Critical Plant System

Transkripsi

1 Kualifikasi SISTEM untuk pabrik Farmasi Heating, Ventilation and Air Conditioning System (HVAC) Sistem Aliran Udara Water System Sistem Air (pengolahan dan distribusi) Compressed Air and other gases Sistem Udara bertekanan dan gas-gas lain Critical Plant System 1

2 Heating, Ventilation and Air- Conditioning (HVAC) Introduction

3 Tujuan Untuk dapat memahami Perlunya HVAC systems peranan HVAC in dalam menjaga /protection: Product Personnel Environment peranan HVAC dalam dust control HVAC system design dan components.

4 Ruang lingkup HVAC systems can have an impact on product quality (HVAC dapat berdampak pada kualitas produk) It can provide comfortable conditions for operators (dapat memberikan suasana yang nyaman pada operator) The impact on premises and prevention of contamination and cross-contamination to be considered at the design stage (memberikan perlindungan terhadap Contamination dan cros contamination ) Temperature, relative humidity control where appropriate

5 Faktor-faktor yang dapat mempengaruhi kualitas produk farmasi Personnel Validated processes Procedures Starting materials Equipment Packing materials Premises Environment

6 Faktor faktor yang harus diperhatiakn di area produksi yang dapat mempengaruhi kualitas produk : 1. Light ( penyinaran / penerangan area produksi ) 2. Temperature ( suhu ) 3. Relative humidity ( kelembaban ) 4. Air movement ( pola aliran udara ) 5. Microbial contamination ( kontaminasi mikroba ) 6. Particulate contamination ( kontaminasi partikel asing ) Lingkungan yang tidak terkontrol akan memicu turunnya kualitas produk seperti produk yang terkontaminasi.

7 Apakah yang dimaksud dengan kontaminasi? Adalah tercampurnya bahan kimia lain, mikro organisme, partikel asing kedalam bahan baku, produk antara ataupun produk jadi selama proses sampling, proses produksi, packing ataupun repacking. Apakah Cross-contamination /kontaminasi silang? Kontaminasi yang disebabkan tercampurnya bahan baku, produk antara ataupun produk jadi dengan bahan baku produk lain dan atau antar produk selama proses produksi.".

8 Cross-contamination dapat disebabkan diantaranya oleh : 1. Jeleknya design, operasional ataupun pemeliharaan (maintenance) dari air-handling systems and dust extraction systems 2. Tidak tersedianya prosedur (SOP) untuk alur personel, material dan peralatan (Inadequate procedures for, and movement of personnel, materials and equipment ) 3. Insufficiently cleaned equipment ( peralatan yang tidak / kurang bersih.

9 Cross-Contamination Contaminant from Environment Operators Contamination Contaminant from Equipment Product from Environment Operators Cross Contamination Product from Equipment

10 Cross-contamination can be minimized by, e.g. 1. Personnel procedures 2. Adequate premises 3. Use of closed production systems 4. Adequate, validated cleaning procedures 5. Appropriate levels of protection of product 6. Correct air pressure cascade

11 HVAC yang baik akan memberikan perlindungan terhadap: Product protection : melindungi produk dari ; Contamination (kontaminasi) Cross-contamination (kontaminasi silang) Environmental conditions (pencemaran lingkungan) Personnel protection Prevent contact ( melindungi kontak personel dengan produk) Comfort conditions ( membuat kondisi lebih nyaman) Environment protection

12 Protection: Product and personnel Area dimana bahan baku dan produk disimpan harus berada pada ruang dengan klasifikasi bersih ( clean areas ). Pencapaian klasifikasi clean area tergantung pada beberapa faktor diantaranya : Building finishes and structure (bangunan dan struktur bangunan ) Air filtration (sistem penyaringan udara) Air change rate (pertukaran udara) Room pressure (tekanan udara dlm ruangan) Temperature (suhu) Relative humidity Material and personnel flow (alur barang dan manusia) Outside environment (lingkungan luar pabrik) Occupancy and type of product (jenis dan tipe dari produk)

