Qualification

Compressed Air System

Herny Prasetya
AIM Consultant

ISPE Indonesia Affiliate Seminar 8 December 2010

Pharmaceutical - Recommendation
ISO 8573 – 1 : 2001 Compressed Air Quality Standard
Solid Particle Water Vapour Oil (incl.
Vapour)
Class Maximum number of particle Pressure mg/m³
per m³ Dewpoint
0.1 – 0.5 µ 0.5 – 1 µ 1 – 5 µ
1 100 1 0 -70 0.01
2 100 1 10 -40 0.1
3 - 10 500 -20 1
4 - - 1 3 5
5 - - 20 7 -
6 - - - 10 -
ISO 8573 – 1 : 2001 Class 1.2.1

Some industry required :

•Zero class
•Viable count : < 1 cfu/ft3
•Hydrocarbon content : < 0.03 ppm

ISPE Indonesia Affiliate Seminar 8 December 2010

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ISO 8573 - COMPRESSED AIR
QUALITY STANDARD
How to read :
ISO 8573.1 : 2001 Class 1.2.1
Equates to :

ISPE Indonesia Affiliate Seminar 8 December 2010

Air Quality Classes

Solid Particle Water Oil (incl.
Vapour Vapour)
mg/m³
Application ISO 8375 - 1 Maximum number of Pressure
Class particle per m³ Dewpoint
0
0.1 – 0.5 µ 0.5 – 1 – 5 C
1µ µ
Product 1.2.1 100 1 0 -40 0.01
contact
Non Contact 2.4.1 100000 1000 10 3 0.01
Food and food 2.2.1 100000 1000 10 -40 0.01
surface
contact
Non Contact- 2.2.1 100000 1000 10 -40 0.01
High Risk

ISPE Indonesia Affiliate Seminar 8 December 2010

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Systems
• To support pharmaceutical production activities, state-
of-the-art factories include systems, which have to be
conceived according to GEP and cGMP.
• Some of these systems have a direct impact on product
quality, some an indirect impact.
• Systems with direct impact must be identified and
documented in a more exhaustive way, and evaluated
in relation to critical GMP parameters.
• QA, Production and Engineering must agree beforehand
on the scope of qualification activities, ideally right at
project start.

ISPE Indonesia Affiliate Seminar 8 December 2010

Impact Assessment
•Identify system

•Develop system
•Boundaries

•Does the system have a •YES

•Direct impact on product
•quality
•No

•Is the system linked to a •YES •“Indirect Impact” •“Direct Impact”

•Direct impact System? •system •system
•No

•“ No Impact” •Develop Supporting

•system •rationale

ISPE Indonesia Affiliate Seminar 8 December 2010

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Impact Assessment

• Direct impact:
Sistem memberikan dampak langsung pada mutu
produk
• Indirect impact :
Sistem terkait dengan / pada sistem direct impact
• No impact :
Tidak terkait dan tidak berdampak pada mutu produk

ISPE Indonesia Affiliate Seminar 8 December 2010

IMPACT ASSESSMENT - Direct Impact

• Purified Water
• Water For Injection
• Clean steam
• HVAC
• Compressed air, special gases

ISPE Indonesia Affiliate Seminar 8 December 2010

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 Indirect Impact :
§§ Raw water
Raw water treatment
treatment
§§ Cooling system
Cooling system
§§ Effluent treatment
Effluent treatment
§§ Heating System
Heating System
§§ Boiler house
Boiler house

ISPE Indonesia Affiliate Seminar 8 December 2010

V-MODEL “DIRECT IMPACT” SYSTEM

•Qualification

•PQ Test Plan

•URS •PQ

•OQ Test Plan

•FS •OQ
•(Incl FAT)

•IQ Test Plan

•DS •IQ
•(Incl PDI)

•Implementation

•ISPE Baseline Pharmaceutical Engineering Guides for New and Renovated Facilities- Volume 5 : Commissioning and
Qualification – March 2001

