Cleaning Validation: HBEL Limit Setting, Visual Inspection, and the Shift to Ongoing Process Verification
Ecolab's global cleaning validation expert on why incorrect limit setting is the industry's top mistake, how health-based exposure limits replace outdated 10PPM criteria, and why ongoing process verification is the next major trend.
Vivek Gera Host
Co-founder · Leucine
Thomas Altmann
Global Technical Manager · Ecolab
About this episode
Vivek Gera speaks with Thomas Altmann, Global Technical Manager at Ecolab, about the persistent mistakes in pharmaceutical cleaning validation — an area increasingly under FDA inspection scrutiny. Altmann argues that incorrect limit setting remains the industry's number one problem: the misunderstanding of health-based exposure limit calculations leads to either unsafe cleaning practices or unnecessarily tight limits that stifle operations. He critiques the continued reliance on outdated methods — the 10 PPM criterion and LD50-based calculations — and makes the case for a risk-based approach where operational limits are set well below health-based exposure limits to allow room for action. The episode closes with a discussion of ongoing process verification as an emerging regulatory expectation, and the wide disparity in visual inspection capability across manufacturing sites globally.
Topics
Key takeaways
- Incorrect limit setting is the number one mistake in cleaning validation — misunderstanding health-based exposure limit calculations leads to either unsafe cleaning or unnecessarily restrictive operations
- The 10 PPM criterion and LD50-based calculations are outdated — HBEL calculations, aligned with ASTM guidance and the risk-map approach from North America, represent the current standard and should be the foundation of every cleaning validation programme
- Operational limits should be set well below health-based exposure limits to allow room for corrective action — the purpose is not to find a limit you can barely meet, but to build a buffer that ensures absolute patient safety
- Ongoing process verification is the next major regulatory trend after cleaning validation: regulators expect that validation is not a one-time exercise but a continuously monitored state, with data reviewed at defined intervals
- Visual inspection capability varies enormously across the industry — from AI-assisted high-resolution camera systems at equipment manufacturers to sites with a single iPad per shift for an entire blood plasma facility; regulators need to account for this disparity
- The range of cleaning validation maturity across the global industry is vast; bringing all sites to the same standard requires not just regulatory pressure but digital tools that make consistent documentation and verification achievable at any scale
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