Hingle, Martin, Arora, Sumit, Pepin, Xavier, Jamei, Masoud, Sharma, Pradeep, Heimbach, Tycho, Wagner, Christian, Bransford, Philip, Kollipara, Sivacharan, Ahmed, Tausif, Dallmann, Andre, Scherholz, Megerle, Stamatis, Stephen, Cano-Vega, Mario, Mistry, Nena, Tannergren, Christer, Borges, Luiza, Stillhart, Cordula, Rullo, Gregory, Mackie, Claire, Mitra, Amitava, Kushner, Joseph, Jain, Krutika Meena Harish and Polli, James (2025) Development of a Physiologically Based Biopharmaceutics Model (PBBM) Report Template: Considerations for Improved Quality in View of Regulatory Submissions. Molecular Pharmaceutics. A-L. ISSN 1543-8384

Abstract

Pharmaceutical innovators and generic companies use Physiologically Based Biopharmaceutics Models (PBBMs) to guide drug product development and potentially waive clinical pharmacokinetic studies for both pre- and post-approval changes. This modelling approach can assist with biopharmaceutics risk assessment and the establishment of patient centric, clinically relevant drug product specifications. However, the variability of possible model strategies and the existence of gaps in scientific knowledge associated with the lack of standardized regulatory expectations for model parameterization, data requirements for model development, and criteria for fit-for-purpose model validation leads to varied acceptance rates and frequent requests for additional information and deficiencies in PBBM submissions across regulatory agencies. During the 2023 M-CERSI PBBM Best Practices for Drug Product Quality: Regulatory and Industry Perspectives workshop, it was identified that a PBBM report template summarizing model considerations and proposing a structure for presenting question(s) of interest, model context, input data, modeling plan and validation, would be beneficial for both industry and regulatory agencies. The present work is not a regulatory guideline but rather a summary of current best practices and considerations for PBBM submissions. The associated template can be downloaded directly from the supplementary information containing help text to guide preparing PBBM reports. The current manuscript discusses the critical elements of the PBBM report template which were identified during the industry-regulators scientific collaboration and interactions.

Item Type:	Article
Keywords:	Physiologically Based Biopharmaceutics Models (PBBMs), Report template, Question of Interest, Context of Use, Model Risk Assessment, Regulatory/Model Impact, Model-Informed Drug Development (MIDD), clinically relevant dissolution specifications (CRDS)
Date Deposited:	27 May 2025 00:46
Last Modified:	27 May 2025 00:46
URI:	https://oak.novartis.com/id/eprint/56169