13 Air filtration and air change rate merupakan penentu untuk tercapainya klasifikasi ruangan Air change rate tergantung pada beberapa faktor diantaranya. Spesifikasi / klasifikasi ruangan Kualitas sistem filtrasi dari suplai udara Particulates generated Konfigurasi ruangan Infiltrasi partikel asing Suhu ruangan Tekanan udara ruanga Air change rate normally varies between 6 20 air changes per hour

14 Pencapaian konsisi ruangan sesuai dg spesifikasinya dilakukan pada kondisi: ( 1 ) "As built" Bare room, without equipment or personnel Ruangan kosong tanpa mesin dan operator

15 (2): "At rest" Equipment may be operating, but no operators present Mesin dalam keadaan operasi, tanpa operator

16 (3): "In operation" Normal production process with equipment and personnel, Proses produksi normal dengan orang dan mesin. Clean up time validated normally in the order of 20 minutes

17 Control of contaminants HVAC External contaminants dapat dicegah dengan filtrasi yang efektif. Internal contaminants dicontrol melalui flushing, or displacement airflow Sehingga cemaran partikel diudara dan sistem filtrasi merupakan critical factor

18 Cleanroom Class A / B Cleanroom Class C Cleanrm. Class D Others Manufacturing Environment requirements Therapeutic risks

19 Level of protection and air cleanliness determined according to (tingkat proteksi dan kebersihan udara ditentukan berdasarkan): Product to be manufactured (produk yg akan dibuat) Process to be used (proses yg akan dilakukan) Product susceptibility to degradation (kerentanan produk terhadap degradasi)

20 Parameter yg berpengaruh pada kualitas udara : Jumlah partikel diudara dan jumlah mikroorganisme diudara dan dipermukaan. jumlah air changes pada tiap ruangan. Air velocity dan airflow pattern Filter (type, position) HVAC Air pressure differentials antar ruangan. Temperature, relative humidity (kelembaban relatif)

21 Selain persyaratan tersebut, ada hal lain yang hrus diperhatikan : appropriate gowning (type of clothing, proper changing rooms) validated sanitation adequate transfer procedures for materials and personnel

22 Cleanroom Class defined by Critical Parameters Air Handling System Additional Measures

23 Examples of levels of protection Level Level 1 Level 2 Level 3 Condition General Protected Controlled Example of area Area with normal housekeeping, e.g. warehouse Area where steps are taken to protect exposed material/product, e.g. dispensing Area with defined, controlled, monitored environmental conditions to prevent contamination and degradation

24 Air Filtration Penyaringan udara Derajad penyaringan merupakan faktor yg penting untuk mencegah kontaminasi. Type filters yg akan dipakai tergantung pada kualitas udara lingkungan,return air dan air change rates

25 Levels of protection and recommended filtration Level of protection Level 1 Level 2 and 3 Level 2 and 3 Recommended filtration Primary filters, e.g. EN779 G4* Production area with 100% outside air: Primary plus secondary filter (e.g. EN779 G4 plus F8 filters) Production area with recirculated plus ambient air with a risk of cross-contamination: Primary plus secondary plus tertiary filter (e.g. EN779 G4 plus F8 plus EN1822 H13 filters) *Filter class should be referenced to the standard test method

26 Contamination dapat dicegah dengan cara: Materials for components and construction (pemilihan bahan dan konstruksi yg baik) Design and appropriate access to dampers, filters and other components (desain dan akses aliran udara ke damper, filter dan komponen lainnya) Personnel operations Airflow direction (arah aliran udara yg baik) Type of diffusers (non-induction type recommended)- tipe dari pendorong udara Air exhaust (normally from a low level) sistem penghisap udara

27 Pola aliran udara

28 Airflow patterns Filtered air entering a production room or covering a process can be (udara tersaring yang masuk ke ruang produksi ada dua tipe : turbulent, or unidirectional (laminar) GMP aspect economical aspect Other technologies: barrier technology/isolator technology.

