Prophage in Phage Manufacturing: Is the Risk Overrated Compared to Other Therapies or Food?

Gabard Jérôme

doi:10.3390/antibiotics9080435

Abstract

The rehabilitation of lytic bacteriophages, as living and replicative biological therapeutic agents, is only 2 decades old in western countries, compared to other therapeutic approaches using chemicals and inactivated or alive biologicals. This paper attempts to provide arguments to address prophage content issues in phage pharmaceutical preparations from a regulatory perspective. The author rebalances the risk associated with the presence of prophages in their pharmaceutical preparations in comparison (i) to lysogenic phages and prophages contained in various therapeutic anti-infective treatments, as well as in food or probiotics, (ii) to adventitious whole retroviruses or fragments contained in vaccines, and (iii) to the massive release of lysogenic phages and prophages induced by antibiotics usage.

Highlights

Phage therapy started [1,2] in 2017 within the western modern pharmaceutical industry
When it comes to antibiotic small molecules or peptides, no data regarding their potential effect on the release of lysogenic bacteriophages or prophages from patient bacterial microbiotas in reaction to treatment is requested by regulatory agencies toward filing for market authorization [41]
In bacteriophage manufacturing for human therapy, the growing regulatory trend is to recommend that strains used to make master and working bacterial lines be exempt of lysogenic bacteriophages or of prophages

Summary

Introduction

Phage therapy started [1,2] in 2017 within the western modern pharmaceutical industry. As antibiotics were discovered from biological organisms and chemically and properly characterized drugs, at reproducible concentration, standardized purity levels and contaminant traces started to rule the world of curative treatments [6]. The active ingredient is a fixed molecule, the production tool is often a living factory more prone to variability than chemical synthesis. Regulatory agencies are hampering the approval of phage therapy by insisting on the absence of prophages from phage preparations used to treat patients. This insistence sets a double standard, because many other approved therapies allows for far greater levels of viral release or contamination without greater evidence of safety

Opinion

Discussion

Conclusions