NIXI LABORATORIES PVT. LTD.

VPO: MOUZA OGLI, SADHAURA ROAD,

KALA AMB DISTT. SIRMOUR (H.P.)

TITLE PERFORMANCE QUALIFICATION PROTOCOL

Performance Qualification Protocol

Of
Heating Ventilation and Air Conditioning System

Document No. NL/EN/PQP/HVAC/00

Equipment/System Identification No. ENG/EQP/AHU-37 to ENG/EQP/AHU-51

Location Service Floor

Effective Date
CTE/DQ/AHU/001, CTE/IQ/AHU/001 and
Reference Document No.
CTE/ OQ /AHU/001

Annexure No.: A/QA/081/07-00

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VPO: MOUZA OGLI, SADHAURA ROAD,
KALA AMB DISTT. SIRMOUR (H.P.)

TITLE PERFORMANCE QUALIFICATION DOCUMENT (Second Page onwards)

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1.0 Protocol Approval:

Signatory Name Designation Department Sign. / Date

Prepared By

Reviewed By

Approved By

2.0 Purpose:

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VPO: MOUZA OGLI, SADHAURA ROAD,
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TITLE PERFORMANCE QUALIFICATION DOCUMENT (Second Page onwards)

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The purpose of this protocol is to provide the procedure for the Performance qualification of Heating
Ventilation and Air Conditioning System of New Lyo facility.

 To provide documented evidence that the system is capable to continuously supply the clean
and conditioned air with the specified quality attributes thereby establishing its dependability.
 To provide the consistent and reliable performance of Heating Ventilation and Air
Conditioning System.

 To prove the adequacy of the engineering design of the HVAC system and the effectiveness of
the operating control and maintenance procedures.

 To establish the operating ranges for the system key control parameters that provide the means
of assessing when the system is operating outside established control parameter limits and
bringing the system back to state of control.
3.0 Scope:
This document includes the Performance qualification procedure of the Heating ventilation and air
conditioning system.

Equipment Name Heating Ventilation Air Condition

Equipment ID ENG/EQP/AHU-37 to ENG/EQP/AHU-51
Area of Operation New Lyophilized Block
Facility New Lyophilized Block
Supplier Name and address Cool Tech Engineers
Site Nixi Laboratories Pvt. Ltd.
4.0 Responsibility:
Responsibilities of different department/ personnel involved in different activities related to the
Performance qualification of Heating Ventilation and air conditioning system are defined below:

Quality Assurance Department:

 Preparation and review of Performance Qualification protocol.
 Approval of Performance Qualification protocol.
 Execution of Performance Qualification protocol along with the co-ordination of other
departments.
 Review of results and compiling of data generated during the execution.

Production Department:
Annexure No.: A/QA/081/07-00
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VPO: MOUZA OGLI, SADHAURA ROAD,
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 Review of Performance Qualification protocol.
 Execution of Performance Qualification protocol along with QA validation team.

Quality Control Microbiology Department:

 Review of Performance Qualification protocol.
 Performing environmental microbial monitoring (Active air sampling, Passive air sampling and
Surface monitoring).
 Handling of OOS (if any)

Engineering:
 Execution of Performance Qualification protocol along with QA validation team.
 Calibration of all measuring / test instruments.
 Rectification of Breakdown during qualification study.
 Review of Performance Qualification protocol.

5.0 Training of personal:

Training shall be provided to the persons involved in Performance qualification and the same shall be
logged in the sheet given below.
Sr. No. Name of Personnel Department Signature
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.

Annexure No.: A/QA/081/07-00

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VPO: MOUZA OGLI, SADHAURA ROAD,
KALA AMB DISTT. SIRMOUR (H.P.)

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Document No. Page No.: 5 of 24
Sr. No. Name of Personnel Department Signature
15.
16.
17.
18.
19.
20.

