Use of the Same Model or Modeling Strategy Across Multiple Submissions: Focus on Complex Drug Products.

Evidence shows that there is an increasing use of modeling and simulation to support product development and approval for complex generic drug products in the USA, which includes the use of mechanistic modeling and model-integrated evidence (MIE). The potential for model reuse was the subject of a workshop session summarized in this review, where the session included presentations and a panel discussion from members of the U.S. Food and Drug Administration (FDA), academia, and the generic drug product industry. Concepts such as platform performance assessment and MIE standardization were introduced to provide potential frameworks for model reuse related to mechanistic models and MIE, respectively. The capability of models to capture formulation and product differences was explored, and challenges with model validation were addressed for drug product classes including topical, orally inhaled, ophthalmic, and long-acting injectable drug products. An emphasis was placed on the need for communication between FDA and the generic drug industry to continue to foster maturation of modeling and simulation that may support complex generic drug product development and approval, via meetings and published guidance from FDA. The workshop session provided a snapshot of the current state of modeling and simulation for complex generic drug products and offered opportunities to explore the use of such models across multiple drug products.

Electric field interactions in pairs of electric fish: modeling and mimicking naturalistic inputs.

Weakly electric fish acquire information about their surroundings by detecting and interpreting the spatial and temporal patterns of electric potential across their skin, caused by perturbations in a self-generated, oscillating electric field. Computational and experimental studies have focused on understanding the electric images due to simple, passive objects. The present study considers electric images of a conspecific fish. It is known that the electric fields of two fish interact to produce beats with spatially varying profiles of amplitude and phase. Such patterns have been shown to be critical for electrosensory-mediated behaviours, such as the jamming avoidance response, but they have yet to be well described. We have created a biophysically realistic model of a wave-type weakly electric fish by using a genetic algorithm to calibrate the parameters to the electric field of a real fish. We use the model to study a pair of fish and compute the electric images of one fish onto the other at three representative phases within a beat cycle. Analysis of the images reveals rostral/caudal and ipsilateral/contralateral patterns of amplitude and phase that have implications for localization of conspecifics (both position and orientation) and communication between conspecifics. We then show how the common stimulation paradigm used to mimic a conspecific during in vivo electrophysiological experiments, based on a transverse arrangement of two electrodes, can be improved in order to more accurately reflect the important qualitative features of naturalistic inputs, as revealed by our model.