Alternative methods of terminal sterilization for biologically active macromolecules

Area of Science:

• Pharmaceutical Manufacturing
• Biotechnology
• Sterilization Technologies

Background:

• Traditionally, injectable drug products containing peptides, proteins, and biopolymers (e.g., poly(DL-lactide), poly(DL-lactide-co-glycolide)) were considered unsuitable for terminal sterilization.
• This perception stemmed from the assumption that only steam sterilization in an autoclave was viable, necessitating aseptic manufacturing for these sensitive active pharmaceutical ingredients (APIs).

Purpose of the Study:

• To review and discuss emerging sterilization techniques for thermally sensitive APIs and biopolymers.
• To evaluate the feasibility of large-scale terminal sterilization for bioactive macromolecules using non-traditional methods.

Main Methods:

• This review focuses on four primary terminal sterilization methods: gamma irradiation, electron beam (e-Beam) irradiation, natural light sterilization, and microwave sterilization.
• The advantages and disadvantages of each technique for large-scale application are discussed based on existing literature.

Main Results:

• Technological advancements, particularly from the food industry, have enabled the development of effective terminal sterilization methods for sensitive pharmaceutical compounds.
• Gamma irradiation, e-Beam, natural light, and microwave sterilization offer alternatives to aseptic processing for specific bioactive macromolecules.

Conclusions:

• The traditional view that peptides, proteins, and biopolymers cannot undergo terminal sterilization is being challenged by new technologies.
• These advanced sterilization techniques provide viable options for the large-scale manufacturing of injectable drug products containing thermally sensitive APIs, potentially improving product safety and manufacturing efficiency.