Institutional hospital-based production of the therapeutic bacteriophages

Introduction
The WHO’s ’silent pandemic’—antimicrobial resistance—may cause 10M deaths/year (Y) by 2050. In response, Phage Therapy Medicinal Products (PTMP) are a promising alternative, requiring highly individualized treatment protocols, continuous adaptation to emerging bacterial strains, and biological variability management. Consequently, vertical integration—encompassing phage discovery, selection, production, purification, formulation, diagnosis, and treatment—by institutions is essential for scalable deployment. PTMP production must meet GMP/Ph.Eur. quality, safety, and efficacy requirements. However, as ultra-personalized therapies, PTMPs require agile development, balancing stringent quality with operational agility—a significant challenge. This study reports PTMP production process qualification in a hospital, describing injectable anti-Staphylococcus aureus bacteriophages (SaBP) suspension development and GMP/Ph.Eur./EMA-compliant qualification.

Method
With patients / clinicians close collaboration, our S. aureus National Reference Center collects/characterizes MultiDrug Resistant Staphylococcus aureus (MDR-SA) strains and select the most active phage candidates. Genomic SaBP characterization (via specialized sequencing) enables non-temperate phage/non-pathogenic strain selection and ISO 20387-compliant biobanking. From biobank, we produce 10¹⁰ PFU/mL suspensions, filtered (0.22 µm) and packaged, then purified, formulated (patented excipient), and aseptically filled (Type I glass) in a grade A room. 12 pilot batches (4 SaBPs) were produced. Risk analysis-defined QC criteria were evaluated. GPP processes were upgraded to GMP.

Results
To support development, PhD student, project manager, quality engineer, and laboratory technician were recruted. Formulation/production/QC development took 3 years; GMP qualification/upgrades took 2 more. All 12 pilot batches were produced. PTMP quality (efficacy/safety/quality) was assessed via 1,700 QC points (release tests + 2-year ICH stability). 5 audits (2 internal, 3 external) resulted in 95 corrective/preventive actions. All processes now comply with GMP (Part II)/Ph.Eur./EMA. Our hospital obtained API manufacturing authorization for hospital preparations.

Conclusion
Relying on two key pillars: existing and dedicated expertise and resources, GMP qualification enables our hospital to produce different formulation of PTMPs for ultra-personalized patient care, while meeting the most stringent quality requirements of GMP and Ph.Eur. standards. This achievement open 2 major advancements: the provision of these promising therapies to our patients, and the integration of biotherapies into our hospital’s pharmaceutical preparations, marking a significant shift toward next-generation treatments.