Clean Room Validation Protocol

(1)

Prepared by: Approved by: Issued by:

Validation Incharge Validation Head Validation Head 01.0 INDEX

Sr. No. Content Page No.

01.0 Index 1 02.0 Pre-Approval Sheet 2 03.0 Objective 3 04.0 Scope 4 05.0 Responsibilities 4 06.0 Introduction 5

07.0 Equipment And Material 6

08.0 Air Velocity Test And Calculation Of Air Changes Per Hour 6

09.0 HEPA Filter Integrity Testing 9

10.0 Air Flow Pattern Test 13

11.0 Non Viable Particulate Count Test 14

12.0 Recovery Study 18

13.0 Differential Pressure Test 19

14.0 Temperature Control Test 20

15.0 Humidity Control Test 21

16.0 Light Intensity Measurement: (Lux Measurement) 22

17.0 Noise Level Measurement 23

18.0 General Requirments 24

19.0 Annexure 25

(2)

Validation Incharge Validation Head Validation Head

2.0 PRE-APPROVAL SHEET:

Signing of this approval page of Performance Qualification protocol no. AR/P/HVAC/01 indicates agreement with the performance qualification approach described in this document. Shall modifications to the performance qualification become necessary, on addendum will be prepared and approved.

PREPARED BY SIGNATURE DATE

CHECKED BY SIGNATURE DATE

(3)

3.0 OBJECTIVE:

To establish that the documented evidence of HVAC System is meeting predetermined specifications performing,

• Air velocity (ACPH) measurement

• HEPA Filter leak testing (using Hot or Cold DOP)

• Air flow pattern test (Smoke test)

• Nonviable particulate counts measurement

• Recovery test

• Monitoring of Differential pressure of the area

• Monitoring of Temperature within the area

• Monitoring of relative humidity within the area

• Area light level measurement (LUX measurement)

(4)

4.0 SCOPE:

The scopes of this study will verify that the HVAC System is effective & reproducible.

FREQUENCY: To be performed once in six months basis except Temperature, Relative Humidity and Differential pressure, monitoring on daily basis.

5.0 RESPONSIBILITIES:

A team comprising of the representatives of the following functions shall be responsible to undertake the qualification studies.

DESIGNATION RESPONSIBILITY

Validation Head Responsible for final review and approval of protocol and

report

Validation Incharge Responsible for perform site work within the time bond

period.

(5)

6.0 INTRODUCTION:

The Heating, ventilation & air conditioning system installed at service floor of any company, It consists of following AHU's & configuration of filters

SR. NO. AIR HANDLING UNITS ROOM NAME HEPA FILTERS CLASS

(6)

7.0 EQUIPMENT AND MATERIAL:

• TSI Hot wire Anemometer / TSI air capture hood • Photometer with Aerosol generator

• Fog generator (Smoke generator)

• Airborne Non viable Particle counter

• Calibrated Temperature & Relative Humidity data logger • Light level meter-Lux meter

• Noise level meter-dBA meter

8.0 AIR VELOCITY TEST AND CALCULATION OF AIR CHANGES PER HOUR: 8.1 OBJECTIVE:To demonstrate that the required air velocity is delivered by HEPA Filters and to calculate the Air changes per hour for each area.

8.2 ACCEPTANCE CRITERIA:

CRITERIA ACCEPTANCE

Air velocity and ACPH As per design NLT + 20 %

8.3 PROCEDURE: [FOR HOT WIRE ANEMOMETER]

STEP ACTION

Start

1 Switch on respective air-handling unit (AHU) of clean room.

2 Ensure that AHU is operational for the last 5 to 10 minutes.

3 Take the relevant details, like No of filters of area, filter size, room volume, AHU No, design CMH/CFM and ACPH for each room.

4 Switch `ON’ the calibrated hot wire Anemometer. Check the “Zero” reading

on the display.

5 Hold the `velocity measurement’-probe at the working height 6 inches

(approx.150 mm) below the face of HEPA filter in clean room.

