PDE / HBEL Calculator
Derive a Permitted Daily Exposure (health-based exposure limit) from a point of departure and the five adjustment factors — PDE = (NOAEL × BW) / (F1·F2·F3·F4·F5) — the toxicological input to a shared-facility cleaning limit. Aligned to the EMA HBEL guideline and the ICH Q3C derivation.
OUTPUT
TIME
Limitations — read before you rely on this
- Selecting the point of departure and the individual factor values requires a qualified toxicologist; the tool does the arithmetic but cannot judge which NOAEL or which factor is correct for your substance.
- The equation assumes systemic toxicity with an identifiable threshold; genotoxic carcinogens and highly sensitising compounds may need the ICH M7/TTC route or dedicated facilities instead.
- This calculator is transparent but it is not a validated system, and its default factor values are conventions an assessor may override.
- Reproduce the PDE in your own qualified system with your toxicologist’s documented factor justifications before it enters a cleaning-validation protocol or a shared-facility risk assessment.
WHAT THIS CALCULATES
Derives a Permitted Daily Exposure — the health-based exposure limit used for cross-contamination control in shared facilities — from a point of departure and the five standard adjustment factors.
THE METHOD
PDE = (NOAEL × BW) / (F1 × F2 × F3 × F4 × F5)- PDE
- Permitted Daily Exposure in mg/day: the dose judged unlikely to cause an adverse effect at daily lifetime exposure.
- NOAEL
- The no-observed-adverse-effect level from the critical study, in mg/kg/day (a LOAEL may substitute, handled inside F5).
- BW
- Body weight of the exposed adult, in kg; the EMA HBEL / ICH convention default is 50 kg.
- F1
- Interspecies extrapolation factor (e.g. 5 rat-to-human, 12 mouse-to-human, 1 for human data).
- F2
- Inter-individual (human variability) factor, conventionally 10.
- F3
- Study-duration factor, up to 10 for the shortest studies.
- F4
- Severity factor for severe toxicity such as carcinogenicity or teratogenicity, typically 1–10.
- F5
- Variable factor for data-quality gaps, e.g. use of a LOAEL instead of a NOAEL, up to 10.
The F1–F5 scheme and its conventional values originate in the ICH Q3C PDE method and are carried into the EMA HBEL guideline for shared-facility limits. The tool multiplies the five factors into a single composite divisor and displays it, because the composite is what an assessor challenges.
THE INPUTS, AND WHAT THEY MEAN
- NOAEL
- The no-observed-adverse-effect level from the pivotal toxicology study the assessor judged critical for this substance, in mg/kg/day.
- Body weight
- The default human body weight for the exposed population; the EMA HBEL convention is 50 kg for adults, lower for paediatric exposure.
- F1 — interspecies
- Accounts for extrapolating from the study species to humans; conventional values are species-specific (5 rat, 12 mouse, 2 dog, 1 human).
- F2 — variability
- Accounts for differences between individual humans, conventionally set to 10.
- F3 — duration
- Accounts for a study shorter than the intended exposure duration, up to 10 for the shortest studies.
- F4 — severity
- Accounts for the nature and severity of the toxicity, higher for carcinogenicity or teratogenicity, typically 1 to 10.
- F5 — deficiency
- Accounts for gaps in the dataset, including using a LOAEL instead of a NOAEL, up to 10.
Health-based exposure limit from a NOAEL.
Enter the point of departure (NOAEL), the body weight (the EMA/ICH convention is 50 kg), and the five adjustment factors. SPEQ computes the Permitted Daily Exposure using the ICH Q3C derivation the EMA HBEL guideline adopts.
HOW TO READ THE OUTPUT
- The PDE is the toxicological input to a cleaning limit, not the cleaning limit itself; it feeds the downstream MACO/HBEL carryover calculation. The 50 kg body weight and the F1–F5 conventions are EMA/ICH thresholds, not SPEQ’s.
- A large composite divisor signals a data-poor substance; the resulting conservative PDE is defensible but may be operationally impractical, which is itself a signal to seek better toxicology data.
- The critical-effect selection drives the answer more than the arithmetic; two toxicologists can defensibly differ, so the PDE record must capture the point-of-departure rationale, not just the number.
- The PDE assumes daily lifetime exposure of a healthy adult; paediatric, occupational, or short-campaign scenarios use different body weights or adjustment logic.
WORKED EXAMPLE
Deriving a PDE for a compound with a 1 mg/kg/day rat NOAEL to set a shared-facility cleaning basis.
- NOAEL
- 1 mg/kg/day
- BW
- 50 kg
- F1..F5
- 5, 10, 1, 1, 1
RESULT
One milligram per day is the daily carryover ceiling the subsequent MACO calculation must keep the next product below; a short-duration or LOAEL-only dataset would raise F3/F5 and shrink this severalfold.
REGULATORY BASIS
- EMA guideline on setting health-based exposure limits (HBEL, 2014)
- Defines the HBEL/PDE approach for cross-contamination control in shared manufacturing facilities.
- ICH Q3C — PDE derivation method
- Provides the original PDE equation and the conventional F1–F5 adjustment-factor values.
- EU GMP Chapters 3 & 5
- Require toxicological-evaluation-based limits (HBEL) to justify shared equipment and facilities.