29 Airflow patterns Turbulent dilution of dirty air Unidirectional/laminar displacement of dirty air

30 Airflow patterns AHU Prefilter Main filter Turbulent Unidirectional Turbulent

31 Airflow patterns (4) Workbench (vertical) Cabin/booth Ceiling

32 Unidirectional airflow (UDAF): Provided where needed over product or material to prevent contamination, or to protect operator UDAF in weighing areas The aim is to provide dust containment (melindungi dari pengaruh debu) Airflow velocity should not affect balance (kecepatan alir udara tidak boleh mempengaruhi timbangan) Position of material, balance, operator determined and validated no obstruction of airflow or risk (posisi dari material, timbangan dan operator tidah berubah dan tervalidasi tidak menimbulkan gangguan atau resiko).

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35 Air Lock Room 1 15 Pa 30 Pa Air Lock Room 2 Passage 15 Pa Note : Direction of door opening relative to room pressure E Room 3 15 Pa Air Lock 15 Pa 0 Pa HVAC Pressure cascade solids Protection from cross-contamination Room 1 Room 2 Room 3 15 Pa 15 Pa 15 Pa Air Lock Air Lock Air 30 Pa E Lock 0 Pa Passage 15 Pa Note : Direction of door opening relative to room pressure

36 Komponen penyusun HVAC sistem

37 Sistem utama dari HVAC Exhaust air treatment Fresh air treatment (make-up air) + Terminal air treatment at production room level Central air handling unit Production Room

38 Components penyusun terdiri dari Weather louvre Silencer Flow rate controller Control damper To prevent insects, leaves, dirt and rain from entering ( mencegahmasuknya serangga, daun, hujan dan cemaran lainnya dari luar ) To reduce noise caused by air circulation ( mengurangi kebisingan yang timbul karena perputaran udara ) Automated adjustment of volume of air (night and day, pressure control) pengendali aliran/volume udara secara otomatis ) Fixed adjustment of volume of air

39 Components (2) Heating unit Cooling unit/ dehumidifier Humidifier Filters Ducts To heat the air to the proper temperature (memanaskan udara sampai pada temperatur yg dikehendaki ) To cool the air to the required temperature or to remove moisture from the air (mendinginkan dan mengurangi kelambaban udara To bring the air to the proper humidity, if too low ( menjaga kelembaban udara) To eliminate particles of predetermined dimensions and/or microorganisms (mencegah masuknya partikel asing dan mikroorganisme) To transport the air

40 Exhaust Air Grille Skema komponen HVAC Silencer Flow rate controller Fan Filter Weather louvre Control damper + Heater Prefilter Humidifier Terminal filter Heating coil Cooling coil with droplet separator Secondary Filter Production Room Recirculated air

41 Air-handling unit Control damper for airflow Humid room air Adsorber wheel Dry air AHU with fan Variable Speed Controller Regeneration air Humid room air De-humidification Air heater Filter Pressure Gauges

42 Humidifier Silencer Heating and cooling units

43 Filter classes Dust filters Standard Aerosol Coarse Fine HEPA ULPA Dp > 10 µ m 10 µ m > Dp > 1 µ m Dp < 1 µ m G1 - G4 F5 - F9 H U EN 779 Standard EN 1822 Standard

44 HEPA or tertiary filter Primary panel filter Secondary filter

45 Positioning of filters (1) AHU mounted final filter Filter in terminal position HEPA Filter + Production Room Production Room HEPA Filter

46 Positioning of filters (2) Prefilter AHU Main filter Ceiling exhausts Low level exhausts

47 Positioning of filters (3) AHU Final filter Prefilter 1 2

48 Filter 2 Tightening frame 3 Register outlet 4 Screw fixation for register Swirl Type air diffusors with terminal filters

49 High induction office type diffusor (avoid) Low induction swirl diffusor (preferred)

50 Regulation of room pressure pressure differentials concept Room pressure gauges Room pressure indication panel

51 Air types Fresh air (make-up air) Supply air + Exhaust air Return air (recirculated) Production Room

52 Ventilation with recirculated air + make-up air Exhaust Unit Central Air-Handling Unit Return air