6 Record air velocity at different points of HEPA filter i.e. Four corners and one center [Terminal HEPA]. For HEPA filter list with AHU & room

(7)

STEP ACTION

8 Average air velocity at each point.

9 Record velocity. [Reference is made to Annexure-I].

End

8.4 CALCULATION OF AIR CHANGES PER HOUR

STEP ACTION

Start

1 Measure the filter face area in square meter.

2 Calculate the actual volume of supplied air in each room as below.

3 Air flow discharge [m3/minute] = Air velocity of HEPA filter [m/s] × Filter area [m2] x 60.

4 Calculate the volume of the room in cubic meter, of which air changes are to

be calculated.

5 Calculate the no. of air changes as follows.

6 _{No. of ACPH = Airflow discharge in room × 60(CMH) ÷ Room volume.}

7 For filling and sealing area, ACPH should not be less than 300.

8 For all the Classified areas, ACPH should not be less than 20.

9 If the air changes in the area are not within the limit, trouble shoot the cause and rectify.

10 Engineering and QA staff should investigate the reason for the deviation.

Engineering will take immediate action to rectify it.

11 Record the ACPH [Annexure-I].

(8)

Validation Incharge Validation Head Validation Head 8.5 PROCEDURE: [BY CAPTURE HOOD]

STEP ACTION

Start

1 Switch on respective air-handling unit (AHU) of clean room.

2 Ensure that AHU is operational for the last 5 to 10 minutes.

3 Take the relevant details, like No of filters of area, filter size, room volume, AHU 4 Take the mean velocity reading of each filter [cfm) by capture hood

5 Calculate CMH of room by sum of all filter cfm multiply into 60.

7 Calculate the ACPH of room i.e.

8 Record the ACPH [Annexure-I]. If done by capture Hood.

(9)

9.0 HEPA FILTER INTEGRITY TESTING:

9.1 OBJECTIVE:To demonstrate and validate the filter integrity –leak monitoring of the HEPA filters installed in different areas like.

HEPA Filter Integrity Test With Using Aerosol

An unacceptable leak is a local reading greater than 0.01%

9.3 PROCEDURE: (FOR GENERATION OF AEROSOL):

STEP ACTION

Start

1 Check the Aerosol oil level in Aerosol generator.

2 Connect Compressed air / Nitrogen gas to aerosol generator & adjust

the pressure regulator to 20PSI.

3 Direct the outlet of the aerosol generator to return duct [riser] or fresh air intake of AHU.

4 Start the aerosol generator by switching on the Compressed air /

Nitrogen gas to produce the upstream concentration required for leak detection till photometer reads the Photometric concentration of 100%.

(10)

Validation Incharge Validation Head Validation Head 9.4 CALIBRATION OF THE INSTRUMENT [PHOTOMETER]

STEP ACTION

Start

1 Put the photometer selector switch on upstream mode.

2 Connect the tube of photometer to upstream port of HEPA filter.

3 Wait until the photometer displays 100% upstream concentration.

4 Remove the tube of photometer and close the upstream port of HEPA filter

and ensure fir zero leakage.

5 Put the photometer selector switch on down stream mode.

6 Wait until photometer display 0 [ZERO].

On any installation the sealing gasket should be considered as part of the filter and this should be scanned separately from the filter pack.

• Select the sample port; scan the filter pack and the gasket at a distance of 50 to 100 mm.

• For a filter to efficiency 0.001% the range selected should be 0.01% and the alarm set for 0.001%, which is 10% of the full scale, which assumes an efficiency of 99.99% against the challenge aerosol.

(11)

Validation Incharge Validation Head Validation Head 9.5 TESTING PROCEDURE [TERMINAL HEPA FILTER WITHOUT INDIVIDUAL UPSTREAM

PORT]

STEP ACTION

Start

1 Ensure that before staring activity AHU is operational for 5 to 10 minutes.

2 Ensure that the air velocity, air balancing and flow adjustments are done

before proceeding to the Filter integrity testing of HEPA filters.

3 Check that a sampling point is provided and accessible immediately

upstream of the filter to be tested.

4 Start the compressed air / nitrogen gas to Aerosol generator to generate the

test aerosol at minimum 20 psi and monitor the pressure.

5 Direct the test aerosol to riser of room.

6 Ensure that it is possible to introduce test aerosol so that 100%

concentration can be detected at the upstream sampling point.