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 V-MODEL “INDIRECT IMPACT” SYSTEM

•Commissioning Plan
•URS •Performance Testing

•Inc FAT
•Setting to work
•FS •Regulation & Adjustment
•Testing

•Inc PDI
•Physical Completion
•DS
•& Inspection

•Implementation

•PDI = Pre Delivery Inspection

•ISPE Baseline Pharmaceutical Engineering Guides for New and Renovated Facilities- Volume 5 : Commissioning
and Qualification – March 2001

Commissioning Overview

• Takes equipment from installation to

operation
• Incorporates a systematic method of testing
and documentation
• Proper commissioning tests and
documentation satisfy many IQ/OQ
requirements

ISPE Indonesia Affiliate Seminar 8 December 2010

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Commissioning/Validation
Documentation Overlap

Commissioning Validation
• Equipment lists • Equipment lists

• Component lists • Component lists

• Utility verification forms • Utility verification forms

• System drawings • System drawings

• Operating procedures • Operating procedures

ISPE Indonesia Affiliate Seminar 8 December 2010

Commissioning/Validation
Documentation Overlap

Commissioning
• Calibration records
• Input/output testing
• Loop checks
• Alarm testing
• Sequence of operations
• Integrated system testing
Validation
• Calibration records
• Input/output testing
• Loop checks
• Alarm testing
• Sequence of operations
• Integrated system testing

ISPE Indonesia Affiliate Seminar 8 December 2010

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Differences Between Commissioning and
Validation

Commissioning
• Supplier Responsibility
• Objective is to identify and
rectify problems
• Approved protocol not required
• Typically operated by supplier
Validation
• User Responsibility
• Demonstrate process is as
specified and under control
• Must follow an approved protocol
• Owned & operated by user

ISPE Indonesia Affiliate Seminar 8 December 2010

Differences Between Commissioning and

Validation

Commissioning Validation

• Not all data and adjustments
are recorded & reviewed
• No written report unless specified
• Reviewed for acceptance
by engineering/project team
• All data & adjustments must be
recorded/reviewed
• Written report is required
• Reviewed and approved by
Quality Assurance

ISPE Indonesia Affiliate Seminar 8 December 2010

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COMPRESSED AIR SYSTEM
QUALIFICATION
• Compressed air system which are in
contact with product is a “Direct Impact”
system
• Qualification work is needed
• OQ/EDR
• IQ
• OQ
• PQ

ISPE Indonesia Affiliate Seminar 8 December 2010

User Requirement Specification

URS consideration should include :

• Quality of air generated from the system
at generation and point of use
• Prevention of contamination
• Capasity
• Safety measure

ISPE Indonesia Affiliate Seminar 8 December 2010

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 Validation Master Plan
1. Introduction
2. Purpose of the system
3. Scope
4. Basic approach to the validation(validation life
cycle) ie:IQ/OQ/PQ,as built drawing
5. Responsibilities
6. Acceptance Criteria
7. Certification and approval
8. References

ISPE Indonesia Affiliate Seminar 8 December 2010

Design Qualification-EDR

• Design of the system including material of contruction

• Function of each sub-system
• Distribution system including welding, receiver and break tank.
Loop vs single pass
• Temperature
• Expected pressure and flow rate
• Initial flushing system to remove all particle, oil and other
contaminant

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ISPE Indonesia Affiliate Seminar 8 December 2010

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 Objective of Installation Qualification
• The unit are constructed and built in conformity with the specification as
specified in the User Requirement Specification
• The unit and all components are installed correctly and the utilities are in
line with the equipment requirement
• The unit and all components meet the current GMP requirement and
regulatory obligation
• All critical instrument have been identified for calibration
• Calibration of the measuring instruments are properly done
• Standard Operating Procedures have been identified and listed
• Operation manuals required for routine operation and maintenance of
the said system are identified and available
• Change control procedure exist and documentation changes system for
the installed state of the equipment are available
• Required spare parts are identified

ISPE Indonesia Affiliate Seminar 8 December 2010

Installation Qualification

• Unit Description
• Collect and compile documentation describing the unit provided by
manufacturer.
• Verify against actual unit installed and record any discrepancies
• Document Verification
• Collect, compile and verify documentation related to the unit including
installation documents, calibration documents and user manuals.
Verification is emphasizing in document availability and completion.

