Standardized bacteriophage purification for personalized phage therapy.

Area of Science:

• Microbiology
• Biotechnology
• Infectious Diseases

Background:

• The rise of antibiotic resistance necessitates alternative infection treatments.
• Phage therapy, using bacteriophages (phages) to target bacteria, is gaining traction.
• Current phage therapy is often administered under expanded-access investigational new drug protocols.

Purpose of the Study:

• To develop a systematic, scalable protocol for producing clinical-grade phage preparations.
• To ensure the safety and efficacy of phage therapy by standardizing production.
• To facilitate the reintroduction of phage therapy into Western medicine.

Main Methods:

• A 16- to 21-day protocol combining modified classic techniques and modern membrane filtration.
• Isolation, liter-scale cultivation, concentration, and purification of medicinal phages.
• Early endotoxin removal using centrifugation, microfiltration, and ultrafiltration.

Main Results:

• Average yield of 23 mL at 10^11 plaque-forming units (PFUs)/mL for tested phages.
• Production of up to 64,000 treatment doses (at 10^9 PFUs) per run.
• Up to 10^6-fold reduction in endotoxins in phage preparations.

Conclusions:

• The developed protocol yields high-quality, clinically safe phage preparations efficiently.
• Standardized phage production is crucial for the successful integration of phage therapy.
• This protocol supports expanded-access and potential clinical trial applications of phage therapy.