interactions, mediated by intestinal transporters, are widely recognized as important determinants of drug toxicity and/or non-response. In marked contrast, transporter-mediated excipient drug interactions in which excipients co-formulated with therapeutic drugs inhibit intestinal drug transporters are less well studied, and very little is known about transporter-mediated drug-nutrient interactions in the intestine. Dr. Giacomini described excipient drug interactions with the intestinal absorptive transporter, OATP2B1. She demonstrated the complex interplay between formulation and drug absorption and suggested that intestinal transporters are important determinants of not only drug-drug interactions, but drug-nutrient and drug-excipient interactions.

The next presentations in that session was on the question ‘Can Endogenous Biomarkers be Applied in Phase I Clinical Trials to Facilitate Subject Phenotyping and DDI Prediction?’ by Yuichi Sugiyama, PhD; RIKEN, Yokohama. He showed recent progress in using endogenous compounds as biomarkers for assessing DDI susceptibility of compounds and genetic polymorphism based interindividual differences involving hepatic transporters in humans. Use of multiple biomarkers will enhance the confidence in the prediction of clinical DDI using endogenous biomarkers. The session concluded with a presentation by Peter Stopfer, PhD, Boehringer Ingelheim on ‘The Effect of Inhibitors of Drug Transport on a Probe-Drug Cocktail Consisting of Digoxin, Furosemide, Metformin, and Rosuvastatin.’

The final session of the meeting was titled ‘DDIs with Hormonal Contraceptives Revisited’ and featured presentations on ‘Regulatory Guidance Versus Clinical Guidance on Drug Interactions of Combined Hormonal Contraceptives’ by Larry Lesko, PhD, University of Florida, ‘Closing the Knowledge Gap on Potential Differences in the Sensitivity to CYP3A4 Induction between Common Progestins used in Oral Contraceptives Relative to Midazolam’ by Joachim Höchel, PhD, and Herbert Wiesinger, PhD, Bayer AG, and ‘Assessment of Drug Interactions with Oral Contraceptives using PBPK Modelling: A Best Practice Approach Using Case Studies’ by Karen Rowland Yeo, PhD, Certara, Sheffield.

The meeting then concluded with five excellent presentations from selected posters presentations and as usual, the final wrap-up discussion of the workshop. As in every year, a wide variety of DDI-related topics were discussed including experimental, clinical and regulatory issues.

Finally, this meeting report would not be complete without mentioning the beautiful Fingerstyle Guitar and Soul, Pop & Jazz Double Concert by Simon Wahl, Michael Diehl and 2enjoy as well as the many networking opportunities for the attendance to engage in informal interaction with colleagues form industry, academia and the regulatory agencies.

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Speakers 2019

Rowland, Malcolm (PhD, DSc)
Professor Emeritus, University of Manchester, Manchester, UK

Lalonde, Richard (PharmD)
University of Florida, Florida, USA

Blake, Kevin (MD, PhD)
EMA, London, UK

Ito, Kiyomi (PhD)
Research Institute of Pharmaceutical Sciences, Musashino University, Tokyo, Japan

Zhao, Ping (PhD)
Bill and Melinda Gates Foundation, Seattle, Washington, USA

Reny, Lean-Luc (MD)
Geneva University Hopital, Geneva, Switzerland

Mikus, Gerd (MD)
Heidelberg University Hospital, Heidelberg, Germany

Giacomini, Kathleen (PhD)
University of California, San Francisco, USA

Sugiyama, Yuichi (PhD)
RIKEN Innovation Center, Yokohama, Japan

Stopfer, Peter (PhD)
Boehringer Ingelheim, Biberach, Germany

Lesko, Lawrence (PhD)
University of Florida, Lake Nona, FL, USA

Höchel, Joachim (DVM, PhD)
Bayer Pharma AG, Berlin, Germany

Rowland Yeo, Karen (PhD)
Certara, Sheffield, UK

Attendee Quotations 2019

  • Dear Robert, thank you to you and the organising committee for a great 10th anniversary meeting. The scientific content was world class as always, I learnt a lot and loved the hospitality at Marbach.
  • Hi Amin – I want to thank you for introducing me to such a great meeting. I enjoyed every minute there, the talks, the posters and conversations with the meeting attendants. Thank you for building a great scientific community on DDI, from in vitro all the way to patients. I learned a lot from various perspectives, and will share with my colleagues.
  • Like the previous year, the whole meeting was a great experience – I personally didn’t miss the castle much, thanks to your excellent organisation, we’ve been compensated generously for this loss…
  • Enjoyed the meeting so much. The talks cover a wide range of DDI related topics.
  • What were the best moments of the workshop for you? The opportunity to share our results with leading experts and receive feedback. Receiving update from the same top experts on hot topics; Environment, atmosphere, social interaction – all priceless!

