Team: Responsible for implementing the cleaning process and ensuring that the equipment meets the established acceptance criteria.

Regulatory Affairs Team: Ensures that the acceptance criteria for cleaning validation comply with regulatory standards applicable to aerosol manufacturing.

4. Accountability

The Manufacturing Manager is accountable for ensuring that the acceptance criteria for cleaning validation are established and met. The overall compliance with this SOP is overseen by the Quality Assurance (QA) Manager.

5. Procedure

5.1. Defining Cleaning Residue Limits

1. The first step in establishing acceptance criteria is to define the maximum allowable levels of residues that can remain on the equipment after cleaning. These include:
   • Active Ingredient Residues: The maximum allowable level of active ingredients from the aerosol products that may remain on the equipment after cleaning. This is typically expressed as parts per million (ppm) or micrograms per square centimeter (µg/cm²).
   • Cleaning Agent Residues: The maximum allowable level of cleaning agents used during the cleaning process. This includes solvents, detergents, or disinfectants.
   • Microbial Contamination: The acceptable level of microbial contamination on the equipment. This may include bacteria, fungi, or other contaminants that could affect product safety and quality.
2. Residue limits should be based on the following:
   • Product safety and regulatory guidelines (e.g., FDA, EMA)
   • The potential effect of residual residues on product quality (e.g., potency, safety, and efficacy)
   • Industry standards and GMP guidelines for cleaning validation

5.2. Determining Analytical Method Sensitivity

1. The sensitivity of the analytical methods used to detect residues must be considered when establishing the acceptance criteria. The chosen methods should be capable of detecting residues at levels below the defined acceptance criteria.
2. Common methods for residue analysis include:
   • High-Performance Liquid Chromatography (HPLC): Used for detecting active ingredients and other compounds in rinse water or swab samples.
   • Spectrophotometry: A method for detecting cleaning agents based on their absorption of light at specific wavelengths.
   • Titration: A technique used to quantify cleaning agent residues by neutralizing the chemical with a known reagent.
   • pH Measurement: Used to detect residues of acidic or alkaline cleaning agents.
3. The analytical method should have a sensitivity that is at least ten times lower than the established acceptance limits to ensure that even trace amounts of residues can be detected.

5.3. Establishing Microbial Acceptance Criteria

1. For aerosol products that are susceptible to microbial contamination, microbial limits must be established for the cleaning validation. This includes:
   • Defining the maximum allowable levels of microbial contamination (e.g., bacteria, mold) on critical equipment surfaces after cleaning.
   • Microbial limits should be established based on product characteristics and regulatory requirements. For example, some products may require sterile equipment, while others may allow low levels of microbial contamination.
   • Methods for detecting microbial contamination include swab sampling followed by incubation or using rapid microbiological testing methods.
2. Microbial limits should be clearly defined and documented as part of the cleaning validation protocol to ensure that the equipment is free from contamination that could affect product safety and quality.

5.4. Documenting and Reviewing Acceptance Criteria

1. The established acceptance criteria for cleaning validation should be documented in the cleaning validation protocol. The protocol should include:
   • A summary of the residue limits for active ingredients, cleaning agents, and microbial contamination.
   • The sensitivity of analytical methods used to detect residues and microbial contamination.
   • The acceptable range for each residue limit and any acceptable deviations, if applicable.
   • Reference to regulatory guidelines and industry standards that support the established criteria.
2. The QA team should review the acceptance criteria to ensure they are appropriate for the cleaning process and the safety requirements of the aerosol products being produced.
3. Once the acceptance criteria are reviewed and approved, they should be included in the cleaning validation protocol and used as the basis for cleaning validation testing.

5.5. Setting Up Revalidation Criteria

1. If any changes are made to the cleaning process, equipment, or materials, the acceptance criteria should be reviewed and updated accordingly. Revalidation may be required to ensure that the revised cleaning process meets the updated criteria.
2. Revalidation criteria should be set for any subsequent changes, including changes to the cleaning agents, equipment, or formulation, to ensure that the cleaning process remains effective and compliant with the established limits.

6. Abbreviations

• GMP: Good Manufacturing Practice
• QA: Quality Assurance
• SOP: Standard Operating Procedure
• HPLC: High-Performance Liquid Chromatography
• CAPA: Corrective and Preventive Action

7. Documents

1. Cleaning Validation Protocol (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: Cleaning Validation Protocol

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 above 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 cleaning validation procedures	To comply with updated GMP regulations	Anjali Sharma	Page 1	[Ref Point]	Updated procedures