Table 4.

The implementation of adaptive licensing pathways for single phage and pre-made or custom phage cocktails.

	Single phage	Pre-made cocktails		Custom cocktails
		Untyped infections	Typed infections	Single species typed infections	Multi-strain typed infections	Polymicrobial typed infections
Phage selection	• One phage with high efficacy against a typed bacterial strain.	• Multiple phages targeting an untyped infection.	• Multiple phages, compromising between efficacy and host range.	• Multiple phages targeting a single typed bacterial strain.	• Multiple phages targeting multiple typed bacterial strains.	• Multiple phages targeting multiple typed bacterial species.
Aim	• Treat MDR/XDR strains only.	• Treat bacterial infections based on symptoms.	• Treat infections caused by multiple strains of the same species.	• Treat patient specific infections caused by a single typed species.	• Treat multiple strains of the same species in a single patient.	• Treat typed polymicrobial infections in a single patient.
Advantages	• Easy to change phages. • Easy analysis.	• Easy recruitment to trials.	• Easy recruitment to trials. • Only limited phage library needed.	• Predicted high efficacy. • Avoids emerging bacterial resistance.	• Wide application.	• Wide application.
Disadvantages	• New phages require additional trials. • Unpredictable results.	• Poor patient recovery rate. • Unpredictable results. • New formulation means new trial.	• Cocktail obsolescence. • New formulation means new trial.	• Unique cocktails increase recruitment difficulty to trials. • Cocktail obsolescence. • Large phage library needed.	• Every cocktail unique, more difficult to recruit trial participants. • Necessary to reformulate cocktail as new strains appear. • Large phage library needed.	• Every cocktail unique, more difficult to recruit trial participants. • Necessary to reformulate cocktail as new strains appear. • Multiple large phage libraries needed.
Iteration	• Phage is discarded or formulation changed as new data emerges.	• Non-effective or hazardous phages are removed as data emerges. • Additional phase I testing if there is poor efficacy or immunogenicity.	• Non-effective or hazardous phages are removed as data emerges. • Additional phase I testing if there is poor efficacy or immunogenicity.	• Cocktail composition altered as data on phages emerge. • Additional phase I testing if there is poor efficacy or immunogenicity.	• Cocktail composition altered as data on phages emerge. • Additional phase I testing if there is poor efficacy or immunogenicity.	• Cocktail composition altered as data on phages emerge. • Additional phase I testing if there is poor efficacy or immunogenicity.
Design	Single site long term or multi-site short term	Single site long term or multi-site short term	Single site long term or multi-site short term	Multi-site long term	Multi-site long term	Multi-site long term
Implementation time	+	+	+	++ or +++*	++ or +++	+++
Cost	$	$$	$$	$$$	$$$	$$$

^*Time to implementation would be affected by the form of treatment chosen. Pre-approved libraries could be implemented faster should suitable criteria be developed.