What are Cleanrooms?

Cleanrooms are controlled environments that maintain low levels of pollutants such as dust, airborne microbes, and chemical vapours. They are essential in pharmaceuticals, biotechnology, and semiconductor manufacturing industries, where even tiny contaminants can adversely affect product quality.

Why Cleanroom Performance Qualification is Required

Performance qualification (PQ) ensures that a cleanroom meets predefined cleanliness standards and operates as intended. It verifies that all systems work correctly in the specified environment, confirming compliance with regulatory and safety standards. PQ is crucial for:

• Product Safety: Ensuring product sterility and quality.
• Regulatory Compliance: Meeting stringent industry standards.
• Operational Consistency: Establishing reliable processes.

Step-by-Step Requirements of Performance Qualification

1. Planning and Documentation
   • Define the scope and objectives.
   • Prepare a detailed PQ protocol outlining methods, acceptance criteria, and responsibilities.
2. Installation Qualification (IQ)
   • Verify that all equipment is installed correctly according to specifications.
   • Document the location, services, and specifications of cleanroom components.
3. Operational Qualification (OQ)
   • Assess whether the cleanroom operates as intended under simulated operational conditions.
   • Conduct temperature, humidity, airflow, pressure differentials, and filtration efficiency tests.
4. Performance Qualification (PQ)
   • Execute cleaning and monitoring processes to validate operational performance.
   • Perform microbial monitoring and particle count tests to ensure cleanliness standards.
5. Documentation Review
   • Compile all results and compare them against acceptance criteria.
   • Document deviations, root causes, and corrective actions if necessary.
6. Final Report
   • Prepare a comprehensive report summarizing the qualification results, methodologies, and compliance with specifications.

Clean Utilities Overview for GMP Manufacturing Sites

HVAC Qualification

Regulatory Requirements for PQ of Cleanrooms

United States (USFDA)

• Guidelines: 21 CFR Part 210/211 emphasizes the need for controlled environments in drug manufacturing.

Health Canada

• Guidelines: Health Canada’s Good Manufacturing Practices (GMP) outline requirements for controlled environments.

ISO

• Standard: ISO 14644 specifies cleanliness levels and testing methods for cleanrooms.

EU-GMP

• Guidelines: EudraLex Volume 4 provides comprehensive guidelines on cleanroom requirements and qualifications.

ANVISA (Brazil)

• Regulations: ANVISA Resolution RDC 16/2013 provides guidelines for pharmaceutical cleanrooms.

TGA (Australia)

• Guidelines: TGA’s GMP standards require proper control and qualification of cleanroom environments.

MCC (South Africa)

• Regulations: MCC guidelines ensure compliance with GMP for sterile products.

IMB (Ireland)

• Regulations: IMB guidelines require stringent control of pharmaceuticals’ cleanroom environments.

Detailed Documentation Content and Structure for Performance Qualification

1. Title Page
   • Title, date, and version of the document.
2. Table of Contents
   • Clear navigation of the document sections.
3. Introduction
   • Purpose and scope of the PQ.
4. Protocol
   • Detailed methodologies for IQ, OQ, and PQ.
   • Acceptance criteria for each phase.
5. Equipment and Systems Description
   • List of cleanroom equipment and systems being qualified.
6. Test Methods and Procedures
   • Step-by-step instructions for all tests performed.
7. Results and Data Analysis
   • Summary of test results, including charts and graphs.
8. Deviation Management
   • Document any deviations and corrective actions taken.
9. Conclusion
   • Summary of findings and overall assessment of cleanroom performance.
10. Appendices
    • Raw data, calibration certificates, and other relevant documents.

Total Number of Tests Required During Performance Qualifications

The number of tests varies by facility and requirements but generally includes:

1. Airborne Particle Count Tests
2. Microbial Monitoring Tests
3. Airflow Velocity and Pattern Tests
4. Temperature and Humidity Checks
5. Pressure Differential Tests
6. HEPA Filter Integrity Tests

Regulatory Warning Letters and 483 Related to Cleanrooms

Regulatory agencies like the FDA and EMA issue 483s (notices of inspectional observations) for non-compliance. Common issues include:

• Inadequate environmental monitoring.
• Failure to validate cleanroom conditions.
• Poor documentation practices.
• Inconsistent adherence to cleaning protocols.

Conclusion

Maintaining cleanroom standards is crucial for ensuring product quality and regulatory compliance. Performance qualification is a comprehensive process requiring meticulous documentation and adherence to regulatory guidelines. By understanding and following these protocols, organizations can ensure safe and effective production environments.

Contact Us

GxP Cellators is a reputable contract services organization that provides comprehensive Good x Practices (GxP) services in Manufacturing, Laboratory, Distribution, Engineering, and Clinical practices to various industries, including Biopharmaceuticals, Pharmaceuticals, and Medical Devices. We closely collaborate with our esteemed life sciences clients to help them establish greenfield or brownfield projects, guiding them from the project stage to regulatory approval for their GxP sites.

Our team consists of highly qualified experts specializing in Good Manufacturing Practices (GMP), Good Laboratory Practices (GLP), Good Clinical Practices (GCP), Good Distribution Practices (GDP), Cleanroom Operations, and Engineering Operations. Our Subject Matter Experts (SMEs) are extensively trained and possess the essential knowledge and skills to excel in their respective domains.

We also have a team of highly skilled validation specialists with expertise in equipment and utilities qualifications, computerized system validations (CSV), thermal validations, clean utilities validation, and cleanroom validations. Please contact us at for assistance qualifying your facilities or site equipment.