Leucine CLEEN replaces the spreadsheet-driven cleaning validation lifecycle with a structured, audit-ready system. It ingests toxicological data, calculates health-based exposure limits (HBELs) and maximum allowable carryover (MACO) for every product-equipment combination, generates worst-case matrices that update automatically when products are added or removed, and produces risk-based protocols with defensible acceptance criteria. Every calculation is traceable, every matrix is current, and every protocol is audit-ready.
Key Highlights
Regulatory Context
Cleaning validation studies for multi-use filling equipment failed to consider all worst-case contaminants, including a compound used in the stopper processing step. Swab sampling excluded small-outlet surfaces that represented harder-to-clean geometries than those actually sampled. Limits of detection were not provided in the validation report for residual active testing.
Cleaning validation had not been performed for non-dedicated equipment used to manufacture US market products. During an inspection walkthrough, what appeared to be product residue was observed on equipment surfaces despite the equipment being identified as "clean" in the system. The firm failed to demonstrate that cleaning procedures were effective in preventing cross-contamination between different batches.
Cleaning validation for product-contact process equipment lacked swab sampling on multiple surfaces during validation runs. The firm could not demonstrate that cleaning procedures were effective in preventing product carryover and cross-contamination between different products manufactured on the same equipment lines.
Non-dedicated manufacturing equipment was not adequately cleaned between product campaigns. Routine cleaning procedures failed to prevent cross-contamination between different drug products processed on shared equipment. The cleaning validation programme did not establish that the procedures were effective for all product-equipment combinations in the manufacturing matrix.
Non-dedicated production equipment used to manufacture US market API products was found in conditions that could alter product safety, identity, strength, quality, or purity. Cleaning and maintenance procedures were not adequate to prevent contamination between different API manufacturing campaigns in the same facility.
Equipment cleaning had not been validated for non-dedicated equipment used to process multiple hazardous APIs. The firm could not provide evidence that cross-contamination between different active pharmaceutical ingredients was prevented. Cleaning documentation lacked the detail necessary to demonstrate that validated limits were achieved consistently.
The Problem
Cleaning Limit Lifecycle in Leucine CLEEN
Leucine CLEEN ingests toxicological data for every product in your portfolio — PDE values, ADE values, OEL classifications, solubility profiles, and therapeutic doses. The system calculates health-based exposure limits using the standard EMA/ISPE methodology, with full traceability from source data to final limit.
Toxicology Sources
CLEEN Engine
Output
CLEEN automatically generates the worst-case product matrix for every equipment train in your facility. It evaluates every product-equipment combination against HBEL-derived limits, solubility, cleaning difficulty, and surface area to identify the true worst case — not the assumed one.
For each equipment train, CLEEN generates a cleaning validation protocol driven by the worst-case matrix. Sampling plans are designed based on equipment geometry, surface characteristics, and hard-to-clean areas. Acceptance criteria are calculated directly from HBEL-derived MACO values — not manually transcribed from spreadsheets.
CLEEN analyses equipment across your facility — and across sites — to identify groups with similar design, cleaning difficulty, and product contact characteristics. Bracketing strategies reduce validation scope without compromising scientific rigour, with defensible grouping rationale documented automatically.
After initial validation, CLEEN continuously monitors the cleaning validation lifecycle. When a new product is introduced, a product is discontinued, new toxicological data is published, or equipment is modified, the system automatically flags affected matrices, recalculates limits, and identifies protocols that require revalidation.
CLEEN compiles audit-ready documentation packages — HBEL calculation summaries, worst-case rationale, validation protocols, execution results, and lifecycle change history — in FDA and EMA-formatted reports. One-click export produces the complete cleaning validation package for any product, equipment train, or facility.
The Solution
Purpose-built cleaning validation lifecycle management — from toxicological data to audit-ready packages — addressing both the regulatory gaps and the operational bottlenecks.
CLEEN calculates health-based exposure limits using structured toxicological data, generates MACO values for every product-equipment combination, and maintains a complete audit trail from source data to final limit. When toxicological data is updated, affected limits are automatically recalculated.
Worst-case product matrices are generated and maintained automatically — evaluated against HBEL-derived limits, solubility, cleaning difficulty, and equipment geometry. Protocols are auto-generated with sampling plans, acceptance criteria, and analytical methods linked directly to the matrix data.
CLEEN operates on the LeucineOS platform, providing enterprise-wide visibility into cleaning validation status across all facilities. A single methodology, a single data model, and a single audit trail — harmonised across sites and regulatory jurisdictions.
FDA Tracker monitors cleaning validation-related 483 observations and warning letters across the industry, identifying trends in what inspectors are citing and how regulatory expectations are evolving. Quality teams see which facilities in their peer group are being cited for cleaning validation gaps.
Before & After
Results
Results from pharmaceutical manufacturers using Leucine CLEEN for cleaning validation lifecycle management.
Next Step
Stop managing cleaning validation in spreadsheets that cannot be audited, cannot enforce lifecycle monitoring, and cannot scale across sites. Leucine CLEEN provides the structured HBEL-based lifecycle that regulatory expectations now demand — from toxicological data to audit-ready packages, across every facility.
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