HVAC System Qualification Protocol (Validation) - Pharmaceutical Guidelines

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HVAC System Qualification Protocol (Validation) - Pharmaceutical Guidelines
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HVAC System Qualification Protocol (Validation)
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Protocol for Qualification and Re-Qualification or Validation of Heating Ventilation and
Air Conditioning (HVAC) system for Clean Room.
HVAC System Qualification Protocol (Validation)
Table of Content – HVAC System Qualification Protocol
S.No.
Table of Contents
1.0
Protocol Approval
2.0
History Sheet
3.0
Objective
4.0
Scope
5.0
Responsibilities
6.0
Equipment Description
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6.1
System Specification
7.0
Requalification tests
7.1
Air velocity/airflow measurement and calculation of air changes:
7.2
Integrity Test Of HEPA Filter
7.3
Differential Pressure Measurement
7.4
Temperature And Humidity Control Test
7.5
Air Flow Pattern Test
7.6
Non- Viable Particle Count
7.7
Recovery Study
7.8
Passive Air Sampling
7.9
Active Air Sampling
7.10
Re-qualification Criteria
8.0
Deficiency and corrective action report
9.0
Requalification summary report
10.0
Approval of requalification report
11.0
List of forms/Annexure
12.0
References
13.0
Abbreviations
1.0 Approval Sheet of Protocol:
Prepared by:
Department
Name
Designation
Signature
Date
Quality Assurance
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Related: SOP for Qualification of HVAC System
Reviewed by:
Department
Name
Designation
Signature
Date
Engineering
Concern
Quality Control /Microbiology
Quality Assurance
Approved by:
Department
Name
Designation
Signature
Date
Head Quality Assurance
2.0
History Sheet :
Rev. No.
Effective date
Nature of change/ reason for revision
Approved by QA
3.0 Objective –HVAC System Qualification Protocol :
The objective of this protocol is to provide an outline for the qualification of the
HVAC system and to establish documentary evidence to demonstrate that the
Air Handling Units (AHU’s) are qualified to perform well within the
predetermined acceptance criteria of performance as per guideline outlined in
this protocol.
4.0 Scope –HVAC System Qualification Protocol :
The scope of this protocol is applicable for the requalification of Air handling
unit (AHU) system,
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5.0 Responsibilities –HVAC System Qualification Protocol :
Department
Responsibilities
Responsible to ensure the overall re-qualification of the HVAC
Quality
Assurance
system. Preparation, review, and approval of protocol and
:
report. Handling of deviations. To impart training of the team
involved in HVAC requalification. Compile and review of
reports.
User
department
:
To provide execution support during requalification. To review
the protocol and report.
To review the protocol and report. To perform and provide
Quality Control /
Microbiology
:
environmental monitoring reports of the manufacturing area
for the microbial load as per schedule to record all the
observations.
Engineering
:
External agency
:
To review the protocol and report. To provide execution
support and ensure proper operation of the system.
Execution of tests as per protocol. Collection of data and
preparation of final test certificates.
Execution Team –HVAC System Qualification Protocol :
Execution team shall comprise of the representative from the following functions:
Department
Name
Designation
Signature
Date
External agency
Engineering
Concern
Microbiology
Quality Assurance
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Pre Requisite:
Daily cleaning of the area.
Availability of area
Required materials and instruments are available.
Calibration and Preventive Maintenance of equipment.
The gowning procedure of plant personnel and external agency shall be done
as per the respective SOP for Entry and exit to the Aseptic area.
Personnel qualification of the external party shall be done as per the respective
SOP “Qualification of personnel for working in the aseptic area”.
Personnel hygiene of personnel.
Fogging cleaning shall be done prior to performing the requalification activity.
External party agreement, respective valid SOP, and traceability certificates of
instruments. Please elaborate. These are the bullet points.
Training records of the external parties.
Calibration of instruments or equipment used for testing like Anemometer,
Aerosol photometer, Non-viable particle counter, etc.
6.0 Equipment Description / Specification:
System Specification:
Details of AHU’s are as follow:-
Sr. No.
AHU
NO.
Area
(In
m 2)
Room
Rooms
ID
Catered
Grade
No.
No. of
/ ISO
of
Return
Grade
HEPA
Risers
Capacity
ACP
CFM
(NLT
Design
Parameters
7.0 Requalification Tests:Detailed below-mentioned parameters shall be performed in the requalification of
AHU’s.
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Sr.
No.
01
TESTS
RE-QUALIFICATION FREQUENCY
Air Velocity Measurement and
Once every six months. At Every Filter
Calculation of Air Changes
replacement.
02
Integrity Testing y HEPA Filter
03
Pressure Differential Test
04
05
Once every six months. At Every Filter
replacement.
For 3 days (Every six month) Continuous
monitoring
Temperature and Relative
For 3 days(Every six month) Continuous
Humidity Test
monitoring
Air Flow Pattern Test
Once in a year.
Cleanliness Class Verification Non
06
Once in every six months for three
Viable Particulate count. At-rest
consecutive days at a defined location. At
condition and in operation for
Every Filter replacement
ISO class 5, 6, 7, and 8
Once in every six months for three
07
consecutive days for ISO classes 5, 6, 7,
Microbial monitoring
and 8 at defined location. Continuous
monitoring in critical / core areas.
