Quality CLEEN

Cross-Contamination Prevention

Manage 1,000+ changeover combinations without spreadsheets. CLEEN calculates PDE-based MAC limits for every product-equipment pair, enforces the correct cleaning procedure per changeover type, and blocks production when cleaning results fail — so cross-contamination risk is controlled by software, not operator memory.

Key Highlights

01 PDE-based MAC limits for every changeover
02 Equipment-specific cleaning SOP enforcement
03 Automatic pass/fail against acceptance criteria
04 Production hold on cleaning failure

Regulatory Context

What FDA Inspectors Cite

21 CFR 211.67 Visible Residue
1 / 6

Visible residue found on equipment marked as clean

Cleaning validation had not been performed for non-dedicated equipment. During walkthrough, product residue was observed on surfaces despite equipment being marked "clean" in the system.

Fareva Amboise · 2025-09-16
21 CFR 211.67 Cross-Contamination
2 / 6

Cross-contamination between drug products on shared lines

Non-dedicated equipment was not adequately cleaned between product campaigns. The cleaning validation programme did not establish procedures were effective for all product-equipment combinations.

Otsuka Pharmaceutical Co., Ltd. · 2024-03-22
21 CFR 211.67 API Contamination
3 / 6

API production equipment not maintained to prevent contamination

Non-dedicated equipment used to manufacture US market API products was found in conditions that could alter product safety. Cleaning procedures were not adequate to prevent contamination between campaigns.

Alembic Pharmaceuticals Limited (Units I and II) · 2025-05-31
21 CFR 211.67 Hazardous API Risk
4 / 6

Cleaning not validated for non-dedicated equipment processing hazardous APIs

The firm could not provide evidence that cross-contamination between different hazardous APIs was prevented. Cleaning documentation lacked detail to demonstrate validated limits were achieved consistently.

F.H. Investments Inc. · 2024-11-08
21 CFR 211.67 Worst-Case Gap
5 / 6

Worst-case contaminants not considered — swab sampling excluded critical surfaces

Cleaning validation for multi-use filling equipment failed to consider all worst-case contaminants. Swab sampling excluded harder-to-clean surfaces. Limits of detection were not provided for residual active testing.

Jiangsu Hengrui Pharmaceuticals Co., Ltd · 2024-01-16
21 CFR 211.67 Sampling Deficiency
6 / 6

Swab sampling not performed during cleaning validation of multi-product equipment

Product-contact equipment lacked swab sampling on multiple surfaces during validation runs. The firm could not demonstrate cleaning procedures prevented product carryover between different products.

Sanofi-Aventis Deutschland GmbH · 2025-01-16

The Problem

Why Cross-Contamination Controls Fail

Challenge 1 1 / 5

Combinatorial Explosion

  • Adding one product creates 40+ new combinations needing MAC calculations
  • Equipment modifications invalidate existing MACO values
  • Gaps in the changeover matrix go undetected until inspection
Challenge 2 2 / 5

Incorrect MAC Calculations

  • PDE-based limits per EMA guidelines are far more complex than the old 10 ppm approach
  • Many facilities still lack PDE data for older products
  • Spreadsheets propagate errors silently across the entire matrix
Challenge 3 3 / 5

Wrong Cleaning Procedure

  • No system enforces correct SOP per from-product/to-product combination
  • Campaign vs. changeover cleaning requires different procedures
  • Production can start with the wrong cleaning procedure applied
Challenge 4 4 / 5

Unlinked Sample Results

  • QA manually looks up acceptance criteria in a separate document
  • Transcription errors cause OOS results to be missed
  • Equipment can be released before QA reviews cleaning results
Challenge 5 5 / 5

No Worst-Case Identification

  • Hard-to-clean equipment and geometry not systematically catalogued
  • Worst-case combinations change with new products but matrices are not recalculated
  • ICH Q9 requires risk-based approaches most companies cannot demonstrate

Cross-Contamination Prevention in Leucine CLEEN

1

PDE-Based MAC Calculation

CLEEN calculates Maximum Allowable Carryover for every product-equipment changeover using PDE values, surface areas, and batch sizes per EMA/ECA guidelines. Full traceability from source data to final limit.

