FDA and the Center for Research on Complex Generics (CRCG) hosted a free virtual public workshop on September 30 and October 1, 2021: Regulatory Utility of Mechanistic Modeling to Support Alternative Bioequivalence Approaches.
The slides and recordings from the workshop are available below.
About the Event:
FDA’s Office of Generic Drugs consistently utilizes mechanistic modeling and simulation to support regulatory decision making and has directly supported the development of modeling platforms through Generic Drug User Fee Amendments (GDUFA) regulatory research funding. These mechanistic modeling approaches include physiologically based pharmacokinetic (PBPK) modeling and computational fluid dynamics (CFD) modeling. FDA staff use these tools in regulatory activities, including the assessment of abbreviated new drug applications (ANDA), pre-ANDA development meetings, citizen petition responses, controlled correspondences and product-specific guidances (PSGs), to address issues related to product bioequivalence (BE). This workshop is intended to provide the generic drug industry and other involved stakeholders with information about how mechanistic modeling and simulation can support product development and regulatory submissions.
FDA has driven advancements in modeling platforms for generic drugs that use complex routes of administration, such as topical/dermal, ophthalmic, and orally and nasally inhaled products. Mechanistic modeling is a tool that can be used to help increase access to complex generics because it provides an acceptable alternative method for establishing BE that does not include the need for lengthy comparative clinical endpoint BE studies in patients. Mechanistic modeling can play a critical role in supporting alternative BE approaches in non-complex oral generic drug products as well.
The purpose of this workshop is to engage the generic drug industry and other involved stakeholders regarding how mechanistic modeling and simulation can support their product development and regulatory submissions, share the current state of mechanistic modeling for BE assessment through case studies, establish a consensus on best practices for using PBPK and CFD modeling for BE assessment to help drive further investment by the generic drug industry into mechanistic modeling and simulation, and roll out the concept of a Model Master File to improve model-sharing between model developers, industry, and FDA.
FDA and the Center for Research on Complex Generics (CRCG)—which is a collaboration between the University of Maryland School of Pharmacy and the University of Michigan College of Pharmacy—are dedicated to advancing programs that stimulate scientific dialogue, disseminate current insights about complex generics, and generate new knowledge in support of FDA’s mission to promote and protect the public health by increasing access to safe and effective generic medicines.
Topics:
- Mechanistic modeling of orally inhaled generic drug products
- Mechanistic modeling of dermal generic drug products
- Mechanistic modeling of other locally-acting generic drug products
- Oral PBPK as alternative BE approach
- Oral PBPK for evaluating the impact of food on BE
- Challenges and successful cases for oral PBPK
- Model acceptance and model sharing for regulatory use
Download speaker biographies to learn more about the experts who will deliver presentations during the workshop.
Workshop Recordings:
Day 1
Introduction, Opening Remarks, Keynote Address, Workshop Day 1 Overview
Symposium I: Mechanistic Modeling of Locally-Acting Generic Drug Products
Session 1: Mechanistic Modeling of Orally Inhaled Generic Drug Products-Speakers and Panel Discussion
Session 2: Mechanistic Modeling of Dermal Generic Drug Products-Speakers and Panel Discussion
