The Center for Complex Generics

FDA and the Center for Research on Complex Generics (CRCG) hosted a free public workshop on October 27-28, 2022: Best Practices for Utilizing Modeling Approaches to Support Generic Product Development

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• Download the speaker bios

About the Event:

Quantitative methods and modeling approaches have been increasingly utilized by the generic drug industry and regulatory agencies, including the FDA, to support generic product development and regulatory assessments. These quantitative methods and modeling involve mechanistic modeling such as physiologically based pharmacokinetic (PBPK) modeling and computational fluid dynamics (CFD) modeling, quantitative clinical pharmacology tool sets such as population pharmacokinetics (PPK) approaches, and advanced data analytics methodologies. Quantitative methods, modeling and simulation approaches are being utilized to support alternative bioequivalence (BE) approaches and to minimize the burden of (or even alleviate the need for) in vivo BE studies.

The purpose of this workshop is to discuss how to modernize approaches for efficiently demonstrating BE, to establish their role in modern paradigms of generic drug development, and to explore and develop best practices for the use of modeling and simulation approaches in regulatory submissions and approval. This workshop will engage experts from regulatory agencies, the generic drug industry, consultants, academia, and others in the field of modeling and simulation to discuss the opportunities and best practices for incorporating modeling and simulation approaches into generic drug development programs and regulatory submissions. The workshop will also identify commonalities in methodologies/workflows or in silico models supporting alternative BE approaches and clarify how a model master file may be leveraged to advance drug product development, facilitate regulatory assessment, and streamline drug product approval.

FDA and the 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:

• Use of model integrated evidence to support demonstrations of BE in a regulatory context
• Use of the same or similar model or modeling strategy across multiple submissions related to complex drug products
• Mechanistic modeling approaches supporting BE assessments for oral drug products
• Applications of quantitative comparative approaches to support the development of complex generic drug products
• Case examples supporting the recently introduced concept of “model master files”

Audience:

The generic and new drug industry, research organizations, academia, international regulatory agencies, and other parties interested in, or whose work supports, the development of generic drug products.

Workshop Recordings:

Day 1

• 2022 Modeling Approaches Workshop Opening Remarks and Session 1 Presentations
• 2022 Modeling Approaches Workshop Session 1 Panel Discussion
• 2022 Modeling Approaches Workshop Session 2 Presentations
  
• 2022 Modeling Approaches Workshop Session 2 Panel Discussion
• 2022 Modeling Approaches Workshop Session 3 Presentations
• 2022 Modeling Approaches Workshop Session 3 Panel Discussion

Day 2

• 2022 Modeling Approaches Workshop Session 4 Presentations
• 2022 Modeling Approaches Workshop Session 4 Panel Discussion
• 2022 Modeling Approaches Workshop Session 5 Presentations
• 2022 Modeling Approaches Workshop Session 5 Panel Discussion, Closing Remarks

Agenda and Workshop Slides:

Day 1: October 27, 2022

Welcome and Opening Remarks
James Polli, PhD, Co-Director, CRCG
Anna Schwendeman, PhD, Co-Director, CRCG

Opening Remarks
Robert Lionberger, PhD, Director, ORS, OGD, CDER, FDA

Workshop Day 1 Overview
Eleftheria Tsakalozou, PhD, Sr. Pharmacologist, DQMM, ORS, OGD, CDER, FDA

Symposium I: Modeling Best Practices for Generic Drug Development

Session 1: Model Sharing, Acceptance, and Communication with FDA

MIE for BE Evaluation to Support Generic Drug Development and Regulatory Approval
Lanyan (Lucy) Fang, PhD, Deputy Director, DQMM, ORS, OGD, CDER, FDA

An Update of the Model-Informed Drug Development (MIDD) Program to Support New Drug Development
Hao Zhu, PhD, Deputy Director, DPM, OCP, OTS, CDER, FDA

EMA Experience on Model-Based BE for Generics
Michiel van den Heuvel, MSc Pharmacokinetics Assessor, Medicines Evaluation Board 