7 Place the aerosol generator in an accessible position, ideally near the riser,

and adjust the aerosol concentration to the specified density.

8 Prior to the generation of the aerosol place the photometer probe down

stream of the HEPA filter until the instrument has stabilized.

9 Put photometer selector switch on upstream mode.

10

Check the upstream concentration of Aerosol at port provided for

representative HEPA filter for each room ;Until photometer displays 100 % upstream.

11 After getting the upstream conc. & put selector switch to clear position and close upstream Aerosol port.

12 Put photometer selector switch on down stream mode.

13 Wait until photometer displays 0.

14 Measure the down stream concentration by holding the probe approx.1 inch

away from the face of filter.

15

The photometer has a sample flow rate of 1 cfm. Hold the probe at a distance between 50 to 100 mm from the filter face and scan the filter and perimeter by passing the probe in slightly overlapping strokes so that the entire area of filter and sealing gasket is sampled. The probe traverse rate should not exceed 10 feet per minute.

16 Observe the percentage of leakage directly on photometer

17 If any leakage observed through the sealing of filter tighten the filter nuts and check again for any leakage.

(12)

STEP ACTION

18 If any leakage is more than 0.01% of the upstream aerosol concentration

then repair it.

19

Repair the patches on filter s should not exceed maximum of 5% of the total filter face area & maximum width / length of each patch should not be more than 1.5 inches. Total no of patches should not exceed 5 number / filter. 20 If above mentioned limit exceeds then replace the filter & check the integrity

of the filter as per above procedure.

(13)

10.0 AIR FLOW PATTERN TEST

10.1 OBJECTIVE:To determine airflow pattern of terminal HEPA filters and laminar air flow units.

Air flow pattern of HEPA filter Unidirectional

10.3 PROCEDURE:

STEP ACTION

Start

1 Start the respective AHU of which airflow pattern is to be checked.

2 Person carrying out airflow pattern activity should follow clean room

gowning.

3 Fog generator should be used for smoke generation.

4 During the process, hands of operator and facemask should be

covered properly with gloves and facemask.

5 Expose the smoke at supply end of the system.

6 Observe the smoke pattern and ensure the following.

• The airflow pattern should be within specification in order to ensure environmental contamination control.

• The smoke should be diffused uniformly at supply grill and pass through return riser.

7 Carry out Videography/ Photography of the entire airflow pattern

checking activity.

8 Record the result [Annexure-III].

(14)

Validation Incharge Validation Head Validation Head 11.0 NON VIABLE PARTICULATE COUNT TEST:

11.1 OBJECTIVE: To establish that zone meets predefined conditions for non-viable particles.

11.2 ACCEPTANCE CRITERIA: As Per EU Guide

Maximum number of permitted particles per cubic meter equal to or above AT REST IN OPERATION Grade 0.5-5µm >5 µm 0.5-5µm >5 µm A 3500 0 3500 0 B 3500 0 350000 2000 C 350000 2000 3500000 20000 Non viable particulate count test

D 3500000 20000 Not defined Not

(15)

Validation Incharge Validation Head Validation Head 11.3 PROCEDURE: ESTABLISHMENT OF SAMPLING LOCATION:

STEP ACTION

Start

1 All components of the clean air system affecting air quality must be operating in accordance with the specification and all aspects of the controlled environment, which contribute to the operational integrity, are complete.

2 Measure on a centered grid pattern determined by dividing the total floor

area, into approximately equal areas such that:

• The number of sub-areas is as specified in any relevant national standard or as agreed between the client and the contractor sampling positions should be at the intersection of the corners of each sub-area and at a height of 900 mm from the floor, unless agreed otherwise by the client.

• Take the required number of samples at the specified flow rate at each point on the grid. These can be determined from the relevant national standards or agreed by the customer.

3 Calculate the number of sampling locations with the formula

N = Square root of Room in cubic meter made it to approx. [Reference is made to ISO14644-1].

4 The sampling location shall be evenly distributed throughout the area of

clean room or clean zone and position at the height of work activity. In case of additional sampling locations their number and position will be specified.