08
Recovery Test
Once in a year.
Air velocity, the Air volume, and Air Changes Per Hour (ACPH)
measurement:
The test shall be performed by the external party as per their respective SOP,
reviewed, and accepted by the plant. Refer the Attachment for SOP
Reference SOP’s and results should be enclosed with the report.
The formula to calculate the ACPH is as followsAir changes per hour (ACPH) =
Total CFM X
60
Room volume
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Apparatus Required:- Anemometer, Capture hood. A calibrated instrument
should be used for measurement.
Acceptance criteria:- Air velocity and Air Change Per Hour (ACPH) shall be
within the design specification. A variation in air volume shall not be ±20% from
the design CFM
Result:- Refer enclosed file named FORM-A of respective AHU requalification
report. Traceability certificates should be enclosed along with the requalification
report.
Integrity test Of HEPA Filter:
The test shall be performed by the external parties as per their respective SOP,
reviewed, and accepted by the plant. Refer the Attachment for SOP Reference
SOP’s and results should be enclosed with the report.
Apparatus Required:- Aerosol Photometer. A Calibrated instrument should be
used for measurement.
Acceptance Criteria:-The leakage rate is NMT 0.01%. Ensure zero (0 %)
leakage at joints.
Result:Refer enclosed file named FORM-B of respective AHU requalification report.
Traceability certificates to be enclosed along with the report.
If any leakage is detected in the joints of filter it shall be repaired with the foodgrade silicon and leak site shall be rescanned.
Upstream concentration should be 100%.
Differential Pressure Measurement:Differential pressure of the room shall be recorded using the calibrated
instrument, once in two hours and it shall be continued for 72 hours.
Acceptance criteria:- Pressure differentials should meet the requirement as
specified in the system specifications.
Result:- Record the differential pressure in the FORM-C of the requalification
report.
Temperature And Humidity Control Test:The air handling system shall be in operation for at least 15 minutes prior to
performing this activity.
In the case of manual recording, record the data for 72 hours at an interval of 2
hours frequency.
If data loggers are using, record the date for a period of 72 hrs at 5 minutes
interval.
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All lights in the critical and controlled areas should be ON during the testing.
Observe the temperature and relative humidity use calibrated thermo
hygrometer.
Temperature and RH in the area shall be checked and recorded in dynamic
conditions.
Acceptance criteria:Temperature and relative humidity should meet the requirement as specified in
the system specifications. Refer point No. 6.1 system specification for
predetermined acceptance criteria.
Result:Measure and record temperature and RH using sling psycho meter, thermo
hygrometer, or data logger. Record the observations on FORM-D of the AHU
requalification report.
Air Flow Pattern Test:The test shall be performed by the external party as per their respective SOP,
reviewed, and accepted by the plant.
The test shall be performed in Rest as well as Dynamic condition.
Reference SOP’s and results should be enclosed with the report.
Video recording shall be performed for the airflow pattern test.
Enclose the unedited CD of flow pattern along with the re-qualification report.
Apparatus required:Fog generator, water generated fog, and digital video camera.
Acceptance criteria:Air should flow from the higher-pressure zone to the lower pressure zone in the
room to room.
The air should flow unidirectionally from supply towards the return air filter or
grill within the room.
In videography show the exact area name and supply return grill’s ID.
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Videography shall be carried out to demonstrate the airflow pattern.
Result recording:Observe the airflow pattern as per the procedure mentioned above and record
in the FORM-E in the requalification report.
Non-Viable Particle Count (NVPC) – HVAC Qualification Protocol:The test shall be performed by the external party as per their respective SOP,
reviewed, and accepted by the plant.
Reference SOP’s and results should be enclosed with the report.
The test shall be performed at rest and in operation both the condition.
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.
The no. of sample locations shall be calculated according to the belowmentioned table.
Refer annexure No.: ­_________ for location details of area.
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Apparatus Required: Particulate Counter. A calibrated instrument should be
used for measurement.
Acceptance Criteria:- The average particle concentration at each of the particle
measuring locations should fall the below-mentioned class limit.
Class /Grade Size
AT
IN
REST
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/5
3,500
0
3,500
0
B/6
3,500
0
3,50,000
2,000
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1. Result Recording
2. Data shall be collected in the datasheet.
3. Measure and Record the particulate count at various locations as the attached
sheet.
4. The recording shall be done in FORM-F of the re-qualification report
5. Attach the calibration certificate of Particle Counter.
6. Recovery Study:
7. The test shall be performed by the external parties as per their respective SOP.
8. Reference SOP’s and results should be enclosed with the report.
9. Attach the print outs, original and photocopy provided by the external agency
of particle form of clean room from the initial stage of contaminated area till
recovery.
10. Ensure that the master instrument is calibrated and enclose the calibration
certificate along with the re-qualification report.
11. Recovery study should be performed for Temperature, RH, and Differential
pressure.
12. Record the readings and evaluate them with the design specification.
13. Recording frequency should be 02-minute time interval by manual entries or
using data loggers.
