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Standard Operating System (SOP) for Qualification and Re-Qualification of Heating Ventilation and Air Conditioning (HVAC) system for Clean Room.

Qualification of HVAC System

1.0   PURPOSE

• • The Purpose of this SOP is to lay down the Procedure for qualification/Requalification, of Heating Ventilation and Air Conditioning System (HVAC).

2.0   SCOPE

• • • This SOP is applicable for the qualification/requalification of the Heating Ventilation and Air Conditioning system (HVAC) in the pharmaceutical drug manufacturing plant.

3.0   RESPONSIBILITY – HVAC QUALIFICATION

• • External agency/vendor is responsible for :

• • Provide current SOP for the qualification of HVAC.

• • To perform the qualification as per SOP.

• • To generate data and test certificates.

• • The technical staff of the EM department is responsible for :

• • To intimate concern department prior to carrying out qualification and requalification activity.

• • Monitoring of HVAC qualification /requalification activity with the external parties.

• • To initiate and execute the activity as per SOP.

Related: Protocol for Qualification (Validation) of HVAC System

• • Quality Assurance shall be responsible for:

• • Monitoring of qualification activities as per compliance with SOP.

• • Preparation of protocol and report.

• • Recording, checking the reading for correctness, and compilation of data in the report.

• • Engineering head shall be responsible for :

• • To attach the SOP provided by an external agency with this SOP as reference.

• • Implementation and monitoring compliance of SOP.

• • Organization & coordination with external party for HVAC qualification / Requalification activities.

• • Reviewing and checking the HVAC qualification/requalification work is followed as per the standard operating procedure.

• • Quality Assurance Head shall be responsible for:

• • Verification of HVAC qualification/validation activities as per schedule and monitoring compliance with SOP.

• • Maintaining data of HVAC qualification/requalification activity & to conclude the activity.

4.0   PROCEDURE FOR HVAC QUALIFICATION

• • General Procedure for HVAC Qualification:

• • The approved protocol shall be prepared and followed for the qualification/requalification of HVAC.

• • The location for viable and non-viable particle count with rational shall be attached to the approved protocol.

Related: Laboratory Instrument Qualification SOP

• • Data shall be recorded in the qualification report by a validation team member as per result provided by an external agency and the report shall be approved by department heads.

• • Confirm the devices used by the external agencies are valid calibration period and a calibration certificate is available. Attach the calibration certificate with the qualification report.

• • Attach the data of different tests with the respective qualification report.

• • Air velocity measurement and calculation of Air Changes (ACPH):

• • Instrument

• • Capture hood, Anemometer.

• • Procedure to calculation ACPH in HVAC System:

• • Air velocity measurement shall be performed as per the current version of SOP provided by an approved external agency.

• • Calculate the total velocity and average velocity of each supply grill and then total airflow rate (in case of an anemometer) and total airflow rate in case of a capture hood method.

• • Then calculate the air changes per hour of room.

• • Acceptance criteria:

• • Average velocity and subsequent air changes per hour shall be within design qualifications.

• • A variation in air volume shall not be more than 20% of the design CFM.

• • INTEGRITY TEST OF HEPA FILTER – HVAC QUALIFICATION :

• • Instrument

• • PAO, Smoke generator, Aerosol photometer, duly calibrated with National /international traceability certificate.

• • Procedure:

• • The integrity of the HEPA filter shall be performed as per the current version of SOP provided by an approved external agency.

• • Observe and record the data given by the external agency in the respective qualification report.

• • Acceptance Criteria:

• • During scanning percentage of the PAO penetration shown by the photometer shall be less than 0.01% through the filter media and shall be ‘zero’ through mounting joints.

• • AIR PRESSURE DIFFERENTIAL TEST – HVAC QUALIFICATION :

• • Instrument

• • Magnehelic gauges

• • Procedure:

• • The air handling system and respective dust collection system shall be in operation during this study.

• • To avoid unexpected changes in air pressure and to establish a  baseline, respective control like all doors in the facility must be closed and no personal movement shall be allowed during the test.

• • Observe the differential pressure through the Magnehelic gauge.

• • Differential pressure of the room shall be recorded once in two hours and it shall be continued for 72 hours.

• • Acceptance Criteria:

• • Pressure differentials shall meet the requirement as specified in system specification along with room specifications included in specific HVAC.

• • AIRFLOW PATTERN TEST – HVAC QUALIFICATION :

• • Instrument

• • Fog generator/smoke generator.

• • Procedure:

• • Airflow pattern study shall be done as per the current version of SOP provided by the approved external agency.

• • Carry out the videography for the same test.

• • Attach the videography with the qualification report.