(16)

Validation Incharge Validation Head Validation Head 11.4 ESTABLISHMENT OF SINGLE SAMPLE VOLUME PER LOCATION:

STEP ACTION

Start

1

Sample a sufficient volume of air at each location such that minimum of 20 particles would be detected if the particle concentration for the relevant class were at the class limit for the largest considered particle size.

2

The single sample volume Vs per location will be determined by Vs =20x1000 / Cnm Where

Vs = is the minimum sample volume per location expressed in liters. Cnm =class limit (number of particles/ m3) for the largest considered particles size specified for the relevant class.

20 = is the defined number of particles that could be counted if particle concentration were at the class limit.

The volume sampled at each location shall be at least 2 liters with a minimum time at each location of 1 minute.

Since particle counter operate at a flow rate of 1CFM, which is equal to 28.3 lits per minute, therefore particle analyzed per cubic feet will need to be multiply with 35.31 to convert to m3.

3

Direct measurement with 1 M3 particle counter,

Specification are: 50 LPM i.e. 1M3 i.e. 1000 liters per 20 minutes.

Sample at each location is taken for 20 minutes, which is equivalent to 50 LPM i.e. 1M3/20 minutes. There fore for grade A/B/C areas [ISO/5/6/7] and for grade D area 1 minute per location. Sampling locations are abased on the criticality of the work zone [Reference is made to AnnexureIV].

(17)

Validation Incharge Validation Head Validation Head 11.5 SAMPLING AT SPECIFIED LOCATIONS AT WORKING HEIGHT:

STEP ACTION

Start

1 Start the sampling and take minimum of single sample volumes from

each location and compute the average particle concentration at specified location.

2 Sampling will be conducted at rest and during operation.

End

11.6 PARTICLE COUNTING AT EACH LOCATION

STEP ACTION

Start

1 Switch on the AHU and let it run for 10-15 minutes.

2 Switch `ON’ the particle counter and set the sampling rate as 1.0 cfm

(Approximately 28.0 liters/minute).

3 Hold the particle counter probe to the working height at different

locations of control/critical areas and take the print out of the particle counts of mentioned locations of control/critical areas.

4 Take the particle count at different location under HEPA filters covering

total area of the control / critical room as mentioned in layout & take printouts of particle count.

6 Switch OFF the particle counter.

7 Get report of the particle count by the external party (Supplier)

8 Such reports should be preserved by the Quality Assurance department.

9 Particle count test of all control /critical rooms under AHUs to be carried

out once in six months or earlier immediately after any major change in AHU facility.

10 Record the results and make the trend of particle count [Reference is

made to Annexure IV].

(18)

12.0 RECOVERY STUDY

12.1 OBJECTIVE:To determine the recovery period for the HEPA filters installed in critical areas.

Recovery period Not more than 10 minutes/As per

Design Specification

12.3 PROCEDURE:

STEP ACTION

Start

1 Measure the clean room or clean zone non-viable particulate counts at

rest [before disturbing the area for Recovery test].

2 Shut OFF the AHU of required zone.

3 Allow the required zone to reach next higher grade (i.e. Grade B To

Grade C).

4 Measure the non-viable particulate counts when area achieve the next

higher grade with help of particle counter for one day.

5 Continue the particle counting for at least 5 counts.

6 Start the AHU and measure the particle counts till it the area achieves

the desired level of counts approximately equivalent to the initial counts taken at rest before the test.

7 Measure time taken to recovery the initial grade.

8 Record the results and enclose the particle count printouts and calculate

the recovery time as-

• 5 minutes-Initial count after AHU shut OFF

• X minutes-Time taken by the area to recover to initial counts after getting the next grade.

• Recovery time = X minutes.

9 Record the result [Reference is made to Annexure-V].

(19)

13.0 DIFFERENTIAL PRESSURE TEST

13.1 OBJECTIVE:To demonstrate the capability of the air system to provide pressure gradient among the different room.

13.2 ACCEPTANCE CRITERIA:

Differential pressure of rooms As per design sheet + 0.5 mm of water

13.3 PROCEDURE:

STEP ACTION

Start

1 All HVAC systems of the clean room facility are to be in continuous

operation when performing these tests.

2 To avoid unexpected changes in pressure and to establish baseline, all

doors in sterile facility must be closed and no traffic is to be allowed through the facility during the test.

