Heter

o
PERFORMANCE QUALIFICATION PROTOCOL
Equipment Name : BREATHING AIR SYSTEM
Equipment Number : O-ENE-011 Facility : Oncology Formulation Facility
Protocol Number : VPO-EN011-00 Effective date :

PERFORMANCE QUALIFICATION PROTOCOL

FOR
BREATHING AIR SYSTEM

Revision Index

Revision No. Date CRN No. Reason for revision

00 NA New Document

O-QA008/F01-00 Page 1 of 11
 Heter
o
PERFORMANCE QUALIFICATION PROTOCOL
Equipment Name : BREATHING AIR SYSTEM
Equipment Number : O-ENE-011 Facility : Oncology Formulation Facility
Protocol Number : VPO-EN011-00 Effective date :

TABLE OF CONTENTS

1.0 Protocol Approval__________________________________________________3

2.0 Objective__________________________________________________________4
3.0 Scope____________________________________________________________4
4.0 Equipment Description______________________________________________4
5.0 Responsibilities and Identification of Execution Team____________________5
6.0 Qualification Test Program and frequency:______________________________6
7.0 Qualification Test Procedure_________________________________________6
8.0 Records of Observations____________________________________________9
9.0 Re Qualification____________________________________________________9
10.0 Discrepancy and Corrective Action Report_____________________________10
11.0 Compilation, Review and Summary Report_____________________________10
12.0 Appendix_________________________________________________________10
13.0 Enclosure________________________________________________________11

O-QA008/F01-00 Page 2 of 11
 Heter
o
PERFORMANCE QUALIFICATION PROTOCOL
Equipment Name : BREATHING AIR SYSTEM
Equipment Number : O-ENE-011 Facility : Oncology Formulation Facility
Protocol Number : VPO-EN011-00 Effective date :

1.0 Protocol Approval

Signing of this approval page of protocol indicates agreement with the qualification
approach described in this document. If any modification in the qualification approach
becomes necessary, a revision through change control shall be prepared, checked
and approved. This protocol cannot be executed until approved by following
personnel.

Department Name Designation Signature & Date

Prepared by

Quality Assurance

Reviewed by

Engineering/
Projects

Production

Quality Assurance

Micro Biology

Approved by

Quality Assurance

O-QA008/F01-00 Page 3 of 11
 Heter
o
PERFORMANCE QUALIFICATION PROTOCOL
Equipment Name : BREATHING AIR SYSTEM
Equipment Number : O-ENE-011 Facility : Oncology Formulation Facility
Protocol Number : VPO-EN011-00 Effective date :

2.0 Objective

The purpose of this protocol is to provide the procedure for the performance
qualification of the BREATHING AIR SYSTEM.

To provide documented evidence that the system is capable to continuously

supply the clean Breathing air with the specified quality attributes thereby
establishing its dependability.
To prove the adequacy of the engineering design of the BREATHING AIR
SYSTEMand 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.
To prove the adequacy of the engineering design of the system and the
effectiveness of the operating control and maintenance procedures.

3.0 Scope

This protocol covers all aspects of Performance Qualification for the Breathing air
distribution System oncology formulation facility of Hetero labs Ltd, Jadcherla.

This protocol will define the methods and documentation used to qualify the Breathing
air Distribution System for PQ.

4.0 Equipment Description

Department Engineering
Name of the Supplier /
M/s. Aswin Micro Filtration Pvt. Ltd.
Manufacturer
Capacity 1000 liters
Location Utility

O-QA008/F01-00 Page 4 of 11
 Heter
o
PERFORMANCE QUALIFICATION PROTOCOL
Equipment Name : BREATHING AIR SYSTEM
Equipment Number : O-ENE-011 Facility : Oncology Formulation Facility
Protocol Number : VPO-EN011-00 Effective date :

4.1 Breathing Air filtration process

Compressed air 3 filter 1 filter 0.1 filter Carbon filter

Distribution line Storage

1 filter tank CO filter CO2 filter

4.2 The breathing air system consists of filters for moisture, particle removal, Co2 & Co removal
before storage air in the vertical receiver. An additional final filtration provided enables
the system to deliver pure air for breathing. Filter elements with filter housing made of
SS 316L with 11/2 tri clover connection.

4.3 Vertical air receiver of capacity 1000L made of SS316 is provided with safety valve and drain
valve and pressure gauge

4.4 Pure air is distributed through pipelines to various identified areas and is installed with pressure
regulators, pressure gauges and quick couplers at relevant points.

5.0 Responsibilities and Identification of Execution Team

5.1 Responsibilities: The group comprising of representatives from each of the following
departments shown in the table below and they shall be responsible for the overall
compliance with this protocol.