Session 3: Mechanistic Modeling of Other Locally-Acting Generic Drug Products-Speakers and Panel Discussion
Day 1 Closing Remarks
Day 2
Introduction, Opening Remarks, Keynote Address, Workshop Day 2 Overview
Symposium II: Mechanistic Modeling of Oral Generic Drug Products
Session 1: Oral PBPK as an Alternative BE Approach and a Tool for Supporting Risk Assessment and Biowaiver-Speakers and Panel Discussion
Session 2: Oral PBPK for Evaluating the Impact of Food on BE-Speakers and Panel Discussion
Session 3: Challenges and Successful Cases for Oral PBPK-Speakers and Panel Discussion
Symposium III: Model Acceptance and Model Sharing for Regulatory Use
Session 4: Model Acceptance and Model Sharing for Regulatory Use-Speakers and Panel Discussion
Day 2 Workshop Summation and Closing Remarks
Workshop Slides:
September 30, 2021
CRCG Welcome Remarks
James Polli, PhD, Co-Director, CRCG
Anna Schwendeman, PhD, Co-Director, CRCG
Opening Remarks
Jacqueline Corrigan-Curay, JD, MD, Principal Deputy Director, CDER, FDA
Keynote Address
Use of PBPK in New Drug Development and Regulatory Review - Clinical Pharmacology Perspective
Shiew-Mei Huang, PhD, Deputy Director, OCP, OTS, CDER, FDA
Workshop Day 1 Overview
Andrew Babiskin, PhD, Team Lead, DQMM, ORS, OGD, CDER, FDA
Symposium 1
Session 1
Mechanistic Modeling of Orally Inhaled Generic Drug Products
Session Lead: Ross Walenga, PhD
Overview of Complex Generic Orally Inhaled Drug Products
Bryan Newman, PhD, Pharmacologist, DTP-I, ORS, OGD, CDER, FDA
ASME V&V 40 for Establishing Credibility of CFD Models
Brent Craven, PhD, Research Scientist, DAM, OSEL, CDRH, FDA
Validation of Computational Predictions of Regional Lung Deposition
Bo Olsson, PhD, Sr. Inhalation Consultant, Emmace Consulting AB
Case Study: Predicting Regional Lung Deposition of Pharmaceutical Aerosols with CFD
Worth Longest, PhD, Prof., Mech. & Nuclear Eng., Pharmaceutics, Virginia Commonwealth University
Modeling to Support Regulatory Needs of OIDPs
Raja Mohamed, PhD, IVIVC Manager, Respiratory & Complex Products, Sandoz
ANDA and Pre-ANDA Experience with OIDP Modeling
Ross Walenga, PhD, Chemical Engineer, DQMM, ORS, OGD, CDER, FDA
Use of Mechanistic Modelling to Determine the Sensitivity of in vitro CQAs to Regional Lung Deposition and Predict PK for OIDPs
Clare Butler, PhD, Head of Global Inhalation IVIVC, Teva
Live Panel Discussion
Moderators: Robert Lionberger, PhD, Director, ORS, OGD, CDER, FDA
Andrzej Przekwas, PhD, CTO, CFD Research Corporation
Panelists: Bryan Newman, PhD, Pharmacologist, DTP-I, ORS, OGD, CDER, FDA
Brent Craven, PhD, Research Scientist, DAM, OSEL, CDRH, FDA
Bo Olsson, PhD, Sr. Inhalation Consultant, Emmace Consulting AB
Worth Longest, PhD, Prof., Mech. & Nuclear Eng., Pharmaceutics, Virginia Commonwealth Univ.
Ross Walenga, PhD, Chemical Engineer, DQMM, ORS, OGD, CDER, FDA
Clare Butler, PhD, Head of Global Inhalation IVIVC, Teva
Raja Mohamed, PhD, IVIVC Manager, Respiratory & Complex Products, Sandoz
Günther Hochhaus, PhD, Prof., Department of Pharmaceutics, Univ. of Florida
Bing Li, PhD, Associate Director for Scientific Innovation, OB, OGD, CDER, FDA
Markham Luke, MD, PhD, Director, DTP-I, ORS, OGD, CDER, FDA
Liang Zhao, PhD, Director, DQMM, ORS, OGD, CDER, FDA
Session 2
Mechanistic Modeling of Dermal Generic Drug Products
Session Lead: Eleftheria Tsakalozou, PhD
Research Overview and Regulatory Experience on Mechanistic Modeling for Generic Dermatological Drug Products
Khondoker Alam, PhD, Staff Fellow, DQMM, ORS, OGD, CDER, FDA
Towards Building a Dermal PBPK model for BE Assessment: The Role of Drug Product Characterization and Drug Product Performance Data
Priyanka Ghosh, PhD, Sr. Staff Fellow, DTP-I, ORS, OGD, CDER, FDA
PBPK Modeling of Dermal Penetration from Topical Formulations
Jessica Spires, PhD, Sr. Scientist II, Simulations Plus, Inc.