14. Recovery test for viable counts should be checked on 15 minutes time interval
15 minutes, 30 minutes, 45 minutes, and 1 hour
15. Apparatus: Particulate Counter, Hygrometer, differential pressure gauge.
16. Acceptance criteria: The recovery time should not be more than 15 minutes
excluding viable count.
17. Result Recording: Record the observations in FORM-G of the re-qualification
report.
18. Microbial Monitoring:
19. To determine the viable particle count test by exposing the settle plate and air
sampling in the defined areas.
20. The procedure shall be followed as per the respective SOP.
21. PASSIVE AIR SAMPLING:22. Procedure:
23. 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.
24. Keep the plates 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
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exposure stand.
25.
26. 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.
27.
28. Plates shall be observed for any microbial growth after 5 days.
29.
30. Frequency:
31.
32. Microbial monitoring shall be done for three consecutive days once every six
months.
33.
34. Acceptance criteria:
Class / Grade
Limit (CFU/Plate)
Alert Limit
Action Limit
Grade A / 5
<1
<1
<1
Grade B / 6
5
3
4
Grade C / 7
50
30
40
Grade D / 8
100
60
80
Result recording: Record the observations in FORM-H of the re-qualification
report.
Active Air Sampling:
Procedure :
Battery of the Air Sampler shall be ensured for fully charged. Sterilized sieve
shall be used during every monitoring exercise in 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 feed parameter of 1000 liters of air
1000 liters of the air shall be withdrawn.
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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.
Frequency: Microbial monitoring shall be done for three consecutive days once
every six months.
Acceptance criteria:
Area (Grade)
Limit (CFU/m3)
Alert Limit
Action Limit
A
<1
<1
<1
B
10
6
8
C
100
60
80
D
200
120
160
Result recording: Record the observations in FORM I of the re-qualification
report.
Re-qualification criteria:
The system should be re-validated under the following conditions.
If any major changes or modification in the system is done.
Any major changes have been done in the respective room or module, which is
affecting the environmental condition.
If any major maintenance has taken place in the system which can affect the
performance of the air handling system.
Periodic re-qualification.
8.0 Deviation (If any):
Any deviation observed during re-qualification shall be recorded and investigated
A) Description of deficiency and date observed.
B) The person responsible for corrective action and date assigned.
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C) Corrective actions are taken and the date conducted.
9.0 Re-qualification Summary :
The re-qualification report shall consist of a summary document, in narrative
form, which shall briefly describe the activity performed along with the
observations recorded in relevant exhibits.
This report shall also include the related documents and attachments/annexures
which were completed at the time of re-validation activity.
10.0 Approval of re-qualification Report:
The report shall be evaluated and proper
references/conclusions/recommendations shall be recorded by Quality
Assurance.
The report shall be evaluated and finally approved by Quality Assurance.
11.0 List Of Form/Annexure:
List Of Form:
Form
Title
A
Air velocity/airflow measurement and calculation of air changes.
B
Filter integrity test.
C
Differential pressure measurement.
D
Temperature and humidity measurement.
E
Airflow pattern test
F
Non-viable particle count test.
G
Recovery
H
Viable particle count- Passive air sampling
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I
Viable particle count- Active air sampling
List of Annexure:
Requalification report shall include the following annexure:-
S. No.
Annexures
01
Report of Air velocity and ACPH.
02
Report of filter integrity.
03
Report of Temperature and Relative Humidity.
04
Report of Differential pressure.
05
Report of Non-viable particle count.
06
Environment Monitoring Report for Passive air sampling.
07
Environment Monitoring Report for Active air sampling.
08
Recovery study test report.
09
CD of Airflow pattern test.
10
Calibration certificate of Differential pressure gauge.
11
Calibration certificate of data loggers.
12
Calibration certificate of Anemometer.
13
Calibration certificate of the aerosol photometer.
14
Calibration certificate of a particle counter.
15
Training Records.
16
SOP of an external agency.
17
Personal Monitoring report.
18
Traceability Certificates
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12.0 References:
WHO-TRS 937 HVAC.
SOP for qualification and requalification Of HVAC
13.0 Abbreviations:
Abbreviation
Definition
AHU
Air Handling Unit
SOP
Standard Operating Procedure
RC
Regulatory Compliance
QA
Quality Assurance
ID
Identification
CFM
Cubic Feet per Minute
P
Protocol
m2
Meter Square
HEPA
High-Efficiency Particulate Air
HVAC
Heating Ventilation and Air Conditioning
ISO
International Organization for Standardization
MOC
Material Of Construction
ACPH
Air Changes Per Hour
%
Percentage
QA
Quality Assurance
Temp.
Temperature
RH
Relative Humidity
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Abbreviation
Definition
WHO
World Health organization
DP
Differential Pressure
CD
Compact Disc
NVPC
Non-viable particle count
SCDA
Soya bean casein digest agar
NLT
Not Less than
NMT
Not more than
HOD
Head of Department
Ltd.
Limited
No
Number
Rev.
Revision
Sign.
Signature
A/L
Airlock
H.P.
Himachal Pradesh
µ
Micron
Cu.
Cubic
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