Physiologically Based Biopharmaceutics Modeling (PBBM) Best Practices for Drug Product Quality

Agenda Speaker Bios

The U.S. Food and Drug Administration (FDA)- in collaboration with the University of Maryland Center of Excellence in Regulatory Science and Innovation (M-CERSI) hosted a three-day in-person workshop entitled “Physiologically Based Biopharmaceutics Modeling (PBBM) Best Practices for Drug Product Quality: Regulatory and Industry Perspectives” on Tuesday, August 29 through Thursday, August 31, 2023.

The aim of this three-day workshop is to provide a forum for experts from regulatory agencies, innovator and generic drug industry, consultants, academia, and commercial software providers and others in the field of modeling and simulation, to discuss the opportunities and best practices for incorporating drug product quality attributes within PBBM models to support development programs and regulatory submissions. The workshop also aims to identify bottlenecks/gaps which hinder the development and efficient utilization of PBBM models to support drug product quality.

The workshop will include morning presentations of PBBM case studies by global regulatory agencies. Afternoon breakout sessions will provide the opportunity to deep dive into challenges highlighted by the case study presentations and delineate best practices.

Topics:

Regulatory strategy and applications of PBBM during clinical development, marketing application, and post approval change
Discussions around a framework for reporting PBBM models
Challenges and considerations in the development of biorelevant/biopredictive inputs such as solubility, dissolution, permeability etc. for the PBBM model development
Scientific considerations for establishing verification and validation strategies for PBBM models for their intended purpose of application

Tuesday 29 August Workshop Agenda: Morning Sessions and Afternoon Sessions

Morning Sessions: Regulators Discussion of Established PBBM Case Studies (Video)
Welcome & Workshop Objective	Speaker: Bhagwant Rege, FDA	Presentation (PDF)
PBBM Impact & Future perspective	Keynote Speaker: Jennifer Dressman, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP	Presentation (PDF)
Discussion of Case Study 1	Speaker: Shereeni Veerasingham, HC	Presentation (PDF)
Discussion of Case Study 2	Speakers: Anders Lindahl, Swedish MPA Flora Musuamba Tshinanu, Belgium FAMHP	Presentation (PDF)
Discussion of Case Study 3	Speaker: Rebecca Moody, FDA	Presentation (PDF)
Discussion of Case Study 9	Speaker: Øyvind Holte, Norwegian Medicines Agency	Presentation (PDF)
Round table discussion on case studies (60 min). Focus areas: best strategies to integrate in vitro data (solubility, permeability, dissolution, and precipitation) in PBBM	Regulators: Rebecca Moody, FDA Luiza Borges, ANVISA Mary Malamatari, MHRA Evangelos Kotzagiorgis, EMA Shereeni Veerasingham, HC Shinichi Kijima, PMDA Moderators: Paul Seo, FDA Sumit Arora, Janssen
Afternoon Hot Topics/Breakout Sessions: Considerations for In Vitro Data Inputs to PBBM
Hot topic A: Solubility: From in vitro best practices to in vivo relevance	Speaker: Deanna Mudie, Lonza	Presentation (PDF)
Breakout Session A: Best practices for solubility as input to PBBM	Moderator 1: Evangelos Kotzagiorgis, EMA Moderator 2: Claire Mackie, Janssen Scribe 1: Tessa Carducci, Merck Scribe 2: Mario Cano Vega, Amgen
Hot topic B: Development of biopredictive dissolution methods	Speaker: Raimar Loebenberg, Univ.of Alberta	Presentation (PDF)
Breakout Session B: Dissolution Part 1: Best practices for data generation as input to PBBM	Moderator 1: Paul Seo, FDA Moderator 2: Nikoletta Fotaki, Univ. of Bath Scribe 1: Parnali Chatterjee, FDA Scribe 2: Ivy Song, Takeda
Hot topic C: Methods for integrating dissolution in PBBM	Speaker: Xavier Pepin, Simulations Plus	Presentation (PDF)
Breakout Session C: Dissolution Part 2: Best practices for modeling dissolution as input to PBBM	Moderator 1: Luiza Borges, ANVISA Moderator 2: Cordula Stillhart, Roche Scribe 1: Grace Chen, Takeda Scribe 2: Megerle Scherholz, BMS
Hot topic D: Precipitation: From in vitro best practices to in vivo relevance	Speaker: Christian Wagner, Merck group	Presentation (PDF)
Breakout Session D: Best practices for integration of precipitation in PBBM	Moderator 1: Poonam Delvadia, FDA Moderator 2: Mark McAlister, Pfizer Scribe 1: André Dallman, Bayer Scribe 2: Elizabeth Gray, FDA
Hot topic E: Permeability: From in vitro best practices to in vivo relevance	Speaker: Hans Lennernäs, Uppsala University	Presentation (PDF)
Breakout Session E: Best practices for integration of permeability in PBBM	Moderator 1: Christer Tannergren, AstraZeneca Moderator 2: Rodrigo Christofoletti, Univ of FL Scribe 1: Xiaojun Ren, Novartis Scribe 2: Eleftheria Tsakalozou, FDA
Feedback from BO Sessions A- E	Speakers: All Moderators and Scribes from five BO sessions (10 min per session)

