ADE/PDE, OEL & Cleaning Validation
Comprehensive cleaning validation services
A cleaning validation programme has to show — with data and clear reasoning — that residues from one product cannot put patients receiving the next product at risk. We help you design or modernise that programme, from health-based limits and worst-case selection to the documentation inspectors review.
- Guideline basis EU GMP Annex 15, EMA HBEL guideline, PIC/S PI 046, WHO TRS 1033 Annex 2
- Typical inputs Product and equipment matrix, current protocols and reports
- You receive Programme strategy, limit calculations and a prioritised gap report
Overview
About Comprehensive Cleaning Validation
Regulators now expect cleaning limits to be based on a toxicological evaluation of each product, not on generic rules of thumb. For a multi-product site this touches every part of the programme: how limits are calculated, which products and equipment are treated as worst case, how many verification runs are needed and how the programme is kept current.
Globaxa works at programme level. We review what you have, derive or confirm health-based limits, and set out a structured approach that your validation team can execute and defend. Where your existing approach is sound, we document why — not every legacy limit needs to change.
Use cases
When this service helps
A new product is joining a shared train
Confirm whether the new product changes the worst case and whether existing cleaning procedures remain adequate.
Inspection observations on cleaning
Respond to findings on how limits were justified or how worst-case products were chosen.
Legacy limits without toxicological basis
Replace or justify limits based solely on dose fractions or fixed ppm criteria.
Site consolidation or technology transfer
Re-baseline the programme when product portfolios or equipment trains change.
Scope
What the service covers
- Review of the cleaning validation master plan, SOPs and recent reports
- Health-based limits for every product on shared equipment (or review of existing PDE/ADE reports)
- Maximum allowable carry-over (MACO) and surface or rinse acceptance limits
- Product grouping and worst-case selection (toxicity, solubility, cleanability, dose)
- Equipment train mapping and shared product-contact surface areas
- Visual-clean and analytical criteria, including method sensitivity versus limits
- Dirty- and clean-hold-time strategy and campaign considerations
- Lifecycle approach: periodic review, change control triggers and continued verification
Who does what
Globaxa prepares the scientific justification, calculations and documentation. Cleaning runs, sampling and laboratory analysis are performed by your site or a laboratory you appoint; we review the data and reports.
How is a MACO derived from a PDE?
A common approach is MACO = PDE of the previous product × minimum batch size of the next product ÷ maximum daily dose of the next product. The MACO is then divided by the shared product-contact surface area to give a surface limit, and adjusted for swab area and recovery. The exact formula depends on your process and should be documented in your strategy.
Should we keep visual-clean and 10 ppm criteria?
HBEL-based limits are expected to be the scientific basis. Many companies keep visual cleanliness and a general residue limit as additional controls where these are more stringent. The rationale should be written down so that the final acceptance limit is clear.
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.
- Gap reviewWe assess your current programme against EU GMP Annex 15, PIC/S and WHO expectations and agree priorities.
- Health-based limitsPDE/ADE values are derived or verified for every product in scope.
- Grouping and worst caseProducts and equipment are grouped with a documented rationale for each worst-case choice.
- Acceptance criteriaLimits are converted into practical swab and rinse criteria, checked against method capability.
- ReportingWe document the strategy and calculations in a format suited to inspection.
Deliverables
What you receive
Cleaning validation strategy
A programme-level document or master-plan section describing limits, grouping, worst case and lifecycle controls.
Limit calculation workbook
Transparent MACO and surface-limit calculations that your team can maintain as products change.
Gap assessment report
Findings ranked by risk, with recommended actions and owners.
Training session
A walk-through for validation, QA and production staff on the rationale behind the limits.
Technical basis
Guidelines we work to
- EU GMP Annex 15 (2015), section 10Expects cleaning limits to be based on a toxicological evaluation and validation to follow a risk-based approach.
- EMA guideline on setting HBELsEMA/CHMP/CVMP/SWP/169430/2012 and its Q&A (EMA/CHMP/CVMP/SWP/246844/2018) describe how PDEs are derived for shared facilities.
- PIC/S PI 046The PIC/S version of the HBEL guideline, used by inspectorates in PIC/S member countries.
- WHO TRS 1033, Annex 2 (2021)WHO “points to consider” on including HBELs in cleaning validation.
- ISPE Risk-MaPP (2nd edition, 2017)Industry guide on risk-based manufacture of pharmaceutical products, including ADE-based limits.
What we need from you
- Product list with strengths, maximum daily doses and minimum batch sizes
- Equipment list with product-contact surface areas and shared trains
- Current cleaning procedures, validation protocols and reports
- Existing PDE/ADE reports or toxicology data, if available
- Analytical methods with limits of detection and quantitation
- Recent inspection observations related to cleaning
Please share confidential information only after an NDA is in place — we are happy to sign one first.
Market and jurisdiction considerations
EU and PIC/S inspectorates explicitly expect HBEL-based limits for shared facilities. WHO-GMP inspections (often relevant for exports to Africa and Asia) follow the same principles through WHO TRS 1033.
India: Revised Schedule M (notified December 2023) brings domestic GMP closer to WHO GMP, including validation expectations. United States: 21 CFR 211.67 requires equipment cleaning procedures, and FDA expects scientifically justified limits.
FAQs
Comprehensive Cleaning Validation: frequently asked questions
Do we need a PDE for every product?
Every product manufactured on shared equipment needs a health-based limit as the starting point for carry-over calculations. Where data are limited, a documented default or banding approach may be justified.
How many cleaning runs are required?
EU GMP Annex 15 does not fix a number; it expects enough runs to demonstrate that the cleaning process is consistently effective, justified by risk. Many companies still use three as a baseline, with a rationale.
Can you support campaign manufacturing?
Yes. We can help define campaign length, between-batch cleaning and hold-time limits as part of the strategy.
Do you perform the sampling or analysis?
No. Sampling and testing are carried out by your site or a laboratory you choose. We define what is needed and review the results.
Talk to us about Comprehensive Cleaning Validation
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