Optimizing the European Regulatory Framework for Sustainable Bacteriophage Therapy in Human Medicine

Abstract

For practitioners at hospitals seeking to use natural (not genetically modified, as appearing in nature) bacteriophages for treatment of antibiotic-resistant bacterial infections (bacteriophage therapy), Europe's current regulatory framework for medicinal products hinders more than it facilitates. Although many experts consider bacteriophage therapy to be a promising complementary (or alternative) treatment to antibiotic therapy, no bacteriophage-specific framework for documentation exists to date. Decades worth of historical clinical data on bacteriophage therapy (from Eastern Europe, particularly Poland, and the former Soviet republics, particularly Georgia and Russia, as well as from today's 27 EU member states and the US) have not been taken into account by European regulators because these data have not been validated under current Western regulatory standards. Consequently, applicants carrying out standard clinical trials on bacteriophages in Europe are obliged to initiate clinical work from scratch. This paper argues for a reduced documentation threshold for Phase 1 clinical trials of bacteriophages and maintains that bacteriophages should not be categorized as classical medicinal products for at least two reasons: (1) such a categorization is scientifically inappropriate for this specific therapy and (2) such a categorization limits the marketing authorization process to industry, the only stakeholder with sufficient financial resources to prepare a complete dossier for the competent authorities. This paper reflects on the current regulatory framework for medicines in Europe and assesses possible regulatory pathways for the (re-)introduction of bacteriophage therapy in a way that maintains its effectiveness and safety as well as its inherent characteristics of sustainability and in situ self-amplification and limitation.

Introducing yesterday‘s phage Therapy in today‘s Medicine

“…There is thus no need for a specific set of documentation for bacteriophage therapy [74]. We do not share this opinion for the reasons discussed below.…”

Novel approach of using a cocktail of designed bacteriophages against gut pathogenic E. colifor bacterial load biocontrol

“…The ability of phages to recognize precisely their hosts, rendered them as favorable antibacterial agents because broad-spectrum antibiotics kill target bacteria along with other beneficial bacteria present in the farm or in the organism body, say intestinal flora [10]. Many studies were applied mainly in the Soviet Union counties showed that application of phages in bacterial therapy or biocontrol is attainable in theory but practicably results were not so successful due to the lack of full coverage of target bacteria and the rapid emergence of bacterial mutations leading to complete resistance against phage infection [11]–[14]. Therefore, phage therapy or phage biocontrol have become unsuccessful [15] and eventually led to replacement of phage therapy with antibiotic treatment [12].…”

“…The exploitation of bacteriophages as a realistic approach to the control of pathogens has attracted considerable interest in recent years [10],[14] because of the emergence of antibiotic resistant bacteria. For example, calves and piglets with diarrhea due to experimentally administered pathogenic E. coli were cured within 8 h following phage administration [16].…”

The Potential of Bacteriophages in the Treatment of Burn Wounds

“…The issue of the clinical use of bacteriophages is once again considered as something new. In consequence, the applicants conducting standard clinical trials concerning the use of bacteriophages are forced to begin the clinical study from scratch (15).…”

“…Bacteriophages should not be classified as a classical therapeutic product, not only because this categorization is scientifically inappropriate, but also it would limit the admission of the product into everyday manufacturing (15).…”