Wednesday 30 August Workshop Agenda: Morning Sessions and Afternoon Sessions

PBBM Base Models, Model Validation and Application Steps

Morning Sessions: Regulators Discussion of Established PBBM Case Studies (Video)
Welcome Day 2	Speakers: Tycho Heimbach, Merck & Co. Kimberly Raines, FDA
PBBM case study	Speaker: Tycho Heimbach, Merck & Co.	Presentation (PDF)
Regulatory Discussion/ Case Study 5 Focus: Data Inputs and Collection	Speaker: Mary Malamatari, MHRA	Presentation (PDF)
Regulatory Discussion/ Case Study 4 Focus: Base Model Development	Speaker: Luiza Borges, ANVISA	Presentation (PDF)
Regulatory Discussion/ Case Study 6 Focus: Model Validation and Application	Speaker: Shinichi Kijima, PMDA	Presentation (PDF)
Roundtable discussions on Day 2 case studies (60 min) Focus areas Model Validation, PK and data inputs, IV and oral data, preclinical data scaling. Independent clinical data use, non-BE, Interpolation/Extrapolation	Regulators: Rebecca Moody, FDA Luiza Borges, ANVISA Mary Malamatari, MHRA Flora Musuamba Tshinanu, Belgium FAMHP Shereeni Veerasingham, HC Shinichi Kijima, PMDA Paul Seo, FDA Moderators: Tycho Heimbach, Merck & Co Claire Mackie, Janssen	Presentation (PDF)
Afternoon: Hot Topics/Breakout Sessions: Considerations for PBBM Models
Hot topic F: Considerations for model development: data inputs, disposition, and absorption parameters, dealing with sparse data	Speakers (10 min each): Tycho Heimbach, Merck & Co. David Turner, Certara Rebecca Moody, FDA	Presentation (PDF) Presentation (PDF) Presentation (PDF)
Breakout Session F	Moderator 1: Lanyan (Lucy) Fang, FDA Moderator 2: Cordula Stillhart, Roche Scribe 1: Philip Bransford, Vertex Scribe 2: Xiaojun Ren, Novartis
Hot topic G: Considerations for model validation, model acceptance/verification criteria in PBBM in view of available clinical data and model risks (impact and consequences)	Speaker: Min Li, FDA	Presentation (PDF)
Breakout Session G	Moderator 1: Shereeni Veerasingham, HC Moderator 2: Nikunj Patel, Certara Scribe 1: David Sperry, Eli Lilly Scribe 2: Hansong Chen, FDA
Hot topic H: Considerations for model application: VBE trials vs. single representative modeling, dealing with within and between subjects variability and parameter uncertainty	Speakers (15 min each): Amin Rostami, Univ. of Manchester Viera Lukacova, Simulations Plus	Presentation (PDF) Presentation (PDF)
Breakout Session H	Moderator 1: Duxin Sun, Univ. of Michigan Moderator 2: Jean-Flaubert Nguefack, Sanofi Scribe 1: Tessa Carducci, Merck & Co Scribe 2: Manuela Grimstein, FDA
Hot topic I: Considerations for model application: Establishing safe space and failure edges, non-BE batches and alternative IVIVR/C	Speakers (10 min each): Xavier Pepin, Simulations Plus Konstantinos Stamatopoulos, GSK Siri Kalyan Chirumamilla, Certara	Presentation (PDF) Presentation (PDF) Presentation (PDF)
Breakout Session I	Moderator 1: Haritha Mandula, FDA Moderator 2: Rob Ju, Abbvie Scribe 1: Michael Wang, Merck & Co Scribe 2: Joan Zhao, FDA
Feedback from BO Sessions F- I	Speakers: All Moderators and Scribes from five BO sessions (10 min per session)

