Optimization of Required and Accessible Manufacturing Made Necessary by an Eminent Sanitary Crisis – Odefrance

The ODEFRANCE project aims to provide the Hauts-de-France region with the capacity to take care of patients in crisis period when marketed pharmaceutical specialties can no longer be transported due to a disruption in the supply chain. Indeed, the latest health crisis has shown that certain specialties that are essential for patient care, such as those containing propofol, could find themselves in a global disruption. However, the complex emulsion formulation of this drug showed that no French hospital or industrial structure was able to produce this specialty, even if the API is available.
The aim of this work is to develop, within the GRITA research unit and the production unit of the pharmacy of Lille University Hospital, pharmaceutical forms that can be produced by a hospital with high production rates. In order to prove the concept, the ODEFRANCE project consists of taking a pilot molecule, propofol, and showing that it is possible to reformulate it in order to obtain a preparation that can be used in conditions similar to the industrial form and that can be produced in large quantities by the Lille University Hospital during a crisis. The steps of this project are 1) to validate the galenic formulation and 2) to qualify the automated production process in a hospital environment.
In the case of our molecule, we propose to solubilise the propofol by complexation with a 2-hydroxypropyl-beta-cyclodextrin. During the COVID-19 crisis, formulation tests were carried out in order to anticipate rupture. During these tests, we validated the proof of concept. The validation of this formulation involves several tasks. The first task consists of the physico-chemical characterisation, quality control and evaluation of the stability of the formulation. The potential toxicity of the cyclodextrins and the cerebral distribution of the complexed propofol will be evaluated on a human blood-brain barrier model. The second task is to verify the benefit/risk ratio of this new formulation in a pilot study. The third task consists of a qualification study of the automated production process, which will be carried out by highlighting the risk analysis in order to facilitate future use in times of crisis and/or, if necessary, industrial transposition. This third step, being based on the automation of the filling process, the stability data will not be modified compared to phase 1. The schedule we have set up since the preliminary tests suggests that the characterisation stage will be validated in 3 months and that the pilot study will last 15 months (6 months for administrative phase, 6 months for inclusions, 3 months for analysis). The qualification phase of the automated manufacturing process will be carried out in the masked time of the previous phase. The envisaged valuation of this work consists of publications, patent registration and the capacity to supply the Hauts-de-France region with drugs during a crisis.