Rationalisation of the purification process for a phage active pharmaceutical ingredient

Area of Science:

• Biotechnology
• Bioprocess Engineering
• Microbiology

Background:

• Phage therapy, a potential alternative to antibiotics, faced challenges in purification and stability.
• The rise of antibiotic resistance necessitates renewed interest and development in phage therapy.

Purpose of the Study:

• To review common impurities in phage lysates.
• To present a four-step purification process for bacteriophages.
• To propose a framework for developing scalable and transferable phage purification processes.

Main Methods:

• Discussion of physicochemical properties of contaminants, phage-related, and propagation-related impurities.
• Elaboration of a four-step purification strategy: clarification, capture/concentration, purification, and polishing.
• Development of a framework considering scalability, transferability, and duration for process design.

Main Results:

• Identification of key impurities in phage lysates and strategies to remove them.
• A structured four-step purification process tailored for bacteriophages.
• A framework to guide the rational development and validation of phage purification processes.

Conclusions:

• Advances in separation technologies enable efficient phage purification.
• The proposed framework aids in selecting and validating unit operations for scalable phage production.
• This work supports the resurgence of phage therapy by addressing critical manufacturing challenges.