Quality Assurance (Validation)

Preparation of PQ protocol
Approval of PQ protocol
Execution of PQ protocol along with the co-ordination of other departments
Review of results and compiling of reports.
Preparation and approval of PQ report

Production

Checking of PQ protocol and Report

Providing necessary support wherever required in execution

Quality control

Checking of PQ protocol and Report

Performing air sampling
Preparation of Analysis Report and submission to Quality Assurance

Engineering / Projects

O-QA008/F01-00 Page 5 of 11
 Heter
o
PERFORMANCE QUALIFICATION PROTOCOL
Equipment Name : BREATHING AIR SYSTEM
Equipment Number : O-ENE-011 Facility : Oncology Formulation Facility
Protocol Number : VPO-EN011-00 Effective date :

Checking of PQ protocol and Report

Preventive Maintenance of breathing air Systems per schedule
Calibration of all measuring / test instruments
Rectification of Breakdown during qualification study

5.2 Identification of Execution Team: All the identified executors involved with this protocol are to
record name, designation, signature and date. Verify the training details in the respective
procedures involved in the protocol. Record the observation in the data sheet attached
as Annexure-1

6.0 Qualification Test Program and frequency:

6.1 Following test procedures are followed to qualify the equipment for its operation.

REVALIDATIO SUGGESTED
S.No TEST PARAMETER N TEST TIME MAXIMUM TIME
FREQUENCY INTERVAL
Oxygen concentration
1. 12 months NMT 15 Days

2. Oil Mist 3 months NMT 1 Week

3. Carbon Dioxide Con. 12 months NMT 15 Days
4. Carbon Monoxide Conc. 12 months NMT 15 Days

6.2 These test perform only core areas

7.0 Qualification Test Procedure

7.1 OIL MIST

Objective:

The Objective of this test is to determine the amount of oil mist content present in
the Breathing air line.

Equipments Used: Gastec Detector tube

Gastec Detector tube method

1. Flush the Breathing air from the user point for 2 minutes, before sampling.
2. Make it assembled the air test kit.
3. Break tips off a fresh detector tube by using the tube tip breaker of the pump.
4. Inset the tube in to the pump inlet with arrow on the tube pointing toward
pump.
5. Read the concentration level at the interface where the stained reagent meets
the unstained reagent.

O-QA008/F01-00 Page 6 of 11
 Heter
o
PERFORMANCE QUALIFICATION PROTOCOL
Equipment Name : BREATHING AIR SYSTEM
Equipment Number : O-ENE-011 Facility : Oncology Formulation Facility
Protocol Number : VPO-EN011-00 Effective date :

6. For oil mist follow the parameters as mentioned below (109AD):

Measuring Range 0.2 5.0 mg/ m3

Sampling Volume 20000 ml
Sampling rate 1 Liter per minute
Sampling Time 20 minutes
Colour Change Pale red Pale Blue
Reaction Principle Oil Mist + Cr6+ Cr3+

7. Coefficient of Variation: 15 % (for 0.2 to 1.0 mg/ m3), 10 % (for 1.0 to 5.0 mg/
m3)

8. As soon as the sampling time has finished, turn off the cylinder or compressor,
and remove tube from the tube holder and then read the colour changed layer
immediately.

9. If necessary, multiply the readings by the correction factors of the pump

strokes and atmospheric pressure respectively
To correct for pressure, use the formula below
Tube reading (ppm) x 1013 (hPa)
Atmospheric Pressure (hPa)
10. Sample volume exceeds the prescribed volume compensate the tube reading
with the following formula

11. True Concentration(mg/m3)=Tube Reading (mg/m3)x[20000(ml)/Sample

Volume (ml)]

Acceptance Criteria:
As per BP - Less than 0.10 mg/m3
As per EP - Less than 0.10 mg/m3
As per ISO 8573-1:2010 (Class II) Less than 0.1 mg/m3

REFERENCES
ISO-8573-1:2010 (Class-II),
EUROPEAN PHARMACOPOEIA,
BRITISH PHARMACOPOEIA

7.2 CARBON DIOXIDE CON (CO 2).

Objective:

The Objective of this test is to determine the amount of carbon dioxide content
detection in the Breathing line.

O-QA008/F01-00 Page 7 of 11
 Heter
o
PERFORMANCE QUALIFICATION PROTOCOL
Equipment Name : BREATHING AIR SYSTEM
Equipment Number : O-ENE-011 Facility : Oncology Formulation Facility
Protocol Number : VPO-EN011-00 Effective date :

Equipments Used: Gastec Detector tube

Gastec Detector tube method

1. Flush the Breathing air from the user point for 2 minutes, before sampling.
2. Make it assembled the air test kit.
3. Break tips off a fresh detector tube in the tube tip breaker of the pump.
4. Inset the tube in to the pump inlet with arrow on the tube pointing toward
pump.
5. Read the concentration level at the interface where the stained reagent meets
the unstained reagent.

6. For Carbon Dioxide follow the parameters as mentioned below (Lot No.2LC )

Measuring Range 100 2000 ppm

Number of pump stroke 1(100 ml for two minutes )
Stroke correction factor 1
Sampling Time 2 minutes
Detecting Limit 20 ppm ( N=1)
Colour Change Pale red Yellow
Reaction Principle CO2 + 2K0H+ K2C003+H20
7. Coefficient of Variation: 150 % (for 100 to 600 ppm), 5% (for 600 to 2000 ppm)
8. If necessary, multiply the readings by the correction factors of the pump strokes
and atmospheric pressure respectively
9. To correct for pressure, use the formula below
Tube reading (ppm) x 1013 (hPa)
Atmospheric Pressure (hPa)

10. As soon as the sampling time has finished, turn off the cylinder or compressor,
and remove tube from the tube holder and then read the colour changed layer
immediately.

