[Regulation of phage therapy medicinal products: developments, challenges and opportunities]

Due to their biological properties, bacteriophages represent a regulatory peculiarity and a challenge for drug approval. Adopted European guidelines on pharmaceutical quality, preclinical, and clinical development are only partially applicable to phage products. The increasing threat of infections with multi-resistant pathogens has not only given a major boost to the development of bacteriophages for the treatment of bacterial infections in recent years but has also led to major progress in the adaptation of regulatory requirements. This review article presents these recent developments and the current status of regulatory requirements for phage therapeutics.In 2024, harmonised quality criteria for phage products and active pharmaceutical ingredients have been implemented in the European Pharmacopoeia for the first time. Both the EU pharmaceutical reform and the national Medical Research Act should enable exemptional regulations taking into account the special features of phage therapeutics and allow novel regulatory pathways. Although increasing clinical data on the use of phage therapeutics have been published, the desired breakthrough in the form of proof of efficacy in randomised controlled clinical trials has not yet been achieved. However, the growing knowledge on phage preparations could be used to adjust the regulatory requirements. The next and decisive step on the path to approval of a defined phage product is the evidence-based proof of efficacy and safety in a randomised controlled clinical trial.