Workshop Programme 2019

9th International Marbach Castle DDI Workshop

May 27-29, 2018

The 9th International Drug-Drug Interaction (DDI) Workshop at Marbach Castle Enjoyed Continued Attention, Appreciation and Endorsement by International Academic, Industry and Regulatory Scientists

More than 80 experts attended the 9th international DDI Workshop and discussed current topics of regulatory requirements and scientific aspects of drug-drug interactions. The meeting was once again fully booked several weeks in advance, indicating that the DDI Workshop series has become a focal point in the calendar for those concerned with the topic and its unmet needs. Thus, the workshop continues to enjoy from an unbroken popularity, appreciation and endorsement by the participating speakers and attendees.

The meeting began with a session on ‘Changes in the US/EU Regulatory Landscapes’ and was started with a presentation by Dr. Joseph Grillo from the FDA on ‘Drug Interactions From Lab to Labeling: A Regulatory Perspective’.

Dr. Grillo pointed out that unanticipated, unrecognized, or mismanaged drug-drug interactions (DDIs) are major causes of preventable morbidity and mortality, and have occasionally caused the withdrawal of approved drugs from the US market. The overarching goal of FDA’s DDI program is to promote public health by effectively leveraging the totality of information submitted or reported throughout a drug or biologic product life-cycle to determine the potential for clinically significant DDI, develop appropriate management strategies for them, and effectively convey this information to the healthcare provider and ultimately the public. In December 2017, FDA published two draft guidances

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to update and replace the 2012 revised draft DDI guidance for industry. The “In Vitro Metabolism and Transporter-Mediated Drug-Drug Interaction Studies” draft guidance focuses on in vitro experimental approaches for evaluating metabolizing enzyme- and transporter-based drug interaction potential and how to extrapolate in vitro data to decide on the need for clinical DDI studies. The “Clinical Drug Interactions Studies—Study Design, Data, Analysis, and Clinical Implications” draft guidance focuses on clinical studies that evaluate the potential for DDIs and advises sponsors on the timing and design of the clinical studies, interpretation of the results, and options for managing DDIs in patients. A DDI-specific prescription drug labeling and other problem specific “modular” guidances are also planned to support these foundational documents. In the US, the prescription drug labeling is the primary mechanism through which FDA and drug manufacturers communicate essential, science-based prescribing information to healthcare providers. The prescription drug labeling should include a summary of essential DDI information that is needed for the safe and effective use of the drug by the healthcare provider. This information can include data and results from prospective clinical DDI studies, population-based analyses, modeling and simulations, postmarketing reports, or data extrapolated from other information. As part of the Agency’s labeling initiative, guidances and best labeling practices for communicating DDI-related information in prescription drug labeling are planned or being created as well as innovative approaches to enhance clarity, utility, and comprehension (e.g., tables, figures, structured text, etc.).

The next presentations in the regulatory session was on ‘The new FDA Guidance on In Vitro Metabolism- and Transporter-Mediated Drug-Drug Interaction Studies’ given by Aleksandra Galetin, PhD, Centre for Applied Pharmacokinetic Research, The University of Manchester, and on ‘The new FDA In Vitro Metabolism- and Transporter-Mediated Drug-Drug Interaction Guidance – A Perspective from Practice’ given by Andrew Parkinson, PhD, XPD Consulting, Shawnee KS, USA.

The three presentations were followed by an intense podium discussion. One focus was the call for even more harmonization between the different guidances to avoid unnecessary duplication of work and different interpretation of the same scientific data in different parts of the world.

In the second part of this Session on “Changes in the US/EU Regulatory Landscapes” there were presentations on ‘PBPK Model Qualification and Reporting Procedures for Regulatory Submissions: A Consortium Perspective’ given by Edgar L. Schuck, PhD, Modeling and Simulation, Clinical Pharmacology Sciences, MDC, Eisai, USA. The next presentation focused on ‘Dynamic Drug Labels for Optimal Management of DDIs in Patient Care’ and was given by David Burger, PharmD, Radboud University Medical Center, Nijmegen, The Netherlands. The session then concluded with a presentation on ‘Assessment of Two DDIs Involving a Distinct Enzyme and Their Consequences on Morbi-Mortality’ given by Béatrice Saint-Salvi, PhD, DDI Unit, ANSM, France. These presentations again were followed by a lively podium discussion with the three speakers.

The subsequent program consisted of three more scientific sessions, as well as selected oral presentations of some of the poster presentations and a concluding Questions & Answer session.

The first session was called ‘Phenotyping Revisited’ with two presentations on ‘Can DDIs of Direct-Acting Oral Anticoagulants (DOACs) be Predicted by Using a Micro-Dosed DOAC Cocktail Approach?’ given by Gerd Mikus, MD, Heidelberg University Hospital, Heidelberg, Germany, and another on ‘Mechanistic Assessment of Pharmacokinetic DDIs – Phenotyping Revisited’ by Uwe Fuhr, MD, University of Cologne, Cologne, Germany.

The second session was about ‘Sensitivity Assessment in PBPK: Foe or Friend’ and featured presentations on ‘Deciphering Sensitivity Analysis in PBPK: Model Credibility, Uncertainty, Verification and Validation’ by George D. Loizou, PhD, Head of Computational Toxicology Team, Health Risks, HSL: HSE‘s Health & Safety Laboratory, Buxton, Derbyshire, UK, as well on ‘In Search of Sensitive Endogenous Markers for Transporter DDIs – Mechanistic Models for Creatinine and Coproporphyrin I’ by Aleksandra Galetin, PhD, Centre for Applied Pharmacokinetic Research, The University of Manchester, Manchester, UK.