Acceptance Criteria:

As per BP Maximum 500ppm V/V

As per EP - Maximum 500ppm V/V

7.3 CARBON MONOXIDE AND OXYGEN CONCENTRATION

Objective:

The Objective of this test is to determine the amount of O2 and CO gas

concentration level present in the Breathing air line.

Equipments Used:

RAE Instruments

O-QA008/F01-00 Page 8 of 11
 Heter
o
PERFORMANCE QUALIFICATION PROTOCOL
Equipment Name : BREATHING AIR SYSTEM
Equipment Number : O-ENE-011 Facility : Oncology Formulation Facility
Protocol Number : VPO-EN011-00 Effective date :

Procedure:

1. Flush the Breathing air from the user point for 2 minutes, before
sampling.
2. The gas is sampled through the probe with a primary pump powered at
constant voltage.
3. The zero drift is automatically corrected by the instrument every time it
is switched ON using fresh air as reference.
4. When analysis takes more time, a new auto zero procedure should be
performed.
5. The measured and calculated parameters are indicated on a LCD
alphanumeric display equipped with automatic back light device for
easy readings.
Gas Sensors:

The analyzer uses long life sensors for O2 and CO measurements. The gas
sensors are electrochemical cells composed by two electrodes (anode and
cathode) and an electrolyte solution. The sampled gas goes through a
selective diffusion membrane. The oxidation process produces an output
electrical signal proportional to the gas concentration. The signal is
evaluated by the electronics, converted to digital, processed by the
microprocessor, displayed and printed with a 0.1 % volume resolution.

Acceptance Criteria:

1. O2 concentration present per cubic meter of Breathing air should be >

20.4 % a
2. CO shall not be more than 5 ppm

Reff: EUROPEAN PHARMACOPOEIA, IS

8.0 Records of Observations

Record the observations of after execution of each test procedures, in the Annexure
(Recording of Observations for Performance Qualification).

If any specification is not meeting against required specification / acceptance criteria,

write No in the Meeting Requirement column, specify the discrepancy under
comments and must be explained in Discrepancy and Corrective Action Report

9.0 Re Qualification
Performance Qualification of BREATHING AIR SYSTEMfor the tests mentioned
above in test matrix of this protocol shall be followed.
The qualification should also be performed additionally in case of following
o Any major modification in equipment after the last performance
qualification. This must be properly documented through a change
control system.

O-QA008/F01-00 Page 9 of 11
 Heter
o
PERFORMANCE QUALIFICATION PROTOCOL
Equipment Name : BREATHING AIR SYSTEM
Equipment Number : O-ENE-011 Facility : Oncology Formulation Facility
Protocol Number : VPO-EN011-00 Effective date :

o Adjustments made in the instruments, to correct the non-compliance of

operational parameters with respect to specifications.

10.0Discrepancy and Corrective Action Report

Document any discrepancies observed during the qualification of the Equipment in the
annexure. Include the corrective actions of the same. When all the discrepancies are
satisfactorily resolved or an approved action plan is developed which ensures that the
discrepancy will be resolved, document that the system is ready for next step in the
qualification.

11.0Compilation, Review and Summary Report

Compile and review that all test procedures have been completed, reconciled and
attached to this protocol. Verify that the approvals for deviations (if any) have been
taken and are resolved appropriately to the satisfaction.

Performance Qualification shall be considered acceptable when all the conditions

specified in the Qualification procedures have been met.

Prepare the Performance Qualification report as per the SOP No. O-QA008 and submit
this for review and approval to the Validation Core Team.

12.0Appendix

12.1 Abbreviations and Definitions

ABBREVIATION FULL FORM

CFU Colony Forming Unit
PQ Performance qualification
LPM Litter per minutes
ml Millilitre
m3 Meter cube
Mg Mille gram
SOP Standard Operating Procedure
No. Number
ppm Parts per million
URS User requirement Specification
CFM Cubic feet per minutes
C Degree Centigrade

O-QA008/F01-00 Page 10 of 11
 Heter
o
PERFORMANCE QUALIFICATION PROTOCOL
Equipment Name : BREATHING AIR SYSTEM
Equipment Number : O-ENE-011 Facility : Oncology Formulation Facility
Protocol Number : VPO-EN011-00 Effective date :

12.2 References

SOP No. : O-QA008 (Installation, Operational and Performance Qualification of

Equipment / Instrument)

13.0Enclosure

Annexure No. Description

1 Identification of the Executors
2 Breathing air sampling locations
3 Observation record of Oil mist and Carbon dioxide concentration
Record Observation of Carbon Monoxide and Oxygen
4
Concentration
5 Discrepancy and Corrective Action

O-QA008/F01-00 Page 11 of 11