Advanced manufacturing, formulation and microencapsulation of therapeutic phages

Abstract

Manufacturing and formulation of stable, high purity and high dose bacteriophage drug products suitable for clinical usage would benefit from improved process monitoring and control of critical process parameters that affect product quality attributes. Chemistry, Manufacturing and Controls (CMC) for both upstream (USP) and downstream processes (DSP) need mapping of critical process parameters (CPP) and linking these to critical quality attributes (CQA) to ensure quality and consistency of phage drug substance (DS) and drug product (DP) development. Single-use technologies are increasingly becoming the go-to manufacturing option with benefits both for phage bioprocess development at the engineering run research stage and for final manufacture of the phage drug substance. Future phage drug products under clinical development will benefit from implementation of process analytical technologies (PAT) for better process monitoring and control. These are increasingly being used to improve process robustness (to reduce batch-to-batch variability) and productivity (yielding high phage titres). Precise delivery of stable phage drug products that are suitably formulated as liquids, gels, solid-oral dosage forms etc., could significantly enhance efficacy of phage therapy outcomes. Pre-clinical development of phage drug products must include at an early stage of development, considerations for their formulation including their characterisation of physiochemical properties (size, charge etc.), buffer pH and osmolality, compatibility with regulatory approved excipients, storage stability (packaging, temperature, humidity etc.), ease of application, patient compliance, ease of manufacturability using scalable manufacturing unit operations, cost, and regulatory requirements.