Issue link: https://www.e-digitaleditions.com/i/1373953
Pharmaceutical Technology BIOLOGICS AND STERILE DRUG MANUFACTURING EBOOK 2021 17 Port systems are now widely used to trans- fer materials into RABS or isolators. These were originally developed for the nuclear industry and have been adapted for aseptic production. Sensors have been designed to measure airf low in RABS systems from the inside of the barrier to the class B-background, continuously monitoring the integ- rity of the barrier. Also, to further reduce opera- tor impact, robots are now used for processes like set-up of the liquid path on the filling line. Even environmental monitoring using settle plates can now be executed by robots. The boldest attempt, however, is gloveless systems, designed to elimi- nate operator involvement in the process. Another technology that has evolved in the past years and plays an essential factor for multiple- used filling lines is a fast and efficient decontami- nation process. Contamination control strategies in line with [the European Union's guideline] Annex 1 are now realized in different ways and with different systems. For example, fully auto- mated decontamination with hydrogen peroxide of the entire cleanroom with RABS barrier tech- nology prior to each batch have been developed. The process itself takes less than three hours and can immediately be followed by the aseptic set-up of the cleanroom for the next product. The new Vetter cleanroom technology (V-CRT) combines the individual benefits of isolators and RABS and is a holistic cleanroom concept that acknowledges all working steps related to aseptic manufacturing, including decontamination, set- up and filling, monitoring, and analytics. This approach uses automated decontamination of the entire cleanroom with hydrogen peroxide, which mitigates the risk of microbe carry-over from grade B to grade A, while still enabling rapid product changeover using a RABS. The RABS acts as a closed system because the doors are not opened following decontamination. This approach meets stringent quality and safety standards that well exceed current good manufacturing practices (CGMP). Another new approach in fill/finish technology is being developed through a collaboration be- tween Vetter and Syntegon Technology. The objec- tive is a CGMP-compliant and f lexible production cell based on isolator technology that addresses the outlined challenges and opportunities for small- scale commercial manufacturing. The microbatch technology is to be used for both the production of very small quantities of up to 50 units, as well as a small filling line for commercial batch sizes of up to 5000 units, both in accordance with interna- tional regulatory requirements. The core of the sys- tem is a robotized filling equipment within an iso- lator. The robot not only does the filling, but also the line set-up and environmental monitoring. To avoid exposure of the packaging components with hydrogen peroxide, the isolator is equipped with a de-bagging and lock system. A broad range of pre- sterilized packaging components can be handled either in a cup-nest or a clip-nest configuration, which allows filling of pre-crimped cartridges, sy- ringes, and vials. Vials can either be crimped on the machine or sealed by press-on caps. With all these process variants, it is essential to have only a few formats parts to guarantee quick changeovers. Finally, 100% fill-weight checks allow a high level of process control; there is a direct feedback-loop, so that the machine adjusts itself. The detailed design phase has been started and we are looking forward to the first mock-ups in the workshop. PT