The final session on ‘Non-CYP Related Metabolic DDIs’ featured a presentation on ‘Non-CYP Related Metabolic DDIs with Particular Emphasis on UGT-based DDIs’ by Janne T. Backman, MD, Department of Clinical Pharmacology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

The meeting then concluded with five excellent presentations from selected posters presentations and as usual, the final wrap-up discussion of the workshop. As in every year, a wide variety of DDI-related topics were discussed including experimental, clinical and regulatory issues.

Finally, this meeting report would not be complete without mentioning the beautiful guitar concert by Eckhard Freund and Özkan Yalkinoglu with inspiring and meditative guitar music, as well as the many networking opportunities for the attendance to engage in informal interaction with colleagues form industry, academia and the regulatory agencies.

The Workshop Organizers

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

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Speakers 2018

Grillo, Joseph A (PharmD)
FDA, Waschington D.C., USA

Galetin, Aleksandra (PhD)
Centre for Applied Pharmacokinetic Research, Manchester, UK

Parkinson Andrew (PhD)
XPD Consulting, Shawnee KS, USA

Schuck Edgar L. (PhD)
Eisai, USA

Burger David (PharmD)
Radboud University Medical Center,Nijmegen,The Netherlands

Saint-Salvi Béatrice (PhD)
DDI Unit, ANSM, France

Mikus, Gerd (MD)
Heidelberg University Hospital, Heidelberg, Germany

Loizou, George D. (PhD)
HSE‘s Health & Safety Laboratory, Buxton, Derbyshire, UK

Fuhr, Uwe (MD)
University of Cologne, Cologne, Germany

Backman, Janne T. (MD)
University of Helsinki and Helsinki University Hospital, Helsinki, Finland

Attendee Quotations 2018

  • Most valuable – DDI perspectives from regulatory agencies and presentations on the changes in the regulatory landscape.
  • The meeting provided an excellent and comprehensive overview on drug interactions from lab to labelling.
  • Wishing to expand my pharmacometrics researches into the translational side, this was a precious chance to get in depth knowledges on current issues of PBPK and DDI.
  • I am to hold internal seminars for my team members with slides and references shared in Marbach workshop. – Tons of tasks to learn further!
  • Thank you for organizing such a nice meeting and all the hospitalities. It was a pleasure to participate in this interactive workshop to learn key DDI issues in depth.
  • I’ll take this opportunity to let you know how vastly I enjoyed the meeting, both its professional and social aspects.
  • The vivid discussions around the topic were truly stimulating.
  • Thank you for the perfect organization of the workshop. I’ve enjoyed the workshop as it has been a great opportunity to discuss challenging topics and to meet interesting people.
  • It was a very good workshop, very well organized. This was a good selection of topics.
  • Many thanks for an excellent and enjoyable workshop! I sincerely hope that you will go on with this tradition!
  • I did enjoy the meeting a lot and had a lot of inspiration and carried new ideas with me home. Also, very valuable contacts of a lot of nice people that I met.
  • The poster session and the related discussions were very good.
  • I’ve enjoyed the open discussions and the collaborative environment.
  • Contact to interesting people, relaxing atmosphere, great place.
  • Great discussions with colleagues at this marvellous location.

Workshop Programme 2018

8th International Marbach Castle DDI Workshop

May 28 to 30, 2017

Speakers 2017

Huang, Shiew-Mei (PphD)
FDA, Silver Spring, MD, USA; 2017

Sinha, Vikram (PhD)
MSD, North Wales, PA, USA

Cole, Susan
MHRA, London, UK

Nordmark, Anna (PhD)
Medical Products Agency (MPA), Uppsala, Sweden; 2017

Reddy, Venkatesh Pilla (PhD)
AstraZeneca, Cambridge, UK; 2017

Blume, Henning (PhD)
SocraTec R&D GmbH, Bad Homburg, Germany; 2017

Olivares-Morales, Andrés (Pharm D, PhD)
F. Hoffmann-La Roche, Basel, Switzerland; 2017

Scherrmann, Jean Michel (PhD)
Inserm, UMR-S Université Paris Descartes, Paris, France; 2017