• • Acceptance criteria:

• • Air shall flow from the higher-pressure zone to the lower pressure zone.

• • Flow towards the return air filter or grill.

• • The air shall demonstrate the unidirectional flow.

• • Videography shall be carried out to demonstrate the airflow.

• • TEMPERATURE AND HUMIDITY CONTROL TEST – HVAC QUALIFICATION :

• • Instrument

• • Thermometer & RH sensor, Sling psychomotor, Thermo hygrometer.

• • Procedure:

• • The air handling system shall be in operation for at least 20 minutes prior to performing these tests. 

• • All lights in the critical and controlled areas shall be switched ON during the testing.

• • Confirm that room occupancy is maintained.

• • Observe the temperature and relative humidity through respective Display unit wherever installed, use thermo hygrometer or temperature and RH sensor to check temperature and RH in rooms/area.

• • Temperature and RH in the area to be checked and recorded in dynamic conditions.

• • Measure and record temperature and relative humidity in the rooms as specified in the system specification.

• • Record the data for a period of 72 hours to demonstrate consistency.

• • Acceptance criteria:

• • Temperature and relative humidity shall meet the requirement as specified in the system specification.

• • NON VIABLE AIRBORNE PARTICLE COUNT TEST – HVAC QUALIFICATION :

• • Equipment

• • Airborne particulate counter, duly calibrated with national/international Tractability certificate.

• • Procedure :

• • Non-viable particle count test shall be carried out as per the current version of SOP provided by an approved external agency.

• • Ensure that the particle counter is in calibrated condition.

• • No of Sample location shall be taken from the attached Annexure No 1

• • Start measuring the non-viable particle count as per SOP.

• • Attach the print out original and one photocopy of original with the qualification report and data shall also be recorded and compiled in the report.

• • Acceptance Criteria

• • The cleanroom or clean zone shall meet the acceptance criteria for airborne particulate cleanliness.

• • The average of the particulate count measured at each location shall fall in or below the class limit.

The limit for the different grade is given below:

GRADE	AT REST		IN OPERATION
	Maximum number of permitted particles per cubic meter equal to or above
	0.5 mm	5.0 mm	0.5 mm	5.0 mm
A	3,500	0	3,500	0
B	3,500	0	3,50,000	2,000
C	3,50,000	2,000	35,00,000	20,000
D	35,00,000	20,000	Not defined	Not defined

 

• • DECONTAMINATION /RECOVERY STUDY – HVAC QUALIFICATION :

• • Equipment

• • Airborne particulate counter, duly calibrated with national/international Traceability. Aerosol generator. Water generated aerosol, Sling psycho meter.

• • Procedure:

• • Ensure that the measuring devices are in calibration status with calibration certificate available.

• • The de-contamination study shall be performed as per the current version of SOP provided by an approved external agency.

• • Attach the print outs and certificate provided by the external agency of particle form of cleanroom (initial stage), contaminated area till recovery.

• • Attach the calibration certificate of measuring devices with the qualification report.

• • Acceptance criteria:

• • The recovery time shall not be more than 15 minutes.

• • MICROBIAL MONITORING (PASSIVE AIR SAMPLING): HVAC QUALIFICATION :

• • Equipment

• • Settle plate, media

• • Procedure for Passive Air Sampling

• • Plates shall be exposed on plate exposure stand at the pre-defined locations mentioned in individual format for each stream for not less than 4 hrs.

• • Keep the plates as per sampling location on the upper platform of plate exposure stand, lift and slide open the lid of the media plate and keep on the lower platform of the plate exposure stand.

• • Exposed plates shall be recovered after 4 hrs. of exposure and incubate at specified conditions; SCDA plates: 20-25ºC for 72 hrs. Then 30-35ºC for 48 hrs.

• • Plates shall be observed for any microbial growth after 5 days.

Acceptance criteria:

Area	Limit (CFU/Plate)	Alert Limit	Action Limit
Grade A	<1	<1	<1
Grade B	5	3	4
Grade C	50	30	40
Grade D	100	60	80

• • MICROBIAL MONITORING (ACTIVE AIR SAMPLING) – HVAC QUALIFICATION:

• • Equipment

• • Air sampler, Media Plate, media

• • Procedure :

• • Ensure the battery of the Air Sampler is fully charged. Sterilized sieve shall be used during every monitoring exercise in the case of an aseptic area.

• • Active sites of the sampler shall be sanitized properly with filtered 70% IPA before each sampling.

• • The pre-incubated media plate shall be placed after opening the lid.

• • The perforated lid shall be placed above the plate & the sampler shall be switched on with a fed parameter of 1000 liters of air.

• • 1000 liters of the air shall be withdrawn.

