Dataset Information

Parameterization of Physiologically Based Biopharmaceutics Models: Workshop Summary Report.

ABSTRACT: This Article shares the proceedings from the August 29th, 2023 (day 1) workshop "Physiologically Based Biopharmaceutics Modeling (PBBM) Best Practices for Drug Product Quality: Regulatory and Industry Perspectives". The focus of the day was on model parametrization; regulatory authorities from Canada, the USA, Sweden, Belgium, and Norway presented their views on PBBM case studies submitted by industry members of the IQ consortium. The presentations shared key questions raised by regulators during the mock exercise, regarding the PBBM input parameters and their justification. These presentations also shed light on the regulatory assessment processes, content, and format requirements for future PBBM regulatory submissions. In addition, the day 1 breakout presentations and discussions gave the opportunity to share best practices around key questions faced by scientists when parametrizing PBBMs. Key questions included measurement and integration of drug substance solubility for crystalline vs amorphous drugs; impact of excipients on apparent drug solubility/supersaturation; modeling of acid-base reactions at the surface of the dissolving drug; choice of dissolution methods according to the formulation and drug properties with a view to predict the in vivo performance; mechanistic modeling of in vitro product dissolution data to predict in vivo dissolution for various patient populations/species; best practices for characterization of drug precipitation from simple or complex formulations and integration of the data in PBBM; incorporation of drug permeability into PBBM for various routes of uptake and prediction of permeability along the GI tract.

SUBMITTER: Pepin X

PROVIDER: S-EPMC11304397 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Parameterization of Physiologically Based Biopharmaceutics Models: Workshop Summary Report.

Pepin Xavier X Arora Sumit S Borges Luiza L Cano-Vega Mario M Carducci Tessa T Chatterjee Parnali P Chen Grace G Cristofoletti Rodrigo R Dallmann André A Delvadia Poonam P Dressman Jennifer J Fotaki Nikoletta N Gray Elizabeth E Heimbach Tycho T Holte Øyvind Ø Kijima Shinichi S Kotzagiorgis Evangelos E Lennernäs Hans H Lindahl Anders A Loebenberg Raimar R Mackie Claire C Malamatari Maria M McAllister Mark M Mitra Amitava A Moody Rebecca R Mudie Deanna D Musuamba Tshinanu Flora F Polli James E JE Rege Bhagwant B Ren Xiaojun X Rullo Gregory G Scherholz Megerle M Song Ivy I Stillhart Cordula C Suarez-Sharp Sandra S Tannergren Christer C Tsakalozou Eleftheria E Veerasingham Shereeni S Wagner Christian C Seo Paul P

Molecular pharmaceutics 20240630 8

This Article shares the proceedings from the August 29th, 2023 (day 1) workshop "Physiologically Based Biopharmaceutics Modeling (PBBM) Best Practices for Drug Product Quality: Regulatory and Industry Perspectives". The focus of the day was on model parametrization; regulatory authorities from Canada, the USA, Sweden, Belgium, and Norway presented their views on PBBM case studies submitted by industry members of the IQ consortium. The presentations shared key questions raised by regulators durin ...[more]

