Top FDA Form 483 Observations: Equipment Qualification

This blog highlights key FDA Form 483 observations on equipment qualification in pharmaceutical manufacturing. Issues include improper cleaning, lack of written procedures, and failure to follow qualification protocols. Root causes include procedural gaps and oversight, with corrective actions like revising protocols, conducting risk assessments, and ongoing training to maintain compliance and prevent cross-contamination or data integrity issues.

1. Equipment and utensils are not cleaned at appropriate intervals to prevent.

‍Summary
Failure to clean equipment and utensils at appropriate intervals, risking drug product safety, identity, and purity.

Excerpt from Observation
Non-dedicated equipment used in the manufacturing of drug products at your firm have not been appropriately cleaned since their installation several years ago.

Justification
Cleaning of non-dedicated equipment is crucial to prevent cross-contamination and maintain drug product quality.

Possible Root Cause

Initial and ongoing equipment qualification protocols may not include sufficient cleaning validation steps.

Corrective Actions

Requalify all affected equipment with special attention to cleaning validation. Validate cleaning procedures.

Preventive Actions

Revise qualification protocols to include robust cleaning validation. Ensure periodic requalification includes cleaning verification.

View detailed analysis of this observation

Reference FDA 483:
Company Name: Granules India Limited
Issue Date: 2024-09-06
Inspection Dates: 26-08-2024 to 06-09-2024
Investigators: Pratik S Upadhyay, Joseph A Piechocki, seph A Piechocki

2. Firm failed to establish written procedures for production and process controls

Summary
Lack of protocol-driven equipment performance qualifications for production equipment causing unqualified equipment usage in process validation.

Excerpt from Observation
The process validation report titled "Process Performance Qualification Report of (b) (4) API" MVD-000146683, ver 3.0, was executed using equipment that was not fully qualified (IQ/OQ/PQ).

Justification
The issue directly pertains to the qualification of equipment (IQ/OQ/PQ), which is essential for ensuring they are suitable for their intended use in production.

Possible Root Cause

Absence of formal procedures for equipment qualification (IQ/OQ/PQ) and lack of pre-approved criteria and summary reports for qualification status.

Corrective Actions

Develop and implement protocol-driven equipment qualification procedures. Perform immediate equipment qualifications for all production equipment with documented acceptance criteria and final summary reports.

Preventive Actions

Establish a standardized protocol for ongoing equipment qualification. Train staff on the importance and execution of qualification protocols, including periodic review and updates.

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View detailed analysis of this observation

Reference FDA 483:
Company Name: Biocon Biosphere Limited
Issue Date: 2024-06-14
Inspection Dates: 10-06-2024 to 14-06-2024
Investigators: Brandy N Lepage

3. Equipment qualification procedures are not followed

Summary
Neglect in following equipment qualification procedures for new API manufacturing equipment.

Excerpt from Observation
Your firm did not follow procedure 1035-G-0042 - Qualification of Equipment...for pharmaceutical ingredient manufacture...has not conducted a risk assessment nor qualification activities for the

Justification
The observation directly relates to a failure in conducting required risk assessments and qualification activities for new equipment, pointing to a deficiency in executing the Equipment Qualification process as per the firm’s own standards.

Possible Root Cause

The primary root cause appears to be a procedural oversight or lack of adherence to existing equipment qualification protocols. This suggests a gap in the implementation of the firm's quality management system, specifically in the oversight and execution of equipment qualification processes.

Corrective Actions

Immediate initiation of risk assessment and qualification activities for the specified equipment, as per procedure 1035-G-0042. Additionally, review and validate all recent equipment acquisitions for adherence to qualification protocols.

Preventive Actions

Enhance training programs for personnel involved in equipment acquisition and qualification processes, emphasizing the importance of following established protocols. Implement a checklist and approval process for equipment qualification that includes mandatory steps such as risk assessment and documentation review. Regular audits of equipment qualification procedures to ensure compliance.

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View detailed analysis of this observation

Reference FDA 483:
Company Name: Cipla Limited
Issue Date: 2024-04-04
Inspection Dates: 28-03-2024 to 04-04-2024
Investigators: Lori M Newman, Sean R Marcsisin

4. Failure to maintain a backup file of data entered into the computer or related system

Summary
Lack of data backup and audit trails for critical monitoring equipment, undermining data integrity.

Excerpt from Observation
Deficiencies regarding accuracy of data and subsequent particle count calculations were also noted during qualification of the NVPCs.

Justification
The observation cites deficiencies in data accuracy and particle count calculations specifically noted during the qualification process of the equipment.

Possible Root Cause

Inadequate qualification protocols and verification processes, which failed to ensure the accuracy of data generated by the equipment.

Corrective Actions

Revise and enhance the equipment qualification protocols to include thorough checks on data accuracy and calculation verification.

Preventive Actions

Implement periodic requalification and validation of equipment to ensure ongoing accuracy and compliance. Ensure all qualification protocols are rigorously followed.

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View detailed analysis of this observation

Reference FDA 483:
Company Name: Eugia SEZ Private Limited
Issue Date: 2024-02-29
Dates: 19-02-2024 to 29-02-2024
Investigators: Ashar P Parikh, Marcellinus D Dordunoo

5. Appropriate controls are not exercised over computers or related systems to assure that changes in master production and control records or other records are instituted only by authorized personnel.

Summary
Unauthorized changes to records and systems indicate significant data integrity issues.

Excerpt from Observation
Equipment qualification activities for these equipment have never been performed by your firm.

Justification
Ensuring equipment qualification is crucial for consistent performance and compliance with regulatory expectations.

Possible Root Cause

Neglect in following qualification procedures either due to inadequate SOPs, oversight, or lack of understanding of regulatory requirements. There may also be an absence of regular audits or reviews of equipment qualification status.

Corrective Actions

Immediately undertake qualification activities for all GMP-related equipment, ensuring all new and existing equipment are qualified before use.

Preventive Actions

Develop and implement a comprehensive Equipment Qualification program that includes Installation Qualification (IQ), Operational Qualification (OQ), and Performance Qualification (PQ) for all equipment. Regularly schedule audits to verify equipment status and re-qualify as necessary.

View detailed analysis of this observation

Reference FDA 483:
Company Name: Jiangsu Hengrui Pharmaceuticals Co., Ltd
Issue Date: 2024-01-16
Inspection Dates: 08-01-2024 to 16-01-2024
Investigators: Arsen Karapetyan, Qiao Y Bobo

Effective Strategies to Prevent FDA 483 Observations

• Stay updated on FDA regulations: Ensure thorough knowledge of the latest GMP and quality control standards.
• Conduct regular internal audits: Proactively assess compliance to identify and correct potential issues.
• Maintain accurate documentation: Keep batch records, SOPs, and logbooks complete, current, and readily accessible.
• Implement a strong CAPA system: Address deviations swiftly through Corrective and Preventive Actions.
• Conduct mock FDA inspections: Practice readiness by simulating inspections to uncover any gaps.
• Ensure facility and equipment maintenance: Keep facilities clean and organized, with properly calibrated equipment.

Leverage QMS Software to Prevent FDA 483 Citations

An effective QMS software can help you stay ahead of compliance challenges by automating quality processes, ensuring accurate documentation, and providing real-time oversight. With Leucine’s QMS, companies can seamlessly manage deviations, implement proactive CAPA systems, and always be inspection-ready, significantly reducing the risk of receiving FDA 483 citations.