Training Given By:

Sign / Date

6.0 Pre-requisite of Performance Qualification:

Pre-Requisite:
Prior to conducting/ executing the Performance qualification protocol following conditions must be
fulfilled:
 System should be safe for execution.
 All utilities shall be available.
 Approval of operational qualification report.
Pre-Qualification Test:
 Verification of Calibration of all measuring instruments of HVAC system.
 Verification of Calibration of all test instruments.
 Verification of Standard Operating Procedure.
 Ensure availability of certificate of all test instruments to be used for qualification viz. certificate
for aerosol photometer reflecting particle size of aerosol, sampling rate of photometer, certificate
of anemometer, certificate of particle counter (as per applicability).

7.0 Test Plan:

7.1 Critical Variable and measuring response:
Qualification Test Program:
 Air flow, volume and distribution test.
 HEPA Filter Integrity Test.
 Differential Pressure Monitoring
 Temperature and Humidity monitoring
Annexure No.: A/QA/081/07-00
 NIXI LABORATORIES PVT. LTD.
VPO: MOUZA OGLI, SADHAURA ROAD,
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 Airborne Particulate Testing (Non-viable particle count testing)
 Microbial Environmental Monitoring
 Recovery Test
 Air Flow Pattern study
 Induction / containment Leak test
Test Matrix:
Following matrix shall be followed for the initial qualification and re-qualification Heating
ventilation and air conditioning system for its performance:

Frequency
Sr.
Test Initial Re –
No.
Qualification Qualification
Pre – Qualification Test
Verification of Calibration status of all Measuring
1 Once Once
Instruments.
2 Verification of Calibration status of all test instruments. Once Once
3 Verification of Standard operating procedure status. Once Once
Qualification Test
Once
1. Air flow, volume and distribution test Once
(Every Six Months)
Once
2. HEPA Filter Integrity Test Once
(Every Six Months)
Once
3. Differential Pressure Monitoring For 3 days
(For 24 Hours)
Once
4. Temperature and Relative Humidity monitoring For 3 days
(For 24 Hours)
Airborne Particulate Testing (Non-viable particle count)
5. For 3 days Once*
(At-rest condition)
Airborne Particulate Testing (Non-viable particle count)
6. For 3 days Once
(In-Operation condition)
7. Microbial Environmental Monitoring (At-rest condition) For 3 days Once*
Microbial Environmental Monitoring (In-Operation
8. For 3 days Once
condition) condition)
9. Recovery Test Once Once in two years
Air Flow Pattern In static condition Once NA
10.
study In dynamic conditions Once Once in two years
11. Induction / Contamination Leak test Once NA
* In case of planned shutdown with HVAC off, area requalification to be performed at rest condition.

7.2 Test Parameter and Specification:

7.2.1 Air Flow, Volume and Distribution Test:

Annexure No.: A/QA/081/07-00

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TITLE PERFORMANCE QUALIFICATION DOCUMENT (Second Page onwards)

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Objective:
 This test is performed to determine the supply airflow rate in a non-unidirectional clean room
and the air velocity distribution in a non-unidirectional clean room.
 The air system is balanced and capable of delivering sufficient air volumes to maintain a
minimum cross-sectional velocity as per design.
 Total airflow rate may, in turn, be used to determine the air exchange rate (air changes per hour)
for a non-unidirectional installation.
 To demonstrate that the number of air changes are equal to or more than the designed number of
air changes.

Test Requirements:
 Calibrated Anemometer.
 Equipment in operation.

