Risk-Based Inspection (RBI) rates a site by the risk it may pose to patients and product quality and then decides the frequency, depth and breadth of inspection accordingly, using Quality Risk Management. CDSCO
In Schedule M (Sterile Products), points 4.5–4.8 are core controls for cleanroom performance, verification and monitoring—so RBI typically gives these areas high inspection depth because failures can directly lead to contamination and batch impact.
4.5 HEPA filter leak testing (installed filter leakage test)
HEPA filters must undergo an installed filter leakage test in accordance with ISO standards, with a recommended interval of every 6 months and not exceeding 12 months. The intent is to confirm the filter media, frame and seal are leak-free. The test aerosol should not support microbial growth and must contain sufficient particle number/mass; HEPA patching is permitted (manufacturer and in-situ) if patch sizes/procedures follow ISO recommendations.
RBI check: integrity test records, deviations for failures, impact assessment on batches, and CAPA effectiveness.
4.6 Cleanroom/clean-air device classification (ISO)
Cleanrooms and clean-air devices must be classified per ISO, and classification must be clearly differentiated from routine process environmental monitoring. Limits for airborne particles are defined for Grades A–D (at rest/in operation). It also specifies minimum sample volumes/locations, use of portable particle counters with short tubing for ≥5 µm particles, and isokinetic heads in unidirectional airflow.
RBI check: qualification package (DQ/IQ/OQ), “at rest” vs “in operation” classification evidence, and whether design supports both states.
4.7 Routine airborne particle monitoring “in operation” (risk-based locations)
During operation, cleanrooms/devices must be routinely monitored, with monitoring locations chosen via formal risk analysis and informed by classification results. Grade A monitoring should cover the full duration of critical processing (capturing interventions/transient events), with similar principles for Grade B (frequency may be reduced based on segregation effectiveness).
RBI check: risk assessment for locations/sample sizes, alarm/limit handling, and trend review.
4.8 Microbiological monitoring of Grades A–D “in operation”
Clean areas must be monitored to control microbiological cleanliness—frequently for aseptic operations using settle plates, volumetric air, and surface sampling. Methods must not compromise zone protection; results must be considered during batch release review, and surfaces/personnel monitored after critical operations (plus monitoring after validation/cleaning/sanitization).