ADE/PDE, OEL & Cleaning Validation
ADE, PDE and OEL calculation services
A health-based exposure limit is only as defensible as the reasoning behind it. We prepare PDE/ADE and OEL monographs that set out the data reviewed, the critical effect, the point of departure and every adjustment factor — so your quality team and inspectors can follow the logic.
- Guideline basis EMA HBEL guideline and Q&A, PIC/S PI 046, ICH Q3C method, ISPE Risk-MaPP
- Typical inputs API identity, dose and route, any in-house toxicology
- You receive Signed HBEL monograph with calculation and references
Overview
About ADE/PDE/OEL Calculation
The permitted daily exposure (PDE) — also called acceptable daily exposure (ADE) — is the dose of a substance below which no adverse effect is expected, even with daily exposure over a lifetime. It is the foundation of cleaning-validation limits in shared facilities. The occupational exposure limit (OEL) applies the same toxicological thinking to workers, expressed as an airborne concentration over a working shift.
For each compound we search and evaluate the available clinical, non-clinical and regulatory data, identify the most sensitive endpoint, select a point of departure and apply adjustment factors appropriate to the data. The result is a monograph signed by the assessing toxicologist.
Use cases
When this service helps
Cleaning validation in shared facilities
Product-specific PDEs to calculate carry-over limits.
New compounds and intermediates
Limits for substances with limited published data, using the best available evidence.
Updating older assessments
Re-evaluating legacy limits against new data or current guideline expectations.
Worker protection
OELs to guide containment, monitoring and personal protective equipment.
Scope
What the service covers
- Structured literature and database search, including regulatory assessment reports and product labelling
- Hazard characterisation: pharmacology, repeat-dose toxicity, genotoxicity, carcinogenicity, reproductive and developmental toxicity, sensitisation
- Identification of the critical effect and point of departure (NOAEL, LOAEL or lowest clinical dose)
- Selection and justification of adjustment factors (F1–F5 or equivalent uncertainty factors)
- Route-to-route extrapolation and bioavailability correction where relevant
- OEL derivation (8-hour time-weighted average) with occupational exposure band
- Expert statement, references and a summary of the assessor’s qualifications
Who does what
Assessments are based on published and client-supplied data. Globaxa does not run toxicology studies; where data gaps are significant we explain the uncertainty and the options.
How is a PDE calculated?
In the EMA approach, PDE = point of departure × weight adjustment ÷ (F1 × F2 × F3 × F4 × F5). The factors account for species differences (F1), variability between people (F2), study duration (F3), severity of toxicity (F4) and use of a LOAEL instead of a NOAEL (F5). A 50 kg body weight is used for the weight adjustment.
What if the compound has very little data?
For intermediates and early-development compounds, the assessment may use structurally similar substances, in silico predictions or a default based on potency and hazard category. The uncertainty is documented and the limit is revisited as data emerge.
Methodology
How we work
A defined sequence, agreed with you at the start, so you always know what happens next and what we need from you.
- Confirm the substanceIdentity, salt form, dose, route and indication are confirmed with you.
- Search and screen dataWe collect clinical and non-clinical evidence and record the search strategy.
- Characterise the hazardEndpoints are evaluated to identify the critical effect and point of departure.
- Derive the limitThe PDE/ADE and OEL are calculated with each adjustment factor justified.
- Review and signA second toxicologist reviews the monograph before it is signed and issued.
Deliverables
What you receive
HBEL monograph
A complete report per compound covering data, critical effect, point of departure, factors and the final PDE/ADE and OEL.
Calculation summary
A one-page summary table that can be referenced in cleaning-validation documents.
References and search record
Full references and the search strategy, so the assessment can be updated later.
Expert credentials
A summary of the assessor’s qualifications, as inspectors commonly request.
Technical basis
Guidelines we work to
- EMA guideline on setting HBELsDefines the PDE approach for shared facilities and the documentation expected (EMA/CHMP/CVMP/SWP/169430/2012).
- EMA Q&A on HBELs (2018)Clarifies expectations for data-poor compounds, the use of clinical data and expert qualifications.
- ICH Q3C and Q3DThe PDE method and modifying factors used for residual solvents and elemental impurities.
- ISPE Risk-MaPPIndustry guidance using the term ADE, consistent with the EMA approach.
What we need from you
- Substance name, structure, CAS number and salt form
- Therapeutic dose(s), route of administration and indication
- Any in-house toxicology, pharmacology or clinical data
- Target markets or the inspectorates you need to satisfy
- Existing assessments to be updated, if any
Please share confidential information only after an NDA is in place — we are happy to sign one first.
Market and jurisdiction considerations
The EMA/PIC/S approach is widely accepted as the reference method and is used by many inspectorates outside Europe. WHO TRS 1033 Annex 2 provides consistent guidance for WHO-GMP markets.
Where a company standard or a customer requires a specific format (for example ADE terminology, or a defined set of adjustment factors), we can align the monograph without changing the underlying science.
FAQs
ADE/PDE/OEL Calculation: frequently asked questions
Can one report cover both the PDE and the OEL?
Yes. Both limits draw on the same data review, so they are usually prepared together in one monograph, with the OEL calculation shown separately.
Will the report be accepted by inspectors?
No consultant can guarantee acceptance. We follow the published guidance, document every assumption and include the assessor’s qualifications, which are the points inspectors typically examine.
How often should PDEs be reviewed?
Whenever significant new data appear (for example new safety findings) and as part of periodic review. A two- to three-year review cycle is common practice.
Can you assess a portfolio of compounds?
Yes. For portfolios we agree a prioritised schedule and provide a summary table across all compounds.
Talk to us about ADE/PDE/OEL Calculation
Share your product, target market and timeline. We will review your requirement and propose a defined scope.
- OfficeFlat no 8-9-3/23/1, Subhash Chandra Bose Colony, Dathunagar, Kanchanbagh, Hyderabad, Telangana 500058, India
Open in Google Maps - Phone+91 81219 33381
+91 99894 74590 - Emailbd@globaxa.in
- Office hoursMonday to Friday, 10:00–19:00 IST