A high containment polymodal pilot-plant fermenter--design concepts

Area of Science:

• Biotechnology
• Bioprocess Engineering
• Containment Technology

Background:

• Biohazardous fermentations require stringent containment measures.
• Existing pilot-plant systems may necessitate extensive secondary containment.
• Need for flexible, high-containment bioreactors for process development.

Purpose of the Study:

• To design and construct a 225 dm3 pilot-plant bioreactor system.
• To achieve containment levels exceeding Good Industrial Large-Scale Practice (GILSP) without whole-plant secondary containment.
• To offer a flexible system for diverse cell culture and microbial applications.

Main Methods:

• Incorporation of steam barriers on seals and lines.
• Use of multiple O-ring seals and dedicated kill tanks for waste.
• Double filtration for inlet/off gases and a mobile isolation unit for ports.
• Adaptable configuration for stirred-tank (top/bottom) or airlift operation.

Main Results:

• The bioreactor system successfully integrates advanced biosafety features.
• Achieved containment levels surpass GILSP requirements without secondary containment.
• Demonstrated flexibility for microbial, animal cell, or airlift cultures.
• System designed for cost-effective process development and production.

Conclusions:

• The designed bioreactor system provides a safe and flexible platform for pilot-scale biohazardous fermentations.
• Features enable compliance with guidelines for large-scale culture of recombinant microorganisms and pathogens.
• The system's adaptability and containment offer significant advantages for bioprocess development.