Unadkat, Jashvant (PhD)
University of Washington, Seattle, WA, USA; 2017

Zolnerciks, Joseph K (PhD)
Solvo Biotechnology, Seattle, USA; 2017

Stopfer, Peter (PhD)
Boehringer Ingelheim, Biberach, Germany; 2017

Neuhoff, Sibylle (PhD)
Certara, Sheffield, UK; 2017

Parkinson, Andrew (PhD)
XPD Consulting, Shawnee, Kansas, USA; 2017

Attendee Quotations 2017

  • The whole meeting was very relevant.
  • All great speakers with interesting and relevant talks. Great for networking as it is a small meeting. Stunning location. Perfect agenda with mix of talks and breaks.
  • I enjoyed all the talks. This is my first Marbach DDI meeting – great location, talks …; looking forward again for this meeting!
  • Overall it’s an excellent workshop. For me the most valuable contents are the formulation dependent DDI and Blood Brain Barrier session.
  • The discussion with colleagues and the presentations of the speakers were most valuable. Panel discussions and Q&A sessions were very informative.
  • Complete and comprehensive presentations, very good and useful examples.
  • High quantity of PBPK presentations (and quality!), good mixture between industry/academic/regulatory presentations. Good number of participants.
  • Hearing from representatives from the FDA and EMA is very valuable!
  • Most valuable to me were the Guideline presentations by different representatives from Health Authoritie.
  • I found the ‘Transporter Probe-Drug Cocktail’ presented by P. Stopfer and discussion extremely valuable.
  • The discussion after each talk, especially when the questions involved the regulatory colleagues and the exchange that occurred.
  • Networking during dinners etc., personal interaction with regulators.

Workshop Programme 2017

7th International Marbach Castle DDI Workshop

May 29 – 31, 2016

THE 7TH INTERNATIONAL DRUG-DRUG INTERACTION (DDI) WORKSHOP AT MARBACH CASTLE ENJOYED CONTINUED ATTENTION, APPRECIATION AND ENDORSEMENT BY INTERNATIONAL ACADEMIC, INDUSTRY AND REGULATORY SCIENTISTS

More than 80 experts attended the 7th international DDI Workshop and discussed current topics of regulatory requirements and scientific aspects of drug-drug interactions. The meeting was once again fully booked several weeks in advance, indicating that the DDI Workshop series has become a focal point in the calendar for those concerned with the topic and its unmet needs. Thus, the workshop continues to enjoy from an unbroken popularity, appreciation and endorsement by the participating speakers and attendees.

The meeting started with a mind-opening key note lecture on “Approaches to DDI Challenges in Global Health” presented by Steven E. Kern from the Bill and Melinda Gates Foundation, Seattle.

Dr. Kern emphasized that treatment of people in a global health context for communicable diseases presents numerous challenges for drug development scientists. Therapies for a single condition typically require multiple therapeutic agents to successfully provide cure. For malaria, this usually involves 2 drugs, for HIV 3 drugs, and tuberculosis 4 drugs as standard therapy.

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Treatment of parasitic diseases may include from 1 to 3 additional agents given concomitantly; and for women of child bearing age, these therapies may be administered on top of a long acting contraceptive agent. With these conditions, the potential for DDIs that produce a clinically significant impact is great. Dr. Kern reported that scientists at the Bill & Melinda Gates Foundation, are working with drug development partners to bring the full strength of model based drug development tools to support development of new therapeutics for these diseases and where relevant, improved use of existing therapeutics. This approach includes significant effort in understanding the mechanisms and risks of drug/drug interactions with the standard therapeutic agents used across disease areas so that developers of new therapeutic agents can benefit from these insights as they move forward with development efforts for these agents.

The subsequent programme consisted of six scientific sessions, as well as a meeting with poster presentations and a concluding Questions & Answer session.

The first session was dedicated to focus on current changes in the US regulatory landscape. Specifically the performance criteria of PBPK modeling for the regulatory assessment of DDI risks were presented (Ping Zhao, PhD, Bethesda, USA), and the latest tools and Guidances in the assessment of food-drug interactions in drug development (Tycho Heimbach, PhD, Novartis, USA).

The second session was about DDIs affecting the renal elimination of drugs, with one presentation elucidating the underlying mechanisms of renal DDIs (Maciej Zamek-Gliszczynski, PhD, Glaxo Smith Kline, USA), and another talk focusing on the clinical relevance of renal DDIs (Prof. Martin Fromm, University of Erlangen-Nürnberg, Germany).

The Marbach event has not been just a venue for presentation of the latest scientific discoveries but it has always dedicated a portion of the timetable to address fundamental principles governing various aspects of DDI. This year was not an exception. Hence, the third session was dedicated to revisiting key concepts such as the proper quantification of the fraction of drugs metabolized (fm; Prof. Amin Rostami-Hodjegan, University of Manchester, UK), and the fraction unbound (fu; Oliver von Richter, PhD; Sandoz Biopharmaceuticals, Holzkirchen, Germany).

The fourth session was designed to illustrate the multiple important aspects of DDIs with hormonal contraceptives including public health and drug development considerations (Prof. Lawrence J. Lesko, University of Florida, Orlando, USA), and the presentation of an industry perspective on their assessment during drug development (Joachim Hoechel, DVM, PhD; Bayer Pharma AG, Germany).

Session five addressed the challenges of the effective clinical management of DDIs. Prof. Walter E. Haefeli (University Hospital Heidelberg, Germany) reported about experiences and common challenges with DDI management systems in the hospital setting. He emphasized that whether or not an issued DDI alert by such systems is considered by the receiver/prescriber depends on the quality of the alert (specificity), setting and process, alert presentation (human factors), and alerting methods (e.g. interruptive alerting). Sustainable DDI decision support systems must therefore integrate the multitude of influential factors to be effective and to prevent alert fatigue of their users. In the second talk of this session, Helen Humphries (Certara, Sheffield, UK) presented approaches to the individualization of DDI management by highlighting the difficulties associated in determining some of the patient attributes which help in personalizing the management of DDI.

