Вы находитесь на странице: 1из 21
Qualification Compressed Air System Herny Prasetya AIM Consultant ISPE Indonesia Affiliate Seminar 8 December 2010
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
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
0.1 – 0.5 µ
Dewpoint
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
ISO 8573 - COMPRESSED AIR QUALITY STANDARD How to read : ISO 8573.1 : 2001 Class
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
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 µ
1 – 5
µ
C
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
surface
contact
Non Contact-
High Risk
2.2.1
100000
1000
10
-40
0.01
2.2.1
100000
1000
10
-40
0.01
ISPE Indonesia Affiliate Seminar 8 December 2010
Systems • To support pharmaceutical production activities, state- of-the-art factories include systems, which have to be
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 •Direct impact on product
Impact Assessment
•Identify system
•Develop system
•Boundaries
•Does the system have a
•Direct impact on product
•quality
•YES
•No
•YES
•Is the system linked to a
•Direct impact System?
•“Indirect Impact”
•“Direct Impact”
•system
•system
•No
•Develop Supporting
•“ No Impact”
•system
•rationale
ISPE Indonesia Affiliate Seminar 8 December 2010
Impact Assessment • Direct impact: Sistem memberikan dampak langsung pada mutu produk • Indirect impact :
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 •
IMPACT ASSESSMENT - Direct Impact
• Purified Water
• Water For Injection
• Clean steam
• HVAC
• Compressed air, special gases
ISPE Indonesia Affiliate Seminar 8 December 2010
Indirect Impact : § Raw water treatment § Raw water treatment § Cooling system § Cooling
Indirect Impact :
§
Raw water treatment
§
Raw water 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 •FS •OQ Test Plan •(Incl FAT)
V-MODEL “DIRECT IMPACT” SYSTEM
•Qualification
•PQ Test Plan
•URS
•PQ
•FS
•OQ Test Plan
•(Incl FAT)
•OQ
•IQ
•DS
•IQ Test Plan
•(Incl PDI)
•Implementation
•ISPE Baseline Pharmaceutical Engineering Guides for New and Renovated Facilities- Volume 5 : Commissioning and
Qualification – March 2001
V-MODEL “INDIRECT IMPACT” SYSTEM •Commissioning Plan •URS •Performance Testing •Inc FAT •FS •Setting to work •Regulation
V-MODEL “INDIRECT IMPACT” SYSTEM
•Commissioning Plan
•URS
•Performance Testing
•Inc FAT
•FS
•Setting to work
•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
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
Commissioning/Validation Documentation Overlap Validation Commissioning • Equipment lists • Equipment lists • Component lists • Utility
Commissioning/Validation
Documentation Overlap
Validation
Commissioning
Equipment lists
• Equipment lists
• Component lists
• Utility verification forms
• System drawings
• Operating procedures
Component lists
Utility verification forms
System drawings
Operating procedures
ISPE Indonesia Affiliate Seminar 8 December 2010
Commissioning/Validation Documentation Overlap Commissioning Validation • Calibration records • Input/output testing • Loop checks • Alarm
Commissioning/Validation
Documentation Overlap
Commissioning
Validation
• Calibration records
• Input/output testing
• Loop checks
• Alarm testing
• Sequence of operations
• Integrated system testing
• Calibration records
• Input/output testing
• Loop checks
• Alarm testing
• Sequence of operations
• Integrated system testing
ISPE Indonesia Affiliate Seminar 8 December 2010
Differences Between Commissioning and Validation Commissioning Validation • Supplier Responsibility • Objective is to identify and
Differences Between Commissioning and
Validation
Commissioning
Validation
• Supplier Responsibility
• Objective is to identify and
rectify problems
• Approved protocol not required
• Typically operated by supplier
• 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 &
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
COMPRESSED AIR SYSTEM QUALIFICATION • Compressed air system which are in contact with product is a
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
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
Validation Master Plan 1. Introduction 2. Purpose of the system 3. Scope 4. Basic approach to
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
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
20
ISPE Indonesia Affiliate Seminar 8 December 2010
Objective of Installation Qualification • The unit are constructed and built in conformity with the specification
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.
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
Installation Qualification • Main Unit Verification • Walk through the unit and verify that the installed
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 •
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
Objective of Operational Qualification Operational Qualification is to ensure that unit installed have fulfilled the following
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.
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
Operational Qualification OQ check should include: • A formal review of all major components in accordance
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
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
Performance Qualification WORKSHEET KUALIFIKASI KINERJA Bagian Seharusnya Hasil Pengamatan Verifikasi 1. Kompressor Udara Tekanan Maksimum =
Performance Qualification
WORKSHEET
KUALIFIKASI KINERJA
Bagian
Seharusnya
Hasil Pengamatan
Verifikasi
1. Kompressor Udara
Tekanan Maksimum = 7,0 bar
IntercoolerPressure = 2,25 bar
2. Tangki Udara
Manual dan automatic water drain ; berfungsi /
bekerja
Tekanan Maksimum= 7,5 bar
3. Refrigran Dryer
4. DesiccantDryer
Manual dan automatic water drain ; berfungsi /
bekerja
Pendinginan bekerja setelah 15 menit
pengoperasiantemperatur mendekati 1° C
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 greenmaximal 0.35 bar / 5 psi
c.
High Efficiency Oil Removal Filtration tidak
bocor dan tidak buntu, dan delta p, pada posisi
greenmaximal 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
PQ – Dew Point Measurement
§
Dew point atau water content, ditentukan
§
dengan alat tertentu seperti :
§
Electrolytic hygrometer
§
Frost point analysis
§
Piezoelectricsorption hygrometer
30
ISPE Indonesia Affiliate Seminar 8 December 2010
Dew Point MS ver. 1 - 2010
Dew Point
MS ver. 1 - 2010
Particle Count • Pemeriksaan jumlah partikel dilakukan terhadap point of use kritikal dari compressed air, dengan
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
PQ – Microbial Measurement Microbial contamination Ø Microba dari compressed air ditangkap dengan melewatkannya pada suatu
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
33
ISPE Indonesia Affiliate Seminar 8 December 2010
PQ – Oil Content Method : • FTIR • Gas chromatography • Chemical indicator test :
PQ – Oil Content
Method :
• FTIR
• Gas chromatography
• Chemical indicator test : used only as
initial investigation
ISPE Indonesia Affiliate Seminar 8 December 2010
PQ – Oil Content § Hydrocarbon § Oli dari compressed air ditangkap dengan cellulose ester filter
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
35
ISPE Indonesia Affiliate Seminar 8 December 2010
Oil Vapour Content – ISO 8573-5 ISPE Indonesia Affiliate Seminar 8 December 2010
Oil Vapour Content – ISO 8573-5
ISPE Indonesia Affiliate Seminar 8 December 2010
Oil Vapour Content – ISO 8573-5 ISPE Indonesia Affiliate Seminar 8 December 2010
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
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
PQ – Oil Content 1. Isi impinger dengan calsium chlorida anhydrous 2. Sambung pada titik sampling
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
Example Testing instrument : multi test
ISPE Indonesia Affiliate Seminar 8 December 2010
Sampling Principle Compressed air Air Regulator Measure > 160 psi impaction flow reduce sampler rate psi
Sampling Principle
Compressed
air
Air
Regulator
Measure
> 160 psi
impaction
flow
reduce
sampler
rate
psi
•Petri Plate
•Particle count
•Dewpoint
•Oil sampler
ISPE Indonesia Affiliate Seminar 8 December 2010
ISPE Indonesia Affiliate Seminar 8 December 2010
ISPE Indonesia Affiliate Seminar 8 December 2010