Health Based Exposure Limits (HBEL)
and Cleaning Validation services
Health Based Exposure Limits
The pharmaceutical industry is responsible for producing various medicinal products in shared facilities, and it is obligated to adhere to the guidelines set by the European Medicines Agency (EMA) regarding Health Based Exposure Limits (HBEL) to avoid any toxicological risk. One such guideline is the Permitted Daily Exposure (PDE) or Threshold of Toxicological Concern (TTC), which is determined by evaluating all available pharmacological and toxicological data, including non-clinical and clinical reports of the specific substance or compound.
The PDE is a substance-specific dose that is unlikely to cause harm if an individual is exposed to it daily for a lifetime. Establishing Permitted Daily Exposure, also known as Acceptable Daily Exposure (ADE), is an essential part of the cleaning validation program due to the risk of residual active substance carryover contamination and the need to comply with various regulatory or cGMP requirements. RABT toxicologists can help you with:
- Permitted Daily Exposure limit determinations
- Cleaning Validations (CV)
- Occupational Exposure Limit (OEL)
Health Based Exposure Limits Our expertise includes:
- PDE calculations in compliance with EMA/CHMP/CVMP/SWP/169430/2012.
- PDE reports approved by board-certified (DABT / ERT) and experienced toxicologists.
- Sound scientific knowledge and experience in identifying critical effects, point of departures (PODs), the no-observed-adverse-effect level (NOAEL) or no observed effect level (NOEL) and lowest-observed-adverse-effect-level (LOAEL) from the most appropriate non-clinical / clinical studies.
- A comprehensive PDE report that includes:
- Hazard alerts/summary
- Review of acute toxicity (LD50 calculations), skin/eye irritation and sensitization potential
- Repeat dose toxicity
- Reproduction and Developmental toxicity
- Genotoxicity
- Carcinogenicity
- Clinical evidence with sensitive and vulnerable populations
- Use of the Threshold of Toxicological Concern (TTC) approach for genotoxic substances [ICH-M3(R2)]
- Derivation of PDE/ADE values for uncommon or alternative routes of exposure
- Establishment of PDE levels for solvents and impurities
- GMP audit support (post/during) including answering agency queries
- Any other technical and protocol support during cleaning validation
We are committed to ensuring the safety and efficacy of your medicinal products through our expertise in PDE and cleaning validation.