The final session comprised four talks on various aspects of complex DDIs, starting with the evaluation of incidence and relevance of complex DDIs in the clinical setting (Youssef Daali, PhD; Geneva University Hospital, Switzerland). Prof. Nina Isoherranen (University of Washington, Seattle, USA) presented considerations on what do when clinical DDI data does not agree with existing in vitro findings and predictions. The two final presentations addressed common pitfalls in the assessment of complex DDIs when conducting PBPK DDI studies (Mohamad Shebley, PhD; Abbvie, USA), and in vitro DDI studies (Brian Houston, BSc, PhD and DSc, University of Manchester, UK).

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Speakers 2016

Daali, Youssef (PhD)
Geneva University Hospital, Geneva, Switzerland; 2016

Fromm, Martin (MD)
University of Erlangen-Nürnberg, Germany; 2016

Haefeli, Walter E. (MD)
Heidelberg University Hospital, Heidelberg, Germany; 2016

Heimbach, Tycho (PhD)
Novartis Pharma, East Hanover NJ, USA; 2016

Höchel, Joachim (DVM, PhD)
Bayer Pharma AG, Berlin, Germany; 2016

Houston, Brian (BSc, PhD and DSc)
Centre for Applied Pharmacokinetic Research, Manchester Pharmacy School, University of Manchester, UK; 2016

Humphries, Helen (PhD)
Certara Sheffield, UK; 2016

Isoherranen Nina (PhD)
University of Washington, Seattle WA, USA; 2016

Kern, Steven E. (PhD)
Bill and Melinda Gates Foundation, Seattle WA, USA; 2016

Lesko, Lawrence J. (PhD)
University of Florida, Lake Nona, FL, USA; 2016

Rostami-Hodjegan, Amin (PharmD, PhD, FCP)
University of Manchester, UK; 2016

Shebley, Mohamad (PhD)
Abbvie, Chicago IL, USA; 2016

von Richter, Oliver (PhD, FCP)
Sandoz Biopharmaceuticals, Holzkirchen, Germany; 2016

Zamek-Gliszczynski, Maciej (PhD)
Glaxo Smith Kline, King of Prussia, PA, USA; 2016

Zhao, Ping (PhD)
Bethesda MD, USA; 2016

Attendee Quotations 2016

  • All presentations were of high quality, notably the clinical aspects of DDI (clinical relevance);
  • Nice spectrum from in vitro to in vivo, in silico, clinical perspective; Construction / design of sessions;
  • The FDA point of view on DDI was really an interesting topic; Food effects in drug development was also an important topic for me as well as the key prinicples presentations about fm and fu;
  • Very good ratio from presentations / discussions; bring together the various standpoints, medicine / PBPK moddeling, in vitro, industry;
  • All presentations were of high quality, notably the clinical aspects of DDI (clinical relevance);
  • As PBPK modeller, I found regulatory presentation & comments very useful as well as many discussion with participants;
  • There is a lot time for discussion; Many opportunities to interact with the rest of participants;
  • I enjoyed the opportunities for interaction between participants & speakers;

Workshop Programme 2016

6th International Marbach Castle DDI Workshop

May 03 – 05, 2015

HIGHLY SATISFIED PARTICIPANTS AT THE SIXTH INTERNATIONAL DRUG-DRUG INTERACTION (DDI) WORKSHOP 2015 AT MARBACH CASTLE, GERMANY

At the sixth International Drug-Drug Interaction Workshop more than 80 experts discussed regulatory requirements and current scientific aspects on the preclinical and clinical investigation of drug-drug interactions. Several scientific highlights proved the high quality of this meeting and the DDI Workshop participants confirmed in the feedback protocols that they were highly satisfied with the 6th DDI Workshop at Marbach Castle.

The Drug-Drug Interaction Workshop series at Marbach Castle enjoys an unbroken popularity and the number of participants has remained consistently high over the years. The organizers of the DDI Workshop are highly pleased to see that the DDI Workshop is widely recognized and well established. This year the DDI Workshop was fully booked several weeks before the Workshop started.

Robert Hermann, member of the organization team, states: “Again the feedback of the participants was very positive and the organization team is very satisfied that the scientific programme was well accepted. All speeches and presentations of the meeting were scientifically on a very high level and the positive assessment of the Workshop participants generates a big challenge for the organization team to prepare such high quality meetings also in the upcoming years.”

Five scientific sessions were designed to focus on drug-drug interactions involving clinical aspects, regulatory aspects, determination of intracellular drug concentrations as well as influences on drug safety. The issues were covered by distinguished international scientists and experts from academia, pharmaceutical companies, contract research organizations, consultancies as well as governmental and regulatory agencies.