Live Panel Discussion

• Moderators: Liang Zhao, PhD, Director, DQMM, ORS, OGD, CDER, FDA, Eleftheria Tsakalozou, PhD, Sr. Pharmacologist, DQMM, ORS, OGD, CDER, FDA
• Panelists:
  Tausif Ahmed, PhD, VP & Head, Biopharmaceutics & Bioequivalence, Global Clinical Management, Dr. Reddy’s Laboratories
  Pradeep Bhadauria, MPharm, President & Global CSO, Cipla
  Lanyan (Lucy) Fang, PhD, Deputy Director, DQMM, ORS, OGD, CDER, FDA
  Robert Lionberger, PhD, Director, ORS, OGD, CDER, FDA
  Amin Rostami, PhD, Prof. of Systems Pharmacology & Director of CAPKR, Univ. of Manchester
  Yu Chung Tsang, PhD, CSO, Biopharmaceutics & Biostatistics, Global Regulatory Affairs, Apotex
  Michiel van den Heuvel, MSc, Pharmacokinetics Assessor, Medicines Evaluation Board
  Hao Zhu, PhD, Deputy Director, DPM, OCP, OTS, CDER, FDA

Session 2: Use of the Same Model or Modeling Strategy Across Multiple Submissions: Focus on Complex Drug Products

Regulatory Perspective on Modeling Strategies Across Multiple Submissions
Andrew Babiskin, PhD, Team Lead, DQMM, ORS, OGD, CDER, FDA
Miyoung Yoon, PhD, Team Lead, DQMM, ORS, OGD, CDER, FDA

Utilizing Mechanistic Dermal Absorption Models to Assess Virtual BE
James F. Clarke, PhD, Sr. Research Scientist, Simcyp Division, Certara

Utilizing M&S Approaches to Support Regulatory Submission for Orally Inhaled Drug Products: Case Examples
Marc Kelly, BSc, Sr. Manager Materials Science, Global Inhalation R&D, Teva

Ophthalmic Drug Products: Leveraging M&S Approaches to Perform Inter-Species Predictions and Support Drug Product Development and Approval
Maxime Le Merdy, PharmD, Sr. Scientist, Simulations Plus

MIE for BE Assessment of Long-Acting Injectable Products: In Silico Continuation to Steady State
Murray Ducharme, PharmD, President & CEO, Learn and Confirm Inc./Prof. Associé, Univ. of Montreal

Live Panel Discussion

• Moderators: Ross Walenga, PhD, Chemical Engineer, DQMM, ORS, OGD, CDER, FDA, Partha Roy, PhD, Director, OB, OGD, CDER, FDA
• Panelists:
  Andrew Babiskin, PhD, Team Lead, DQMM, ORS, OGD, CDER, FDA
  Sid Bhoopathy, PhD, Sr. VP & Head, Pharmaron US Lab Services and CGT
  Jan De Backer, PhD, CEO, FLUIDDA INC.
  Murray Ducharme, PharmD, President & CEO, Learn and Confirm Inc./Prof. Associé, Univ. of Montreal
  James F. Clarke, PhD, Sr. Research Scientist, Simcyp Division, Certara
  Marc Kelly, BSc, Sr. Manager Materials Science, Global Inhalation R&D, Teva
  Maxime Le Merdy, PharmD, Sr. Scientist, Simulations Plus
  Miyoung Yoon, PhD, Team Lead, DQMM, ORS, OGD, CDER, FDA

Session 3: Using Mechanistic Modeling Approaches to Support BE Assessments for Oral Products

Using PBPK Model to Support Risk Assessment for Oral Products, from a Regulatory Perspective
Fang Wu, PhD, Sr. Pharmacologist & Scientific Lead, DQMM, ORS, OGD, CDER, FDA

PBPK Modeling to Support Risk Assessment for Oral Drug Products, Including Waiver of Fed BE Studies
Rebeka Jereb, PhD, Scientist, Clinical Development, Sandoz

Oral PBPK to Support BE Evaluation for Pediatric Drugs
Hannah Batchelor, PhD, Prof., Strathclyde Institute of Pharmacy and Biomedical Sciences, Univ. of Strathclyde

Approaches in Establishing BE Safe Space for Oral Solid Dosage Form
Sumon Chakraborty, MPharm, Scientific Leader, Biowaiver & Biocorrelation, Apotex

Live Panel Discussion

• Moderators: Tycho Heimbach, PhD, Biopharmaceutics Expert/Director, Biopharmaceutics & Specialty Dosage Group, Merck, Ethan Stier, PhD, Associate Director, Lifecycle Management, OCP, OTS, CDER, FDA
• Panelists:
  Hannah Batchelor, PhD, Prof., Strathclyde Institute of Pharmacy and Biomedical Sciences, Univ. of Strathclyde
  Sumon Chakraborty, MPharm, Scientific Leader, Biowaiver & Biocorrelation, Apotex
  Rebeka Jereb, PhD, Scientist, Clinical Development, Sandoz
  Filippos Kesisoglou, PhD, Distinguished Scientist, Merck
  Myong-Jin (MJ) Kim, PharmD, Acting Director, DTP-II, ORS, OGD, CDER, FDA
  Sivacharan Kollipara, MPharm, Team Lead, Biopharmaceutics, Dr. Reddy’s Laboratories
  Fang Wu, PhD, Sr. Pharmacologist & Scientific Lead, DQMM, ORS, OGD, CDER, FDA
  Yuching Yang, PhD, Co-Lead of PBPK Program, DPM, OCP, OTS, CDER, FDA
  Lei Zhang, PhD, Deputy Director, ORS, OGD, CDER, FDA

