From:  Bacteriophage therapy in the era of antimicrobial resistance: clinical evidence, translational challenges, and emerging regulatory frameworks (2020–2026)

 Key manufacturing and quality control (QC) elements in contemporary phage therapy frameworks.

Manufacturing/QC componentKey regulatory or operational considerationsIllustrative examples/Reported practicesReferences
Host cell banksUse of validated production hosts organized into master and working cell banksStructured cell-banking systems reported in the Belgian compassionate-use program [10]
Phage seed stocksControlled phage seed lots with genomic characterization and traceabilitySeed-lot systems aligned with Ph. Eur. 5.31 expectations [9]
Genomic safety screeningScreening for toxin genes, antimicrobial resistance determinants, lysogeny modules, and prophage contaminationThe Belgian cohort screened both phages and production hosts against virulence and resistance databases [10]
Potency testingStandardized plaque assays or equivalent functional assays for titre determinationClinical preparations generally ranged from ~106 to 1010 PFU/mL, depending on formulation and route[8, 10, 39, 41]
Impurity and endotoxin controlControl of host-cell impurities, pyrogenicity testing, and endotoxin thresholds for systemic administrationMedian endotoxin level of 5 EU/mL and weight-adjusted endotoxin thresholds reported in the Belgian program [5, 10]
Microbiological quality/SterilitySterility requirements for sterile PTMPs and microbiological specifications for non-sterile formulationsRegulatory guidance from Ph. Eur. and EMA draft framework [9, 11]
Stability testingStability evaluation for shelf life, storage, and transport conditionsEMA draft guidance includes structured stability assessment procedures [11]
Change-control and platform reproducibilityDefined procedures for post-manufacturing updates and comparability managementProposed platform-based lifecycle protocols permitting adaptive phage updates within validated manufacturing frameworks [11, 19, 21, 35]

Ph. Eur.: European Pharmacopoeia; EMA: European Medicines Agency.