Coordination with the regulatory authorities

The long-term perspective of the joint project Phage4Cure is the approval of bacteriophages for the treatment of bacterial infections. Although bacteriophages have been used as therapy for more than one hundred years, there are many different aspects to be considered when compared with traditional drugs. Until now, drug approval procedures have been based on classical chemical and biotechnological substances and can therefore not simply be translated to phages. In order to pave the way for the approval of phage therapy, the project members aim to discuss the necessary steps regularly with the regulatory authorities. Already at the end of September 2017, the Paul Ehrlich Institute (PEI) hosted a meeting in Langen near Frankfurt. In February 2018 the first meeting took place at the Federal Institute for Drugs and Medical Devices (BfArM) in Bonn. Meanwhile, the responsibility of the authorities has been clarified: the BfArM will be in charge.

The project team visiting the BfArM (Febr. 2018) F.l.t.r.: Prof. Dasenbrock (ITEM), Dr. Rohde (DSMZ), Dr. Hüser (CRO), Dr. Roß (ITEM), Dr. Hertrampf (CRO), Fr. Lehmann (CRO), Dr. Ziehr (ITEM), Prof. Witzenrath (Charité)
The project team visiting the PEI (Sept. 2017) F.l.t.r.: Dr. Rohde (DSMZ), Dr. Uhle (CRO), Dr. Hertrampf (CRO), Dr. Seitz (ITEM), Prof. Witzenrath (Charité), Prof. Dasenbrock (ITEM), Dr. Ziehr (ITEM), Dr. Roß (ITEM), Dr. Hüser (CRO).

Interim report of the DSMZ laboratory

The first stage „selection of phages“ within the joint project „Phage4Cure“ consists of the targeted search for bacteriophages, their clonal purification, characterization, comparison, propagation and appropriation for further pharmaceutical development. These steps form the essential phage biology in the initial part of the project. Aim of this joint project is to prepare a variety of phages, that complement one another in terms of their host spectrum; as antiinfective agents against the multiresistant bacterium Pseudomonas aeruginosa.

Electron-microscopical shot of pseudomonads with docked bacteriophages. Copyright M. Rohde, HZI

During this process a great variety of Pseudomonas phages will be tested for their effectiveness against a broad spectrum of Pseudomonas strains. These bacterial strains were isolated from a variety of patients in international clinics. Phages are now met with the challenge to win the fight against multiresistant bacteria after the failure of antibiotics. The most difficult aspect of phage biology is the physicochemical receptor recognition of phages when coming into contact with bacterial surfaces. The effectiveness of this highly specific ability of each phage to bind with the bacteria ultimately leads to the destruction of the bacteria.

Since the start of the project the screening of phages in the laboratories of Leibniz-Institut DSMZ GmbH has already produced some promising results. Quantitative comparison of phage efficiency, morphology, and genetic make-up have produced evaluation patterns that represent the next milestone for Phage4Cure. This will be the selection of the therapeutically most effective phages for transfer to Fraunhofer ITEM where a production procedure for the growth and purification of the phages will be put into place. Ultimately this reproducible procedure should produce pharmaceutically pure phages that can then be used in the next steps of the project.

Media tip

In the evening of October 18th there was a documentary on the public TV channel 3sat about the international antibiotic crisis (as part of the series “Unsere Zukunft” / our future). The documentary did a good job in illustrating the global problems with bacterial resistances. It is available at Youtube and the project Phage4Cure is mentioned starting around minute 43:00 (though not referenced by name). (Update March 2018: unfortunately the video has meanwhile been removed)