Modeling and Simulation Approaches of Topically Applied Drugs to Support Formulation Optimization, Clinical Development and Regulatory Assessment – Case Studies Discussion
Sebastian Polak, PhD, Sr. Scientific Advisor, Simcyp Division, Certara UK
Scientific and Regulatory Considerations on Dermal PBPK Modeling for Virtual BE Assessments and Decision-making
Eleftheria Tsakalozou, PhD, Staff Fellow, DQMM, ORS, OGD, CDER, FDA
Live Panel Discussion
Moderators: Sam Raney, PhD, Associate Director for Science, ORS, OGD, CDER, FDA
Sumit Arora, PhD, Sr. Scientist, Biopharmaceutics, Janssen R&D
Panelists: Khondoker Alam, PhD, Staff Fellow, DQMM, ORS, OGD, CDER, FDA
Priyanka Ghosh, PhD, Sr. Staff Fellow, DTP-I, ORS, OGD, CDER, FDA
Eleftheria Tsakalozou, PhD, Staff Fellow, DQMM, ORS, OGD, CDER, FDA
Jessica Spires, PhD, Sr. Scientist II, Simulations Plus, Inc.
Sebastian Polak, PhD, Sr. Scientific Advisor, Simcyp Division, Certara UK
Lanyan (Lucy) Fang, PhD, Deputy Director, DQMM, ORS, OGD, CDER, FDA
Srinivasa Sammeta, PhD, Associate Director, Product Development, Teva
Ping Zhao, PhD, Sr. Program Officer, Quantitative Sciences, Bill & Melinda Gates Foundation
Session 3
Mechanistic Modeling of Other Locally-Acting Generic Drug Products
Session Lead: Ming-Liang Tan, PhD
GDUFA Research Update on Mechanistic Modeling Approaches for Generic Ophthalmic, Nasal, Implant and Injectable Drug Products
Ming-Liang Tan, PhD, Staff Fellow, DQMM, ORS, OGD, CDER, FDA
Current Scientific Considerations in Modeling for In Vitro BE of Topically Administered Ophthalmics
Sajeev Chandran, PhD, Director, Advanced Drug Delivery & IVIVC, Biopharmaceutics, Lupin
PBPK Modeling for Different Locally-Administered Drug Products
Rebeka Jereb, MSc Scientist, Clinical Development, Sandoz
Live Panel Discussion
Moderators: Andrew Babiskin, PhD, Team Lead, DQMM, ORS, OGD, CDER, FDA
Maxime Le Merdy, PharmD, Sr. Scientist, Simulations Plus, Inc.
Panelists: Ming-Liang Tan, PhD, Staff Fellow, DQMM, ORS, OGD, CDER, FDA
Sajeev Chandran, PhD, Director, Advanced Drug Delivery & IVIVC, Biopharmaceutics, Lupin
Rebeka Jereb, MSc, Scientist, Clinical Development, Sandoz
Khondoker Alam, PhD, Staff Fellow, DQMM, ORS, OGD, CDER, FDA
Robert Bies, PharmD, PhD, Prof., Department of Pharmaceutical Sciences, SUNY
Darby Kozak, PhD, Deputy Director, DTP-I, ORS, OGD, CDER, FDA
Ross Walenga, PhD, Chemical Engineer, DQMM, ORS, OGD, CDER, FDA
Closing Remarks – Day 1
Lanyan (Lucy) Fang, PhD, Deputy Director, DQMM, ORS, OGD, CDER, FDA
October 1, 2021
Welcome and Opening Remarks
Sally Choe, PhD, Director, OGD, CDER, FDA
Keynote Address
PBPK Models: Opportunities for Enhancements
William Jusko, PhD, Prof., Department of Pharmaceutical Sciences, SUNY
Workshop Day 2 Overview
Lei Zhang, PhD, Deputy Director, ORS, OGD, CDER, FDA
Symposium 2
Mechanistic Modeling of Oral Generic Drug Products
Session 1
Oral PBPK as an Alternative BE Approach and a Tool for Supporting Risk Assessment and Biowaiver
Session Lead: Fang Wu, PhD
PBPK Absorption Modeling to Support Risk Assessment and Biowaiver for Generic Oral Products
Fang Wu, PhD, Sr. Pharmacologist and Scientific Lead, DQMM, ORS, OGD, FDA
PBPK Biopharmaceutics Guidance and Progress on Risk Assessment
Kimberly Raines, PhD, Branch III Chief, DB, ONDP, OPQ, CDER, FDA
Impact of Excipients on Drug Permeation to Support Biowaivers for Non-Q1/Q2 Products
Chris Bode, PhD, Vice President Scientific & Corporate Communications, Absorption Systems
Are We Ready to Apply Oral PBPK Modeling for BE Determination?
