address all manufacturing equipment and ancillary items.

PIC/S PI 006-3: Validation of cleaning processes should demonstrate the effectiveness of procedures across all relevant surfaces and equipment.

Failing to qualify storage or transfer equipment could result in cross-contamination observations, especially when handling different product batches in shared facilities. For related cleaning SOP templates, visit PharmaSOP.in.

Scope of Cleaning Qualification

The cleaning qualification for trolleys, bins, and storage vessels applies to various types:

• Stainless steel or plastic mobile trolleys
• Granule or powder holding bins (IBC containers)
• Drum trolleys used for raw material movement
• Material dispensing and sampling carts
• Storage racks and staging containers in cleanrooms

The level of qualification required depends on risk. For example, containers exposed to open product must follow stricter limits than closed bins used only for packaging materials.

Cleaning Methodology Overview

The cleaning process may be manual, semi-automatic, or automated (e.g., bin washers). In all cases, the process must be documented with clear steps such as:

• Pre-cleaning inspection and removal of gross residue
• Detergent application (validated type and concentration)
• Rinse with purified water or WFI
• Visual inspection for cleanliness
• Drying with filtered air (if applicable)

Cleaning should be reproducible and traceable. If cleaned manually, the qualification must include operator variability, cleaning aids, and detergent residue removal studies.

Cleaning Validation Protocol Elements

A robust cleaning qualification protocol must include the following:

• Objective: To demonstrate effective and consistent cleaning of bins, trolleys, and storage containers.
• Equipment description: List equipment ID, location, material of construction, and usage pattern.
• Cleaning procedure reference: Attach the relevant SOP number.
• Worst-case selection: Choose the dirtiest equipment (e.g., bin exposed to APIs) for validation.
• Sampling plan: Define the number and location of swab and rinse samples.
• Acceptance limits: Based on MACO, PDE, and TOC thresholds.
• Analytical methods: TOC, HPLC, UV, or microbiological swabbing.
• Documentation: Protocol, data sheets, deviation records, and summary report.

Sampling Techniques and Strategy

Surface cleanliness is verified using swab sampling and rinse sampling:

• Swab Sampling: Performed on hard-to-clean areas such as corners, lids, or joints. Swab 25 cm² per location using pre-validated TOC swabs.
• Rinse Sampling: Used when internal surfaces are inaccessible. Collect rinse samples post-cleaning and analyze for residual actives or TOC.
• Microbiological Sampling: Especially for equipment used in aseptic or cleanroom areas. Sample pre- and post-cleaning using contact plates or swabs.

Sample locations must be justified as worst-case sites. Swab recovery efficiency must be validated and documented. For reference recovery studies, visit StabilityStudies.in.

Calculation of Acceptance Criteria

Acceptance limits are calculated using product-specific and cleaning-specific parameters. The two most common approaches are:

1. MACO (Maximum Allowable Carryover)

MACO ensures that traces of the previous product do not cause adverse effects in the next product. Formula:

MACO (mg) = (Minimum batch size of next product × PDE of previous product) / Maximum daily dose of next product

Example:

• Minimum batch size of next product = 100,000 tablets
• PDE of previous product = 10 mg/day
• Max daily dose of next product = 4 tablets/day
• MACO = (100,000 × 10) / 4 = 250,000 mg = 250 g

2. TOC or Analytical Residue Limit

For general cleaning verification, a TOC limit of ≤10 ppm (parts per million) or residue ≤1 µg/cm² is typical.

Equipment Type	Max Residue (µg/cm²)	TOC Limit (ppm)
SS Bin (closed)	1.0	10
Plastic Trolley (open)	0.5	5
Drum Cart (non-contact)	2.0	15

Example Study Results Summary

Sample ID	Location	TOC Result (ppm)	Acceptance
TROL-001	Trolley corner weld	3.2	Pass
BIN-002	Bin inner lid	8.9	Pass
STOR-005	Storage drum base	12.3	Fail

Handling Failures and CAPA

If cleaning fails to meet the acceptance limits, a structured root cause and corrective action must follow:

• Re-clean and re-test the failed equipment
• Investigate cleaning SOP compliance, detergent concentration, operator technique
• Revise training or sampling methodology if variability is high
• Document failure in deviation management system
• Assess impact on batches produced with unqualified cleaning

For deviation templates and CAPA forms, explore pharmaregulatory.in.

Documentation Requirements

The entire cleaning qualification should be supported by clear, traceable documents:

• Validation protocol and test plan
• Executed sampling forms
• Swab and rinse test data (TOC, HPLC, micro)
• Equipment ID log and calibration records
• Analytical method validation summary
• Final report with QA approval

Lifecycle Requalification Strategy

Cleaning qualification is not a one-time activity. The following triggers require requalification:

• Change in cleaning agent, detergent supplier, or method
• Equipment modification or replacement
• Multiple cleaning failures or CAPAs
• Extension of equipment usage to a different product class (e.g., cytotoxics)

Checklist for Cleaning Qualification of Bins and Trolleys

• [ ] Has each equipment type been identified with a unique ID?
• [ ] Is there a risk-based rationale for equipment inclusion?
• [ ] Are all cleaning agents validated for efficacy and removal?
• [ ] Has the worst-case equipment been selected for the study?
• [ ] Have swab and rinse sampling plans been justified and documented?
• [ ] Are recovery studies available for each method?
• [ ] Is the final report reviewed and approved by QA and validation?

Conclusion

Cleaning qualification of trolleys, bins, and storage containers is a key GMP requirement that ensures materials handling does not become a contamination risk. Regulatory scrutiny is increasing in this area, especially in shared facilities and multi-product plants. A structured approach to protocol design, analytical testing, documentation, and lifecycle updates is essential for audit readiness and compliance.

To explore cleaning protocols and validation forms, check PharmaGMP.in and PharmaSOP.in.