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Herny Prasetya
AIM Consultant
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
1
ISO 8573 - COMPRESSED AIR
QUALITY STANDARD
How to read :
ISO 8573.1 : 2001 Class 1.2.1
Equates to :
2
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.
Impact Assessment
•Identify system
•Develop system
•Boundaries
3
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
• Purified Water
• Water For Injection
• Clean steam
• HVAC
• Compressed air, special gases
4
Indirect Impact :
§§ Raw water
Raw water treatment
treatment
§§ Cooling system
Cooling system
§§ Effluent treatment
Effluent treatment
§§ Heating System
Heating System
§§ Boiler house
Boiler house
•Implementation
•ISPE Baseline Pharmaceutical Engineering Guides for New and Renovated Facilities- Volume 5 : Commissioning and
Qualification – March 2001
5
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
•ISPE Baseline Pharmaceutical Engineering Guides for New and Renovated Facilities- Volume 5 : Commissioning
and Qualification – March 2001
Commissioning Overview
6
Commissioning/Validation
Documentation Overlap
Commissioning Validation
• Equipment lists • Equipment lists
Commissioning/Validation
Documentation Overlap
Commissioning Validation
• Calibration records • Calibration records
• Input/output testing • Input/output testing
• Loop checks • Loop checks
• Alarm testing • Alarm testing
• Sequence of operations • Sequence of operations
• Integrated system testing • Integrated system testing
7
Differences Between Commissioning and
Validation
Commissioning Validation
• Supplier Responsibility • User Responsibility
• Objective is to identify and • Demonstrate process is as
rectify problems specified and under control
• Approved protocol not required • Must follow an approved protocol
• Typically operated by supplier • Owned & operated by user
Commissioning Validation
• Not all data and adjustments • All data & adjustments must be
are recorded & reviewed recorded/reviewed
• No written report unless specified • Written report is required
• Reviewed for acceptance • Reviewed and approved by
by engineering/project team Quality Assurance
8
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
9
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
Design Qualification-EDR
20
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
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.
11
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
Installation Qualification
12
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.
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.
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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).
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
14
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
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ISPE Indonesia Affiliate Seminar 8 December 2010
15
Dew Point
MS ver. 1 - 2010
Particle Count
16
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 : used only as
initial investigation
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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
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Oil Vapour Content – ISO 8573-5
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PQ – Oil Content
20
Sampling Principle
Compressed
air
Air
> 160 psi Regulator Measure
impaction
reduce flow
rate sampler
psi
•Petri Plate
•Particle count
•Dewpoint
•Oil sampler
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