Yu Chung Tsang, PhD, CSO, Biopharmaceutics & Biostatistics, Apotex
Live Panel Discussion
Moderators: Hongling Zhang, PhD, Acting Division Director, DB-II, OB, OGD, CDER, FDA
Tycho Heimbach, PhD, Sr. Principal Scientist/Director, Pharmaceutical Sciences, Merck
Panelists: Fang Wu, PhD, Sr. Pharmacologist and Scientific Lead, DQMM, ORS, OGD, FDA
Kimberly Raines, PhD, Branch III Chief, DB, ONDP, OPQ, CDER, FDA
Chris Bode, PhD, Vice President Scientific & Corporate Communications, Absorption Systems
Yu Chung Tsang, PhD, CSO, Biopharmaceutics & Biostatistics, Apotex
Amitava Mitra, PhD, Director, Clinical Pharmacology & Pharmacometrics, Janssen R&D
James Polli, PhD, Prof. in Industrial Pharmacy and Pharmaceutics, Univ. of Maryland
Liang Zhao, PhD, Director, DQMM, ORS, OGD, CDER, FDA
Yi Zhang, PhD, Sr. Advisor, DTP-II, ORS, OGD, CDER, FDA
Session 2
Oral PBPK for Evaluating the Impact of Food on BE
Session Leads: Fang Wu, PhD, and Miyoung Yoon, PhD
Development of PBPK Model for Predicting Food Impact on BE Assessment
Abdullah Al Shoyaib, PhD, ORISE Fellow, DQMM, ORS, OGD, CDER, FDA
Predicting the Power of Food: Assessing Confidence in PBPK Modeling of Food Effect
Arian Emami Riedmaier, PhD, Sr. Principal Scientist and PBPK Lead, Bristol Myers Squibb
Impact of Food and Formulation on Bioequivalence: A Generic Industry Perspective
Anita Kumar, MPharm, MSc, Vice President, R&D, Amneal
Live Panel Discussion
Moderators: Partha Roy, PhD, Director, OB, OGD, CDER, FDA
Neil Parrot, MSc, Distinguished Scientist, Research Innovation Center Basel, Roche
Panelists: Arian Emami Riedmaier, PhD, Sr. Principal Scientist and PBPK Lead, Bristol Myers Squibb
Anita Kumar, PhD, Vice President R&D, Amneal
Lanyan (Lucy) Fang, PhD, Deputy Director, DQMM, ORS, OGD, CDER, FDA
Rebeka Jereb, MSc, Scientist, Clinical Development, Sandoz
Nilufer Tampal, PhD, Acting Associate Director for Scientific Quality, OB, OGD, CDER, FDA
Fang Wu, PhD, Sr. Pharmacologist and Scientific Lead, DQMM, ORS, OGD, FDA
Yuching Yang, PhD, PBPK Co-Lead, DPM, OCP, OTS, CDER, FDA
Session 3
Challenges and Successful Cases for Oral PBPK
Session Leads: Youssef Mousa, PhD, and Fang Wu, PhD
Integrating Biopharmaceutic Data and Gastrointestinal Physiology Using Mechanistic Modeling
Rodrigo Cristofoletti, PhD, Assistant Prof., Department of Pharmaceutics, Univ. of Florida
Modeling for Success: A Case Example for Oseltamivir Phosphate
Youssef Mousa, PhD, Staff Fellow, DQMM, ORS, OGD, CDER, FDA
Live Panel Discussion
Moderators: Lanyan (Lucy) Fang, PhD, Deputy Director, DQMM, ORS, OGD, CDER, FDA
Filippos Kesisoglou, PhD, Distinguished Scientist, Merck