Acceptance Criteria:
 Total Number of air changes per hour in each room supplied by different AHUs should not be
less than the corresponding values indicated below:
ACPH
AHU No. Area Catering Room ID No. Classification
(NLT)
Female Change room- I E1003 NC
Female Change room- II E1004 NC
Female Change room- III E1005 NC
Male Change room- I E1006 NC
Male Change room- II E1007 NC For Information
AHU-01
Male Change room- III E1008 NC Only
Main Male Entry E1009 NC
Main Male Change room I E1010 NC
Main Male Change room II E1011 NC
Change room Air lock E1012 NC
Lyo Technical Area E1040 NC For Information
AHU-02
SCADA room E1041 NC Only
PPM E1001 CNC
Solvent Handling area E1002 CNC
For Information
AHU-03 1.2m Wide corridor E1013 CNC
Only
Production office E1021 CNC
Secondary Material Passage E1039 CNC
External vial washing area E1036 CNC
For Information
AHU-04 Packing area E1037 CNC
Packing day store E1038 CNC
Decartoning Area E1014 D NLT 20
AHU-05
Change Room -I E1016 D NLT 20
Annexure No.: A/QA/081/07-00
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VPO: MOUZA OGLI, SADHAURA ROAD,
KALA AMB DISTT. SIRMOUR (H.P.)

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ACPH
AHU No. Area Catering Room ID No. Classification
(NLT)
Material Air lock E1015 C NLT 40
Change room- II E1017 C NLT 40
Change Room-III E1018 C NLT 40
AHU-06
IPQA Office E1019 C NLT 40
Washing Area E1020 C NLT 40
Clean corridor E1022 C NLT 40
Vial washing and
E1023 C NLT 40
AHU-07 sterilization area
Autoclave area E1025 C NLT 40
AHU-08 Compounding area E1024 C NLT 40
B-Entry change room- I E1026 C NLT 40
AHU-09 B-Exit change room- II E1030 C NLT 40
Vial Sealing area E1035 C NLT 40
B-Entry change room- II E1027 B NLT 60
B-Entry change room- III E1028 B NLT 60
AHU-10
B-Exit change room- I E1029 B NLT 60
Aseptic Corridor E1031 B NLT 60
AHU-11 Autoclave unloading area E1032 B NLT 60
AHU-12 Holding area E1033 B NLT 60
Vial Filling, Stoppering & NLT 60
AHU-13 E1034 B
Lyo loading/unloading area
Air Lock E2001 CNC For Information
Corridor 1.5m E2002 CNC Only
Approved Area-I E2007 CNC
Unapproved Area-I E2008 CNC
AHU-14 Approved Area-II E2009 CNC
Unapproved Area-II E2010 CNC
Warehouse Office E2011 CNC
Part wash Office E2012 CNC
Garment Storage area E2013 CNC
Change room E2003 D NLT 20
AHU-15
Corridor E2004 D
Dispensing Area E2005 D
Sampling Area E2006 D
Procedure:
 The test can be performed by in house or external agency.
 These tests should be executed in each room where absolute terminal HEPA filters are installed.
 Ensure that the measuring and testing instruments being used are calibrated.
 Measure airflow velocities at the four corners and center of each terminal HEPA filter below 6
inches downstream of the filter as shown in the following figure 1.
 Calculate Total airflow and number of air changes in the subjected room.

Annexure No.: A/QA/081/07-00

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VPO: MOUZA OGLI, SADHAURA ROAD,
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Figure-1

V1 V2

V5

V3 V4

Average Velocity of each HEPA:

Calculate the Average Velocity (V, in feet per minute) of each HEPA filter as:
V= ( v i) / i

Where,
i = 1 to 5

v = Velocity observed at each point.

Air Flow of a HEPA filter (V1 in Cubic Feet per Minute)

V1 = V X Area of HEPA Filter

Where, V1 = Air Flow of the HEPA Filter-1

Total Air Flow:

Calculate the Total Air Flow (Vn, Cubic Feet per Minute)

Vn = (V1+ V2 + V3 + ---------)

Air Changes per Hour of a Room:

Calculate the Air Changes Per Hour of a Room (ACPH)

Air Changes = Total Air Flow (Vn) X 60

Room Volume (In Cubic Feet)

Note: For ACPH calculation refer Annexure No. 02 (Room Data Sheet) for room volumes, no. of
HEPA filters & HEPA filter surface area.
Result:
Report and summarize the results in the report.

