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ISPE Good Practice Guide: Heating, Ventilation, and Air Conditioning (Second Edition) cover image

ISPE Good Practice Guide: Heating, Ventilation, and Air Conditioning (Second Edition)

Published:September 2024

Pages:272

Heating, Ventilation, and Air Conditioning (HVAC) systems can critically affect the ability of a pharmaceutical facility to meet its objective of providing a safe and effective product to the patient. The design of these systems requires a blend of Good Manufacturing Practice (GMP) and Good Engineering Practice (GEP) to help provide a safe and healthy workplace, protect the environment, and manage energy responsibly.

The need to update this Guide has become increasingly evident since its original publication in 2009 as options available to HVAC designers and engineers have evolved due to technological advancements and shifting project pressures. The updates reflect these changes, providing readers with a more current perspective on the challenges and resources involved.

This Guide aims to clarify GMP HVAC issues that are critical to the safety, identity, strength, purity, and quality of pharmaceuticals, biopharmaceuticals, advanced therapy medicinal products, and medical devices, from raw materials to finished products. It covers HVAC control and monitoring requirements and addresses GEP issues related to sustainability, economics, and environmental health and safety. The Guide provides best practices for implementing international regulatory and industry guidance, with appendices containing industry examples and templates for the reader’s reference.

Applicable to HVAC engineers regardless of experience level, this Guide also provides Quality professionals with an understanding of system parameters important to product quality and patient safety. An overview of HVAC-specific building automation controls and environmental monitoring is presented. Business driven specifications are also discussed, such as redundant systems and custom air handlers.

Additional topics include:

  • Supporting information and HVAC practices for different facility types
  • Establishing HVAC Design Criteria
  • Energy Use and Sustainability Considerations
  • System Configurations by Facility Type
  • HVAC and Environmental Controls and Monitoring
  • Commissioning, Qualification, and Quality Risk Management
  • Lifecycle Documentation, Operations, and Maintenance

The information provided in this Guide reflects the cumulative knowledge and experiences of the authors, editors, and reviewers with input from members of the ISPE HVAC Community of Practice (COP).

