HVAC System Qualification Protocol (Validation)

In short: HVAC qualification should show, with documented evidence, that the installed system and the controlled rooms meet their approved design and intended use. The tests and acceptance criteria depend on the system, room classification, product risks, and applicable requirements; this outline is a template for a site to adapt and approve.

Purpose and scope

Use this outline to plan initial qualification or a documented requalification of an air handling and cleanroom system. Define the system boundary, rooms and processes covered, applicable room states, responsibilities, instruments, approved specifications, sampling plan, deviations, and report approvals before execution.

For sterile manufacturing, WHO GMP for sterile pharmaceutical products (TRS 1044, Annex 2, 2022) describes cleanroom and clean-air equipment qualification and distinguishes qualification, including classification, from routine environmental monitoring. For non-sterile products, consult the scope and system guidance in WHO TRS 1010, Annex 8 (2018). Select requirements that apply to the actual facility and product; this page is not a substitute for either document or a site contamination control strategy.

Related lifecycle documents: Installation Qualification (IQ), Operational Qualification (OQ), and Performance Qualification (PQ).

Responsibilities and prerequisites

Assign preparation, technical review, execution, microbiological testing where applicable, deviation investigation, and final approval to qualified site functions. External test providers may execute work under an approved agreement and procedure, but the site should review the method, raw data, instrument status, and conclusions.

Before testing, approve the protocol and room/system list; confirm that construction, commissioning, maintenance, cleaning, and relevant utilities are complete; identify the intended operating states; and verify that instruments are suitable and within calibration. Record personnel, equipment identifiers, calibration traceability, test methods, and any conditions that could affect results. Site prerequisites and sequencing are example in-house criterion and require local approval.

System description and approved criteria

Document each AHU and the rooms it serves, including room identifiers and use, design airflow, filtration arrangement, pressure relationships, control and alarm points, applicable cleanliness classification, and approved temperature or humidity ranges where relevant. Include drawings or a system schematic and identify critical parameters and their rationale.

The approved design specification and risk assessment should define acceptance criteria before execution. Do not copy generic air-change rates, pressure differentials, temperature ranges, humidity limits, or microbial limits into a protocol without confirming they apply to the specific rooms and processes. These values are example in-house criterion when established by the site.

Qualification and requalification tests

Select tests based on design, intended use, and risk. WHO TRS 1044, Annex 2, section 4.25 (2022) lists, where relevant, installed-filter leakage/integrity, airflow volume and velocity, pressure differential, airflow direction and visualisation, airborne and surface microbial contamination, temperature, relative humidity, recovery, and containment leakage. Section 4.26 states that cleanroom classification is part of qualification and should be distinguished from routine operational environmental monitoring.

For each selected test, record the approved method and revision, room state, locations, equipment, raw data, calculations, criteria and rationale, results, and any deviations. The qualification plan may include:

• Filter installation and integrity/leakage testing using an approved method.
• Supply and return airflow measurements, air volume, and any derived air-change calculation required by the design.
• Room pressure differentials and, where needed, airflow direction or visualisation across boundaries and within critical zones.
• Temperature and relative humidity measurements where controlled for the intended use.
• Particle classification in defined room states using the applicable classification method and approved sampling plan.
• Recovery and containment testing where relevant to the design and risk.
• Viable airborne or surface monitoring when specified by the applicable programme. Keep qualification evidence distinct from routine monitoring records.

For ISO cleanroom classification, WHO TRS 1044, Annex 2, section 4.28 (2022) points to ISO 14644 Part 1 for minimum sampling locations and positioning. WHO TRS 1010, Annex 8 (2018) states that its ISO 14644 references imply the latest revision and all separate parts. ISO 14644-1:2015 is retained here as a user-specified reference; the ISO catalogue (iso.org) lists the 2015 second edition as the published edition of Part 1, which replaced the 1999 edition, and ISO 14644-2:2015 covers monitoring to provide evidence of continued compliance. Because the WHO texts refer to the ISO 14644 series and its latest revision rather than an edition year, check on the day of use that the edition named in your protocol is the current one in your controlled standards library, and take the number of sampling locations and the sampling plan from that edition of Part 1 rather than from this article.