Thursday 31 August Workshop Agenda: Morning Sessions and Afternoon Sessions

Applications of PBBM - Current State & New Horizons

Morning Sessions: Presentations on Current and Future Applications of PBBM (Video)
Welcome Day 3	Speakers: Bhagwant Rege, FDA Amitava Mitra, Kura Oncology
Application of PBBM in generic product development	Speaker (virtual): Sivacharan Kollipara, Dr. Reddy’s Lab	Presentation (PDF)
OGD perspective on PBBM applications for generics	Speaker: Fang Wu, FDA	Presentation (PDF)
Application of virtual BE trials to support formulation bridging	Speaker: Claire Mackie, Janssen	Presentation (PDF)
Utility of the advanced oral absorption modeling for clinical pharmacology assessment	Speaker: Miyoung Yoon, FDA	Presentation (PDF)
Prediction of regional/colon absorption & MR drug product performance	Speaker: Christer Tannergren, AstraZeneca	Presentation (PDF)
Application of PBBM in regulatory submissions – Clinical, NDA/MAA & post approval	Speakers: (10 min each) Kimberly Raines, FDA Luiza Borges, ANVISA Mary Malamatari, MHRA Evangelos Kotzagiorgis, EMA Shereeni Veerasingham, HC Hiroyuki Tsuji, PMDA	Presentation (PDF) Presentation (PDF) Presentation (PDF) Presentation (PDF) Presentation (PDF) Presentation (PDF)
Afternoon Sessions: Hot Topics/Breakout Sessions: Applications of PBBM
Hot topic K: Introduction & case study on application of PBBM for generics	Speaker: Yunming Xu, FDA	Presentation (PDF)
Breakout Session K: PBBM in generics drug product development	Moderator 1: Yi-Hsien Cheng, FDA Moderator 2: Rajendra Singh, Teva Moderator 3: Maitri Sanghavi, Certara Scribe 1: Rajesh Savkur, FDA Scribe 2: Martin Hingle, Novartis
Hot topic L: Introduction & case study on virtual BE applications	Speaker: Amitava Mitra, Kura Oncology	Presentation (PDF)
Breakout session L: Virtual BE applications	Moderator 1: Andrew Babiskin, FDA Moderator 2: Amitava Mitra, Kura Oncology Scribe 1: Parnali Chatterjee, FDA Scribe 2: Erik Sjögren, Pharmetheus
Hot topic M: Introduction & case study on safe space & extrapolation	Speaker: Sandra Suarez-Sharp,Simulations Plus	Presentation (PDF)
Breakout Session M: Safe space & extrapolation	Moderator 1: Kimberly Raines, FDA Moderator 2: Sandra Suarez-Sharp, Simulations Plus Scribe 1: Kevin Wei, FDA Scribe 2: André Dallmann, Bayer
Hot topic N: Introduction & case study on MR PBBM applications	Speaker: Rebecca Moody, FDA	Presentation (PDF)
Breakout Session N: Regional absorption & MR PBBM applications	Moderator 1: Anitha Govada, FDA Moderator 2: Christer Tannergren, AstraZeneca Scribe 1: Anders Lindahl, Swedish MPA Scribe 2: Sherin Thomas, FDA
Feedback Breakout Sessions K-N	Speakers: All Moderators and Scribes from four BO sessions (~10 min per session)
Concluding Remarks	Speaker: Greg Rullo, AstraZeneca	Presentation (PDF)

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About the Event

Workshop Details: Day 1

Tuesday 29 August Workshop Agenda: Morning Sessions and Afternoon Sessions

Morning Sessions: Regulators Discussion of Established PBBM Case Studies (Video)

Afternoon Hot Topics/Breakout Sessions: Considerations for In Vitro Data Inputs to PBBM

Workshop Details: Day 2

Wednesday 30 August Workshop Agenda: Morning Sessions and Afternoon Sessions

Morning Sessions: Regulators Discussion of Established PBBM Case Studies (Video)

Afternoon: Hot Topics/Breakout Sessions: Considerations for PBBM Models

Workshop Details: Day 3

Thursday 31 August Workshop Agenda: Morning Sessions and Afternoon Sessions

Morning Sessions: Presentations on Current and Future Applications of PBBM (Video)

Afternoon Sessions: Hot Topics/Breakout Sessions: Applications of PBBM