• • The plate shall be removed by taking care; not to touch the surface of the media & re-place the lid of the plate.

• • After each sampling Air Sampler perforated lid shall be moped with 70% IPA.

• • The plate shall be recovered after sampling and incubate at specified conditions; SCDA plates: 20-25ºC for 72 hrs. then 30-35ºC for 48 hrs (Refer SOP no APBC/MB/029).

• • The Sampling shall be done for three consecutive working days.

Acceptance criteria:

Area	Limit (CFU/m3)	Alert Limit	Action Limit
Grade A	<1	<1	<1
Grade B	10	6	8
Grade C	100	60	80
Grade D	200	120	160

• • SOUND LEVEL TEST – HVAC QUALIFICATION :

• • Equipment

• • Sound level meter

• • Procedure

• • All the noise/sound-making system in the proximity of the area shall be switched off.

• • Start the AHU and take the sound level reading for supplied areas.

• • ON the sound level meter, set it at fast response mode and take the reading in the area.

• • Acceptance criteria:

• • The sound level shall be up to 80 DB in the working area.

• • LIGHT INTENSITY TEST – HVAC QUALIFICATION :

• • Instrument

• • Lux meter

• • Procedure

• • All lighting of the area shall be on before starting the study.

• • Then take the intensity of light at working height with a lux meter.

• • Acceptance criteria

• • The light shall not be less than 250 lux

• • The light shall not be less than 400 lux in the inspection

• • QUALIFICATION OF VLAF/RLAF/MOBILE LAF – HVAC QUALIFICATION:

• • Procedure: Following test shall be performed for VLAF/RLAF mobile LAF with same Procedure as defined in HVAC qualification

• • Air velocity measurement

• • Filter integrity test.

• • Air pressure differential test.

• • Airflow pattern test.

• • Non-viable airborne particle count test.

• • Decontamination/Recovery study.

• • Microbial monitoring test.

• • Sound level test.

• • Light intensity test

• • Recovery test

• • Acceptance criteria:

• • Air velocity for ISO class 5 grade A shall be 0.45 meter/second ± 20%, which is equivalent to 90 Feet/minute ± 20%.

• • QUALIFICATION OF DYNAMIC PASS BOX(DPB) – HVAC QUALIFICATION:

• • Procedure: following test shall be performed for DPB with the same Procedure as defined in HVAC qualification.

• • Air velocity measurement.

• • Filter integrity test.

• • Airflow pattern test.

• • Non-viable particle count test.

• • Pressure gradient test.

• • Sound level test.

• • Viable particle count test.

5.0   HVAC REVALIDATION / REQUALIFICATION FREQUENCY:

	TESTS	RE-QUALIFICATION FREQUENCY
1.	Air Velocity Measurement and Calculation of Air Changes	Once every six months. At Every Filter replacement.
2.	Integrity Testing of 0.3 microns, 99.997 % efficiency HEPA Filter	Once in every six months. At Every Filter replacement.
3.	Pressure Differential Test	For 3 days (Every six month)
4.	Temperature and Relative Humidity Test	For 3 days(Every six month)
5.	Air Flow Pattern Test of Area and LAF Units.	Once in a year.
6.	Cleanliness Class Verification Non Viable Particulate count. (At-rest condition)and in operation for ISO class 5, 6, 7, and 8	Once every six months. At Every Filter replacement
7.	Microbial monitoring	Once in every six months for three consecutive days for ISO classes 5, 6, 7, and 8.
8.	Recovery Test	Once in a year.
9.	Sound level test	Yearly
10.	Light intensity test	Once in a year.

 

6.0   REFERENCES – HVAC QUALIFICATION :

• • ISO 14644-1/2/3:   Clean rooms and associated controlled environments.

• • Schedule M: Non-viable particle count

7.0   ABBREVIATIONS AND DEFINITIONS

• • DQ:   Design qualification

• • HVAC:   Heat Ventilation and Air conditioning

• • EM:   Engineering and Maintenance

• • ACPH:   Air Changes per Hour

• • AHU:   Air Handling Unit

• • APU:   Air Preparation Unit

• • LAF:   Laminar Air Flow

• • RLAF:   Reverse Laminar Air Flow

• • PAO:   Poly Alfa Olefin

• • CFM:   Cubic Feet Minute

• • DPB:   Dynamic pass box

• • UV:   Ultraviolet

• • CFM:   Cubic feet meter
  • ISO:   International organization for standardization

• • SCDA:   Soyabean casein agar media 

6.0   ATTACHMENTS – HVAC QUALIFICATION :

Annexure 1:  Sampling Location of Defined Area

Annexure 2:  Sampling Location of Defined Area