5th PQRI FDA Conference on Advancing Product Quality
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Day 1 – December 1, 2021
Biopharmaceutics: Biopharmaceutical Considerations for Product Design and Development
Development of robust pharmaceutical products requires comprehensive/orthogonal evaluation of the link between critical quality attributes (e.g., dissolution, release) and absorption properties along with the use of computational tools to predict in vivo performance. The judicious use of physiological based pharmacokinetic modelling and simulation (PBPK) along with patient-centric approaches for drug product development is essential to the delivery of transformative therapies.
Bios for December 1, 2021 Speakers
| Topic/Speaker | Abstract | |
| Introduction to Conference
Lawrence X. Yu, Ph.D. Director, Office of New Drug Products, OPQ/CDER US FDA |
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| Keynote: Advancing Pharmaceutical Product Quality
Michael Kopcha, Ph.D., R.Ph. Director, Office of Pharmaceutical Quality, CDER US Food and Drug Administration |
The FDA’s Office of Pharmaceutical Quality in the Center for Drug Evaluation and Research actively supports innovations that assure every dose of a drug is safe and effective and free of contamination and defects. Patients and consumers deserve consistently available quality medicine. Innovations can advance pharmaceutical product quality and also improve the reliability and robustness of the manufacturing supply chain. | |
| SESSION 1: Patient-centric Dissolution and International Harmonization | ||
| Moderator: Filippos Kesisoglou, Ph.D., Distinguished Scientist, Merck and Co., Inc. | ||
| How Do We Improve Predictions of Drug Concentration-Time Profiles?
Swati Nagar, Ph.D. Professor and Director of Graduate Studies Temple University |
Prediction of drug pharmacokinetics is critical in drug discovery and development. New approaches to develop predictive models for drug absorption, distribution, and elimination will be discussed. Models based on preclinical as well as clinical datasets will be described. | |
| The Link Between the Human Gastrointestinal Tract and Oral Drug Absorption: Theory and Case Examples
Bart Hens, Pharm.D., Ph.D. Biopharmaceutics Scientist and Drug Product Design Biomodeler Pfizer, Sandwich, UK |
An in-depth overview of the physiology of the human gastrointestinal tract with a specific focus on the different hurdles a drug product needs to conquer prior to reaching systemic circulation. The emphasis will be crucial physiological parameters that have a major impact on drug release, dissolution and absorption and how these parameters can be integrated into predictive in vitro and in silico tools. | |
| Risk-based Approach to Establishing Patient-Centric Dissolution Specifications
Elsbeth Chikhale, Ph.D. Biopharmaceutics Team Leader Division of Biopharmaceutics ONDP/OPQ/CDER US Food and Drug Administration |
It is important to set risk-based, patient-centric dissolution specifications (method and acceptance criteria(ion)) to ensure the safety and efficacy of solid oral and other drug products. Ways to determine the risk and approaches to set dissolution specifications based on risk will be discussed. Case studies with examples to build a safe space will be presented to illustrate the concepts. | |
| SESSION 2: Biopharmaceutics for Complex Drug Products | ||
| Moderator: Wenlei Jiang, Ph.D., Senior Science Advisor, Office of Research and Standards (ORS), Office of Generic Drugs (OGD), US Food and Drug Administration | ||
| Biopharmaceutics and Inhaled Drugs – Development of an iBCS
Jayne E. Hastedt, Ph.D. Managing Director JDP Pharma Consulting LLC PQRI iBCS WG Presentation is not available |
This presentation will introduce a proposed inhalation-based biopharmaceutics classification system (iBCS) and describe the fundamental principles, framework, and methodologies that are being used to develop the system. The iBCS is based on the principles used to develop the well-established biopharmaceutics classification system for oral immediate release drugs (giBCS). Therefore, it is proposed that the rate and extent of absorption from the airway lumen into the lung tissue is controlled by the attributes of solubility, dose, dissolution rate, and permeability. However, the framework of an iBCS must be modified from that used in the giBCS in order to accommodate the physiology and clearance mechanisms associated with the inhaled route of administration. To create the iBCS grid, a PBPK mechanistic model has been used to assess the sensitivity of parameters representing the rate (drug half-life in the lung luminal space) and the extent (the fraction of the luminal dose absorbed into and across the airway epithelium) to changes in in vitro iBCS-defined drug and drug product attributes. The proposed iBCS grid is still under development, but the anticipated impact of a drug being assigned to a specific iBCS class will be discussed. In terms of value, the classification system is expected to provide an assessment of the technical and clinical risks associated with the development of an inhaled drug product and is not intended to predict the bioequivalence (BE) of inhaled drugs. Also, knowing the iBCS classifiers and boundaries can facilitate the identification of inhaled drug candidates with better targeting attributes. | |
| Modeling and Simulation of Long-Acting Injectable Psychiatric Products
Hao Zhu, Ph.D. Deputy Division Director, Division of Pharmacometrics OCP/OTS/CDER US Food and Drug Administration |
Modeling and simulation have been widely applied to support new drug development. This approach is especially useful to determine dosing regimen, alternative dosing, and dosage adjustment for long acting injectables without unnecessary clinical trials. In this presentation, we would like to share some of our experience by applying modeling and simulation to determine appropriate dosing in patients with schizophrenia. | |
| Biopharmaceutics of Complex Parenteral Drug Products – IVIVC and Development In Vitro Release Testing
Diane J. Burgess, Ph.D. Distinguished Professor University of Connecticut Presentation is not available |
The development of discriminatory and robust in vitro release testing methods for complex parenteral drug products will be discussed, including: microsphere, intrauterine systems, and in situ forming gels. The use of such in vitro methods to develop IVIVCs (animal models) for these complex drug products will also be presented. | |
| HOT TOPIC: Biopharmaceutics for Nano-Drug Delivery | ||
| Moderator: Mehran Yazdanian, Ph.D., Vice President, R&D Operations, Teva Pharmaceuticals | ||
| Overlooked Biopharmaceutics of Nanomedicines /NanoVaccines Impacts Clinical Dose/Efficacy/Safety
Duxin Sun, PhD. |
Nano drug/vaccine deliveries have been extensively investigated in academia and pharmaceutical industries, which leads to FDA approval of many nanomedicines and nanovaccines. The most recent successful examples are nano delivery mRNA vaccines against COVID-19. However, in contrast to oral biopharmaceutics of oral drug products, biopharmaceutics of nano drug/vaccine deliveries are very different and not well investigated. In contrast, some of the nanomedicine design strategies for I.V. administrated nanomedicines (such as anticancer nanomedicines) may not be entirely correct based on the research in animal models vs. in clinical patients. Further, the delivery behaviors of nanovaccines to lymph nodes after S.C. administration are completely different from that of I.V. administrated nanomedicines. The biopharmaceutics of nano drug/vaccine deliveries, which links the properties of nanoformulations, DMPK properties, and clinical does/efficacy/toxicity, needs to be carefully optimized to balance the benefit/risk ratios in clinical patients. | |