Regulating phage therapy: The biological master file concept could help to overcome regulatory challenge of personalized medicines.

Abstract

In a note published in The Lancet in December 1915, Frederic Twort described the discovery of an infectious, filterable agent that causes the glassy transformation and eventual killing of bacteria, now identified as Staphylococcus hyicus [1]. Two years later, Felix d'Herelle independently described an invisible microbe antagonistic to dysentery bacilli in a note to the Comptes Rendus de l'Academie des Sciences [2]. These two reports are the first published descriptions of bacteriophages, a term coined by d'Herelle, who foresaw the therapeutic potential of these newly identified bacteriolytic agents. > The key issue is whether phage therapy medicinal products (PTMPs) require a marketing authorization or not. Yet, phage therapy, despite varying degrees of success during the 20th century, never made it into widespread clinical use owing to the discovery of antibiotics [3]. However, the increasing antibiotic resistance among major pathogens such as Staphylococcus or Mycobacterium has become a critical public health problem—in the European Union (EU) alone, around 25,000 patients die each year from an infection with drug‐resistant bacteria (http://ecdc.europa.eu/en/publications/publications/0909\_ter\_the\_bacterial\_challenge\_time\_to\_react.pdf). Although difficult to estimate, the annual global death toll attributable to antimicrobial resistance might range from the hundreds of thousands to as much as millions in the coming decades (https://amr-review.org/sites/default/files/AMR%20Review%20Paper%20-%20Tackling%20a%20crisis%20for%20the%20health%20and%20wealth%20of%20nations\_1.pdf). In light of this growing health crisis, phage therapy has attracted renewed interest as an alternative to antibiotics [3]. ### Regulatory challenges for phage therapy However, this reemergence raises regulatory concerns. There has been intense discussion on how to classify phage‐based therapeutics within the EU's regulatory framework [4], [5], [6] with some consensus among Members States' regulatory authorities and the European Medicines Agency that these would be regulated as biological medicinal products [7]. Nonetheless, positions still vary because the current medicinal product regulation is not well suited for this unorthodox therapeutic …