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Modelling and Simulation database - regulatory requirements?



  • Adnaan Mohamed
    30/04/2021 11:42
    We are planning on putting together a GastroPlus database of scenarios in order to qualify the basic functionalities of the core software and the “PBPKPlus” and “metabolism and transporter” modules. This would allow the company to show regulators that the software has proven utility in accurately predicting a number of scenarios. We are intending to use a range of data sources (literature and past project) to build the qualification database to cover a large range of scenarios including chemical space – acid, base neutral etc, BCS class, formulation space – IV, solution, suspension, IR and MR tablets, physiology – fed/fasted/PPI pre-treated, dissolution model – Johnson/z-factor, enzyme/transporter inclusion etc etc. The modelling and simulation work is undertaken ahead of typically defined clinical trial activities however, the following questions have arisen: Questions: 1) Would regulators ever want to have access to the GastroPlus database on which we had performed qualification? 2) (following on from Q1) What would regulators expect to see if we stated we had qualified GastroPlus? 3) It seems the FDA have a position on this, do the MHRA have a similar position? Thanks
  • Colin Wilsher
    30/04/2021 18:42
    I'm hoping that other will answer. I assume that inspectors will want access to the DB
  • Dominique Chesnais
    01/05/2021 17:19
    As you have succinctly described a highly complex system, my advices are consequently limited, but authorities and also potential users would expect a rigorous and scientific approach to the whole project. They would look at 1. Scope and purpose of the system/model, 2. Model conceptualisation (structure and scientific representation), 3. Model parameterisation, 4. Computer implantation to solve the model calculation, 5. Model performance, with validation, sensitivity, variability, uncertainty analyses and predictive capacity, 6. Applicability and 7. System reporting, in addition to all good development, scientific and documentation practices.
  • Adnaan Mohamed
    19/05/2021 13:02
    Thank you Dominique.
  • Adnaan Mohamed
    20/05/2021 11:08
    Dominique, would you be able to elaborate on point 4 please? Our SOPs seems to cover the rest of your points but I wasn't sure what you were referring to for point 4. Thank you in advance for your guidance. Adnaan
  • Pubrica healthcare
    16/06/2021 03:09
    For regulatory assessments, the submitted report should contain the validity and bio feasibility of input data and its characteristics, the ambiguity involving the calculation or prediction of parameter outputs, transparencyand coherency in information regarding themodel assembly and itsoptimization procedures, and a write-up about the end effects of the presumptions. The check pointers include objective and regulatory intention, background particulars,qualification, model parameters, model development,simulation of the proposed setting, system and drug model evaluation, parameter sensitivity evaluation, results and discussion about the regulatory writing services. All these checkpointers should be extensively and explicitly described.
  • Adnaan Mohamed
    17/06/2021 13:08
    Thank you very much.
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