Scientific rationale:

Annexure No.: A/QA/081/07-00

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VPO: MOUZA OGLI, SADHAURA ROAD,
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TITLE PERFORMANCE QUALIFICATION DOCUMENT (Second Page onwards)

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 Air velocity requirement is as per Guidance for Sterile Drug Produced by Aseptic Processing,
USFDA, September 2004.
 Air velocity requirement is as per Annexur-1 to EU GMP.

7.2.2 HEPA Filter Integrity Test

Objective:
 To ensure that the HEPA filters installed are not damaged during transit, installation, or
operation and / or fixed properly in the appropriate place, such that there is no leakage from the
filter media and the other joints gaskets, frames etc.
 To verify that the filters are free of defects (small holes and other damages in the filter medium
and frame seal).

Test Requirements:
 PAO aerosol generator.
 PAQ aerosol photometer.
 AHU shall be in ON condition.

Procedure:
 The test shall be performed by external agency or in house.
 The operation of testing instrument shall be carried out as per the contract agency SOP or
inhouse SOP.
 The filter integrity test shall be performed by the qualified personnel of the contract agency in
the presence of Nixi representative.
 The testing instruments being used shall be calibrated with reference to the NABL or
equivalent traceable reference standard.
 The filter testing shall be performed after operational velocities have been verified and adjusted
where necessary.
 With the help of aerosol generator, introduce the PAO aerosol in the upstream port of the
supply air duct to verify terminal HEPA filters integrity.
 Adjust the upstream concentration of the aerosol between 1 mg/m3 to 100 mg/m3 of air (Ref:
ISO 14644-3).
 Set the observed upstream aerosol to 100% scale of the upstream concentration at upstream of
the HEPA filter on the aerosol photometer.

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 Measure upstream concentration at the beginning, intermediate and after completion of HEPA
filter integrity test with the help of aerosol photometer.
 Record the actual upstream particle concentration in raw data sheet/vendor raw data sheet at
beginning, intermediate and after completion of HEPA filter integrity test.
 Individual value of the upstream concentration being measured at the beginning, intermediate
and after completion of the filter integrity test should not vary by more than ± 15 % of the
average of these three measured values.
 Select downstream scanning mode on the aerosol photometer.
 Scan the subjected HEPA filter by holding the photometer probe approximately 1inch below
the filter face.
 Pass the probe in slightly overlapping strokes, at a rate of not more than 5 cm/s so that the
entire filter face is sampled. (Ref: ISO 14644-3)
 Scan the entire periphery of the filter.
 Note down the observed percent leakage in the HEPA filter, as displayed on the aerosol
photometer screen while downstream scanning.
 Repeat the same procedure for all others supply terminal HEPA filters.
 Record the distance from filter face, sampling rate of photometer, size of the aerosol particle
and scanning rate during the test in Annexure No. 03.

Acceptance Criteria:
The leak shall be less than 0.01% of upstream concentration.
Upstream concentration of the filters should not vary more than ±15% in time about the average
measured value.

Result:
 Record the observations of the HEPA filters for each AHU’s in Annexure No 03 for terminal
HEPA filters.
 Attach the Certificate of compliance provide by vendor for each HEPA filter.

Scientific rationale:
 The acceptable limit of leak is as per Guidance for Sterile Drug Produced by Aseptic
Processing, USFDA, September 2004.
 The acceptable limit of leak and procedure of testing is as per ISO-14644-3.

7.2.3 Differential Pressure Monitoring

Annexure No.: A/QA/081/07-00

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Objective:
The objective of this test is to show that absolute and differential pressures between rooms are meeting the desired specification.

Test Requirements:

AHUs shall be in operation

Test Procedure:

During HVAC Qualification, monitoring of the absolute and differential pressure shall be performed for both controlling and monitoring the differential pressures.

Data shall be recorded for absolute pressure of the room for the recommended period as defined shall be collected from BMS and shall be reviewed against the acceptance

criteria.

The differential pressure from room to room shall be determined by mathematical calculation through difference of absolute pressures of individual rooms with respect to the

other room. The differential pressure values shall then be evaluated against the acceptance criteria.

