Search

Within this first part of the two-part series on phage manufacturing, we will give an overview of the process leading to bacteriophages as a drug substance, before covering the formulation into a drug product in the second part. The principal goal is to provide the reader with a comprehensive framework of the challenges and opportunities that present themselves when developing manufacturing processes for bacteriophage-based products. We will examine cell line development for manufacture, upstream and downstream processes, while also covering the additional opportunities that engineered bacteriophages present.

Bacteriophages have been used for diagnostic purposes in the past, but a lack of parallelizable engineering methods had limited their applicability to a narrow subset of diagnostic settings. More recently, however, advances in DNA sequencing and the introduction of more sensitive reporter systems have enabled novel engineering methods, which in turn have broadened the scope of modern phage diagnostics. Here we describe advanced methods to engineer the genomes of bacteriophages in a modular and rapid fashion.

Synthetic biology is an emerging engineering field focused on designing artificial biological systems with novel functionalities for use in therapeutics, basic science, biotechnology, and diagnostics [1,2]. Continuous advancements in DNA synthesis and sequencing technologies coupled with new techniques for genomic modification and assembly have opened the door for harnessing the power and diversity of biology for applications. For example, natural bacteriophage products, such as ListShield (Intralytix) and Agriphage (Omnilytics), are commercially available for reducing unwanted bacterial contamination.