More (News release)

Speakers 2015

Antoine, Daniel J (PhD)
University of Liverpool, UK

Derendorf, Hartmut (PhD, FCP)
College of Pharmacy, University of Florida, USA

Faller, Bernhard (PhD)
Novartis Institutes for BioMedical Research, Basel, Switzerland

Gosh, Avijit (PhD)
Johnson & Johnson, Pennsylvania, USA

Hermann, Robert (MD, FCP)
cr.appliance, Germany

Juurlink, David (MD, PhD)
Sunnybrook Health Science Center, Toronto, Canada

Ke, Alice (PhD)
Certara, Cary NC, USA

Lesko, Larry (PhD)
University of Florida, Lake Nona, FL, USA

Nordmark, Anna (PhD)
Medical Products Agency (MPA), Uppsala, Sweden

Pollak, Sebastian (PhD)
Jagiellonian University, Krakow, Poland & Certara, Sheffield, UK

Snoeys, Jan (PhD)
Janssen, Beerse, Belgium

Sugiyama, Yuichi (PhD)
RIKEN Innovation Center, Yokohama, Japan

Attendee Quotations 2015

  • Practical and regulatory approaches of clinical DDI studies; Use of PBPK models to waive part of DDI studies: regulatory position & real experience from the field.
  • The program overall was very varied and at the same time very focused; Good networking opportunities.
  • The diversity – in vitro – in vivo – clinical – regulatory etc.; Organization – the slides are available. Q&A is encouraged.
  • The discussions and feedback during the breaks. Day I more interesting compare to day 2 (except Sugiyama).
  • Fruitful discussion with colleagues during the whole workshop.
  • All discussions were of high quality and interest, particularly data from modelisation, simulations!
  • DDIs clinical settings, real-world clinical practise DDIs, regulatory aspects, ketoconazole, FDA food-drug interactions, PBPK.

Workshop Programme 2015

5th International Marbach Castle DDI Workshop

May 25 to 27, 2014

THE 5TH DRUG-DRUG INTERACTION (DDI) WORKSHOP AT MARBACH CASTLE IS HIGHLY RATED BY PARTICIPANTS

More than 70 experts in drug development and drug-drug interactions from 14 countries took part in the scientific meeting entitled “DDI 2014 – 5th International Workshop on Regulatory Requirements and Current Scientific Aspects on the Preclinical and Clinical Investigation of Drug-Drug Interactions” at Marbach Castle on Lake Constance between 25 and 27 May. Feedback on the workshop from participants was consistently positive. The DDI Workshop is now confirmed as a scientific platform that has proven itself as an event for the exchange of ideas between representatives from academic, regulatory health authorities and industry. This was also evident at the anniversary event this year, which focussed on new approaches to studying drug-drug interactions in drug development, the significance of transporter based interactions, and the new draft of the Japanese guideline. These areas were also complemented by the topic of food-drug and herb-drug interactions. The new addition of a poster presentation was well received and is to be included in the programme again next year.

More (Press release)

Speakers 2014

Butterweck, Veronika (PhD)
Graduate School for Life Sciences / Institute for Pharmaceutical Technology,
Muttenz / Basel, Switzerland

Fromm, Martin (MD)
University of Erlangen-Nürnberg, Germany

Hermann, Robert (MD, FCP)
cr.appliance, Germany

Hisaka, Akihiro (PhD)
The University of Tokyo Hospital, Japan

Lesko, Larry (PhD)
University of Florida, Lake Nona, FL, USA

Maeda, Kazuya (PhD)
The University of Tokyo Hospital, Japan

Meyer zu Schwabedissen, Henriette (MD)
University of Basel, Switzerland

Parkinson, Andrew (PhD)
XPD Consulting, Shawnee, Kansas, USA

Rostami-Hodjegan, Amin (PharmD, PhD, FCP)
University of Manchester, UK

Schwab, Dietmar
Hoffmann La Roche Pharmaceuticals, Basel, Switzerland

Stevens, Lloyd (PhD)
Quotient Clinical, Nottingham, UK

von Richter, Oliver (PhD, FCP)
Dept. Exploratory Medicine, Merck Serono, Germany

Weitschies, Werner (PhD)
University of Greifswald, Germany

Attendee Quotations 2014

  • One of the best meetings joined within the last years; Highly interactive; Quite a few ‘mind-widening’ talks.
  • Discussion after the talks war very open and informative; I also found the broad range of backgrounds and quality of speakers was excellent.
  • Networking opportunities. Getting to knew colleagues on more professional and personnel level; Nice to see many regular and new attendees; Really enjoyed Henriette Meyers and Andrew Parkinson’s presentations.
  • Sufficient breaks for networking, program not overload, great food, great concert; Great location (except infrastructure).
  • Small group talks during spare time with other participants.
  • Room for easy interaction between participants; Bringing regulators, academia & industry together.
  • Interaction with other people; Poster session with presentation on protein content / transporter functionality; session on chemistry <–> transporter liability.
  • A very useful workshop; All issues – incl. social activities – were very useful and of high quality; Will join the workshop 2015
  • Congrats to the organisers, thanks.