ISPE Indonesia Affiliate Seminar 8 December 2010

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 Installation Qualification
• Main Unit Verification
• Walk through the unit and verify that the installed main component is
according to its documentation.
• Utility and Instrument Verification
• Walk through the unit and verify that utility for operation of the unit has
been installed properly according to its documentation.
• Similar check is applied to instrumentation, probe and measuring device
installed to the unit.
• Software and programming installation is verified by compiling
programming documentation and printouts, if any

ISPE Indonesia Affiliate Seminar 8 December 2010

Installation Qualification

IQ check the installation and should include :

• Compressor type and capacity
• Receiver, dryer and filter capacities
• Materials of construction
• Correct installation and services supplied
• Pressure/leak tests
• Pipework has been cleaned or blown clear
• Instrument calibration
• Preventative maintenance

ISPE Indonesia Affiliate Seminar 8 December 2010

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Objective of Operational
Qualification
Operational Qualification is to ensure that unit
installed have fulfilled the following criteria:
• Unit and all components are operating with given
specification.
• All of operation can be carried out by those
component and comply with given condition.

ISPE Indonesia Affiliate Seminar 8 December 2010

Operational Qualification
• Procedure Verification
• Verification of procedure document to be used with the unit.
• Operation Verification
• Operation testing of all components of the unit, including the
instrumentation and utilities. All components must be operable at
its intended use, at normal condition with specified limit of
tolerance.
• Walk through and have all components of the unit, including
utilities and instrumentation tested for operability in normal
condition according to documentation.
• Record tolerance limit and deviations, if any.

ISPE Indonesia Affiliate Seminar 8 December 2010

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Operational Qualification
OQ check should include:
• A formal review of all major components in accordance
with their intended purpose (PWO-particle,Water,Oil
etc).

• The system is well maintained through an inspection of

the components and records of preventive and non
routine maintenance as well as deviations.

• All monitoring devices are calibrated and operating as

per design.

ISPE Indonesia Affiliate Seminar 8 December 2010

Qualification Outline - PQ
• Document Verification
• Verification of complete documentation of the unit, including but
not limited to Installation and Operational Qualification, Standard
Operating Procedures of the unit, calibration record of instrument
used and related drawing.

• Operational Verification
• Verification of operational condition, that the unit and
component are performing as intended and producing the
compressed air with predetermined pressure and flow rate.
• Air Quality Verification
• Verification of the air quality produce at discharge
point.
ISPE Indonesia Affiliate Seminar 8 December 2010

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 Performance Qualification
WORKSHEET
KUALIFIKASI KINERJA
Bagian Seharusnya Hasil Pengamatan Verifikasi
1. Kompressor Udara Tekanan Maksimum = 7,0 bar
Intercooler Pressure = 2,25 bar
Manual dan automatic water drain ; berfungsi /
bekerja
2. Tangki Udara Tekanan Maksimum= 7,5 bar
Manual dan automatic water drain ; berfungsi /
bekerja
3. Refrigran Dryer Pendinginan bekerja setelah 15 menit
pengoperasian temperatur mendekati 1° C
4. Desiccant Dryer Penyerapan udara lembab berlangsung, udara
tekan yang dikeluarkan tidak kurang dari - 40°
C Dew Point
5. Filter-Filter a. water separatore tidak terjadi kebocoran

b. High Efficiency General Purpose Protection

tidak bocor dan tidak buntu, dan delta p, pada
posisi green maximal 0.35 bar / 5 psi
c. High Efficiency Oil Removal Filtration tidak
bocor dan tidak buntu, dan delta p, pada posisi
green maximal 0.35 bar / 5 psi.
d. General Purpose Dust Filtration tidak bocor
dan tidak buntu, dan delta p, pada posisi green
maximal 0.35 bar / 5 psi .

