Sterile Processing

  • Are the aseptic manufacturing areas and operations consisted with the WHO guidelines for sterile pharmaceutical products provided in TRS 823, Section 17, page 59ff?
  • Does the aseptic manufacturing area include: Smooth, hard non-particulate generating cleanable floors, walls and ceiling? Able to withstand cleaning, disinfecting reagents? No horizontal pipes of conduits located over exposed components, in-process material, and production or product contact surfaces? Environmental controls, e.g. temperature, humidity and viable and non-viable particles? Are there specifications for these controls? Has the system been validated? Air supplied through HEPA filters? (Terminal filters should be employed for final formulation and filling activities), Environmental monitoring system, e.g. temperature, humidity and particulates? Fixtures (electrical outlets and lighting, etc.) flush mounted and sealed to prevent air leakage, water access? Identification of all pipes or conduits for air clean steam or liquids?Properly equipped gowning area/air lock? The ability to achieve appropriate air standards (Grade A,B,C,D) during operation? Appropriate air flow design including segregated air systems for different aspects of the processing, e.g fermentation and filling? Appropriate air flow design so that the area is flushed by HEPA filtered air exhausted through return ducts (not blocked by equipment), The ability to maintain the appropriate pressure differentials between work areas with different Grades of air?
  • Does the aseptic manufacturing area exclude:Access doors for servicing equipment and fixtures? (should only be from outside area), Drains? Sinks?
  • Is the vaccine processing area isolated and independent of any space used for any other purpose?
  • Are the facilities appropriately designed and validated to comply with relevant containment levels assigned to organisms involved in the manufacturing process?
  • Is the aseptic manufacturing area cleaned according to a validated procedure? Is it followed? Is the cleaning data recorded?

Cleaning and Maintenance

  • Is the equipment suitably located to facilitate its use, cleaning and maintenance?
  • Are equipment and utensils cleaned, maintained and sanitized as appropriate to prevent malfunction or cross-contamination?
  • Are piping systems, valves and vent filters properly designed to facilitate cleaning and sterilization? NOTE: Maintaining closed systems through the use of “clean in place” and “sterilize in place” if preferable.
  • Are the valves on primary containment vessels (e.g. fermenter) steam sterilized?
  • Are non-fiber releasing filters used for filtration?
  • Are filters used for sterile filtration integrity tested before and after use?
  • Are calibrations and validation being performed adequately?
  • Are autoclaves and sterilizing ovens fitted with effective, proper air filters and are these integrity tested? Are HEPA filters used for the ovens?
  • Are supplies and equipment which are exposed to pathogens during processing kept separate from unused items to prevent cross-contamination?