Equipment and utensils:

• Product-contact surfaces of equipment must be sterilized using a validated method (vibratory feed systems may be exempted from this requirement provided they are high level decontaminated with a sporicidal agent in-situ)
• Sterilization-in-place and clean-in-place should be used wherever possible
• Equipment should be assembled to the fullest extent possible prior to sterilization
• Equipment and utensils should be sterilized in sealed containers (the use of paper and tape is not recommended)
• Equipment and utensils should be introduced in a manner that retains at least one layer of sterilized-protective covering or wrap until entry into the critical zone
• Equipment and utensils should be sterilized/depyrogenated using a just-in-time approach
• Inventories of materials in the aseptic environment should be minimized
• Equipment should be selected for high reliability, ease of changeover, and adjustment
• Remote adjustment of equipment should be utilized where possible
• Tool free change over from one format to another should be possible
• Equipment should be tolerant of container-closure miss-feeds, jams, and other problems to minimize the need for interventions
• Equipment (and to some extent facility) should use process analytical technology and other feedback systems for ease of control, operation, and documentation
• Non-product contact portions of the equipment should be easily decontaminated and non-invasive of the critical zone
• All equipment surfaces should be resistant to the potential corrosive action of sanitizing and decontamination agents.

Containersand closures:

Product:

• Product materials must be prepared and sterilized using validated methods
• Product delivery should be made directly into the critical zone
• Where product is supplied to the critical zone in sterile container (e.g., sterile powders), it should be introduced in a manner that retains at least one layer of sterilized-protective covering or wrap until entry into the critical zone.

Personnel:

• Personnel must receive initial and periodic training in current good manufacturing practice, aseptic processing, microbiology, aseptic gowning, and job specific tasks
• Where appropriate, personnel should be initially and, periodically thereafter, assessed for their proficiency in aseptic gowning
• Personnel should be initially and, periodically thereafter, assessed for their proficiency in aseptic technique
• Personnel should be monitored upon each exit from the aseptic core (gloves on enclosures should be monitored at the end of the batch or campaign)
• Gown materials should be cleaned and sterilized using validated methods
• Gloves on enclosures should be replaced periodically, sterilized, and integrity tested
• Personnel should be trained and diligent in their adherence to aseptic techniques
• Manual filling by aseptically-gowned personnel should be recognized as an anachronistic throwback to an earlier time and no longer used for aseptic processing.

Procedures:

• Procedures should be reviewed to eliminate unnecessary work steps and simplify aseptic processes
• Interventions should be designed for minimal risk of contaminating sterile materials
• Interventions performed during aseptic processing must be recognized as increasing the risk of contamination dissemination
• All interventions should be performed using sterilized tools whenever possible
• Intervention procedures should be established in detail for all inherent interventions and, more broadly, for corrective interventions (where some flexibility is necessary due to their greater diversity).