PMID: 38946085

Similar Datasets

Project description:Colon absorption is a key determinant for the successful development of modified-release (MR) formulations, and the risk that colon absorption may limit the in vivo performance of an MR product can be assessed early by various in vitro tests or by preclinical in vivo regional absorption studies in dogs. Mechanistic physiologically based biopharmaceutics modeling (PBBM) is becoming increasingly accepted to predict in vivo performance and guide formulation development; however, no evaluation of the ability to predict colon absorption has been performed. The purpose of this study was to investigate if regional and colon absorption of drugs in dogs could be predicted with sufficient accuracy using PBBM to enable the replacement of in vivo dog studies in the early assessment of colon absorption limitation risks. This was done by predicting the regional and colon absorption and plasma exposure of 14 drugs after administration to the dog colon according to an a priori approach using the in silico absorption models GI-Sim and GastroPlus. Predictive performance was primarily assessed by comparing observed and predicted plasma concentration-time profiles, AUC0-t, and the relative bioavailability in the colon (Frel,colon) as compared to an oral/duodenal reference. Trends in dependency of prediction performance on predicted fraction absorbed, permeability, and solubility/dissolution rate were also investigated. For GI-Sim, the absolute average fold error (AAFE) values for AUC0-t and Frel,colon were within a 2-fold prediction error for both solutions (1.88 and 1.51, respectively) and suspensions (1.58 and 1.99, respectively). For GastroPlus, the AAFE values for AUC0-t and Frel,colon were outside the set 2-fold prediction error limit for accurate predictions for both solutions (3.63 and 2.98, respectively) and suspensions (2.94 and 2.09, respectively). No trends for over- or underprediction were observed for GI-Sim, whereas GastroPlus showed a slight trend for underprediction of both AUC0-t and Frel,colon for compounds with low permeability. In addition, regional differences in the plasma profiles were qualitatively predicted in the majority of cases for both software. Despite the differences in prediction performance, both models can be considered to predict regional differences in absorption as well as AUC0-t and Frel,colon with acceptable accuracy in an early development setting. The results of this study indicate that it is acceptable to replace in vivo regional absorption studies in dogs with the evaluated models as a method for the early assessment of the risk for colon absorption limitation of MR drug product candidates.

Project description:The genetic resources of aquatic biomedical model organisms are the products of millions of years of evolution, decades of scientific development, and hundreds of millions of dollars of research funding investment. Genetic resources (e.g., specific alleles, transgenes, or combinations) of each model organism can be considered a form of scientific wealth that can be accumulated and exchanged, typically in the form of live animals or germplasm. Large-scale maintenance of live aquatic organisms that carry these genetic resources is inefficient, costly, and risky. In situ maintenance may be substantially enhanced and backed up by combining cryopreserved germplasm repositories and genetic information systems with live animal culture. Unfortunately, cryopreservation has not advanced much beyond the status of an exploratory research for most aquatic species, lacks widespread application, and methods for successful cryopreservation remain poorly defined. For most aquatic species biological materials other than sperm or somatic cells are not comprehensively banked to represent and preserve a broad range of genetic diversity for each species. Therefore, new approaches and standardization are needed for repository-level application to ensure reproducible recovery of cryopreserved materials. Additionally, development of new technologies is needed to address preservation of novel biological materials, such as eggs and embryos of aquatic species. To address these goals, the Office of Research Infrastructure Programs (ORIP) of the National Institutes of Health (NIH) hosted the Cryopreservation of Aquatic Biomedical Models Workshop on January 7 to 8, 2017, in conjunction with the 8th Aquatic Animal Models of Human Disease Conference in Birmingham, Alabama. The goals of the workshop were to assess the status of germplasm cryopreservation in various biomedical aquatic models and allow representatives of the scientific community to develop and prioritize a consensus of specific actionable recommendations that will move the field of cryopreservation of aquatic resources forward. This workshop included sessions devoted to new approaches for cryopreservation of aquatic species, discussion of current efforts and approaches in preservation of aquatic model germplasm, consideration of needs for standardization of methods to support reproducibility, and enhancement of repository development by establishment of scalable high-throughput technologies. The following three broad recommendations were forwarded from workshop attendees: 1: Establish a comprehensive, centralized unit ("hub") to programmatically develop training for and documentation of cryopreservation methods for aquatic model systems. This would include development of species-specific protocols and approaches, outreach programs, community development and standardization, freezing services and training of the next generation of experts in aquatic cryopreservation. 2: Provide mechanisms to support innovative technical advancements that will increase the reliability, reproducibility, simplicity, throughput, and efficiency of the cryopreservation process, including vitrification and pipelines for sperm, oocytes, eggs, embryos, larvae, stem cells, and somatic cells of all aquatic species. This recommendation encompasses basic cryopreservation knowledge and engineering technology, such as microfluidics and automated processing technologies. 3: Implement mechanisms that allow the various aquatic model stock centers to increase their planning, personnel, ability to secure genetic resources and to promote interaction within an integrated, comprehensive repository network for aquatic model species repositories.

Dataset Information

Parameterization of Physiologically Based Biopharmaceutics Models: Workshop Summary Report.

Publications

Parameterization of Physiologically Based Biopharmaceutics Models: Workshop Summary Report.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets