Health Based Exposure
With the implementation of the European Medicines Agency’s (EMA’s), ‘Guideline on setting health-based exposure limits for use in risk identification in the manufacture of different medicinal products in shared facilities (EMA/CHMP/CVMP/SWP/169430/2012)’, the importance of Health-based Exposure Limits (HBEL) through scientific toxicological risk assessment has increased in the pharmaceutical industry.
Permitted Daily Exposure (PDE) / Acceptable Daily Exposure (ADE) Calculations
The EMA guideline insists pharmaceutical manufacturing facilities or Contract Manufacturing Organization (CMO) to derive and establish Permitted Daily Exposure (PDE) also known as Acceptable Daily Exposure (ADE) an integral part of cleaning validation program to comply with various Regulatory or cGMP requirements.
To control the risk of cross-contamination establishment of NOEL/NOAEL of critical effects and application of adjustment factors as per the EMA, 2014, ICH Q3C, ISPE and VICH GL18 further determine the maximum acceptable carryover (MACO values) for separate dedicated equipment and facilities.
Occupational Exposure Limit (OEL) Calculations and OEL Banding
Occupational Exposure Limit (OEL) are typically expressed in milligrams of contaminant per cubic meter of air (mg/m3). Skin notation is used to indicate the possibility of skin absorption in the overall exposure to an airborne concentration of a chemical. OELs are a measure for minimizing worker exposure to hazardous substances in the workplace. The OEL calculation is set by considering, all available information on the hazards of a substance.
OEL calculation has been recommended by the Occupational Safety and Health Administration (OSHA) and several other Agencies including the American Conference of Governmental Industrial Hygienists (ACGIH), National Institutes of Occupational Safety and Health (NIOSH), Japan Society for Occupational Health (JSOH) and European Chemical Agency (ECHA).
REVIVE Motto
- PDE calculation 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 identification of 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 most appropriate non-clinical / clinical studies.
- Comprehensive PDE report encompassing the following details:
- Hazard alters indications/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 the sensitive and vulnerable population
- Use of Threshold of Toxicological Concern (TTC) approach for genotoxic substances [ICH-M3(R2)]
- Derivation of PDE/ADE values for uncommon or other routes of exposure (example, nasal, ocular, otic, topical/dermal including intravenous infusions)
- Establishment of PDE levels for solvents and impurities
- GMP audit support (post/during) including answering the Agency queries
- Any other technical and protocol support during cleaning validation
REVIVE Advantages
- Qualified team of toxicologists and non-clinical experts involved in the drafting of the reports.
- Robust quality control checks right from document compilation to sign-off stages
- Quick turnaround time for PDE and OEL reports as per client’s timelines
- Flexibility to adapt to client-specific templates and requirements including priority deliveries of the reports within the shortest time.