3 Adjust the Magnehelic gauge to give a reading of zero in accordance with

the manufacturers instructions.

4 Connect one end of the tubes to the higher-pressure side of the Magnehelic

gauge(Calibrated) & place the other end of the tube in the area of higher pressure such that it is free from obstruction and directed away from any airflows.

5 Next, connect one end of the second tube to the lower pressure input side

of the Magnehelic gauge and place the other end of the tube in the area of lower pressure such that it is free from obstruction and directed away from any airflows. If the tubing passes a surface ensure that any gap surrounding the tube are sealed.

6 Record the pressure displayed on the Magnehelic gauge three times ,for

design differential pressure.

7 Record the result [Reference is made to Annexure-VII].

(20)

14.0 TEMPERATURE CONTROL TEST

14.1 OBJECTIVE:To demonstrate the ability of the AHU's to provide the required temperature in critical and controlled areas.

Temperature of controlled areas NMT 25 0C

14.3 PROCEDURE

STEP ACTION

Start

1 Verify that the air conditioning system is operating in the stable condition and all equipment that is specified is running.

2 Divide the room area in four equal zones test as required by the

specification or on a grid pattern of 3m x 3m.

3 Use calibrated Data logger to record the temperature.

4 Record the temperature for location in each room .

5 Record the result [Reference is made to Annexure-VI].

(21)

15.0 HUMIDITY CONTROL TEST

15.1 OBJECTIVE:To demonstrate the capability of air handling system to control relative humidity at the specified level in each room in critical area and controlled areas.

Relative humidity in critical area NMT 50 %

Relative humidity in controlled area NMT 55%

15.3 PROCEDURE:

STEP ACTION

Start

1 Execute humidity control test after all the air balancing procedure have been concluded and air conditioning system is completely in operation and stable conditions have been achieved

2 Use calibrated Data Logger to record the relative humidity.

3 Record the relative humidity in room as per layout of relative humidity record in each room.

4 Record the result for three consecutive days [Reference is made to Annexure-VI].

(22)

16.0 LIGHT INTENSITY MEASUREMENT: LUX MEASUREMENT

16.1 OBJECTIVE:To determine the lighting level and its uniformity throughout an area at pre-determined points

Light level Not less than 300 lux / As per Design Specification

16.3 PROCEDURE

STEP ACTION

Start

1 Record the light levels on a pre-determined grid pattern/ layout of lux

level or in the absence of a specification on a 3m x 3m grid pattern.

2 Divide the room into four equal locations.

3 Record the light level at working height or 750 mm above finished floor

height.

4 The area under test must have all fitted lights working and the area

structure should be complete also if required emergency lighting levels can be recorded.

5 Record the light levels in lux for each position on the grid [Reference is

made to AnnexureVII].

6 Note down all variations from the specification if any.

(23)

17.0 NOISE LEVEL MEASUREMENT:

17.1 OBJECTIVE:To determine the noise level and its uniformity throughout an area at pre-determined points.

Noise level Not more than 85 dB / As per Design Secification

17.3 PROCEDURE

STEP ACTION

Start

1 Verify that the air conditioning system is operating in the stable condition and all equipment that is specified is running [In operational condition].

2 Map out the area under test as required by the specification in a 2400 mm

x 2400 mm x grid or on a previously agreed location basis i.e divide the area into fur equal parts.

3 Set the instrumentation to work and ensure unauthorized entry and exits

from the room are prevented.

4 Measure the sound levels at work surface height or 750 mm from the

finished floor level and layout of noise level.

5 Record the data [Reference is made to Annexure- VII].

6 Note down all variations from the specification if any.

(24)

18.0 GENERAL REQUIRMENTS:

18.1 The protocol should be signed off (prior to start validation activities).

18.2 Under responsibility of the Validation Head, Performance Qualification will be executed. 18.3 After execution of required tests, the Validation Head should

• Check the results versus the Acceptance Criteria. • Write the report.

18.4 The report will be approved by the same persons (or same designations) who has

Undersigned the protocol.

18.5 The report should contain the following information:

• Report of all measurements and/or analytical results • List of all documentation and or certifications.

