HVAC Qualification and Validation: Key Terms

In short: This glossary explains common HVAC design, qualification and validation terms for non-sterile pharmaceutical facilities. The definitions are concise paraphrases of WHO guidance; terminology can vary in other settings, and separate requirements may apply to sterile or hazardous products.

Scope

The terms below follow the context of the World Health Organization’s guidance for heating, ventilation and air-conditioning systems used mainly in facilities making non-sterile dosage forms. WHO notes that the same terms may have different meanings elsewhere and that other product types can have additional requirements. (WHO Technical Report Series No. 1010, Annex 8 (2018))

HVAC and room conditions

• Air-handling unit (AHU): Equipment that conditions air and supplies the airflow needed within a facility. (WHO TRS No. 1010, Annex 8 (2018))
• Airlock: An enclosed space with two or more doors between rooms. Its arrangement helps control airflow when people or materials pass between areas; personnel airlocks (PALs) and material airlocks (MALs) serve different traffic. (WHO TRS No. 1010, Annex 8 (2018))
• As-built: State after installation and services are complete and working, before production equipment, materials or staff are present. (WHO TRS No. 1010, Annex 8 (2018))
• At-rest: State with equipment installed and operating as agreed, while personnel are absent. (WHO TRS No. 1010, Annex 8 (2018))
• Central air-conditioning unit: See air-handling unit; WHO’s glossary directs readers to that term. (WHO TRS No. 1010, Annex 8 (2018))
• Clean area (cleanroom): A room or zone with defined controls for particulate and microbial contamination, designed and used to reduce contamination entering, arising within or remaining in the area. (WHO TRS No. 1010, Annex 8 (2018))
• Infiltration: Air entering a controlled area from an external zone. The term alone does not specify the amount or cleanliness of that air. (WHO TRS No. 1010, Annex 8 (2018))
• Pressure cascade: Air movement from an area maintained at higher pressure toward an area at lower pressure. The actual pressure relationships are design-specific; this definition supplies no setpoint. (WHO TRS No. 1010, Annex 8 (2018))
• Relative humidity (RH): The actual water-vapour pressure divided by the saturated water-vapour pressure at the same temperature, expressed as a percentage. (WHO TRS No. 1010, Annex 8 (2018))
• Turbulent airflow: Air supplied into a controlled space that mixes with room air through induction; it is also called non-unidirectional airflow in the WHO glossary. (WHO TRS No. 1010, Annex 8 (2018))
• Unidirectional airflow (UDAF): Air moving across a clean zone with a steady velocity and approximately parallel streamlines. WHO distinguishes this from turbulent airflow and notes that its guideline uses “unidirectional airflow” rather than “laminar flow.” (WHO TRS No. 1010, Annex 8 (2018))

