The European Medicines Agency (EMA) has recently published the Guideline on quality, safety, efficacy of veterinary medicinal products specifically designed for phage therapy. The aim of the guideline is to establish the regulatory, technical, and scientific requirements applicable to veterinary medicinal products (VMPs) specifically designed for phage therapy and composed of bacteriophages. Bacteriophages are viruses that infect bacteria and do not have the capacity to infect eukaryotic cells; their action is linked to their lytic activity, generally restricted to specific bacterial strains.
Phage therapies are classified as novel therapies (NTs) by Regulation (EU) 2019/6 and as such, the centralised marketing authorisation procedure is mandatory. Regulation (EU) 2021/805 amending Annex II to Regulation (EU) 2019/6 includes general and specific requirements applicable to NTs, and specific provisions for phage therapy.
The area is extremely complex because VMP based on bacteriophages are expected to require frequent changes in composition for the bacteriophage strain(s) in order to maintain efficacy/circumvent resistance development in relation to the intended indication. This guideline addresses how these provisions can be applied in practice and covers:
- Administrative information to be provided in the marketing application,
- Quality documentation, including requirements for phage products with fixed and flexible qualitative and quantitative composition, product development, characterisation, production and control of starting materials, control tests on the finished product, batch-to-batch consistency, and stability tests,
- Safety requirements including toxicology, safety tests, user safety and environmental risk assessment,
- Efficacy requirements, encompassing pre-clinical studies and clinical trials, taking into account the unusual pharmacology of bacteriophages,
- Concomitant use of bacteriophages with conventional antibiotics,
- Post-marketing authorisation change: quality, safety and efficacy requirements for already authorised bacteriophage products.
The adoption of this guideline signifies a substantial advancement in the regulation of veterinary bacteriophages medicinal products. It is anticipated to benefit academia, industry, and regulators, facilitating and expediting the development and authorisation of such medicinal products. This contribution will help increase the availability of the veterinary medicinal products, offering a promising avenue for addressing antibiotic-resistant bacterial infections in veterinary medicine.