EMA approves phage therapy guidelines

The organization said it hopes to encourage the development ​​of such innovative therapies, offering the necessary support to developers in bringing phage therapy products to the European market.

There is increasing interest in the use and promotion of bacteriophages due to their potential to reduce the use of antibiotics and help in the fight against antimicrobial resistance (AMR). Phage therapy uses viruses known as bacteriophages that naturally attack bacteria to treat infections in animals and humans.

Phage therapies are considered novel under Regulation (EU) 2019/6 and require marketing authorization through a centralized procedure. While Annex II of Regulation (EU) 2019/6 lays down some requirements for veterinary medicinal products specifically designed for bacteriophage therapy, the EMA said there was a need for a more specific guidance in relation to these products.

Commentators on social media welcomed the EMA approval of the guidelines, saying the move opens up the opportunity to extend the medical toolbox.

Industry had long decried the lack of clear regulatory guidelines or processes in relation to commercialization of bacteriophages.

A number of dossiers for bacteriophage products have been submitted to the EU, but to date none have yet been authorized, either as a feed additive (EFSA) or as a drug (EMA).

“There is a risk that the EU will be left behind without appropriate and robust regulatory frameworks and clear pathways for authorization for bacteriophage products both as feed additives as well as veterinary medical products,” concluded Jaroslaw Dastych earlier this year​​. He is the CEO of Proteon Pharmaceuticals, and a founding member of Phage EU, an industry and scientific stakeholder coalition group that wants to realize the full potential of phages in Europe.

International research 

A number of research projects on phages are underway in the EU. 

In May, Denmark’s Innovation Fund, together with a raft of Danish and British companies, announced an investment of over 20 million DKK​​ (US$2.9m) in an initiative focused on the use of bacteriophages to control bacterial diseases in aquaculture, namely trout.

That project is a collaborative effort between the University of Copenhagen, the Technical University of Denmark, the Danish Technological Institute, Danish companies, DanAqua, KSK Aqua, and Aller Aqua, alongside UK firms, Carus Animal Health, and Fixed Phage, and is set to run for three years.

“We have been working with isolation, characterization and application of phages against these specific pathogens for many years, and this is the next step where we aim at developing and testing prototype products,” Professor Mathias Middelboe, Department of Biology, University of Copenhagen, told FeedNavigator. He is coordinating the project.

Aquaculture is the fastest growing industry in animal food production in the world, but disease in the larval and brood stages of fish constitutes a significant bottleneck in fish production and causes large economic losses in the industry. Fish fry cannot be vaccinated, and antibiotics are therefore often used in the treatment of diseases. This entails a risk of the development and transfer of antibiotic resistance.

The antimicrobial products being developed through this project are aimed at reducing disease outbreaks in trout production, to be used preventively as feed supplements or applied to biological filters in recirculated breeding facilities. “Products that reduce fish mortality and support sustainable production have great commercial potential.”

Meanwhile, the Center for Evolutionary Hologenomics at the Globe Institute announced in July 2022 that it was leading a phage therapy project involving international researchers. The team, with financial backing from the Norwegian Seafood Research Fund, are looking to develop a safe and efficient phage therapy to control the bacteria, Pasteurella, in Atlantic Salmon farms.

Phage R&D is complex 

Skretting’s parent company, Nutreco, has also been supporting the development of next-generation technologies like bacteriophages to provide solutions to the critical health challenges of aquaculture.

Charles McGurk, R&D director at fish feed manufacturer, Skretting, speaking to this publication earlier this year, commented ​​on the potential of the approach. 

“On the fundamental level of whether they work there is no question, bacteriophages kill bacteria, that is how they propagate, that is their modus operandi. But then, of course, when you are looking to make a product containing a cocktail of bacteriophages that will give the desired effect, that's when it gets much, much more complex. And that is where you need to be really sophisticated in the approaches you take, to select the correct bacteriophages and to find a way of delivering those that can give an efficacious response.

“But there are a lot of biotech companies using very innovative solutions and technologies now, and we see that there is really scope for a breakthrough on the horizon."

IP game 

According to UK developer, FixedPhage, successfully commercializing bacteriophage-based products involves navigating complex regulatory landscapes, securing robust IP protection​​, and creating strategic market entry and distribution plans.

"Because bacteriophages are naturally occurring substances, their patentability often relies on significant modification or novel usage. Furthermore, their high specificity and evolutionary nature may complicate attempts at broad patent protection and consistent reproducibility – key aspects of the patenting process. Enforcing patents can also be difficult, given potential competitors’ claims about prior knowledge or usage. Some companies may opt for trade secret protection over patents, maintaining confidentiality around proprietary phage cocktails or production processes, though this requires rigorous internal controls. Additionally, the ever-evolving and challenging regulatory guidelines for bacteriophage product approval could impact IP strategies."