In the spectrum of pharmaceutical manufacturing facilities, injectable product manufacturing facilities represent the most sophisticated and challenging to design, build, qualify and operate, particularly when products manufactured in these facilities are rendered sterile when complete, ready to inject directly into a human. For this reason, very careful consideration must be made when developing such a facility.
At the core of the sterile manufacturing operation, process technology drives the ability to safely, efficiently and repeatedly produce sterile products. Early developments of sterile manufacturing facilities were centered on the (at times open) aseptic processing in a cleanroom environment, with personnel in the critical work area. This approach created risk of particulate and bioburden contamination. Thus, as sterile manufacturing technologies and practices developed, the drive to close the process and separate the critical manufacturing environment from personnel became a key driver in the development of the core process technology.
Today, the most commonly prescribed approach is to close the manufacturing process and locate it behind a fully contained ISO 5 isolator system in an ISO 7 or ISO 8 background cleanroom environment. In contrast, when the ISO 5 zone is open to the surrounding environment, the background environment is commonly designed to meet ISO 5 or ISO 6, thus increasing the complexity and management of materials and personnel in this condition.
Sterile manufacturing operations are rigorously scrutinized for integrity and consistency to maintain patient safety. Accordingly, process equipment supporting or controlling sterile operations is designed to meet strict regulatory guidelines and design requirements.
Major design considerations in process equipment include:
- Operability and ergonomics
- Cleanability of the system automatic)
- Ability to sterilize the system
- Smooth, hard and crevice-free finishes of all product contact surfaces
- Fully controllable, consistent and repeatable functions (manual or Closed versus open process systems
- The ability to control the manufacturing environment to a prescribed level