Post on 26-Mar-2015
transcript
1
QualificationCompressed Air System
Herny PrasetyaAIM Consultant
ISPE Indonesia Affiliate Seminar 8 December 2010
Pharmaceutical - RecommendationISO 8573 – 1 : 2001 Compressed Air Quality Standard
Solid Particle Water Vapour Oil (incl. Vapour) mg/m³Class Maximum number of particle
per m³Pressure Dewpoint
0.1 – 0.5 µ 0.5 – 1 µ 1 – 5 µ
1 100 1 0 -70 0.012 100 1 10 -40 0.13 - 10 500 -20 14 - - 1 3 55 - - 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
2
How to read :ISO 8573.1 : 2001 Class 1.2.1Equates to :
ISO 8573 - COMPRESSED AIR QUALITY STANDARD
ISPE Indonesia Affiliate Seminar 8 December 2010
Air Quality Classes
Solid Particle Water Vapour
Oil (incl. Vapour) mg/m³
Application ISO 8375 - 1 Class
Maximum number of particle per m³
Pressure Dewpoint
0.1 – 0.5 µ 0.5 –1 µ
1 – 5 µ
0C
Product contact
1.2.1 100 1 0 -40 0.01
Non Contact 2.4.1 100000 1000 10 3 0.01 Food and food
surface contact
2.2.1 100000 1000 10 -40 0.01
Non Contact-High Risk
2.2.1 100000 1000 10 -40 0.01
ISPE Indonesia Affiliate Seminar 8 December 2010
3
Systems
• To support pharmaceutical production activities, state-of-the-art factories include systems, which have to beconceived according to GEP and cGMP.
• Some of these systems have a direct impact on productquality, some an indirect impact.
• Systems with direct impact must be identified and documented in a more exhaustive way, and evaluatedin relation to critical GMP parameters.
• QA, Production and Engineering must agree beforehandon the scope of qualification activities, ideally right atproject start.
ISPE Indonesia Affiliate Seminar 8 December 2010
Impact Assessment•Identify system
•Develop system •Boundaries
•Does the system have a•Direct impact on product•quality
•Is the system linked to a•Direct impact System?
•“Indirect Impact”•system
•“Direct Impact”•system
•“ No Impact”•system
•Develop Supporting•rationale
•YES
•YES
•No
•No
ISPE Indonesia Affiliate Seminar 8 December 2010
4
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
5
Indirect Impact :§ Raw water treatment
§ Cooling system
§ Effluent treatment
§ Heating System
§ Boiler house
§ Raw water treatment
§ Cooling system
§ Effluent treatment
§ Heating System
§ Boiler house
ISPE Indonesia Affiliate Seminar 8 December 2010
V-MODEL “DIRECT IMPACT” SYSTEM
•URS
•FS
•DS
•Implementation
•IQ
•OQ
•PQ•PQ Test Plan
•OQ Test Plan
•IQ Test Plan
•(Incl FAT)
•(Incl PDI)
•Qualification
•ISPE Baseline Pharmaceutical Engineering Guides for New and Renovated Facilities- Volume 5 : Commissioning and Qualification – March 2001
6
V-MODEL “INDIRECT IMPACT” SYSTEM
•URS
•FS
•DS
•Implementation
•Physical Completion•& Inspection
•Setting to work•Regulation & Adjustment•Testing
•Performance Testing•Commissioning Plan
•Inc FAT
•Inc PDI
•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
7
Commissioning/Validation Documentation Overlap
Commissioning• Equipment lists
• Component lists
• Utility verification forms
• System drawings
• Operating procedures
Validation• Equipment lists
• Component lists
• Utility verification forms
• System drawings
• 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
8
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 & 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
9
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
10
Validation Master Plan 1. Introduction2. Purpose of the system3. Scope4. Basic approach to the validation(validation life
cycle) ie:IQ/OQ/PQ,as built drawing5. Responsibilities6. Acceptance Criteria7. Certification and approval8. References
ISPE Indonesia Affiliate Seminar 8 December 2010
20
• 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
Design Qualification-EDR
ISPE Indonesia Affiliate Seminar 8 December 2010
11
• 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
Objective of Installation Qualification
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
12
• 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
Installation Qualification
ISPE Indonesia Affiliate Seminar 8 December 2010
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
Installation Qualification
ISPE Indonesia Affiliate Seminar 8 December 2010
13
Objective of Operational QualificationOperational 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
14
OQ check should include:• A formal review of all major components in accordance
with their intended purpose (PWO-particle,Water,Oiletc).