Acceptance Criteria:

The acceptance criteria for the absolute pressure and differential pressures between different rooms are defined as below.

Room Absolute Absolute DP Alarm

Room ID vs Room Name Room ID
Name Pressure Pressure Limit

Results

Data of Differential Pressure shall be taken for recommended period and the result shall be summarized in the report.

Annexure No.: A/QA/081/07-00

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8.2.1 Temperature and Relative Humidity Monitoring
Objective:

Objective of this test is to ensure that the AHU system is capable of achieving and maintaining the desired temperature and RH consistently within the acceptable limits.

Records of temperature and RH thrice in a day till the qualification period and observations shall be recorded.

Test Procedure:

During HVAC Qualification, monitoring of the Temperature, % Relative Humidity shall be performed by using data from BMS system, as the BMS system is in place for

both controlling and monitoring the Temperature, % Relative Humidity of the rooms.

Print out of Temperature and Relative Humidity data of the recommended period and shall be reviewed against the acceptance criteria.

Acceptance Criteria:

Class of Area Temperature Relative Humidity

Class C NMT 25°C NMT 55%

Class D NMT 25°C NMT 55%

Results

Reading of Temperature and Relative humidity shall be taken for recommended period and the observation of the same shall be summarized in the report.

8.2.2 Airborne Particulate Testing (Non-viable Particle Count Testing)

Objective:

The objective of this test is to verify that the HVAC facilities can provide the required clean room classifications as defined in international standards.

Test Requirements:

 Calibrated non-viable Particle counter.

 AHUs shall be in working condition.
Procedure:

 The airborne particle test should be performed by the qualified personnel of the contract agency
in the presence of Nixi representative.
 The test should be carried out after area cleaning as per respective procedure.
 Set up the particle counter according to respective test operating procedures at the different
sampling locations as per Annexure No. 04.
 The particle counter being used should be calibrated with reference to the NABL traceable
reference standard.

Annexure No.: A/QA/081/07-00

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 After completion of qualification, graphical representation shall be prepared & recorded in the
report.
Note:

The minimum number of sampling location shall be calculated based on the area of the room. The minimum number of sample locations taken in each room shall be as per

ISO-14644 (2015) and the table mentioned below.

Area of clean room (m2) Minimum number of sampling

less than or equal to locations to be tested (NL)
2 1
4 2
6 3
8 4
10 5
24 6
28 7
32 8
36 9
52 10
56 11
64 12
68 13
72 14
76 15
104 16
108 17
116 18
148 19
156 20
192 21
232 22
276 23
352 24
436 25
636 26
1000 27
>1000 See formula
Formula for NVPC location having area more than 1000 m2

NL= number of location

Minimum Sample volume collection during airborne particle count testing:
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The Sample volume or Vs per location is determined by the equation below:

 Vs is the minimum single sampling volume per location, expressed in liters.

 Cn,m is the class limit (number of particles per cubic meter) for the largest considered particle
size, specified for the relevant class.
 20 is the defined number of particles that could be counted if the particle concentration were at
the class limit.
 Minimum sample volumes for each grade areas in liters are listed in below mentioned table.

At Rest In Operation
Grade
Minimum Sample Volume (Ltr.) Minimum Sample Volume (Ltr.)

C 7 2*

D 2* Not Defined

*The volume sampled at each location shall be at least 2 liters, with a minimum sample time of 1
minute for each sample at each location.
Reference: As per ISO 14644 Parts-I and EU Annexure 1.
For at rest conditions:
Grade C & D
 Minimum sampling time should be 1 min.
 Minimum sample volume should be 7 and 2 ltrs respectively. (100 Ltr / 50 Ltr based on
particle counter capacity).
For In operation conditions:
Grade C & D
 Minimum sampling time should be 1 min.
 Minimum sample volume should be 100 Ltr / 50 Ltr based on non-viable particle counter
capacity.

Instruction:
 The sampling locations should be evenly distributed throughout the area of the room and
positioned at the height of the work activity.