6. Valve Dapat menyalurkan udara tekan bila dibuka

dan terputus bila ditutup, udara tekan tidak ada
yang bocor.

ISPE Indonesia Affiliate Seminar 8 December 2010

PQ – Dew Point Measurement

§ Dew point atau water content, ditentukan

§ dengan alat tertentu seperti :
§ Electrolytic hygrometer
§ Frost point analysis
§ Piezoelectricsorption hygrometer

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ISPE Indonesia Affiliate Seminar 8 December 2010

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Dew Point

MS ver. 1 - 2010

Particle Count

• Pemeriksaan jumlah partikel dilakukan terhadap

point of use kritikal dari compressed air, dengan
menggunakan particle counter
• Udara dialirkan melalui flow reducer sebelum diperiksa
dengan particle counter.
• Flow udara tekan diukur menggunakan anemometer
sebanyak 6 kali pengukuran, kemudian diambil rata-
ratanya.

ISPE Indonesia Affiliate Seminar 8 December 2010

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 PQ – Microbial Measurement

Microbial contamination
Ø Microba dari compressed air ditangkap dengan
melewatkannya pada suatu media a.l phosphate buffer pH 7
atau pepton water
Ø Mikroba difilter dengan filter steril 0,22 m, filter kemudian
diletakkan pada petridish berisi media padat dan dinkubasi
pada suhu dan waktu yang sesuai

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ISPE Indonesia Affiliate Seminar 8 December 2010

PQ – Oil Content
Method :
• FTIR
• Gas chromatography
• Chemical indicator test : used only as
initial investigation

ISPE Indonesia Affiliate Seminar 8 December 2010

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PQ – Oil Content

§ Hydrocarbon
§ Oli dari compressed air ditangkap dengan cellulose
ester filter dengan pore size 0,8 m atau 5,0 m dengan
diameter 37 mm
§ Oli pada filter dilarutkan dalam CCl4
§ Kemudian diperiksa dengan FTIR pada panjang
gelombang 2940 cm-1

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ISPE Indonesia Affiliate Seminar 8 December 2010

Oil Vapour Content – ISO 8573-5

ISPE Indonesia Affiliate Seminar 8 December 2010

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Oil Vapour Content – ISO 8573-5

ISPE Indonesia Affiliate Seminar 8 December 2010

Oil Vapour Content – ISO 8573-5

• Extract main zone using carbon disulphite in
a shaker for 30 minutes
• Use bemzene, toluene, ethylbenzene and
octane as internal standard
• Analyze on gas chromatograph with mass
spec detector

ISPE Indonesia Affiliate Seminar 8 December 2010

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PQ – Oil Content

1. Isi impinger dengan calsium chlorida anhydrous

2. Sambung pada titik sampling
3. On kan vacuum
4. Setelah selesai keluarkan Calcium chloride, masukkan kedalam labu pemisah
5. Ekstrak dengan larutan organik dan pisahkan larutan minyaknya menggunakan
Rotary Evaporator
6. Ukur dengan GC

ISPE Indonesia Affiliate Seminar 8 December 2010

Example Testing instrument : multi test

ISPE Indonesia Affiliate Seminar 8 December 2010

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Sampling Principle

Compressed
air
Air
> 160 psi Regulator Measure
impaction
reduce flow
rate sampler
psi

•Petri Plate
•Particle count
•Dewpoint
•Oil sampler

ISPE Indonesia Affiliate Seminar 8 December 2010

ISPE Indonesia Affiliate Seminar 8 December 2010

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