plans, ensuring sample integrity, and validating the cleaning process based on sample results.
Production Supervisors: Oversee the sampling procedures to ensure that operators are following the proper protocols and handling samples correctly.
Validation Team: Develops the sampling plan, defines acceptable residue limits, and ensures that samples are collected and analyzed according to the established procedures.
Laboratory Personnel: Responsible for analyzing the samples to assess residue levels and ensuring that the analytical methods used are valid and accurate.

4) Procedure

The following steps should be followed for proper sampling during cleaning validation:

1. Sample Collection Plan Development:
1.1 Develop a sampling plan that specifies the number of samples to be collected, sampling locations, and the frequency of sampling during cleaning validation.
1.2 Ensure that the sampling plan covers all critical areas of the equipment that may retain residues, including hard-to-reach areas.
1.3 Define the types of residues to be measured (e.g., API residues, excipients, cleaning agents, and microbial contamination).
1.4 Ensure that the sampling points are chosen based on the flow of materials, potential contamination areas, and worst-case scenarios where residue may be more difficult to remove.
1.5 Ensure that sampling methods and techniques are appropriate for the equipment being tested, taking into account the materials used and the surfaces to be sampled.

2. Sampling Methods:
2.1 Use appropriate sampling tools, such as swabs, wipes, or rinse samples, depending on the equipment and surfaces being tested.
2.2 Swab sampling should be performed using sterile wipes or swabs that are pre-moistened with a suitable solvent (e.g., water, ethanol) to ensure residue collection.
2.3 Ensure that the swabbing technique covers the entire critical surface area, paying attention to corners, joints, and other hard-to-reach areas.
2.4 For rinse sampling, collect rinse water from equipment after cleaning to check for residues in the rinse water.
2.5 Ensure that sampling tools are sterile to avoid contamination of samples and that they are used only once to prevent cross-contamination.
2.6 Document the sampling locations and ensure that each sample is labeled with relevant information, such as equipment ID, sample ID, date, and time of collection.

3. Handling and Transport of Samples:
3.1 Handle all samples with care to prevent contamination or degradation of the residue.
3.2 Transport the samples to the laboratory under appropriate conditions, ensuring they remain in a controlled environment (e.g., temperature-controlled transport) until analysis.
3.3 Ensure that all sample containers are properly sealed, labeled, and transported in a way that prevents any change in the sample composition or contamination from external sources.

4. Analytical Testing:
4.1 Perform appropriate analytical tests on the samples to quantify residue levels. These may include chromatographic methods (e.g., HPLC, GC), microbiological testing, or other analytical methods suitable for the residues being tested.
4.2 Ensure that the analytical methods used are validated and suitable for the type of residue being measured.
4.3 For residue analysis, establish acceptable limits based on regulatory requirements and product safety standards.
4.4 Analyze the samples and document the results in the sampling report, including the testing method used, sample identification, residue levels, and comparison to acceptable limits.

5. Documentation and Reporting:
5.1 Record all sampling data, including sample collection details, analytical methods used, test results, and any deviations from the standard procedure.
5.2 Ensure that all forms and records are signed and dated by the personnel responsible for sample collection and analysis.
5.3 Prepare a cleaning validation report that includes a summary of the sampling results, any deviations or corrective actions, and conclusions regarding the effectiveness of the cleaning process.
5.4 The cleaning validation report should be reviewed and approved by the Quality Assurance (QA) department, ensuring that all residue limits have been met and that the equipment is ready for use in the next production cycle.

6. Requalification:
6.1 Requalify the sampling procedure if significant changes are made to the manufacturing equipment, cleaning agents, or cleaning processes.
6.2 Perform requalification of the cleaning validation sampling process periodically to ensure that it remains effective in detecting residues and contamination.
6.3 Document all requalification activities, ensuring compliance with GMP and regulatory requirements.

5) Abbreviations

• API: Active Pharmaceutical Ingredient
• QA: Quality Assurance
• GMP: Good Manufacturing Practice
• SOP: Standard Operating Procedure
• HPLC: High-Performance Liquid Chromatography
• GC: Gas Chromatography

6) Documents

• Sampling Plan
• Cleaning Validation Protocol
• Sample Collection Forms
• Analytical Test Results
• Deviation and Corrective Action Reports
• Final Cleaning Validation Report

7) Reference

• FDA Guidance for Industry: Equipment Cleaning and Sanitation
• International Council for Harmonisation (ICH) Q7: Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients
• ISO 9001: Quality Management Systems – Requirements
• USP Chapter 1072: Cleaning and Sanitization of Manufacturing Equipment

8) SOP Version

Version 1.0 – Effective Date: DD/MM/YYYY

Annexure

Template 1: Sample Collection Log

Date	Time	Sample Location	Operator Initials	Sample Type (Swab/Rinse)	Comments
DD/MM/YYYY	HH:MM	Location Description	Operator Name	Swab/Rinse	Comments

Template 2: Analytical Test Results

Sample ID	Test Method	Residue Level	Acceptance Criteria	Pass/Fail	Operator Initials
Sample ID	Test Method	Residue Level	Acceptance Criteria	Pass/Fail	Operator Name

Template 3: Deviation Report

Deviation ID	Date	Operator Initials	Deviation Description	Corrective Actions
Deviation ID	DD/MM/YYYY	Operator Name	Deviation Description	Corrective Actions