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 Performance qualification to be performed for 03 days in case of initial qualification and once
during re-qualification.

Condition where the installation is complete with equipment

At rest Condition installed and operating in a manner, but no personnel present. (To be
performed only during initial qualification system.)
Condition where the installation is functioning in the specified
In Operational
manner, with the specified number of personnel present and working
Condition
in the manner agreed upon
Acceptance Criteria:

Maximum Permitted number of Particle per m3 equal to or

greater than the tabulated size
Grade At Rest In Operation
0.5µ 5µ 0.5µ 5µ
C 352000 2930 3520000 29300
D 3520000 29300 3520000 29300
(Ref: As Per EU GMP Annex 1)

 Each location average count shall meet the required limit.

Results:
The original printout and photocopy of the location wise particle count data shall be attached with the report.

Scientific rationale:
 The particle requirement is as per Guidance for Sterile Drug Produced by Aseptic Processing,
USFDA September 2004.
 The particle requirement is as Annexure-1 to EU GMP.
 ISO-14644-1.

8.2.3 Microbial Environmental Monitoring

Objective:
The objective of this test is to verify that the HVAC facilities can provide the required cleanliness with respect to microbiological contamination as defined in international

Standards.

Test Requirements:
 AHU shall be in working condition
 Active air sampler

Annexure No.: A/QA/081/07-00

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 Media plates
Test Procedure:
o Passive Air Sampling
o Active air sampling
o Surface sampling
 The microbial environmental sampling shall be performed for 03 days during initial
qualification and once during re-qualification.
 The number of sampling location decided as per risk assessment.
 Microbial environmental monitoring shall be performed as per procedure.
Acceptance Criteria:
Limit for microbial monitoring for clean room.
Microbial
Contact Plates
Limit Air Sample Settle plate
(Dia. 55mm) CFU /
s (CFU/m3) (Dia. 90mm) CFU / Plate / 4 Hrs
Plate
Grade C 100 50 25

Grade D 200 100 50

(Ref: As per USP/EP/EU Annex 1)

Results:
The report and the observation shall be recorded and compiled in Annexure No. 05 for Grade C &
D analysis.

After completion of qualification, graphical representation shall be prepared & recorded in the
report.
Scientific rationale:
 The microbial requirement is as per current version of Guidance for Sterile Drug Produced by
Aseptic Processing, USFDA.
 The microbial requirement is as per current version of Annexure-1 to EU GMP and USP.
 The location of microbial monitoring is taken considering the location as worst case.

8.2.4 Recovery Test

Objective:
 The purpose of the test is to verify the capability of HVAC system to eliminate airborne
particulates from respective controlled processing areas.
 This test is to be performed for determining performance and efficiency of HVAC system by:
 Non-viable particulate count.
Annexure No.: A/QA/081/07-00
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VPO: MOUZA OGLI, SADHAURA ROAD,
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Test Requirements:
 AHU shall be in operation
 Non-viable particle counter
 Aerosol generator.
Test Procedure:
This test shall be performed as per the following methodology:
 This test is performed for non-unidirectional airflow system and area.
 Setup the non-viable particle counter at room/area mentioned in Annexure No. 06.
 Ensure particle counter is placed where maximum particle count is observed during non-
viable particle count test (Critical locations or suspected worst-case locations).
 Ensure that particle counter is not placed directly below the terminal HEPA filter.
 Measurement of Non-viable particulate count should be taken at every one-minute interval.
 02 Nos. of Non-viable particle counts (initial particle count) should be taken before exceeding
the particle count 10 times or more from its area/ room grade limit.
 Start the aerosol generator and contaminate area/room with aerosol while the air-handling
units are in operation condition.
 The particle counting shall be taken continuously till the particle counts reach 10 or more
times of the non-viable particulate count limit as per respective area/ room grade limit and
stop the aerosol generator.
 02 Nos. of non-viable particle count measurement should be taken after achieving the particle
count within the area / room grade limit.
 Record all the observations in Annexure No. 06.