Workshop Programme 2014

4th International Marbach Castle DDI Workshop

May 26 to 28, 2013

FOUR YEARS OF THE INTERNATIONAL DDI WORKSHOP IN MARBACH CASTLE – A REAL SUCCESS STORY

The organisation team of the international Drug-Drug Interaction (DDI) Workshop in Marbach Castle on Lake Constance was happy to report the great acceptance and success of the events series in its fourth year. More than 70 drug development experts and representatives of health authorities participated in the scientific event “DDI 2013 – 4th International Workshop on Regulatory Requirements and Current Scientific Aspects on the Preclinical and Clinical Investigation of Drug-Drug Interactions”. The fourth DDI Workshop (26th – 28th May) was once more represented internationally. In attendance were nine speakers from the USA, three from Great Britain, three from Germany and one from Switzerland and Sweden respectively. The participants came from 10 countries in total.

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Speakers 2013

Back, David J (PhD)
University of Liverpool, UK

Derendorf, Hartmut (PhD, FCP)
College of Pharmacy, University of Florida, USA

Gil Berglund, Eva (PhD)
Medical Product Agency (MPA), Sweden

Fahmi, Odette A. (PhD)
Pfizer Inc., Global Research & Development, Groton, USA

Greenblatt, David J (MD)
Tufts University, Boston, USA

Hennessy, Sean (PharmD, PhD)
University of Pennsylvania, USA

Meibohm, Bernd (PhD, FCP)
College of Pharmacy, University of Tennessee, Memphis, USA

Mikus, Gerd (MD)
University of Heidelberg, Germany

Obach, R. Scott (PhD)
Pfizer Inc., Global Research & Development, Groton, USA

Parkinson, Andrew (PhD)
XPD Consulting, Shawnee, Kansas, USA

Rodvold, Keith A. (PharmD, FCCP, FIDSA)
University of Illinois, Chicago, USA

Rostami-Hodjegan, Amin (PharmD, PhD, FCP)
University of Manchester, UK

Russmann, Stefan (MD)
University Hospital Zurich, Switzerland

Shepard, Terry (PhD)
Medicines and Healthcare Products Regulatory Agency (MHRA), London, UK

von Moltke, Lisa (MD, FCP)
Genzyme, Cambridge, United States

Attendee Quotations 2013

  • Bringing together world-wide leaders in the field of DDI in an inspiring and “entertaining” setting.
  • Combining in-vitro/preclinical, clinical development and this year also post marketing views and perspectives on DDI in a well balanced way.
  • The time for discussion of questions.
  • Networking with others at break time & dinner.
  • Highly professional overall organization!
  • Very interesting guests to interact with.
  • Lots of interesting talks & discussions. Thank you very much.

Workshop Programme 2013

3th International Marbach Castle DDI Workshop

May 06 to 08, 2012

ALUABLE SCIENTIFIC DISCUSSIONS AT THE THIRD INTERNATIONAL DDI WORKSHOP AT MARBACH CASTLE, LAKE CONSTANCE

The organisation team of the Third International DDI (drug-drug interactions) Workshop has expressed great satisfaction with the course of the scientific meeting. The participants of the DDI Workshop commended the very high scientific level of the presentations and valuable and inspiring discussions of the different topics. Without a doubt, the DDI Workshop at Marbach Castle is a well established platform for the annual exchange between experts, scientists, members of the industry and regulatory bodies regarding DDI affairs. This year more than 80 experts from 14 countries attended the DDI Workshop. The speakers came from 6 different countries (USA, Germany, Great Britain, Finland, Sweden, and New Zealand), thereof 5 from the US. They presented scientific news, the content of the draft guidelines and state of the art lectures. The scientific sessions covered different aspects to current regulatory issues, UGT-based DDIs, transporter-based DDIs and pharmacodynamic DDIs.

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Speakers 2012

Derendorf, Hartmut (PhD, FCP)
College of Pharmacy, University of Florida, USA

Gil Berglund, Eva (PhD)
Medical Product Agency (MPA), Sweden

Hermann, Robert (MD, FCP)
cr.appliance, Germany

Härtter, Sebastian (PhD)
Boehringer Ingelheim Pharma GmbH, Germany

Keppler, Dietrich (MD)
German Cancer Research Center (DKFZ), Heidelberg, Germany

Lee, Caroline (PhD)
on behalf of the PhRMA ABCB1 IC50 consortium, USA

Lesko, Larry (PhD)
University of Florida, Lake Nona, FL, USA

Niemi, Mikko (MD)
University of Helsinki, Finland

Parkinson, Andrew (PhD)
XPD Consulting, Shawnee, Kansas, USA

Rostami-Hodjegan, Amin (PharmD, PhD, FCP)
University of Manchester, UK

Vieira, Manuela
College of Pharmacy, University of Florida, USA

von Richter, Oliver (PhD, FCP)
Dept. Exploratory Medicine, Merck Serono, Germany

Winter, Helen (PhD)
School of Pharmacy, University of Otago, New Zealand

Attendee Quotations 2012

  • Polling session was good attempt to foster discussion.
  • Many excellent presentations.
  • Information on all the in vitro studies available to perform DDI studies.
  • Very informative lectures.
  • Meeting colleagues/experts.
  • Wonderful location…
  • The regulatory perspectives were the most valuable; Besides, the poll session was very insightful.
  • The musical performance – Compliments to the organizers for a job well done!

