Supplementary Training Modules on Good Manufacturing Practice Heating

Supplementary Training Modules on Good Manufacturing Practice Heating, Ventilation and Air. Conditioning (HVAC) WHO Technical Report Series, No. 961, 2011. Annex 5 Part 4: Commissioning, qualification and maintenance Section 8 HVAC | Slide 1 of 27 2013

HVAC Objectives l To understand key issues in commissioning, qualification and maintenance of HVAC systems 8. HVAC | Slide 2 of 27 2013

HVAC Documentation requirements to assist in commissioning, qualification and maintenance l l l l HVAC | 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 ― programme and records Slide 3 of 27 2013

HVAC Commissioning (is integrated in qualification) and includes: l Setting up, balancing, adjustment and testing of entire HVAC system l It helps to ensure it meets URS and capacity l Acceptable tolerances for parameters set before commissioning l Precursor to qualification 8. 1. 1, 8. 1. 4, 8. 1. 6 HVAC | Slide 4 of 27 2013

HVAC Commissioning (2) Records and data include: l Installation records – documented evidence of measured capacities of the system l Acceptance criteria set for system parameters l Training of personnel (e. g. operation and maintenance) – O&M manuals, schematic drawings, protocols, reports 8. 1. 2, 8. 1. 3, 8. 1. 5 HVAC | Slide 5 of 27 2013

HVAC Qualification l Validation is an extensive exercise l Qualification of the HVAC system is one component in the overall approach that covers premises, systems/utilities, equipment, processes, etc. l Risk-based approach for HVAC qualification l See also full guidelines on "Validation" in WHO TRS No 937, 2005, Annex 4. 8. 2. 1 HVAC | Slide 6 of 27 2013

HVAC Qualification l Described in a Validation Master Plan (VMP) l Reflects the nature and extent, test procedures, and protocols l DQ, IQ, OQ, and PQ l Risk analysis to determine critical and non-critical parameters, components, subsystems and controls 8. 2. 2 - 8. 2. 5 HVAC | Slide 7 of 27 2013

HVAC Qualification l Direct impact components and critical parameters should be included l Non-critical systems and components are subjected to Good Engineering Practices (GEP) l Acceptance criteria and limits defined in design stage l Design conditions, normal operating ranges, alert and action limits 8. 2. 6 - 8. 2. 11 HVAC | Slide 8 of 27 2013

HVAC l Design conditions and normal operating ranges set to achievable limits l OOL results recorded and investigated 8. 2. 10 – 8. 2. 12 HVAC | Slide 9 of 27 2013

HVAC Qualification – examples of aspects to consider l DQ – Design of the system, URS – (e. g. components, type of air treatment needed, materials of construction) l IQ – Verify installation – e. g. relevant components, ducting, filters, controls, monitors, sensors, etc. – includes calibration where relevant HVAC | Slide 10 of 27 2013

HVAC Qualification Typical parameters to be included in qualification (based on risk assessment): l Temperature l Relative humidity l Supply, return and exhaust air quantities l Room air change rates l Room pressures (pressure differentials) 8. 2. 13 HVAC | Slide 11 of 27 2013

HVAC Qualification Typical parameters to be included in qualification (based on risk assessment) (2): l Room air flow patterns l Room clean-up rate l Particulate matter, microbial matter (viable and non-viable) l HEPA filter penetration tests l Containment system velocity l Warning/alarm systems HVAC | Slide 12 of 27 2013 8. 2. 13.