  • 1 Introduction
  • 1.1 Background
  • 1.2 Purpose and Objectives
  • 1.3 Scope
  • 1.4 Benefits
  • 1.5 Summary of Revisions
  • 1.6 Key Concepts and Terms
  • 2 Purpose of HVAC in Pharmaceutical Facilities (Basic Concepts)
  • 2.1 Regulations
  • 2.2 Product Quality
  • 2.3 Cleanroom Classification – ISO 14644 versus GMP Regulation
  • 2.4 Environmental Classification and Monitoring: Occupancy States
  • 2.5 Contamination Control
  • 2.6 Airlocks
  • 3 Specification and Design Qualification Process
  • 3.1 Introduction
  • 3.2 Quality by Design (QbD)
  • 3.3 Concept Design
  • 3.4 User Requirements Specification
  • 3.5 Identification of HVAC CPPs and SPPs
  • 3.6 Basis of Design
  • 3.7 Detailed Design
  • 3.8 Design Review and Risk Assessment
  • 4 System Design Configuration and Components
  • 4.1 Equipment Specification
  • 4.2 Fans
  • 4.3 Motors and Drives
  • 4.4 Airflow Control Devices
  • 4.5 Control Valves
  • 4.6 Coils
  • 4.7 Additional Equipment
  • 4.8 Sound Attenuators
  • 4.9 Air Filters
  • 4.10 HVAC System Configuration
  • 4.11 Pressure Control Strategies
  • 4.12 AFDs and AFIDs
  • 5 Energy and Environment
  • 5.1 Introduction
  • 5.2 Energy Demand Reduction
  • 5.3 Waste Energy Recovery
  • 5.4 Energy-Efficient Design
  • 5.5 Measure/Verify/Optimize
  • 5.6 Refrigerants
  • 5.7 Water Use Reduction
  • 5.8 Lifecycle Cost Considerations
  • 5.9 Building Rating Systems
  • 5.10 Sustainable Design for HVAC Systems
  • 6 Design Considerations
  • 6.1 Introduction
  • 6.2 General Design Considerations
  • 6.3 AHU and Control Considerations
  • 6.4 Airflow Diagrams by Facility Type
  • 6.5 Process Equipment Integration
  • 7 Controls/BMS/EMS
  • 7.1 Introduction
  • 8 Commissioning and Qualification (C&Q)
  • 8.1 Equipment Installation and Startup
  • 8.2 Commissioning and Qualification Planning
  • 8.3 Commissioning and Qualification of HVAC Systems
  • 9 Lifecycle Documents – Documentation Requirements
  • 9.1 Introduction
  • 9.2 Engineering Document Life Cycle
  • 10 Equipment Operation and Maintenance
  • 10.1 Introduction
  • 10.2 Air Handling Units
  • 10.3 Fans
  • 10.4 Heating and Cooling Coils
  • 10.5 Steam Humidifiers
  • 10.6 Desiccant Dehumidifier
  • 10.7 Air Filtration [60]
  • 10.8 Ductwork
  • 10.9 Dampers and Louvers
  • 10.10 Diffusers and Registers
  • 10.11 Ultraviolet Lights
  • 10.12 Fume Exhaust/Extraction Systems
  • 10.13 Building
  • 10.14 Air Balancing
  • 10.15 Spare Parts
  • 11 Appendix 1 – Psychrometrics
  • 11.1 Introduction
  • 11.2 Dry-Bulb Temperature
  • 11.3 Wet-Bulb Temperature
  • 11.4 Dew Point Temperature
  • 11.5 Relative Humidity (Percentage of Saturation)
  • 11.6 Barometric or Total Pressure
  • 11.7 Specific Enthalpy
  • 11.8 Specific Volume
  • 11.9 Humidity Ratio or Specific Humidity
  • 11.10 Vapor Pressure
  • 11.11 Eight Fundamental Vectors
  • 11.12 System Mapping
  • 12 Appendix 2 – System Risk Assessment
  • 12.1 Suggested Approach for the Classification of HVAC/Facility Monitoring Instruments
  • 12.2 SRA for an HVAC System – with the System Boundary including the HVAC System and Final HEPA Filter
  • 12.3 SRA for a Room – with the System Boundary including the Room and Final HEPA Filter
  • 13 Appendix 3 – Design Review and Design Qualification Examples
  • 13.1 Design Review Process
  • 14 Appendix 4 – Sample Test and Balance Report
  • 15 Appendix 5 – Continuous Dilution Modeling for Air Change Rates in Non-Unidirectional Cleanrooms
  • 15.1 Introduction
  • 15.2 Assumptions
  • 15.3 Example Input Data
  • 15.4 Solution
  • 15.5 Conclusion
  • 15.6 Discussion
  • 16 Appendix 6 – References
  • 17 Appendix 7 – Glossary
  • 17.1 Acronyms and Abbreviations
  • 17.2 Definitions
  • Christopher L. Anderson, PE, CPIP (Co-Lead), Hikma, USA
  • Martina Antalova, BSc, MSc, AstraZeneca, United Kingdom
  • Keith M. Beattie, EECO2 (Energy Efficiency Consultancy Ltd.), United Kingdom
  • Yusuf Bhetasiwala, Encon Expertise Pvt. Ltd., India
  • Colin Dennedy, EWA Controls Ireland Ltd., Ireland
  • Douglas E. Ebert, PE, Eli Lilly, USA
  • Michael Egan, Novo Nordisk, Ireland
  • William (Bill) Gantz, BMS, USA
  • Nick Haycocks, USA
  • Kevin LaPlante, PE, CHA Consulting, Inc., USA
  • Martin McKeon, Novo Nordisk, Ireland
  • Mark Muench, AbbVie, USA
  • Ian Noble, EECO2 (Energy Efficiency Consultancy Ltd.), United Kingdom
  • James A. Quinn, PE, CPIP, CRB Group, USA
  • Edward Rosario, BMS, USA
  • Josh L. Williams, PE (Co-Lead), Genesis AEC, USA

Heating, Ventilation, and Air Conditioning (HVAC) systems play a critical role in a pharmaceutical facility’s ability to deliver safe and effective products to patients. The design of these systems requires a combination of Good Manufacturing Practice (GMP) and Good Engineering Practice (GEP) to ensure a safe and healthy workplace, environmental protection, and responsible energy management. HVAC systems can account for a significant portion of a facility’s energy use, making them a key consideration in any company’s sustainability and carbon management policies.

This Guide aims to clarify GMP HVAC issues critical to the Safety, Quality, Identity, Potency, and Purity of pharmaceuticals, biopharmaceuticals, advanced therapy medicinal products, and medical devices from raw materials to finished products. It includes requirements for HVAC control and monitoring, and also covers GEP issues related to sustainability, economics, and environmental health and safety.

The Guide Team seeks to provide the Life Science Community with a unified understanding of critical HVAC issues, guidance on industry best practices, and a consolidated resource for HVAC information previously included various ISPE Baseline® Guides [1].

The need to update this Guide has become increasingly evident since its original publication. Advancements in pharmaceutical product offerings, such as the rapid development of cell and gene therapies. Additionally, technological advancements and evolving project demands, including heightened sustainability requirements and faster construction timelines, have influenced HVAC design and engineering. The updates in this Guide reflect these changes, offering readers a current perspective on these challenges and resources.

This Guide is intended for a global audience, with a particular focus on facilities regulated by the US FDA and the European EMA.

The information provided in this Guide reflects the collective knowledge and experiences of the authors, editors, and reviewers with contributions from members of the ISPE HVAC Communities of Practice (COPs). There is no single approach to satisfy every HVAC situation; therefore, this Guide does not address every HVAC situation. A recurring theme throughout the Guide is the importance of understanding the role of HVAC performance in safeguarding product integrity, personnel, and the environment.

Appendices in this Guide provide industry examples and templates that may be useful to readers.