Imke H. E. Korf (Brunswick / DE), Melanie Häfner (Berlin / DE), Sarah Wienecke (Brunswick / DE), Christine Rohde (Brunswick / DE), Johannes Wittmann (Brunswick / DE), Morten Leddin (Berlin / DE), Werner Wenzel (Berlin / DE), Kai Halama (Berlin / DE), Drudea Garbe (Berlin / DE), Marcus Stichling (Berlin / DE), Holger Ziehr (Brunswick / DE), Christian Willy (Berlin / DE)
Question:
The use of phages, viruses that specifically kill bacteria, is a promising approach to treating infections, as numerous successful individual cases show. However, phage therapy has not yet been established as standard medicine in Germany.
Therfore we aimed at the investigation of the practicability of phage therapy with focus on ESKAPE pathogens under the infrastructural conditions available in Germany in compliance with legal requirements.
Methods:
The general procedure is as follows: After isolation, characterisation, and selection of phages / bacterial hosts that allow an efficient production, phage active pharmaceutical ingredients (API) are manufactured according to quality standards assigned in consultation with the authorities. Before bulk APIs are delivered to the pharmacy, GMP-compliant release testing must be carried out to verify the identity, purity and content of the APIs. Phages are formulated by the pharmacy according to the indication, as specified by the microbiology and the treating physician .
Results:
Three phages against P. aeruginosa out of 140 were selected for production based on host range analysis, genetic properties, and lysis efficacy by the DSMZ. A platform-like manufacturing process has been established for phage-APIs, in which essential process parameters in cultivation and purification must be adapted to the individual phage to ensure successful production by Fraunhofer ITEM. Requirements for phage APIs in terms of documentation, specifications and analytics were agreed with the relevant authorities. After their release, the first three phage-APIs were delivered to the clinical partners. Sensitivity testing (phagogram) was performed by the department of microbiology, phage cocktails were formulated by the hospital pharmacy and patient treatment was performed by different clinical departments of the Military Hospital Berlin.
Conclusion:
Current requirements for phage GMP production necessitate a time-consuming process, which has led to a lack of available phages in the project. To make phage therapy accessible to many patients, it will be necessary to expand production and sensitivity testing capacities.