Source-template values requiring verification

The following values appeared in the imported template. They are not presented here as regulatory requirements. Retain them in a site protocol only if the current approved design, risk assessment, applicable standard, and documented rationale support them; otherwise replace them with approved site criteria. Each is an example in-house criterion pending that review.

• The template proposes six-month intervals for airflow, filter integrity, pressure, temperature/humidity, classification, and microbial monitoring; annual airflow-pattern and recovery testing; and additional tests after filter replacement. These frequencies are not universal requirements. Set the periodicity of each test and the triggers for repeat testing (for example filter replacement or a change to the HVAC system) on a documented, risk-based basis in the approved protocol or contamination control strategy.
• It proposes airflow volume within ±20% of design, HEPA leakage not more than 0.01% and zero leakage at joints, and an upstream aerosol concentration of 100%.
• It proposes differential-pressure and temperature/RH recording every two hours for 72 hours, or data-logger recording every five minutes for 72 hours, and a 15-minute HVAC run-up.
• It proposes settle-plate exposure for at least four hours, staged incubation at 20–25 °C for 72 hours and 30–35 °C for 48 hours, 1,000 L active-air samples, and six-month viable monitoring over three consecutive days.
• It proposes recovery readings at two-minute intervals, viable checks at 15-minute increments up to one hour, and a recovery limit of 15 minutes.
• Its particle-count table is incomplete and its viable monitoring tables contain grade-specific limits and alert/action levels.

Deviations, reporting, and approval

Document each deviation with the observed condition, impact assessment, investigation, corrective action, owner, and disposition. Assess whether results remain valid and whether additional testing is needed. The final report should identify the approved protocol and revisions, summarize execution and results against each criterion, include raw data and attachments, list deviations and their disposition, state limitations, and provide a clear conclusion. Route the report for the site’s required technical and quality approvals before relying on qualification status.

Requalification triggers and periodicity should be defined in the site quality system using system performance, product and process risk, changes, maintenance, and applicable requirements. Changes to rooms, equipment, controls, or operating conditions should be assessed for impact and documented; a fixed interval alone does not establish continued control.

Frequently asked questions

Is HVAC requalification always required every six months?

The cited WHO guidance does not establish that universal interval. Set and justify the frequency in the approved site programme based on system and product risk, performance history, change control, and applicable requirements.

Are cleanroom classification and environmental monitoring the same activity?

No. WHO TRS 1044, Annex 2, sections 4.24–4.26 (2022) treats classification as part of qualification and says qualification should be clearly differentiated from operational environmental monitoring.

Which tests belong in an HVAC qualification protocol?

Select tests that are relevant to the installation and intended operation. WHO TRS 1044, Annex 2, section 4.25 (2022) gives examples including filter integrity, airflow, pressure, airflow visualisation, temperature, humidity, recovery, microbial contamination, and containment leakage.

References

• World Health Organization. WHO good manufacturing practices for sterile pharmaceutical products. WHO Technical Report Series No. 1044, Annex 2, 2022, especially sections 4.23–4.29. Official WHO document.
• World Health Organization. Guidelines on heating, ventilation and air-conditioning systems for non-sterile pharmaceutical products. WHO Technical Report Series No. 1010, Annex 8, 2018. Official WHO document.
• International Organization for Standardization. ISO 14644-1:2015, Cleanrooms and associated controlled environments — Part 1: Classification of air cleanliness by particle concentration. Current published edition as listed on the ISO catalogue (iso.org); check the edition in force in your controlled standards library before use. Related: ISO 14644-2:2015, Part 2: Monitoring to provide evidence of cleanroom performance related to air cleanliness by particle concentration.

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