Establishing the suitability of model‐integrated evidence to demonstrate bioequivalence for long‐acting injectable and implantable drug products: Summary of workshop

Abstract

On November 30, 2021, the US Food and Drug administration (FDA) and the Center for Research on Complex Generics (CRCG) hosted a virtual public workshop titled “Establishing the Suitability of Model‐Integrated Evidence (MIE) to Demonstrate Bioequivalence for Long‐Acting Injectable and Implantable (LAI) Drug Products.” This workshop brought relevant parties from the industry, academia, and the FDA in the field of modeling and simulation to explore, identify, and recommend best practices on utilizing MIE for bioequivalence (BE) assessment of LAI products. This report summerized presentations and panel discussions for topics including challenges and opportunities in development and assessment of generic LAI products, current status of utilizing MIE, recent research progress of utilizing MIE in generic LAI products, alternative designs for BE studies of LAI products, and model validation/verification strategies associated with different types of MIE approaches.

Increasing impact of quantitative methods and modeling in establishment of bioequivalence and characterization of drug delivery

“…For MIE, industry is particularly interested in MIE implementation, precedents set through access to MIE case studies for regulatory purposes, and detailed guidance (e.g., recommendations in the productspecific guidances) for those challenging areas. As indicated by Figure 1, articles included in this special issue contain the summaries of the two most recent modeling focused public workshops organized by the FDA in collaboration with the Center for Research on Complex Generics (CRCG), engaging multiple stakeholders, including generic industry, academia, and government, 3,4 as well as this FDA public workshop. We believe the progress we have seen in MIE is attributable to the FDA's continuous investment in research and dissemination of outcomes advancing QMM in collaboration with experts in academia and other stakeholders as well as industry's efforts to leverage and adopt innovative QMM approaches in their development programs.…”

Advances in quantitative methods and modeling for complex generic drugs and opportunities to hybridize learnings between innovator and generic drug developers

“…An overview of the learnings from the locally acting and oral generic drug product workshops are presented by Babiskin et al 7 in a mini‐review. Product category‐specific learnings are presented by Walenga et al 8 for oral inhalation, Tsakalozou et al 9 for dermal, Tan et al 10 for ophthalmic, nasal, injectable, and implantable, and Gong et al 11 for long‐acting injectable. Oral generic products, which represent a large proportion of generics, but are not routinely labeled as complex, have been identified as having lingering knowledge gaps in PBPK model development, use, and validation for absorption models and food effect assessment 12 and as an alternative BE approach and tool for risk assessment and biowaiver 13 .…”