• 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.
Operational Qualification
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
15
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 menitpengoperasian temperatur mendekati 1° C
4. Desiccant Dryer Penyerapan udara lembab berlangsung, udaratekan yang dikeluarkan tidak kurang dari - 40°C Dew Point
5. Filter-Filter a. water separatore tidak terjadi kebocoran
b. High Efficiency General Purpose Protectiontidak bocor dan tidak buntu, dan delta p, padaposisi greenmaximal 0.35 bar / 5 psi
c. High Efficiency Oil Removal Filtration tidakbocor dan tidak buntu, dan delta p, pada posisigreenmaximal 0.35 bar / 5 psi.
d. General Purpose Dust Filtration tidak bocordan tidak buntu, dan delta p, pada posisi greenmaximal 0.35 bar / 5 psi .
6. Valve Dapat menyalurkan udara tekan bila dibukadan terputus bila ditutup, udara tekan tidak adayang bocor.
Performance Qualification
ISPE Indonesia Affiliate Seminar 8 December 2010
30
§ Dew point atau water content, ditentukan§ dengan alat tertentu seperti :
§ Electrolytic hygrometer§ Frost point analysis§ Piezoelectricsorption hygrometer
PQ – Dew Point Measurement
ISPE Indonesia Affiliate Seminar 8 December 2010
16
Dew Point
MS ver. 1 - 2010
Particle Count
• Pemeriksaan jumlah partikel dilakukan terhadappoint of use kritikal dari compressed air, denganmenggunakan 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
17
33
Microbial contaminationØMicroba dari compressed air ditangkap dengan
melewatkannya pada suatu media a.l phosphate buffer pH 7atau pepton waterØMikroba difilter dengan filter steril 0,22 m, filter kemudian
diletakkan pada petridish berisi media padat dan dinkubasipada suhu dan waktu yang sesuai
PQ – Microbial Measurement
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
18
35
§ Hydrocarbon§ Oli dari compressed air ditangkap dengan cellulose
ester filter dengan pore size 0,8 m atau 5,0 m dengandiameter 37 mm § Oli pada filter dilarutkan dalam CCl4§ Kemudian diperiksa dengan FTIR pada panjang
gelombang 2940 cm-1
PQ – Oil Content
ISPE Indonesia Affiliate Seminar 8 December 2010
Oil Vapour Content – ISO 8573-5
ISPE Indonesia Affiliate Seminar 8 December 2010
19
Oil Vapour Content – ISO 8573-5
ISPE Indonesia Affiliate Seminar 8 December 2010
• 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
Oil Vapour Content – ISO 8573-5
ISPE Indonesia Affiliate Seminar 8 December 2010
20
1. Isi impinger dengan calsium chlorida anhydrous2. Sambung pada titik sampling3. On kan vacuum4. Setelah selesai keluarkan Calcium chloride, masukkan kedalam labu pemisah5. Ekstrak dengan larutan organik dan pisahkan larutan minyaknya menggunakan
Rotary Evaporator6. Ukur dengan GC
PQ – Oil Content
ISPE Indonesia Affiliate Seminar 8 December 2010
Example Testing instrument : multi test
ISPE Indonesia Affiliate Seminar 8 December 2010
21
Sampling Principle
Compressed air
> 160 psiAir impaction sampler
Regulatorreducepsi
Measure flow rate
•Petri Plate•Particle count•Dewpoint•Oil sampler
ISPE Indonesia Affiliate Seminar 8 December 2010
ISPE Indonesia Affiliate Seminar 8 December 2010