Workshop Programme 2012

2th International Marbach Castle DDI Workshop

May 01 to 03, 2011

HIGH SCIENTIFIC LEVEL AT THE SECOND INTERNATIONAL WORKSHOP ABOUT DRUG-DRUG INTERACTIONS AT MARBACH CASTLE, LAKE CONSTANCE

The organisation team of the Second International DDI (drug-drug interactions) Workshop has expressed great satisfaction with the course of the scientific meeting. This was also confirmed by the outcome of a feedback survey given to the participants. Both the scientific level of the presentations and discussions as well as the breadth of the topics covered were judged positively. Many already expressed interest in the third DDI Workshop in 2012. Thus the DDI Workshop at Marbach Castle is on its way to become an established platform for the annual exchange between experts, scientists, members of the industry and regulatory bodies regarding DDI affairs.

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Speakers 2011

Bolger, Michael (PhD)
Simulations Plus, Inc., Lancaster, USA

Christians, Uwe (MD, PhD)
University of Colorado, Denver, USA

de Mey, Christian (MD, PhD)
ACPS – Applied Clinical Pharmacology Services, Mainz-Kastel, Germany

Derendorf, Hartmut (PhD, FCP)
College of Pharmacy, University of Florida, USA

Gramatté, Thomas (MD, PhD)
Drug Development Consulting, Munich, Germany

Haverkamp, Wilhelm (MD, PhD)
Department of Cardiology, Charité Berlin, Germany

Hermann, Robert (MD, FCP)
cr.appliance, Germany

Machavaram, Krishna (PhD)
Simcyp Ltd., Sheffield, UK

Parkinson, Andrew (PhD)
XPD Consulting, Shawnee, Kansas, USA

von Richter, Oliver (PhD, FCP)
Dept. Exploratory Medicine, Merck Serono, Germany

Rostami-Hodjegan, Amin (PharmD, PhD, FCP)
University of Manchester, UK

Sparreboom, Alex (PhD)
St. Jude Children ́s Research Hospital, Memphis, TN, USA

Venkatakrishnan, Karthik (PhD)
Millennium, Cambridge, USA

Attendee Quotations 2011

  • Relevant presentations; venue & staff at venue!; organisers!!
  • Very good time discipline of speakers!
  • Great workshop were session I and the presentations on DDI in oncology were the most valuable for me. In addition the discussions following the presentations were very valuable as well.
  • Excellent meeting overall – great location/facility.
  • Excellent location/venue; Clinical aspects on DDIs; Concert.

Workshop Programme 2011

1th International Marbach Castle DDI Workshop

May 30 to June 01, 2010

Organizers of international workshop on drug-drug interactions register high acceptance from participants which are acknowledging the great benefit

The organisation team reports a big success regarding the drug-drug-interaction (DDI) workshop, which was held from May 30th to June 01st at Marbach Castle, Lake Constance in Germany. More than 60 experts from 11 countries and 5 participants at the industry exhibition joined the meeting on DDIs.

New methods and approaches for the investigation of drug candidates have become necessary due to the increasing complexity of this scientific area. Changes in the existing guideline on drug interactions must follow. Recently the European Medicines Agency (EMA) published a draft of the revised guideline, which was discussed in several talks at the DDI Workshop. In the US a new version of the existing FDA drug interaction guideline is under discussion but not published yet. Discussion of the current scientific status between representatives of the industry, regulatory bodies, and academia are of great importance and were successfully realized at the DDI Workshop.

More than 60 experts for drug development participated in the international DDI Workshop at Marbach Castle. Over a period of two days they listened to 14 expert presentations and discussed intensively the latest scientific and regulatory trends in the investigation of DDIs. Most of the participants were experts from the pharmaceutical industry. Almost all big companies were represented at the workshop. It was a big advantage that speakers and participants from regulatory bodies as well as academic institutions were also present generating useful and inspiring discussions and interdisciplinary exchange.

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Speakers 2010

Derendorf, Hartmut (PhD, FCP)
College of Pharmacy, University of Florida, USA;

Fuhr, Uwe (MD)
Clinical Pharmacology, University of Cologne, Germany;

Gil Berglund, Eva (PhD)
Medical Product Agency (MPA), Sweden;

Hermann, Robert (MD, FCP)
cr.appliance, Germany;

Parkinson, Andrew (PhD)
XPD Consulting, Shawnee, Kansas, USA;

Ragueneau-Majlessi, Isabelle (MD)
Dept. of Pharmaceutics, University of Washington, USA;

Rostami-Hodjegan, Amin (PharmD, PhD, FCP)
University of Manchester, UK;

von Richter, Oliver (PhD, FCP)
Sandoz Biopharmaceuticals, Holzkirchen, Germany;

Attendee Quotations 2010

  • The creation of such a platform is of great importance!
  • Small size allowed good interactions among participants & speakers;
  • This workshop provided a comprehensive overview of DDIs across the scientific, clinical and regulatory aspects, making it a unique educational experience and providing opportunity for active scientific and strategic discussion and debate in this emerging inter-disciplinary area;
  • Excellent overview and forum; Perfect timing for discussing the new guidance;
  • Providing presentation on a USB drive = excellent;
  • Boat trip, music, coffee, snacks etc = brilliant!

Workshop Programme 2010