Description
Evaluation of equivalence for complex drug products, such as locally acting drug products and non-biological complex parenteral drug products, is challenging. In general, the challenges for those drug products are to relate critical quality contributes to in vitro performance, to relate in vitro performance to in vivo performance, including drug distribution at the site of action and plasma drug distribution, and ultimately to relate in vitro drug performance to clinical performance. Physiologically based absorption and PK models capture the best current understanding of the complex interplay between product attributes and human physiology. Therefore they can aid FDA in developing regulatory science and policies in these complex areas and aid the generic industry in designing high quality products that meet public expectations for equivalence. Objectives:The objectives of this project are to develop, evaluate and improve physiologically based absorption and pharmacokinetic models for the following areas to support and facilitate generic drug guidance development, product development, and application review, in these areas.Subtopic 1: Physiologically based pharmacokinetic modeling and simulation of dermal absorptionSubtopic 2: Physiologically based pharmacokinetic modeling and simulation of ocular absorptionSubtopic 3: Physiologically based pharmacokinetic modeling and simulation for non-biological complex parenteral drug products (including liposomes, nanosuspension, micelles, microspheres, implants, and hydrogels)Subtopic 4: Physiologically based pharmacokinetic modeling and simulation of lung absorption via oral inhalationSubtopic 5: Physiologically based pharmacokinetic modeling and simulation of absorption from nasally delivered products (including nasal solutions, suspensions as well as nasal insufflation as a potential route of abuse) For each subtopic, the models should include but are not limited to formulation properties, drug substance properties, in vitro release mechanisms, physiology geometry, and microenvironment physiological parameters. The models should be based on the understanding of formulations, drug substance, physiology, mechanisms of drug delivery and mechanisms of drug transport. The final models should be able to predict drug concentration at the site of action, and drug plasma/blood concentration from various formulations.Proposals should at least include a description of the model, and model validation plans. In the proposal, applicants should indicate the formulations/drug products that will be used as model drug products for model validation and evaluation. If solutions are used in model development and validation, they should not be the only formulations used for model validation.