The final Annex 1 version calls organizations to adopt a new mindset that goes top-down, is holistic and may ask for cultural changes. Considerations are expected to be given to novel technologies, such as deployment of barrier technology, online CCIT and rapid/alternative monitoring methods. All geared toward the purpose of improving product quality and, ultimately, patient safety. Isolators or Barrier Systems are beneficial in assuring required conditions and minimizing microbial contamination associated with direct human interventions in the critical zone. Their use should be considered in the CCS. Some specific elements are choosen to compare them to their reliability under the guidelines of the new Annex 1.