Risk-Based Inspection (RBI) is a GMP approach where regulators plan the frequency, depth and breadth of inspections according to the estimated risk to patients and product quality, using Quality Risk Management and risk signals from a site’s history.
Schedule M – Point 4.10 (What it requires)
Schedule M point 4.10 (within sterile/clean area controls) requires that appropriate alert and action limits are established for particulate and microbiological monitoring results. If action limits are exceeded or a trend is identified in alert limits, an investigation must be initiated and appropriate corrective actions taken as per written procedures.
How RBI inspects compliance with 4.10 (practical expectations)
Because environmental monitoring (EM) directly protects sterile assurance and contamination control, RBI typically samples this area deeply and checks for evidence that limits are science-based, risk-based, and effective:
- How limits were set (justification)
Inspectors expect a documented rationale showing limits derived from qualification/classification data, process simulations (e.g., aseptic runs), historical EM performance, and the risk of the operation/grade (A/B/C/D). Limits should be specific to locations and methods (air, settle plates, contact plates, glove prints, particle sizes). - Alert vs action governance
- Alert limit = early warning; triggers assessment, heightened monitoring, cleaning/disinfection review, operator practice checks.
- Action limit = potential loss of control; triggers formal deviation, investigation, impact/risk assessment on batches, and CAPA.
RBI checks that these triggers are written, understood, and consistently applied.
- Trending (the “trend” requirement in 4.10)
RBI will review trend charts and periodic EM reviews to confirm the site detects: repeated alerts at the same point, seasonal drift, shifts after maintenance/HVAC changes, or operator-related spikes—before they become failures. - Investigation quality & CAPA effectiveness
Inspectors test whether investigations identify true root causes (HVAC upset, cleaning failure, gowning behavior, material flow, utility excursion), define batch impact, and implement CAPA with effectiveness checks (not just “reclean and close”).
If 4.10 is weak (limits unjustified, alerts ignored, poor trending), RBI usually expands into aseptic controls, sanitation, HVAC qualification, deviation system, and batch release decisions.