Standard Operating Procedure for Cleaning Validation of Ampoule Filling Machines
1) Purpose
The purpose of this Standard Operating Procedure (SOP) is to define the process for performing cleaning validation of ampoule filling machines used in pharmaceutical manufacturing. This SOP ensures that cleaning procedures are validated to effectively remove residues of active pharmaceutical ingredients (APIs), excipients, cleaning agents, and microbial contaminants from ampoule filling machines. The cleaning validation process verifies that the cleaning methods used are effective, reproducible, and compliant with regulatory standards to ensure product quality, safety, and sterility.
2) Scope
This SOP applies to the cleaning validation of ampoule filling machines used in the pharmaceutical manufacturing process. The cleaning validation includes Installation Qualification (IQ), Operational Qualification (OQ), and Performance Qualification (PQ) to verify that cleaning methods remove contaminants from the equipment surfaces to acceptable limits. This SOP is applicable to new ampoule filling machines, as well as those that have undergone repairs, upgrades, or relocation. It ensures that all cleaning processes are adequately validated for compliance with good manufacturing practices (GMP) and regulatory requirements.
3) Responsibilities
Operators: Responsible for performing the cleaning procedures as per the validated cleaning process and ensuring that all parameters such as time, temperature, and cleaning agent concentration are correctly applied.
Quality Assurance (QA): Ensures that the cleaning validation process is conducted in accordance with this SOP and regulatory requirements. QA is responsible for reviewing and approving cleaning validation reports, ensuring that any deviations are addressed, and verifying the efficacy of cleaning methods.
Production Supervisors: Oversee the cleaning validation process, ensuring that operators follow the procedure and that the ampoule filling machines are cleaned as per the validated protocol.
Validation Team: Responsible for developing cleaning validation protocols, conducting IQ, OQ, and PQ runs, analyzing results, and ensuring that cleaning methods meet all required performance standards.
Maintenance Personnel: Ensures that the ampoule filling machines are properly maintained and calibrated to ensure proper cleaning performance and consistency in results.
4) Procedure
The following steps should be followed for the IQ, OQ, and PQ of cleaning validation for ampoule filling machines:
1. Installation Qualification (IQ):
1.1 Review the cleaning validation protocol and ensure that it includes the required criteria for cleaning effectiveness (e.g., acceptable residue limits, cleaning agents, procedures).
1.2 Verify that the ampoule filling machines are installed according to the manufacturer’s specifications and are free from any contaminant residues from previous use.
1.3 Ensure that all equipment used in the cleaning process, such as water sources, cleaning solutions, and brushes, is appropriately qualified and ready for use.
1.4 Confirm that cleaning areas meet the necessary environmental conditions such as cleanliness, lighting, and temperature.
1.5 Complete the IQ documentation, including installation reports and checklists, and ensure that all required information is recorded and signed off by responsible personnel.
2. Operational Qualification (OQ):
2.1 Verify that all operational parameters for cleaning, such as cleaning agent concentration, temperature, time, and method, are within the validated limits.
2.2 Test the cleaning procedures to ensure that they effectively remove residue from all accessible surfaces of the ampoule filling machines.
2.3 Conduct visual inspection and swab sampling to ensure that cleaning procedures remove visible residues of APIs, excipients, and cleaning agents.
2.4 Perform microbiological testing on swab samples to ensure that no microbial contamination remains on surfaces.
2.5 Verify that the ampoule filling machines function normally after cleaning, ensuring that no cleaning residues are left that could affect the next batch of products.
2.6 Document the results of the OQ, noting any deviations or issues encountered and corrective actions taken.
3. Performance Qualification (PQ):
3.1 Conduct the cleaning process under typical production conditions to monitor its performance during routine cleaning operations.
3.2 Perform multiple cleaning cycles to verify the consistency of cleaning results and ensure that all critical surfaces of the ampoule filling machines are thoroughly cleaned.
3.3 Measure and document cleaning effectiveness by testing for the presence of API residues, cleaning agent residues, and microbial contamination at predefined critical points in the ampoule filling machines.
3.4 Conduct repeated swab sampling and visual inspections after each cleaning cycle to verify consistency.
3.5 Document the results of the PQ, including any deviations, corrective actions, and confirmation that the cleaning process meets the established criteria for cleaning effectiveness and residue removal.
3.6 Prepare and finalize the cleaning validation report, including details of the cleaning cycle, swab results, microbial testing, and cleaning agent efficacy.
4. Documentation and Reporting:
4.1 Record all data during the IQ, OQ, and PQ processes, including equipment logs, cleaning agent usage, swab results, temperature and time measurements, and microbiological test results.
4.2 Ensure that all forms, reports, and certificates are completed, signed, and approved by the appropriate personnel.
4.3 Perform statistical analysis on the collected data to assess the consistency and reliability of the cleaning process. This analysis should confirm that the system operates consistently and effectively within predefined parameters and meets the acceptance criteria for cleaning and residue removal.
4.4 Prepare a final cleaning validation report, summarizing the results of the IQ, OQ, and PQ, including any deviations, corrective actions, and conclusions regarding the cleaning validation of the ampoule filling machines.
5. Requalification:
5.1 Requalify the cleaning process if significant changes are made to the ampoule filling machines, such as replacement of major components, relocation, or modification of cleaning equipment.
5.2 Periodically perform requalification to ensure that the cleaning process continues to meet the required standards and remains in compliance with regulatory requirements.
5) Abbreviations
- IQ: Installation Qualification
- OQ: Operational Qualification
- PQ: Performance Qualification
- API: Active Pharmaceutical Ingredient
- QA: Quality Assurance
- SOP: Standard Operating Procedure
6) Documents
- IQ/OQ/PQ Protocol
- Cleaning Validation Protocol
- Cleaning Agent Specifications
- Equipment Cleaning Logs
- Swab Sampling Results
- Microbiological Testing Logs
- Deviation and Corrective Action Reports
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: Cleaning Validation Test Record
| Date | Time | Operator Initials | Test Type (IQ/OQ/PQ) | Test Results | Comments |
|---|---|---|---|---|---|
| DD/MM/YYYY | HH:MM | Operator Name | IQ/OQ/PQ | Pass/Fail | Comments |
Template 2: Swab Sampling Log
| Batch No. | Test Date | Sampling Area | Residue Level | Pass/Fail | Operator Initials |
|---|---|---|---|---|---|
| Batch Number | DD/MM/YYYY | Sampling Area | Residue Level | Pass/Fail | Operator Name |
Template 3: Microbiological Testing Log
| Batch No. | Test Date | Microbial Load (CFU) | Pass/Fail | Operator Initials |
|---|---|---|---|---|
| Batch Number | DD/MM/YYYY | Microbial Load | Pass/Fail | Operator Name |