In a risk-based inspection (RBI), Schedule M – point 4.17 (as captured in the CDSCO RBI checklist under water systems) is treated as a critical utility control because Water for Injection (WFI) can rapidly become a contamination source if storage/distribution allows microbial growth and biofilm. The checklist expectation around this point is to confirm whether WFI is stored and circulated above 70°C (and to verify the SOP followed for this control). CDSCO
From an RBI perspective, inspectors focus on whether the “hot loop” strategy is scientifically justified and consistently achieved in routine operation. International sterile GMP guidance reinforces this principle: WFI should be stored and distributed to minimize microbial growth, for example by constant circulation above 70°C.
What inspectors typically verify (high-risk evidence points):
- System design & qualification: documented URS/DQ/IQ/OQ/PQ showing the loop can maintain ≥70°C at all points of use, including temperature mapping and worst-case return temperatures.
- Continuous circulation controls: pump capacity, recirculation logic, temperature control points, insulation, and verified alarms/interlocks for low-temperature events (since these can enable microbial proliferation).
- Sanitary design to prevent biofilm niches: hygienic piping, slope/drainability, minimal “dead legs,” sanitary valves, and documented engineering drawings/as-built verification (because stagnation undermines hot-loop benefits). World Health Organization
- Monitoring & trending: routine recording/trending of loop temperature, return temperature, and microbiological/endotoxin monitoring with alert/action limits, plus investigation/CAPA for excursions.
- Maintenance & restart discipline: defined controls after shutdowns (post-maintenance sanitization, flushing, sample release) before WFI is used for compounding, rinsing, or sterilizer feed.
Common RBI red flags: temperature “setpoint” exists but no proof of ≥70°C at distal points, frequent low-temp alarms without robust CAPA, poor trend review, or weak change control on insulation/piping modifications.