The revised EU GMP Annex 1 “Manufacture of Sterile Medicinal Products” came into force on 25 August 2023. It significantly tightened requirements for aseptic manufacturing and made barrier technologies — isolators and RABS — the preferred way to protect the product. Here is what this means when choosing equipment.
Contamination control strategy
Annex 1 requires a contamination control strategy (CCS) covering the whole process: premises, equipment, personnel, materials, cleaning and decontamination, and monitoring. An isolator or RABS is a key element of this strategy, so it is selected for the process and the cleanroom rather than in isolation.
Isolator or RABS
- Isolator — a fully closed system with a controlled Grade A environment and its own automated bio-decontamination. It minimises operator impact and allows the equipment to be placed in a lower-grade room.
- RABS — a restricted access barrier system. Grade A inside, but the background room must be at least Grade B. Often chosen for upgrading existing lines.
Background cleanroom grade
For open isolators the background should generally be at least Grade C, for closed isolators at least Grade D, and for RABS at least Grade B. This choice drives the cost of cleanrooms, gowning and monitoring.
Bio-decontamination
The internal surfaces of an isolator undergo validated bio-decontamination — most often with vaporised hydrogen peroxide (VPHP). The cycle must be reproducible and confirmed with biological indicators. Materials are transferred through pass-through chambers with bio-decontamination and RTP ports.
Gloves — the weakest point
Gloves and ports are the most likely point of barrier failure. Annex 1 requires regular visual inspection and physical leak testing of the glove system, typically at the beginning and end of each batch or campaign. Automatic glove and RTP port leak testers help here, as do gloves made of materials compatible with decontamination and process substances.
What to consider when choosing
- process: aseptic filling, sterility testing, HPAPI handling, cell therapy;
- whether the operator needs protection, not only the product (this defines the isolator pressure);
- the grade of existing rooms and whether it can be changed;
- bio-decontamination and material transfer method;
- glove integrity testing and data integrity (21 CFR Part 11).
AT Engineering supplies isolators and RABS, pass-through chambers with bio-decontamination, integrity testing systems and isolator gloves. Describe your process and cleanroom grade and we will propose a configuration.
