Pharmacometric Modeling and Simulation for Generic Drugs Evaluation

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Computational modeling and simulation is one of the priority areas of Fiscal Year 14 GDUFA (Generic Drug User Fee Act) Regulatory Research program. It is essential to developing a modern ANDA (Abbreviated New Drug Application) review process that fully utilizes available computational and analytical tools. The focus of this FOA/RFA is to utilize pharmacometric modeling and simulation and develop quantitative methodology for generic drugs evaluation in several areas.Objectives:The objectives of this project are to develop quantitative models for generic drugs evaluation in the following areas:1. Population pharmacokinetic and pharmacodynamic, dose-efficacy, and dose-toxicity modeling and simulation for narrow therapeutic index (NTI) drugs. The goal is to develop models and modeling approaches that will help FDA classify drugs as having a narrow therapeutic index and identify those products that have a clinical use profile that requires tighter control of product quality and equivalence attributes.2. Pharmacometric modeling and simulation for generic drug substitutability evaluation and post marketing risk assessment. The goal is to develop pharmacometic approaches (including clinical trial simulation and clinical use/substitution simulation) that will aid OGD in the evaluation of post-market risk and the interpretation of post-market adverse event reports or product substitution complaints.3. Pharmacometric modeling and simulation for partial AUC (area under the concentration vs. time curve) as bioequivalence criteria. The goal is to develop modeling and simulation tools that will aid FDA in identifying which generic drug products require greater degrees of pharmacokinetic profile similarity in order to assure therapeutic equivalence.Detailed Description:Applicants who wish to apply for more than one subtopic should submit separate proposals for each subtopic as listed below: Subtopic 1: Population pharmacokinetic and pharmacodynamic, dose-efficacy, and dose-toxicity modeling and simulation for narrow therapeutic index (NTI) drugs.The objective of this subtopic is to develop population pharmacokinetic and pharmacodynamic, dose-efficacy, and dose-toxicity modeling and simulation for narrow therapeutic index (NTI) drugs. The quantitative model will be used to (1) define whether the drug candidate is belonged to NTI drugs, and (2) evaluate bioequivalence criteria for NTI drugs.Subtopic 2: Pharmacometric modeling and simulation for generic drug substitutability evaluation and post marketing risk assessment.The objective of this subtopic is to develop pharmacometric modeling and simulation methodology to evaluate generic substitutability to address concerns about generic drug substitutability and for post marketing risk assessment. The suggested model drug products include but are not limited to antiepileptic drugs, attention deficit hyperactivity disorder drugs, and antidepressants.Subtopic 3: Pharmacometric modeling and simulation for partial AUCs (area under the concentration vs. time curve) as bioequivalence criteria.The objective of this subtopic is to develop pharmacometric modeling and simulation methodology to evaluate partial AUCs as bioequivalence criteria. Some examples of specific questions to answer are (1) whether partial AUCs are needed for these drug products, (2) what are the appropriate partial AUCs for evaluation of bioequivalence.

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