Background and Importance To stern antibiotic resistance -the death toll of which is predicted to reach 10 million deaths per year by 2050- new strategies are explored such as phage therapy. It takes advantage of the ability of bacteriophages or phages – viruses of bacteria – to infect, replicate and lyse their host.

Aim and Objectives PHAG-ONE project (20-PAMR-0009) allowed the creation of an Etablissement Français des Phages Thérapeutiques (EFPT) working with French hospitals to treat patients who reached therapeutic dead ends. This work details the future approach for hospital production of phage suspensions.

Material and Methods Selection of production host: An in-silico approach, based on a bioinformatics pipeline, was developed to select the bacterial strains the most free of virulence factors and resistances.

Selection of high therapeutic potential phages: Phages were sampled from their natural environment, identified by genetic sequencing; their activity range was tested on a bacterial panel representative of the clinical and genetic diversity of the pathogen. Phages with broad activity spectrum and complementary activities were selected for further pharmaceutical development.

Production After amplification on the selected hosts, phages were purified by tangential flow filtration and ultrafiltration. The output was qualified as an active pharmaceutical ingredient (API) authorised by the French regulatory health agency (ANSM). This API can enter hospital preparations.

Formulation and quality control The excipients for the hospital preparations were selected to (i) enhance the phage suspension stability and (ii) be suitable for clinical use. The quality controls target (i) the phage identity and activity; (ii) the risks associated with the administration route; (iii) the risks associated with the production process. The hospital preparation’s stability is explored following both ICH and predictive approaches.

Conclusion and Relevance The authorisations to produce phage API and hospital preparations of phage suspensions will be asked according respectively to the fabrication (part 2 and appendix 2) and preparation good practices and to the future general chapter ‘Phage therapy active substances and medicinal products for human and veterinary use (5.31)’. Inspired by the French blood establishment, EFPT’s purpose will be to offer phage suspensions against multi resistant bacteria or to treat patients with infectious recurrences and other bacterial therapeutic dead ends in a personalised approach.

Conflict of Interest No conflict of interest.