PDE-Based MACO Surface Area Integration Batch Size Factoring Limit Traceability

Input Data

PDE/ADE Values
Equipment Registry
Product Portfolio
Batch Size Data

CLEEN Engine

MAC Calculation
Surface Area Mapping
Limit Validation

Output

MAC Limit Matrix
Audit Trail
2

Cleaning SOP Mapping

The correct cleaning procedure is mapped to every from-product/to-product/equipment combination. High-potency, standard, and campaign changeovers each get the right validated procedure — enforced digitally.

Changeover Classification SOP Assignment Potency-Based Routing Campaign Detection
3

Sample Tracking & Pass/Fail

CLEEN links each analytical result to the specific equipment, changeover event, and acceptance criteria. Pass/fail is automatic. Production is blocked if results fail.

Result Ingestion Criteria Comparison Pass/Fail Determination Production Hold
4

Digital Equipment Release

Operator confirms execution, QA reviews results, equipment is released or flagged for re-cleaning. Every step is timestamped with electronic signatures.

Approval Chain Electronic Signatures Re-Cleaning Triggers Status Management
5

Campaign vs. Changeover Logic

The system distinguishes same-product batches (simpler cleaning) from product changeovers (full validated cleaning) and enforces the correct protocol automatically.

Schedule Analysis Changeover Detection Protocol Selection Hold Time Enforcement

The Solution

How Leucine Solves This

Purpose-built tools addressing both the patient safety risk and the operational complexity of multi-product cleaning.

CLEEN

MAC Calculations & SOP Enforcement

Automated MAC limits for every changeover, equipment-specific SOP mapping, and digital verification workflows that block production when cleaning fails.

  • Automated MAC calculations for every product-equipment combination
  • Equipment-specific cleaning SOP enforcement
  • Campaign vs. changeover logic with automatic procedure selection
CLEEN Sample Tracking

Swab/Rinse Tracking with Production Hold

Analytical results automatically compared against acceptance criteria. Equipment cannot be released until cleaning is verified.

  • Automatic rinse/swab comparison against acceptance criteria
  • Instant pass/fail linked to specific changeover events
  • Digital equipment release with electronic signatures
LeucineOS

Multi-Site Controls with 21 CFR Part 11

Enterprise-wide visibility into cleaning status across all facilities. Single methodology, consistent MAC calculations, harmonised procedures.

  • Centralised cross-contamination controls across all sites
  • 21 CFR Part 11 — electronic signatures, audit trails, version control
  • Real-time equipment status dashboard across facilities

Before & After

The Shift

Dimension
Spreadsheet-Based
Leucine CLEEN
MAC limits
Manual Excel calculations — errors propagate silently
Automated PDE-based MAC for every combination with audit trail
SOP selection
Operators choose by experience — no enforcement
Correct SOP enforced per from-product/to-product/equipment
Sample evaluation
Manual comparison to criteria in a separate document
Automatic pass/fail against pre-calculated acceptance criteria
Equipment release
Paper sign-off — production can start before QA review
Digital workflow blocks production until QA approves
New product
Manual recalculation of 40+ combinations — takes weeks
Automatic MAC recalculation across all equipment in minutes
Worst-case ID
Static assumptions — not updated with portfolio changes
Dynamic ranking updated automatically per ICH Q9

Results

Measurable Impact

Real results from manufacturers using CLEEN for cross-contamination prevention.

1,000+
Changeover Combinations
Product-equipment combinations with automated MAC limits
100%
Calculation Errors
Elimination of manual MAC errors — Zydus achieved zero errors with CLEEN
80%
Cleaning Validation Cycles
Faster — from weeks to days across 7+ Zydus facilities

Next Step

Get Started

Stop managing cross-contamination risk in spreadsheets. Leucine CLEEN automates MAC calculations, enforces correct cleaning procedures, and blocks production when cleaning fails.

Get Started
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