Preclinical evaluation of the tolerance of an injectable bacteriophage suspension developed in an academic setting
30 September 2026
C. Marchand 1, B. Lapras 1, M. Medina 2, M. Grimopont 1, C. Merienne 1, F. Laurent 2,3, F. Pirot 1,41. FRIPHARM Platform, Hospital Pharmacy Groupement Hospitalier Centre, Hospices Civils de Lyon, France
2. Institute of Infectious Agents, Groupement Hospitalier Nord, Hospices Civils de Lyon, France
3. Claude Bernard Lyon 1 University, INSERM U1111- CNRS UMR5308 CIRI (International Center for Infectiology Research), 69007 Lyon, France
4. Université Claude Bernard Lyon 1, Faculty of Pharmacy of Lyon, Tissue Biology and Therapeutic Engineering Laboratory (LBTI) UMR CNRS 5305, Lyon, France
Objective
Injectable preparations produced in hospital pharmacies typically involve well-characterized chemical substances. In contrast, this work focuses on the development of a complex and innovative biological medicine: an injectable bacteriophage suspension targeting anti-Staphylococcus aureus produced in an academic hospital setting, from a bacterial strain purified using validated processes, with a patented formulation whose toxicity profile is not characterized. The objective of this study was to evaluate the local and systemic tolerance of an injectable preparation combining four bacteriophages, administered intravenously.
Methods
A regulatory repeated-dose toxicity study, conducted in accordance with Good Laboratory Practice, was performed by Charles River in New Zealand White rabbits. Animals received a daily intravenous injection for 14 days of a combination of four bacteriophages at a dose of 0.6 × 10⁹ PFU/kg (ten times the target clinical dose), followed by a two-week recovery period. Evaluations included clinical observations, local tolerance, physiological and biological parameters, as well as macroscopic and microscopic anatomopathological examinations.
Results
No deaths, clinical signs, local effects, or abnormalities in biological parameters were observed during the study. Macroscopic examinations and organ weights showed no treatment-related effects. Only a minimal to moderate increase in the cellularity of splenic germinal centers was observed in treated animals, persisting after the recovery period. In the absence of involvement of other lymphoid tissues, associated inflammatory reaction, or clinical translation, this variation was considered non-adverse.
Discussion - Conclusion
This study confirms the favorable tolerance profile of a bacteriophage preparation formulated and produced using a hospital pharmaceutical approach, at a supra-therapeutic dose. Beyond the toxicological findings, this work illustrates the ability of a hospital-university platform to design, formulate, and evaluate a phage therapy medicine meeting the requirements of pharmaceutical development for injectable forms. This work paves the way for the first clinical uses of GMP-manufactured bacteriophages produced in France by a public institution.
Keywords: Phage therapy, Toxicology, Preclinical safety