FDA and the Center for Research on Complex Generics (CRCG) are hosting a public workshop on October 12, 2023: Advances in PBPK Modeling and its Regulatory Utility for Oral Drug Product Development
Workshop Date and Time:
October 12, 2023; 8:30 a.m. – 5:30 p.m.
- Register Now (if attending in person, please register by October 4, 2023)
- Agenda
- Speaker Bios
About the Event:
The applications of physiologically-based pharmacokinetic (PBPK) absorption modeling and simulation (M&S) have been expanding in recent years for both new drug and generic drug development. For example, PBPK absorption M&S has been used to evaluate alcohol dose dumping (ADD) risks for bioequivalence (BE), to support BE study justifications (e.g., using single sex versus both sexes in BE study), to evaluate the impact on BE of a formulation excipient in a test product, to predict the systemic and local bioavailability (BA) of locally-acting products to support BE assessments, and to assess the relative BA and BE of pediatric drug products. In fact, the regulatory utility of PBPK modeling to support scientific rationales, guide in vitro and in vivo study designs, and further inform pharmacological effects of drugs is specifically discussed in recent FDA Guidances for Industry (e.g., for assessing the impact of food on drug exposure, and for evaluating gastric pH-dependent drug interactions with acid-reducing agents) as well as in the draft ICH M13A Guideline on BE for immediate-release solid oral dosage forms. To facilitate the utility of modeling and simulation in such contexts, it is imperative to discuss recent scientific advances and to address practical challenges for the implementation of PBPK absorption modeling and virtual BE analysis.
The purpose of this workshop is to discuss the challenges, experiences, and advances for the development of PBPK absorption modeling to support the establishment of bio-predictive in vitro testing (e.g., dissolution) and to address risks associated with the extrapolation of BE in various contexts, such as from a fasting to a fed state, from subjects with normal to elevated gastric pH, for a biopharmaceutics classification system (BCS)-based biowaiver, assessing BE in pediatrics and with other risk-based BE assessments for oral products. This workshop will include live presentations and interactive panel discussions for all attendees (including virtual attendees), as well as additional workshop activities for in-person attendees, including round table discussions with deliberations among industry, academic and regulatory experts on a selection of the most important topics and key issues that will influence best practices in this field.
Hybrid Experience:
The workshop will offer both in-person and virtual (remote) attendance options. The event will be held at the Universities at Shady Grove in Rockville, Maryland.
Workshop Topics:
- Advances of PBPK Modeling in Regulatory Contexts and to Support Harmonization
- PBPK Modeling to Evaluate Food Impact on Bioequivalence Supporting ICH M13A
- PBPK Modeling to Support BA and BE Assessments in Pediatric Populations
FDA and the Center for Research on Complex Generics (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.
Audience:
This workshop is primarily developed for the new and generic drug industries and other involved collaborators, including consultants and contract research organizations whose work supports new and generic drug applications.
Registration Fees:
The cost for in-person attendance is $250 and will cover event-related expenses. This workshop is free for virtual attendees.
Workshop Outline:
Introduction to the Workshop
The introduction to the workshop will offer a brief overview of the latest advances in PBPK modeling and of regulatory applications of this modeling to oral drug product development, highlighting the utility of PBPK modeling in recent FDA Guidances for Industry, and the ICH M13A Guideline.
- Presentations by experts from FDA
Session 1: Advances of PBPK Modeling in Regulatory Contexts and to Support Harmonization
This session will focus on the latest scientific advances and practical challenges with utilizing PBPK absorption modeling and virtual simulation for regulatory purposes (e.g., to facilitate formulation design, risk assessment, and harmonization among regulatory agencies). Speakers from regulatory agencies and industry will present specific cases involving PBPK absorption modeling and virtual simulation to assess BE, to evaluate alcohol dose dumping (ADD) risks, to support BE study design (e.g., using parent versus metabolite as analytes for BE assessment), and to evaluate the impact of formulation excipients on BE. The second part of this session will focus on PBPK modeling approaches to predict the systemic and local bioavailability of locally-acting products to support BE assessments. Presentations and discussions will focus on the knowledge gap and associated limitations of using PBPK modeling for these products in healthy volunteers vs. patient populations. The exploration of appropriate in vitro approaches/data to inform in vivo product performance will also be discussed.
- Presentations by experts from FDA, academia, and the drug industry
- Audience Q&A with panelists from FDA, academia, and the drug industry
Session 2: PBPK Modeling to Evaluate Food Impact on BE Supporting ICH M13A
This session will focus on latest scientific advances and practical challenges with evaluating the impact of food on oral drug absorption (BA and BE), including the importance of in vitro bio-predictive dissolution for PBPK modeling. The session will also discuss the use of PBPK modeling to support waivers of fed BE studies.
- Presentations by experts from academia and the drug industry
- Audience Q&A with panelists from FDA, academia, and the drug industry
Session 3: PBPK Modeling to Support BA and BE Assessments in Pediatric Populations
This session will focus on the application of PBPK absorption modeling in pediatric populations. and will include discussions of the latest scientific advancements and implementation challenges for PBPK modeling to support the development of pediatric drug products, and the assessment of relative BA and BE in regulatory submissions. This session will also discuss the development of bio-predictive in vitro dissolution methods to support assessing bioavailability and bioequivalence in pediatric population.
- Presentations by experts from FDA and the drug industry
- Audience Q&A with panelists from FDA, academia, and the drug industry
In Person Round Table Discussion and Summary for Session 1, 2 and 3
These round table discussions with deliberations among industry, academic and regulatory experts will focus on a selection of the most important topics and key issues that will influence best practices in PBPK absorption modeling for BA and BE assessment and harmonization. The topics are related to the utility of PBPK modeling in regulatory contexts and harmonization, for evaluating food impact on BE per ICH M13A, and for BA and BE assessments in pediatric populations. The subsequent summary session will synthesize the viewpoints, challenges and future directions that are discussed and consider actionable next steps. The summary of these key discussion points will also serve as a supporting material for a potential white paper or workshop report.
For more information: If you have any questions about this workshop please contact info@complexgenerics.org.
