The Medicinal Phage—Regulatory Roadmap for Phage Therapy under EU Pharmaceutical Legislation

Faltus, Timo

doi:10.3390/v16030443

Cited by 8 publications

(2 citation statements)

References 104 publications

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“…This simple fact highlights the challenges in successfully advancing phage therapy in a clinical setting. The European Medicines Agency (EMA) has recently acknowledged that certain principles from the “Guideline on the evaluation of medicinal products indicated for the treatment of bacterial infections” can be extended to the application of phages [ 200 ]. In the European Union (EU), due to the absence of a phage-based medicine license for human use, phage therapies are typically employed either as an independent experimental therapy or as a component of a clinical study.…”

Section: Discussionmentioning

confidence: 99%

Does Phage Therapy Need a Pan-Phage?

Bozidis,

Markou,

Gouni

et al. 2024

Pathogens

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The emergence of multidrug-resistant bacteria is undoubtedly one of the most serious global health threats. One response to this threat that has been gaining momentum over the past decade is ‘phage therapy’. According to this, lytic bacteriophages are used for the treatment of bacterial infections, either alone or in combination with antimicrobial agents. However, to ensure the efficacy and broad applicability of phage therapy, several challenges must be overcome. These challenges encompass the development of methods and strategies for the host range manipulation and bypass of the resistance mechanisms developed by pathogenic bacteria, as has been the case since the advent of antibiotics. As our knowledge and understanding of the interactions between phages and their hosts evolves, the key issue is to define the host range for each application. In this article, we discuss the factors that affect host range and how this determines the classification of phages into different categories of action. For each host range group, recent representative examples are provided, together with suggestions on how the different groups can be used to combat certain types of bacterial infections. The available methodologies for host range expansion, either through sequential adaptation to a new pathogen or through genetic engineering techniques, are also reviewed.

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Section: Discussionmentioning

confidence: 99%

Does Phage Therapy Need a Pan-Phage?

Bozidis,

Markou,

Gouni

et al. 2024

Pathogens

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“…Therefore, the genetic engineering of bacteriophages has been recommended to (1) alter host ranges, (2) improve environmental stability, (3) enhance antibacterial activity, (4) enhance antibiofilm activity and (5) induce lysogenic conversion [ 62 , 63 , 64 ]. In addition, several legal regulations require attention, including the designation of the therapy to a specific class of medicinal products, and the determination of the appropriate legal framework for the various technical methods of manufacturing and administration of genetically modified bacteriophages [ 65 ]. Thus, while genetically engineered bacteriophages exhibiting improved efficacies could potentially be used throughout the consumer water cycle, comprehensive studies are required to assess the safety and efficacy of the genetically engineered bacteriophages prior to their applications as biological control agents.…”

Section: Genetically Engineered Bacteriophages For Improved Biocontro...mentioning

confidence: 99%

Benefits and Challenges of Applying Bacteriophage Biocontrol in the Consumer Water Cycle

Reyneke,

Havenga,

Waso-Reyneke

et al. 2024

Microorganisms

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Bacteria (including disinfection- and antibiotic-resistant bacteria) are abundant in the consumer water cycle, where they may cause disease, and lead to biofouling and infrastructure damage in distributions systems, subsequently resulting in significant economic losses. Bacteriophages and their associated enzymes may then offer a biological control solution for application within the water sector. Lytic bacteriophages are of particular interest as biocontrol agents as their narrow host range can be exploited for the targeted removal of specific bacteria in a designated environment. Bacteriophages can also be used to improve processes such as wastewater treatment, while bacteriophage-derived enzymes can be applied to combat biofouling based on their effectiveness against preformed biofilms. However, the host range, environmental stability, bacteriophage resistance and biosafety risks are some of the factors that need to be considered prior to the large-scale application of these bacterial viruses. Characteristics of bacteriophages that highlight their potential as biocontrol agents are thus outlined in this review, as well as the potential application of bacteriophage biocontrol throughout the consumer water cycle. Additionally, the limitations of bacteriophage biocontrol and corresponding mitigation strategies are outlined, including the use of engineered bacteriophages for improved host ranges, environmental stability and the antimicrobial re-sensitisation of bacteria. Finally, the potential public and environmental risks associated with large-scale bacteriophage biocontrol application are considered, and alternative applications of bacteriophages to enhance the functioning of the consumer water cycle, including their use as water quality or treatment indicators and microbial source tracking markers, are discussed.

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