Risk-Based Inspection (RBI) is a GMP inspection approach where the frequency, depth and breadth of inspection are adjusted based on estimated risk to patients/product quality. ECA Academy+1
For this topic, note that the numbering covers different themes in the two references:
- Schedule M (9.1–9.6) = Sterile manufacturing process controls.
- WHO TRS 986 (9.1–9.6) = Personnel system and key roles.
Schedule M (9.1–9.6): what RBI checks in sterile operations
9.1 requires sterile manufacture only under defined conditions (controlled areas).
9.2 requires periodic bioburden monitoring of bulk raw materials and bulk solution before membrane filtration (recommended limit stated).
9.3 requires minimizing and defining the maximum permissible hold time between solution preparation and sterilization/filtration (product-specific).
9.4 requires sterile gases contacting product to be filtered through two 0.22 µ hydrophobic filters in series, with integrity testing; cylinders must not enter aseptic areas.
9.5 requires washed containers to be sterilized immediately before use (or re-rinsed and re-sterilized if beyond an established time).
9.6 requires filling each finished lot in one continuous operation; if split, lots are held separately and sterility tested separately.
RBI evidence sampling: cleanroom qualification status, EM trending tied to “defined conditions”, bioburden test method suitability and sampling points, hold-time studies and deviations, gas filter integrity/maintenance records, cylinder segregation controls, container sterilization cycle validation and “sterile hold time” controls, plus batch records showing continuous filling / lot segregation and sterility-test governance.
WHO TRS 986 (9.1–9.6): personnel controls RBI links to sterile assurance
TRS requires sufficient qualified personnel, clearly defined responsibilities (written), an organization chart, adequate staffing so duties don’t create quality risk, GMP awareness + ongoing training, controls preventing unauthorized entry into production/storage/QC, and defined key personnel (heads of production, quality unit(s), authorized person) with independence between production and quality.
RBI verification: role/job descriptions vs actual practice, shift staffing adequacy for sterile operations, training effectiveness (not just signatures), access control logs, and interviews to confirm that personnel controls support the Schedule M sterile process requirements.