HVAC Conduct of the tests: l Time intervals and procedure to be defined by the manufacturer - based on risk assessment (influenced by the type of facility and level of protection) l See also ISO 14644 for procedures l Requalification, and change control l Documents: system airflow schematics, room pressure cascade drawings, zone concept drawings, air-handling system allocation drawings, particle count mapping drawings 8. 2. 14 – 8. 2. 18 HVAC | Slide 13 of 27 2013

HVAC Qualification l Tests performed according to protocols and procedures for the tests l Results recorded and presented in report (source data kept) l Traceability, e. g. devices and standards used, calibration records; and conditions specified HVAC | Slide 14 of 27 2013

HVAC Schedule of tests to demonstrate continuing compliance Test Parameter Objective Considerations Test procedure* and key aspects Particle count test Verifies cleanliness Number of readings and positions Particle counter. Readings and positions Air pressure difference Absence of crosscontamination Continuous. Defined limits Measure pressure difference Airflow volume Verify air change rates See ISO 14644 Measure supply and return air, calculate air change rate Airflow velocity Verify unidirectional Velocity and airflow and or containment condition *Test procedure as per ISO 14644 HVAC | Slide 15 of 27 2013 Velocity measurement 8. Table 3

HVAC Recommended optional strategic tests Test Parameter Objective Considerations Test procedure* and key aspects Filter leakage Verify filter integrity For HEPA filters Filter media and filter seal integrity Containment leakage Verify absence of cross-contamination Containment, smoke and air pressure Airflow direction and pressure differential Recovery (time) Verify clean-up time Certain classes Time taken maximum 20 minutes Airflow visualization Verify required airflow Clean to dirty area, patterns uniformly. Video *Test procedure as per ISO 14644 HVAC | Slide 16 of 27 2013 Airflow direction, documented evidence 8. Table 3

HVAC Cleanroom monitoring program (1) l Routine monitoring program as part of quality assurance l Additional monitoring and triggers, e. g. 1. Shutdown 2. Replacement of filter elements 3. Maintenance of air-handling systems 4. Exceeding of established limits HVAC | Slide 17 of 27 2013

HVAC Cleanroom monitoring programme (2) Particles and Microbiological contaminants l l l HVAC 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 See also ISO 14644 zone/class | Slide 18 of 27 2013

HVAC Cleanrooms should be monitored for microorganisms and particles Example of a sampling points HVAC | Slide 19 of 27 2013

HVAC Qualification – examples of aspects to consider in qualification (OQ, PQ) Uni-directional airflow / LAF Test Turbulent / mixed airflow Differential pressure on filters 2 2 Room differential pressure N/A 2, 3 Airflow velocity / uniformity 2, 3 Optional Description 1 : = As built (ideally used to perform IQ) 2 = At rest (ideally used to perform OQ) 3 = Operational (ideally used to perform PQ) Airflow volume / rate 2 2 Parallelism 2 N/A Airflow pattern 2 3 HVAC | Slide 20 of 27 2013

HVAC Maintenance l Procedure, programme and records for planned, preventative maintenance – e. g. cleaning of filters, calibration of devices l Keep O&M manuals, drawings etc. l Appropriate training for personnel l Change of HEPA filters by suitably trained persons l Impact of maintenance on: – Product quality and Qualification HVAC | Slide 21 of 27 2013 8. 3. 1 – 8. 3. 6

HVAC Premises may influence HVAC design / performance. Therefore consider: l Adequate airlocks, change rooms, passages l Required pressure cascades l Detailed diagrams available with pressure cascades, air flow directions and flow routes for personnel and materials should be prepared and maintained; l Change room classification HVAC | Slide 22 of 27 2013 9

HVAC Inspecting the air-handling system l Verification of design documentation, including ä description of installation and functions ä specification of the requirements l Operating procedures l Maintenance instructions l Maintenance records l Training logs l Environmental records l Discussion on actions if OOS values l On site verification (walking around the site) HVAC | Slide 23 of 27 2013

HVAC Take home message. What is essential? l Appropriate design of AHUs and HVAC system l Correct components, and MOC l Ensuring appropriate cleanliness of air, environmental conditions (e. g. temperature and RH), and area classification to prevent contamination and cross-contamination l Qualification data to support claims l Regular calibration, maintenance and cleaning HVAC | Slide 24 of 27 2013

HVAC 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 l l l HVAC | Slide 25 of 27 2013

HVAC Group Session HVAC | Slide 26 of 27 2013

HVAC Group Session – modified layout MAL = Material Air Lock PAL = Personnel Air Lock HVAC | Slide 27 of 27 2013