Best Practice Manufacturing and Quality Standards for Bacteriophage Therapy Products: Australian Consensus Statements

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Abstract Objective As antimicrobial resistance (AMR) continues to threaten global public health, bacteriophage therapy products (BTPs) offer a promising alternative to conventional antimicrobials. However, translation into routine clinical practice requires best practice standards for manufacturing and quality control to ensure the consistent safety, quality, and reliability of personalised BTPs produced for individual patients or small cohorts. Design A modified Delphi methodology was used to develop consensus statements, engaging experts from Australia’s National Bacteriophage Therapy Regulatory Working Group across the fields of clinical microbiology, phage biology, good manufacturing practice (GMP), regulatory science, and government. The process comprised three iterative phases: (1) structured statement development, (2) an anonymous REDCap survey, and (3) a hybrid consensus meeting. The strength of evidence and recommendations was assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework. Results Consensus was reached on 35 statements to provide best practice manufacture and quality control guidance for BTPs. These statements address requirements for phage identification and characterisation; define the point at which GMP-aligned processes commence for ubiquitous phages; outline quality control expectations for phage active pharmaceutical ingredient (pAPI) production and maintenance of BTP and host cell repositories. Additional guidance covers quality management systems, including documentation, traceability, and governance. Conclusion These consensus statements provide comprehensive best practice recommendations for the manufacture and quality control of BTPs in Australia. By promoting consistent, safe, and quality-assured approaches to personalised BTPs, they aim to facilitate clinical implementation while remaining aligned with existing international pharmacopoeial standards and regulatory frameworks. Significance of this study What is already known on this subject? Bacteriophage Therapy Products (BTPs) have re-emerged as a potential solution to antimicrobial resistance (AMR), supported by growing clinical evidence and global research activity. Data available to the regulatory working party includes more than 70 high-risk patients treated with dozens of different bacteriophages under a national open-label protocol (unpubl.). Published guidance from the European Pharmacopoeia, European Medicines Agency (EMA), UK Medicines & Healthcare products Regulatory Agency (MHRA), and World Health Oragnization (WHO) exists, yet no practical standards for personalised BTP manufacture have been established. What are the new findings? Recommendations have been made to define minimum quality and manufacturing stasndards for the safe, consistent production of BTPs. This is the first expert endorsed, risk-based framework to support the translation of personliased BTPs into routine clinical practice, cobering manufacture, repository management, quality control and supply. How might it impact on clinical practice in the foreseeable future? These consensus statements, developed by Australia’s National Bacteriophage Therapy Regulatory Working Group, can assist researchers, clinicians and regulatory authorities to develop BTP production protocols.

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