Note:
 Test shall be performed at Rest-condition.
 Only 0.5µm particle size shall be considered during the recovery test and 5.0 µm particle size
limits shall be taken for information only.

Acceptance Criteria:
Recovery time should be less than 15 to 20 minutes.
Observation and Results

The observation of the above-specified tests shall be recorded and compiled in the attached
Annexure-06.

Annexure No.: A/QA/081/07-00

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8.2.5 Air Flow Pattern study (Static Conditions)

Objective:
To demonstrate / verify that the airflow pattern at critical area(s) in static condition (Below the
HEPA Filters) are within the acceptance criteria i.e. air movement from high-pressure area to low
pressure area and to detect, if air is stagnant in the clean area.

Test Procedure:
The static airflow study shall be performed as per procedure.
Acceptance Criteria:

Sr. No. Description Acceptance Criteria

01 Smoke study Airflow should be always from high pressure zone to low pressure zone.

There should be time and date stamp.

Airflow Pattern must be visualized to provide visible evidence of their

flow direction.

Airflow Patterns should be evaluated live during filming. The

assessment of airflow pattern acceptability should be primarily based on
the real-time data. The recorded footage should be used for
documentation and therefore should be primarily assessed for its
suitability for the purpose and for adequate filming technique.

At times, the observation and the filming of the airflow patterns may be
impeded by space constraints. Employing remote controlling of the
camera and wireless transmission of the footage in combination with
remote assessment from outside of the Work Zone / Critical Area
should be considered in these cases. In general, live assessment of the
airflow pattern should be preferred.
Observations and Results:

Attach the CD/DVD to the report.

Annexure No.: A/QA/081/07-00

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VPO: MOUZA OGLI, SADHAURA ROAD,
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8.2.6 Air Flow Visualization (Dynamic Condition)
Objective:

To demonstrate / verify that the airflow pattern at critical area(s) in dynamic condition (Below the
HEPA Filters) are within the acceptance criteria i.e. air movement from high pressure area to low
pressure area and to detect, if air is stagnant in the clean area.
Test Procedure:

The dynamic airflow study shall be performed as per SOP/QAD/0079. Airflow pattern study shall
be performed from terminal HEPA to area, from room to return risers high-pressure area to low
pressure area and to detect, if air is stagnant in the clean area. (Video recording for air flow
pattern study shall be done and attached with this test sheet).
Acceptance Criteria:

Sr. No. Description Acceptance Criteria

01 Smoke study Air movement shall be from terminal HEPA to area, from room to
return risers high-pressure area to low pressure area.

There should be time and date stamp.

Airflow Pattern must be visualized to provide visible evidence of their

flow direction.

Airflow Patterns should be evaluated live during filming. The

assessment of airflow pattern acceptability should be primarily based on
the real-time data. The recorded footage should be used for
documentation and therefore should be primarily assessed for its
suitability for the purpose and for adequate filming technique.

At times, the observation and the filming of the airflow patterns may be
impeded by space constraints. Employing remote controlling of the
camera and wireless transmission of the footage in combination with
remote assessment from outside of the Work Zone / Critical Area
should be considered in these cases. In general, live assessment of the

Annexure No.: A/QA/081/07-00

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VPO: MOUZA OGLI, SADHAURA ROAD,
KALA AMB DISTT. SIRMOUR (H.P.)

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Sr. No. Description Acceptance Criteria

airflow pattern should be preferred.

Observations and Results:

Attach the CD/DVD to the report.

8.2.7 Induction Leak Test

Objective:

To demonstrate that there is no intrusion of unfiltered air into the clean work areas from outside
the clean-room enclosure through joints in the walls, ceilings, etc. other than from the pressurized
air supply system and to determine that unfiltered air intrusion into the clean room through open
entrance doorways.
Test Requirements:

 Smoke generator
 AHU shall be in running condition
Test Procedure:

 Pressurize each clean zone and make positive with respect to atmosphere and surrounding
unclean area.
 Generate the smoke inside the room near to the joints and doorways.
 Visually check from other side of the room for flow of smoke to outside near the joints.
 Execute the test in each room where joints in the walls, ceilings and open entrance or ways.
Acceptance criteria:

No construction joint leaks or intrusion through open doors should be observed visually.
Observations and Results:

The observation of the above-specified tests shall be recorded and compiled in the attached
Annexure No. 07.

