Cleaning Validation ensures that equipment used in pharmaceutical manufacturing is cleaned consistently and effectively to prevent cross-contamination, carryover, and microbial risks. PrimeGMP provides full lifecycle cleaning validation services, including MACO calculations, sampling strategies, method validation, and execution aligned with global GMP requirements.

Objectives of Cleaning Validation

• Demonstrate that cleaning procedures consistently remove residues
• Verify that chemical, microbial, and detergent residues are below acceptable limits
• Establish validated MACO / PDE-based limits
• Confirm cleaning effectiveness for worst-case products & equipment
• Support changeover, multiproduct facility, and contamination control strategy
• Ensure compliance with regulatory expectations (USFDA, EU, WHO, MHRA, PIC/S)

Scope of Cleaning Validation

Cleaning validation is performed for:

• Manufacturing equipment (RMG, FBD, Blender, Compression line, Capsule fillers)
• Sterile & aseptic process equipment
• Mixing vessels, reactors & holding tanks
• Transfer piping, hoses, ducts, and manifolds
• CIP/COP systems
• Filling & packaging lines
• Granulation, coating and milling systems
• Utilities (where relevant: PW, WFI, Pure Steam contact surfaces)

Cleaning Validation Lifecycle

1. Risk Assessment & Strategy Development

• Identification of worst-case product based on:
  • Potency
  • Toxicity / PDE
  • Solubility
  • Batch size
  • Equipment contact surface area
• Selection of worst-case equipment
• Review of cleaning procedures (manual/automatic)
• Evaluation of cleaning agents, detergents, and sanitizers

2. Acceptance Criteria (MACO / PDE / VISUAL)

• Calculation of Maximum Allowable Carryover (MACO)
• Integration of toxicology-based limits (PDE / ADE)
• 10-ppm criteria (if applicable)
• Visual cleanliness acceptance criteria
• Microbial limits for equipment, where applicable

3. Analytical Method Development & Validation

• Validation of swab and rinse sampling methods
• Recovery studies for all product-specific analytes
• LOQ/LOD establishment for low-residue detection
• Specific & non-specific methods (TOC conductivity, UV, HPLC)
• Method robustness & repeatability

4. Cleaning Validation Execution (Protocols / Studies)

• Preparation of CV protocol (equipment, sampling points, residues)
• Swab sampling at defined hardest-to-clean points
• Rinse sampling for inaccessible areas
• Verification of visual cleanliness
• Microbial swabs for bioburden sensitive equipment
• Evaluation of:
  • Dirty Equipment Hold Time (DEHT)
  • Clean Equipment Hold Time (CEHT)
  • Number of cleaning cycles (1X, 3X validation)

Sampling Strategy

• Dead-legs and low-flow areas
• Gaskets, manholes, valves, nozzles
• Agitator blades & shafts
• Filter housings & spray balls
• Critical contact surfaces
• Long transfer lines & recirculation loops

Sampling is performed using validated swabs, rinses, or soak methods.

Documentation Provided

• Cleaning Validation Master Plan (CVMP)
• Residue limit justification (MACO/PDE calculations)
• Swab and rinse method validation reports
• Recovery study reports
• DQ/IQ/OQ/PQ (where CIP systems are involved)
• Cleaning Validation Protocols (cycle-wise)
• Executed batch records & raw data
• Analytical results & trending
• Final Cleaning Validation Summary Report
• Cleaning SOPs & revision recommendations

Regulatory Standards Followed

• EU GMP Annex 15
• WHO TRS 937 / 970 / 1019
• USFDA 21 CFR 210/211
• PIC/S PI 006
• ICH Q7 & Q9
• ISPE Baseline Guide – Cleaning Validation

Why Choose PrimeGMP for Cleaning Validation?

• Strong expertise in multiproduct facilities
• Experienced team for PDE integration and MACO calculations
• Complete lifecycle support from planning to execution
• Precise analytical method validation for low-level residues
• Audit-ready documentation with clear scientific justification
• Troubleshooting support for recovery, residue failures, and DEHT/CEHT deviations