HCL Becomes the First Public Institution in the European Union Authorized to Manufacture GMP Therapeutic Phages for Human Use

For several years now, the Hospices Civils de Lyon have occupied a special place in the revival of phage therapy in Western Europe. While interest in bacteriophages has increased worldwide as antimicrobial resistance continues to spread, the teams in Lyon have pursued an objective that extends beyond clinical experimentation. Their ambition has been to reconstruct an entire therapeutic phage ecosystem, from the isolation of phages in the environment to the production of pharmaceutical-grade preparations suitable for human administration.

© Hospices Civils de Lyon

This long-term effort reached an important milestone in May 2026, when the French National Agency for Medicines and Health Products Safety granted the Hospices Civils de Lyon authorization to manufacture therapeutic phages as pharmaceutical starting materials intended for human use. The authorization concerns both the production of phage intermediates and purified therapeutic preparations produced according to Good Manufacturing Practice standards, the same quality framework applied to biological medicines.

This development is the culmination of years of work carried out by clinicians, microbiologists, pharmacists and researchers who have progressively built a complete production pipeline dedicated to therapeutic bacteriophages. Rather than relying on industrial partners or imported preparations, the Lyon teams chose to establish a public and integrated infrastructure capable of producing phages locally while meeting modern pharmaceutical standards.

The initiative began in 2017 with the creation of PHAGEinLYON, a multidisciplinary program involving infectious disease specialists, bacteriologists, pharmacists and clinical researchers. The objective was not only to provide phage therapy to selected patients facing multidrug-resistant infections, but also to rebuild expertise that had largely disappeared from France after the decline of phage therapy during the antibiotic era.

The scientific challenges were substantial. Therapeutic phages are not generic antimicrobial agents. Their biological specificity, which constitutes one of their greatest advantages, also makes their development more complex than conventional antibiotics. A bacteriophage generally infects only a limited number of bacterial strains. Consequently, therapeutic success depends on the availability of extensive phage collections and on the ability to identify rapidly those active against a patient's bacterial isolate.

To address this challenge, researchers at Lyon established an extensive phage discovery and biobanking strategy. Environmental samples became an important source of candidate phages. Wastewater, aquatic ecosystems and other bacteria-rich environments were systematically explored. Among the earliest successful isolations were phages recovered from the surroundings of the Parc de la Tête d'Or in Lyon. Over time, these efforts resulted in collections comprising more than one hundred characterized phages active against clinically relevant pathogens.

Electron microscopy image of the therapeutic bacteriophage V1SA19 targeting Staphylococcus aureus, developed at the Hospices Civils de Lyon - © Hospices Civils de Lyon

Each isolated phage undergoes extensive characterization before being considered for therapeutic use. Researchers sequence the complete viral genome to exclude genes associated with lysogeny, bacterial virulence or antibiotic resistance transfer. Morphological characterization using electron microscopy is combined with studies of adsorption kinetics, host range and replication efficiency. Only strictly lytic phages demonstrating favorable safety and biological properties are retained for further development.

The Therapeutic Phage Laboratory at the Hospices Civils de Lyon, headed by Professor Frédéric Laurent, plays a central role in these activities. The laboratory is responsible for phage isolation, genomic characterization, selection of therapeutic candidates, biobanking and large-scale amplification of phages with clinical potential. These production steps are performed under Good Manufacturing Practice requirements, ensuring traceability and reproducibility throughout the process.

The Therapeutic Phage Laboratory at the Institut des Agents Infectieux, where phages are isolated, characterized and produced under GMP conditions - © Hospices Civils de Lyon

However, obtaining large quantities of phages is only part of the challenge. Amplification produces concentrated lysates that may contain bacterial proteins, nucleic acids, endotoxins and other contaminants incompatible with human administration. The purification of therapeutic phages has therefore become a major research and pharmaceutical objective.

This aspect of the program is led by the FRIPHARM platform under the responsibility of Professor Fabrice Pirot. Located at Edouard Herriot Hospital, FRIPHARM specializes in pharmaceutical manufacturing and innovation. Within the framework of therapeutic phage production, the platform has progressively developed purification, formulation and quality control procedures capable of transforming crude phage lysates into pharmaceutical preparations suitable for clinical use. According to the information released by the institution, more than twenty-five quality controls are performed throughout the manufacturing process and on the final products. Stability studies have also demonstrated that purified phage suspensions can remain active for more than eighteen months under standard refrigerated conditions.

FRIPHARM, the pharmaceutical platform responsible for purification, formulation and quality control of therapeutic phages - © Hospices Civils de Lyon

The manufacturing process itself resembles that used for many biological medicines, although phages present their own specific challenges. Production begins with carefully selected bacterial strains used as hosts for phage amplification. The resulting lysates are then subjected to purification procedures designed to eliminate impurities while preserving viral infectivity. Molecular quality controls, including PCR analyses and genome sequencing, are performed repeatedly throughout the manufacturing chain. The final objective is to produce preparations whose safety, stability and biological activity satisfy the same standards expected for any injectable biological product.

Alongside these technological developments, clinical experience has steadily expanded. Since 2017, more than 120 patients facing severe therapeutic dead ends have been treated through phage therapy programs at the Hospices Civils de Lyon. Many suffered from chronic infections associated with multidrug-resistant bacteria, including osteoarticular infections and prosthetic joint infections that had failed to respond to prolonged antibiotic treatments.

One of the earliest patients treated in Lyon had developed a chronic Staphylococcus aureus infection involving a knee prosthesis. After years of unsuccessful antibiotic therapy, transfemoral amputation had become a realistic option. The patient eventually received intra-articular therapeutic phages specifically selected against the infecting bacterium. According to the medical teams, this intervention contributed to controlling the infection and preserving the limb, illustrating the potential role of phage therapy in situations where conventional treatments offer few remaining options.

The experience accumulated over the years has also stimulated larger research initiatives. In 2021, the PHAG-ONE project received support through the French Priority Research Program on antimicrobial resistance, coordinated by the French National Research Agency and INSERM. The project obtained public funding amounting to 2.85 million euros with the objective of transforming an emerging expertise into a complete pharmaceutical production sector dedicated to therapeutic phages. More recently, additional support has been provided through the RHU THERAPhage initiative, further strengthening research and translational activities in this field.

The PHAG-ONE project - ©  https://www.phag-one.fr/

The work carried out in Lyon illustrates a broader evolution occurring throughout the phage therapy community. The central question is no longer whether bacteriophages possess antibacterial activity, as this has been demonstrated repeatedly. The challenge now lies in establishing robust manufacturing procedures, extensive phage libraries, rapid bacterial susceptibility testing and clinical evidence capable of integrating phage therapy into routine medical practice.

The Lyon model addresses many of these issues simultaneously. By bringing together environmental phage isolation, genomic characterization, GMP manufacturing, pharmaceutical quality control and clinical expertise within a single institution, the Hospices Civils de Lyon have progressively built an infrastructure that may contribute to shaping the future of therapeutic phages not only in France, but potentially throughout Europe. The project now extends beyond the treatment of individual patients and raises broader questions regarding the organization of phage banks, the sharing of production strains and the establishment of sustainable therapeutic phage networks adapted to the challenges posed by antimicrobial resistance.

Written and reviewed by The Phage Therapy Team - Adapted from the HCL press release (https://teamhcl.chu-lyon.fr/autorisation-production-phages-therapeutiques) with their permission. Images belong to HCL and attributions are indicated. For any comments, please contact thephagetherapy@gmail.com.