Panelists: Rodrigo Cristofoletti, PhD, Assistant Prof., Department of Pharmaceutics, Univ. of Florida
Youssef Mousa, PhD, Staff Fellow, DQMM, ORS, OGD, CDER, FDA
Jianghong Fan, PhD, Sr. Staff Fellow, DPM, OCP, OTS, CDER, FDA
Tycho Heimbach, PhD, Sr. Principal Scientist/Director, Pharmaceutical Sciences, Merck
Myong-Jin Kim, PhD, Director, DTP-II, ORS, OGD, CDER, FDA
Duxin Sun, PhD, Prof., Director of PK Core, College of Pharmacy, Univ. of Michigan
Yu Chung Tsang, PhD, CSO, Biopharmaceutics & Biostatistics, Apotex
Banu Zolnik, PhD, Acting Biopharmaceutics Team Lead, DB, ONDP, OPQ, CDER, FDA
Symposium 3
Session 4: Model Acceptance and Model Sharing for Regulatory Use
Session Lead: Andrew Babiskin, PhD
Regulatory Perspective: Challenges and Opportunities to Enhance Model Sharing upon Regulatory Use
Andrew Babiskin, PhD, Team Lead, DQMM, ORS, OGD, CDER, FDA
Nonregulatory Perspective: Challenges and Opportunities to Enhance Model Sharing upon Regulatory Use
Carl Peck, MD, Adjunct Prof., Bioengineering, School of Pharmacy, UCSF
Regulatory Perspective: What Can Be a Model Master File and How to Share It?
Liang Zhao, PhD, Director, DQMM, ORS, OGD, CDER, FDA
Nonregulatory Perspective: What Can Be a Model Master File and How to Share It?
Amin Rostami-Hodjegan, PhD, Prof. of Systems Pharmacology, Univ. of Manchester / CSO, Certara
Live Panel Discussion
Moderators: Liang Zhao, PhD, Director, DQMM, ORS, OGD, CDER, FDA
Donald Mager, PhD, Prof. and Vice Chair, Department of Pharmaceutical Sciences, SUNY
Panelists: Andrew Babiskin, PhD, Team Lead, DQMM, ORS, OGD, CDER, FDA
Carl Peck, MD, Adjunct Prof., Bioengineering, School of Pharmacy, UCSF
Amin Rostami, PhD, Prof. of Systems Pharmacology, Univ. of Manchester / CSO, Certara
Lanyan (Lucy) Fang, PhD, Deputy Director, DQMM, ORS, OGD, CDER, FDA
Stella Grosser, PhD, Director, DB-VIII, Office of Biostatistics, OTS, CDER, FDA
Viera Lukacova, PhD, Chief Scientist, Lancaster Division, Simulations Plus, Inc.
Erik Sjögren, PhD, Assoc. Prof., Biopharmaceutics, Uppsala Univ. / Sr. Consultant, Pharmetheus
Hao Zhu, PhD, Deputy Director, DPM, OCP, OTS, CDER, FDA
Workshop Summation
Liang Zhao, PhD, Director, DQMM, ORS, OGD, CDER, FDA
Closing Remarks
Robert Lionberger, PhD, Director, ORS, OGD, CDER, FDA
Audience:
Generic drug industry and other involved stakeholders, including the Contract Research Organizations that support generic drug applications, academia, international regulatory agencies, and the new drug industry.
For More Information:
If you have any questions about this workshop please contact complexgenerics@rx.umaryland.edu.
