with regulatory standards. QA also reviews the analysis results to ensure that they meet acceptance criteria.

Validation Team: Responsible for ensuring that the residual cleaning agent analysis methods are validated and effective for detecting cleaning agents.

Regulatory Affairs Team: Ensures that the analysis methods for residual cleaning agents comply with applicable regulatory guidelines and standards.

4. Accountability

The Manufacturing Manager is accountable for ensuring that residual cleaning agent analysis is performed according to this SOP. The overall compliance with this SOP is overseen by the Quality Assurance (QA) Manager.

5. Procedure

5.1. Selecting Residual Cleaning Agent Analysis Methods

1. The method used to analyze residual cleaning agents should be chosen based on the type of cleaning agents used and the material of the equipment. Common analysis methods include:
   • High Performance Liquid Chromatography (HPLC): Used for detecting and quantifying specific cleaning agents in rinse water or swab samples.
   • Spectrophotometry: Used for detecting certain types of cleaning agents based on their ability to absorb light at specific wavelengths.
   • Titration: A chemical method for determining the concentration of cleaning agents by adding a reagent until a reaction endpoint is reached.
   • pH Measurement: Used to detect the presence of acidic or alkaline residues from cleaning agents.
2. The method should be validated for the specific cleaning agents used and the sensitivity required for detecting residue levels within acceptable limits.
3. The chosen method should be documented in the cleaning validation protocol and approved by the QA team.

5.2. Sampling for Residual Cleaning Agent Analysis

1. Sampling for residual cleaning agent analysis should be conducted immediately after the cleaning process and before the equipment is used for production. The following sampling techniques are commonly used:
   • Rinse Water Sampling: Collect a sample of the water used to rinse the equipment after cleaning. The first rinse is typically the most representative of the residues remaining on the equipment.
   • Surface Swab Sampling: Swab surfaces of the equipment that are most likely to retain residues, such as nozzles, valves, and pumps. The swab should be moistened with a suitable solvent for cleaning agent analysis.
2. Sampling should be done following the sampling plan defined in the cleaning validation protocol, ensuring that all critical surfaces and areas are sampled.
3. Samples should be properly labeled with relevant information, such as the batch number, equipment cleaned, sampling point, and date of collection.
4. The collected samples should be sent to the laboratory for analysis without delay to avoid contamination or degradation of the sample.

5.3. Analyzing Residual Cleaning Agents

1. Once the samples are collected, they should be sent to the laboratory for analysis using the validated method outlined in the cleaning validation protocol.
2. The laboratory should perform the analysis on both rinse water and swab samples, as per the sampling plan. The following should be analyzed:
   • Rinse water samples for residual cleaning agents using methods such as HPLC or spectrophotometry.
   • Swab samples for residual cleaning agents using appropriate techniques such as titration or HPLC, depending on the cleaning agents used.
3. All laboratory results should be compared to the acceptance criteria established in the cleaning validation protocol. Acceptance criteria are typically based on predefined thresholds for cleaning agent residues, ensuring that levels are below established limits for safe use.
4. If the results show that cleaning agent residues exceed acceptable limits, the cleaning process should be reviewed, and corrective actions should be taken. This may include re-cleaning the equipment or modifying the cleaning procedure to achieve better residue removal.

5.4. Documenting Residual Cleaning Agent Analysis Results

1. The results of the residual cleaning agent analysis should be documented in the Residual Cleaning Agent Analysis Report (Annexure-1). The report should include:
   • The sampling points and equipment cleaned
   • The methods used for analyzing the samples
   • The results of the analysis, including residue levels for each cleaning agent tested
   • Comparison of results to the acceptance criteria
   • Corrective actions taken if necessary
2. Any deviations observed during the analysis should be documented in the Deviation Log (Annexure-2), including a description of the issue, the investigation conducted, and any corrective actions implemented.
3. All records should be reviewed by the QA team and other relevant departments to ensure that they meet regulatory and GMP standards. Once reviewed, the records should be approved and archived for future reference and audits.

5.5. Revalidation of Cleaning Procedures

1. If residual cleaning agent levels exceed the acceptable limits, the cleaning process should be revalidated. The revalidation should include:
   • Reviewing the cleaning procedure and sampling techniques
   • Adjusting the cleaning process or equipment settings to improve residue removal
   • Re-performing the cleaning validation to ensure the process meets the required standards
2. Revalidation should be documented and reviewed by the QA team to ensure that the cleaning process is effective and that the equipment meets cleanliness standards before being used for production.

6. Abbreviations

• GMP: Good Manufacturing Practice
• QA: Quality Assurance
• SOP: Standard Operating Procedure
• HPLC: High Performance Liquid Chromatography
• CFR: Code of Federal Regulations
• CAPA: Corrective and Preventive Action

7. Documents

1. Residual Cleaning Agent Analysis Report (Annexure-1)
2. Deviation Log (Annexure-2)

8. References

This SOP is based on the following regulatory guidelines and industry standards:

• Good Manufacturing Practice (GMP) Guidelines
• FDA Code of Federal Regulations (CFR) Title 21, Part 211
• International Council for Harmonisation (ICH) Guidelines

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Residual Cleaning Agent Analysis Report

Batch Number	Test Date	Residue Level	Acceptance Criteria	Result
Batch-001	10/02/2025	Detergent	Less than 5 ppm	Pass

Annexure-2: Deviation Log

Deviation ID	Deviation Description	Corrective Action	Assigned To	Status
DEV-12345	Residue level exceeded limit	Adjusted cleaning procedure	Rajesh Patel	Completed

12. Revision History:

Revision Date	Revision No.	Revision Details	Reason for Revision	Approved By	Page No.	Ref. Point No.	Details of Revision
01/01/2024	V 1.0	Initial Release	First Issue	Anjali Sharma	Page 1	[Ref Point]	First Release
01/01/2025	V 2.0	Updated analysis procedures	To comply with updated GMP regulations	Anjali Sharma	Page 1	[Ref Point]	Updated procedures