8.0 Acceptance Criteria

All test result should be recorded in annexure and complies the limit.

Annexure No.: A/QA/081/07-00

 NIXI LABORATORIES PVT. LTD.
VPO: MOUZA OGLI, SADHAURA ROAD,
KALA AMB DISTT. SIRMOUR (H.P.)

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9.0 Deviations and corrective actions

Performance Qualification of Heating Ventilation and air conditioning system will be performed
once in year as per the test matrix mentioned in the protocol.

Air change per hour and HEPA filter integrity shall be performed once in Six Month.

The qualification should also be performed additionally in case of following:

 Any major modification in equipment after the last performance qualification. This must be
properly documented through a change control system.
 Any change in operational parameters with respect to that specified.
 Any other factors based on Risk Assessment.

In case of failure to meet acceptance criteria of any test as mentioned in the protocol a thorough
investigation is to be initiated to find out the root cause and the complete study or a part of the
study may be repeated after the corrective action based on a suitable Risk Assessment of the
Situation. However, if the failure is due to some obvious reason like power failure during the runs,
then the affected run may aborted and repeat run shall initiated but the aborted run result along
with description of the incident must be reported in the PQ report.

10.0 Abbreviation
ABBREVIATIONS FULL FORM
HVAC Heating Ventilation Air Conditioning
PQ Performance Qualification
SOP Standard Operating Procedure
No. Number
QA Quality Assurance
BMS Building Management System
AHU Air Handling Unit
RH Relative Humidity
OQ Operation Qualification
IQ Installation Qualification
µ Micron
°C Degree Centigrade
US FDA United States food and Drug Administrator
ISPE International Society of Pharmaceutical Engineering
PAO Poly alpha olefin
NABL National Accreditation Board for Testing and Calibration
Annexure No.: A/QA/081/07-00
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VPO: MOUZA OGLI, SADHAURA ROAD,
KALA AMB DISTT. SIRMOUR (H.P.)

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ABBREVIATIONS FULL FORM
Laboratories
µg/L Microgram per Liter
FPM Feet per minute
CFM Cubic feet per minute
ACPH Air changes per hours
QC Quality control
CFU Colony forming unit
CD Compact disc
NMT Not more than
NLT Not less than
HEPA High efficiency particulate air

11.0 Reference
Following documents are referred during preparation of the protocol.
 Procedure for operation of HVAC system.
 Preventive Maintenance of HVAC system.
 Procedure for BMS
 Monitoring of environmental conditions

12.0 Attachment

Annexure No. Description

01 Room Data Sheet
02 HEPA Filter Integrity Test for Terminal HEPA
03 Number of Sampling Locations for Non-viable Particle count
04 Microbial Environmental Monitoring for Grade C & Grade D area
05 Recovery Study
06 Induction / contamination leakage study

13.0 Summary and Conclusion

Based on the review of results a conclusion shall be drawn and documented in the performance
qualification report. Conclusion shall be a clear statement of compliance or non compliance of the
Heating Ventilation and air conditioning system with respect to the acceptance criteria of the
performance qualification protocol.

Annexure No.: A/QA/081/07-00

 NIXI LABORATORIES PVT. LTD.
VPO: MOUZA OGLI, SADHAURA ROAD,
KALA AMB DISTT. SIRMOUR (H.P.)

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14.0 Report Approval

Signatory Name Designation Department Sign. / Date

Prepared By

Reviewed By

Approved By

15.0 Performance Certification

Based on the review of results performance certification of HVAC system will be issue.

Annexure No.: A/QA/081/07-00