Lyon hospital validates GMP production of therapeutic bacteriophages
GERPAC Congress 2026 highlights
Hospices Civils de Lyon (HCL) is now able to produce therapeutic bacteriophages in-house to GMP standards and has obtained authorisation to manufacture them as active substances, according to Camille Merienne (HCL Pharmacy department and FRIPHARM®, Lyon).
Antimicrobial resistance is a growing global threat and could lead to 10 million deaths annually by 2050. Bacteriophages are a promising alternative to antibiotics but phage therapy medicinal products (PTMPs) are ultra-personalised treatments. They must be matched to each patient’s bacterial strain and continually adapted as new strains emerge. Dr Merienne explained that this requires vertical integration within a single institution, covering phage discovery, selection, production, purification, formulation, diagnosis and treatment. At the same time, the products must meet the same quality, safety and efficacy requirements as other medicines.
The team developed injectable suspensions of bacteriophages against Staphylococcus aureus, working closely with clinicians and patients. The French National Reference Centre for staphylococci collected and characterised multidrug-resistant S. aureus strains, and the most active phages were selected. Genomic sequencing ensured that only non-temperate phages and non-pathogenic host strains were used, and these were stored in a biobank compliant with ISO 20387. Phages were amplified to 10¹⁰ plaque-forming units/mL and filtered. They were then purified by tangential flow filtration and formulated with a patented excipient system. Finally, they were aseptically filled into Type I glass vials in a grade A environment.
Twelve pilot batches of four different phages were produced. Quality control criteria were defined by risk analysis in line with the European Pharmacopoeia chapter on phage therapy (5.31). They covered efficacy (titre and genomic identification), the requirements for a sterile injectable suspension, and process-related impurities such as host cell proteins and DNA, endotoxins and residual reagents. In total, 1,700 quality control points were assessed, including release tests and a two-year ICH stability study. A toxicity and tolerance study was also carried out in rabbits.
Development of the formulation, production process and quality control took three years, and GMP qualification took a further two. A dedicated team was recruited: a PhD student/project manager, a quality engineer and a laboratory technician. Five audits (two internal and three external) led to 95 corrective and preventive actions. All processes now comply with EU GMP Part II, the European Pharmacopoeia and EMA requirements. The French medicines agency (ANSM) has authorised the FRIPHARM platform to manufacture active substances for hospital preparations.
The authors concluded that this achievement means phage therapy can be offered to patients and that biotherapies can be integrated into the hospital’s pharmaceutical preparations. Phase I/II clinical trials are planned. Phages against Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae are being developed next.
Merienne C,Marchand C, Lapras B et al. Institutional hospital-based production of therapeutic bacteriophages. Short communication. GERPAC Congress 2026
Image: Camille Merienne