Quality and engineering terms

• Acceptance criteria: Numerical limits, ranges or other suitable measures used to decide whether test results are acceptable. Criteria should be defined for the specific test; this glossary sets no values. (WHO TRS No. 1010, Annex 8 (2018))
• Action limit: A boundary reached when acceptance criteria for a critical parameter are exceeded, requiring the specified action and investigation. (WHO TRS No. 1010, Annex 8 (2018))
• Alert limit: A boundary reached when a critical parameter moves outside its normal operating range, signalling that corrective measures may be needed to prevent an action-limit excursion. (WHO TRS No. 1010, Annex 8 (2018))
• Change control: A formal review of proposed or actual changes by qualified representatives of relevant disciplines to assess their effect on validated status and any action needed to maintain it. (WHO TRS No. 1010, Annex 8 (2018))
• Commissioning: Documented work that checks installation against specifications, places equipment or systems into service and confirms their operation. WHO describes commissioning as occurring at different stages of construction and before validation. (WHO TRS No. 1010, Annex 8 (2018))
• Containment: A process or device intended to keep product, dust or contaminants within one zone and prevent their escape into another. (WHO TRS No. 1010, Annex 8 (2018))
• Contamination: Unwanted chemical or microbial impurities, or foreign matter, introduced into or onto material or product during activities such as production, sampling, packaging, storage or transport. (WHO TRS No. 1010, Annex 8 (2018))
• Critical parameter or component: A process parameter, such as temperature or RH, that affects product quality, or a component that may directly affect product quality. (WHO TRS No. 1010, Annex 8 (2018))
• Cross-contamination: Contamination of a starting material, intermediate or finished product by another starting material or product during production. (WHO TRS No. 1010, Annex 8 (2018))
• Design condition: The specified range or accuracy for a controlled variable that the designer uses to set an engineered system’s performance requirements. (WHO TRS No. 1010, Annex 8 (2018))
• Design qualification (DQ): A documented review of planning documents and technical specifications to check that the proposed design fits the process, manufacturing needs, GMP and applicable regulatory requirements. (WHO TRS No. 1010, Annex 8 (2018))
• Direct-impact system: A system expected to affect product quality directly. WHO’s glossary says such systems are designed and commissioned using good engineering practice and are also subject to qualification practices. (WHO TRS No. 1010, Annex 8 (2018))
• Facility: The built environment containing the clean-area installation, related controlled environments and supporting infrastructure. (WHO TRS No. 1010, Annex 8 (2018))
• Good engineering practice (GEP): Established engineering methods and standards applied through a project lifecycle to produce suitable, cost-effective solutions. (WHO TRS No. 1010, Annex 8 (2018))
• Indirect-impact system: A system not expected to affect product quality directly but that may support a direct-impact system. WHO describes its design and commissioning as following GEP. (WHO TRS No. 1010, Annex 8 (2018))
• No-impact system: A system assessed as having no direct or indirect effect on product quality. WHO describes its design and commissioning as following GEP. (WHO TRS No. 1010, Annex 8 (2018))
• Noncritical parameter or component: A parameter or component whose operation, contact, data control, alarm or failure has an indirect or no impact on product quality. (WHO TRS No. 1010, Annex 8 (2018))
• Normal operating range: The range of values selected by the manufacturer for normal operation of a parameter; WHO places this range within the operating range. (WHO TRS No. 1010, Annex 8 (2018))
• Operating limits: Minimum or maximum values intended to ensure product and safety requirements are met. The actual values depend on the qualified system and its intended use. (WHO TRS No. 1010, Annex 8 (2018))
• Operating range: The range of validated critical-parameter values within which acceptable products can be manufactured. (WHO TRS No. 1010, Annex 8 (2018))
• Operational condition: The state used for room-classification testing when the normal production process is running, equipment is operating and the usual staff are present. (WHO TRS No. 1010, Annex 8 (2018))
• Oral solid dosage form: An orally administered solid medicine, such as a tablet, capsule or powder. (WHO TRS No. 1010, Annex 8 (2018))
• Point extraction: Local air extraction positioned to capture dust effectively near where it is generated. (WHO TRS No. 1010, Annex 8 (2018))

Qualification and validation terms

• Installation qualification (IQ): Documented evidence that premises, HVAC equipment, supporting utilities and equipment were built and installed against the approved design specification. (WHO TRS No. 1010, Annex 8 (2018))
• Operational qualification (OQ): Documented evidence that equipment works to its design specifications in its normal operating range and performs as intended across anticipated operating ranges. (WHO TRS No. 1010, Annex 8 (2018))
• Performance qualification (PQ): Documented evidence that the process, or the system-related process as a whole, performs as intended across anticipated operating ranges. (WHO TRS No. 1010, Annex 8 (2018))
• Qualification: Planning, performing and recording tests on equipment or a system that forms part of a validated process to show that it performs as intended. (WHO TRS No. 1010, Annex 8 (2018))
• Standard operating procedure (SOP): An authorised written instruction for an operation. A general SOP may cover activities such as equipment operation, maintenance, cleaning, validation or environmental control and may support product-specific master or batch documentation. (WHO TRS No. 1010, Annex 8 (2018))
• Validation: Documented evidence that a procedure, process, equipment, material, activity or system consistently leads to its intended result. (WHO TRS No. 1010, Annex 8 (2018))
• Validation master plan (VMP): A high-level plan that sets the overall approach to validation for a project and guides technical and resource planning. WHO notes that it may also be called a master qualification plan. (WHO TRS No. 1010, Annex 8 (2018))

Frequently asked questions

Are these definitions universal?

No. WHO states that its glossary definitions apply to terms in that guideline and may differ in other contexts. Use the definitions and controlled terminology established for the applicable project and quality system. (WHO TRS No. 1010, Annex 8 (2018))

How do OQ and PQ differ in this glossary?

OQ records evidence about equipment operation against design specifications and anticipated operating ranges. PQ records evidence that the process or system-related process performs as intended across those ranges. (WHO TRS No. 1010, Annex 8 (2018))

Can this non-sterile HVAC glossary be used for sterile facilities?

Use it only as a terminology aid. WHO TRS 1010 Annex 8 focuses mainly on non-sterile dosage forms and points out that sterile products and other product types may have additional, specific requirements. (WHO TRS No. 1010, Annex 8 (2018))

See also

• HVAC system qualification protocol
• Qualification stages for equipment, facilities and utilities
• Installation qualification protocol and report

References

• World Health Organization. WHO Expert Committee on Specifications for Pharmaceutical Preparations: Fifty-second report. WHO Technical Report Series No. 1010, Annex 8, “Guidelines on heating, ventilation and air-conditioning systems for non-sterile pharmaceutical products” (2018). Official WHO PDF.