Qualification Compressed Air SystemHP

Qualification Compressed Air System Herny Prasetya AIM Consultant

ISPE Indonesia Affiliate Seminar 8 December 2010

Pharmaceutical - Recommendation Class

ISO 8573 – 1 : 2001 Compressed Air Quality Standard Solid Particle Water Vapour Oil (incl. Vapour) 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 2 100 1 3 10 4 5 6 ISO 8573 – 1 : 2001 Class 1.2.1

0 10 500 1 20 -

-70 -40 -20 3 7 10

0.01 0.1 1 5 -

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 Vapour

Application ISO 8375 - 1 Maximum number of Class particle per m³

Product contact Non Contact Food and food surface contact Non ContactHigh Risk

1.2.1

0.1 – 0.5 µ 0.5 – 1 – 5 1µ µ 100 1 0

Oil (incl. Vapour) mg/m³

Pressure Dewpoint 0

C

-40

0.01

2.4.1 2.2.1

100000 100000

1000 1000

10 10

3 -40

0.01 0.01

2.2.1

100000

1000

10

-40

0.01

ISPE Indonesia Affiliate Seminar 8 December 2010

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Systems • To support pharmaceutical production activities, stateof-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 •quality

•YES

•No •Is the system linked to a •Direct impact System?

•YES

•“Indirect Impact” •system

•“Direct Impact” •system

•No

•“ No Impact” •system

•Develop Supporting •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 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

•OQ Test Plan •(Incl FAT)

•FS

•IQ Test Plan •DS

•(Incl PDI)

•OQ

•IQ

•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

•Inc FAT •FS

•DS

•Inc PDI

•Performance Testing

•Setting to work •Regulation & Adjustment •Testing

•Physical Completion •& 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

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

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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 • Not all data and adjustments are recorded & reviewed • No written report unless specified • Reviewed for acceptance by engineering/project team

Validation • 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. 2. 3. 4. 5. 6. 7. 8.

Introduction Purpose of the system Scope Basic approach to the validation(validation life cycle) ie:IQ/OQ/PQ,as built drawing Responsibilities Acceptance Criteria Certification and approval 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

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 1. Kompressor Udara

Seharusnya

Hasil Pengamatan

Verifikasi

Tekanan Maksimum = 7,0 bar Intercooler Pressure = 2,25 bar

2. Tangki Udara

3. Refrigran Dryer 4. Desiccant Dryer

5. Filter-Filter

Manual dan automatic water drain ; berfungsi / bekerja Tekanan Maksimum= 7,5 bar Manual dan automatic water drain ; berfungsi / bekerja Pendinginan bekerja setelah 15 menit pengoperasian temperatur mendekati 1° C Penyerapan udara lembab berlangsung, udara tekan yang dikeluarkan tidak kurang dari - 40° C Dew Point 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

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 rataratanya.

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

ISPE Indonesia Affiliate Seminar 8 December 2010

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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

ISPE Indonesia Affiliate Seminar 8 December 2010

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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. 2. 3. 4. 5.

Isi impinger dengan calsium chlorida anhydrous Sambung pada titik sampling On kan vacuum Setelah selesai keluarkan Calcium chloride, masukkan kedalam labu pemisah 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 > 160 psi

Regulator reduce psi

Measure flow rate

Air impaction sampler

•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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