• Check of the results against the Acceptance Criteria. • Conclusions concerning this validation study

• Name and designations of persons who has executed the protocol

• Any (relevant) deviation from the prescriptions in this protocol and the Justification for the deviation.

(25)

19.0 ANNEXURE

ANNEXURE I (Air Velocity & ACPH Calculation)

Ambient Condition:- NMT 25° & 50-55%RH

Area/Room Name : Test Performed Date :

Department : Test End Date :

Code No. : Next Due Date :

AHU No. : Acceptance Criteria : ± 20%

Test : Air Velocity & ACPH Calculation Occupancy State : At rest/ At operation

Equipment Used : Test Method :

Observation Table: Obs. Rdg. (m/s)/(ft/min) Sr. No. Filter Tag No. 1 2 3 4 5 Avg. Velocity CMM/ CFM Total CMM/ CFM Room Volume ACPH

Graphical Representation: Filters v/s CMH & Filters v/s ACPH

Filters v/s CMH Filters v/s ACPH

Conclusion:

(26)

ANNEXURE II (Filter Integrity test (DOP/PAO)

AHU No. _: Acceptance Criteria _: 0.01% As Per ISO 14644

Test : Filter Integrity test (DOP/PAO) Occupancy State : At rest/ At operation

Observation Table: Sr. No. Filter Tag No. Concentration Upstream Conc. % Leak in % DOP/ PAO

Test Result Remark

1 ---- ----

Graphical Representation: Filters v/s Leak in %

Conclusion:

(27)

ANNEXURE III (Air Flow Visualization)

AHU No. : Test Method : Trace Injection Air Flows Visualization

Test : Air Flow Visualization Occupancy State : At rest/ At operation

Equipment Used : Observation Table:

Sr. No. Filter Tag No. Flow Pattern Observed Remark

Photographic Representation:

Conclusion:

(28)

ANNEXURE IV (Non – Viable Particle Count Measurement)

Area/Room Name : Test Performed Date :

AHU No. : For Class :

Test : Non – Viable Particle Count. Meas. Occupancy State : At rest/ At operation

Observation Table:

No. of Particles Per CFM/CMM Location No. Occupancy State _≥0.5µ _≥5µ Remark 1 At rest 2 At operation Conclusion:

(29)

ANNEXURE V (Recovery)

AHU No. : Acceptance Criteria :

Test : Recovery Occupancy State : At rest

Observation Table:- For Class

No. of Partical Per CFM/CMM Location AHU

STATUS

Time

Required _≥0.5µm _≥5µm Remark

Conclusion:

(30)

ANNEXURE VI (Temp. & RH Mapping)

Department : Mapping Duration :

Code No. : Frequency of Rdg. :

Test : Temp. & RH Mapping Next Due Date :

Equipment Used : No. of Channel :

Occupancy State : At rest/ At operation Schematic Diagram:

(31)

Validation Incharge Validation Head Validation Head Mapping Observations Table:

Positions

P1 P2 P3 P4 P5

Time

(32)

Validation Incharge Validation Head Validation Head Graphical Representation: [Temperature (OC) v/s Time]

Graphical Representation: [Relative Humidity (% RH) v/s Time]

Conclusion:

(33)

ANNEXURE VII (Differential Pressure & Lux Level Measurement)

Test : Test Method :

Equipment Used : Occupancy State : Observation Table: (For Differential Pressure)

Actual Press. (mm of H2O) Designed Press. mm of of H2O 1 2 3 mm of H2O Average Remark Conclusion:

Certified As Per Design Qualification.

Observation Table: (For Lux Level)

Actual (Lux) Designed (Lux) 1 2 3 Average (Lux) Remark Conclusion:

(34)

ANNEXURE VIII (Sound Level (dB))

Observation Table: (For Sound Level) Actual (dB) Design (dB)

1 2 3 Average (dB) Remark

Conclusion:

(35)

Validation Incharge Validation Head Validation Head 20.0 REFERENCE:-

NO. CODE TITLE

1 ISO 14644 Clean Room & Associated Environment

2 VMP-2006 Validation Master Plan.

3 SCH.M Pt. I-A Drug and Cosmetics act 1940.

4 Annex 6 WHO Technical report series No 902, 2002.

5 USP 2005 USP NF the Official compendia of standards.