Closing Remarks
Lanyan (Lucy) Fang, PhD, Deputy Director, DQMM, ORS, OGD, CDER, FDA

Day 2: October 28, 2022

Workshop Day 1 Overview
Yuqing Gong, PhD, Pharmacologist, DQMM, ORS, OGD, CDER, FDA

Symposium I/Session 4: Development of Quantitative Comparative Approaches to Support Complex Generic Drug Development

Use of Data Analytics Approaches to Support Regulatory Assessment - FDA Perspective
Meng Hu, PhD, Team Lead, DQMM, ORS, OGD, CDER, FDA

Challenges in Demonstrating API Sameness for Drug Product with Complex APIs
Francis-Xavier Barretto, MSc, CSO, Swati Spentose Pvt. Ltd.

Statistical Experience and Challenges in Similarity Assessment of Dissolution Profile, Particle Size Distribution, and Drug Products with Complex APIs
Yi Tsong, PhD, Director, DB-VI, OB, OTS, CDER, FDA

Evaluation of Dissolution Profile Similarity for BE Assessment
Youssef Mousa, PhD, Pharmacologist, DQMM, ORS, OGD, CDER, FDA

Live Panel Discussion

• Moderators: Ke Ren, PhD, Acting Deputy Director, DB-III, OB, OGD, CDER, FDA, Yuqing Gong, PhD, Pharmacologist, DQMM, ORS, OGD, CDER, FDA
• Panelists:
  Francis-Xavier Barretto, MSc, CSO, Swati Spentose Pvt. Ltd.
  Meng Hu, PhD, Team Lead, DQMM, ORS, OGD, CDER, FDA
  Darby Kozak, PhD, Deputy Director, DTP-I, ORS, OGD, CDER, FDA
  Youssef Mousa, PhD, Pharmacologist, DQMM, ORS, OGD, CDER, FDA
  Meiyu Shen, PhD, Team Lead, DB-VI, Office of Biostatistics, OTS, CDER, FDA
  Yi Tsong, PhD, Director, DB-VI, Office of Biostatistics, OTS, CDER, FDA
  Liang Zhao, PhD, Director, DQMM, ORS, OGD, CDER, FDA

Symposium II: Model Sharing, Acceptance, and Communication with FDA

Potential Types of Model Master Files
Liang Zhao, PhD, Director, DQMM, ORS, OGD, CDER, FDA

A Population PK Based Model-Integrated BE Platform
Andrew Hooker, PhD, Prof. of Pharmacometrics, Dept. of Pharmacy, Uppsala Univ.

Building Mechanistic IVIVC
Viera Lukacova, PhD, Chief Scientist, Simulations Plus

Improving Model Reusability via the Concept of Model Master File: What the Literature Data Tell Us
Amin Rostami, PhD, Prof. of Systems Pharmacology & Director of CAPKR, Univ. of Manchester

Live Panel Discussion

• Moderators: 
  Lanyan (Lucy) Fang, PhD, Deputy Director, DQMM, ORS, OGD, CDER, FDA
  Mark Sale, MD, VP, IDD, Certara
• Panelists:
  Stella Grosser, PhD, Director, DB-VIII, Office of Biostatistics, OTS, CDER, FDA
  Andrew Hooker, PhD, Prof. of Pharmacometrics, Dept. of Pharmacy, Uppsala Univ.
  Rebeka Jereb, PhD, Scientist, Clinical Development, Sandoz
  Viera Lukacova, PhD, Chief Scientist, Simulations Plus
  Carl Peck, MD, Adjunct Prof., UCSF/Cofounder & Expert Consultant, NDA Partners/ProPharma
  Amin Rostami, PhD, Prof. of Systems Pharmacology & Director of CAPKR, Univ. of Manchester
  Rada Savic, PhD, Prof., School of Pharmacy and Medicine, UCSF
  Liang Zhao, PhD, Director, DQMM, ORS, OGD, CDER, FDA

Closing Remarks
Liang Zhao, PhD, Director, DQMM, ORS, OGD, CDER, FDA

For More Information:

If you have any questions about this workshop please contact info@complexgenerics.org.