Qualification of HVAC systems

Tony Gould

WHO reference
WHO Technical Report Series, No. 937, 2006 - Annex 2
"Supplementary guidelines on good manufacturing practices for heating, ventilation and air-conditioning systems for non-sterile pharmaceutical dosage forms" Comprehensive guide May also be applied to other dosage forms Not intended to be prescriptive risk principles apply

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Objectives
To understand key issues in

commissioning,
qualification and maintenance of HVAC systems
8.

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Documentation requirements to assist in commissioning, qualification and maintenance

Description of design, installation and functions Specifications, requirements Manuals Operating procedures Instructions for performance control, monitoring and records Maintenance instructions and records Training of personnel program and records

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Commissioning
Precursor to qualification
Includes setting up, balancing, adjustment and testing of entire HVAC system to ensure it meets requirements in URS and capacity Acceptable tolerances for parameters Training of personnel

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Commissioning (2)
Records and data maintained include:
Installation records documented evidence of measure capacities of the system Data: Design and measurement for e.g. air flow, system pressures

O&M manuals, schematic drawings, protocols, reports

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Qualification
Validation is an extensive exercise
Qualification of the HVAC system is one component in the overall approach that covers premises, systems/utilities, equipment, processes etc. See also full guidelines on "Validation" in WHO TRS No 937, 2006, Annex 4. Risk based approach for HVAC qualification

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Qualification (2)
Described in a Validation Master Plan (VMP)
VMP to include the nature and extent of tests, and protocols DQ, IQ, OQ, and PQ

Risk analysis to determine critical and non-critical parameters, components, sub-systems and controls

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Qualification (3)
Direct impact components and critical parameters should be included
Non-critical systems and components are subjected to Good Engineering Practices (GEP) Acceptance criteria and limits defined in design stage

Design conditions, normal operating ranges, operating ranges, alert and action limits

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Design conditions and normal operating ranges set to achievable limits OOS results recorded
ACTION LIMIT ALERT LIMIT ALERT LIMIT ACTION LIMIT

Design Condition

Normal Operating Range

Operating Range - Validated Acceptance Criteria

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Qualification examples of aspects to consider
DQ Design of the system, URS
(e.g. components, type of air treatment needed, materials of construction)

IQ Verify installation
E.g. relevant components, ducting, filters, controls, monitors, sensors etc Includes calibration where relevant

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Qualification (7)
Tests performed according to protocols and procedures for the tests Results recorded and presented in report (source data kept)
Traceability e.g. devices and standards used, calibration records; and conditions specified

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Qualification (6)
Conduct of the tests:
Time intervals and procedure to be defined by the manufacturer Influenced by the type of facility and level of protection See also ISO 14644 for methods of testing Re-qualification, and change control

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Qualification (4)
Typical parameters to be included in qualification (based on risk assessment):

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Temperature Relative humidity Supply, return and exhaust air quantities Room air change rates Room pressures (pressure differentials)

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Qualification (5)
Typical parameters to be included in qualification (based on risk assessment) (2):

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Room clean up rate Particulate matter, microbial matter (viable and non-viable) HEPA filter penetration tests Containment system velocity Warning/alarm systems

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Schedule of tests to demonstrate continuing compliance
Test Parameter
Particle count test

Objective
Verifies cleanliness

Maximum time interval

Test procedure* and key aspects

6 months or 12 Particle counter. months depending on Readings and Class positions

12 months 12 months Measure pressure difference Measure supply and return air, calculate air change rate Velocity measurement

Air pressure difference Airflow volume

Absence of crosscontamination Verify air change rates

Airflow velocity

Verify unidirectional 12 months airflow and or containment condition

*Test procedure as per ISO 14644

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Recommended optional strategic tests
Test Parameter
Filter leakage
Containment leakage Recovery (time)

Objective
Verify filter integrity
Verify absence of cross-contamination Verify clean-up time

Maximum time interval

12 months
12 months 12 months

Test procedure* and key aspects

Filter media and filter seal integrity
Airflow direction and pressure differential Time taken maximum 15 minutes

Airflow visualization

Verify required airflow patterns

12 months

Airflow direction, documented evidence

*Test procedure as per ISO 14644

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Cleanroom monitoring program (1)
Routine monitoring program as part of quality assurance Additional monitoring and triggers e.g. Shutdown Replacement of filter elements Maintenance of air handling systems Exceeding of established limits

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Cleanroom monitoring program (2) Particles and Microbiological contaminants

Number of points/locations for monitoring determined, specified, documented in procedure and or protocol Sufficient time for exposure, and suitable sample size Identification and marking of sampling points Definition of transport, storage, and incubation conditions Results to reflect the procedure/protocol followed Define alert and action limits as a function of cleanliness zone/class
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Cleanroom monitoring program (3)
Cleanrooms should be monitored for micro-organisms and particles
air

Example of a sampling point

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Definition of Conditions
as built
air

at rest
air

in operation
air

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Qualification examples of aspects to consider in qualification (OQ, PQ)
Test Uni-directional airflow / LAF 2 Turbulent / mixed airflow 2 Description

Differential pressure on filters

Room differential pressure

Airflow velocity / uniformity Airflow volume / rate Parallelism Air flow pattern

N/A
2, 3 2 2 2

2, 3
Optional 2 N/A 3

1 := As built (ideally used to perform IQ)

2 = At rest (ideally used to perform OQ)

3 = Operational (ideally used to perform PQ)

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Qualification examples of aspects to consider in qualification (OQ, PQ)

Test Recovery time Room classification (airborne particle) Temperature, humidity

Uni-directional airflow / LAF N/A 2 2

Turbulent / mixed airflow

Description 1 := As built (ideally used to perform IQ) 2 = At rest (ideally used to perform OQ) 3 = Operational (ideally used to perform PQ)

2,3

N/A

2,3

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Maintenance
Procedure, program and records for planned, preventative maintenance
E.g. Cleaning of filters, calibration of devices

Appropriate training for personnel

Change of HEPA filters by suitably trained persons

Impact of maintenance on:

Product quality Qualification

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Inspecting the air handling system

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Verification of design documentation, including description of installation and functions specification of the requirements Operating procedures Maintenance instructions Maintenance records Training logs Environmental records Discussion on actions if OOS values On site verification (walking around the site)

PQ Workshop, Abu Dhabi | October 2010

HVAC and Quality Risk Management

What about risk assessment/risk management in HAVC systems?
Recommended risk assessment prior to qualification

Design requirements
Qualification (GMP) vs GEP Ongoing performance Ongoing maintenance
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HVAC and Quality Risk Management

Type of products and materials
Product range Campaign Cleaning

Design, age, changes

Monitoring results (OOLs)

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Conclusion
Air handling systems:

Play a major role in the quality of pharmaceuticals Should be designed properly, by professionals Should be treated as a critical system

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